Research Profile

of the Egyptian National Cancer Insitute (ENCI)

on the PubMed

Prepared by

Ahmed A. Zeeneldin, MD
Assoiate Professor of Medical Oncology

Director of ENCI Research Center

Editing help

Ahmed A. El Hamed

Secretary of ENCI Research Center

2012

1
Preface

2
Table of Contents

THE ARTICLE ............................................................................................................................................4

ABSTRACTS ............................................................................................................................................21

Animal Studies .......................................................................................................................................21

Bladder Cancer studies..........................................................................................................................28

Brain, Head &Neck, Thyroid Studies .....................................................................................................46

Breast Cancer Studies............................................................................................................................69

GIT Cancer Studies...............................................................................................................................100

Leukemia Studies.................................................................................................................................108

Lung Cancer and Mesothelioma..........................................................................................................132

Miscellaneous studies .........................................................................................................................152

Gynecological Cancers.........................................................................................................................191

Appendix-1: Publications by Departments..........................................................................................196

3
 THE ARTICLE

Research Profile of the Egyptian National Cancer Institute (ENCI) in the

PubMed
Ahmed A. Zeeneldin, MD
Director of ENCI Research Center

Abstract:
Background: the Egyptian National Cancer Institute (ENCI) is the largest cancer center in Egypt,
Africa and the Middle East. It is concerned not only with cancer treatment, but also with education
and research. This study was conducted to assess the publications affiliated to ENCI in the PubMed.

Methods: on 29th of October 2012, the PubMed was searched for publications that are affiliated to
the ENCI, Cairo University, Egypt. Records were manually scrutinized to extract relevant information.

Results: 391 records were retrieved. Publication volume showed a giant step in 2004. Most ENCI
articles are hosted by the ENCI journal. Departments of Surgery, Cancer Biology, Medical Oncology,
Radiotherapy and Pathology made the greatest contribution to the publications of the Egyptian
National cancer Institute in the PubMed contributing 23%, 20%, 14%, 13% and 11%, respectively.
One author from Cancer Biology Dept. topped ENCI authors’ lists. Cancers of the breast followed by
the urinary bladder, head, neck & thyroid, leukemias and lymphomas were the most common
diseases included in JENCI publications in the PubMed representing 14%, 11%, 9.5%, 9%, and 7%,
respectively. The main theme of the publications were the investigation of how a test(s) perform(s)
in certain clinical settings (40%), of a new technique(s) (e.g. surgical, radiotherapy, stem-cell
transplantation; 27%), of a drug(s) or a drug regimen(s) (12%) or to report the epidemiologic
features of a disease. only 31 publications (7.9%) were reporting on clinical trials of whom 18 were
randomized clinical trials. We did not encounter a single phase I trial publication.

Conclusion: research output of the ENCI needs to be leveraged both in quality and volume. Research
specific training programs as well as research strategic planning will be of great help. Supporting the
new-laid ENCI research center may be a step in the right direction.

Key words: Egyptian National Cancer Institute, Cancer, Publication volume, PubMed

4
Introduction:
The Egyptian National Cancer Institute (ENCI) affiliated to Cairo University is the largest cancer
center in Egypt, Africa and the Middle East with a capacity of 600 beds, 10 major departments and a
staff of more than 1200 including about 300 physicians; 50% of whom are MD holders. Since its
official inauguration in 1969, ENCI mission includes 4 major domains; therapeutic services, education
and training, research, and planning cancer care at the national level [1]. Yearly, the ENCI receives
about 20000 new cancer patients, provides about 180000 follow-up outpatient visits, and admits
12000 patients. Research is a key ENCI mission. ENCI research focused mainly on those cancers that
are common in Egypt including particularly urinary bladder cancers [2].

The PubMed is a database of citations and abstracts for biomedical literature from MEDLINE and life
science journals. It was developed and maintained by the National Center for Biotechnology
Information (NCBI)[3]. PubMed is a free Web literature search service that contains millions of
abstracts and citations from over 5000 journals and is frequently updated. This makes PubMed the
first choice for electronically searching and retrieving biomedical literature. Almost 5 million queries
are issued to PubMed each day by users around the globe [4], who rely on such access to keep
abreast of the state of the art and make discoveries in their own fields [5].

The aim of this study was to describe the research profile of the ENCI on the PubMed. This will shed
lights on areas of strength and weakness to inform strategic planning of research at ENCI.

Methods
This PubMed search was performed on October 29th, 2012 at 2 PM. In the search builder of the
PubMed advanced search page (http://www.ncbi.nlm.nih.gov/pubmed), we searched for the
affiliation: (National Cancer Institute[Affiliation]) OR NCI[Affiliation] AND (Egypt*[Affiliation]) OR
Cairo[Affiliation]. This yielded a total of 392 citations. All were manually reviewed and NCI affiliation
was manually rechecked. The above affiliation was confirmed in 391 records and only one record
belonged to NCI of the United States of America. Thus the false positive error rate was 1 in 392
(0.3%). To ensure that we did not miss NCI affiliation, the search was again repeated using the
affiliation: ((Egypt*[Affiliation]) OR Cairo[Affiliation] NOT (National Cancer Institute[Affiliation])
OR NCI[Affiliation]). This new search yielded 21601 records. Each 50th record was manually checked
giving a total of 433 records. The mentioned affiliation was confirmed in all of them. Thus the false
negative rate was 0% (table 1). Data on the number of ENCI staff and disease frequencies were
extracted from the official ENCI website [6,7].

Results
As of 29th of October 2012, there were 391 articles listed in the PubMed database that are affiliated
to the Egyptian National Cancer Institute (ENCI). The number of annual ENCI publications increased
from 3 in 1987 to 45 in 2011 (figure 1). There was a sharp rise in the numbers of ENCI publications
starting in the year 2004 and apparent decline in 2012 compared to that of 2011.

The departments of Surgery, Cancer Biology, Medical Oncology, Radiotherapy and Pathology made
the greatest contribution to the publications of the ENCI in the PubMed contributing 23%, 20%, 14%,
13% and 11%, respectively. Department of Surgery had the highest staff and publications. Biology

5
and Medical Oncology departments had publications that exceed their staff percentage. On the
other hand, Departments of Anesthesia, Radio-diagnosis and Clinical Pathology had publications
lower than their staff percentage (figure 2).

ENCI publications spanned over 127 different journal titles. Only two of them were Egyptian
journals, namely the Journal of the Egyptian National Cancer Institute (JENCI) and the Egyptian
journal of immunology (EJI). Only 27 journals (27%) are cancer-related journals. The most common
journals that hosted ENCI publications were JENCI (44%), EJI (1.8%), the Urologic Oncology Journal
(1.5%) and the Virology Journal (1.5%; table 2). Most publications appeared in the September or
March issues followed by the December or June issues (figure 3). Departments of surgery, Pediatric
Oncology, Dental Medicine and Radio-diagnosis published most of their articles in the JENCI. On the
Other hand, Departments of Epidemiology, Cancer Biology, Anesthesia, Medical Oncology and
radiotherapy published most of their articles in journals other than the JENCI (figure 4)

Cancers of the breast followed by the urinary bladder, head, neck and thyroid, leukemias and
lymphomas were the most common diseases included in ENCI publications in the PubMed
representing 14%, 11%, 9.5%, 9%, and 7%, respectively. Publications did not perfectly match
frequency of the disease. for example percentage of publications exceeded that of disease frequency
in liver cancers, gynecologic cancers and lymphoma (figure 5). The main theme of the publications
were the investigation of how tests perform in certain clinical settings (40%), of new techniques (e.g.
surgical, radiotherapy, stem-cell transplantation; 27%), of drugs or a drug regimens (12%) or to
report the epidemiologic features of a disease (3%; figure 5).

All publications were written in English. They involved human subjects and female sex more
frequently than non-human species or female sex (table 3). Adults were the commonest age group
represented while infants and those aged 80 years or above were infrequently involved. In addition
to cancer as the main subject of the publications, other subjects included were toxicology,
complementary medicine, veterinary science, AIDS, dietary supplements and history of medicine.
Clinical trial was the most frequent article type particularly the randomized clinical trial.

The 391 articles carried 1769 authors. About 52% of publications had 4 or less authors per article
and very few had 9 or more authors (figure 7). As first authors, the following NCI staff members
were the most frequently encountered (table 4): Abdel-Rahman N Zekri (Cancer Biology Dept.),
Mohamed Saad Zaghloul (Radiotherapy Dept.), Hussein M Khaled (Medical Oncology Dept.), Hadir A
El-Mahallawy (Clinical Pathology Dept.), Hatem A Azim (Medical Oncology Dept.), Abeer A Bahnassy
(Pathology Dept.) and Nazli Gad el-Mawla (Medical Oncology Dept.). As an author, not necessarily
the first, Abdel-Rahman N Zekri maintained the list top, followed by Hussein M Khaled, Abeer A
Bahnassy, Mohamed Saad Zaghloul, Rabab M Gaafar (Medical Oncology Dept.), Nadia M Mokhtar
(Pathology Dept.) and Azza M Kamel (Clinical Pathology Dept.).

Discussion
By no means we can claim that this few number of publications is the complete research output of
the ENCI. Our study is limited to articles that carry ENCI affiliations in the PubMed. Publications by
NCI staff that failed to affiliate to ENCI will not be included. Publications in non-PubMed journals will

6
not also be included. Author lists faced some problems mostly related to the multiple variations in
names for the same author. Whenever possible, we corrected this manually. However, we believe
that some authors were under-scored based on this fact. For example when the author Abdel-
Rahman N Zekri was individually searched, his records as first author with ENCI affiliation counted 24
instead of 23 and his total records that carried ENCI affiliation are 39 and not 37. Similarly, when the
author Mohamed S Zaghloul was individually searched, his records as first author with ENCI
affiliation counted 18 instead of 16 and his total records that carried ENCI affiliation are 28 and not
22. However, our study shows the ENCI research profile in the most searched biomedical literature
database.

To improve the ENCI profile in the PubMed, authors are encouraged to submit their manuscripts to
PubMed indexed journals and to properly affiliate themselves to the ENCI. Also, local Egyptian
journals are encouraged to apply for indexing in the PubMed. Authors are encouraged to publish
their work using a unique and single author name for better tracking of their work.

We cannot accurately guess how much ENCI publications in PubMed represent out of ENCI total
publications. This is because there is no complete and exhaustive record that lists all ENCI
publications. The number of ENCI staff that holds an MD or PhD degrees approximates 400. Thus the
ratio of staff to PubMed publications is approximately 1:1. Assuming that the ENCI MD/PhD holder
will publish a minimum of 10 papers to normally promote from Lecturer to Assistant Professor then
to Professor post, then the total ENCI publication output may be approximately 4000 publications.
Hence, the ration of PubMed ENCI publications to total ENCI publications may be 1:10.

The total number of NCI theses in the ENCI MD theses now exceeds 600. Thus, the ratio of ENCI MD
theses to ENCI PubMed publications is approximately 1.5:1. Many researches done as part of
academic degrees (MD or MSc.) do not get published as articles in journals. Reasons for this are
many. First, it was not mandated by the university or institutional policy. Second, many students are
not enthusiastic enough or do not appreciate the value of publishing their theses. Many students see
their theses as only a pre-requisite for their degree and they do not appreciate the value of the
research itself. Many students do not play a role in choosing or deciding the topic of their research
either because they show no particular interest in specific research topics or they were enforced to
adopt the research ideas of their supervisors. Third, after the theses are discussed and accepted,
supervisors do not have the power or authority to enforce candidates to publish their work. Fourth,
supervisors may not have the time and may not be interested in doing the job of publishing. Fifth,
the research itself may not be novel or may yield negative trials that the candidate or supervisor may
see as not worthy of getting published.

It is recommended that ENCI starts a program that comprehensively captures all ENCI publications.
The new mandate that MD and MSc students will not awarded their academic degree unless they
publish their research work as papers is a step in the right direction. Students should be trained on
research methodology and should be encouraged to develop their research ideas and choose their
supervisors whenever possible. Students and supervisors need to appreciate that negative studies or
non-novel ones are worth publishing.

The number of ENCI articles in PubMed showed a sharp rise in the year 2004. This coincided with the
availability of the JENCI that carries 44% of ENCI publications on the web and inclusion of its articles
in the PubMed. The JENCI was first published in 1982 and launched to the internet in 2004 and

7
Medline-indexed in March, 2005 [8]. The decline in publication numbers in 2012 compared to 2011
can be related to time of performing the study (end of October 2012). Thus, there are two months
remaining to have the full pattern. November and December usually have about 14% of ENCI
publications and the JENCI journals is a quarterly journal thus the December issue will carry many
ENCI publications.

The ENCI publications were spanned over 127 journal titles, 27% of whom are cancer-specific
journals. This may indicate author preference as well as journal accessibility. Authors need some
guidance on how to choose the best journal for publishing their research and this can be one task of
the new ENCI research center.

Out of 127 journals, only two were Egyptian journals and the JENCI alone carried 44% of ENCI
publications. Authors may prefer the JENCI because it is their home journal, PubMed indexed, now
hosted by Elsevier publisher, had a reasonable impact factor, easy accessible with simple and clear
submission process and fast acceptance [9]. However, this does not exclude the possibility that some
the work by ENCI staff may be difficult to be published in non-Egyptian journals because it is of
relevance only to the local community and not on a global scale. This highlights the need of choosing
research topic by researchers that are both of local as well as global interests. Also, it is
recommended that the relevant authorities in the country adopt an initiative of getting all Egyptian
journals indexed in MEDLINE, particularly those related to cancer. This mandates resource allocation
and getting dedicated staff assigned to those journals and finding a suitable hosting publishing
house. The initiative of the JENCI can be taken as a model in this regard.

Surgery, Cancer Biology, Medical Oncology, Radiotherapy and Pathology departments made the
greatest contribution to the ENCI publications. This may reflect the volume of staff in each
department (e.g. Surgery is the most staffed department and Dental department is the least). It
could also reflect research interests and time devoted to research (e.g. Cancer biology is a
department with research as it main scope). It could also reflect the interest of individual
researchers in these departments (e.g. Abdel-Rahman N Zekri from the Cancer Biology department
tops both author lists; Hussein M Khaled, Nazli Gad el-Mawla and Rabab M Gaafar from the Medical
Oncology Department; Mohamed Saad Zaghloul from Radiotherapy Department; Abeer A Bahnassy,
Nadia M Mokhtar and Iman G Farahat from the Pathology Deprtment). While Surgery tops the ENCI
departments, surgeons step back in individual authors’ lists (10th as first authors and 17th as any
author).

To increase ENCI research and publication, research should not only reflect one single factor. In this
regard, NCI should adopt a policy that encourages and mandates all NCI staff to perform research.
The highest research out-put can be achieved when we multiply departmental staff number by
departmental research interest by individual research interest and time devoted for research.
Increasing NCI staff is not the solution to increase NCI publications. However, adopting a research
plan at both the institutional level and departmental level will be of help particularly when all
concerned parties participate in its setting. Increasing individual staff interest in research can be
achieved through education, encouragement and may be obligation. Research allocated time can be
of great help particularly for the departments that are very busy with their routine work (e.g.
surgery).

8
Diseases presented in ENCI publications largely reflect the frequency of those diseases among the
ENCI patients [7]. Breast cancer represents 14% of ENCI publications and 20% of patients’ volume,
urinary bladder cancer represents 11% of publications and 9% of patients’ volume, head, neck and
thyroid cancers appears early in publication but late in patients’ volume, leukemias represents 9% of
publications and 7% of patients’ volume, lymphomas represents 7% of publications and 8% of
patients’ volume, liver cancer represents 4% of publications and 6% of patients’ volume, thoracic
cancers represent 5.5% of publications and 4% of patients’ volume.

The occasional non-perfect matching between ENCI publications and patients’ volume can be
explained by researchers’ interests in these diseases. For example head and neck cancers come early
in the publication list despite late in the patients’ volume due to interests of the surgeons (Ayman A
Amin and others in this disease), thoracic cancers reflects the interest of the lung cancer group
(Rabab Gaafar, Abdelrahman M Abdelrahman and others), liver cancer pattern reflects the poor
outcome of the disease and the relative lack of clinician interest in this disease. However, it should
be noted that liver cancer ranks first among Egyptian cancers and should be the focus of research
not only at the institutional but also at the national level.

The publication themes were either tests, techniques, drugs or epidemiologic features. Investigation
tests prevailed in ENCI publications because it was the main topic of articles by many departments
(e.g. Cancer Biology, Pathology, and Clinical Pathology) and an integral component of many
departments (e.g. Medical and Pediatric Oncology). Investigating a technique was prevalent in 27%
and this reflects them main core of surgery and radiotherapy publications and some of Medical
Oncology publications (e.g. stem cell transplantation). Drugs were less frequent and this reflects the
issue that many drugs are developed in foreign countries with limited access in ENCI. Encouraging
the testing of locally developed drugs should be a priority.

Most ENCI publications reported on females and this is exactly similar to the percentage of female
patients among ENCI total patients’ volume with breast cancer being the commonest malignancy in
females and both genders combined [7]. About 7% of publications reported on species other than
humans and this reflects the preclinical work of the Cancer biology department. However, animal
studies should be encouraged more as research in animal is an important step that informs further
trials on humans.

The fraction of publications classified as clinical trials was quite low (about 8%) particularly the gold
standard randomized controlled trials (RCTs; about 5%). This is because 43% of publications reported
on tests or epidemiology, and many of the trials that reported on techniques were retrospective in
nature. While preclinical studies and observational studies in humans are valuable, yet clinical trials
particularly the RCTs carry a very high rank and should be encouraged. This needs special training
and resources that include, but not limited to, inclusion of epidemiologists and statisticians very
early at the stage of study design, providing comprehensive training in research methodologies,
getting the logistic support form key research team members like research nurses, research
pharmacists, study coordinators, data managers. The absence of phase I trials in ENCI publications is
striking. It reflects the paucity of drugs that are developed in Egypt and also the many obstacles set
by the ministry of health on those kinds of trials. This also reflects the lack of expertise on dealing
with such trials and the lack of infrastructure set to deal with such trials. This issue needs to be
addressed at the national level.

9
Conclusion
Research profile of the ENCI in the PubMed is quite low and does not accurately reflect the value of
the ENCI as the largest and most comprehensive cancer center in the region. To improve this, we
encourage ENCI staff to publish their work in PubMed indexed periodicals, urge Egyptian journals to
be PubMed-indexed. ENCI should develop a strategic plan that aims at increasing its research
productivity.

Author Disclosures: The authors have declared no conflicts of interest.

Sources of Funding: This work is investigator initiated with no external funding.

10
References
1. The Egyptian National Cancer Institute. Word of the National Cancer Institute [online]. Available
at: http://cu.edu.eg/userfiles/NCI_en.pdf (accessed 29 October, 2012).

2. The Egyptian National Cancer Institute. Administrative report [online]. Available at:
http://nci.cu.edu.eg/lectures/NCI%20adminst.pdf (accessed 29 October, 2012).

3. National Center for Biotechnology Information, US: PubMed Help, Bethesda (MD) 2005 [online]
available at: http://www.ncbi.nlm.nih.gov/books/NBK3830/(accessed 15 June 2011).

4. Islamaj Dogan R, Murray GC, Névéol A, et al. Understanding PubMed user search behavior
through log analysis. Database 2009; doi:10.1093/database/bap018. [online] available at:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797455/?tool=pubmed (accessed 15 June, 2011)

5. Lu Z. PubMed and beyond: a survey of web tools for searching literature. Database 2011 (Oxford).
2011; 2011:baq036. Print 2011.doi: 10.1093/database/baq036 [online] available at:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025693/ (accessed 15 June, 2011)

6. The Egyptian National Cancer Institute. Administration [online]. Available at:

http://www.nci.cu.edu.eg/adminstration.aspx (accessed 29 October, 2012).

7. Ali eldin N. Cancer statistics 2002 – 2007, Preliminary report [online]. Available at:
http://nci.cu.edu.eg/lectures/Cancer_statistics2002-2007.pdf (accessed 30 October, 2012)

8. National Center for Biotechnology Information. NLM Catalog: "Journal of the Egyptian National
Cancer Institute"[Jour] [online]. Available at:
http://www.ncbi.nlm.nih.gov/nlmcatalog?cmd=historysearch&querykey=1 (accessed 30 October,
2012)

9. Journal of the Egyptian National Cancer Institute. Description [online]. Available at:
http://www.elsevier.com/journals/journal-of-the-egyptian-national-cancer-institute/1110-
0362#description (accessed 30 October, 2012)

11
Figures and legends
Figure 1. Number of yearly publications affiliated to the Egyptian National cancer Institute in the

PubMed.

Figure 2. Departmental contribution to the publications of the Egyptian National cancer Institute in

the PubMed compared to the staff volume.

Figure 3. Percentage of the publications of the Egyptian National cancer Institute in the monthly

issues of the publishing journals.

Figure 4. Departmental publications to Journal of the Egyptian National cancer Institute (JENCI) or

non-JENCI journals

Figure 5. Disease representation in the publications of the Egyptian National cancer Institute in the

PubMed compared to their frequency among ENCI patients.

Figure 6. Main theme of the publications of the Egyptian National cancer Institute in the PubMed.

Figure 7. Number of authors per publication

12
 50
45
40
No of Yearly Publications

35
30
25
20
15
10
5
0
1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012
Year

Figure 1. Number of yearly publications affiliated to the Egyptian National cancer Institute in the
PubMed.

Nuclear Medicine
Dental
Epidemiology
Radiodiagnosis
Pharmacology
Anaesthesia
Pediatric Oncology
Clinical Pathology Staff %
Pathology Publication %
Radiotherapy
Medical Oncology
Biology
Surgery
0.0 5.0 10.0 15.0 20.0 25.0
Percentage

Figure 2. Departmental contribution to the publications of the Egyptian National cancer Institute in
the PubMed compared to the staff volume.

13
 Dec

Nov

Oct

Sep

Aug
Issue/Month

Jul

Jun

May

Apr

Mar

Feb

Jan

0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0
% of publications

Figure 3. Percentage of the publications of the Egyptian National cancer Institute in the monthly
issues of the publishing journals.

Epidemiology
Pharmacology
Biology
Anaesthesia
Medical Oncology
Nuclear
Radiotherapy
Clinical Pathology JENCI %
Pathology Non_JENCI %
Radiodiagnosis
Dental
Pediatric Oncology
Surgery
0.0 20.0 40.0 60.0 80.0 100.0 120.0
Percentage

Figure 4. Departmental publications to Journal of the Egyptian National cancer Institute (JENCI) or
non-JENCI journals

14
 Cell lines
Animal Studies
Uterus, Cervix
Brain
Liver
GIT
Lung, Mesothelioma NCI %
Lymphoma
PubMed %
Leukemia
H&N, Thyroid
Bladder
Breast
0.0 5.0 10.0 15.0 20.0 25.0
Percentage

Figure 5. Disease representation in the publications of the Egyptian National cancer Institute in the
PubMed compared to their frequency among ENCI patients.

Epidemiology
Main Theme of the Publication

Drug

Technique

Test

0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0
%

Figure 6. Main theme of the publications of the Egyptian National cancer Institute in the PubMed.

15
Number of authors/Publication 11
10
9
8
7
6
5 %
4
3
2
1

0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0 20.0
Percentage

Figure 7. Number of authors per publication

16
Tables and captions

Table 1. Affiliations of publications from ENCI in PubMed

Affiliation checked manually

Egypt AND ENCI Egypt NOT ENCI Total
Affiliation by search Egypt AND ENCI 391 1 392
strategy Egypt NOT ENCI 0 433 433
Total 391 434 825
ENCI: Egyptian National Cancer Institute

17
Table 2. Journals that hosted the publications from the Egyptian National Cancer Institute that were
listed in the PubMed

Journal Title No %
Journal of the Egyptian National Cancer Institute 172 44.0
The Egyptian journal of immunology 7 1.8
Urologic oncology journal 6 1.5
Virology journal 6 1.5
International journal of radiation oncology, biology, physics 5 1.3
Pharmacological research 5 1.3
Annals of oncology 4 1.0
The Annals of thoracic surgery 4 1.0
Anti-cancer drugs 4 1.0
Bone marrow transplantation 4 1.0
The Gulf journal of oncology 4 1.0
Journal of pediatric hematology/oncology 4 1.0
Lung Cancer 4 1.0
Pediatric blood & cancer 4 1.0
Tumori 4 1.0
Applied immunohistochemistry & molecular morphology 3 0.8
Biological & pharmaceutical bulletin 3 0.8
the Cancer journal 3 0.8
Cancer treatment reviews 3 0.8
The Clinical journal of pain 3 0.8
European journal of cancer & clinical oncology 3 0.8
Expert review of anticancer therapy 3 0.8
Journal of medicinal food 3 0.8
Journal of reconstructive microsurgery 3 0.8

18
Table 3. Categorization of the publications from the Egyptian National Cancer Institute that were
listed in the PubMed

Category Subcategory No %
Language: English 391 100
Species: Human 240 61.2
Other species 26 6.6
Sex: Male 169 43.1
Female 202 51.5
Age: Infant: 0-23m 16 4.1
Child: 0-18y 69 17.6
Adolescent: 13-18y 60 15.3
Adult: 19+ y 162 41.3
Adult: 19-44y 144 36.7
Middle aged: 45-64 142 36.2
Aged: 65+y 89 22.7
Aged: 80+ 18 4.6
Subject: Cancer 391 100
Toxicology 78 19.9
Complementary Medicine 21 5.4
Veterinary Science 13 3.3
AIDS 11 2.8
Dietary Supplements 7 1.8
History of Medicine 2 0.5
Bioethics 0 0.0
Article type: Clinical Trial 31 7.9
Phase I 0 0.0
Phase II 6 1.5
Phase III 2 0.5
Controlled Clinical Trial 2 0.5
Randomized Controlled Trial 18 4.6
Case report 5 1.3
Review article 19 4.8
Systematic Reviews 6 1.5
In Vitro experiment 3 0.8
Multicenter Study 2 0.5
Retracted Publication 1 0.3

19
Table 4. The most frequently encountered first authors of NCI Publications in the PubMed

First Author N % Any authors N %

1. Abdel-Rahman N Zekri 23 5.9 1. Abdel-Rahman N Zekri 37 2.1
2. Mohamed S Zaghloul 16 4.1 2. Hussein M Khaled 34 1.9
3. Hussein M Khaled 11 2.8 3. Abeer A Bahnassy 32 1.8
4. Hadir A El-Mahallawy 9 2.3 4. Mohamed S Zaghloul 22 1.2
5. Hatem A Azim 9 2.3 5. Rabab M Gaafar 21 1.2
6. Abeer A Bahnassy 8 2.0 6. Nadia M Mokhtar 18 1.0
7. Nazli Gad el-Mawla 8 2.0 7. Azza M Kamel 15 0.8
8. Azza M Kamel 7 1.8 8. Hadir A El-Mahallawy 14 0.8
9. Mohamed M Sayed-Ahmed 7 1.8 9. Iman G Farahat 13 0.7
10. Ayman Abdel-Wahab Amin 6 1.5 10. Mohamed R Hamza 13 0.7
11. Ekram M Saleh 6 1.5 11. Hamdi A Azim 12 0.7
12. Rabab M Gaafar 6 1.5 12. Saad Eissa 12 0.7
13. Abdel Rahman M Abdel Rahman 5 1.3 13. Mohamed A Nouh 12 0.7
14. Mohamad El-Zohairy 5 1.3 14. Sabry Shaarawy 12 0.7
15. Omaya A H Nassar 5 1.3 15. Manar M Moneer 11 0.6
16. Akmal Safwat 4 1.0 16. Gad-el-Mawla N 10 0.6
17. Ali H Mebed 4 1.0 17. Magdi El-Sherbiny 9 0.5
18. El-Sayed Ashraf Khalil 4 1.0 18. Hafez MM 9 0.5
19. Hamdy El-Marakby 4 1.0 19. Mohamed Lotayef 9 0.5
20. Hassan K Awwad 4 1.0 20. Ekram M Saleh 9 0.5
21. Magdy El-Sherbiny 4 1.0 21. Ahmed A Zeeneldin 9 0.5
22. Nesreen H Hafez 4 1.0 22. Alam El-Din HM 8 0.5
23. Sherif F Naguib 4 1.0 23. El-Awady RA 8 0.5

20
 ABSTRACTS

Animal Studies
PMID: 17102822

Abatement by naringenin of doxorubicin-induced cardiac toxicity in rats.

Arafa HM; Abd-Ellah MF; Hafez HF

Doxorubicin is one of the most active cytotoxic agents in current use. It has proven efficacy in various
malignancies either alone or combined with other cytocidal agents. The clinical usefulness of the anthracycline
drug has been precluded by cardiac toxicity. Many therapeutic interventions have been attempted to improve
the therapeutic benefits of the drug. Few, however, have been efficacious in this setting.We have addressed in
the current study the possible protective effects of naringenin, a flavonoid known to have anti-oxidant
properties, on doxorubicin-induced cardiac toxicity in male Swiss albino rats.Forty male Swiss albino rats were
used in this study. Naringenin (25 mg/kg body weight) was administered daily by gavage for 7 consecutive days
before a cumulative single dose of doxorubicin (15 mg/kg body weight, ip).Doxorubicin induced marked
biochemical alterations characteristic of cardiac toxicity including, elevated activities of serum total lactate
dehydrogenase (LDH) and creatine phosphokinase (CPK), enhanced lipid peroxidation measured as
malondialdehyde (MDA). The anthracycline drug has also reduced the cardiac enzymatic activities of
superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT). Besides, it reduced
significantly the reduced glutathione (GSH) level, but it increased the total NO content in heart tissue. Prior
administration of naringenin ahead of doxorubicin challenge ameliorated all these biochemical markers.Taken
together, one could conclude that naringenin has a protective role in the abatement of doxorubicin-induced
cardiac toxicity that resides, at least in part, on its anti-radical effects and regulatory role on NO production.
PMID: 12033498

Comparison of hypoxic cell radiosensitizers, KIN-804, KIN-844, KIN-806 and TX-1877, on

brain and liver metabolizing capacities in mice bearing Ehrlich ascites carcinoma.

Abou-Bedair FA; Hori H; Nagasawa H; Uto Y; Abu-Zeid M; Inayama S

The biochemical effects of the 2-nitroimidazole hypoxic cell radiosensitizers KIN-804, KIN-806, and their
analogues KIN-844 and TX-1877 on brain acetylcholinesterase (AChE) and hepatic free radical scavenging
systems, such as reduced glutathione (GSH) and glucose-6-phosphate dehydrogenase (G-6-PDH) levels, and
hepatic antioxidants, such as superoxide dismutase (SOD) and catalase, were evaluated in Ehrlich ascites
carcinoma (EAC)-bearing Swiss albino mice. The assay of brain AChE revealed nonsignificant changes with all
drugs examined. To evaluate the hepatic metabolic capacity, groups of mice were divided into control, EAC-
inoculated, 10-Gy local gamma-irradiated, and KIN-804, KIN-844, KIN-806, or TX-1877 (50 mg/kg body weight,
i.p.) groups, and gamma-irradiation was combined with each drug. EAC inoculation markedly suppressed GSH,
G-6-PDH, SOD, and catalase levels. On the other hand, treatment with gamma-irradiation significantly
enhanced them. The treatment of EAC-bearing mice with each drug alone in the absence of gamma-irradiation
revealed that KIN-806 and its derivative TX-1877 showed antitumor activity through their significant recovery
of GSH and SOD levels, respectively, in the EAC-bearing mice group. Similarly, the combined treatment of EAC-
bearing mice with gamma-irradiation with each of the drugs tested showed that KIN-806 and TX-1877
significantly increased GSH and SOD, and to a lesser extent G-6-PDH and catalase levels. On the other hand,
KIN-804 and KIN-844 had only a nonsignificant effect on all parameters examined. In conclusion, these data
reveal that the administration of KIN-806 and TX-1877 with or without subsequent gamma-irradiation,
resulted in significant recovery of GSH and SOD activities that were inhibited by EAC inoculation.
PMID: 3383943

21
 Effect of soybean feeding on experimental carcinogenesis--III. Carcinogenecity of nitrite
and dibutylamine in mice: a histopathological study.

Mokhtar NM; el-Aaser AA; el-Bolkainy MN; Ibrahim HA; Badr El-Din NK; Moharram NZ

The potential carcinogenic effect of nitrosamine precursors, DBA (dibutylamine) and nitrite, was clearly
demonstrated pathologically in the liver and bladder of male Swiss albino mice. Benign tumours were induced
in the bladder with an incidence of 40%, and hepatomas were detected in the liver in 27% of the cases. The
protective effect of soybean and ascorbic acid, added separately to the diet or to the drinking water
respectively, was demonstrated by a marked reduction in dysplastic features and absence of tumour in both
the liver and the urinary bladder.
PMID: 14502848

Effect of soybean, Vicia faba, and vitamin C on the carcinogenicity of DMBA.

el-Aaser AA; Zakhary NI; el-Guindy SM; Hafiez AR; Halawa F; Mokhtar N

A single dose of 10 mg of 7,12-dimethylbenz[a]anthracene (DMBA), administered to rats through intragastric

intubation, was sufficient to induce many biochemical and histopathological changes in their mammary tissue.
Significant increases were observed in the activity levels of the enzymes acid ribonuclease, 5-nucleotidase,
alkaline phosphatase, and beta-glucuronidase in mammary tissue homogenates of DMBA-treated rats after an
experimental period of five months. Histopathological studies of the mammary tissue also revealed malignant
epithelial tumors (cribriform carcinoma) induced among 85% of the treated rats, with an incidence of 4 tumors
in 12 mammary glands. Nevertheless, administration of 30% soybean in the diet of rats or 5,000 ppm ascorbic
acid in their drinking water in addition to DMBA revealed a significant chemoprotective effect against the
carcinogenesis induced by DMBA alone. This chemoprotective effect was demonstrated by the normalization
of the activity levels of the enzymes studied in mammary tissue homogenates, because most of the enzymes
were maintained at near the levels in the control animals. The incidence and number of tumors were also
decreased. Cribriform carcinoma was observed in 50% of the rats, and the incidence of the affected glands was
2 in 12 mammary glands among both groups. On the other hand, a less chemoprotective effect was observed
due to Vicia faba administration.
PMID: 11589785

Increased plasma endothelin-1 and cardiac nitric oxide during doxorubicin-induced

cardiomyopathy.

Sayed-Ahmed MM; Khattab MM; Gad MZ; Osman AM

The major limiting factor in long-term administration of doxorubicin is the development of cumulative dose-
dependent cardiomyopathy and congestive heart failure. Although several mechanisms have been suggested
to explain the exact cause of doxorubicin-induced cardiomyopathy, the role of the vascular endothelium-
derived vasoactive mediators in the pathophysiology of this toxic effect is still unknown. Accordingly, the
present study has been initiated to investigate whether the changes in plasma level of endothelin-1 and nitric
oxide along with cardiac nitric oxide are associated with the development of doxorubicin-induced
cardiomyopathy. Doxorubicin was injected with a single dose of 5 mg/kg and every other day with a dose of 5
mg/kg, intraperitoneally, to have four cumulative doses of, 10, 15, 20 and 25 mg/kg in five separate groups of
male rats. An additional group receiving a single dose of 20 mg/kg and one receiving normal saline were also
included in the study. Twenty-four hr after the last dose, the animals were sacrificed and the plasma levels of
endothelin-1 and nitric oxide in addition to cardiac nitric oxide were determined. The results show that
doxorubicin caused a statistically significant increase of 85%, 76% and 97% in plasma endothelin-1 at a
cumulative dose levels of 10, 15 and 20 mg/kg, respectively. However, the level of plasma nitric oxide
remained unchanged. Furthermore, doxorubicin treatment resulted in a significant dose-dependent increase

22
in serum lactate dehydrogenase and creatine phosphokinase. In contrast, the increase in nitric oxide
production in cardiac tissue by doxorubicin was not dose-dependent with the maximum increase (81%) at a
cumulative dose of 10 mg/kg. It is worth mentioning that plasma endothelin-1 and cardiac nitric oxide were
significantly increased at 24 hr after the single dose of 20 mg/kg doxorubicin. The increase of plasma
endothelin-1 and cardiac nitric oxide with the cardiomyopathy enzymatic indices, may point to the conclusion
that both endothelin-1 and cardiac nitric oxide are increased during the development of doxorubicin-induced
cardiomyopathy.
PMID: 8040027

Interleukin 1 increases thymidine labeling index of normal tissues of mice but not the
tumor.

Zaghloul MS; Dorie MJ; Kallman RF

This study was conducted to investigate the action of human recombinant interleukin 1 as a radioprotector for
different mouse normal cells other than bone marrow cells.Semi-continuous injections of tritiated thymidine
were administered every 6 h, over 24 h to determine thymidine labeling index. Mice were injected with
recombinant human interleukin 1 24 h prior to tritiated thymidine and were compared to control animals that
did not receive interleukin 1. Mice were killed 1 h after the last thymidine injection. The 24 h thymidine
labeling index for normal tissues and RIF-1 tumor was determined. Labeling indices were also determined 1-14
days after a series of fractionated irradiations with or without pretreatment with a single dose of interleukin 1
administered 24 h prior to the first radiation.The thymidine labeling index of normal tissues was higher
following the injection of recombinant human interleukin 1 24 h before radiolabeling. This was found in all
normal tissues tested, including the lip and tongue mucosal basal cell layers, crypt cells of the duodenum,
alveolar cells of the lung, hepatocytes, and basal skin cells. The thymidine labeling index of RIF-1 fibrosarcoma
was not affected by interleukin 1 injection. A single interleukin 1 injection 24 h before the first radiation
fraction also increased the thymidine labeling indices of normal tissues after localized fractionated irradiation.
The thymidine labeling index of RIF-1 tumor was not increased by interleukin 1 administration except after
relatively high radiation doses (20 Gy in five fractions). The ability of interleukin 1 to enhance the thymidine
labeling index declined after the first day following the completion of fractionated irradiation.Recombinant
human interleukin 1 increased the 24 h thymidine labeling index in normal tissues in mice, but not in RIF-1
tumor. Fractionated irradiation could maintain the effect of a single dose of interleukin 1, administered 24 h
prior to the first fraction, up to 24 h after the end of radiation.
PMID: 22530140

Isoflavones-Enriched Soy Protein Prevents CCL(4)-Induced Hepatotoxicity in Rats.

Sarhan NA; El-Denshary ES; Hassan NS; Abu-Salem FM; Abdel-Wahhab MA

The burden of liver disease in Egypt is exceptionally high due to the highest prevalence of hepatitis C virus
(HCV) resulting in rising rates of hepatocellular carcinoma (HCC). The aim of the current study was to
determine the isoflavones in soy and to evaluate the protective role of soy against CCl(4)-induced liver damage
in rats. Four experimental groups were treated for 8 weeks and included the control group, soy-supplemented
diet (20% w/w) group, the group treated orally with CCl(4) (100 mg/kg bw) twice a week, and the group fed
soy-supplemented diet and treated with CCl(4). Blood and liver tissue samples were collected for biochemical
analyses and histological examination. The results indicated that protein content was 45.8% and the total
isoflavones recorded 167.3 mg/100 g soy. Treatment with CCl(4) resulted in a significant biochemical changes
in serum liver tissue accompanied with severe oxidative stress and histological changes. Supplementation with
soy succeeded to restore the elevation of liver enzymes activities and improved serum biochemical
parameters. Moreover, soy supplementation improved the antioxidant enzymes, decreased lipid peroxidation,
and improved the histological picture of the liver tissue. It could be concluded that soy-protein-enriched
isoflavones may be a promising agent against liver diseases.
PMID: 7646934

23
 Late renal damage after total body irradiation and bone marrow transplantation in a
mouse model: effect of radiation fractionation.

Safwat A; Nielsen OS; el-Badawy S; Overgaard J

In response to the accumulating evidence that renal damage is now becoming an important late complication
after total body irradiation (TBI) and bone marrow transplantation (BMT), we have tested the effect of
fractionated and hyperfractionated TBI on late kidney damage in a mouse model. TBI was given as fractionated
(three fractions in 3 days, Fx 3), or hyperfractionated (nine fractions in 3 days, Fx 9) treatment. Kidney damage
was evaluated using [51Cr]EDTA residual activity, blood urea nitrogen (BUN) and percentage haematocrit
(%Hct) as end-points. We were able to detect progressive renal damage with no evidence of recovery or
plateau in the Fx 3 and Fx 9 schedules. The time latency before the expression of renal damage was dependent
on both total dose and end-point and it was shorter the higher the dose. [51Cr]EDTA detected renal damage at
the same doses as BUN but earlier in time whereas %Hct detected renal damage at doses lower than both BUN
and [51Cr]EDTA. Reducing the dose per fraction spared the kidney from TBI damage. The dose-response curves
for renal damage (using the [51Cr]EDTA end-point) were steep, and tended to shift towards lower doses with
longer follow-up times. The dose-modifying factors defined as the dose needed to cause renal damage in 50%
of the animals (ED50) using single fraction TBI divided by the ED50 using fractionated TBI were 1.3 and 1.9 for
the Fx 3 and Fx 9, respectively. These results may indicate that patients treated with TBI and BMT should be
assessed for late kidney damage and that fractionation and particularly hyperfractionation may protect the
kidneys from TBI-induced renal damage.
PMID: 11529691

L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic

rabbits.

Sayed-Ahmed MM; Khattab MM; Gad MZ; Mostafa N

This study has been initiated to investigate, in hypercholesterolaemic rabbits, whether L-carnitine deficiency
could be an additional risk factor in atherosclerosis, and if so, whether L-carnitine supplementation could
prevent the progression of atherosclerosis. Hypercholesterolaemia was induced by feeding rabbits 2%
cholesterol-enriched diet for 28 days, whereas, carnitine deficiency was induced by daily i.p. administration of
250 mg kg(-1) of D-carnitine for 28 days. Histopathological examination of aorta and coronaries from
hypercholesterolaemic rabbits revealed severe atherosclerotic lesions, intimal plaques and foam cell
formation. Also, hypercholesterolaemic diet resulted in a significant 53 and 43% decrease in reduced
glutathion (GSH) levels and a significant (1.87-fold) and (14.1-fold) increase in malonedialdhyde (MDA) levels in
aorta and cardiac tissues, respectively. Daily administration of L-carnitine (250 mg kg(-1)) for 28 days,
completely prevented the progression of atherosclerotic lesions induced by hpercholesterolaemia in both
aorta and coronaries. Conversely, daily administration of D-carnitine (250 mg kg(-1)) for 28 days increased the
progression of atherosclerotic lesions with the appearance of foam cells and apparent intimal plaques which
are even larger than that seen in hypercholesterolaemic rabbits. Both L-carnitine and D-carnitine produced
similar effects on the lipid profile, GSH and MDA which may point to the conclusion that: (1) L-carnitine
prevents the progression of atherosclerotic lesions by another mechanism in addition to its antioxidant and
lipid-lowering effects; (2) endogenous carnitine depletion and/or carnitine deficiency should be viewed as an
additional risk factor in atherogenesis.
PMID: 8082409

24
 Pharmacokinetic profile of methotrexate and 5-fluorouracil in normal and bilharzial-
infested mice.

Osman AM; Saad SF; Saad SY; el-Aaser AB; el-Merzabani MM

The pharmacokinetics of two commonly used anticancer drugs, methotrexate (MTX) and 5-fluorouracil (5-FU),
were investigated in normal and bilharzial-infested mice. Liver glucose-6-phosphatase activity and antipyrine
clearance were used as parameters of liver function. Liver glucose-6-phosphatase activity was significantly
reduced in bilharzial-infested mice compared with the normal controls. Bilharzial infestation caused a
significant reduction in the elimination (beta) and clearance rate (Cl) of antipyrine, whereas its elimination
half-life (t1/2 beta) was increased in comparison with the normal controls. A similar pattern was also obtained
after MTX and 5-FU administration in bilharzial mice, compared to controls. These results indicate that hepatic
bilharziasis causes a significant reduction in the hepatic clearance and elimination of MTX and 5-FU, whereas
their areas under the concentration-time curve were significantly increased. These findings may have to be
considered in the treatment of bilharzial cancer patients.
PMID: 15347908

Progression of cisplatin-induced nephrotoxicity in a carnitine-depleted rat model.

Sayed-Ahmed MM; Eissa MA; Kenawy SA; Mostafa N; Calvani M; Osman AM

This study has been initiated to investigate whether endogenous carnitine depletion and/or carnitine
deficiency is an additional risk factor and/or a mechanism in cisplatin-induced nephrotoxicity and to gain
insights into the possibility of a mechanism-based protection by L-carnitine against this toxicity.60 male
Sprague-Dawley rats were divided into six groups of 10 animals each and received one of the following
treatments: The first three groups were injected intraperitoneally with normal saline, L-carnitine (500 mg/kg),
and D-carnitine (750 mg/kg), respectively, for 10 successive days. The 4th, 5th, and 6th groups were injected
intraperitoneally with the same doses of normal saline, L-carnitine and D-carnitine, respectively, for 5
successive days before and after a single dose of cisplatin (7 mg/kg). Six days after cisplatin treatment, the
animals were sacrificed, and serum as well as kidneys were isolated and analyzed.A single dose of cisplatin
resulted in a significant increase in blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA) and
nitric oxide (NO) and a significant decrease in total carnitine, reduced glutathione (GSH) and adenosine
triphosphate (ATP) content in kidney tissues. Interestingly, L-carnitine supplementation attenuated cisplatin-
induced nephrotoxicity manifested by normalizing the increase of serum creatinine, BUN, MDA and NO and
the decrease in total carnitine, GSH and ATP content in kidney tissues. In the carnitine-depleted rat model,
cisplatin induced a progressive increase in serum creatinine and BUN as well as a progressive reduction in total
carnitine and ATP content in kidney tissue. Histopathological examination of kidney tissues confirmed the
biochemical data, i.e. L-carnitine supplementation protected against cisplatin-induced kidney damage,
whereas D-carnitine aggravated cisplatin-induced renal injury.Data from this study suggest that: (1) oxidative
stress plays an important role in cisplatin-induced kidney damage; (2) carnitine deficiency should be viewed as
an additional risk factor and/or a mechanism in cisplatin-induced renal dysfunction, and (3) L-carnitine
supplementation attenuates cisplatin-induced renal dysfunction.
PMID: 11419959

Propionyl-L-carnitine as protector against adriamycin-induced cardiomyopathy.

Sayed-Ahmed MM; Salman TM; Gaballah HE; Abou El-Naga SA; Nicolai R; Calvani M

Propionyl- l -carnitine (PLC) is a naturally occurring compound that has been considered for the treatment of
many forms of cardiomyopathies. In this study, the possible mechanisms whereby PLC could protect against
adriamycin (ADR)-induced cardiomyopathy were carried out. Administration of ADR (3 mg kg(-1)i.p., every
other day over a period of 2 weeks) resulted in a significant two-fold increase in serum levels of creatine
phosphokinase, lactate dehydrogenase and glutamic oxaloacetic transaminase, whereas daily administration
of PLC (250 mg kg(-1), i.p. for 2 weeks) induced non-significant change. Daily administration of PLC to ADR-

25
treated rats resulted in complete reversal of ADR-induced increase in cardiac enzymes except lactate
dehydrogenase which was only reversed by 66%. In cardiac tissue homogenate, ADR caused a significant 53%
increase in malonedialdehyde (MDA) and a significant 50% decrease in reduced glutathione (GSH) levels,
whereas PLC induced a significant 33% decrease in MDA and a significant 41% increase in GSH levels. Daily
administration of PLC to ADR-treated rats completely reversed the increase in MDA and the decrease in GSH
induced by ADR to the normal levels. In rat heart mitochondria isolated 24 h after the last dose, ADR induced a
significant 48% and 42% decrease in(14)CO(2)released from the oxidation of [1-(14)C]palmitoyl-CoA and [1-
(14)C]palmitoylcarnitine, respectively, whereas PLC resulted in a significant 66% and 54% increase in the
oxidation of both substrates, respectively. Interestingly, administration of PLC to ADR-treated rats resulted in
complete recovery of the ADR-induced decrease in the oxidation of both substrates. In addition, in rat heart
mitochondria, the oxidation of [1-(14)C]pyruvate, [1-(14)C]pyruvate and [1-(14)C]octanoate were not affected
by ADR and/or PLC treatment. Moreover, ADR caused severe histopathological lesions manifested as toxic
myocarditis which is protected by PLC. Worth mentioning is that PLC had no effect on the antitumour activity
of ADR in solid Ehrlich carcinoma. Results from this study suggest that: (1) in the heart, PLC therapy completely
protects against ADR-induced inhibition of mitochondrial beta -oxidation of long-chain fatty acids; (2) PLC has
and/or induces a powerful antioxidant defense mechanism against ADR-induced lipid peroxidation of cardiac
membranes; and finally (3) PLC has no effect on the antitumour activity of ADR.
PMID: 15469721

Protective effect of soybean against hepatocarcinogenesis induced by DL-ethionine.

Aiad F; El-Gamal B; Al-Meer J; El-Kerdasy Z; Zakhary N; El-Aaser A

There has been increasing interest in the value of using soybean to delay or reduce the tumor incidence. This
study was undertaken to investigate the possible protective effects of soybean against hepatocarcinogenesis
induced by DL-ethionine. Accordingly, we measured biochemical changes occurring in serum and liver of rats
treated with DL-ethionine in the presence or absence of soybean. Male albino rats were fed a control diet
containing the hepatocarcinogen, DL-ethionine, or the control diet plus soybean 30%, or the control diet plus
soybean plus DL-ethionine 0.25% for three months and then returned to a control diet for up to nine months.
Rats fed a control diet plus DL-ethionine showed a gradual decrease in liver DNA, RNA, total protein, and liver
weight and enzyme activities of liver transaminases (GOT and GPT) and alkaline phosphatase over the 7-month
study period. This was followed by a large increase in the liver parameters at the end of the 9(th) month,
except for 5'-nucleotidase and glucose-6-phosphatase that showed a large decrease. On the other hand, a
gradual increase in the serum enzyme activities of GOT, GPT, 5-nucleotidase, alkaline phosphatase, and in the
albumin/globulin (A/G) ratio is observed in the group of rats fed a control diet plus DL-ethionine compared to
the control group over 8 months, and this was followed by a large increase in all serum parameters studied at
nine-months. The administration of 30% soybean to the rat diet in addition to DL-ethionine maintained all
parameters studied at near control values until the end of the 9(th) month. This study suggests that soybean
has a protective effect against the hepatocarcinogenesis induced by DL-ethionine.
PMID: 7631026

Renal damage after total body irradiation in a mouse model for bone marrow
transplantation: effect of radiation dose rate.

Safwat A; Nielsen OS; abd el-Bakky H; Overgaard J

Late renal damage after total body irradiation (TBI) and bone marrow transplantation (BMT) is a recently
recognised morbidity. We have tested the effect of single fraction TBI given at two different dose rates on late
kidney damage in a mouse model. TBI was given at either high dose rate (HDR; 0.71 Gy/min) or low dose rate
(LDR; 0.08 Gy/min). Transplantation with syngeneic marrow cells was done 4-6 h after TBI. Kidney damage was
tested using 51CrEDTA residual activity, blood urea nitrogen (BUN) and percentage haematocrit (Hct). TBI
alone given at HDR or LDR caused progressive renal damage with no evidence of recovery or plateau. The time
latency before the expression of damage was dependent on both dose and the end point used. It was shorter
the higher the dose. 51CrEDTA detected renal damage at the same doses as BUN but earlier in time, while
%Hct showed evidence of renal damage at doses lower than both BUN and 51CrEDTA. Using the 51CrEDTA the

26
dose-response curves for renal damage were steep and continuously shifting towards lower doses as follow-up
time after treatment increased. There was a sparing effect of reducing the dose rate that was more evident at
follow-up times of less than a year than at 66 weeks after TBI. Thus, the dose modifying ratio (DMF), defined as
the dose needed to cause renal damage in 50% of irradiated animals (ED50) using LDR divided by the ED50
using HDR, was dependent on the time of evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 10706382

Studies of methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) 1: effect on free radical

scavenging system in mice bearing Ehrlich ascites carcinoma.

Abu-Zeid M; Hori H; Nagasawa H; Uto Y; Inayama S

Methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) is a 2-nitroimidazole derivative containing a

hydroxamate side chain designed to enhance the radiosensitization response of hypoxic cells. The possible
sensitization of tumor tissue by KIN-804 can be evaluated through investigation of the levels of the free radical
scavengers; namely, glutathione (GSH) and its complex enzyme system including glutathione reductase (GR)
and glutathione peroxidase (GSH-Px), as well as glucose-6-phosphate dehydrogenase (G-6-PD). Female albino
mice were inoculated with Ehrlich carcinoma in the thigh. Administration of KIN-804 (i.p. 80 mg/kg body
weight) was carried out 20 min before localized irradiation of 10 Gy. The data revealed that KIN-804
administration, followed or not by gamma irradiation, resulted in a significant decrease in GSH content in
tumor tissues associated with inhibition in GR and G-6-PD activities. Blood GSH-Px was enhanced in tumor
inoculated mice and the administration of KIN-804 returned it to the normal value. These changes were more
noticeable in tumor bearing mice exposed to both KIN-804 and irradiation.
PMID: 10706383

Studies of methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) 2: effect on certain

antioxidant enzyme systems in mice bearing Ehrlich ascites carcinoma.

Abu-Zeid M; Hori H; Nagasawa H; Uto Y; Inayama S

In order to decrease toxicity and/or increase radiosensitizing activity, a new 2-nitroimidazole derivative,
methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804), was synthesized to solve the problem of tumor
hypoxia. Evaluation of the efficiency of KIN-804 was carried out through studying the antioxidant enzyme
system: The superoxide dismutase (SOD), catalase and lipid peroxide levels provide a rough index of the
balance between free radical generation and scavenging. Female albino mice were inoculated with Ehrlich
ascites carcinoma (EAC) in the thigh. The administration of KIN-804 (i.p. 80 mg/kg body weight) was carried out
20 min before localized irradiation of 10 Gy. In general, the data revealed that KIN-804 administration,
followed or not by gamma irradiation, exerted significant inhibition of SOD and catalase activities accompanied
by a significant increase in lipid peroxide level in tumor-bearing mice.
PMID: 19459743

The role of Curcuma longa against doxorubicin (adriamycin)-induced toxicity in rats.

Mohamad RH; El-Bastawesy AM; Zekry ZK; Al-Mehdar HA; Al-Said MG; Aly SS; Sharawy SM; El-Merzabani MM

The major component, called curcumin, of turmeric (Curcuma longa L.) (Family Zingiberaceae) powder is
responsible for its biological actions. The present study aimed to prove the protective effect of turmeric
extract against doxorubicin (DOX)-induced cardiac, hepatic, and renal toxicity as evaluated in rats. Body weight
and urine volume of the animal groups under investigation were recorded daily throughout the experimental
period. Also, the cardiac, hepatic, and renal toxicities were determined by estimating the changes in serum
activities of the enzymes lactate dehydrogenase (LDH) and creatine kinase (CK), serum levels of alanine
aminotransferase, aspartate aminotransferase, nitric oxide, albumin, and calcium, and kidney and liver tissue
activities of superoxide dismutase and glutathione peroxidase, as well as the contents of glutathione and
malondialdehyde. Hyperlipidemia was also determined, and protein and albumin changes in urine were

27
estimated. Biochemical and histopathological findings demonstrate that turmeric extract has multiple
therapeutic activities that are beneficially protective, and it has an ameliorative effect against DOX-induced
cardiac toxicity and hepatotoxicity and blocks DOX-induced nephrosis. Similarly, turmeric extract inhibited the
DOX-induced increase in plasma cholesterol, LDH, and CK. The present findings conclude that the turmeric
extract has multiple therapeutic activities that block the cardiac, hepatic, and renal toxicities induced by DOX,
and it also possibly acts as a free radical scavenger.

Bladder Cancer studies

PMID: 10908847

A phase II study of gemcitabine plus cisplatin chemotherapy in advanced bilharzial bladder

carcinoma.

Khaled HM; Hamza MR; Mansour O; Gaafar R; Zaghloul MS

Bilharzial bladder cancer represents a distinct clinicopathological entity. To investigate whether gemcitabine-
cisplatin is also active against bladder cancer of bilharzial origin, we performed a phase II study of previously
untreated patients with stage III/IV disease. Standard eligibility criteria were used. Patients received
gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 and cisplatin (70 mg/m(2)) on day 2 of every 28-day cycle.
The 32 males and 5 females had a median age of 59 years (range: 29-81 years). Of 33 evaluable patients, 8
(24%) achieved complete responses, and 10 (30%) partial responses, for an overall response rate of 55%. 3
patients had minor responses. Responses were observed at all disease sites including lung and liver lesions.
Myelosuppression was significant but manageable. Non-haematological toxicity was limited mainly to nausea
and vomiting and raised liver enzymes. Thus, these data suggest that gemcitabine plus cisplatin induces high
response rates in patients with bilharzial bladder cancer with a moderate toxicity profile.
PMID: 10792158

A predictive model of survival after radical cystectomy for carcinoma of the bladder.

Ghoneim MA; El-Mekresh MM; Mokhtar AA; Gomha MA; El-Baz MA; El-Attar IA

To evaluate the effect of patient and tumour characteristics on the disease-free survival after radical
cystectomy for infiltrating bladder cancer, and to use these to help in constructing a meaningful prognostic
index.The disease-free survival was initially evaluated in 1026 patients (the reference series, 1969-1990). A
multivariate analysis showed that the tumour P stage, grade and nodal involvement were the only factors
which had an independent and significant association with survival. The computed regression coefficients were
then used to classify patients into one of four risk categories and the results then validated by applying the
model to a prospective test series (1991-1995).The 5-year disease-free survival of both groups was similar.
When the results for the risk categories of the reference series were compared with those of the test series,
there was no significant difference.This comprehensive prognostic model for the results of radical cystectomy
was validated and verified in a prospective group of patients. Adjuvant therapies are indicated for patients
with a high risk score.
PMID: 16018940

A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder

cancer.

Khaled H; El Hattab O; Moneim DA; Kassem HA; Morsi A; Sherif G; Darwish T; Gaafar R

Bladder cancer is still the most common solid tumor among adult males in Egypt because of the prevalence of
bilharzial infestation, especially in the countryside. In this prospective study, we have recorded the prognostic

28
factors for 180 patients with invasive bladder cancer for whom standard radical cystectomy had been
performed to develop a prognostic index (bladder prognostic index) that defines high risk patients who are
more vulnerable to disease relapse after surgery and who may benefit from additional therapy.The study was
performed between January 1997 and December 1999, in which 180 patients with histopathologically proved
invasive bladder cancer associated with bilharziasis underwent radical cystectomy or anterior pelvic
exenteration. After surgery, patients were regularly followed for a minimum of 2 years.Our patients included
141 males and 39 females. Squamous cell carcinoma was the most common type (53.3%), and most of the
tumors were grade II (61.1%). A total of 173 patients had their tumors operable, while 7 were inoperable. We
had 5 (2.8%) operative related mortalities. At 5 years postoperatively, free and overall survival rates for the
whole group of patients were 31.44%+/-5.9% and 32.5%+/-6.8%, respectively. Tumor pathologic stage, grade,
and nodal affection were the only significant factors with impact on survival (P=0.008, 0.051, and 0.004,
respectively). These 3 prognostic indexes were used to design a model to predict an individual patient's risk
factor for recurrence. Patients were then assigned to one of the 4 risk groups according to the score achieved
in this prognostic index (0=low risk, 1=intermediate risk, and 2 or 3=higher risk). These 4 risk groups had
distinctly different rates of disease-free survival, i.e., 91.7%, 53%, 13%, and 7% for low, intermediate, and
higher risk groups, respectively.Although this prognostic index appears to be of a significant clinical relevance,
it needs to be more validated on a larger number of patients, and it could be a surrogate variable for biologic
factors responsible for the heterogeneity of bladder cancer.
PMID: 21353794

A prospective randomized trial for postoperative vs. preoperative adjuvant radiotherapy

for muscle-invasive bladder cancer.

El-Monim HA; El-Baradie MM; Younis A; Ragab Y; Labib A; El-Attar I

PURPOSE: Although radical cystectomy is considered to be the primary treatment for muscle-invasive bladder
cancer, it is associated with unfavorable outcome. Local recurrence is still a major problem. Survival rates as
well as quality of live are far from being satisfactory. Postoperative radiotherapy is considered the standard
adjuvant treatment in the NCI-Egypt. This is a prospective randomized study conducted to compare
preoperative with postoperative radiotherapy as regard the survival and complication rates. PATIENTS AND
METHODS: In the period from May, 2004 to June 2007, 100 eligible patients were included into the study, 50
patients in each treatment arm. Pelvic irradiation was identical in both groups aiming at 50 Gy/25 Fs/5 wk.
Radical cystectomy was the standard surgery. Locoregional control, survival rates, and complications rates
were compared in both arms. RESULTS: Patients had a median follow-up period of 32 months (range 0-69
months). Patients had an average age of 54.8 ± 9.5 years with a male/female ratio 3:1. In the present study,
transitional cell carcinoma constitutes (51%), while squamous cell carcinoma was reported in 46% of cases.
Grades II and III pathology were 81% and 17%, respectively. Pathological stage P(2b) was encountered in 39.5%
of the patients followed by P(3)b (33.3%) and P(3)a (14.6%). For the preoperative group, the 3-year overall
survival, disease-free survival, locoregional control, and metastases-free survival rates were 53.4%, 47.4%,
89.3%, and 61.5%, respectively. The corresponding figures for the postoperative group were 51.8%, 34.1%,
80.6%, and 55.7% for the postoperative group. None of the patients had serious radiation reactions.
CONCLUSION: In our study, preoperative radiotherapy was almost equivalent to postoperative radiation
therapy as regard OS, DFS, as well as complication rates. Given the recent physical developments in radiation
therapy techniques and the biological rationale for treating the pelvis after cystectomy, adjuvant radiotherapy
should be re-evaluated world wide. Preoperative radiotherapy may re-emerge as a useful tool for adjuvant
treatment.
PMID: 20354750

A prospective, randomized, placebo-controlled trial of zoledronic acid in bony metastatic

bladder cancer.

Zaghloul MS; Boutrus R; El-Hossieny H; Kader YA; El-Attar I; Nazmy M

Zoledronic acid treatment reduces the incidence of skeletal-related events (SREs) in patients with bone
metastases from breast, lung, and urologic cancers including prostate and renal cancer. The aim of this study

29
was to evaluate the effect of zoledronic acid on SREs in patients with bone metastases from bladder
cancer.Patients with bone metastases from bladder cancer who were receiving palliative radiotherapy were
randomized to placebo or zoledronic acid (4 mg intravenous monthly) for 6 months.The patients (n = 40) were
evenly distributed between the two treatment groups, and the baseline demographics of the two groups were
similar. The follow-up varied from 8 to 65 weeks (median 24 weeks). Compared with patients receiving
placebo, those receiving zoledronic acid had a lower mean incidence of SREs (2.05 +/- 1.0 vs. 0.95 +/- 0.9,
respectively), and a larger proportion did not experience an on-study SRE (2 vs. 8 patients, respectively).
Zoledronic acid also prolonged the median time to first SRE compared with the placebo (16 vs. 8 weeks,
respectively). Multiple event analysis of SREs revealed that zoledronic acid decreased the risk of SRE
development by 59% (hazard ratio 0.413). Zoledronic acid also increased the 1-year survival rate compared
with placebo (36.3 +/- 11.2 vs. 0%, respectively). Zoledronic acid was generally well tolerated in our patient
population.Zoledronic acid therapy decreased the incidence of SREs and improved the 1-year survival rate of
patients with bone metastases from bladder cancer, potentially through its anticancer activity.
PMID: 2054316

A randomized pilot study of high-dose epirubicin as neoadjuvant chemotherapy in the

treatment of cancer of the bilharzial bladder.

Gad el Mawla N; Mansour MA; Eissa S; Ali NM; Elattar I; Hamza MR; Khaled H; Habboubi N; Magrath I; Elsebai
I

Seventy-one patients with T2 and T3 bladder cancer were randomized to receive either two courses of
epirubicin 120 mg/m2 i.v. push every 21 days pre-operatively, and four additional courses post-operatively
(group I = 34 patients), or radical surgery (group II = 37 patients). At a median follow-up of 24 months (range
22 months to 38 months) 25 patients from group I and 14 patients from group II are still alive and disease-free.
The estimated two-year disease-free survival percentages were 73.5 and 37.9%, respectively (P = 0.05). After
initial chemotherapy, resected specimens were subjected to histopathological study of chemotherapeutic
effects. Necrosis was detected in 95% of cases with squamous cell carcinoma and in 57.3% of cases with
transitional cell carcinoma. We conclude that the benefit which was obtained by pre-operative and post-
operative chemotherapy with epirubicin is promising and may represent a significant improvement in the
treatment of patients with carcinoma of the bilharzial bladder.
PMID: 20624129

Adjuvant and neoadjuvant radiotherapy for bladder cancer: revisited.

Zaghloul MS

To date, radical cystectomy has continued to be the treatment of choice for muscle-invasive bladder cancer. It
is associated with a 5-year disease-free survival rate ranging from 27-55%. This outcome is significantly worse
when reporting upon locally advanced cases. The independent prognostic factors include: tumor stage, grade,
pelvic nodal involvement and some other additional factors. Beside the higher reported incidence of distant
metastasis, local recurrence either alone or combined with systemic relapse has been shown to be
experienced by 23-50% of locally advanced patients - a rate that was much more frequent than previously
believed. Nonrandomized trials of preoperative radiotherapy have suggested improved survival rates.
However, only one out of the six randomized preoperative trials in the literature published in English has
proved to be significant. On the other hand, the only randomized trial and most retrospective studies dealing
with postoperative radiotherapy revealed a significant increase in disease-free survival. Late complications of
post operative radiotherapy, contrary to former belief, were acceptable and generally depended upon the
volume of the irradiated normal tissues and the radiotherapy techniques used. Most of these adjuvant or
neoadjuvant reports were performed in the 1970s and 1980s using conventional radiation techniques. Modern
radiotherapy, delivering higher doses to the tumor while saving a significant amount of the surrounding
normal structure, has not been rigorously tested. However, these techniques have already succeeded in
improving treatment end results in other pelvic tumors.
PMID: 16430078

30
 Adjuvant radiation therapy for muscle-invasive bladder cancer.

Zaghloul MS
PMID: 19034337

Bilharziasis and bladder cancer: a time trend analysis of 9843 patients.

Gouda I; Mokhtar N; Bilal D; El-Bolkainy T; El-Bolkainy NM

To explore any changes in bladder carcinoma during 37 years period, in regard to: its frequency, bilharzia
association, histological profile and demographic data.This is a retrospective study on 9843 patients treated at
the National Cancer Institute (NCI), Cairo University, during the years 1970-2007. Three groups were selected:
series (A) included 3212 patients during 1970-1974, series (B) 3988 patients during 1985-1989 and series (C)
2643 patients during 2003-2007. For statistical analysis, data of series (A), (B) and (C) were compared to
determine the significance of difference (p value 0.005).A significant decline of the relative frequency of
bladder cancer was observed from 27.63% in the old series to 11.7% in the recent series. Bilharzia association
dropped from 82.4% to 55.3%. There was a significant rise of transitional cell carcinomas from 16.0% to 65.8%,
becoming at present the most common tumor type, with a significant decrease in squamous cell carcinomas
from 75.9% to 28.4%. There was an increase in the median age of patients from 47.4 years to 60.5 years and a
decrease of male: female (M/F) ratio from 5.4 to 3.3.The decline in the relative frequency of bladder cancer is
associated with a decline in bilharzia egg positivity in the specimen and is probably related to better control of
bilharziasis in the rural population in Egypt. This was accompanied by a change in the histological profile of
tumors, with significant predominance of transitional cell carcinoma and an increase in the age of patients, a
pattern rather similar to that in western reports.
PMID: 11301380

Bladder cancer in Africa: update.

el-Mawla NG; el-Bolkainy MN; Khaled HM

Carcinoma of the bladder is the most prevalent cancer in Egypt and in most African countries. At the National
Cancer Institute (NCI), Cairo, it constitutes 30.3% of all cancers. The median age at diagnosis is 46 years, with a
male preponderance of 5:1. Whether in Egypt or other African countries such as Sudan, Kenya, Uganda, Gold
Coast, and Senegal, it is mostly of the squamous cell type, and arises in a background of schistosomiasis or
bilharziasis. Tumors are usually advanced at the time of presentation. Bladder carcinogenesis is probably
related to bacterial and human papilloma virus (HPV) infections, usually associated with bilharzial infestation.
Management is mainly surgery, with 5-year survival rates after radical cystectomy increasing from 35% in the
1970s to 48% in the 1990s. The addition of adjuvant and neoadjuvant radiotherapy and chemotherapy to
surgery since 1976 significantly improved both disease-free and overall survival rates. Molecular genetic
studies concerning potential prognostic markers, tumorigenesis, and tumor progression in bilharzial bladder
cancer are limited. However, a comprehensive detailed analysis of these factors is underway. Bilharzial bladder
cancer is a preventable malignant disease. Primary prevention could be possible if the parasite is eliminated
nationwide. Chemoprevention using retinoids or cyclooxygenase 2 (COX-2) inhibitors is a possible alternative.
Semin Oncol 28:174-178.
PMID: 17671529

Bone metastases in muscle-invasive bladder cancer.

Taher AN; Kotb MH

To address the necessity of incorporating isotopic bone scan in the routine staging work-up of muscle invasive
bladder cancer patients, we analyzed the data in our files to determine the incidence of bone metastasis in
such patients. The rate of subsequent development of bone metastasis along the natural history of the disease
was also investigated.A total of 179 files of consecutive bladder cancer patients who presented to the National

31
Cancer Institute, Cairo University, between January 2000 and December 2001 were reviewed to check the
percentage of positive bone scans on presentation and to check the subsequent development of distant
metastases and bone metastasis in these patients' records.Amongst the 179 patients, 26 (14.5%) had bone
metastasis on presentation, a finding that showed a statistically significant correlation with the increasing
depth of muscle invasion; 61.5% of the metastatic cases had deep muscle invasion,19.2% had superficial
muscle invasion and there was no muscle invasion in 7.7% (p=0.000). Transitional cell carcinoma was the
pathology in 92.3% of those patients, while only 7.7% had squamous cell carcinoma (p=0.036). The cumulative
3-year incidence of bone-metastasis in the non metastatic patients after treatment mounted to 19.4 +/- 4.4%.
The cumulative 3-year bone metastasis incidence in the 153 patients was higher with increasing clinical stage;
8.4 +/- 8% for c-stage 2 and 49.1 +/- 18.5% for c-stage 4 (p=0.046). As for the p-category of the tumor in the
130 patients who underwent operation, the incidence increased with higher p-stages (p=0.006). Though pelvic
nodal involvement was not associated with statistically significant increase in the incidence of bone
metastases, yet when incorporated as one of the 3 risk factors (grade>3, p (3) 4a and LN positive at surgery)
according to which patients were grouped, there was a statistically significant difference in the incidence
between patients with no risk factors, only 1 and 2 or more factors (p=0.021).Meticulous search for bone
metastasis alone or as a component of distant failure in the newly diagnosed bladder cancer patients is crucial
to offer them the proper management and avoid undue radical surgical procedures. Thus bone scan is
suggested to be performed routinely in patients with evidence of muscle invasion.
PMID: 3147281

Carcinoma of the urinary bladder associated with schistosomiasis in Egypt: the possible
causal relationship.

Tawfik HN

Carcinoma of the urinary bladder is the most common malignancy in Egyptians. At the National Cancer
Institute in Cairo, it accounts for 27.6% of all cancers--38.5% of cancers in the male and 11.3% in the female.
This very high frequency is attributed to underlying schistosomiasis. The infection can lead to malignancy
through local tissue damage, mechanical irritation, bilharzial toxins or through secondary bacterial infection.
Bacterial products include nitrate reductase capable of synthesizing nitrosoamines and beta glucuronidase
enzymes, active at pH 7. Through liver involvement and dysfunction, tryptophan metabolism is disturbed, with
the excretion of carcinogenic metabolites. Vitamin A deficiency is responsible for the squamous metaplasia
and the high frequency of squamous cell carcinoma observed in the bladder. The characteristic clinico-
pathological features of cancer of the urinary bladder are outlined, mainly the occurrence at a young age, the
male predominance, especially farmers, and the high association with schistosomiasis. The tumors are often
first seen in an advanced stage, arising from the posterior bladder wall and vault. The trigone is only affected
in 8.5% of the cases. Histologically, squamous cell carcinomas of low grade are the most frequent cell type.
Lymph node involvement is low in spite of the advanced stage of the tumor. Therefore, the results of radical
surgery are encouraging. The results of a special study correlating the above parameters with the intensity of
ova deposition are presented. Patients with heavy infection at a slightly earlier age but other tumor
parameters the same are similar to those of egg-negative cases. This study indicates that other factors also
play a role in the induction of tumors that are enhanced by the schistosomal infection. In Fayoum Province,
schistosomiasis is decreasing while bladder cancer is increasing. Urine cytology as a screening tool is effective
in detecting early bladder cancer. Studies are now in progress to detect tumor associated antigens in sera and
urine of patients.
PMID: 2706136

Chemotherapy in invasive carcinoma of the bladder. A review of phase II trials in Egypt.

Gad-el-Mawla N; Hamza MR; Zikri ZK; el-Serafi M; el-Khodary A; Khaled H; Abdel-Wareth A

Since 1976, a series of phase II studies with screening of various chemotherapeutic agents in invasive bladder
cancer have been conducted at the National Cancer Institute, Cairo. Different drugs were screened, one by
one, in groups of 20-25 patients with inoperable, metastatic, or recurrent carcinomas. Evaluation was done by
clinical bimanual examination, radiography, sonography, cystoscopy, and urine cytology. In these trials

32
bleomycin and doxorubicin were ineffective. Tenoposide, 5-fluorouracil, methotrexate, and cisplatin had
minimal or moderate effect (response rates 4-16%). More pronounced effect was found for dibromodulcitol,
cyclophosphamide, pentamethylmelamine, etoposide, hexamethylmelamine, ifosfamide, vindesine,
vincristine, and epidoxorubicin (response rates 18-60%). Some complete responders remained in response for
a period of 3-7 years. Drugs seemed to be more effective in metastatic than in local lesions.
PMID: 10526537

Chromosomal aberrations in Bilharzial bladder cancer as detected by fluorescence in situ

hybridization.

Aly MS; Khaled HM

Cancer of the bladder is a frequent malignancy in Egypt and other developing countries in which bladder
infection with the parasite Schistosoma haematobium is common. Several epidemiological, histopathological,
and clinical characteristics of cancer of the Bilharzial bladder suggest that it is distinct from bladder cancer
seen in other places in the world. No numerical aberrations of chromosomes that might be specific for
Bilharzial bladder carcinoma have been established. In this study, we used fluorescence in situ hybridization
(FISH) with centromere-specific probes for chromosomes 3, 4, 7, 8, 9, 10, 11, 16, and 17 to detect numerical
aberrations of these chromosomes in frozen-stored samples of 31 Egyptian patients affected with Bilharzial
carcinoma. Among 5 types of chromosomes examined, imbalance was observed; the most common imbalance
was a loss of chromosome 9 (48.4%), with numerical aberration of chromosome 17 being the second most-
frequent anomaly (19.4%). The presence of such anomalies, especially losses of chromosome 9, are associated
with a younger age group of patients, as well as with a lower grade tumor and negative pelvic node
involvement by the disease. Fluorescence in situ hybridization analysis thus proved to be a useful method for
detecting numerical aberrations of individual chromosomes, with application to touch preparations of frozen-
stored tissue having the advantage of exact sampling of cancer foci. This result also suggests that the
mechanism of genetic progression of bladder cancer is independent of its etiology.
PMID: 15610858

Chromosomal aberrations in Cis and Ta bilharzial bladder cancer: a theory of

pathogenesis.

Khaled HM; Aly MS; Mokhtar N

Bladder cancer manifests many different forms ranging from superficial to aggressive muscle invasive stages,
which suggests that various genetic alterations are involved. Several attempts have been made to establish
correlations between specific genetic alterations and various stages of the disease. At the National Cancer
Institute (NCI), Cairo, bladder cancer constitutes 30.3% of all cancers. Bladder cancer observed among
Egyptians has a clinico-pathological profile that differs from transitional cell carcinoma (TCC) seen in the
western world.We used fluorescence in situ hybridization to detect numerical chromosome changes in 25
patients presenting with carcinoma in situ and Ta lesions. Twenty-four cases had transitional cell carcinoma
and one case had squamous cell carcinoma.Five out of 24 TCC cases had diploid chromosome count with all
the probes. Numerical chromosome aberrations were detected in 19 cases (79%). In eight cases, a loss of
chromosome 9 was observed. In one case, an additional loss of chromosome 17 was detected. One case
demonstrated a loss of chromosome 17, whereas another three cases showed a gain of chromosome 7. Loss of
chromosome Y was observed in nine of the 22 male cases studied (40.9%). The only case with SCC had normal
diploid chromosome count with all the probes used.When the genetic basis of bilharzial related bladder cancer
is fully understood, new diagnostic and therapeutic strategies will be developed, which in turn may promote
better clinical management by pathologists and urologists. A theory of bilharzial related bladder cancer
pathogenesis is suggested.
PMID: 19171060

33
Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder
cancer.

Khaled HM; Bahnassy AA; Raafat AA; Zekri AR; Madboul MS; Mokhtar NM

Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological
prognostic markers. We assessed the correlation between nm23-H1, Rb, EGFR and p53 in relation to the
clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC).nm23-H1, Rb, EGFR and
p53 expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-
PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the
overall survival (OS) rate.Overexpression of EGFR and p53 proteins was detected in 66.1% and 35.6%;
respectively. Loss of nm23-H1and Rb proteins was detected in 42.4% and 57.6%; respectively. Increased EGFR
and loss of nm23-H1 RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant
correlation between p53 and EGFR overexpression (p < 0.0001), nm23 loss (protein and RNA), lymph node
status (p < 0.0001); between the incidence of local recurrence and EGFR RNA overexpression (p= 0.003) as well
as between the incidence of metastasis and altered Rb expression (p = 0.026), p53 overexpression (p < 0.0001)
and mutation (p = 0.04). Advanced disease stage correlated significantly with increased EGFR (protein and
RNA) (p = 0.003 & 0.01), reduced nm23-H1 RNA (p = 0.02), altered Rb (p = 0.023), and p53 overexpression (p =
0.004). OS rates correlated significantly, in univariate analysis, with p53 overexpression (p = 0.011), increased
EGFR (protein and RNA, p = 0.034&0.031), nm23-H1 RNA loss (p = 0.021) and aberrations of > or = 2 genes.
However, multivariate analysis showed that only high EGFR overexpression, metastatic recurrence, high tumor
grade and the combination of > or = 2 affected markers were independent prognostic factors.nm23-H1, EGFR
and p53 could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological
prognostic factors, a combination of these markers (> or = 2) has synergistic effects in stratifying patients into
variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease
progression and death.
PMID: 8905036

Combination chemotherapy for advanced bilharzial bladder carcinoma.

Khaled HM; Gad el-Mawla N; el-Said A; Hamza MR; Gaafar R; el-Attar I; Abu Rabia A; Magrath I

Carcinoma of the bilharzial bladder, the most common cancer in Egyptian patients has been, until recently,
largely treated by surgery. We have studied the activity of a series of single agents in phase II trials and
identified a number of active agents. Here we report the results of a trial in which therapeutic combinations of
the most active agents were administered in alternating cycles to patients who had never received
chemotherapy.The study included 30 patients with histologically proven inoperable (20), recurrent (5, 2 of
whom subsequently developed metastases), or metastatic disease (5). There were 27 males and 3 females,
with a median age of 48.5 years (range 29-65 years). Fourteen patients had squamous cell carcinoma, 12 had
transitional cell carcinoma, 2 had adenocarcinoma, and the remaining 2 had undifferentiated carcinoma.
Chemotherapy consisted of epidoxorubicin (120 mg/sqm i.v. d1) and vincristine (1.4 mg/sqm i.v., days 1 and 8)
alternating with etoposide (100 mg/sqm i.v. infusion over 1 hour, days 1 to 5) and ifosfamide (1800 mg/sqm
i.v. infusion over 2 hours, days 1 to 5). Mesna was given as a uroprotector at 40% of the ifosfamide dose at 0,
4, and 8 hours after the ifosfamide infusion. Courses were repeated every 3-4 weeks.Among the 22 evaluable
patients, 8 (36.5%) had a partial and one (4.5%), a complete response, giving a response rate of 46%. Three
more patients had responses that were less than a partial remission, and 6 patients showed disease
stabilisation on chemotherapy. Toxicities were tolerable and consisted mainly of myelosuppression. Results
were further analysed in relation to pathologic subtype, disease status at the start of chemotherapy, and the
delivered dose intensity. No relationship was found between any of these parameters and response to
therapy.Advanced bilharzial bladder cancer is relatively sensitive to combination chemotherapy, but complete
remission and prolonged survival is rare in this subgroup of patients with advanced disease. Further studies
will be needed to determine the relative efficacy of single agents and drug combinations.

34
PMID: 16799657

Comparative study of NMP-22, telomerase, and BTA in the detection of bladder cancer.

Abd El Gawad IA; Moussa HS; Nasr MI; El Gemae EH; Masooud AM; Ibrahim IK; El Hifnawy NM

The diagnostic efficacy of Nuclear Matrix Protein-22 (NMP-22), bladder tumor antigen (BTA TRAK), and
telomerase activity was evaluated in urine in a trial to assess their value in the detection of bladder cancer and
to compare it to that of routine urine cytology.The study included 46 newly diagnosed bladder cancer patients,
diagnosed by cystoscopy and histopathological typing, in addition to 20 patients with benign bladder lesions
and 20 healthy age and sex matched volunteers as a control group. Fifty percent of the cancer patients (23/46)
had proven bilharzial history. Most patients (27/46) had transitional cell carcinoma (TCC), 17/46 had squamous
cell carcinoma (SCC), while only 2 patients had adenocarcinoma. A single freshly voided urine sample
(approximately 100ml) was collected from each patient and control subject and aliquoted for each test. All
assays were conducted according to the manufacturer's guidelines and the results were compared to those of
urine cytology.The optimal cutoffs for NMP-22, BTA and telomerase activity as calculated by ROC curves were
12.1 U/ml, 78 U/ml, 0.48 (Ratio) respectively. The levels of the three parameters were significantly higher in
the malignant group compared to either the benign group or normal controls, (p<0.001) and the positive rates
were also higher in the malignant group for all 3 parameters. The overall sensitivity of urine cytology, NMP-22,
BTA and telomerase was 54.3%, 91.3%, 100% and 80.4% respectively. For bilharzial cancer bladder respective
sensitivities were 69.6%, 95.6%, 100% and 73.9%, while for nonbilharzial cancer bladder the respective
sensitivities were 39.1%, 87%, 100% and 87%. The overall specificities with urine cytology, NMP-22, BTA and
telomerase was 100%, 87.5%, 92.5% and 95.0%, respectively. Combined sensitivity of voided urine cytology
with one or more of the 3 biomarkers, or the use of these biomarkers in double or triple combinations gave
higher positivity than each biomarker alone.BTA showed the highest sensitivity in all the studied parameters in
the bladder cancer group, bilharzial bladder cancer subgroup, and non bilharzial bladder subgroup, (100%),
while the highest specificity was recorded with urine cytology (100%), followed by telomerase (95%), then BTA
(92.5%), and lastly NMP- 22 (87.5%). Use of markers in combination with cytology, or in a panel, improved the
sensitivity, and specificity.
PMID: 20571597

Delayed Cystectomy for T1G3 Transitional Cell Carcinoma (TCC) of the Urinary Bladder,
NCI Retrospective Case Series.

Fakhr I; El-Hossieny H; Salama A

We aim to evaluate the National Cancer Institute (NCI) treatment protocol and its outcome regarding
recurrence, progression and survival in patients with T1G3 urinary bladder transitional cell carcinoma.In a
retrospective study, between January 2001 and December 2007, all 34 patients with T1G3 bladder transitional
cell carcinoma (TCC), after complete transurethral resection (TURBT), received intravesical BCG as adjuvant
therapy. A conservative approach was adopted, whereby those with superficial recurrences were eligible to
TURBT, with delayed cystectomy for progression to muscle invasion. Overall, recurrence, and progression-free
survival were analyzed.Thirty-three patients were included, 29 were males and 4 were females. The mean age
was 61 years (range 35-89 years). Final analysis was made at median follow-up of 15 months (Range of 3-68
months, mean 18 months) for survival. Eleven (33.3%) patients had multifocal tumors. Associated
schistosomiasis was present in 12 (36.6%) patients. Twenty-two (66.67%) patients showed recurrence. Eleven
out of these 22 (50.0%) patients progressed to muscle invasion and underwent radical cystectomy. Ten out of
34 (30.3%) patients received postcystectomy radiotherapy. Two (20.0%) of them, were staged as TNM stage II,
6 (60.0%) as TNM stage III and 2 (20.0%) patients were TNM stage IV. Eight (72.7%) of these 11 patients had
post-cystectomy radiotherapy alone; while the 2 (6.0%) other patients with stage IV had adjuvant concomitant
Cisplatin and Gemcitabine chemotherapy. Five (14%) patients of those cystectomy patients died of TCC. Three
(60%) patients died from metastatic disease (to lung, liver and bone), one patient died from advanced
locoregional disease and another patient died from postoperative complications. Among those patients who
received radiotherapy alone, 62.5% are alive. Although, we report a biologically more aggressive behavior of
T1G3 than that reported by some authors, for this conservative approach, the overall survival (OS) was (84.4%)

35
and the recurrence-free survival (RFS) was (41.3%), at 18 months; which are comparable to those reported in
the literature for the delayed cystectomy approach.Adjuvant intravesical therapy with BCG with repeated
cystoscopies, and delayed radical cystectomy until progression to the invasive disease carries a significant risk
of mortality from invasive disease. This treatment policy may be acceptable for T1G3 bladder TCC, without
concomitant carcinoma in situ (CIS), who don't recur after intravesical BCG, however, patients who progress to
invasive disease may skip stage II disease and present with stage III or IV, with consequent poor survival.
Therefore, due to the aggressive biologic behavior of T1G3 cancer, a determination of a cutoff number for
recurrence(s) or better evaluation parameters are needed, to proceed with cystectomy without awaiting
muscle invasion. KEY WORDS: Superficial bladder cancer - T1G3 TCC - Delayed cystectomy - BCG.
PMID: 16430058

Descriptive statistics of urogenital cancer in Egypt and Asian area.

Ibrahim AS
PMID: 8616767

Distant metastasis from bilharzial bladder cancer.

Zaghloul MS

Distant metastasis is rarely described among bilharzial bladder cancer patients. However, with improved 5-
year survival rates following adjuvant local therapy, distant metastasis is now reported with increasing
frequency.Three-hundred-fifty-seven bilharzial bladder cancer patients were treated at the National Cancer
Institute in Cairo, Egypt, during the period 1981-1990. They were treated with either cystectomy alone,
cystectomy preceded by a short course of preoperative radiotherapy (2000 cGy/5 fractions/1 week), or
cystectomy followed by postoperative irradiation (5000 cGy/25 fractions/5 weeks or 3750 cGy/30 fractions/2
weeks). These patients were retrospectively analyzed.The overall 5-year actuarial rate of distant metastasis
was 23% (95% confidence interval, 21-25%), which was essentially the same in the 3 therapeutic groups. Both
univariate and multivariate analyses revealed that the independent risk factors for distant metastasis were
pelvic lymph node involvement (P = 0.005), pathologic stage (P = 0.004), and histopathologic grade (P = 0.05).
Histologic type and local pelvic recurrence appeared in the univariate analysis as working risk factors; however,
they were proven by multivariate analysis to be dependent on other risk factors. Patients who had none of the
independent risk factors had a lower rate of distant metastasis (II%) and a high local control rate (88%). Those
who had more than one risk factor had high distant metastasis rate (51%) and low local control rate (41%),
regardless of the therapeutic modality used. The identified independent risk factors determined both the
distant metastasis and the local control rates.Unlike previous reports, this rigorous study of distant metastasis
in bilharzial bladder cancer revealed an occurrence rate of 23%. This high rate was associated with pelvic
lymph node involvement, pathologic stage, and histopathologic grade. Histologic type, local pelvic recurrence,
or the addition of pre- or post-operative radiotherapy proved not to be independent risk factors.
PMID: 11173945

Evaluation of the BTA tests for the detection of bilharzial related bladder cancer: the Cairo
experience.

Khaled HM; Abdel-Salam I; Abdel-Gawad M; Metwally A; El-Demerdash S; El-Didi M; Morsi A; Ishak L

To evaluate the clinical performance of the BTA stat test and the BTA TRAK assay in the diagnosis of bilharzia-
related bladder cancer and to calculate a new 'Egyptian' cut-off value for the BTA TRAK (quantitative)
assay.Urine samples of 149 individuals were tested for the presence of the human complement factor H-
related protein, the antigen detected by the BTA stat and BTA TRAK tests. The group consisted of 53 healthy
volunteers, 20 patients with active bilharziasis, 11 patients with other urologic disorders including prostate
cancer, and 65 patients with histologically proven bladder cancer. All samples were obtained prior to surgery
or therapy.The BTA stat test was positive in 64 of 65 samples from patients with bladder cancer, for an overall
sensitivity of 99%. With a BTA TRAK assay cut-off of 60 U/ml (set at 97% specificity in the healthy population),

36
the sensitivity of the TRAK assay was 94%. There was no statistically significant difference between the
sensitivities of the two BTA tests in patients diagnosed with squamous cell carcinoma and those with
transitional cell carcinoma. The overall specificity of the BTA stat test was 67% ranging from 15% in patients
with bilharziasis to 94% in healthy volunteers. The overall specificity of the TRAK assay was 66%, again with
negative results in 15% of the patients with bilharziasis.The BTA stat test and TRAK tests are extremely
sensitive in the detection of bladder cancer in the Egyptian population. Positive results (85%) are also observed
in patients with active bilharziasis, which often leads to bladder cancer. Longitudinal follow-up of these
positive cases is needed to determine whether these positive results are false or predictive of bladder cancer.
PMID: 21860467

Evaluation of the Value of Combined Urine Cytology and Cystoscopy for Follow-up of
Superficial Transitional Cell Carcinoma of the Urinary Bladder.

Tahoun NS; Abdel Maksoud AM; Mohamed DB

Cystoscopic biopsy is the most accurate technique used to assess the efficacy of treatment and to detect
recurrence of superficial TCC of urinary bladder. Implementation of voided urine cytology to detect tumor cells
in urine samples may represent an additional tool. The aims of this study are: (1) To estimate the reliability of
combined cystoscopy and urine cytology examination in the follow-up of cases of superficial urinary bladder
carcinoma, which might help to restrict cystoscopic biopsies for these cases with its morbidity and cost, (2) To
discuss the diagnostic pitfalls of cytologic examination in these cases.This is a prospective study, on 93 patients
with superficial TCC of urinary bladder who were initially treated by complete TUR with or without adjuvant
intravesical therapy with Bacillus Calmette - Guerin (BCG) (120mg÷instillation) every week for 6 weeks.
Cystoscopic findings, urine cytology and histologic results of cystoscopic biopsies were assessed.By histologic
examination, 41 (44%) cases were recurrent TCC and 52 (56%) were reported as negative for recurrence. By
cystoscopic examination there were 36 positive cases, 4 of them were false positive. Out of the 57 negative
cases for recurrence cystoscopically, 9 were histologically positive and were considered as false negative
results. By cytology, 28 cases were positive, 3 were false positive, and 65 were negative for recurrence, 16 of
them were false negative. Most of false negative cases were low grade TCC. Sensitivity of cytology and
cystoscopy in the detection of recurrence was 61% and 78% respectively. When the two examinations were
combined, sensitivity was 100%, and specificity was 92.3%.For follow-up of superficial bladder carcinoma, the
combination of negative cystoscopic findings and negative urine cytology may replace routine biopsies with
their morbidity and cost. KEY WORDS: Superficial bladder carcinoma - Cytology and Cystoscopy - Follow-up.
PMID: 21492915

Experience with ureteroenteric strictures after radical cystectomy and diversion: open
surgical revision.

Nassar OA; Alsafa ME

To evaluate the long term results of the treatment of benign ureteroenteric strictures as a serious
complication after urinary diversion and to highlight on the precautions for the active intervention. The
outcomes of endoureteral and open surgical revisions in our patients are described.Of 658 patients who had
undergone radical cystectomy for bladder cancer from 1999 to 2009, 58 had developed benign stricture. The
diversions used in this subgroup were orthotopic neobladder (53.4%), ileal conduit (27.6%), and ureterocolic
(19%). The median interval to the diagnosis was 6 months, and 63.8% were on the left side. Endouretral
interventions (dilation and stent or endoureterotomy) were the initial treatment in 37 patients. Thirty-two
patients including patients who failed endoluminal interventions and patients with bilateral strictures
underwent open surgery. Success was defined as radiologic improvement and the absence of flank pain,
infection, or the need for a ureteral stent or nephrostomy tube.Endoscopic intervention was successful in 19
(51.3%) of 37 patients, principally those with strictures <1 cm with no difference between side, diversion type,
or implantation technique. A total of 32 patients underwent open stricture resection and repair by direct
implantation or tissue interposition to bridge long defects (6 Boari flaps and 7 ileal segments). At a median
follow-up of 47 months, 25 patients had long-term success (78%) and 36 (83.7%) of 43 repaired units had
improvement. Improvement was superior for right-sided strictures compared with left-sided strictures (100%

37
vs 75.8%) and for neobladder compared with other diversions (90% vs 69%). Both anastomotic and ureteral
strictures were repaired with equivalent results (87.5% vs 82.8%).Although endouretral procedures are viable
treatment alternatives, open surgical revision is the preferred long-term definitive treatment. Bilateral and
long left-sided strictures >1 cm long are indications for early open surgery.
PMID: 15716994

Extended lymphadenectomy to the lower paraaortic nodes during radical cystectomy.

El-Shazli S; Anwar H; Ramzy S; Al-Didi M

Evaluation of the diagnostic, prognostic and possible therapeutic role of extended lymphadenectomy to lower
para-aortic area in operable bladder cancer patients.One hundred and nine patients were subjected to the
procedure in the National Cancer Institute of Cairo University, and in Minea Oncology Center, Ministry of
Health by the same group of surgeons, during the period from September 2000 to March 2003. The lymph
nodes dissected were labeled to the following groups: perivesical, lymph node of Cloquet, external iliac,
internal iliac and obturator, common iliac and paraaortic groups both right and left. These nodes were
subjected with the primary tumor to serial sectioning for histopathologic examination. Preoperatively, all
patients were subjected to routine laboratory investigations. In addition to cystoscopy, biopsy and histologic
examination, bone scan, chest X-ray and computerized tomography with I.V. contrast examination for the
abdomen and pelvis were done for clinical staging of the disease.34.4% of the node positive patients have
been found to harbor the disease in the para-arotic lymph nodes above the common iliac bifurcation.
Obturator, external iliac, internal iliac, para-aortic, common iliac, perivesical and lymph node of Cloquet are
the higher incidence groups of positive lymph nodes sequentially. The clinical and C.T. staging are inaccurate
methods of diagnosis due to high overall error up to 70.6% of patients. There is no higher incidence of
morbidity, mortality, operative time or intraoperative blood loss related to the addition of lower para-arotic
dissection to the routine radical cystectomy.Extension of lymphadenectomy to include the lower para-arotic
area in addition to the standard pelvic lymphadenectomy during radical cystectomy for bladder cancer is a
more accurate technique for diagnosis and staging of bladder cancer patients and it may help in determining
the benefit of adjuvant chemotherapy +/- radiotherapy. By itself, it gives a better recurrence-free survival rate
without adding higher morbidity or mortality than the standard pelvic lymphadenectomy.
PMID: 11693804

Human papilloma virus infection and overexpression of p53 protein in bilharzial bladder
cancer.

Khaled HM; Raafat A; Mokhtar N; Zekri AR; Gaballah H

An association between human papilloma virus (HPV) and bladder cancer has been reported. However, the
role of HPV in bilharzial bladder cancer and its prevalence have not yet been clarified.We investigated 50 cases
for HPV types 16/18 by in situ hybridization. Also, p53 protein expression by immunohistochemistry was
evaluated in 41 of the 50 cases, with correlation of these factors to clinicopathologic parameters and tumor
relapse after primary treatment.HPV was detected in 46% of Egyptian bladder carcinomas (23/50 cases).
Positivity was 47.8% for squamous cell carcinoma and 36.4% for transitional cell carcinoma. There was a
possible viral-bilharzial association as 52.8% of Bilharzial cases, whereas only 12.5% of non-Bilharzial cases
were HPV positive (P <0.05). P53 protein was found in 19/41 (46.3%) cases. There was a concordance between
HPV and p53 in 58.5% of cases. Neither factor was related to tumor recurrence after primary treatment.HPV
may thus be implicated in the etiology of bilharzial bladder cancer, but a definite causal relationship remains to
be demonstrated. HPV together with p53 alterations work in synergy to accelerate the carcinogenic process, as
there was concordance in the results of both parameters in 24/41 (58.5%) cases.
PMID: 16536777

38
 Ileocaecal vs ileal neobladder after radical cystectomy in patients with bladder cancer: a
comparative study.

Khafagy M; Shaheed FA; Moneim TA

To compare an ileocaecal orthotopic bladder, (which has been the standard procedure in Egypt for >30 years)
with the ileal neobladder, as there is no ideal continent orthotopic bladder replacement for patients after
cystectomy for bladder cancer.Between June 1999 and December 2001, 60 patients with invasive bladder
cancer were randomized into two groups. Group A comprised 29 patients who had radical cystectomy and
reconstruction with an ileal neobladder (median age 50 years, 27 men and two women) and group B included
31 who had an ileocaecal bladder substitution after radical cystectomy (median age 51 years, 28 men and
three women).The complication rate after surgery in group A was 17%, with two deaths, one from acute
myocardial infarction and the other from haematemesis. In group B, the complication rate was 13%, with two
deaths, one from a massive pulmonary embolism and the other from liver cell failure. Daytime continence was
achieved in 93% of patients in group A and 90% in group B. The mean (sd) postvoid residual urine volume was
larger in group A than group B, at 90 (72) vs 12 (20) mL. Acidosis and hyponatraemia were evident in the
patients in group A but in none in group B (P < 0.05). The pelvicalyceal systems were preserved in 85% of
patients in group A and 93% in group B during the 2-year follow-up. The mean (sd) renal cortical thickness was
less in group A than in group B, at 1.8 (0.5) and 1.9 (0.2) cm, respectively. Although the cystometric capacity
was greater and the basal pressure less in group A than B, these were not reflected in the degree of diurnal
and nocturnal continence or back pressure on the renal units.Continence in both pouches was similar but the
renal units were preserved better in the ileocaecal than in the ileal neobladder. Residual urine volume was
greater in the ileal neobladder, with its potential complications of infection and stone formation, and acidosis
was more evident.
PMID: 21554043

Joint genitourinary cancer symposium between Egyptian and American centers.

Zaghloul MS

A joint symposium between Mansoura and Cleveland Universities, and the University of California, San
Francisco (CA, USA) was held by the Egyptian Cancer Society in Mansoura, Egypt. The Symposium extensively
discussed two topics: prostate and bladder cancer. The experiences of American and Egyptian scientists were
shared in a trial to increase understanding, improve management, increase treatment outcome and decrease
morbidity. Comparisons between treatment policies, management techniques and survival end results in Egypt
and the USA, as well as internationally, were performed in both bladder and prostate cancer in order to
determine the best policies for their management.
PMID: 21503002

Long term complications following ileal conduit urinary diversion after radical cystectomy.

Khalil el-SA

To study the long term complications of ileal conduit urinary diversion in 36 patients with invasive urinary
bladder cancer who lived more than 5 years after surgery.A retrospective study included 36 long term
survivors (survival 5 years or greater) with invasive bladder cancer who did radical cystectomy or anterior
pelvic excentration with ileal conduit urinary diversion at the National Cancer Institute, Cairo University before
January 2004.A total of 36 patients, 28 Males and 8 females, with median age at surgery of 62 years.
Complications developed in 22 (61%) patients and surgical re-intervention was needed, in 14 patients (39%).
Stoma related complications developed in 7 (19%) patients, bowel related complications developed in 4 (11%),
urinary tract infection and pyelonephritis was observed in 9 (25%) patients, conduit/ureteral anastomosis
related complications developed in 5 (14%) patients, urolithiasis developed in 4 (11%) patients. Renal function

39
deterioration (morphological and functional) was observed in 9 (25%) patients, nephrectomy was required in 2
patients, hemodialysis was required in 1 patient, and 1 patient had persistent hyperchloremic acidosis.Long
term follow-up for patients with ileal conduit urinary diversion shows high complication and high surgical re-
intervention rates following this technique. Longer follow-up period for 20 or more years is needed for all
urinary diversion techniques to prove either the ileal conduit will remain the gold standard for urinary
diversion or other newly developed techniques will take its place. KEY WORDS: Urinary diversion - Treatment
outcome - Renal function tests - Postoperative complications.
PMID: 16414487

Long-term results of primary adenocarcinoma of the urinary bladder: a report on 192

patients.

Zaghloul MS; Nouh A; Nazmy M; Ramzy S; Zaghloul AS; Sedira MA; Khalil E

To evaluate the clinical presentation and treatment end results of primary adenocarcinoma of the urinary
bladder, and to determine the significant independent prognostic factors that determine this outcome.Of 3659
patients who underwent cystectomy, 192 had adenocarcinoma of the urinary bladder, with a relative
frequency of 5.2%. Most of these patients (68.2%) presented in late stages (P3 + P4). The incidence of pelvic
lymph nodes involvement was 25.5%. Mucinous adenocarcinoma was reported in 28 patients (14.6%),
papillary in 20 (10.4%), signet ring in 14 (7.3%), while not otherwise specified was reported in 130 (67.7%) in
the cystectomy specimens.Mucinous and signet-ring histologic subtypes showed increased frequency of high
stages and high grades, and more nodal involvement than the papillary and not otherwise specified. All
patients were treated with radical cystectomy and pelvic lymphadenectomy with (69 patients) or without (123)
postoperative radiotherapy. The 5-year disease-free survival rate was 46 +/- 4% for all patients with
adenocarcinoma. Postoperative radiotherapy improved the disease-free survival significantly. The 5-year
disease-free survival rate for the postoperative radiotherapy group was 61 +/- 6% compared to 37 +/- 5% for
the cystectomy alone group (P = 0.002). Local control rate was significantly improved from 53 +/- 7% for
cystectomy alone to 96 +/- 3% for postoperative radiotherapy patients (P = 0.00001). Distant metastases were
the leading cause of death in the postoperative radiotherapy group.Within the limitations provided by
retrospective studies, it could be concluded that postoperative radiotherapy improved the disease-free
survival through its effect on local control. The disease-free survival independent prognostic variables were
tumor stage, postoperative radiotherapy, nodal involvement, and adenocarcinoma subclassification. These
factors, except the adeno-subclassification, were also found to determine the local control rate. On the other
hand, the independent prognostic factors for distant metastasis were lymph nodal involvement, stage, and
adeno-subclassification.
PMID: 21503004

Modified le bag pouch after radical cystectomy: continence, urodynamic results and
morbidity.

Nassar OA

To revaluate ileocolonic pouch for orthotopic neobladder reconstruction, a cohort of patients with bladder
cancer was selected to undergo radical cystectomy and modified Le Bag pouch. Evaluation concentrates on
continence and associated morbidity observed on close follow-up.A total of 37 patients including 16 females
with T2-3 bladder cancer (19 transitional, 15 squamous and 3 adenocarcinoma) were treated by radical
cystectomy and totally detubularized ileocolic neobladder. Post operative morbidity, continence and
urodynamic studies were evaluated. Mean time to have full daytime continence was tested against age,
gender, postoperative complications, technique of pouch creation either stapler or hand suture and adjuvant
irradiation.Cystometry 12 months post surgery showed 493 ml median capacity with basal and maximum
reservoir median pressures of 16 and 38cmH2O respectively. Uroflowmetry had maximum voiding volume of
370ml, voiding time 45s and maximum flow rate of 11.6ml/s. Within the first 2 months post operative 44%
were continent by day, 33% by night and 67% had stress incontinence. By 12 months post surgery 89% were
continent by day, 73% by night and 27% had stress incontinence. Two years post surgery 94% were continent
by day and 81% had complete day and night control of urine. Urinary leakage was the most frequent early

40
complication (10.8%). Late complications were urinary tract infection (13.5%), metabolic acidosis (13.5%) and
reflux (10.8%). Pouch over distension (5.4%) was consistent with bladder neck obstruction. Patient's gender
and postoperative morbidity were statistically significant factors to increase the mean time to continence;
whereas, age, use of stapler and adjuvant radiotherapy had no significant effect.Modified Le Bag pouch is a
simple technique with adequate pouch capacity that offers excellent slowly progressing continence rates with
minor morbidity rate. Post operative morbidity and female sex delayed continence satisfaction. KEY WORDS:
Continent urinary diversion - Orthotopic neobladder - Ileo colonic pouch - Modified Le Bag pouch.
PMID: 22776840

Orthotopic neobladder reconstruction after radical cystectomy in patients with a solitary

functioning kidney: Clinical outcome and evaluation.

Helmy Aly A; Ezzat A; Hamed A

To evaluate, in a prospective study, the clinical outcome of orthotopic neobladder reconstruction after radical
cystectomy in patients with a solitary functioning kidney at the time of surgery.This study included a total of 28
patients (25 males and three females) with muscle invasive bladder cancer and a solitary functioning kidney at
the time of surgery who underwent radical cystectomy (anterior pelvic excentration for females) and urinary
reconstruction using orthotopic neobladder at The National Cancer Institute, Cairo University between
February 2004 and April 2009. The surgical procedures included ileocaecal neobladder in 19 patients, ileal
neobladder (Studer) in five and sigmoid neobladder in four. All perioperative and long-term complications
were recorded. The renal functions were evaluated using mainly serum creatinine level, abdominal
ultrasonography and intravenous urography (IVU).The mean age of patients was 51.4years (range of 38-
62years) while the mean follow-up period was 41.4months (range 18-62months). Early complications included
wound infections in five patients, urine leakage in six, abdominal dehiscence with deep venous thrombosis in
two, intestinal obstruction and prolonged ileus in three. During the follow-up period, 21 renal units (75%)
remained stable with normal serum creatinine level and normal radiological configuration of the kidney. The
remaining seven patients (25%) developed varying degrees of renal deterioration either due to uretero-
intestinal stricture in three patients (10.7%), who were all treated by open surgical revision of the anastomotic
sites or due to stricture at the vesico-urethral anastomosis in four patients (14.3%) that had been successfully
managed by endoscopic dilatation and internal urethrotomy with stabilization of renal function. Severe
metabolic acidosis occurred in one patient while mild forms occurred in three. These four patients required
sodium bicarbonate therapy and their metabolic status was normalized thereafter.Selecting the type of urinary
diversion is important in patients with a solitary functioning kidney after radical cystectomy. Orthotopic
neobladder reconstruction is a good choice in properly selected patients and could provide comparatively
satisfactory results. Accordingly, a solitary functioning kidney should not be regarded as a contraindication for
neobladder reconstruction after radical cystectomy.
PMID: 21552959

P53 mutations in egyptian bladder-cancer.

Weintraub M; Khaled H; Zekri A; Bahnasi A; Eissa S; Venzon D; Magrath I; Bhatia K

Cancer of the bladder is a frequent malignancy in Egypt and other developing countries in which bladder
infection with the parasite Schistosoma haematobium is common. Several epidemiological, histopathological
and clinical characteristics of cancer of the Bilharzial bladder suggest that it is distinct from bladder cancer
seen in industrialized countries. Little is known, however, about molecular aberrations in Egyptian bladder
cancer. We studied the status of p53 in a series of 25 cases of Egyptian bladder cancer using
immunohistochemistry to detect the p53 protein and SSCP/sequencing to identify mutations in the p53 gene.
Ten of 25 (40%) tumor samples showed a mutation by SSCP/sequencing. Mutations were seen in both the
squamous and transitional cell variants. The presence of mutations was associated with advanced stage of
disease. Immunohistochemistry had a sensitivity of 70%, and a Specificity of 85% for detecting p53 mutations.
Our data show that p53 mutations are a common event in Egyptian bladder cancer, and may be an indicator of
advanced disease. Immunohistochemistry is both sensitive and specific for detecting p53 mutations in this
tumor, and may be used to assess the prognostic value of p53 mutations in this disease.

41
PMID: 1612951

Postoperative radiotherapy of carcinoma in bilharzial bladder: improved disease free

survival through improving local control.

Zaghloul MS; Awwad HK; Akoush HH; Omar S; Soliman O; el Attar I

Two hundred thirty-six patients with T3 bladder cancer who survived radical surgery and proved to have P3a,
P3b, or P4a tumors were randomized in two phases into three groups: (a) no further treatment (83 patients);
(b) postoperative radiotherapy multiple daily fractionation (MDF), using 3 daily fractions of 1.25 Gy each, with
3 hr between fractions, up to a total dose of 37.5 Gy in 12 days (75 patients); and (c) postoperative
radiotherapy conventional fractionation (CF), for a total dose of 50 Gy/5 weeks (78 patients). The tolerance of
the patients to postoperative radiotherapy was quite acceptable, with equal acute reactions in MDF and CF
groups. The 5-year disease-free survival (DFS) rates amounted to 49 and 44% in MDF and CF postoperative
radiotherapy groups, respectively, compared to 25% in the cystectomy-alone group. The 5-year local control
rates were 87% and 93% for those treated with multiple daily fractionation and conventional fractionation
while it was 50% in the surgery-alone group. The therapeutic benefit of postoperative irradiation was
consistent for all tumor types, histological grades, and pathological stages for both the disease-free survival
and local control. Patients with nodal metastases demonstrated lower recurrence rates in the postoperative
radiotherapy groups, but this was not associated with improved disease-free survival. Multivariate analysis
using the Cox Model confirmed these results. The independent prognostic factors affecting both disease-free
survival and local control were the addition of postoperative radiotherapy, the nodal status, the pathological
stage, and the tumor grade. Late complications of radiotherapy in the skin, small intestine, rectum, and the
anastomotic site of the urinary division were lower with MDF than with conventional fractionation.
PMID: 18312930

Primary chemotherapy with low-dose prolonged infusion gemcitabine and cisplatin in

patients with bladder cancer: a Phase II trial.

Khaled H; Emara ME; Gaafar RM; Mansour O; Abdel Warith A; Zaghloul MS; El Malt O

Gemcitabine is an active agent in the treatment of bladder cancer. The enzyme deoxycytidine kinase catalyzes
the phosphorylation of gemcitabine into the active gemcitabine triphosphate. After an infusion during 30
minutes, this enzyme will be saturated, therefore, accumulation of higher intracellular concentrations of the
active gemcitabine triphosphate could be achieved by prolonging the infusion time of gemcitabine.Based on
previously published Phase I trials, the efficacy and safety of a combination of cisplatin and gemcitabine given
as prolonged infusion were tried in a Phase II study of 57 untreated patients with stage III/IV bladder cancer,
which is the most common malignant tumor among Egyptian males. Patients received gemcitabine (250
mg/m(2) during 6-hour infusion) on days 1 and 8, and cisplatin (70 mg/m(2)) on day 2 every 21-day cycle.The
41 males and 16 females had a median age of 55 years (range 37-77). A total of 37 patients had transitional
cell, 15 had squamous cell, 2 had adenocarcinoma, and 3 had undifferentiated cell carcinoma. The median
number of cycles given to these 57 patients was 4 (range 1-6). Of 54 evaluable patients, 5 (9.4%) had complete
remission, and 27 (50%) partial remission, for an overall response rate of 59.4%. These results are comparable
to those of a previous Phase II study of the same combination but with gemcitabine given in the standard dose
and schedule. Responses were observed at all disease sites. Both hematologic and nonhematologic toxicity
were treatable and not severe.Prolonged infusion of gemcitabine and cisplatin is an effective treatment for
advanced bilharzial-related bladder cancer. Toxicity, especially myelosuppression, is surprisingly mild. This
combination deserves to be tried in other different disease categories.
PMID: 20084724

42
 Prognostic index for primary adenocarcinoma of the urinary bladder.

Zaghloul MS; El Baradie M; Nouh ; Abdel-Fatah S; Taher A; Shalaan M

To determine the working independent prognostic factors and the prognostic index of adenocarcinoma of the
urinary bladder. The effect of adding postoperative radiotherapy to radical cystectomy on this prognostic index
was also investigated.Two hundred and sixteen patients having adenocarcinoma of the urinary bladder were
treated with radical cystectomy and pelvic lymphadenectomy with (82 patients) or without (134)
postoperative radiotherapy. Postoperative radiotherapy (PORT) was given to the whole pelvis in a dose of 50
Gy/25 fractions over 5 weeks, and started 4-10 weeks after surgery.The 5-year disease-free survival rate was
44 +/- 4% for the whole group. Postoperative radiotherapy improved the disease-free survival significantly
from 33 +/- 6% for cystectomy alone Introduction to 58 +/- 6% for PORT patients (P = 0.002). The independent
prognostic factors for DFS were the pathological stage, histological subtypes, nodal involvement and the
addition of postoperative radiotherapy. The stratification of patients using prognostic indices according to the
pathological findings produces identifiable prognostic groups. Postoperative radiotherapy improved the DFS
significantly in the intermediate and high risk indices (p = 0.0004 and 0.0002 respectively).The identified
prognostic indices with their prognostic group could be used not only as a predictor of disease-free survival but
also as a good predictor for the need to add adjuvant therapy in adenocarcinoma of the urinary bladder.
PMID: 20586027

Prognostic value of membrane type 1 and 2 matrix metalloproteinase expression and

gelatinase A activity in bladder cancer.

Mohammad MA; Ismael NR; Shaarawy SM; El-Merzabani MM

To analyze the behavior of matrix metalloproteinases (MMPs) in their active state in patients with bladder
cancer.A retrospective study of 50 patients with localized bladder cancer who underwent tumor resection
between June 2006 and June 2007 at the National Cancer Institute in Cairo, Egypt was carried out. Tissue
samples were collected and the expression of membrane type 1 (MT1) and type 2 (MT2) MMPs was
determined by Western blotting. Gelatinase A (MMP-2) activity was estimated by zymographic analysis in
tissue samples of each patient and the values were correlated with clinical tumor stage and lymph node
status.The behavior of MMP-2 showed statistical significance in 90% of tumor tissues compared with 22% of
adjacent normal tissues (p<0.001). MT1-MMP was expressed in 88% of tumor tissues compared with 24% of
normal tissues (p<0.001); MT2-MMP was expressed in 74% of tumor tissues compared with 12% of normal
tissues (p<0.001). While there was a highly significant association between MMP-2 activity and MT1-MMP
expression in tumor tissues (p<0.001), there was a moderately significant association between MMP-2 activity
and MT2-MMP expression (p=0.018). The results also revealed an association between MT1-MMP and MT2-
MMP expression in tumor tissues (p<0.001). MMP-2 activity and MT2-MMP expression in tumor tissues were
statistically associated with high tumor stage (p=0.039 and p=0.014, respectively), while the expression of
MT1-MMP showed no association with tumor stage (p=0.139).MMP-2 activity is associated with an increase in
MT2-MMP expression and with lymph node metastasis. No association was found between MT1-MMP
expression and lymph node metastasis.
PMID: 17102820

Role of loss of heterozygosity on chromosomes 8 and 9 in the development and

progression of cancer bladder.

Abdel Wahab AH; Abo-Zeid HI; El-Husseini MI; Ismail M; El-Khor AM

Loss of heterozygosity (LOH) in tumor samples is believed to be a marker for the absence of a functional tumor
suppressor gene. Non-random chromosome deletion and LOH at specific chromosomal regions are identified
in a number of common human cancers including carcinoma of the bladder, which is considered the most
predominant cancer in Egypt due to the prevalence of schistosomiasis.The main objective of the present study
is to clarify the role of chromosomes 8 and 9 in the establishment and/or progression of schistosomiasis-

43
related bladder cancer through detection of LOH of 8 microsatellite markers on both chromosomes. It also
aims to compare the LOH pattern of the tested markers between schistosomiasis- associated and non
schistosomiasis-associated bladder cancer.To achieve this purpose, DNA was extracted from the tumor
specimens and the corresponding peripheral blood samples of 42 primary bladder cancer patients
(schistosomal and non schistosomal). Twenty nine of these were diagnosed as squamous cell type (SCC), 11
were transitional (TCC), and 2 were adenocarcinoma (with different stages and grades). LOH at chromosomes
8 and 9 was evaluated for 8 highly polymorphic microsatellite markers distributed at different regions of both
chromosomes using the dinucleotide repeat-PCR technique.The overall percentage of LOH in chromosome 8
was 74% in at least one marker. The highest incidence of LOH was recorded for D8S84 (41%) followed by 37%
for D8S87, 29% for D8S85, and 25% for D8S88. Deletions at chromosome 8 were shown to be associated with
high grade of the tumor and LOH at D8S85 was associated with metastatic lymph nodes. The overall
percentage of LOH in chromosome 9 was 54% and its highest incidence was for D9S126 (36%), followed by
26%, 21%, 19% for D9S166, D9S128 and D9S180, respectively. Fifty nine percent (59%) of the cases with LOH
at 9q were diagnosed as squamous cell type (SCC), whereas 9% only were transitional cell type (TCC). No
significant association was recorded between the presence of schistosomiasis and LOH detected in all markers
used in this study.Our data indicate that more than one tumor suppressor gene on chromosomes 8 and 9 are
involved in high grades of bladder carcinogenesis, one at 8p12 and another at 8q21.1 regions. Also, a region at
8q23-quarter may harbor tumor suppressor gene that involved in metastasis of bladder cancer. Our study also
revealed that 9p21 (p16INK4) region is involved in both types of the tumor (SCC & TCC). PTCH located at
9q22.3, as well as the TSC gene at 9q34 are involved in squamous cell carcinoma rather than transitional
carcinoma. Region 9q12-13 is considered to be a critical region of urothelial tumor suppressor genes. Finally,
the present study shows no line of demarcation between schistosomiasis-associate and non schistosomiasis-
associated bladder cancer in terms of LOH of the tested microsatellite markers on chromosome 8 and 9. This
suggests that data obtained from schistosoma-associated bladder cancer can be extrapolated to bladder
cancer induced by a schistosomiasis independent mechanism.
PMID: 22716492

Schistosomiasis and bladder cancer: similarities and differences from urothelial cancer.

Zaghloul MS; Gouda I

Through the years, schistosoma-associated bladder cancer was believed to be a unique entity of disease,
different from urothelial cancer. As carcinogenesis is a highly complex process resulting from the accumulation
of many genetic and epigenetic changes leading to alterations in the cell proliferation and regulation process,
confirmation of their minute differences or similarities are extremely difficult. In bladder cancer, many of these
carcinogenic cascades were not fully documented in spite of the efforts undertaken. The control of
schistosomiasis and the subsequent decrease in the intensity of infestation showed feature changes
approaching that of urothelial tumors. However, schistosoma-associated bladder cancer still presents in more
advanced stages than schistosoma-non-associated urothelial cancer. Furthermore, many data were collected
proving that, upon applying the same treatment protocol and management care, stage-by-stage comparison of
the treatment end results were found to be similar in bladder cancer patients with the different etiologies.
PMID: 15729596

Squamous cell carcinoma of the bilharzial and non-bilharzial urinary bladder: a review of
etiological features, natural history, and management.

El-Sebaie M; Zaghloul MS; Howard G; Mokhtar A

Squamous cell carcinoma of the urinary bladder, though uncommon in Europe and the United States, is the
most common variety of bladder tumor in countries where urinary bilharziasis prevails. A great controversy
still exists regarding its natural history and management. Here, we review the literature of bilharzial and
nonbilharzial squamous cell carcinoma of the urinary bladder, focusing on large series. Our aim was to gather
most of the published data about this disease entity, report it in a systematic comparative review, and attempt
to identify the adverse features and variables behind its dismal outcome. The conclusions are that squamous
cell carcinoma, whether bilharzial or nonbilharzial, has distinctive clinicopathological features, different from

44
those of the transitional cell variety. These tumors usually present in advanced (muscle-invasive) stages. Pelvic
nodal metastases are not common, and the incidence of distant metastases is less than that reported with
transitional cell carcinoma. Local treatment, including cystectomy and adjunctive radiotherapy, is the most
acceptable way of treating such tumors.
PMID: 16892094

Systemic management of bladder cancer in Egypt: revisited.

Khaled HM

Bladder cancer is still the most frequent malignant tumor among Egyptian males. It has a peculiar biologic,
clinico-pathologic features and responsiveness to chemotherapy profile than that observed in Western
countries. The current review aims to demonstrate the present state-of- art in using systemic therapy as part
of the management options available to treat such patients at different stages of their disease. Individualizing
therapy for these patients based on more rationale basis is the challenge that oncologists must face in the near
future.
PMID: 11418321

Telomerase activity in bilharzial bladder cancer. Prognostic implications.

Abdel-Salam IM; Khaled HM; Gaballah HE; Mansour OM; Kassem HA; Metwaly AM

Background: Bladder cancer is a common malignancy in Egypt and other developing countries in which
infection with Schistosoma haematobium is prevalent. Bladder cancer caused by bilharziasis has different
clinical and biological characters than that observed in the western world. In this study, we used the TRAP
technique to estimate telomerase activity in bilharzial bladder cancer specimens and we correlated the
findings with other clinical and pathological findings. Patients and methods: Bladder cancer specimens were
obtained from 57 patients who underwent radical cystectomy and pathological diagnosis was obtained in all
patients. Tissue samples were frozen in liquid nitrogen and stored at -80 degrees C. Telomerase activity by
PCR-ELISA technique was measured using TRAP technique. Results: Our patient group included 45 males and
12 females with a median age of 49 years. The majority of our patients (35/57) have squamous histology and
they have proven bilharzial history shown in the pathology specimens. Stage P3b was encountered in 29/57
patients whereas thirty-five patients have grade II tumors. The majority of our patients (41/57) were negative
for pelvic nodes metastases. Telomerase activity was detected in 27/57 patients (47.4%). The mean level of
telomerase was 0.85+/-0.77 in positive patients and 0.029+/-0.025 in negative patients. The expression of
telomerase and its mean level in patients above age of 60, in males and in those with squamous pathology,
higher grade of tumors or positive node was higher than those without but the difference did not reach
statistical significance (P>0.05). Alternatively, expression was significantly higher in those with stages (P1-P3a)
compared with P3b-P4a disease stages (66.6% vs. 37.1, P=0.03). Conclusion: Telomerase activity is increased in
bilharzial bladder cancer although to a lesser degree than that reported for TCC in the western world, which
could be explained, by different biological behavior or different assay methods. Further larger studies with
more number of patients are still needed to determine its potential value for early detection and possible use
as a therapeutic target.
PMID: 20029473

Time-trend in epidemiological and pathological features of schistosoma-associated

bladder cancer.

Zaghloul MS; Nouh A; Moneer M; El-Baradie M; Nazmy M; Younis A

To investigate the different emerging trends in the features of bladder cancer along 17 years.During a 17-year
period (1988- 2004), 5071 epithelial bladder cancer patients underwent radical cystectomy at the National
Cancer Institute (NCI), Cairo University, Egypt. The time was divided into 3 time periods to detect changes of
the clinicopathologic features of patients in these periods.There was a significant progressive increase in the

45
patients' age with time and decrease in squamous/transitional ratio, with transient increase in male
predominance during the 2nd time period. Moreover, there was a decrease in the well differentiated (grade 1)
tumor (p<0.001) and an increase in the frequency of pelvic nodal involvement (p<0.001). Transitional cell
carcinoma (TCC) patients were significantly older than those with squamous cell carcinoma (SCC) (p<0.001).
Progressive increase of age with time was evident in TCC, SCC and adenocarcinoma patients. Male to female
ratio changed significantly in TCC and SCC.Time trend was confirmed with relative decrease in frequency of
SCC and increase of TCC with changes in their pathological details. The differences between their
characteristics and that of the Western countries are decreasing.

Brain, Head &Neck, Thyroid Studies

PMID: 16508679

A randomized study of accelerated fractionation radiotherapy with and without

mitomycin C in the treatment of locally advanced head and neck cancer.

Ezzat M; Shouman T; Zaza K; Safwat A; El-Khoudary A; El-Senosi M; Ezzat I

This single-institution study evaluates the feasibility of accelerated fractionation radiotherapy (AF) with and
without mitomycin C (MMC) in the treatment of locally advanced head and neck cancer.Between May 1998
and October 2001, sixty patients with locally advanced stage III and IV of head and neck cancer were
randomized into three treatment arms: (1) conventional fractionation radiotherapy (CF) (5 fractions per week);
(2) accelerated fractionation radiotherapy (AF) (6 fractions per week); and (3) AF plus Mitomycin C (MMC).The
2-year overall survival (OS) of the whole group was 21%. The OS according to treatment arm was 23%, 20%,
and 28% in CF, AF, and AF+MMC arms respectively (p<0.19). The 2-year loco-regional control (LC) rate was 22%
for the whole group of patients. The LC was 10%, 25%, and 30% for the CF, AF, and AF+MMC respectively
(p=0.27). The only significant parameters for OS and LC were performance status and pre-treatment
hemoglobin level. Mucositis grades 3 & 4 occurred in 70% and 90% of the patients in the AF and AF+MMC arm
respectively compared to 55% of patients in the CF arm (p=0.04). However the addition of MMC did not
significantly increase the incidence or severity of mucositis between AF and AF+MMC (p=0.13). Hematological
toxicity grades 3 & 4 were significantly higher after MMC (occurred in 40% of patients versus 10% and 5% in CF
and AF arms respectively, p=0.04). There was no statistically significant difference in the incidence of grade 3
dryness of mouth (p=0.06), fibrosis (p=0.6), or lymphoedema (p=0.39) among the three arms.There was a
trend for improvement of LC and OS rates with the use of AF and the addition of MMC to AF compared to CF
radiotherapy, although the difference was not statistically significant. The small number of the patients in each
treatment arm and the inclusion of multiple tumor sites may contribute to these statistically insignificant
results. Accordingly we advise 85 to continue the trial with inclusion of a larger number of patients and restrict
tumor sites to one major site.
PMID: 11870530

Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the

postoperative radiotherapy of locally advanced head and neck cancer: influence of
proliferation.

Awwad HK; Lotayef M; Shouman T; Begg AC; Wilson G; Bentzen SM; Abd El-Moneim H; Eissa S

Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after
surgery, the possibility that treatment acceleration would offer a therapeutic advantage in postoperative
radiotherapy of locally advanced head and neck cancer was investigated. The value of T(pot) in predicting the
treatment outcome and in selecting patients for accelerated fractionation was tested. Seventy patients with
(T2/N1-N2) or (T3-4/any N) squamous cell carcinoma of the oral cavity, larynx and hypopharynx who
underwent radical surgery, were randomized to either (a) accelerated hyperfractionation: 46.2 Gy per 12 days,
1.4 Gy per fraction, three fractions per day with 6 h interfraction interval, treating 6 days per week or (b)

46
Conventional fractionation: 60 Gy per 6 weeks, 2 Gy per fraction, treating 5 days per week. The 3-year
locoregional control rate was significantly better in the accelerated hyperfractionation (88 +/- 4%) than in the
CF (57+/- 9%) group, P=0.01 (and this was confirmed by multivariate analysis), but the difference in survival (60
+/- 10% vs 46 +/- 9%) was not significant (P=0.29). The favourable influence of a short treatment time was
further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the
overall treatment time between surgery and end of radiotherapy. Early mucositis progressed more rapidly and
was more severe in the accelerated hyperfractionation group; reflecting a faster rate of dose accumulation.
Xerostomia was experienced by all patients with a tendency to be more severe after accelerated
hyperfractionation. Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation
and probably represent consequential reactions. T(pot) showed a correlation with disease-free survival in a
univariate analysis but did not prove to be an independent factor. Moreover, the use of the minimum and
corrected P-values did not identify a significant cut-off. Compared to conventional fractionation, accelerated
hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate
was noted. This limits the use of T(pot) as a guide for selecting patients for accelerated hyperfractionation. For
slowly growing tumours, tumour control and survival probabilities were not significantly different in the
conventional fractionation and accelerated hyperfractionation groups. A rapid tumour growth was associated
with a higher risk of distant metastases (P=0.01). In conclusion, tumour cell repopulation seems to be an
important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of
a definite association between T(pot) and treatment outcome. In fast growing tumours accelerated
hyperfractionation provided an improved local control but without a survival advantage. To gain a full benefit
from treatment acceleration, the surgery-radiotherapy gap and the overall treatment time should not exceed
6 and 10 weeks respectively.
PMID: 19652671

Aggressive surgical therapy for locally invasive differentiated thyroid carcinoma : an

experience of nineteen ( 19 ) cases.

Mebed AH

It is well recognized that the optimum resection of locally advanced differentiated thyroid cancer invading
adjacent vital neck structures is still controversial. This report analyzes patients and tumor characteristics,
anatomic structures invaded, surgical procedures, postoperative complications, adequacy of tumor resection,
and follow-up of all patients.To re-evaluate the role of extended surgical therapy regarding its impact on local
disease control and disease-free survival in patients with locally invasive differentiated thyroid carcinoma.This
is a prospective study, carried in the National Cancer Institute, Cairo University, between January 2002 and
January 2008 on 19 patients with primary differentiated thyroid carcinoma extending extrathyroid and
invading surrounding neck structures. All patients were followed for a period of 4 to 60 months and received a
form of adjuvant therapy.The median age at diagnosis was 54 years. There was slight female predominance (
1:1.1 ) , 84.2 % of the tumors were papillary, 63.2 % were grade 2 and 31.6 % were clinically cervical node
negative. The most common structure involved was the skin of the neck ( 36.8 % ) , which was reconstructed
by deltopectoral fascio-cutanuous flap in the majority of these cases. There was an incidence of 15 % wound
complications, 10 % permanent and 37 % transient hypoglycaemia, 22 % hoarseness of voice and 16 %
incidence of Honer-Syndrome. The safety margin was positive in 10 % of the patients. Disease-free survival was
85.6 % at the end of the first year and 66.5 % at the end of the second.Microscopic positive safety margins did
not compromise disease-free survival in the nineteen patients when surgery was followed by adjuvant
therapy. This treatment protocol is suitable in tumors with surface invasion of the upper aeorodigestive tract
and those invading the recurrent laryngeal nerve. Key Words : Differentiated thyroid cancer - Deltopectoral
flap - Shave procedures - Extended surgery.
PMID: 21132032

47
 Cancer of Oral Cavity Abutting the Mandible; Predictors of Loco-regional Failure.

Saber TK; Hussein HA; Mebeed AH; El Sebai HI; Sami I; Farahat IG

: The purpose of this study is to analyze the causes of Loco-regional failure in 51 patients with tumors of the
oral cavity abutting the mandible.This cross-sectional study (27 patients were operated upon in the
retrospective section and 24 patients in the prospective section of the study) was done in the department of
Surgical Oncology, National Cancer Institute, Cairo University, from January 2003 to January 2008. Fifty-one
patients, with oral cavity cancerous lesions abutting the mandible, were operated upon by segmental
mandibulectomy en-bloc with primary tumor resection in addition to modified radical or selective neck
dissection according to the status of the cervical lymph nodes.During a median follow-up of 2 years, 29
patients (56.8%) had local recurrences, the incidence of nodal recurrence after neck dissection was detected in
4 patients (7.8%). On multivariate analysis, tumor depth, tumor grade, oral mucosa, soft tissue and bone
surgical margins in addition to metastatic lymphadenopathy were independent prognostic factors of loco-
regional failure and disease-free survival.Oral cavity cancers abutting the mandible should be treated with
great caution by a multidisciplinary oncology team (resection and reconstruction surgeons) as it has a very
aggressive biologic behavior. Negative intraoperative pathological margins should be attempted since this is
the critical point for patients with cancers abutting the mandible? Further research on the biologic margin and
genetic study is required. KEY WORDS: Oral cavity cancer abutting the mandible - Predictors of loco-regional
failure.
PMID: 18228210

Clinical significance of metabolic superscan in patients with hyperthyroidism.

Kotb MH; El-Maghraby T; Khalafallah K; Omar W; Grace BD; Al-Nahhas A

Hyperthyroid patients commonly complain of generalized bony aches, which are frequently overlooked due to
the more prominent symptoms of cardiovascular and nervous disturbances. Hyperthyroid patients are
expected to have abnormal bone metabolism as part of the generalized hypermetabolic status. The aim of this
study is to verify the presence of metabolic bone superscan in association with the hypermetabolic stats in
various groups of hyperthyroidism. Secondly, to correlate these superscan features with the various laboratory
results in hyperthyroid patients.Forty-five hyperthyroid patients confirmed by clinical and laboratory results
were enrolled in this work. In all patients, a (99m)Tc-pertechnetate thyroid uptake scan was acquired. On a
different day, total body bone scan was acquired three hours post IV injection of 555-925 MBq of (99m)Tc-
MDP. Serum FT3, FT4, TSH, Ca++, alkaline phosphatase (AP) and parathyroid hormone (PTH) were monitored
in all patients as markers of thyroid and bone metabolism. Ten cases with no thyroid diseases were included as
a control group. Patients with thyroiditis or long history of antithyroid drugs for more than one year were
excluded from the study.The patients were subdivided into three groups: Graves disease (GD) (n = 30), toxic
nodular goiter (TNG) (n = 10) and autonomous toxic adenoma (AT) (n = 5). The TSH for the whole group was
significantly suppressed compared to the control group with higher suppression in the Graves disease group
than in the TNG or AT groups. (99m)Tc-pertechnetate uptake values in the Graves disease group were
significantly higher than the TNG and AT groups (p < 0.05). Metabolic superscan (MSS) was noted in 90% of the
Graves cases, 20% in TNG and in none of the AT group. There were no significant differences regarding Ca+, AP
and PTH between the Graves and non-Graves groups (p > 0.05).Disturbances in bone metabolism are more
prevalent in Graves disease than in other types of hyperthyroidism. The addition of the bone scan to the
diagnostic work up of patients with Graves disease is a sensitive indicator for metabolic bone changes and
could help in the future management and follow up for this group of patients.
PMID: 21132035

48
Continuous validity of pedicled myocutaneous and myofascial flaps in reconstruction after
surgery for head and neck cancer.

Elshafiey MM; Mebed AH; Abd Elmaksoud AE; Attia AA

The aim of this study was to reevaluate the role and effectiveness of pedicled myocutanous and myofascial
flaps in reconstruction after resection of head and neck cancer.This study represents the authors own
experience using pedicled myocutanous and myofascial flaps in reconstruction after resection of malignant
tumors of different sites in the head and neck. The study included 121 patients with head and neck cancer
operated upon at the National Cancer Institute, Cairo University and Alminia Cancer Center over 3 years
duration, between July 2005 and the end of July 2008. Four types of flaps were used namely the Pectoralis
major (Group I), lower trapezius (Group II), Latissimus dorsi (Group III), and the temporalis ((Group IV) flaps.
Utility of the different types of these flaps was reevaluated in terms of indications, advantages, and
postoperative complications.This study included 121 patients, 83 males and 38 females. The mean age was 56
years (range, 14- 65 years). Oral malignancies represented most of the cases (71 cases). Pectoralis major
myocutaneous (PMMC) flap was the most commonly used flap (84 cases) and its main indication was oral and
pharyngeal defects. Lower trapezius and Latissimus dorsi myocutaneous flaps were used in 14 and 12 cases
respectively. Their main indications were tumors in the occiput, ear pinna, parotid and neck regions. The
Latissimus dorsi myocutaneous flap was also used for reconstruction of oral and pharyngeal defects in 7
female patients with large breasts and for salvage reconstruction after failure of reconstruction by (PMMC)
flap in one patient and for reconstruction after excision of local recurrence on top of previous (PMMC) flap in
another patient. Temporalis myofascial flap was used in 12 cases and the main indication was orbital defects.
The overall postoperative complications was 19.8% (24/121). It was 20% (17/84) in group I, 28.6% (4/14) in
group II, and 25% (3/12) in group III. No flap related complications were reported in group IV. All complications
were successfully managed except for one case in (Group I), in which a major flap loss developed and was
successfully salvaged by pedicled latissimus dorsi myocutaneous flap.Pedicled myocutanous and myofascial
flaps are still indicated in composite head and neck reconstruction. Their reliability, safety, and high degree of
resistance to infection make them essential specially the (PMMC) flap previously described as the spare wheel
of head and neck reconstructive surgery. It is suitable for lateral mandibular defects in edentulous patients and
in partial pharyngeal defects in irradiated patients. Other pedicled myocutaneous flaps are still valid in certain
occasions and sites. KEY WORDS: Head and neck cancer - Pectoralis major - Trapezius - Latissimus dorsi -
Temporalis myocutaneous - Myofascial flaps - Reconstruction.
PMID: 20601969

Critical appraisal of nasolabial flap for reconstruction of oral cavity defects in cancer
patients.

Mebeed AH; Hussein HA; Saber TKh

Re-evaluation of nasolabial flap in lip and oral cavity reconstruction and role of each of its variants in
reconstructing various intermediate size defects was addressed.Case-series study was conducted in National
Cancer Institute, Cairo University over the period from July 2005 - January 2009 which included 23 patients
with clinically T-1 N0, T-2 N0 invasive squamous cell carcinoma of buccal mucosa and the vermilion border of
the lower lip. Immediately after surgical excision, one stage reconstruction of the defect was done using a type
of nasolabial flap. All patients were followed and the median follow-up period was 7.5 month.Twelve patients
with the lower lip carcinoma and 11 patients with the carcinoma of buccal mucosa underwent surgical excision
under frozen section control. 19 fasciocutaneous nasolabial flap and 4 facial artery musculomucosal flaps were
used for reconstruction. Minor wound complications occurred in 2 flaps and one patient required secondary
suture. Flap viability was reliable and was not affected by performance of a synchronous neck dissection.
Functional results were satisfactory, cosmetic results were good in most of the patients and excellent when
facial artery musculomucosal flap was used.The nasolabial flap is a reliable and minimally traumatic local flap
for one stage reconstruction of medium size defects in the oral cavity. The abundant blood supply allowed its
modification in order to cover larger defects or to obtain better cosmetic results. This versatility makes it more

49
widely used thus minimizing the use of local tongue flaps and split thickness grafts for covering these medium
size defects in cases of buccal mucosa cancer or affecting the other lip or commissure in cases of lip cancer. It
has a high viability rate, low complication rate; it is quick and easy to perform in addition to its satisfactory
functional and cosmetic results. KEY WORDS: Nasolabial flap (NLF) - Facial artery musculomucosal (FAMM) flap
- Reconstruction of oral cavity - Squamous cell carcinoma (SCC) - Buccal mucosa - Lower lip reconstruction.
PMID: 20571594

Diagnostic accuracy and pitfalls of preoperative fine needle aspiration cytology in salivary
gland lesions.

Tahoun N; Ezzat N

Evaluation of diagnostic accuracy of preoperative fine needle aspiration cytology (FNAC) in salivary gland
lesions.This is a retrospective study of 82 patients presented at NCI, Cairo University with salivary gland lesion
who underwent preoperative FNAC diagnosis with subsequent excision and histopathologic assessment.
Cytology results were classified as negative, positive, suspicious for cancer and inadequate. The definitive
histopathologic report according to WHO Histological typing was the gold standard diagnosis against which
FNAC was compared.Our study included 82 patients who underwent preoperative FNAC of major salivary
glands with subsequent surgical excision. Male to female ratio was 1.4: 1. The median age was 42 years.
Parotid gland was involved in (68.3%), submandibular in (28%) and submental gland in (3.7%). Forty cases
(48.8%) were cytologically diagnosed as benign lesions, 26 (31.7%) were malignant and 10 (12.2%) were
suspicious. Cytological findings were nondiagnostic in 6 (7.3%). The most common benign cytologic diagnosis
was pleomorphic adenoma; 16 out of 40 cases (40%), while the most common malignant tumor was
carcinoma; 22 out of 26 cases (84.6%). Cytologic diagnoses were compared with histopathologic ones and
were true-negative in 37 (92.5%), true-positive in 33 (91.6%), false-negative in 3 (8.3%) and false-positive in 3
(7.5%) cases regarding detection of malignant tumors. The cytologic diagnosis achieved a sensitivity of 91.7%;
a specificity of 92.5%, PPV 91.6%, NPV 92.5% and diagnostic accuracy 92%. The rates of agreement of
histopathologic type for benign and malignant tumors were 89.2% and 91%, respectively.The sensitivity,
specificity and diagnostic accuracy of FNAC were 91.7%, 92.5% and 92%, respectively. Attention to subtle
morphologic changes, pitfalls and limitations are important to increase diagnostic accuracy. Multidirectional
aspiration is preferred to avoid selective sampling. Re-aspiration of solid portion after cyst fluid aspiration is
necessary to decrease the rate of inadequacy. KEY WORDS: FNAC - Salivary gland lesions - Accuracy - Pitfalls.
PMID: 22099936

Did salvage ICE chemotherapy improve the outcome in primary resistant/relapsing stage
III/IV neuroblastoma?

Abdel Rahman H; Moussa EA; Zekri WZ; El Debawy E; Mostafa NE; Yones A; Ezzat S; El Rahman Rayan A

Neuroblastoma is the most common extracranial and deadly solid tumor in children. It accounts for 15% of the
deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at "high
risk" of treatment failure. The aim of this study is to evaluate the response rate of salvage chemotherapy by
the ICE (Ifosfamide, Carboplatin, and Etoposide) regimen when administered to previously treated primary
refractory or progressive high risk neuroblastoma patients.Sixty-six patients from the National Cancer Institute
(NCI), Cairo University and the Children Cancer Hospital Egypt (CCHE) received salvage chemotherapy (ICE)
either due to primary resistance in 51/66 (77.2%) or due to disease progression on primary chemotherapy in
15/66 (22.8%).They were 40 males (60.6%) and 26 females (39.4%). Patients' age ranged between 3months
and 12.5years. The most common tumor site was suprarenal, followed by retroperitoneal mass. Two patients
(3%) died from chemotherapy toxicity during ICE administration. Evaluation of tumor response in the
remaining 64 patients showed the following: CR/PR in 24 patients (36.5%), SD in 11 patients (16.6%), and PD in
29 patients (43.9%). Fourteen patients (21.2%) were considered eligible for auto BMT, while 50/64 patients
(78.8%) failed this second line (salvage) chemotherapy and had palliative lines of therapy. By the end of the
study (May 2010), 47/66 (71.2%) of the patients were still alive, while 19/66 (28.8%) were dead. Two out of 14
patients (14.2%) who underwent HSCT died from post transplantation disease progression, while 12/14
(85.8%) were in CCR.Chemotherapy by ICE for primary resistant or progressive stage III/IV NB seems well

50
tolerated. With a 36.6% response rate, 18% CCR, and 3% treatment mortality rate, it could be considered a
good salvage therapy in the category of patients who are condemned for palliation
PMID: 2246587

Direct extension of laryngeal carcinoma to the skin of the neck.

Rifai M; Mebed H; Bassiouni M

Invasion of the skin of the neck by laryngeal carcinoma is relatively uncommon. Twelve cases of cancer of the
larynx fungating through the cervical skin are presented. They mostly followed initial treatment by deep X-ray
therapy or partial laryngectomy. A high tracheostomy was also considered to be a contributing cause for the
occurrence of such a mishap. The management and follow-up of these patients is described.
PMID: 22099965

Evaluation of morphological/immunohistochemical versus nuclear medicine imaging

modalities in detecting metastatic bone and/or marrow deposits in neuroblastoma
patients.

Zaher Ael-S; Zaher AM; Moneer MM; El Gamal BM

In planning diagnostic or follow-up investigational strategies, neuroblastoma (NB) metastatic deposits in bone
and/or bone marrow (BM) should be detected as early as possible. Therefore, all investigational detection
tools should be conducted simultaneously for precise staging. However, because of the financial conditions in
our developing countries and in view of the cost/benefit relationship, the question is, can one detection tool
only become satisfactory and replacing others? The purpose of our study is to compare simultaneous results of
bone and metaiodobenzylguanidine (MIBG) scans versus BM biopsies with immunohistochemical (IHC)
staining; in detecting bone and/or BM metastatic deposits in NB patients.This study included 138 NB patients;
46 were de novo and 92 were under follow-up. They were subjected to bilateral BM biopsies, IHC staining
(using NSE McAb) and Tc-99m methylene diphosphonate (Tc-99m MDP) bone scan (BS). Only 57/138 patients
were, in addition, subjected to I-131 MIBG scan.Matched results between IHC-stained BM sections and bone
scans (BSs) 107/138 (77.5%) were higher than the un-matched ones 31/138 (22.5%). There was a moderate
agreement between the two methods in all studied cases (Kappa=0.538) and it was higher among de novo
(Kappa=0.603) than follow-up group (Kappa=0.511). Among the 31 un-matched results, the most frequent
(17/31) were due to the presence of minute amount of infiltrating NB cells that could be detected by IHC-
stained BM sections and not by BSs. The less frequent (12/31) were due to the presence of metastatic deposits
outside pelvic bones that could be detected by BSs and not by IHC-stained BM sections mainly in the follow-up
cases (11/12) rather than de novo cases (1/12). The matched results between IHC-stained BM sections and
MIBG scans 54/57 (94.7%) were higher than the un-matched ones 3/57 (5.3%). The agreement between the
two methods was higher among de novo (Kappa=1.000) than follow-up group (Kappa=0.847). The agreement
between IHC-stained BM sections and MIBG scans was substantial (Kappa=0.890) while that between IHC-
stained BM sections and BSs was moderate (Kappa=0.538).We suggest a step-wise strategy to be applied, at
least in developing countries, in approaching de novo and follow-up NB cases for detecting bone and/or BM
metastatic deposits. This strategy might be beneficial if it is considered during application of NB guide-lines for
diagnosis and follow-up.
PMID: 11917950

Fasciocutaneous free flaps for hypopharyngeal reconstruction.

Amin AA; Bassiouny M; Elsebai H; Riffat M; Fakhry S; Hewidi S; Khafagy M

Considerable controversy persists regarding the optimal technique for hypopharyngeal reconstruction. The
ideal procedure should provide low mortality and morbidity, short hospitalization, a high success rate, few
complications, and the greatest potential for neopharyngeal speech and deglutition. In this study, a variety of
fasciocutaneous free flaps were used for reconstruction of the hypopharynx. Over a two-year period,

51
fasciocutaneous flaps were used for reconstruction of pharyngoesophageal segments following total
laryngopharyngectomies in 16 patients at The National Cancer Institute, Cairo University, Cairo, Egypt. Flap
survival, recipient vessels used, and complications were examined. The ultimate functional and cosmetic
outcomes of free flaps were compared. Of the 16 patients included in this study, nine were males, and seven
were females. Free flaps used for reconstruction included the radial forearm (8), lateral arm (2), anterolateral
thigh (3), and posterolateral thigh (3) flaps. Free flaps were successful in 15 patients. One patient had total flap
loss. Salvage surgery was successful for one flap that developed venous congestion. Eleven patients received
adjuvant radiation therapy. The commonly used recipient vessels were the small arteries of the neck and the
external jugular vein. Five patients developed minor pharyngocutaneous fistulas that healed spontaneously.
Six patients developed anastomotic line stricture. Donor-site morbidity was more significant with the radial
forearm flap, compared to other flaps. Fasciocutaneous free flaps have a definite place in pharyngoesophageal
reconstruction. The flap should be selected with reference to the type of the defect and patient obesity;
however, donor-site morbidity should also be considered.
PMID: 17237855

Feasibility of sentinel lymph node detection in nodular thyroid disease.

Abdalla HM

Sentinel lymph node biopsy has been proven to be successful and accurate in predicting the nodal status in
melanoma and breast cancer. Occult lymph node metastases are common in well differentiated thyroid cancer
(WDTC). Although the prognostic significance of these occult lymph node metastases remains controversial,
identifying these patients may help direct therapy. The purpose of the study was to assess the technical
feasibility and the safety of the sentinel lymph node biopsy in uni-nodular thyroid disease.Patients of
previously untreated benign solitary thyroid nodule, diagnosed preoperatively by fine-needle aspiration
cytology without any palpable cervical lymph node were prospectively studied. The nodule was injected with
isosulfan blue vital dye. Blue stained lymphatics were traced. Then, hemithyroidectomy was performed.A total
of 30 patients underwent sentinel lymph node biopsy; lymphatics were observed in 23 patients and sentinel
lymph nodes were found in 18. In 5 patients, blue stained lymphatics were traced to the outside of the central
compartment but no sentinel lymph node was identified. Sentinel lymph nodes were located in the central
compartment in 14 cases, in the lateral compartment in 3 cases and in one patient 2 sentinel lymph nodes
were found in both the central and the lateral compartments. Overall detection of sentinel lymph nodes was
possible in 60% of cases. There were no intra or postoperative complications.The role of sentinel lymph node
biopsy has yet to be determined in the thyroid setting. Certainly the technique can be performed safely, but its
accuracy needs further refinement and investigation on larger series of patients before it can be
recommended in the routine management of thyroid neoplasia.
PMID: 16456769

Free anterolateral thigh flap for reconstruction of major craniofacial defects.

Amin A; Rifaat M; Civantos F; Weed D; Abu-Sedira M; Bassiouny M

Free-tissue transfer has revolutionized skull-base surgery by expanding the ability to perform cranial base
resection and by improving the quality of reconstruction. The anterolateral thigh flap has come recently into
use in the field of head and neck reconstruction. Its role in craniofacial and midface reconstruction has not
been specifically defined. This study involved a total of 18 patients who were treated over a 5-year period from
1998 to 2003. Seventeen patients had locally advanced head and neck cancer, requiring craniofacial resection,
and one patient had a complicated gun shot wound of the forehead. Thirteen patients were treated at the
National Cancer Institute, Cairo University, Egypt, and five patients at the University of Miami, Florida. The
patients presented with defects of the anterior skull base (5), lateral skull base (3), scalp and calvarium (3), and
the midface (7). The anterolateral thigh flap was used as a myocutaneous flap in 11 cases and as a perforator
fasciocutaneous flap in seven cases. Musculocutaneous perforators supplied the majority of flaps (17/18).
Total flap survival occurred in 17 cases; one patient developed complete flap necrosis. The most commonly
used recipient vessels were the facial vessels and the external jugular vein. Major complications included one
case with meningitis; the patient died after failure of treatment. Another patient died 6 weeks postoperatively

52
from pulmonary embolism. One patient developed CSF leak that stopped spontaneously. In addition, two
patients developed minor wound dehiscence that healed spontaneously. The donor-site wound healed
without problems except in two cases. One patient had an incomplete take of the skin graft; the other
developed wound infection and superficial sloughing. Both wounds healed spontaneously. In addition to the
feasibility of simultaneous flap harvesting with tumor resection, the flap's advantage in skull base
reconstruction is its reliable blood supply, which can provide adequate dural cover and protection of the brain.
Its size and moderate thickness are suitable for reconstruction of scalp and calvarial defects. The abundance of
reliably vascularized fat in the flap may be an advantage in long-term maintenance of the volume of the flap in
midface reconstruction. Similar to other soft tissue flaps, additional skeletal reconstruction may still be
required to achieve an optimal functional and aesthetic result.
PMID: 20601966

Hyperparathyroidism with bone tumor-like presentation, approach for diagnosis and

surgical intervention.

Hussein HA; Mebeed AH; Saber TKh; Farhat IG

This work aims to find out a clinical approach for diagnosis of cases with hyperparathyroidism presented with
bone tumor like condition as first and main presentation in order to differentiate primary bone tumors or
secondary bone metastases from different types of hyperparathyroidism and to clear out the indications and
type of surgery in such cases.It is a prospective case series study done in the National Cancer Institute from
April 2000 to May 2009. During this period we followed 45 cases of hyperparathyroidism (HPT) presented with
a main complaint of bone tumor-like lesion. We started by clinical evaluation, laboratory
investigationsincluding: Parathormone hormone, total and ionic calcium, renal function tests, alkaline
phosphatase, 24h urine calcium, C-AMP in urine or inappropriate parathormne like peptide if needed and
radiological investigations for preoperative localization including neck ultrasound, Tc99m Sestamibi scan, C-T
neck and superior mediastinum or M.R.I. Intraoperative ultrasound was used in some cases. Postoperative
bone desimetry and plain-X ray to follow bone mineral deposition were done.Preoperative diagnosis was: 80%
cases of primary hyperparathyroidism (pHPT), 15.5% cases of secondary hyperparathyroidism (sHPT), 4.5%
tertiary hyperparathyroidism (tHPT), benign adenoma in 73.3%, diffuse hyperplasia in 8.8% and one case of
parathyroid carcinoma. Neck ultrasound localized 29/38 adenoma (sensitivity = 73.3%), sestamibi localized
23/38 including another 2 cases of diffuse hyperplasia not detected by ultrasound (sensitivity = 63.8%), C-T
scan detected adenoma in upper mediastinum. Total preoperative localization was 84.2%. We used unilateral
exploration in 27 cases, and bilateral in 11 cases. Intraoperative ultrasound was useful in detection of 2
additional cases in the thyroid lobe tissue. Intraoperative parathormone hormone after 10 minutes dropped in
all of cases. Recurrence of the disease occurred in 2 cases during follow-up (5.2%). Postoperative sever
hypocalcemia occurred in 4 cases necessitating longer hospitalization and longer period of oral calcium.
Healing in cortical bone was faster than cancellous bone.Hyperparathyroidism should be suspected in all cases
with bone tumor-like presentation or even in earlier disease complain of bony or muscle aches. Intact P.T.H
and calcium (total &ionic), renal functions, 24 hours urine calcium, neck ultrasonography, and Tc 99m
pertechnitate/Tc99m sestsmibi subtraction scan can establish the diagnosis. Surgical treatment with unilateral
approach or bilateral when indicated with intraoperative ultrasound localization, frozen section examination
and assessment of intraoperative 10 minutes-P.T.H is very successful with minimal rate of recurrence and
complications. KEY WORDS: Hyperparathyroidism - Bone tumor-like presentation - Diagnosis - Surgical
approach.
PMID: 21863076

In vivo animal histomorphometric study for evaluating biocompatibility and

osteointegration of nano-hydroxyapatite as biomaterials in tissue engineering.

Abd El-Fattah H; Helmy Y; El-Kholy B; Marie M

The coming decade will bring new and even more complex advances that will transform oral and maxillofacial
surgery practice if the specialty is capable of transferring the advances of basic science into clinical practice.
Such advances include those in tissue engineering and nanotechnology. Three groups of eight animals (rats),

53
each was evaluated by grouting bone graft substitutes into 3 mm holes that were made into the
anteromedialtibialmetaphyses of rats. Two different formulations varying as to the type of hydroxyapatite
(HA) were used; Group 1: Nano-hydroxyapatite, Group 2: Control with HA only. Group 3: Control without any
bone graft substitutes (empty defects). Animals of each of the three groups were sacrificed in groups of eight
at postoperative week four. Histologic analysis revealed superior biocompatibility and osteointegration of
bone graft substitutes when nanohydroxyapatite was employed. At four weeks, there was more reactive new
bone formation in this group when compared to the hydroxyapatite group. The control group showed
incomplete closure of the defect. This study demonstrated that nano-hydroxyapatite improves the bioactivity
of bone implant and repair materials. Nanohydroxyapatite has good biocompatibility, finer mechanical
properties, adjustable degradation properties, good osteointegration and offers a wide range of potential
applications in the tissue engineering. KEY WORDS: Osteointegration- Nano-Hydroxyapatite- Biomaterials-
Tissue engineering.
PMID: 20601970

L-asparaginase therapy with concomitant cranial venous thrombosis: can MRI help
avoiding stroke.

Eloraby AM

To prospectively use MRI in the early detection of intracranial sino-venous thrombosis during the L-
asparaginase induction therapy of acute leukemia thus preventing the evolution of brain venous infarct.The
study population consisted of seventy patients receiving L-asparaginase induction therapy for acute leukemia
in the National Cancer Institute of Cairo University presenting with clinical neurological signs suggestive of
aseptic intracranial venous thrombosis. All the patients were studied by 1.5 Tesla magnet using conventional
MRI pulse sequences and MR venographic studies. The imaging findings were processed as regards the
detection of venous thrombosis, its signal criteria and the evaluation of any companion brain parenchymal
ischemic insults.Eleven patients were diagnosed with dural venous sinus thrombosis with subsequent specific
signal pattern of the thrombus that could be linked to the duration of thrombosis. The MR venographic studies
detected the thrombosis in nine cases out of eleven. Ten cases scored brain parenchymal signal abnormality
that could indicate infarction, eight of them were hemorrhagic in nature.L-asparaginase therapy is
accompanied by high risk of venous thrombosis that could involve the intra-cranial sino-venous structures.
MRI could be used effectively in the early diagnosis of such serious, curable complication using a combination
of conventional spin echo pulse sequences and MR venographic studies. Hemorrhagic venous infarcts should
draw the attention to underlying established venous thrombosis. KEY WORDS: Asparaginase - Venous
thrombosis-MRI.
PMID: 17671535

Locally advanced tumors of the scalp: the Egyptian National Cancer Institute experience.

Abo Sedira M; Amin AA; Rifaat MA; El-Sebai HI; El-Badawy MA; Aboul Kassem HA

It is well recognized that recurrent disease can occur following malignancy in the head and neck region. This is
particularly true for basal cell & squamous cell carcinoma, whereby recurrence may occur many years
following initial surgery or other modalities. We report here on skin malignancy occurring in the scalp with
skull invasion down to the dura mater. Composite resection of scalp, craniectomy, dural resection and
reconstruction including a free tissue transfer was analyzed.To evaluate our experience in full thickness scalp
resection and reconstruction.At the National Cancer Institute, Cairo University, twelve patients with locally
advanced tumors of the scalp invading the calvarium were treated with wide local excision of the scalp
combined with underlying craniectomy and dural resection if needed. Reconstruction was completed using
fascial graft for the dura, methyl methacrylate for the skull, and either giant rotational flap or free tissue
transfer.Between 1998 and 2002, twelve patients with locally advanced tumors of the scalp were subjected to
this surgery. All patients successfully tolerated the procedure and completely recovered with minimal
morbidity with acceptable cosmetic results.With the advent of free tissue transfer to cover large defects in the
skull and the availability of polymethyl methacrylate (bone cement) for cranioplasty, large defects in the
calvarium can be successfully resected and grafted with satisfactory outcome, improved salvage rate, and

54
prolonged survival.

PMID: 18301456

Lower lip reconstruction after tumor resection; a single author's experience with various
methods.

Rifaat MA

Squamous cell carcinoma is the most frequently seen malignant tumor of the lower lip. The more tissue is lost
from the lip after tumor resection, the more challenging is the reconstruction. Many methods have been
described, but each has its own advantages and its disadvantages. The author presents through his own clinical
experience with lower lip reconstruction at the NCI, an evaluation of the commonly practiced techniques.Over
a 3 year period from May 2002 till May 2005, 17 cases presented at the National Cancer Institute, Cairo
University, with lower lip squamous cell carcinoma. The lesions involved various regions of the lower lip
excluding the commissures. Following resection, the resulting defects ranged from 1 /3 of lip to total lip loss.
The age of the patients ranged from 28 to 67 years and they were 13 males and 4 females. With regards to the
reconstructive procedures used, Karapandzic technique (orbicularis oris myocutaneous flaps) was used in 7
patients, 3 of whom underwent secondary lower lip augmentation with upper lip switch flaps. Primary Abbe
(Lip switch) flap reconstruction was used in two patients, while 2 other patients were reconstructed with
bilateral fan flaps with vermilion reconstruction by mucosal advancement in one case and tongue flap in the
other. The radial forearm free flap was used only in 2 cases, and direct wound closure was achieved in three
cases. All patients were evaluated for early postoperative results emphasizing on flap viability and wound
problems and for late results emphasizing on oral continence, microstomia, and aesthetic outcome, in addition
to the usual oncological follow-up.All flaps used in this study survived completely including the 2 free flaps. In
the early postoperative period, minor wound breakdown occurred in all three cases reconstructed by utilizing
adjacent cheek skin flaps, but all wounds healed spontaneously. The latter three cases involved defects greater
than 2 /3 of lower lip and one of them was previously irradiated. Those patients then suffered from occasional
drooling of saliva. The best results in terms of oral continence and cosmetic outcome were achieved in those
cases reconstructed with flaps utilizing residual lower lip or upper lip tissues (i.e; the Karapandzic technique
(orbicularis oris myocutaneous flaps, and the Abbe (upper lip switch flaps). Nevertheless, microstomia
developed in four patients primarily reconstructed with the Karapandzic technique in which defects were
greater than one half of the lip. Only one of those patients tolerated her microstomia and required no further
treatment. The remaining three patients showed marked improvement after augmenting the lower lip with
bilateral paraphiltral lip switch flaps from upper lip in a second stage. The follow-up period ranged from 6
months to three years during which no patient had developed local recurrence or distant metastasis.Lower lip
reconstruction aims to restore function and appearance with the best results obtained by utilizing residual
normal lip tissues incorporating potentially innervated muscle fibers. With larger defects, reconstruction is less
than optimal, but every effort should be taken to obtain an adequate sphincter function and lip continence to
saliva, both of which are the most important goals to achieve in lip reconstruction.
PMID: 21503005

Management Head and Neck Ewing's Sarcoma Family of Tumors: Experience of the
National Cancer Institute, Cairo University.

Abdel Rahman H; El-Baradie T; El-Baradie M; Bahaa S; Shalan M

Ewing's sarcoma accounts for 4-6% of primary malignant bone tumors and it affects the head and neck in only
1-4% of cases. The purpose of this study was to review the NCI experience with Ewing's sarcoma of the head
and neck in children.A retrospective analysis of patient files with head and neck Ewing's sarcoma treated at the
National Cancer Institute, Cairo University, Egypt, during the period from 1997 to 2008 was done. Files were
reviewed and data for patients, tumor and treatment profile were extracted.Twenty patients out of 280 with
Ewing's sarcoma were identified during an 11-year period. Patients had a median age of 11.5 years (range 5

55
months - 22 years) with a male to female ratio of 1:1. The most common tumor site was in the mandible (9/20,
45%) followed by a neck mass (4/20, 20%) and a clavicular mass (3/20, 15%). Six patients (30%) were
metastatic at presentation. Most of the patients (19/20, 95%) received chemotherapy. Local therapy was in
the form of radical radiotherapy for 8 patients (40%), 2 patients (10%) had surgery alone, while five patients
(25%) had surgical resection and postoperative radiotherapy. Overall survival ranged from 1 to 128 months,
with a median of 36 months. At the end of the study, 9 patients (45%) were alive in CR, 6 (30%) were lost to FU
in disease progression, while 5 patients died from disease progression.Ewing's sarcoma of the head and neck is
a disease of a rare incidence with debate about the optimum local therapy. Small non-metastatic tumors with
good response to chemotherapy have abetter outcome. KEY WORDS: Ewing's sarcoma - Head and neck -
Management.
PMID: 15716996

Management of parapharyngeal space tumors at the National Cancer Institute, Egypt.

Attia A; El-Shafiey M; El-Shazly S; Shouman T; Zaky I

The purpose of this study is to evaluate parapharyngeal space (PPS) tumors as regards clinicopathological
features, preoperative assessment, different surgical approaches, perioperative complications, patterns of
recurrence and the role of non-surgical treatment.This study included twenty-five patients with (PPS) tumors
presented to NCI, Cairo University, from October 2001 to March 2003. The data of each patient included age,
sex, presenting symptoms and signs, provisional diagnosis, preoperative investigations, operative data,
histopathological examination, non-surgical treatment and state of follow up. All were collected and
analyzed.This study included 12 males and 13 females. The mean age was 37.1 years. The main presenting
symptom and sign was neck swelling. All patients were subjected to CT scan, while 9 patients had MRI.
Nineteen patients underwent fine needle aspiration cytology (FNAC) which was conclusive in only 16 patients.
Benign lesions were found in 12 patients (48%) and malignant lesions in 13 patients (52%). Parotid gland
tumors (40%) and neurogenic tumors (16%) were the commonest. Surgical excision was done in 22 cases.
There was no postoperative mortality and overall postoperative morbidity was 9% (2/22). Eight patients
received postoperative radiotherapy. Three patients with lymphoma were treated with chemotherapy and two
of them received involved field radiotherapy to the Waldyer's ring region. On follow up to 12-30 months, there
were only one local and two distant recurrences in the malignant group.Surgery is the mainstay treatment for
tumors of the (PPS). The addition of postoperative radiotherapy in certain indications in malignant tumors of
the (PPS) will improve the local control.
PMID: 19190695

Maxillary swing approach for surgical resection of recurrent nasopharyngeal tumors.

Amin AA

Purpose : To evaluate the efficacy of salvage nasopharyngectomy for locally recurrent nasopharyngeal tumors
through the maxillary swing approach. Methods : Antero -lateral access to the nasopharynx and its vicinity
through the maxillary swing approach was used. Through a Weber-Fergusson-Longmire incision, the whole
maxilla is freed and swung laterally while remaining attached to the masseter muscle and cheek flap. The
nasopharynx, para-pharyngeal space and infratemporal fossa are now exposed facilitating complete resection
of the tumor. Results : Seven patients were treated with this approach at the National Cancer Institute, Cairo
University. There were 6 males and one female with a range of age 16-57 years. Three patients had recurrent
carcinoma of the nasopharynx after primary radiation therapy, while four patients had locally advanced
recurrent juvenile nasopharyngeal angiofibroma (JNA). Using the operating microscope, complete tumor
resection was achieved in all patients except one patient with intracranial extension of JNA. There was no
surgical mortality. Complications occurred in three patients, one patient developed osteoradionecrosis
following re-irradiation, a patient had epiphora while palatal fistula occurred in another patient. The follow-up
period ranged from 3 months to 6 years, one patient died from distant disease and another patient is alive
with residual intra-cranial disease. Conclusion : Salvage nasopharyngectomy is a valid option for selected
patients with recurrent nasopharyngeal tumors. The maxillary swing approach allows safe and complete
resection for nasopharyngeal carcinoma as well as juvenile angiofibroma with intracranial extension. Key

56
Words : Recurrent nasopharyngeal tumors -Salvage nasopharyngectomy -Juvenile nasopharyngeal
angiofibroma.
PMID: 19847286

Microvascular radial forearm fasciocutaneous free flap for palatomaxillary reconstruction

following malignant tumor resection.

Elsherbiny M; Mebed A; Mebed H

The aim of this study is to report on the patient's quality of life and outcomes after reconstruction of
palatomaxillary defects by microvascular radial forearm fasciocutaneous free flap (RFFF) and dental
obturator.During the period between 2005-2007, 10 patients who had palato maxillary defects were
immediately reconstructed using RFFF to restore physiologic oronasal separation. All patients were treated for
malignant tumors of hard palate or maxilla and all had preservation of orbital floor. Vascular anastomoses
were done with the facial vessels in the neck. All the patients underwent a lateral thigh split-thickness skin
graft for closure of the donor site. Outcome measurements included post-operative assessment of flap survival
and healing, speech, swallowing and diet evaluation and quality of life. Dental rehabilitation was done 3
months postoperatively for all patients.Flap survival was successful in all cases. In the first 2 weeks post
operatively, 80% of patients had very good swallowing, speech and diet ability in the form of soft chewable
foods and by the end of 6 months, all patients had very good swallowing and speech function and were able to
eat all types of foods. Dental rehabilitation with obturator was easily applied and the presence of the flap did
not interfere with its application. The technique improved chewing ability and cosmosis. Complications
included, small oronasal fistula in 2 patients (20%) who required secondary sutures and delayed wound healing
of donor site in one patient.RFFF for soft tissue reconstruction after maxillectomy is a reliable technique that
provides a definitive physiologic separation between oral and nasal cavity. This allows very early improvement
of speech and swallowing without being totally dependent on obturator. Dental rehabilitation to improve
chewing and cosmoses can be done easily with minimal home care. Subsequently, the quality of life is
markedly improved.
PMID: 15912146

Midfacial degloving approach for malignant maxillary tumors.

Zaghloul AS; Nouh MA; Fatah HA

The aim of this work is to study the use of this technique in extirpation of malignant tumors of the maxillary
sinus. This includes the exposure for adequate tumor resection and the preservation of as much as possible
functional tissue integrity. This approach will be evaluated including the advantages and disadvantages as
regards the physiological function, aesthetic outcome and the complications related to the
procedure.Fourteen patients underwent the midfacial degloving technique for excision of malignant maxillary
sinus tumors during the period from 1999 to 2003 at the National Cancer Institute, Cairo University. This
procedure uses 4 basic incisions; sublabial incision, bilateral intercartilaginous incision, septocolumellar-
complete transfixion incisions, and bilateral pyriform aperture incisions extending to the vestibule. Immediate
reconstruction of the palatal defect was done in all cases by prosthetic obturator.All patients successfully
underwent the planned procedures through the midfacial degloving approach for the treatment of malignant
lesions of the maxilla without significant complications. Fifty of the patients had immediate postoperative face
edema which resolved within a week. Oral infection occurred in 4% of patients. Other sequelae were nasal
crusting and infraorbital hypoesthesia, both of which resolved within 2 to 3 months.The midfacial degloving
approach offers a good exposure of the mid third of the face with excellent cosmetic results. This approach
may be combined with down fracture of the maxilla for access to expose and resect sinonasal malignancies.
The midfacial degloving technique can be considered as a valuable procedure with low mortality and excellent
cosmetic outcome.
PMID: 15716993

57
Near total laryngectomy: a versatile approach for voice restoration in advanced T3 and T4
laryngeal cancer: functional results and survival.

Maamoun SI; Amira G; Younis A

Creation of a tunneled mucosal shunt between the trachea and pharynx that is controlled by remaining
intrinsic laryngeal musculature with its nerve supply is an acceptable voice restoration procedure for advanced
T3 and T4 laryngeal cancer. Such a tunnel will allow unilateral direction of air from lung to pharynx during
phonation and will prevent aspiration since deglutition is a vagal mediated response which will induce
contraction of tubed laryngeal musculature preventing aspiration. We previously reported our preliminary
experience with the technique and we adopted the voice restoration approach based on the concept of the
near total laryngectomy thereafter.Forty five patients with histologically proven squamous cell carcinoma of
the larynx were included in this study (between January 1998 and February 2001). They were 42 males and 3
females with a mean age of 52.6 years. Criteria for selection were a normal vocal process and arytenoid
cartilage on the opposite side of the lesion as evidenced by endoscopy and CT scan with no major subglottic
extension. In two patients supraglottic laryngectomy was carried out and in four other patients, complete
tumor extirpation necessitated total laryngectomy. Accordingly, near total laryngectomy was carried out in the
remaining 39 patients. Following a near total laryngectomy, where all laryngeal mucosa and cartilages are
resected sparing the contralateral arytenoid cartilage with the overlying mucosa and surrounding musculature,
the shunt was created by tubing the remaining mucosa with augmentation by pyriform sinus mucosa if
necessary. The resulting tube was fashioned over 14 FG catheter for diameter control only and the remaining
muscles were sutured over the tube. A permanent tracheostomy was established. Voice training was started
postoperatively following resumption of oral feeding.Only one patient died in the immediate postoperative
period due to massive myocardial infarction. One patient developed reactionary hemorrhage that was
explored and controlled. Minor salivary fistula developed in nine patients (23.1%) and all were managed
conservatively, none required intervention. Two patients (7.6%) had a retracted tracheostomy that required
refashioning. Thirteen patients (33.3%) suffered transient aspiration that resolved spontaneously, non
required intervention. Six patients developed recurrent disease (15.8%). The overall two year disease free
survival was 76%. None of the cases developed laryngeal mucosal recurrences. Intelligible speech was
achieved in 31 patients (81.6%). In the seven patients with shunt failure, insertion of a one way valve was
successful in five patients in restoring a good quality voice.Near total laryngectomy is an oncologically safe
procedure with acceptable complications that are well tolerated. It represents an ideal solution for patients
with advanced T3 and T4 laryngeal cancer. Voice quality is very good and it does not require further
management as is the case with prosthetic voice shunt valves.
PMID: 11669328

Neoadjuvant chemotherapy plus conventional radiotherapy or accelerated

hyperfractionation in stage III and IV nasopharyngeal carcinoma--a phase II study.

El-Weshi A; Khafaga Y; Allam A; Mosseri V; Ibrahim E; El-Serafi M; El-Badawi S

A prospective phase II trial was initiated in previously untreated patients with locally advanced nasopharyngeal
carcinoma (NPC). The goal was to achieve improvement in locoregional control, disease-free interval and
overall survival using induction chemotherapy and to compare conventional fractionation (CF) with an
accelerated hyperfractionation (AHF) regimen. Fifty patients were treated (5 AJCC Stage III, 45 Stage IV) with
induction chemotherapy consisting of two cycles of cisplatin and 5-fluorouracil. Patients were then
randomized between CF and AHF therapy. A clinical response to induction chemotherapy was reported in 86%
of patients prior to radiotherapy (44% complete response, 42% partial response). Patients with complete or
major partial responses to induction chemotherapy had a significantly better 5-year overall survival (60%) and
disease-free interval (59%) than those with no response or minor partial response (15% and 18% p = 0.009 and
0.0009). Acute radiation reactions were more pronounced in the AHF group (p = 0.0002), and the incidence of
late normal tissue injury was more frequent (p = 0.08). At 5 years, the locoregional control rate was higher in
the AHF arm (76%) than in the CF group (54%), but the difference was not significant (HR, 0.52; 95%, Cl, 0.15-

58
2.83; p = 0.186). With a median follow-up period of 55 months (range 4-120), the 5-year disease-free interval
and overall survival rates were more favorable in the AHF group than in the CF group, but the differences were
not significant (59% and 54% vs. 34% and 36%, respectively, HR for disease-free interval = 0.71; 95% CI, 0.27-
1.88; p=0.198 and HR for overall survival = 0.81; 95% CI, 0.37-1.78; p=0.433). The overall treatment failure rate
was 48%. Locoregional failures occurred in 12 patients (24%) and the incidence of distant metastases reached
30%. Response to induction chemotherapy is strongly predictive for locoregional control, disease-free interval
and overall survival. Accelerated hyperfractionation was associated with high incidence of acute and late
toxicity without significant improvement in locoregional control rate. The optimal chemotherapy dose and
sequencing with radiotherapy needs to be investigated in future studies. Distant metastases remain the main
cause of treatment failure in NPC.
PMID: 22570651

Overexpression of s6 kinase 1 in brain tumours is associated with induction of hypoxia-

responsive genes and predicts patients' survival.

Ismail HM

mTOR/S6K pathway is a crucial regulator of cell growth and metabolism. Deregulated signalling via S6K has
been linked to various human pathologies, including metabolic disorders and cancer. Many of the molecules
signalling upstream of S6K have been shown to be either mutated or overexpressed in tumours, leading to S6K
activation. The role of S6K1 in brain tumours is not fully investigated. In this study, we investigated the gene
expression profile of S6 kinases in brain and CNS tumours using the publically available Cancer Microarray
Database. We found that S6K1 but not S6K2 gene is overexpressed in brain tumours and this upregulation is
associated with patients' poor survival. Furthermore, we interrogated Oncomine database for the expression
profile of hypoxia-induced genes using a literature-defined concept. This gene list included HIF1A, VEGFA,
SOX4, SOX9, MMP2, and NEDD9. We show that those genes are upregulated in all brain tumour studies
investigated. Additionally, we analysed the coexpression profile of S6K1 and hypoxia responsive genes. The
analysis was done across 4 different brain studies and showed that S6K1 is co-overexpressed with several
hypoxia responsive genes. This study highlights the possible role of S6K1 in brain tumour progression and
prediction of patients' survival. However, new epidemiological studies should be conducted in order to confirm
these associations and to refine the role of S6K1 in brain tumours as a useful marker for patients' survival.
PMID: 22099963

Parotidectomy for benign parotid tumors: An aesthetic approach.

Amin A; Mostafa A; Rifaat M; Nabawi A; Shallan M; Rabie A; Elzohairy M

The sternocleidomastoid (SCM) partial thickness muscle flap is among the various methods described to
correct parotidectomy defects, but its indications and limitations are not clearly demonstrated in several
reports. This study was done to test the aesthetic outcome of this method, its indications and limitations. The
technique was combined with a face lift incision to further improve the outcome.At the National Cancer
Institute, Cairo University, Egypt, 23 patients presenting with benign tumors underwent parotidectomy, 19 had
superficial parotidectomy and four had total parotidectomy done. The superiorly based (SCM) muscle flap was
used to correct the contour deformity. The aesthetic result was evaluated by assessing and scoring the overall
appearance of the scar, the degree of symmetry of the reconstructed parotid region and the site of the donor
muscle to their contralateral normal sides. The overall aesthetic appearance was then calculated by the
summation of the scores of the latter three parameters. Patients' satisfaction was assessed by patients'
questionnaire.The overall aesthetic appearance was good in 17 patients, and moderate in six patients. 16/23
patients had an overall deep satisfaction with the result. The residual hollowness of the parotid following
reconstruction of the total parotidectomy defect and the poor quality of scars were the main reasons affecting
the aesthetic outcome.Superficial parotidectomy through facelift incision with immediate reconstruction with
superiorly based partial thickness SCM flap allows adequate resection of most benign parotid tumors with a
satisfactory aesthetic outcome and minimal donor site morbidity.
PMID: 3507426

59
 Pharyngeal repair after laryngopharyngectomy: 4-year experience.

Rifai M; Amer F; Abdel-Meguid H; Mebed H

The most common forms of surgical intervention carried out at the National Cancer Institute of Cairo for
patients initially seen with hypopharyngeal carcinoma are (1) laryngopharyngectomy and pharyngeal repair
using the pectoralis major myocutaneous flap (PMMF) and (2) extrapleural total
pharyngolaryngoesophagectomy with gastric transposition (GT) and pharyngogastrostomy. The advantages
and disadvantages with both techniques will be discussed on the basis of results of 69 patients with different
tumor distributions over a 4-year period.
PMID: 21863077

Pre-prosthetic surgical alterations in maxillectomy to enhance the prosthetic prognoses as

part of rehabilitation of oral cancer patient.

Abdel Fattah H; Zaghloul A

After maxillectomy, prosthetic restoration of the resulting defect is an essential step because it signals the
beginning of patient's rehabilitation. An obturator used to restore the defect should be comfortable, restore
adequate speech, deglutition, and mastication, and is acceptable cosmetically, Success will depend on the size
and location of the defect and the quantity and integrity of the remaining structures, in addition to pre-
prosthetic surgical preparation of the defect sit. Preoperative cooperation between the surgeon oncologists
and the maxillofacial surgeon may allow obturation of a resultant defect by preservation of the premaxilla or
the tuberosity on the defect side and maintaining the alveolar bone adjacent to the defect of an abutment
tooth. This study was carried out to evaluate the importance of Pre-prosthetic surgical alterations at the time
of maxillectomy on the enhancement of the prosthetic prognoses as part of rehabilitation of the oral cancer
patient. The present study was carried out on 66 cancer patient, 41 males 25 females ages ranging from 33 to
72 years, seeking treatment between 2003-2008 at The National Cancer Institute, Cairo university they
underwent immediate prosthetic rehabilitation after maxillectomy surgery to remove the malignant tumor as
apart of cancer treatment. Patients were divided into groups according to preprosthetic surgical preparation
before prosthetic restoration. GROUP(A): Resection of maxilla followed by preprosthatic surgical preparation
24 cancer patients (13 males- 11 femals). GROUP(B): Resection of maxilla without any preprosthetic surgical
preparation. 42 cancer patients (28 males and 14 females). Outcome variables measured included facial
contour and aesthetic results, speech understandability, ability to eat solid foods, oronasal separation,
socializing outside the home, and return-to-work status. Flap success and donor site morbidity were also
studied. This study concluded that the cornerstone to improve the prosthetic restoration of the maxillary
defect resulting maxillary resection as part of the treatment of maxillofacial tumor depend on the close
cooperation between the prosthodontist and the surgeon, this can be achieved by combination of surgical and
prosthetic technique which can be controlled by pre-prosthetic surgery during maxillect omy. KEY WORDS:
Maxillary re-construction- Pre-prosthetic surgery- Oral cancer.
PMID: 21508824

Reconstruction of medium-sized defects of oral commissure by combining double full-

thickness cheek rhomboidal flaps and a small lip switch flap.

Rifaat MA

Reconstruction of oral commissure defects aims at securing oral competence and providing an acceptable
appearance. The methods described by using either a cross lip flap or a flap from the adjacent cheek skin and
mucosa may not be able to achieve such goals if each method is used on its own. We have combined double
full-thickness cheek rhomboidal flaps with a small lip switch flap from the remaining lip segment to reconstruct
medium-sized full-thickness defects of the oral commissure, following tumor excision in 7 patients. The
functional and aesthetic outcomes were assessed by the evaluation of 3 parameters under each category. Each
parameter received a score of good, moderate, or poor. Six patients had a good overall functional score.

60
Microstomia was noted only in 1 patient. The overall aesthetic score for all the 7 patients was moderate. In
conclusion, reconstruction of medium-sized commissural defects by the present technique achieves adequate
oral competence and a satisfactory cosmetic result.
PMID: 22776815

Reliability of fine needle aspiration cytology (FNAC) as a diagnostic tool in cases of cervical
lymphadenopathy.

Hafez NH; Tahoun NS

The aim of this work is to evaluate the reliability and diagnostic accuracy of fine needle aspiration cytology
(FNAC) of cervical lymph nodes with an emphasis on discordant cases between the cytology and the
histopathology.This retrospective study was conducted on 157 selected patients with cervical
lymphadenopathy that had undergone FNAC. Cervical nodal enlargement was the first clinical manifestation of
the patients in all cases. Hypocelluar slides were excluded from the current study. The cytopathological
diagnoses were compared with the histopathological results of the same excised nodes. For all discordant
cases, special attention was focused on the cytomorphological features. Diagnostic sensitivity, specificity,
positive predictive value (PPV), negative predictive value (NPV), accuracy, and discordance rate were
calculated.The cytological diagnoses were found to be benign in 48 cases (30.6%) and malignant in 109 cases
(69.4%). The overall diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of
FNAC of cervical lymph nodes were 90.9%, 67.2%, 82.6%, and 81.3%, respectively. The overall diagnostic
accuracy was 82.2% (129/157), while the overall discordance rate was 17.8% (28/157). The diagnostic accuracy
of reactive lymphoid hyperplasia, chronic necrotizing lymphadenitis, chronic granulomatous lymphadenitis,
metastatic carcinoma, Hodgkin lymphoma, and Non Hodgkin lymphoma was 85%, 83.3%, 70%, 100%, 77.8%,
and 75%, respectively.The overall diagnostic accuracy of FNAC of cervical lymph nodes was 82.2% while the
overall discordance rate was 17.8%. The evaluation of FNA in patients with no previously diagnosed
malignancy should be interpreted by an experienced cytopathologist in the context of clinical, radiological, and
laboratory finding and if any of these findings is suspicious, further investigation is justified to overcome the
limitations and pitfalls of the cytomorphological features when applied alone.
PMID: 15959545

Re-operation for the treatment of well differentiated thyroid cancer: necessity, safety and
impaction on further management.

El-Zohairy M; Zaher A

The diagnosis of thyroid carcinoma during the course of lobectomy for a dominant nodule occasionally cannot
be rendered on the basis of frozen section. Once the diagnosis of carcinoma is made, the question of
completion thyroidectomy arises.During a period of 3 years, 28 patients diagnosed with well-differentiated
thyroid cancer (WDTC), and operated upon with less than total thyroidectomy, were admitted to our
department. Patients had no clinical or radiological evidence of any residual disease at the time of admission.
All were submitted for total thyroidectomy.There were 7 men and 21 women (1:3), and the average age was
38.6+/-1.3 years (range, 20 to 62 years). The postoperative morbidity in completion thyroidectomy consisted
of transient hypoparathyroidism in 2 patients (7.1 %), permanent hypoparathyroidism in 1 patient (3.5%),
there was no recurrent laryngeal nerve palsy, there were haematoma in 2 patients, and seroma in 1 patient.
Completion thyroidectomy resulted in detecting 9 patients (32.1%) having residual disease that was not
clinically manifest.Although many surgeons advocate total or near-total thyroidectomy for differentiated
thyroid carcinoma, some of these surgeons hesitate to complete thyroidectomy after lobectomy for thyroid
nodule when there is no clinical evidence to suggest bilateral disease, for fear of added morbidity to the
patients. However, as demonstrated in this study, completion thyroidectomy was shown to be a fairly safe
procedure, which carries a low incidence of complications. It also facilitates further management and follow-
up with radioactive iodine. The decision to perform completion thyroidectomy for WDTC should be based on
the patient's risk category, and not on a concern for risk of complications from the second procedure.

61
PMID: 20601971

Role of 131-I MIBG Therapy in the Treatment of Advanced Neuroblastoma.

Riad R; Kotb M; Omar W; Zaher A; Khalafalla K; Fawzy M; El-Wakil M; Ebeid E

Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most extracranial malignant
solid tumor of childhood. Many therapeutic strategies has evolved over the last 20 years, based upon work by
international cooperative groups and smaller cohort studies. Novel therapies to improve initial disease
response and treatment of minimal residual disease are required to improve survival for these children with
highrisk neuroblastoma. Radio-labeled MIBG therapy has been tried in the treatment of advanced stage 3&4
neuroblastoma in an attempt to improve patients' outcome. The use of radio-labeled MIBG to treat
neuroblastoma has arisen from the high sensitivity and specificity of in-vivo MIBG imaging for detection of
primary and metastatic tumors.To determine the impact of MIBG therapy on neuroblastoma patients'
outcome and its impact on their quality of life.Thirty pediatric patients with stage 4 pathologically proven
neuroblastoma are included in this study. Eighteen of the study patients (60%) were males and 12 (40%) were
females. All the patients had partially responsive tumor to first-line therapy +/- surgey. 131-I MIBG doses
ranged from 100 to 150mCi with number of courses ranged from 1-7 according to response and toxicity.Two
patients achieved complete remission (CR) and were still disease-free after 64 &69 months. Nine patients
showed partial remission (PR) to 131-I MIBG, all the nine patients were alive at 16-57 months (mean 30.6
months) among whom seven were alive with stable disease and two patients were alive with progressive
disease (PD) at the end of study. Eighteen patients remained stable after 131-I MIBG therapy, among them six
were alive with PD and four were alive with stable disease at the end of study, while the remaining eight
patients died. The last patient developed PD and died within 15 months. The 5 years event free survival (EFS)
was 48.2% and the overall survival (OS) was 69%.We concluded that 131-I MIBG therapy has favorable
therapeutic effect for advanced neuroblastoma patients. Controlled clinical trials should be considered to
evaluate the true potential of 131-I MIBG therapy. KEY WORDS: MIBG therapy - Advanced neuroblastoma.
PMID: 20601968

Role of pectoralis major myocutanuos flap in salvage laryngeal surgery for prophylaxis of
pharyngocutaneuos fistula and reconstruction of skin defect.

Mebeed AH; Hussein HA; Saber TKh; Zohairy MA; Lotayef M

This study was carried out to minimize the incidence of pharyngocutaneous fistula (PCF) following salvage
laryngeal surgery using vascularized pedicle pectoralis major myocutaneous flap (PMMC) for enhancing wound
healing, rapid intake of oral feeding, reconstruction of desqauamated irradiated skin, achieving short hospital
stay and protection against catastrophic blow out mortality.This case series study of sixteen patients carried
out from May 2005 to July 2009, at the National Cancer Institute, Cairo University where we applied PMMC
flap in salvage laryngeal surgery for those with high risk to develop complications: Patients of poor general
conditions (anemia, hypoproteinemia, diabetics) and/or poor local conditions for healing (irradiated neck,
extensive local or nodal recurrence with skin desquamation, infiltration or tumor fungation which need
extensive resection). Five cases had been treated with primary cobalt radiotherapy laryngeal field only and 4
cases laryngeal field with draining neck nodes, while photon therapy was given in 4 cases as laryngeal field
only and 3 cases laryngeal field with draining neck nodes. All cases were squamous cell carcinoma (13 cases
grade 2, 2 cases grade 3 and one case grade 1) proved before radiotherapy. Supraglottic recurrence was
detected in 7 cases (43.75%) and glottis in 9 cases (56.25%). Following salvage surgery, 11 cases were staged
T3 N0, N1 and N2, 3 cases were T2 N0 or N1 and 2 cases were T4 N2 with skin infiltration. Tracheostomy was
there in 4 cases.The study included fifteen males (93.75%) and one female (6.25%), age was between 38-73
years (mean=55.5 years). Five cases were operated on as total laryngectomy with excision of skin flaps +
PMMC flap, 4 cases as total laryngectomy with skin flap excision + functional block neck dissection + PMMC
flap and 7 cases as total laryngectomy + block neck dissection with skin excision (modified radical in 4 cases
&radical in 3 cases) + PMMC flap reconstruction. Flaps survived in all cases, PCF developed in 2 cases (12.5%)
with wound infection but healed conservatively within 2 weeks. Dropped shoulder occurred in 3 cases
(18.75%) treated by physiotherapy. Mild postoperative chest infection developed in 7 cases (36.84%) improved

62
by broad spectrum antibiotics and chest physiotherapy.Routine use of pectoralis major myocutaneous flap in
salvage laryngeal surgery is of great help in such high risk patients to minimize incidence of
pharyngocutaneous fistula and to allow primary skin wound healing. This flap will give the patient the
advantage of early oral feeding, good tracheostomy care, short hospital stay and protection against
catastrophic vascular blow out mortality. KEY WORDS: Pectoralis major myocutaneous flap - Prevention of
pharyngocutaneous fistula - Salvage laryngectomy.
PMID: 20424656

Stepladder reconstructive options in post-ablative complex surgical defects in the head

and neck.

El Marakby HH; Naguib SF; El-Sawy Ael-H; Amin AA

Reconstruction of head and neck defects can pose many challenges to the reconstructive head and neck
surgeon. Achieving the best cosmetic and functional results without compromising the safety of oncologic
surgery are the primary reconstructive goals. Speech and articulation are particularly important in oral
reconstructive procedures. In addition, preservation of the integrity and function of the donor sites should
always be considered in all reconstructive procedures.The aim of the study is to evaluate different
reconstructive options in complex defects of the head and neck region after resection of malignant tumours.
The feasibility of the reconstructive ladder starting from simple techniques such as local flaps and skin grafts
up to free flaps will be assessed.In this study we evaluated different reconstructive procedures used in 50
patients with complex head and neck defects undertaken at the department of surgery at the National Cancer
Institute between July 2003 and December 2007.The average age of patients was 52 years and the range was
26-67 years. Most of the tumours were either squamous cell carcinoma (74 %) or Basal cell carcinoma (20 %).
Tumour sites included the nose (6 %), lip (10 %), cheek (12 %) scalp (6 %) as well as mucosal defects of the oral
cavity (40 %) and the hypopharynx (20 %). We used local flaps and skin grafts in reconstruction in 36 % of cases
and pedicled flaps in 32% while free flaps were used in 32 % of cases. Complications occurred in 32 % of
patients of which total flaps loss constituted 6 % and partial flap loss 4 %. Minor complications such as oro-
cutaneous fistulae, wound infection, seroma and haematoma were noticed in 22 % and all of them were
treated conservatively. The final functional and aesthetic results were satisfactory in 60% of cases while poor
results were encountered in patients who suffered some degree of flap loss. KEY WORDS: Head and neck
reconstruction - Pedicled flaps - Free flaps.
PMID: 22776812

Stereotactic radiosurgery and radiotherapy in benign intracranial meningioma.

Eldebawy E; Mousa A; Reda W; Elgantiry M

To investigate the role of stereotactic radio surgery (SRS) and hypo-fractionated stereotactic radiotherapy
(SRT) in treatment of benign intracranial meningioma.Between 2003 and 2010, 32 patients with a median age
of 44years (range 21-67years) were treated with SRS (n=19), and hypo-fractionated SRT (n=13) for intracranial
meningioma. Fourteen patients underwent SRS or SRT as their primary treatment, while 18 patients
underwent post operative SRS or SRT (PORT). Cumulative progression free survival, overall cumulative survival,
toxicity and symptomatology were evaluated.The median follow up period was 39months (range 6-72months).
The 5year overall survival and progression free survival were 90±5% and 94±4% after SRT or SRS respectively.
Symptoms were improved or stable in 94% of patients. Acute toxicity was mild, and was seen in 41% of
patients. Clinically significant late morbidity or new cranial nerve palsies did not occur.Stereotactic radio
surgery (SRS) and hypo-fractionated stereotactic radiotherapy (SRT) are effective and safe treatment modality
for local control of meningioma with low risk of significant late toxicity. In case of large tumor size and
adjacent critical structures, hypo-fractionated SRT is highly recommended.
PMID: 19652672

63
 Straight midline mandibulotomy: technique and results of treatment.

El-Zohairy MA

Mandibulotomy is an important surgical approach to tumors of the oral cavity and oropharynx. However the
approaches and complications associated with this procedure varies in many studies.The objective of this
study is to discuss the feasibility of the technique and to evaluate its advantage and related complications.A
prospective study of 23 consecutive patients undergoing planned straight midline mandibular osteotomies as
part of the ablative surgery for intraoral carcinoma. Twelve patients had primary lesions affecting the anterior
two-thirds of the tongue, four at floor of mouth, three at posterior two-thirds of the tongue, two at deep lobe
of parotid, one at soft palate and one at tonsil. Thirteen cases had T3 tumours, seven had T2 lesions and three
had T4 tumors. In 5 patients the mandibulotomy was combined with a marginal mandibulectomy. Nineteen
patients received post-operative radiotherapy. Various flaps were used for reconstruction : Pectoralis major
myocutaneous flap ( n=7 ) , tongue flap ( n=4 ) and radial forearm free vascular flap ( n=2 ) cases. Primary
closure using remaining mucosa was achieved in 10 patients. Adequate margins were achieved in all patients
as proved by histopathology.Primary healing of the osteotomy was noted in all patients and 5 ( 21.7 % )
patients had mandibulotomyrelated complications. One patient has lost one of the incisors adjacent to the
mandibulotomy site during the operation. Dental problems with resorption of the alveolar margin and
loosening of the teeth adjacent to the osteotomy were observed in 3 patients, one of them had lost his
teeth.Straight midline mandibulotomy provides excellent exposure for oral and oropharyngeal tumours, it is an
easy procedure with low complication rate. Key Words : Straight midline mandibulotomy - Mandibulotomy -
Mandibular swing - Oral cavity and orophayngeal neoplasms - Rigid fixation.
PMID: 22227539

Supine Craniospinal Irradiation in Children: Patient position modification, dose uniformity

and early adverse effects.

Zaghloul MS; Eldebawy E; Attalah E; Ahmed S; Nazmy M; Aboel Anin H

Background: Different craniospinal irradiation techniques are complex. The homogeneity of the dose to the
target and the normal tissues at risk affect both the control rate and the level of adverse effects. Patients and
methods: Thirty one patients were treated with CSI in the supine position. Custom-made Styrofoam was
tailored for each patient to straighten the convexity and concavity of the spinal axis allowing better dose
distribution uniformity during CSI technique. In the first 6 patients, CT simulation were performed twice: one
time with the patient lying directly on the vacuum mattress without the foam (the conventional way) and the
second while lying on the foam. Dose distribution was calculated using a 3D conformal planning. The gap
between the fields was determined using isodose alignment method. All treatment portals were verified
during the first 3 treatment sessions and once weekly thereafter using either cone-beam or portal image
device. Weekly feathering (shifting of the junction between the 2 adjacent radiation fields) was routinely
performed. Results: The 95% dose distribution had better coverage with the foam (p=0.042) while the hot
volume of 110% and 105% dosage were significantly lesser than conventional technique (both p=0.028). The
organs at risk received nearly similar radiation doses in the 2 positions. The CSI led to minimal immediate
adverse effects that were reversible. Weight loss was experienced by 55% of patients. Conclusion: This
modified technique of CSI is simple, ensuring better dose distribution to CSI target without increasing the dose
to the surrounding organs at risk. It is tolerable and safe to apply. Key words: Craniospinal irradiation, supine,
Medulloblastoma, CNS leukemia, Conformal radiotherapy, 3D-CRT, Immediate adverse effects.
PMID: 21863070

64
 Telomerase expression as complementary prognostic factor in neuroblastoma.

Bahnassy AA; Fawzy M; El-Wakil M; Al-Bolkainy TM; Kamel MM; Abd El-Azim H

Neuroblastoma (NB) is an aggressive tumor of childhood with a highly heterogeneous course. Identification of
standard prognostic factors has several limitations. Hence, there is an increasing demand to identify new
prognostic factors and tools that help in risk stratification of patients for proper treatment.To assess the
prognostic and predictive impact of quantitative telomerase expression in NB patients.We investigated
quantitative telomerase expression by immunohistochemistry in 44 neuroblastoma patients. Results were
correlated with standard prognostic factors, n-myc amplification by chromogen in situ hybridization (CISH) and
patients' response to treatment and survival.High telomerase expression and n-myc expression were reported
in 52.3% and 56.8% ; respectively. There was a significant relation between telomerase expression and n-myc
amplification. Stage 3 and 4 represented 91% of patients. Thirteen patients showed complete remission, 9
partial remission, 19 no response and 3 showed progressive disease. The median followup was 3 years with
80% overall and 72% progression free survival for the low teleomerase expression group; and 52.2% and 55.4%
for high teleomerase expression group. High Telomerase expression by immunohistochemistry was
significantly associated with n-myc amplification and with poor response to treatment with a trend toward
lower overall and progression free survival.Telomerase expression by immunohistochemistry is a simple
potential tool for risk stratification of NB patients. CISH can serve as a readily available alternative simple tool,
compared to FISH, in identifying neuroblastoma cases with abnormal n-myc gene copy number. KEY WORDS:
Telomerase expression- N-myc amplification- Prognosis- Neuroblastoma.
PMID: 20571599

The paraneoplastic limbic encephalitis: MRI characterization of a deceiving neurological

disorder.

Eloraby AM

Establishing diagnostic MRI criteria for such a pathological entity to enable the oncologist to modify the
treatment plan combating the neurological deficits from a different diagnostic prospective, hence improving
the quality of life of cancer patients.Sixty patients from the National Cancer Institute (Cairo University)
diagnosed with different types of cancer at time interval of one year were included in the study pool. Twenty
patients were known to have lung cancer, 15 patients with breast cancer, 10 patients with lymphoma and 15
patients with leukemia. No age or sex predilection. All patients performed cranial MRI before and after
intravenous contrast media injection, backed by the clinical assumption of encephalopathy and wide spectrum
of neurological symptoms as seizures, dementia and behavioral disorders. Some of the patients with positive
MRI studies performed serological test to detect onconeuronal antibodies. The study was carried out from
January till December 2007.Thirty three patients' revealed definite MRI signal abnormality involving the limbic
system proper and further temporal lobes affection while five patients revealed mixed pattern of regional
encephalitic changes including the cerebellum, frontal lobes and brain stem. The rest of the study group
exhibited no signs of encephalitis.Specific MRI appearance could be traced in paraneoplastic limbic
encephalitis thus establishing diagnostic pattern for such entity that could help characterizing the disease with
subsequent impact upon the treatment protocol resulting in regaining normal brain faculties and better life
quality for such cancer patients. KEY WORDS: Paraneoplastic - Limbic encephalitis - MRI.
PMID: 17237850

The reliability of pectoralis major myocutaneous flap in head and neck reconstruction.

El-Marakby HH

The pectoralis major myocutaneous pedicle flap (PMMPF) has been considered to be the "workhorse" of
pedicled flaps in head and neck reconstruction. Several series of PMMPF procedures in head and neck
reconstruction have been reported in the literature. Even with the worldwide use of free flaps, the flap is still
considered the mainstay head and neck reconstructive procedures in many centers. However, the flap is

65
usually associated with a high incidence of complications in addition to its large bulk compared with the free
fasciocutaneous flaps. Also the final functional and the aesthetic results are not comparable to free flaps head
and neck reconstruction.The aim of the study is to evaluate the reliability of such flap in selected cases of head
and neck reconstruction. The indications, technique, complications and the functional as well as the aesthetic
results of the flap utilization were evaluated.Between May 2002 and May 2005 a 26 consecutive head and
neck reconstruction procedures using the PMMPF were carried out on 25 patients at the Department of
Surgery, National Cancer Institute, Cairo University. The indications for the flap use were defects due to
resection of stage II-IV cancer in the head and neck region. The site, stage of the disease and the presence or
absence of distant metastasis were assessed. Also preoperative assessment included the fitness of patients for
such an extensive procedure. The total operative time, the need for blood transfusion, the postoperative
complications, were all documented. The length of hospital stay, the follow-up of patients as well as the
incidence of local recurrence underneath the flap were all evaluated.Pectoralis major myocutaneous pedicled
flap reconstructions were used to reconstruct defects in the following sites: oral cavity (10 patients);
oropharynx/ hypopharynx, (5 patients); and neck or face (10 patients). Of the 26 PMMPF reconstructions, 22
flaps were carried out as primary reconstructive procedures, whereas 4 flaps were "salvage" procedures
(reconstruction after fistula, free flap failure, coverage of exposed mandibular prosthesis). Fifteen patients
(60%) had complications such as wound dehiscence, infection, hematoma, seroma, partial flap failure, total
flap failure, fistula, and donor site complications. A higher complication rates were associated with the
utilization of the flap as a salvage procedure, number of co morbidities, and in oral cavity
reconstructions.Although the PMMPF is a versatile flap in head and neck reconstruction, being in the proximity
of the region with good reach to different areas of the face, oral cavity, and the pharynx; the flap is fraught
with a high complication rate. The wide use and the reliability of free flaps in head and neck reconstruction
have superseded the use of the PMMPF flap in comparable circumstances. However, the flap still has a place in
head and neck reconstruction, particularly after resection of locally advanced tumours. Also the flap can be still
used as a salvage procedure after free flaps failure or when there is a shortage of the microsurgery facility.
PMID: 22185515

The submental flap for oral cavity reconstruction: extended indications and technical
refinements.

Amin AA; Sakkary MA; Khalil AA; Rifaat MA; Zayed SB

The submental flap is gaining popularity as a simple technique for reconstruction of small to moderate size
defects of the oral cavity. However, its role in composite defects involving the jaw is not clearly defined.
Indeed, controversy exists about the flap's interference with an oncologically sound neck dissectionA total of
21 patients with oral cavity cancers over a three year period were included. All patients underwent surgical
resection and immediate reconstruction with submental flap except one patient who had delayed
reconstruction with reversed flap. The flap was used for reconstruction of intra-oral soft tissue defect in 13
patients and composite defects in 8 patients.Of 21 patients 12 were males and 9 were females, age ranged
from 32 to 83 years. The primary tumor sites included buccal mucosa (7), tongue (4), alveolar margin (3), floor
of mouth (5) and lip (2). Eventually in this study, we adopted completing the neck dissection first before flap
harvest. Complete flap loss occurred in 2 whereas 3 patients had partial flap loss. Follow up ranged from 3 to
44 months, one patient died from metastatic disease. Four patients developed neck recurrences.The
submental flap is a valid option for reconstruction of intra-oral soft tissue as well as composite oral defects
particularly in elderly patients. However, oncologically sound neck dissection should be assured.
PMID: 18228214

The value of simultaneous co-registration of 99mTc- MDP and 131Iodine in metastatic

differentiated thyroid carcinoma.

Kotb MH; Omar W; El-Maghraby T; El-Bedwihy M; El-Tawdy M; Mustafa H; Al-Nahhas A

The lack of anatomical details in standard (131)Iodine whole body scanning ((131)I WBS) interferes with the
proper localization of metastatic differentiated thyroid carcinoma (DTC) lesions. In addition, nearby or
overlapping variable physiological distribution of (131)I may affect the specificity of (131)I uptake, giving

66
indeterminate results. The aim of this study was to demonstrate the clinical usefulness of simultaneous co-
registration of (99m)Tc MDP bone scanning as an anatomical landmark with (131)I scanning in the evaluation
of metastatic DTC.Twenty-five patients (16 females and 9 males, mean age +/- SD = 52 +/- 13 years) with
metastatic DTC (17 papillary, 8 follicular), were included. Whole body scanning using a 256 x 1024 matrix and
an 8 cm/min scan rate were obtained 48 hours after oral administration of 185-370 MBq 131I and 2 hours
after IV administration of 185-370 MBq (99m)Tc MDP using a dual head gamma camera equipped with high
energy parallel hole collimators. Occasionally, additional simultaneous co-registration of localised detailed
images was also performed using a 256 x 256 matrix size. The two planar images were fused with optional
fusion of SPECT images. The data from standard (131)I scanning and fused (131)I/ (99m)Tc-MDP scanning were
separately assessed by two nuclear medicine physicians. Fusion images were considered to improve image
interpretation in comparison with standard (131)I scanning when they provided better localization of
lesions.All lesions in the present study were validated by radiological images and clinical follow up for at least
12 months. Forty-eight metastatic lesions were confirmed as follows: 2 in the skull, 10 in the neck, 20 in the
thorax, 12 in the pelvic-abdominal region and 4 in the extremities. Standard (131)I WBS showed 54 extra-
thyroidal foci with 8 false positive lesions of which 2 were located in the scalp and 6 in the pelvic-abdominal
region extra-skeleton (i.e. sensitivity 100%, specificity 86%). Out of the 48 validated lesions, 16 were
indeterminately localized: 10 in the thorax (3 mediastinal nodal lesions, 5 vertebral lesions and 2 ribs) and 6 in
the pelvic-abdominal region (2 upper sacral, 2 sacroiliac region and 2 ischial bone). Fusion images confirmed
the precise localization of the pathological uptake in the validated 48 lesions (sensitivity 100%, specificity
100%). There were 2 (4%) indeterminate lesions in fused planar imaging that were clearly localized via fused
SPECT images.Fusion images using simultaneous co-registration of (131)I and (99m)Tc MDP scanning is a
simple and feasible technique that improves the anatomically limited interpretation of scintigraphy using
(131)I alone in patients with metastatic differentiated thyroid carcinoma. The diagnostic advantage of this
technique seems to be more apparent in the thoracic and pelvic- abdominal regions in contrast to the neck
and extremities.
PMID: 17102819

The versatile naso-labial flaps in facial reconstruction.

El-Marakby HH

Surgical excision of tumors from the face may create a defect that is difficult to restore. Skin grafts can only
cover superficial defects and has a natural tendency to contract and may not take properly. Also, because of
the colour mismatch, it is not cosmetically identical to the face. The use of regional flaps such as the median
forehead flaps are usually bulky, can not cover a wide range of facial reconstruction and usually require the
donor area to be grafted. The naso-labial flaps are very useful and versatile local flaps, with robust vascularity
that can be readily elevated without a delay. The flap can be superiorly based to reconstruct defects on the
cheek, side wall or the dorsum of the nose, alae, collumula and the lower eye lid. Inferiorly based flaps can be
used to reconstruct defects in the upper lip, anterior floor of the mouth and the lower lip. The flap can be
turned over and used as a lining of the nose and the lip.In the current study we present our experience with
utilization of the nasolabial flaps in facial reconstruction. We evaluated the indications, flap designs, technique,
and complications. We will also assess the final functional and aesthetic results.The study included 20 patients
(12 males and 8 females) presented at the surgical department, National Cancer Institute (NCI) Cairo University
with skin cancer at different areas of the face. Preoperative assessment includes. Assessment of the stage of
the disease, the flap design and patient general condition.The mean age of the patients was 56.3 +/-6 years
(range 16-62 years). Fifteen patients presented with basal cell carcinoma, 2 squamous cell carcinoma, one
malignant melanoma, one keratoacanthoma, and one xeroderma pigmentosa. Nasal defects constituted 75%
of cases, the rest were lower eye lid (2), one upper lip and one oral commisure beside a case of cheek
reconstruction. There was no major complication; only one patient suffered a reactionary hemorrhage that
required re-exploration to secure the bleeder. A single procedure was adequate in most of the patients (80%),
only 4 patients required revision of the scar at the donor site. The overall aesthetic results were very
satisfactory in the majority of patients (16), and satisfactory in 2 cases. Only 2 patients were not satisfied by
the final aesthetic results, one suffered from ectropion and the other had a donor site wound healing
problem.The nasolabial flap is a versatile, simple, easy to harvest local flap that can cover a variety of defects
in the face. It is ideally suitable for covering small and moderate sized defects in the eye lid, cheek, nose, the
anterior floor of the mouth and the lip.

67
PMID: 20029474

Treatment results of adults and children with medulloblastoma NCI, Cairo University
experience.

Khalil EM

To evaluate treatment outcome and prognostic factors of adults and pediatric medulloblastoma patients
treated by adjuvant postoperative craniospinal irradiation (CSI) and chemotherapy.Between 1997 and 2004,
67 patients were treated in the National cancer Institute- Cairo University; 51 pediatric patients with a median
age of 7 years and 16 adult patients with a median age of 25 years. According to the Chang staging system;
50%-35% , 37.5%-47% and 12.5%-18% had T2, T3 and T4 tumors of adults and pediatric patient's population
respectively. M1, M2 and M4 were reported in 16% , 3% and in 1.5% respectively. All patients underwent
primary surgical resection; near total resection in 25% , Subtotal resection in 61% ; with tumor residual <
1.5cm(2) in 49% compared to 51% with > 1.5cm(2) residual tumor and 14% , had biopsy only. All patients were
treated by craniospinal radiotherapy (RT); with a median dose of 34Gy to the whole brain, 54Gy to the
posterior fossa and 32Gy to the spinal axis. The median interval between surgery and RT was 45 days and 38
days for the pediatric and adult groups respectively. The median duration of RT was 54 days and 52 days for
pediatric and adult patients respectively. Thirty four pediatric patients (67% ) received concomitant
chemotherapy, while 61% received adjuvant (postoperative) chemotherapy and 57% received sequential
chemotherapy. Only 33% of patients did not receive chemotherapy. The median follow-up was 49 months for
the whole group of patients (range 11-121).For the pediatric and adult patients, the 5- and 7-year overall and
disease-free survival rates were 89% & 78% Vs. 84% & 56% and 80% & 68% Vs. 79% & 52% respectively.
Fourteen patients (21% ) relapsed (10 pediatric and 4 adults) at a median time of 11 months vs. 23 months and
a median follow-up period of 8 and 12 months respectively; Neuro-axis was the most common site of relapse
(11 patients). Ninety percent (9/10) of the pediatric relapses were of the high risk group (8 received no
chemotherapy) and took place within 2 years; similarly all adult relapses were of the high risk group; three
relapses took place after 2 years. In univariate analysis, T stages, M stages, extent of surgery, CSF seedling and
risk category were significant prognostic factors for disease free survival for the pediatric age group. At 5 years,
87% , 87% , 78% , 85% and 85% of T2, M0, near total resection, negative CSF seedling and low risk patients
were estimated to be disease-free respectively, compared to none of the T4, M +, biopsy only, positive CSF
seedling patients and only 41% of the high risk patients achieved 5 years without recurrence (p=0.001, <0.001,
<0.001, <0.001, <0.001). Patients who did not receive chemotherapy had a 69% 5-year DFS Vs. 76% (p=0.286).
For adult patients; only the risk category was a significant prognostic factor with 5-year disease-free survival
rate of 100% Vs. 40% for low and high risk respectively (p=0.03). On multivaiate analysis only the risk category
and the T-stage were significant prognostic factors for disease free survival for the pediatric age group
(p=0.042 and 0.031).Survival rates of medulloblastoma pediatric patients were better than the adult ones.
Neuro-axis relapse was the most common site of relapse for pediatric patients. Late relapses, lateral tumor
location and shorter median follow up were noted in adult patients. Advanced tumor stage, metastases at
presentation, limited tumor resection were powerful prognostic factors among the pediatric patients. In
addition, high risk category was shown to be a prognostic factor for both pediatric and adult patients.
PMID: 22553813

Value of immunohistochemical expression of p27 and galectin-3 in differentiation

between follicular adenoma and follicular carcinoma.

Abulkheir IL; Mohammad DB

Thyroid neoplasms represent a broad spectrum of tumors with different biologic behaviors. Follicular
neoplasms are classified as benign or malignant depending on the presence or absence of capsular and/or
vascular invasion; however, evaluation of these features can be challenging on histopathologic examination.
Galectin-3 is a member of lectin family and seems to play a significant role in a number of biological processes.
p27 is a key regulator of progression from G1 to S phase.In this study, we investigated the differential
expression of both p27 and galectin-3 in both follicular adenomas and follicular carcinomas. The study was
conducted on archival blocks retrieved from the pathology department at National Cancer Institute, Cairo

68
University, diagnosed between 2001 and 2009 and included 22 cases of follicular adenomas, 22 cases of
follicular adenomas with atypical features, 13 cases of minimally invasive follicular carcinomas, and 25 cases of
widely invasive thyroid carcinomas.p27 and galectin-3 immunohistochemical results were significantly
different between follicular adenomas including those with atypical features and minimally and widely invasive
follicular carcinomas with highly statistically significant difference, recording sensitivity of 100%, specificity of
97.4% as regards p27 and sensitivity of 71%, specificity of 86.36% as regards galectin-3.p27 is a reliable marker
in distinguishing follicular adenomas including atypical types from follicular carcinoma. Galectin-3 is also a
fairly reliable marker in distinguishing follicular adenomas from carcinomas; however, it should be combined
with other markers to increase its accuracy. We recommend the use of immunohistochemical panels of
markers in follicular patterned thyroid lesions, notably in controversial cases.

Breast Cancer Studies

PMID: 14965588

A new surgical strategy for breast conservation in locally advanced breast cancer that
achieves a good locoregional control rate: preliminary report.

Moneer M; Ismael S; Khaled H; El-Gantery M; Zaghloul MS; El-Didi M

The scope of breast conserving surgery has recently expanded to include locally advanced breast cancer (LABC)
patients who are downstaged following neoadjuvant chemotherapy (NACT). However, the efficacy of this
approach in achieving adequate locoregional control of disease is in doubt. Some reports have attributed the
failure to the association of NACT-induced tumour downstaging which can leave multifocal in situ and invasive
lesions around the main tumour mass. In the present study, in order to eradicate all possible tumour satellites,
a very wide local excision that included the whole original tumour-bearing area was performed regardless of
the expected wide defect. This defect was then immediately reconstructed by an ipsilateral pedicled latissimus
dorsi myocutaneous (LDM) flap. The study included 26 patients with LABC without evidence of primary
tumour-multicentricity. Tumours were downstaged following NACT. The early cosmetic outcome was good in
the majority of cases. Early complications were minimal. Twenty-two patients had a mean follow up period of
30.2 (range 7-50) months. In those evaluable cases, locoregional control of the disease was excellent (100%)
but distant metastases occurred in seven cases (31.8%).
PMID: 1797193

A phase II study of epirubicin in breast cancer.

el Mawla NG; Hamza MR; el Khodari A; Khaled H; Gaafar R; el Zawahry H; abdel Wareth A; Dardir
MD; Habboubi N

We evaluated the efficacy of epirubicin in a phase II trial in breast cancer, as well as its cardiac toxicity. The
study was carried out on 40 female patients with advanced, metastatic, or recurrent breast cancer. The
patients were grouped into two groups: group I received 30 mg/m2 epirubicin weekly, and group II 90 mg/m2
epirubicin every 3 weeks. Cardiac monitoring was by ECG, roentgenography, echocardiography and
endomyocardial biopsies. Clinical results were 35.3% overall response in group I, and 50% overall response in
group II. No untoward cardiac toxicities were encountered. We conclude that epirubicin is an effective agent in
breast cancer with relatively little cardiac toxicity.
PMID: 10493959

69
 Allelic instability as a predictor of survival in Egyptian breast cancer patients.

Zekri AR; Bahnassi AA; Bove B; Huang Y; Russo IH; Rogatko A; Shaarawy S; Shawki OA; Hamza MR;
Omer S; Khaled HM; Russo J

This work was designed with the purpose of determining whether the presence of allelic imbalances (AI) such
as microsatellite instability (MSI) and loss of heterozygosity (LOH) in chromosomes 2, 11, 13, and 17 in primary
breast cancer could be used as prognostic indicators of patient survival. The DNA from breast cancers removed
from 29 patients who were followed-up for up to five years was analyzed for MSI and LOH using a panel of 24
markers located at chromosome 2 (TPO, D2S131, D2S144, D2S171, D2S177, D2S119, D2S123, D2S147 and
D2S136), chromosome 11 (C-RAS, Int-2, D11S940, D11S912), chromosome 13 (D13S289, D13S260, D13S267,
D13S218, D13S263, D13S155, and D13S162), and chromosome 17 (D17S513, TP53, D17S855, and D17S785).
The frequency of AI in the markers studied ranged from 30-55%, being highest for D11S912, D2S171, TP53 and
D17S855. Univariate analysis showed association between overall survival rate and AI in 9 out of the 24
markers tested. Five of them were located at the area of the mismatch repair gene (MMR)-2 gene, two at 11p,
one at 13q and one at 17p. Using multivariate analysis, it was observed that only pathological and clinical stage
(defined as stage II or not) and AI at D2S171, D11S912, or D17STP53 generated significant predictive models
for survival.
PMID: 19593673

Altered expression of proliferation-inducing and proliferation-inhibiting genes might

contribute to acquired doxorubicin resistance in breast cancer cells.

Saleh EM; El-Awady RA; Abdel Alim MA; Abdel Wahab AH

This study was designed to investigate the molecular changes that may develop during exposure of breast
cancer cells to anticancer agents and that may lead to acquired resistance. We used two breast cancer cell
lines, a parental (MCF7/WT) and a doxorubicin-resistant (MCF7/DOX) one. Cell survival, cell cycle distribution
and RT-PCR expression level of genes involved in DNA damage response, MDR1, GST and TOPOIIalpha were
measured. MCF7/DOX cells were five-fold more resistant to doxorubicin (DOX) than the MCF7/WT cells. DOX
treatment causes arrest of MCF7/DOX cells in G1 and G2 phases of cell cycle whereas MCF7/WT cells were
arrested in S-phase. The molecular changes in both cell lines due to DOX treatment could be classified into: (1)
the basal level of p53, p21, BRCA1, GST and TOPOIIalpha mRNA was higher in MCF7/DOX than MCF7/WT.
During DOX treatment, the expression level of these genes decreased in both cell lines but the rate of down-
regulation was faster in MCF7/WT than MCF7/DOX cells. (2) The expression level of MDR1 was the same in
both cell lines but 48 and 72 h of drug treatment, MDR1 disappeared in MCF7/WT but still expressed in
MCF7/DOX. (3) There was no change in the expression level of BAX, FAS and BRCA2 in both cell lines.
Conclusively, after validation in clinical samples, overexpression of genes like BRCA1, p53, p21, GST, MDR1 and
TOPOIIalpha could be used as a prognostic biomarker for detection of acquired resistance in breast cancer and
as therapeutic targets for the improvement of breast cancer treatment strategies.
PMID: 22099935

Assessment of Her-2/neu gene amplification status in breast carcinoma with equivocal 2+

Her-2/neu immunostaining.

Mostafa NA; Eissa SS; Belal DM; Shoman SH

Amplification of Her-2/neu gene occurs in 25-30% of breast carcinomas. FDA approved trastuzumab
(Herceptin) is effective only in tumors having the gene amplification. Immunohistochemistry (IHC) for Her-
2/neu protein is widely used but false positive and false negative results exist. Fluorescence in-situ
hybridization (FISH) has both excellent sensitivity and specificity in detecting Her-2/neu amplification.
Comparative studies have shown discordant results in proportion of cases with equivocal 2+ immunostain. This
study is thus conducted to ascertain the frequency of Her-2/neu gene amplification by FISH in breast
carcinoma specified as score 2+ by IHC and to correlate these findings with parameters of prognosis in breast

70
cancer.From October 2008 till May 2010 all paraffin blocks from cases with invasive breast carcinoma which
were scored as 2+ by IHC were eligible for the study, there were 50 cases. Immunohistochemical evaluation of
Her-2/neu was performed using the HercepTest. All cases were immunohistochemically evaluated for ER and
PR. FISH was performed using FDA approved Path-Vysion Her-2/neu/CEP 17 dual color probe.Nine cases (18%)
out of 50 cases scored as Her-2/neu 2+ by IHC showed true gene amplification with a median value of scoring
ratio 4.28 ranging from 2.37 to 13.26. Another two cases showed low level of amplification but when corrected
for Her-2/neu/CEP ratio they did not show true amplification as they were associated with polysomy 17. With
the exception of tumor size, neither patient's age, histologic grade nor lymph node status were correlated with
Her-2/neu gene amplification. Significant inverse correlation existed between Her-2/neu gene amplification
and ER (P=0.01), PR status (P<0.001).Even though FISH is a more complex and expensive procedure, it should
be considered the method of choice for assessment of Her-2/neu gene status especially for equivocal cases by
IHC that are not accompanied by true gene amplification in the majority of breast carcinoma cases.
PMID: 21863073

Assessment of the reliability of immunocytochemical detection of estrogen and

progesterone receptors status on the cytological aspirates of breast carcinoma.

Hafez NH; Tahoun NS

Evaluation of the reliability of immunocytochemical staining for estrogen and progesterone receptor status on
previously papanicolaou-stained fine needle aspiration smears of breast carcinoma cases.This is a
retrospective study conducted on destained smears of fine needle aspirates (FNA) obtained from 90 breast
carcinoma cases. These cases underwent subsequent tumor resection and immunohistochemical detection of
estrogen and progesterone receptors allowing a comparison between the immunocytochemical and
immunohistochemical results (Gold Standard). Hypocelluar slides were excluded from the current study. Only
the nuclear staining was considered specific. The results were scored on the basis of the percentage of the
positive nuclei among the total epithelial malignant cells after examination of the entire slide. Smears were
interpreted as positive if 10% of the examined cells demonstrated nuclear staining. These results were then
compared with the immunohistochemical results.For estrogen receptor immunocytochemistry, the overall
cyto-histologic accuracy was 91.1% (82÷90) while the discordance rate was 8.9% (8÷90). The diagnostic
sensitivity, specificity, positive predictive value, and negative predictive value were 93%, 84.2%, 95.7%, and
76.2% respectively. For progesterone receptor immunocytochemistry, the overall cyto-histologic accuracy was
88.9% (80÷90) while the discordance rate was 11.1% (10÷90). The diagnostic sensitivity, specificity, positive
predictive value, and negative predictive value were 87.1%, 95%, 98.4%, and 67.9%
respectively.Immunocytochemistry is considered as an efficient tool in evaluating estrogen and progesterone
receptor status in breast carcinoma. The application of estrogen and progesterone receptor
immunocytochemistry on previously Papanicolaou-stained slides provides an overall accuracy of 91.1% for
estrogen receptor and 88.9% for progesterone receptor when compared with the immunohistochemical
results. KEY WORDS: Estrogen receptor- Progesterone receptor- Breast carcinoma- FNA-
Immunocytochemistry.
PMID: 15751939

Breast cancer in Egypt: a review of disease presentation and detection strategies.

Omar S; Khaled H; Gaafar R; Zekry AR; Eissa S; el-Khatib O

Carcinoma of the breast is the most prevalent cancer among Egyptian women and constitutes 29% of National
Cancer Institute cases. Median age at diagnosis is one decade younger than in countries of Europe and North
America and most patients are premenopausal. Tumours are relatively advanced at presentation. The majority
of tumours are invasive duct subtype and the profile of hormone receptors is positive for estrogen receptors
and/or progesterone receptors in less than half of cases. This overview examines genetic changes, potential
and established predictive and prognostic markers and end results of surgery, radiotherapy and systemic
therapy for early, locally advanced and metastatic disease stages. Disease presentations common to the region
and early detection strategies are presented.

71
PMID: 21199580

Cathepsin B: a potential prognostic marker for inflammatory breast cancer.

Nouh MA; Mohamed MM; El-Shinawi M; Shaalan MA; Cavallo-Medved D; Khaled HM; Sloane BF

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine
protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is
known about its role in IBC.In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used
for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the
levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to
caveolar membrane microdomains in cancer cell lines including IBC, and therefore, we also examined the
expression of caveolin-1 (cav-1), a structural protein of caveolae in IBC versus non-IBC tissues. In addition, we
tested the correlation between the expression of CTSB and cav-1 and the number of positive metastatic lymph
nodes in both patient groups.Our results revealed that CTSB and cav-1 were overexpressed in IBC as compared
to non-IBC tissues. Moreover, there was a significant positive correlation between the expression of CTSB and
the number of positive metastatic lymph nodes in IBC.CTSB may initiate proteolytic pathways crucial for IBC
invasion. Thus, our data demonstrate that CTSB may be a potential prognostic marker for lymph node
metastasis in IBC.
PMID: 22527932

Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-

MMP) in human breast cancer tissue.

Mohammad MA; Zeeneldin AA; Abd Elmageed ZY; Khalil EH; Mahdy SM; Sharada HM; Sharawy SK;
Abdel-Wahab AH

Breast cancer (BC) is the most common neoplasm among women in most developed countries, including
Egypt. Elevated levels of certain proteins in human BC are associated with unfavorable prognosis and
progressive stages of the disease. The aim of our study was to evaluate the protein expression profile and
prognostic significance of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), MMP-9 and
membrane type 1-MMP (MT1-MMP) and their interaction in operable BC patients. The protein expression of
COX-2, MMP-2 and MT1-MMP were evaluated by western blot technique, whereas enzymatic activity of MMP-
2 and MMP-9 was determined by zymography in 47 breast cancer patients as well as normal adjacent tissues.
Also, the correlation between these proteins and age, tumor size, LN stage, TNM stage, estrogen receptor,
progesterone receptor, disease-free survival, and overall survival (OS) has been investigated. As compared to
adjacent normal tissues, COX-2, MMP-2 and MT1-MMP were over-expressed in 43, 64, and 60 % of tumor
tissues, respectively. In the same pattern, the activity of MMP-2 (62 %) and MMP-9 (45 %) was elevated in BC
tissues. Multivariate analysis showed a positive correlation between the protein expression of COX-2, MMP-2,
and MT1-MMP and the activity of MMP-2 and MMP-9 in BC patients. However, the enzymatic activity showed
no correlation with clinicopathological features. This study confirms the preclinical evidence that COX-2
increased the expression of MT1-MMP, which in turn activates MMP-2. The lack of correlation with
clinicopathological features, OS or disease-free survival ascertains the complexity of tumor progression and
metastasis with many pro- and counter regulatory factors.
PMID: 16508678

Computerized treatment planning in radiation therapy of intact breast: influence of

number of CT-cuts.

Shouman T; El-Taher Z; Radwan A

To compare the accuracy of 2D algorithm with an established 3D algorithm, and to define the number of CT-
slices needed for treatment planning of intact breast irradiation.Twenty patients with breast cancer treated
with conservative surgery were included in this study, ten of them had right breast cancer and the other 10

72
patients had cancer of the left breast. For each patient, 3-D calculations (HeLax-TMS) were performed using
one CT-slice (central), 3 CT-slices (central, caudal, and cephalic) and full set CT-slices in addition to 2D
calculations (Multidata System) on the digitized central cut. All calculations were done using 6MV-
photon.When using 2D planning with lung correction, a large hot area of 105% was found at the medial and
lateral subcutaneous (SC) regions. Comparison of 2D-treatment planning using Multidata System (2D-physics)
and 2D-planning using HeLax System (3D-physics) showed that the 2D planning using Multidata System gave a
large hot area of 105% compared with HeLax-2D at the subcutaneous region. The central axis dose
distributions obtained from 2D and 3D calculations using HeLax system were compared. No differences were
found in the two planes (central cut plane) and this was because the two planes were based on the same
algorithm. The only difference was that the hot area (110%) was found at the superior or the inferior border of
the field. Also, a comparison using the 3D-system for the central slice and the multiple slices showed a
difference in calculating the maximum dose to the target of 2.19%, which was Statistically significant
(p=0.001). For all left sided patients, the maximum dose to the heart was significantly different from one to full
CT-cuts. It was 12.0+/-6.0% when using one CT-cut versus 6.6+/-1.3% when using full CT-cuts (p<0.03). We
compared isodose distributions using three and full CT-cuts for both small and large breasts. For the large
breast patients, larger differences in isodose distributions were observed in the cephalic and the caudal planes
than for small breast patients.Dose distributions based on a single CT cut through the central axis using 2D or
even 3D treatment planning system will lead, quite often, to hot volumes in 76 excess of 105%. For patients
whose breast contours vary slowly within the tangential fields, a three-slice CT scan appears to be adequate
for clinical decision. However, for patients with large variation of contours within the tangential fields, a full CT
scan gives more accurate dose distributions than the three-slice model.
PMID: 14734470

Detection of micrometastatic disease and monitoring of perioperative tumor cell

dissemination in primary operable breast cancer patients using real-time quantitative
reverse transcription-PCR.

Ismail MS; Wynendaele W; Aerts JL; Paridaens R; Gaafar R; Shakankiry N; Khaled HM; Christiaens
MR; Wildiers H; Omar S; Vandekerckhove P; Van Oosterom AT

We previously found a statistically significant number of cytokeratin 19 (CK19)+ cells in peripheral blood (PB)
of stage IV breast cancer (BC) patients compared with those of healthy volunteers, using a quantitative real-
time reverse transcription-PCR. We aimed to apply the technique on bone marrow (BM) of primary operable
BC patients. Pre- and postoperative PB samples of these patients were further analyzed to investigate possible
shedding of CK19+ cells during the operation.In 54 primary operable BC patients, we analyzed 50 BM samples
taken preoperatively and 297 PB samples. PB samples were collected before surgery; immediately after
surgery; on the first, second, and fifth day postoperatively; and one month postoperatively.In BM of controls
and BC patients, we detected a median of 28 and 568 CK19+ cells/5 x 10(6) leukocytes, respectively (P <
0.001). In preoperative blood (B-1) samples, we measured a median of 109 CK19+ cells. Using the upper limit
of 95% confidence interval of controls as cutoff, 74% and 52% of BM and (B-1), respectively were considered
CK19+. There was no significant correlation between CK19+ cells in BM and (B-1) and classical prognostic
factors. We found no significant difference between blood samples at different time points with respect to the
average CK19+ cells.In primary BC patients, we detected high numbers of CK19+ cells in BM and PB (B-1)
samples compared with controls. However, no significant correlation between the presence of CK19+ cells in
BM and PB and classical prognostic factors was found. We detected no statistically significant influence of
surgical manipulation on CK19+ cells.
PMID: 22099933

73
 Distribution of axillary lymph node metastases in different levels and groups in breast
cancer, a pathological study.

Khafagy M; Mostafa A; Fakhr I

It was observed during dissection of heavy deposits of axillary lymph nodes (LNs) in breast cancer that there
were grossly positive LNs outside the confines of classical axillary dissection.To know the extent of LN
metastases in these new basins by dissecting and labeling them separately, for pathological examination and
proper staging of those patients.From 2005 to 2009, 59 private patients with breast cancer who had positive
axillary LNs were subjected to axillary dissection with accurate leveling according to its relation to pectoralis
minor. In addition to the classical three levels, the brachial, thoracoacromial, humeral, scapular and Rotter's
lymph nodes were dissected.Levels I, II and III axillary LNs were involved in 91.5%, 62.7%, and 52.5%,
respectively. Skip metastases (without the involvement of level one) were found in 5/59 patients (8.4%).
Brachial, acromiothoracic, humeral and Rotter's LNs were involved in 10.1%, 15.2%, 5% and 1.7%, respectively,
with no metastatic deposits encountered in scapular LNs. In our patients, lymphedema of the ipsilateral upper
limb was nearly of the same incidence as after classical axillary dissection.In addition to the classic complete
axillary lymph node dissection (ALND) indicated in patients with breast cancer with axillary LNs metastases,
dissection of the brachial, acromiothoracic, humeral, Rotter's and scapular LNs, is recommended for proper
staging.
PMID: 22929919

Does fasting during Ramadan trigger non-adherence to oral hormonal therapy in breast
cancer patients?

Zeeneldin AA; Gaber AA; Taha FM

To estimate the effect of fasting during Ramadan (the ninth lunar month) on adherence to oral hormonal
therapies (OHT) among breast cancer (BC) patients.During Ramadan 2010, 139 BC patients were interviewed
at the Egyptian National Cancer Institute. They were asked about fasting as well as intake of OHT in Ramadan
and in the preceding month.The median age was 50years and most patients were postmenopausal with good
performance status and non-metastatic disease. The median number of fasting days was 18% and 93% of
patients were fasting 80% or more of Ramadan. Tamoxifen and aromatase inhibitors were used in 64% and
36%, respectively. Adherence to OHT during Ramadan and its preceding month were 94.2% and 95.7%,
respectively (p=0.77). In univariate analysis, non-adherence prior to Ramadan and shorter duration of OHT
were predictors of non-adherence during Ramadan (P<0.001, 0.003, respectively). Fasting, age, performance
status, presence of metastases and type of hormonal therapy were not good predictors of adherence.While
most of patients receiving OHT for BC are fasting during Ramadan, this does not negatively impact compliance
with treatment.
PMID: 22866165

Effect of tumour necrosis factor-alpha on estrogen metabolic pathways in breast cancer

cells.

Kamel M; Shouman S; El-Merzebany M; Kilic G; Veenstra T; Saeed M; Wagih M; Diaz-Arrastia C; Patel

D; Salama S

Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that has been linked to breast cancer
development. Estrogen metabolic pathway is also involved in breast carcinogenesis and DNA adducts
formation. In this study we investigated the effect of TNF-α on the estrogen metabolic pathway in MCF-7, a
breast cancer cell line. Capillary liquid chromatography/mass spectrometry (LC/MS) and High performance
liquid chromatography (HPLC) were used for analysis of estrogen metabolites and estrogen-DNA adducts levels
respectively. Reporter gene assay, Real time reverse transcription polymerase chain reaction (real time RT-
PCR) and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes. TNF-α
significantly increased the total EM and decreased the estrone (E1) / 17-β estradiol (E2) ratio. Moreover, it

74
altered the expression of genes and enzymes involved in E2 activation and deactivation pathways e.g.
Cytochrome P-450 1A1 (CYP1A1), Cytochrome P-450 1B1 (CYP1B1), Catechol-O-methyl transferase (COMT) and
Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase 1 (NQO1). In addition, there were
increased levels of some catechol estrogens e.g. 4-hydroxy-estrone (4-OHE1) and 2-hydroxyestradiol (2-OHE2)
with decreased levels of methylated catechols e.g. 2-methoxy estradiol (2-MeOE2). DNA adducts especially 4-
OHE1-[2]-1-N3 Adenine was significantly increased. TNF-α directs the estrogen metabolism into more
hormonally active and carcinogenic products in MCF-7. This may implicate a new possible explanation for
inflammation associated breast cancer.
PMID: 22776816

Epidemiology and management of breast carcinoma in Egyptian males: Experience of a

single Cancer Institute.

Elshafiey MM; Zeeneldin AA; Elsebai HI; Moneer M; Mohamed DB; Gouda I; Attia AA

To assess the epidemiological and clinico-pathological features, surgical and reconstructive techniques,
adjuvant treatments and clinical outcome of breast carcinoma in males (BCM) at the Egyptian National Cancer
Institute (NCI).Thirty-two males with breast carcinoma presented to NCI between January 2000 and December
2002. They were evaluated by complete history, physical examination, laboratory and radiological
investigations.Median age was 59years. Left sided and retroareolar breast lumps were the commonest
presentations. Grade II tumors positive for hormone receptors were very common. Stages I, II, III and IV of the
disease were encountered in 6.2%, 34.4%, 34.4% and 25.0% of patients, respectively. Curative surgery was
done in 22 patients; they received adjuvant hormonal therapy, chemotherapy and radiotherapy in 22, 16 and
10 patients, respectively. Eight metastatic patients were treated with palliative measures. Surgery was done in
25 patients; the most common procedure was modified radical mastectomy (40.6%). Primary closure was
feasible in 17 patients (68%), local flaps were needed in 4 cases (16%), while myocutaneous flap was done in 3
cases (12%). The commonest complication was the development of seroma (9 cases). The overall survival (OS)
at 5years was 65.4%. The disease free survival (DFS) at 5years was 53.9%. Stage and curative surgery
significantly affected OS, while type of surgery was the only variable significantly affecting DFS.Male breast
carcinoma occurs at older ages than females, usually in advanced stage. This necessitates directing attention of
males and awareness on the prevalence and risk factors for this disease.
PMID: 22929918

Epstein-Barr virus and breast cancer: Epidemiological and Molecular study on Egyptian
and Iraqi women.

Zekri AR; Bahnassy AA; Mohamed WS; El-Kassem FA; El-Khalidi SJ; Hafez MM; Hassan ZK

The role of Epstein-Barr virus (EBV) in breast carcinogenesis is still controversial. Unraveling this relationship is
potentially important for better understanding of breast cancer etiology, early detection and possibly
prevention of breast cancer. The aim of the current study is to unravel the association between EBV and
primary invasive breast cancer (PIBC) in two different Arab populations (Egyptian and Iraqi women).The study
was done on paraffin-embedded tissues of 40 Egyptian and 50 Iraqi patients with PIBC in addition to 20 normal
breast tissues as controls for each group. Both controls and neoplastic tissues were assessed for the expression
of EBV genes and proteins (EBNA-1, LMP-1, and EBER) as well as CD21 marker by immunohistochemistry (IHC),
in situ hybridization (ISH) and PCR techniques.Our gold standard for EBV reactivity in breast cancer cases was
positivity of both EBNA1 by PCR and EBER by in situ hybridization. EBV was detected in 18/40 (45%) and 14/50
(28%) of Egyptian and Iraqi women; respectively where p=0.073, compared to 0/20 (0%) of their control
groups (p<0.05). Regarding the association between EBV positivity and tumor grade, there was not any
statistical significant difference between EBV presence and tumor grade in both populations where p=0.860
and p=0.976 and the calculated rank biserial correlation coefficient was 0.114 and 0.269 for Egyptian and Iraqi
women respectively.Our findings show that EBV might act as a promoter for the development of PIBC and it
might contribute to increased tumor aggressiveness in Egyptian and Iraqi patients.
PMID: 17671531

75
Expanding the role of breast conservation surgery by immediate volume replacement with
the latissimus dorsi flap.

Naguib SF

Many women with early breast cancer are treated with Mastectomy, instead of Breast Conservation Surgery
(BCS), for fear of suboptimal tumor removal or cosmetic failure due to volume and shape loss. These women
can be satisfactorily treated by BCS and immediate volume replacement. Synchronous breast augmentation by
the autologous Latissimus Dorsi (LD) Muscle or Myocutaneous Flaps in the treatment of relatively large and/or
retroareolar breast tumors was investigated in this study held at the National Cancer Institute of Cairo
University and at the Aswan Cancer Center.Between October 2000 and March 2003, 29 patients with
histologically proven breast cancer were treated by BCS and immediate volume replacement with LD muscle or
myocutaneous flaps. Patients' age ranged from 32 to 57 years. Tumors' size ranged from 28 to 69mm. Axillary
dissections revealed positive lymph glands in 58.6% of cases. Tumor location was in the central quadrant in
45%, in the upper quadrants in 41% and in the lower quadrants in 14% of cases. The LD myocutaneous flap
was used in 21 cases while, in the remaining 8 cases, only the LD muscle was needed.The median size of the
lumpectomy specimen was 219cm3. The safety margins obtained ranged between 9 and 28mm. The mean
combined operating time was 238 minutes. The mean blood loss was 320ml and no patient required blood
transfusion. The median hospital stay was 5 days. Persistent seroma in the back occurred in 52% of patients,
requiring a median of 5 weekly aspirations. No sepsis or flap viability problems were encountered. Cosmetic
results were satisfactory in 69% of patients. Only 17% showed some asymmetry in size, 7% some discrepancy
in skin color and 7% a mild difference in Nipple Areola Complex (NAC) level.Mastectomy can be avoided in a
large number of women with small breast/tumor ratio or retroareolar tumors. Immediate volume replacement
with LD flap can extend the role of BCS to these patients. This can be achieved without compromising the
adequacy of resection, with minimal morbidity, very satisfactory cosmetic results, no need for prosthesis or
contra lateral mammaplasty and no effect on postoperative clinical or radiological follow-up.
PMID: 17192687

Expression of cyclooxygenase-2 and 12-lipoxygenase in human breast cancer and their

relationship with HER-2/neu and hormonal receptors: impact on prognosis and therapy.

Mohammad AM; Abdel HA; Abdel W; Ahmed AM; Wael T; Eiman G

A number of studies have shown over-expression of cox-2 in breast cancer. Also it has been recorded that
human breast cancer expresses high level of cox-2 and 12-lipoxygenase which may be beneficial in future
therapy plan for those patients.The present study aims to examine the level of transcripts of cox-2 and 12-
lipoxygenase in Egyptian breast cancer patients and to compare between the expressions of both enzymes and
TNM staging, hormone receptors status (including estrogen and progesterone) and HER2/neu expression.Total
cellular RNA was extracted from 64 frozen tissue samples of breast carcinoma and their corresponding normal
adjacent tissues. Cox-2 and 12-lipooxygenase expressions were detected using RT-PCR. Hormonal receptors as
well as HER2/neu were detected immuno-histochemically for each patient.About 47 and 62.5% of carcinoma
samples showed over-expression of cox-2 and 12-lipooxygenase respectively as compared to their
corresponding normal tissues. The results revealed that cox-2 significantly associated with TNM staging (P =
0.0047) and hormonal receptors status (P = 0.0201). The relationship between cox-2 and HER2/neu expression
was close to a significant value (P = 0.0747). 12-lipooxygenase showed only significant association with TNM
staging (P = 0.0076). Neither hormonal receptors nor HER2/neu showed significant association with this
enzyme.Elevated levels of cox-2 and 12-lipoxygenase expression were detected in human breast cancer. Also,
the results revealed that cox-2 and 12-lipooxygenase mRNA expressions are associated with TNM staging in
human breast cancer. Furthermore, there is an inverse association between cox-2 expression and hormonal
receptor status. This observation may drive us to the possible role of those two enzymes in determining the
plan of therapy of breast cancer patients.
PMID: 21557333

76
FHIT gene and flanking region on chromosome 3p are subjected to extensive allelic loss in
Egyptian breast cancer patients.

Ismail HM; Medhat AM; Karim AM; Zakhary NI

The fragile histidine triad gene (FHIT) is a candidate tumor suppressor gene at chromosome 3p14.2. Deletions
in FHIT gene were reported in different types of cancer including breast cancer. In this study, we investigated
the loss of heterozygosity (LOH) incidence that target FHIT genomic structure and chromosome 3p in
cancerous and pre-neoplastic lesions of Egyptian breast patients. Genomic DNA was isolated from tumor
tissues and their normal counterparts of 55 Egyptian patients diagnosed with breast cancer and 11 patients
diagnosed with preneoplastic breast lesions. LOH was detected in 51% of breast cancer cases in at least one
microsatellite marker of the four investigated markers. While, none of the markers showed LOH among the
pre-neoplastic breast lesions. We also observed a significant association between LOH and invasive ductal
carcinoma (IDC) histopathological type while no association observed between LOH and patients' age, tumor
grade, or lymph node involvement. We also investigated FHIT gene expression profiles in breast cancer using
Oncomine database. We found that FHIT is significantly reduced in all investigated studies. We conclude that,
FHIT is underexpressed in breast cancer tissues compared to their normal counterparts due to the extensive
allelic loss that is observed in its gene structure.
PMID: 21178606

Fluoroscopic stellate ganglion block for postmastectomy pain: a comparison of the classic
anterior approach and the oblique approach.

Nabil Abbas D; Abd El Ghafar EM; Ibrahim WA; Omran AF

Stellate ganglion block is usually performed with the classic anterior paratracheal approach. The anatomy of
the stellate ganglion being in close proximity to various critical structures renders a number of complications,
which are potentially associated with its blockade. The aim of this study was to assess the analgesic efficacy
and safety of a new approach of the stellate ganglion block using an oblique fluoroscopic view.Fifty patients
with postmastectomy pain syndrome were randomly allocated into 1 of 2 groups: the anterior paratracheal
stellate block group and the oblique fluoroscopic stellate block group. Four blocks were performed for each
patient using the same approach each time. The results were evaluated in terms of pain intensity as assessed
by the visual analog scale score, morphine consumption, and allodynia surface area (in cm). Patient
satisfaction score (PSS), skin temperature, side effects, and complications were recorded and compared
between the 2 studied groups after each block had been performed.The mean visual analog scale score, daily
morphine consumption, and areas of allodynia were significantly decreased and the PSS was significantly
increased after each block and for up to 3 months after the last block in both the groups. However, there were
no statistically significant differences between the 2 groups at the same study period apart from PSS, which
was statistically more significant in group oblique at certain times. The incidences of side effects were
significantly more in group classic than in group oblique.The oblique fluoroscopic approach of the stellate
ganglion block is as effective as the anterior paratracheal approach but is safer and more satisfactory to the
patients.
PMID: 17671530

Gemcitabine plus doxorubicin as first-line treatment in advanced or metastatic breast

cancer (MBC), a phase II study.

El Serafi MM; El Khodary AI; El Zawahry HR; Mansour OM; Gaballa HE

Introduction: Doxorubicin and Gemcitabine have promising antineoplastic activity and manageable toxicity as
a single agent in the treatment of patients (pts) with advanced breast cancer. Aim of the Study: This study
evaluated the efficacy and toxicity of the combination of gemcitabine plus doxorubicin as first-line treatment

77
of advanced or MBC patients. Patients and Methods: Patients with advanced or MBC received gemcitabine
1250mg/m2 IV on days 1 and 8 plus doxorubicin 60mg/m2 IV on day 1 every 21 days for a maximum of 6
cycles. Results: Thirty-five patients were included, and all are evaluable for safety and efficacy. Median age was
47 years (range, 33 to 60 years). Fourteen patients (40%) were post-and 21 (60%) were premenopausal. Prior
treatment included mastectomy (23pts); adjuvant nonanthracycline containing combination chemotherapy
(18pts); adjuvant hormonal therapy (3pts) and 2 pts did not receive any adjuvant therapy. Twelve patients had
metastatic disease at presentation. Seventeen pts were chemonaive. Hormonal receptors were positive in 6,
negative in 21, and unknown in 8 pts. Site of metastasis included one site in 15 pts, two sites in 14, and three
sites in 6 pts. Complete remission was observed in 6/35 (17.1%) and partial remission in 14/35 (40%) pts, for
an overall response rate of 57.1%. Stable disease was observed in 8 (22.9%) and progressive disease in 7 (20%)
pts. The median time to tumor progression was 7 months (range, 5-23 months; 95% CI, 6-8 months) and the
median survival time was 16 months (range, 6-43 months; 95% CI, 13-19 months). The overall survival at 1 and
2 years was 74.2% and 34.2%; respectively; with 4/35 (11.4%) patients alive at 40 months. A total of 186 cycles
of treatment were administered (range2-6 cycles, median 6 cycles). The doses of both doxorubicin and
gemcitabine were modified after interim analysis of toxicity following the first 22 cycles administered to the
first 10 patients [Mucositis grade 3-4 occurred in 6/10 (60%), grade 3-4 neutropenia in 3/10 (30%), and febrile
neutropenia grade 3 in 2/10 (20%) patients] to doxorubicin 50mg/m2 on day 1 and gemcitabine to 1000
mg/m2 on days 1 and 8 in the remaining cycles. After doses reduction, the toxicity was generally tolerable.
CONCLUSION: The combination of gemcitabine plus doxorubicin after doses modification can be safely
administered every 21 days with promising response as first-line therapy for MBC. The response rate, time to
disease progression and overall survival rates of this regimen are comparable to other standard therapies for
MBC, as well as other gemcitabine combinations.
PMID: 10778762

Hormonal profiles and estrogen receptors in Egyptian female breast cancer patients.

Abu-Bedair FA; El-Gamal BA; Ibrahim NA; El-Aaser AA

Hormones are considered to be an important factor in the etiology of breast cancer. Serum hormonal profiles
of premenopausal and postmenopausal breast cancer patients as well as estrogen receptor (ER)
concentrations in breast cancer tissues were examined in an attempt to establish a possible association
between hormones and breast cancer risk and to elucidate the biological features of the disease among
Egyptian female patients.Levels of estradiol (E2), testosterone (T), progesterone (P), LH, FSH, prolactin, T3, T4
and TSH were measured by highly specific radioimmunoassays in the sera of women with breast cancer and
compared to those of control subjects. ER concentrations in breast tumor tissues were measured using 125I-
radioreceptor assay.Levels of T and prolactin showed a significant increase in both premenopausal and
postmenopausal patients. E2 and P levels were significantly increased in follicular premenopausal and
postmenopausal patients. Luteal E2 showed non-significant changes, whereas the luteal P level was
significantly decreased. No significant alterations were found in the levels of serum LH, FSH, T3, T4 and TSH
either in premenopausal or postmenopausal patients. Higher levels of ER were found in the tumors of
postmenopausal than in those of premenopausal patients. A positive correlation was found between levels of
ER and age of the patients (r = 0.35), whereas a negative correlation was observed between ER and serum E2 (r
= -0.26).This study provides evidence of an association between high levels of serum E2 and T and increased
risk of breast cancer in postmenopausal women. Abnormalities in serum P and prolactin are probably
associated with a breast cancer risk and ER may be considered as a biochemical marker for breast cancer
development.
PMID: 15959551

78
 Hypofractionation versus conventional fractionation radiotherapy after conservative
treatment of breast cancer: early skin reactions and cosmetic results.

Taher AN; El-Baradie MM; Essa H; Zaki O; Ezzat S

To compare in a prospective trial the acute skin reaction and late cosmetic effects of normal fractionation
versus hypofractionation radiotherapy after breast conserving surgery.Thirty patients with T 1-2N0M0 breast
cancer who underwent breast conserving surgery (BCS) were included in the study. Half of the patients
received whole breast irradiation, consisting of 50 Gy/25f/5w+boost 10Gy/5f/1w to tumor bed (group A). The
other half received 42.5Gy/16f/22 days (group B). The two groups were comparable otherwise. Early skin
reaction and late cosmetic results were graded according to RTOG guidelines.The study showed no statistical
significant difference between the two treatment groups as regards acute skin reactions and cosmetic
appearance. However, the maximum skin reaction occurred 2 weeks earlier for patients within group B (3rd
week) compared to group A (5th week). Apart from breast volume, there was no significant correlation
between any of the patients or tumor factors and the incidence of acute skin reactions in either group of
patients. Patients with large breast volume >1100cc had a higher rate and a longer duration of maximum skin
reaction in group A (4 weeks versus 2 weeks in patients with small breast volume </= 1100cc), while in group
B, all patients had a maximum duration of 4.5 weeks. This difference was not statistically significant. After
median follow-up of 22 months, again there was no difference between the two groups as regard the cosmetic
outcome. Lumpectomy volume and lumpectomy/breast volume ratio (regardless of the tumor volume) were
the only factors that significantly affected the cosmetic appearance.Preliminary results support the use of a
shorter fractionation schedule of 42.5Gy/16f/22 days in patients with breast conserving surgery. The study is
still going on to study the late effects on a larger number of patients for final evaluation of this regimen.
PMID: 2347057

Ifosfamide, methotrexate, and 5-fluorouracil: effective combination in resistant breast

cancer.

Gad-el-Mawla N; Hamza MR; Zikri ZK; Elserafi M; el-Khodari A; Khaled H; Gafaar R

Ifosfamide has definite efficacy in many malignant tumours, including breast cancer. In the present study we
substituted cyclophosphamide with ifosfamide in the combination CMF (cyclophosphamide, methotrexate,
and 5-fluorouracil) regimen in 25 patients with breast cancer whose disease was refractory to CMF or who had
relapsed after previous response. Ifosfamide was given in an i.v. infusion at a dose of 1.2 g/m2 daily for 5 days,
together with mesna as a uroprotector (at 20% of the ifosfamide dose). Methotrexate was given at a dose of
40 mg/m2 and 5-fluorouracil was given at 600 mg/m2, both by i.v. push. Courses were repeated every 21 days.
The 24 evaluable patients received 3-12 courses (average, 5 courses); results included a complete remission in
3 patients (12.5%) and a partial remission in 3 (12.5%). Among the remaining patients, improvement was seen
in 4 (16.6%); stable disease, in 7; and progressive disease, in 7 (29.2%). The complete responses lasted for 11+,
13+, and 15+ months, and partial remissions, for 2, 6, and 9 months. The responses were detected in soft-
tissue as well as visceral lesions, but not in bony lesions. The responders remain under follow-up. This study
shows the efficacy of ifosfamide-containing chemotherapy in breast cancer. As toxicities were tolerable, higher
doses of ifosfamide could safely be used in these patients. Use of this combination as first-line therapy in
breast cancer could be considered for a future study.
PMID: 17496938

Immediate breast reconstruction with expander assisted latissimus dorsi flap after skin
sparing mastectomy.

Abdalla HM; Shalaan MA; Fouad FA; Elsayed AA

The latissimus dorsi myocutaneous flap (LDMF) used to be the standard practice for breast reconstruction;
however, with the increased use of tissue expanders and the development of the transverse rectus-abdominis
myocutaneous flap for autologous tissue breast reconstruction, its use has decreased. To reassess the role of

79
the LDMF in breast reconstruction, a prospective study was performed to evaluate women who had a skin
sparing mastectomy followed by immediate reconstruction with a latissimus dorsi flap and tissue expander
implant.Twenty-five women with early breast cancer underwent immediate latissimus dorsi myocutaneous
flaps with tissue expander after skin sparing mastectomy. The oncologic safety of skin sparing mastectomy, the
postoperative aesthetic results and complications were evaluated.Between May 2003 and April 2005, 25
consecutive women diagnosed with breast cancer underwent skin sparing mastectomy and expander assisted
immediate latissimus dorsi breast reconstruction. Their median age was 42 years, ranging from 34 to 48 years.
The procedure duration ranged from 2.5 to 6 hours, with a median of 3.9 hours, however, expansion was
completed by 4 months (range 1 to 8 months). Patients were discharged 7 days after surgery with a range of 5
to 15 days. The complication rate was low, manifesting with skin flap necrosis in 12%, wound infection in 4%,
and port site extrusion in 4%. There was no flap loss. With the exception of seroma formation, the donor site
morbidity was low (seroma 40%, hematoma 4%, back pain 8%, and limited arm movement 4%). No local
recurrence was recorded. The aesthetic result of surgery was rated as excellent in 20%, good in 60%, fair in
24%, and poor in 4% of cases. The duration of post-operative follow up was 14.7 months, ranging from 6 to 24
months.Skin sparing mastectomy and immediate breast reconstruction is an oncologically safe technique. The
use of latissimus dorsi myocutaneous flap with tissue expansion has proved to be an effective and aesthetic
method of immediate breast reconstruction after skin sparing mastectomy.
PMID: 16353083

Importance of serum IL-18 and RANTES as markers for breast carcinoma progression.

Eissa SA; Zaki SA; El-Maghraby SM; Kadry DY

Interleukin-18 (IL-18), a cytokine that plays an important role in the T-cell-helper response, acts as an
angiogenic factor and a tumor suppressor. RANTES (regulated upon activation normal T-cells expressed and
secreted) is a member of the C-C chemokine family with chemoattractant activity for a variety of cell types.
High incidence and intensity of RANTES were noted in advanced breast carcinoma.To correlate the levels of
RANTES and IL-18 in serum of breast cancer patients with bone or other organ metastasis compared to breast
cancer patients without metastasis and healthy controls and to estimate the role of each of them as a
prognostic marker for the progression of the disease.The study was conducted on 60 breast cancer patients
(25 cases with no metastasis and 35 cases with metastasis) who were admitted to the outpatient clinic of the
NCI, Cairo University during the period from March 2004 to September 2004 and 30 apparently healthy
controls who were volunteers at the blood bank of the NCI, Cairo University.Showed that there was a
statistically significant difference between the level of IL-18 in breast cancer patients without metastasis and
the control group (p<0.05) while there was a highly significant difference between the metastatic group and
the control group (p<0.001). There was a significant increase in IL-18 levels between metastatic and non-
metastatic cases (p<0.01). RANTES showed a significant increase in breast cancer cases with no metastasis and
the control group (p<0.05) and it showed a highly significant increase in metastatic patients compared to
controls (p<0.001). There was no significant increase in the level of RANTES in metastatic compared to non-
metastatic patients (p>0.05).IL-18 is an important non invasive marker suspecting metastasis. Even though
RANTES levels were higher in cancer patients compared to controls, its role in staging of breast cancer was not
clear in this study.
PMID: 22570674

Inflammatory breast cancer: is it really a separate entity?

Bastawisy A; Gaafar R; Eisa S; Amira G; Helal M

Inflammatory breast cancer (IBC) is the most aggressive form of primary breast carcinoma and is associated
with a dismal outcome despite the availability of multi-modality treatment options.This is a prospective case
control study comparing two groups of newly diagnosed patients; the first with inflammatory breast cancer
(IBC) and the second with locally advanced non inflammatory breast cancer (LABC). In both groups MIB1, ER,
PR, Her2neu were assessed. Neo-adjuvant chemotherapy consisted of four cycles of FEC100 followed by
modified radical mastectomy according to clinical response, postoperative chemotherapy with two courses of
the same regimen followed by radiotherapy. Tamoxifen 20 mg po daily for 5 years in ER and/or PR positive

80
tumours, starting after the completion of radiotherapy. Primary end points were a) comparison of MIB-1 score
in both groups, b) comparison of clinical and pathological responses in both groups. Secondary endpoints were
comparison of progression free survival and overall survival.From a total of 42 patients, 21 were stage III B
(T4d, N0-2 M0) IBC and 21 were stage III B (T4a-c, N0-2, M0) LABC. Patients in the age range from 28 to 68
were included and followed from November 2007 until February 2010 with a median follow-up period of 22.5
months. Toxicity of both arms, mainly haematologic, nausea and vomiting, was in general acceptable with no
treatment-related deaths. Of the patients with IBC 81.3% had a high MIB-1 score as compared with 43.8% of
patients with LABC (P-value = 0.028). Objective clinical response to neo-adjuvant chemotherapy in the IBC arm
was 57.1% (4.8% complete response (CR)) as compared with 81% (9.5% CR) in LABC (P-value = 0.09). Overall
pathological response (complete pathological response (pCR)+partial pathological response (pPR)) was 35.3%
in the IBC arm compared with 40% in LABC arm (P-value = 0.618). One year, 2 year and median progression
free survival (PFS) were 55.87%, 37.71% and 21.7 months, respectively in the IBC arm compared with 85.71%,
66.67% in LABC (median PFS was not reached) (P-value = 0.072). One and 2 year overall survival (OS) were
69.82% and 51.20%, respectively in the IBC arm compared with 95.24% and 95.24% in LABC arm (P-value =
0.0038).IBC should be considered as a separate entity. A high MIB-1 score is a potential molecular marker for
IBC.
PMID: 19847283

Intra-operative diagnosis of breast mass-lesions: comparison of the validity of touch

smear preparation and frozen section techniques.

El-Bolkainy TM; Shabaan HA; Abodeif WT; El-Bolkainy MN; El-Tony A

A reliable intra-operative pathological diagnosis is a mandatory before proper surgery of breast cancer. So far,
The Frozen Section Technique (FS) is the standard technique with a relatively high level of validity. However,
when the special facilities of FS are unavailable, Touch Smears Preparation technique (TSP) could be
alternatively adopted.Our objective is to compare the validity of TSP in the intraoperative diagnosis of breast
mass lesions, with that of FS technique. An additional aim is to determine the special advantages of both
techniques.The study was conducted on 130 breast mass lesions, obtained from operable cases, requesting
intra-operative diagnosis at the Pathology Department at the National Cancer Institute (NCI), Cairo University,
during the years 2004-2007. The specimens were subjected to the two diagnostic techniques, namely: FS and
TSP. Then both were examined separately, by two different observers. The results were expressed as: positive
for malignancy, negative for malignancy or deferred diagnosis. The validity of each FS and TSP is tested by
using the validity statistical formulas and then results of both were compared. Paraffin section was the golden
standard for the true diagnosis.The accuracy of FS was found to be higher than TSP (100%). Thus, a sensitivity
of 100% and a specificity of 100%. Whereas, TSP had a sensitivity of 92.99%, a specificity of 93.33% and an
overall accuracy of 92.5%. TSP had also a negative predictive value of 80% and the positive predictive value
was 97.65%. The rate of deferred diagnosis was lower in FS (1.5%) than TSP (6.2%).The study concluded that
The FS is much superior to TSP in intra-operative the diagnosis of breast mass. However, when the special FS
equipment is lacking, TSP could be a reliable alternative provided that an experienced cytopathologist is
available. Analysis of predictive value rates revealed that a positive cytological report is more reliable than a
negative one. Moreover, TSP could also be an adjuvant to FS.
PMID: 17671527

Ipsilateral in-breast tumor relapse after breast conservation therapy: true recurrence
versus new primary tumor.

Abd-Alla HM; Lotayef MM; Abou Bakr A; Moneer MM

Ipsilateral breast tumor relapse (IBTR) occurs in approximately 8-20% of women 10 years after breast
conservation therapy (BCT). The aim of this study is to classify ipsilateral breast tumor relapses in patients
treated with conservative surgery and radiation therapy as true recurrences or new primary and to show the
clinical significance of classification into these two types of recurrences.Out of 267 patients treated at National
Cancer Institute, Cairo University in the period extending from 1993 to 2000, 29 patients have experienced
ipsilateral tumor relapse as the first site of recurrence. These relapses were classified as true recurrence if it

81
was located within 3cm of the primary tumor bed and was of the same histologic subtype. All other ipsilateral
breast tumor relapses were considered as new primary. The patients were followed-up until January
2005.After a mean follow-up period of 7.9 +/- 2.6 years following the original diagnosis, the overall ipsilateral
breast tumor relapse rate was 9.6% (29/267). Relapses were classified as TR in 21 patients (72.4%) and were
considered as a new primary in 8 cases (27.6%). Patients diagnosed with a new primary had a longer mean
time to breast relapse (6.09 years for NP Vs 3.09 years for TR, p < 0.001) and were significantly younger than
true recurrence patients (38.38 years Vs 47.54 years, p=0.006). Patients with a new primary had a 10- year
overall survival of 87.5%; whereas, it was 61.90% for TR cases (p=0.13).It appears that a significant portion of
patients who experience ipsilateral breast tumor relapse following conservative surgery and radiation therapy
have new primary tumors as opposed to true recurrences. Patients with a new primary had better survival
rates than those with true recurrence. Distinguishing new primary breast carcinoma from local disease
recurrence may have importance in therapeutic decisions and chemoprevention strategies.
PMID: 20571596

Isolation and Immuno-Phenotypic Characterization of Tumor Infiltrating Lymphocytes

(TILs) Obtained from Breast Malignant Tumor Tissues of Egyptian Patients.

El-Houseini ME; Sleem MM; Bahnassy AM; Shaaban KM; Saber TK; El-Sherbini M; Hussein TD

Isolation and phenotypic characterization of tumor infiltrating lymphocytes (TILs) in some malignant tumors
have been shown. TILs possess a good prognostic value as well as a therapeutic effect in these solid tumors.
Our preliminary work shed some light on a good possibility of synthesis and secretion of specific protease
enzyme system with a dimeric structure above 92 kDa for the lytic activity of TILs against breast tumor cells
propagated ex vivo.This work aims at first isolation, activation and immuno-phenotypic characterization of TILs
derived from malignant tumor tissues of breast cancer patients. Second, to optimize the conditions for the
biological therapeutic efficiency of the identified TILs subpopulations as targeted cell therapy against breast
cancer.The present work presented twelve patients with breast cancer from NCI, Cairo. Tcell isolation,
activation, immunophenotyping and immunohistochemical investigations were performed. Enzymatic
digestion method, mesh with pore size 355 & 45mm and flow cytometric analysis were used.The results
revealed that, lymphocytes infiltrating the malignant tumor tissues were mainly of the Tcell type indicated by
CD45RO positive markers as shown by immunohistochemical observations. The immunophenotypic analysis of
the isolated TILs obtained from breast tumor tissues specimens and activated with interleukin- 2 (IL-2), showed
that the ratio of CD4+/CD8+ was 0.89 which represents helper and cytotoxic sub-populations of TILs,
respectively. Meanwhile, the ratio of CD4+/CD25+ was 16.03 representing the regulatory system of TILs
subpopulation. In the peripheral blood of patients, the percentages of the CDs positive cells were different and
the ratio of CD4+/CD8+ was 1.14+/-0.57 whereas the ratio of CD4+/CD25+ was 18.38+/-5.95. After mixing the
isolated TILs and the T-lymphocytes obtained from the peripheral blood, the ratio of CD4+/CD8+ increased
insignificantly to 1.45+/-0.67. Also the ratio of CD4+/CD25+ increased rough insignificantly, to 23.64+/-
9.83.The isolated and identified TILs subpopulations have to be tested for their biological therapeutic efficacy
first at ex-vivo level using the cr51 release assay; second at in-vivo level using experimental animal models as a
sub-clinical investigation before going further to clinical study of using TILs as targeted bio-immunotherapy
against human cancers. KEY WORDS: TILs - Immunohistochemistry - Immunophenotyping - Breast cancer.
PMID: 15717000

Loss of heterozygosity at BRCA1, TP53, nm-23 and other loci on chromosome 17q in
human breast carcinoma.

Saleh EM; Wahab AH; Elhouseini ME; Eisa SS

In Egypt, breast cancer ranks number one among the female malignancies. Activation of oncogenes and
inactivation of tumor suppressor genes are thought to play an important role in the development and
progression of breast cancer.The present study is a trial to investigate the role of chromosome 17 in sporadic
invasive ductal carcinoma of the breast through detection of LOH for 6 highly polymorphic microsatellite loci,
two of which are located at BRCA1 gene (D17S855 and D17S856), one at TP53 gene, one at nm-23 gene and
finally two at 17q12-12.3 (D17S183 and D17S250).Tissue samples and their corresponding safety margin

82
normal tissues were collected from 25 patients with invasive ductal carcinoma of the breast of grades 2 and 3.
LOH was detected for the 6 highly polymorphic microsatellite markers mentioned previously using PCR
assay.The percentage of overall LOH recorded was 68% of the cases examined. The highest LOH recorded in
D17S855 and D17S856 (43% and 32% respectively), both markers are located at BRCA1 gene, followed by 32%
LOH in nm-23 gene. D17S183 and D17S250, which are localised telomeric and centromeric to BRCA1 gene,
showed 24% and 28% LOH, respectively. The lowest percentage of LOH was observed in the TP53 gene (14%).
No significant correlation was found between each of the six markers used and lymph node status, grade, or
menopausal status. LOH at the nm-23 marker exhibited a significant association with lymph node
involvement.It can be concluded from the present study that BRCA1 gene may be involved in carcinogenesis of
some sporadic breast cancer cases. Deletion in nm-23 gene is associated with advanced stage of the disease.
Finally, another gene located at 17q12-12.3 region may be involved in some sporadic breast cancer cases.
PMID: 21415863

Management of early breast cancer with breast conservative surgery. An egyptian

experience.

El-Marakby H

Breast conservative surgery (BCS) has been an established method for treatment of early breast cancer. The
volume of the procedure varies from a wide local excision to partial mastectomy and ipsilateral axillary
lymphadenectomy. The nipple and areola complex sparing, depends on their proximity to the tumour.
Radiotherapy, chemotherapy and or hormonal treatment play an integral role in the treatment of early breast
cancer.In the present study we present our experience at National Cancer Institute, Cairo University with
breast conservative surgery in treatment of female patients with early (T1-T2) breast cancer. The aim is to
examine the evidence based management of those cases and the outcome of treatment in terms of loco
regional recurrence and/or distant metastasis.The study includes 200 with early breast cancer patients who
presented to the department of surgery, National Cancer Institute between May 2002 and February 2007. The
average age was 46±6.5 years and the range was (26-72 years). Bilateral mammography, chest X-ray and full
blood count were done routinely in the entire patients' group. The inclusion criteria included all patients
presented with a breast tumor up to 4cm in greatest dimension (T1-2N0).Sixty Eight percent of patients
underwent wide local excision, 20%underwent quadrantectomies, and 12% underwent partial mastectomy
with or without nipple and areola preservation. All patients who underwent quadrantectomy or partial
mastectomy required an augmentation mammoplasty to restore the breast volume. A latissmus dorsi
myocutaneous flap was used in the majority of cases (70%), the rest were reconstructed with either a
prosthetic implant or transverse rectus abdominis flap. The complications involved a total flap loss in 2
patients, partial flap loss in 2, nipple and areola sloughing in 4, wound infection in 5, haematoma in 4, seroma
in 60, and donor site morbidity in 12 patients. Ninety three percent of patients had a radical radiotherapy
treatment (4500G) and 86 percent received adjuvant chemotherapy while only 74% were given hormonal
treatment based on the protocol of treatment and the histopathological findings. Late complications in the
form of fat necrosis took place in 12% of patients, local recurrence developed in 7% of patients and distant
metastasis in 8%, whereas 3% had both local recurrence and distant metastasis.The results of the current
study showed that evidence based management of early breast cancer with breast conservative surgery; in
terms of the incidence of locoregional recurrence matches favorably with the reported international studies.
The present study showed an increased risk of local recurrence in younger patients, patients with high grade
disease and those with lymph node metastasis with capsular invasion. Those patients In particular, should be
followed up on a regular basis for several years so that any sign of local failure can be diagnosed early and
treated accordingly. KEY WORDS: Breast conservative surgery - Loco regional recurrence - Evidence based
management of breast cancer.
PMID: 21132030

83
 Measured and Calculated Dose to the Junction between Supraclavicular Field and
Tangential Fields Using Different Techniques in Post-Mastectomy Radiotherapy.

El-Mongy M; Mehany GA; Tolba AR

Appropriately delivered post-operative radiotherapy is an integral part in the multidisciplinary approach for
the treatment of invasive breast cancer.Is to find the most effective simple way to achieve homogeneous dose
distribution to the junction of the supraclavicular beam and tangential beams, in absence of CT planning
facilities, through measurement/calculation of dose using different techniques.Alderson human phantom was
planned and irradiated through 4 different techniques. Technique I, simple abutment of fields; technique II,
table rotation in tangential fields; technique III, table rotation in tangential beams and half beam block in
supraclavicular field; and technique IV, simple triangular block in supraclavicular field. Dose to the junctional
area was both measured using film dosimetry, and calculated using CT planning (Precise plan).Simple
abutment of fields resulted in a significant junctional overdose in both measured (125%) and calculated (171%
to 20% of junctional volume) dose. Best results were seen in technique III (table rotation and half beam block)
where the measured dose was 89% and calculated dose was 89% to 20% of junctional volume. Technique II
and IV resulted in 120%, 120% measured dose and 128%, 138% calculated dose to 20% of volume of junctional
area, respectively.Table rotation in tangential beams and half beam block in supraclavicular beam seems to be
an effective and simple method to prevent junctional overlap in the sitting of post-mastectomy radiotherapy
for breast cancer in case of absence of CT-based treatment planning and conformal radiotherapy. KEY WORDS:
Radiotherapy - Postmastectomy - Supraclavicular field - Tangential field.
PMID: 19190691

Missed breast carcinoma; why and how to avoid?

Kamal RM; Abdel Razek NM; Hassan MA; Shaalan MA

Introduction : Despite the advances in mammography techniques, it still has a number of limitations. It is
estimated that about 10 to 25% of lesions are overlooked in mammograms out of which about two thirds are
detected retrospectively by radiologists and oncologists. Causes of missed breast cancer on mammography can
be secondary to many factors including those related to the patient (whether inherent or acquired), the nature
of the malignant mass itself, poor mammographic techniques, provider factors or interpretive skills of
radiologists and oncologists (including perception and interpretation errors). Aim of Work : The aim of this
study is to investigate the aforementioned factors hindering early breast cancer detection and in turn lowering
mammographic sensitivity and to outline the major guidelines to overcome these factors aiming to an
optimum mammographic examination and interpretation by radiologists and oncologists. Subject and
Methods : We conducted this multicenter study over a two-year interval. We included 152 histopathologicaly
proven breast carcinomas that were initially missed on mammography. The cases were subjected to
mammography, complementary US, MRI and digital mammography in some cases and all cases were
histopathologically proven either by FNAB, CNB or open biopsy. Results : Revision of the pathological
specimens of these 152 cases revealed 121 infiltrating ductal carcinomas, 2 lobular, 4 mucinous, 14
inflammatory carcinomas, 6 carcinomas in situ (3 of which were intracystic), 2 intraductal papillary carcinomas
and 3 cases with Paget's disease of the nipple. In analyzing the causes responsible for misdiagnosis of these
carcinomas we classified them into 4 causative factors; patient, tumor, technical or provider factors. Tumor
factors were the most commonly encountered, accounting for 44.1%, while provider factors were the least
commonly encountered in 14.5 %. Carcinomas were detected using several individual or combined
complementary techniques. These techniques mainly included double reading, additional mammography
views, ultrasound and MRI examinations. Forty four carcinomas were detected on double and re-reading by
more experienced radiologists. Additional mammographic views were recommended in 35 (23%) cases.
Complementary ultrasound examination was performed for all 152 cases (100%) and showed a higher
sensitivity than mammography in carcinoma detection. It was diagnostic in 138 (90.8%) cases only. In the
remaining 14 cases, further MRI and biopsy were performed. Conclusion : Why can breast carcinoma be
missed? Four main factors are responsible for missing a carcinoma: (1) Patient factors (Inherently dense

84
breasts or acquired dense breasts). (2) Tumor factors (subtle carcinoma, masked carcinoma, multifocal
carcinoma and multicentric carcinoma). (3) Technical factors (bad exposure factors, malpositioned breasts and
bad processing quality). (4) Provider factors (bad perception and misinterpretation). How to avoid missing a
breast carcinoma? Review clinical data and use US and other adjunct techniques as MRI and biopsy to assess a
palpable or mammographically detected mass. Be strict about positioning and technical factors. Try to
optimize image quality. Be alert to subtle features of breast cancers. Always consider the well defined
carcinoma. Compare current images with multiple prior studies to look for subtle increases in lesion size. Look
for other lesions when one abnormality is seen. Judge a lesion by its most malignant features. Double reading
and the use of computer aided diagnosis (CAD) and finally FFDM (Full Field Digital Mammography). Close
cooperation between the oncologist, radiologist and pathologist is essential to avoid missing any case of breast
carcinoma. Key Words : Missed breast carcinoma -Mammography - Ultrasonography -MRI.
PMID: 22295218

Multiple Patterns of FHIT Gene Homozygous Deletion in Egyptian Breast Cancer Patients.

Ismail HM; Medhat AM; Karim AM; Zakhary NI

Fragile histidine triad (FHIT) gene encodes a putative tumour suppressor protein. Loss of Fhit protein in cancer
is attributed to different genetic alterations that affect the FHIT gene structure. In this study, we investigated
the pattern of homozygous deletion that target the FHIT gene exons 3 to 9 genomic structure in Egyptian
breast cancer patients. We have found that 65% (40 out of 62) of the cases exhibited homozygous deletion in
at least one FHIT exon. The incidence of homozygous deletion was not associated with patients'
clinicopathological parameters including patients' age, tumour grade, tumour type, and lymph node
involvement. Using correlation analysis, we have observed a strong correlation between homozygous
deletions of exon 3 and exon 4 (P < 0.0001). Deletions in exon 5 were positively correlated with deletions in
exon 7 (P < 0.0001), Exon 8 (P < 0.027), and exon 9 (P = 0.04). Additionally, a strong correlation was observed
between exons 8 and exon 9 (P < 0.0001).We conclude that FHIT gene exons are homozygously deleted at high
frequency in Egyptian women population diagnosed with breast cancer. Three different patterns of
homozygous deletion were observed in this population indicating different mechanisms of targeting FHIT gene
genomic structure.
PMID: 16263653

No correlation between radiosensitivity or double-strand break repair capacity of normal

fibroblasts and acute normal tissue reaction after radiotherapy of breast cancer patients.

El-Awady RA; Mahmoud M; Saleh EM; El-Baky HA; Lotayef M; Dahm-Daphi J; Dikomey E

The aim was to study the relationship between cellular radiosensitivity or double-strand break (dsb) repair
capacity of skin fibroblasts and the extent of acute reaction after radiotherapy for breast cancer. The study
was performed with 25 breast cancer patients submitted to the radiotherapy unit of the Egyptian National
Cancer Institute after conserving surgery. Dermal fibroblasts, established from skin biopsies, were used to
determine the cellular radiosensitivity via colony assay and the capacity of dsb repair by constant-field gel
electrophoresis. Acute reactions were scored using the Radiation Therapy Oncology Group (RTOG)
classification. The spectrum of acute reactions varied from grade 1 to 4, whereby most patients developed a
grade 1 reaction after total doses ranging between 46 and 70 Gy. Skin fibroblasts showed a pronounced
variation in both cellular radiosensitivity expressed as the mean inactivation dose (Dbar) (coefficient of
variation, CV=25%) as well as in the number of residual dsb (CV=33%) with no significant correlation between
these two endpoints (r2=0.20, p=0.14). Both parameters did not correlate with the extent of acute reaction of
the respective patient. The data obtained indicate that the sensitivity of fibroblasts measured either by colony
assay or by dsb repair capacity is not a major parameter determining the extent of acute reaction after
radiotherapy of breast cancer patients.
PMID: 18301457

85
 Oncoplastic resection of retroareolar breast cancer: central quadrantectomy and
reconstruction by local skin-glandular flap.

Naguib SF

Patients with central breast neoplasms account for 5 to 20% of breast cancer cases and, for a long time, they
have been denied Breast Conservation Surgery (BCS) and conventionally treated with mastectomy. The high
incidence of Nipple-Areola-Complex (NAC) involvement usually associated with these tumors necessitates
nipple and areolar resection together with an adequate safety margin around the tumor, which yields an
unacceptable cosmetic result. With the help of Oncoplastic Surgical Techniques, BCS can be offered to these
patients. In this study central quadrantectomy and breast reconstruction by an infero-laterally based pedicled
flap were evaluated.This study comprised 23 women with central breast tumors treated at the National Cancer
Institute (NCI), Cairo University and at the Aswan Cancer Center, Egyptian Ministry of Health. Their ages
ranged from 31 to 62 years (mean: 48.4+/-10.2 years). Twenty-two had a palpable mass, while only 1 had
Paget's disease of the nipple without mass. The size of their tumors ranged from 4 to 33 m (mean: 16.9+/-
8.6mm). Only 9 women showed clinical suspicion of NAC involvement in the form of nipple retraction.
Seventeen cases had their tumors strictly in the retro-areolar region, while 5 had tumors extending for a
maximum of 1.5 cm beyond the areolar edge. All patients underwent central quadrantectomy with NAC
resection removing a cylinder of breast tissue reaching down to the pectoral muscle together with axillary
dissection. Advancement of an infero-laterally based skin-glandular flap was then carried out. All patients
received adjuvant radiotherapy with or without chemotherapy or hormonal therapy.Fourteen patients showed
pathological evidence of nipple infiltration (60.8%). The free safety margin (SM) ranged from 9 to 13 mm
(mean: 10.2+/-0.9 mm). This could be accomplished from the first attempt in 18 patients;however, in 5
patients a second wider excision was needed to obtain an adequate margin. Positive axillary nodes were found
in 10 / 23 patients (43.5%). The procedure lasted a mean time of 195+/-12.7 minutes and blood loss was
estimated at a mean of 225+/-64.8 mL. Hospital stay ranged from 2 to 10 days (median: 4 days). Post-
operatively, superficial flap sloughing occurred in 2 / 23 patients and full thickness sloughing in 1 /23 patients.
Cosmetic results were evaluated by both patient and surgeon according to a scoring system and were found
excellent in 26.1%, good in 34.8%, satisfactory in 30.4%, poor in 8.7% and very poor in none. The procedure
did not delay the start of adjuvant treatment nor did it hamper clinical and mammographic follow-
up.Oncoplastic techniques have succeeded in expanding the role of BCS to retro-areolar tumors. Central
quadrantectomy with repair by a skin-glandular flap is a relatively simple procedure that yields very
satisfactory cosmetic results with minimal complications and it may be considered as one of the noteworthy
therapeutic options for patients with central breast tumors.
PMID: 22776844

Oncoplastic volume replacement with latissimus dorsi myocutaneous flap in patients with
large ptotic breasts. Is it feasible?

El-Marakby HH; Kotb MH

Oncoplastic breast conservative surgery has evolved as a safe alternative to the standard mastectomy in the
treatment of early breast cancer. The procedure involves tumour resection with an adequate safety margin
and either breast reshaping with volume displacement procedures (large or ptotic breasts) or volume
replacement with latissimus dorsi myocutaneous flap (LDF) (small to medium sized non-ptotic breasts). A
contra lateral mastopexy procedure is usually necessary with the volume displacement oncoplastic surgery, a
procedure that is often rejected by a significant number of patients. This limits the choice of the reconstruction
of breast defects in such patients to autologous tissues i.e. LDF.Aim is to evaluate the feasibility of volume
replacement oncoplastic breast conservative surgery with latissimus dorsi myocutaneous flaps for patients
with large ptotic breasts. This involves testing the oncologic safety in terms of adequate safety margin, the
complications rate and the final cosmetic outcome. The loco regional recurrence rate will be recorded and
compared with oncoplastic volume displacement for similar sized breast defects.A group of 50 female patients
with early breast cancers (T2) who presented to the department of surgery at the National Cancer Institute,

86
Cairo, Egypt in the period between January 2004 and November 2009 were included in the study. Bilateral soft
tissue mammography was carried out in all patient groups and was used to annually follow up the patients. All
patients were detected with T2 N0 breast cancer by both clinical and radiological examinations. All patients
underwent partial mastectomy and reconstruction with LDFs.The average age at presentation was 46.5±9years
and the range was 26-65years. Most of the patients were subjected to partial mastectomy in 30 patients
(60%), excision of a single quadrant from the four major quadrants was carried out in 15 patients (30%) where
skin sparing wide local excision was carried out in only five patients (10%). The safety margin ranged from 1.1
to 3.2cm with an average of 1.8±0.5cm. There was no total flap loss in any patient where as we reported
partial flap loss in two patients. Nipple and areola sloughing were reported in two patients, wound infection in
five patients, haematoma in four patients, seroma in 16 patients, and donor site morbidity in six patients. The
vast majority of patients were either satisfied (score >3 out of 5) (62%) or very satisfied (score 4 or more)
(18%) with the results of reconstruction.The results of the current study showed the feasibility and the
versatility of volume replacement oncoplastic surgery in patients with large ptotic breasts with myocutaneous
flaps. The adequacy of safety margin and the acceptable complications rate as well as the comparable local
recurrence rate to volume displacement oncoplastic surgery, make it a suitable alternative in a subset of
patients who object an immediate contra lateral mastopexy procedure.
PMID: 10752778

Pathological assessment of the response of locally advanced breast cancer to neoadjuvant

chemotherapy and its implications for surgical management.

El-Didi MH; Moneer MM; Khaled HM; Makarem S

The effectiveness of breast-conserving surgery for patients with locally advanced breast cancer (LABC) after
neoadjuvant chemotherapy (NACT) is still a controversial issue, and variable incidences of locoregional failures
have been reported. The present study was conducted to pathologically assess the response of LABC to NACT,
and also to evaluate the efficacy of preoperative clinical examination and mammography in detecting these
pathological changes. A total of 38 patients with LABC received NACT in the form of three cycles of
fluorouracil/adriamycin/cyclophosphamide and were then subjected to a mastectomy. The residual tumors in
the mastectomy specimens were measured, mapped, and compared to the pretreatment and preoperative
clinical and mammographic findings for evaluation. An objective response to NACT was observed in 70.4% of
the patients; however, only 26.7% of them were suitable candidates for conservative surgery. The rest of the
responders showed an increased incidence of multifocality and in situ lesions localized within the original
tumor-bearing area. Both clinical examinations and mammography were inadequate for the selection of
candidates for breast conservation. Tumor regression by NACT is probably induced by a process of tumor
segmentation. It is also associated with an increased incidence of multifocality and in situ lesions.
PMID: 22897908

Peripheral blood mammaglobin gene expression for diagnosis and prediction of

metastasis in breast cancer patients.

Radwan WM; Moussa HS; Essa ES; Kandil SH; Kamel AM

Aim: To evaluate the value of peripheral blood mammaglobin (MG) gene expression for diagnosis and
prediction of metastasis in breast cancer patients. Methods: MG expression was detected by nested reverse-
transcription polymerase chain reaction in the peripheral blood of 46 females (32 breast cancer, 12 benign
breast lesions, 2 no breast abnormalities). In total 28 breast cancer patients were followed up through a period
of 34 months for the development of metastasis. Results: MG expression was detected in 16/32 (50%)
breast cancer patients but not in patients with benign lesions or healthy participants. Five patients had
metastasis at diagnosis. During the 34 months of follow up, five more MG-positive patients showed
metastatic lesions and none of the MG negative patients who were followed up developed metastasis.
Conclusion: The study suggests blood MG expression is a specific molecular marker for detection of occult
mammary carcinoma cells of patients with operable breast cancer. It might be of value as a predictor of
subsequent metastasis. Large-scale studies and longer follow-up periods are needed.

87
PMID: 16799658

Planning of the internal mammary field based on lymphoscintigraphy localization before

postoperative radiotherapy of breast cancer.

Lotayef MM; Barsoum MS; Zaki OE; Nasr MA; Abdel Aziz RA; Koteb M; Radwan A

Internal mammary irradiation is still an issue of great debate. Although treatment of internal mammary lymph
nodes was routinely given in the majority of randomized trials, data in its value are still limited. The aim of this
study is to determine the variability of position of the internal mammary lymph nodes using
lymphoscintigraphy and to compare the dose of radiation that reaches these lymph nodes, the heart and lungs
if only tangential fields are used.This is a prospective study that included 30 breast cancer patients treated in
the department of radiation oncology of the Egyptian National Cancer Institute, Cairo University, planned for
postoperative radiotherapy. Lymphoscintigraphy was done for all patients for detection of the exact site of the
internal mammary lymph nodes. Dose volume histogram (DVH) was done to measure the dose to the heart
using CT planning. Two plans were done for each patient, the first with internal mammary field (plan I), and
the second without but with contralateral crossing of the midline by 1cm (plan II).The mean percentage of the
internal mammary lymph nodes included in the internal mammary field (plan I) was 70.03% while in plan II it
was 3.05%. The mean dose percentage reaching the heart in plan I was 54.5% of total dose, while in plan II it
was 9.16% of total dose with significant p value<0.001. The mean dose to the heart decreased as the heart
volume increased, this significant difference between the 2 plans was maintained for the different heart
volumes. Also, the radiation dose to the heart in plan I varied significantly (p: 0.001) between the right side vs
the left side with a mean dose of 48.02% and 63.5%, respectively. The mean dose percentage reaching the
lungs in plan I and plan II was 46.53% and 24.5% respectively, with significant p value<0.001.If irradiation of
internal mammary chain is intended, then a direct internal mammary field should be used. The planning of
internal mammary field should be adjusted according to lymphoscintigraphy so as to include most of the
draining internal mammary lymph nodes. The risk of late cardiac and pulmonary complications will increase
when using direct internal mammary field, but the risk of cardiac complications will be less in irradiation of
right side internal mammary lymph nodes compared to that of irradiation of the left side.
PMID: 11917941

Plasma bcl-2 and nitric oxide: possible prognostic role in patients with metastatic breast
cancer.

Gaballah HE; Abdel Salam I; Abdel Wahab N; Mansour OM

Interest in translational studies on breast cancer is presently devoted to identifying biological predictors of
disease prognosis and response to treatment. In this study, we determined the plasma levels of bcl-2 and nitric
oxide in 45 patients with metastatic breast cancer using an ELISA technique and correlated them with clinical
and biological factors that may affect the outcome of disease. The results were as follows. The mean level of
bcl-2 was 278.44 +/- 383.2 U/L compared with 64.42 +/- 14.4 U/L (p = 0.007) for controls. Levels of bcl-2 were
higher in patients less than 50 yr old, premenopausals., GIII tumors, positive nodes, ER positive tumors (p =
0.6, 0.5, 0.9, 0.4, and 0.005, respectively). The site of metastatic disease and the number of metastatic sites did
not show statistically significant influences over bcl-2 levels. Furthermore, there was a trend, although not
significant, toward improvement of survival in patients with higher levels of bcl-2. The mean level of the nitric
oxide (NO) was 297.12 +/- 220.54 microM compared with 13.91 +/- 1.1 microM for controls (p = 0.003). The
levels were higher in patients over 50 yr, postmenopausal patients, those with visceral deposits, grade III
tumors, positive lymph nodes, and those with disease-free survival of less than 6 mo following primary
treatment (p = 0.1, 0.2, 0.1, 0.09, 0.4, and 0.08 respectively). Furthermore, there was no correlation between
NO levels and survival (r = 0.002). This study demonstrates a potential role for NO and bcl-2 as prognostic
factors in patients with metastatic breast cancer. However, larger studies with more patients together with a
comparison of serum levels (ELISA) and tissue levels (MOAb) are still required.
PMID: 17496937

88
Predictive factors of local recurrence and survival following primary surgical treatment of
phyllodes tumors of the breast.

Abdalla HM; Sakr MA

The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. Local
recurrence and death from metastases are occasional, but consistent, theme in reports of patients with
phyllodes tumors (PTs). The aim of this study was to determine parameters that influence outcome in this
uncommon neoplasm.Data from 79 patients with phyllodes tumors were reviewed retrospectively,
reclassifying the pathological material using the World Health Organization (WHO) criteria.The median age of
the patients was 42 years with a range from 16 to 70 years. The tumor size ranged from 2.5 to 24 cm, with a
median of 11 cm. Based on the criteria proposed by WHO, 31 cases were benign tumors (39.2%), 27 borderline
tumors (34.2%), and 21 malignant tumors (26.6%). The median duration of follow up was 60 months ranging
from 3 to 138 months. Following local excision, the local recurrence rates were 14.3%, 50%, and 75% in
patients with benign, borderline, and malignant tumors; respectively, while after wide local excision the local
recurrence rates were 0%, 36.3% and 40%; respectively. Whereas, 0%, 8.3%, and 8.3% of patients with benign,
borderline and malignant tumors; respectively, locally recurred after mastectomy. The 5-year disease free
survival was 63.3% after local excision, 70% after wide local excision, and was 87% after mastectomy (p=0.04).
Distant metastases (DM) were recorded in 10 patients (12.6%) after a median duration of 14 months (range 3-
36). All cases with DM died after an average of 5 months with a range of 1 to 11 months. Distant metastases
developed in 3.2%, 11.1%, and in 28.6% of patients with benign, borderline and malignant tumors;
respectively. The 5-year survival with no evidence of disease was 90% for the patients with benign tumors
compared to 69% for borderline and 61% for malignant PTs (p= 0.02).The histotype of phyllodes tumors and
resection margins were the principal determinants of local recurrence and distant metastases. Complete
surgical excision by either wide local excision or mastectomy if necessary is important in the primary surgical
treatment of phyllodes tumors.
PMID: 16799652

Quadrantectomy and nipple saving mastectomy in treatment of early breast cancer:

feasibility and aesthetic results of adjunctive latissmus dorsi breast reconstruction.

Bassiouny M; El-Marakby HH; Saber N; Zayed SB; Shokry A

Breast conserving surgery has been a recognised method of treatment of early breast cancer. The treatment
methods include quadrantectomy or skin sparing mastectomy combined with ipsilateral axillary nodal
dissection followed by radiotherapy. In the current study we evaluate the feasibility and oncologic safety of
the quadrantectomy and SSM operations with preservation of the nipple and areola, and the cosmetic results
of immediate reconstruction by using the latissmus dorsi flap.A breast conservative surgery (quadrantectomy
or nipple sparing mastectomy) was carried out in a group of 55 patients with invasive breast cancer treated at
the Department of Surgical Oncology, NCI, between January 2001 and April 2004. The selection criteria
included those patients who presented with T1 or T2 breast cancer and were located at least 2 cm from the
nipple as the centre for the nipple areola complex.The age of the patients ranged from 32 years to 65 years.
The follow up period ranged from 2 to 33 months with an average of 21 months. Pathological assessment of
the specimens showed a negative safety margin in all cases. Most of our cases were invasive duct carcinoma
grade 1-2 (42) (75%). The complications of the flap reconstruction included one major sloughing of the
latissmus dorsi flap, 4 partial flap sloughing, 4 sloughing of the nipple and fat necrosis in 6 patients. The donor
site healed normally in all of our cases except for one patient who suffered from a hypertrophic scar which
settled down during the follow up period. The aesthetic assessment of the patients, showed an excellent to
good results in the majority of cases (42) (75%) while in 6 (12%) results were fair and in 7 (13%) results were
poor.Breast conservative surgery with quadrantectomy or skin sparing technique with preservation of the
nipple and areola combined with immediate LD flap reconstruction is a valid procedure for treatment of early
breast cancer. Immediate reconstruction by using the extended latissmus dorsi is as safe, relatively easy
procedure which can provide an adequate volume replacement for small to moderate sized breasts.
PMID: 19652667

89
 Review article optimizing the use of her-2/neu targeting agents in breast cancer : a
developing nation perspective.

Azim HA; Azim HA

Her-2/nue positive breast cancer is an aggressive disease with a higher potential of invasion and metastasis. It
constitutes around 20% of all the breast cancer cases and even a higher incidence has been reported in Egypt.
Agents targeting Her-2 have been shown to be associated with improvement in response rate, disease free and
overall survival.Different biomarkers have recently emerged to predict the benefit of trastuzumab and/or
lapatinib. Phosphatase and tensin homolog (PTEN), topoisomerase 2 alpha (TOPO2A) AND p95HER2 have been
associated with appealing results in selecting patients who may or may not respond to these grants.Despite
the impressive results of Her-2/nue targeting agents in both the adjuvant and metastatic phases, still a
significant fraction of patients are not offered these agents particularly those in countries with limited
resources due to their high cost. In this review, we will discuss how we can optimally use these agents from
developing nation perspective. We will elaborate on different schedules available and will highlight the
importance of incorporating different biomarkers to assist in proper selection of patients who can optimally
benefit these agents.
PMID: 21860470

Role of Sonoelastography in the Differentiation between Benign and Malignant Breast

Lesions.

Aly AM; Helal MH; Shabana AM

To prospectively evaluate the accuracy of real time elastography (ultrasound strain imaging) for distinguishing
between benign and malignant solid breast lesions with the pathologic results as the reference standard. We
also evaluated if the fat÷lesion ratio could semiquantitatively evaluate the stiffness of breast
lesions.Conventional ultrasonography (US) and real time elastography were performed in 100 women with
breast masses with the mean age is 50 years. Elasticity images were given an elasticity score according to the
degree and distribution of the strain induced by light compression with 1-3 is benign and 4-5 is malignant. We
also calculated the ratio of the normal breast tissue to that of the lesion (fat÷lesion ratio) of the different
breast lesions with the fat as the reference. The cutoff point was 4.8 with ratio below this level is considered
benign and above this level is considered malignant.For elasticity score, the mean standard deviation was 4.1
for malignant lesions and 2.1 for benign lesions (p<0.001). When a cutoff point between 3 and 4 was used,
elastography had 87.2% sensitivity, 90.6% specificity and 90% accuracy. The fat÷lesion ratio (F÷L ratio) of the
benign lesions was different from that of the malignant ones.US strain imaging can facilitate improved
classification of benign and malignant breast masses and has the potential to aid their diagnosis. By using the
F÷L ratio, the stiffness of breast lesions could be semiquantitated and this method may provide another
diagnostic method in addition to the scoring system. KEY WORDS: Breast - Sonoelastography - Strain imaging -
Fat-lesion ratio.
PMID: 12913081

Serum lipids and tissue DNA content in Egyptian female breast cancer patients.

Abu-Bedair FA; El-Gamal BA; Ibrahim NA; El-Aaser AA

Several clinical studies suggest the prognostic significance of serum lipid levels and tissue DNA content in
breast cancer. In the course of investigating the biological features of this disease among Egyptian female
patients, we examined the serum lipid levels and tissue DNA content of premenopausal and postmenopausal
breast cancer patients.Levels of total lipid, total cholesterol, and triglycerides were measured in the sera of
women with breast cancer and compared with those of the control women. The DNA content in breast cancer
tissue was also measured in these patients.Total lipid levels showed a significant increase in both
premenopausal (follicular and luteal) and postmenopausal patients. Total cholesterol levels significantly
increased in premenopausal (follicular and luteal) patients with no significant change in postmenopausal

90
women. Triglyceride levels showed a significant increase in postmenopausal women, whereas no significant
differences were observed in premenopausal patients. Tumors of premenopausal patients, in both follicular
and luteal phases, showed a higher DNA content as compared with those of postmenopausal patients. Breast
cancer tissues of grade III showed significantly higher DNA content than those of grade I and grade II.This study
suggests an association between high levels of serum, total lipid and total cholesterol, and increased breast
cancer risk in premenopausal women. Such an association is also suggested for the high total serum lipid and
triglyceride levels in postmenopausal women. The DNA content in breast cancer tissue might be useful in
determining a suitable therapy for individual cases, based on the malignancy grade.
PMID: 19282568

Survival effects of cyclooxygenase-2 and 12-lipooxygenase in Egyptian women with

operable breast cancer.

Zeeneldin AA; Mohamed AM; Abdel HA; Taha FM; Goda IA; Abodeef WT

Breast cancer (BC) is the commonest among women in Egypt as well as in many other countries. Cyclo-
oxygenase-2 (COX-2) and 12-lipo-oxygenase (12-LOX) are over-expressed in 30-40% of patients and carry a
poor prognosis. The objectives of this study were to correlate COX-2 and 12-LOX expression with various
clinico-pathologic patients' characteristics and their impact on overall survival (OS) and disease free survival
(DFS) in Egyptian women with operable BC.This prospective study included 57 consecutive BC cases presenting
to the Egyptian National Cancer Institute. Sections from BC and nearby normal tissues were examined for
expression of COX-2 and 12-LOX using reverse transcriptase polymerase chain reaction.The patients' median
age was 45 years. Fifty-three percent were premenopausal. Stage II and III disease represented 25 and 75%
respectively. Adjuvant chemotherapy, radiotherapy and tamoxifen were used in 90, 75 and 60% respectively.
Sixty percent had hormone-receptor positive tumors and 28% over-expressed HER2/neu. Forty-nine and sixty-
five percent showed over-expression of COX-2 and 12-LOX respectively. Patients with higher TNM stage or
who developed visceral metastases had significantly higher COX-2 expression. For the whole group of patients,
the median DFS was 37 months, while the median OS was not reached. OS or DFS did not differ significantly
between patients with normal and over-expression of COX-2. DFS but not OS was significantly higher in 12-LOX
over-expression compared to normal expression.COX-2 over-expression was associated with poor prognostic
criteria in BC, but did not affect DFS or OS. 12-LOX over-expression was associated with better DFS, but not OS.
PMID: 17496933

The prognostic impact of some cell cycle regulatory proteins in Egyptian breast cancer
patients.

Kamel A; Mokhtar N; Elshakankiry N; Yassin D; Elnahass Y; Zakarya O; Elbasmy A; Elmetenawy W

The particular goal of this work is to study some cell cycle regulatory proteins and their potential impact on
prognosis of breast cancer; p53, cyclin D1 and p27 are potential effectors being the major contributors to the
control of the restriction (R) check point of the cell cycle. We also aimed to evaluate different techniques used
to detect these cell cycle proteins.Forty five breast cancer patients as well as 10 controls with non malignant
pathology were assessed for cell cycle regulators each by 2 different techniques; p53 was assessed by enzyme
immunoassay (EIA) and immunohistochemistry (IHC), cyclin D1 by Western Blotting (WB) and IHC and p27 by
WB and IHC. The cut-off was calculated as the mean of the normal controls +2 SD. Patients were followed up
for 4 years and their laboratory data were correlated with different clinical parameters and with other studied
regulators.Eighty seven percent of cases (39/45) were positive for p53 by EIA with a range from 20 to 4300,
and a mean of 464 +/- 971 pg/mg protein. By IHC, 80% (24/30) of the cases showed varying degrees of
positivity. Using WB, cyclin D1 showed high expression levels above cut off values in 69% of patients (31/45)
and in 67% (20/30) by IHC. The corresponding positive figures for p27 were 82% (37/45) and 73% (22/30) using
the two techniques, respectively. No significant association was found between p53, cyclin D1 and p27 on one
side and different clinical parameters as lymph node status, tumor size or presence of distant metastases on
the other side. Survival was poor in patients with high p53 expression. Cyclin D1 positive cases showed
comparable survival with negative cases, whereas high p27 levels favored a longer disease free
survival.Techniques more suitable for assessment of each of these markers in our consideration were EIA for

91
p53, WB for cyclin D1 and IHC for p27. Moreover, this study demonstrated that these markers were relevant to
the biological behavior of the tumor cell per se with a possible impact on prognosis and survival, independent
of other clinical prognostic factors.

PMID: 21860469

The Role of P63 Immunocytochemistry for Myoepithelial Cells in the Diagnosis of Atypical
and Suspicious Cases in Breast Fine Needle Aspiration Cytology (FNAC).

Hafez NH; Tahoun NS

Evaluation of the usefulness of p63 immunocytochemical marker for myoepithelial cells in the diagnosis of
atypical and suspicious lesions in breast cytology.This is a retrospective study on 122 selected patients
presented at Cytology Unit, Pathology Department, NCI, Cairo University, in three years interval from 2007 to
2009, with breast lumps who underwent preoperative FNAC and diagnosed cytologically as atypical or
suspicious breast lesion for biopsy then they were followed by excisional biopsy for histopathologic
assessment that was considered as the golden standard diagnosis against which FNAC diagnoses were
compared. Paucicellular cytologic slides as well as cases with no corresponding final histopathological
diagnosis were excluded. The destained cytologic slides were subjected to p63 immunocytochemical staining.
Only the nuclear immunoreactivity for p63 was considered specific, cytoplasmic and membranous staining was
considered nonspecific. The stained slides with p63 marker were quantified according to the percentages of
positive epithelial cell clusters and positive single bare nuclei in the BACKGROUND. The immunocytochemical
results were compared with histopathologic diagnoses.Of the 122 studied breast aspirates, 84 cases with
atypical findings and 38 cases with suspicious findings were included. The two categories yielded malignant
diagnoses in 53 cases (63.1%) and 31 cases (81.6%), respectively. Invasive duct carcinoma was the most
common malignant diagnosis in both categories. The most common benign diagnosis in the atypical group was
fibrocystic changes (48.4%), while atypical ductal hyperplasia was the most common non-malignant diagnosis
in the suspicious group (42.8%). P63 consistently stained the nuclei of myoepithelial cells, either overlying
clusters and/or single bare nuclei. Of the histologically confirmed malignant cases 69% and 91.7% showed no
p63 nuclear staining in cell clusters or bare nuclei, respectively; while cases showed staining pattern similar to
that of benign lesions. On the other hand, 84.2% and 57.9% of the benign cases showed staining in more than
75% of the clusters and bare nuclei, respectively. The staining pattern of p63 was significantly different
between malignant and benign lesions (p-value <0.005). The p63 sensitivity, specificity, positive, and negative
predictive value were 90.5%, 84.2%, 92.7%, and 80%, respectively. Scattered p63 positive ductal cells ( <10% of
duct cells) were detected in 6% of all malignant cases.The p63 was a reliable nuclear marker of myoepithelial
cells in breast cytology. Benign and malignant breast lesions showed significantly different staining pattern for
p63 on inconclusive breast cytology. The diagnostic sensitivity, specificity, positive and negative predictive
value of p63 marker were 90.5%, 84.2%, 92.7%, and 80% respectively. The p63 immunostaining may be used
as a diagnostic adjunct to the routine fine needle aspiration cytology in cases of breast lesions with atypical
and suspicious results. KEY WORDS: P63 immunocytochemistry - Breast FNAC - Inconclusive diagnoses.
PMID: 22929921

The validity of immunocytochemical expression of cyclin D1 in fine needle aspiration

cytology of breast carcinoma.

Ezzat N; Hafez N

The aim of this work is to study the validity of cyclin D1 expression, a cell cycle regulatory protein, on (fine
needle aspiration cytology) FNAC samples in patients with breast carcinoma using immunostaining
technique.This is a study done on 70 patients with primary breast carcinoma, presented to Cytology Unit,
Pathology Department, National Cancer Institute, Cairo University. They underwent preoperative FNAC and
diagnosed as breast carcinoma. The cytologic and tissue section slides were subjected to cyclin D1
immunocytochemical staining. Only the nuclear immunoreactivity for cyclin D1 was considered specific. The
rate of concordance, and discordance, and kappa value were calculated. Relation between cytologic
expression of cyclin D1 and different clinicopathologic parameters was evaluated.Cyclin D1

92
immunocytochemical expression was observed in 53/70 cases (75.7%) in cytologic smears. In histologic
sections of the corresponding cases, cyclin D1was detected in 48/70 cases (68.6%). The concordance rate of
cyclin D1 expression in the FNA and histologic sections was 87.1% while the discordance rate was 12.9%.
Kappa showed a value of 0.65. A statistically significant relation was found between cyclin D1
immunocytochemical expression and hormonal status as well as nuclear grade.Cyclin D1 immunocytochemical
expression can be performed successfully on cytologic samples with a high concordance rate and agreement
with histologic results. This can help in determining tumor biology, and plan for patients' treatment. The
marker showed a significant relation with hormone receptor status and nuclear grade.
PMID: 22236813

The value of mastectomy flap fixation in reducing fluid drainage and seroma formation in
breast cancer patients.

Sakkary MA

Prolonged and excessive drainage of serous fluid and seroma formation constitute the most common
complications after mastectomy for breast carcinoma. Seroma formation delays wound healing, increases
susceptibility to infection, skin flap necrosis, persistent pain and prolongs convalescence. For this, several
techniques have been investigated to improve primary healing and minimize seroma formation.Between June
2009 and July 2010 forty patients with breast carcinoma, scheduled for modified radical mastectomy, were
randomly divided into 2 groups, the study group (20) and the control group (20). In the study group; the
mastectomy flaps were fixed to the underlying muscles in raws, at various parts of the flap and at the wound
edge using fine absorbable sutures. In the control group; the wound was closed in the conventional method at
the edges. Closed suction drains were used in both groups. Patients, tumor characteristics and operative
related factors were recorded. The amount and color of drained fluid were recorded daily. The drains were
removed when the amount become less than 50 cc. The total amount and duration of drained fluid and the
formation of seroma were recorded and the results were compared between the two groups.In the flap
fixation group, the drain was removed in significantly shorter time compared to the control group (p < 0.001).
Also, the total amount of fluid drained was significantly lower in the flap fixation group (p < 0.001). The flap
fixation group showed a significantly lower frequency of seroma formation compared to the control group,
both clinically (p = 0.028) and ultrasonographically (p = 0.047).The mastectomy flap fixation technique is a
valuable procedure that significantly decreases the incidence of seroma formation, and reduces the duration
and amount of drained fluid. However, it should be tried on a much wider scale to prove its validity.
PMID: 17102817

TRAM flap for immediate post mastectomy reconstruction: comparison between pedicled
and free transfer.

Bassiouny MM; Maamoun SI; El-Shazly Sel-D; Youssef OZ

Breast reconstruction after mastectomy is primarily carried out to improve the patients' quality of life. The
most commonly used autologous tissue for reconstruction is the transverse rectus abdominis
musculocutaneous flap (TRAM). The TRAM flap could be transferred either as pedicled or a free flap with
microvascular anastomosis. The following work was carried out to evaluate the two techniques.Thirty-one
female patients with operable breast cancer consented to immediate breast reconstruction during the period
from June 1998 to December 2000. Fifteen patients had a free TRAM flap reconstruction. In sixteen patients, a
pedicled TRAM flap was used. Three patients in the pedicled group underwent bilateral breast reconstruction,
thus there were 19 pedicled flaps available for evaluation. Four patients in the pedicled flap group underwent
reduction mammoplasty of the normal breast and in five other patients a bipedicled flap was used to achieve
size matching with the reconstructed breast. Criteria for analysis included operative data, hospital stay, donor
site morbidity, abdominal wall integrity, flap related complications, fat necrosis and final aesthetic result.There
was no difference between the two groups as regards age and, operative time. The pedicled flap group had
shorter hospital stay and less blood loss than the free flap group, which was statistically significant (p=0.007
and p=0.001, respectively). In the pedicled flap group, two patients (10.5%) experienced partial flap loss and
fat necrosis was detected in two other patients. For the free flap group, two patients (13.3%) developed

93
complete flap loss, but none suffered fat necrosis. Donor site morbidity was equal in both groups. The total
number of complications was higher in the pedicled group (7/19) (36.8.8%) than in the free flap group (5/15)
(33.3 degrees k) but this was not statistically significant (p=0.27). None of the patients in both groups
developed abdominal wall hernia, but abdominal wall weakness was evident in eight patients in the pedicled
flap group that gradually improved over 2-3 months. Aesthetic results were comparable in both groups with a
slightly better figure for the free flap group, but this was not statistically significant (p=0.23).Although free
TRAM flap seems to provide several advantages over the pedicled group, namely skin volume available for
harvesting, preservation of abdominal wall integrity, and better flap contouring, yet the pedicled TRAM flap is
a reliable and easy technique that will produce matching aesthetic results.
PMID: 1390313

Use of ifosfamide in the management of breast cancer.

Gad-el-Mawla N

Ifosfamide, a cytostatic drug highly active in vivo, has slight superiority over cyclophosphamide. It proved
effective in experimental tumor systems including the C3H mammary carcinoma. Clinical studies of ifosfamide
as monotherapy in breast cancer, begun in 1974 by Ahmann et al., reported a 20% objective response.
Subsequent trials were conducted from 1974 through 1977 using ifosfamide as monotherapy, and ifosfamide
was also combined with other chemotherapeutic agents. In 1975, Hartwich and coworkers used the
combination ifosfamide/vincristine with a 25% overall response. With the introduction of the uroprotector
mesna, more studies were instituted. In 1984, using the IMF combination (ifosfamide/methotrexate/5-
fluorouracil), we reported a 25% overall response. Other groups also reported good results for ifosfamide-
containing combinations, with overall responses ranging from 25% to 79%. Recently, Sanchiz and Milla used
high-dose ifosfamide to treat metastatic breast cancer, with a 40% overall response. In conclusion, ifosfamide's
efficacy in breast cancer has been confirmed and the drug is highly recommended in combination
chemotherapy as a first-line treatment.
PMID: 19672288

Value of internerve tissue dissection during axillary lymphadenectomy for early breast
cancer.

Rabie AS; Eldweny HI; Abdel Maksoud IG; Elbasmy AA

Breast cancer is one of the most commonly occurring malignancies in females in the Eastern Mediterranean
Region. Axillary clearance is an integral part of the surgical treatment of breast cancer. Precise analysis of
lymph node involvement for proper staging and adjuvant therapy is therefore necessary. During axillary
dissection, lymph nodes at levels I, II and III are removed, while the important axillary structures ( axillary vein,
long thoracic and thoracodorsal nerves ) are preserved. The latter two structures are particularly vulnerable to
injury when dissecting the tissue between them ( the internerve tissue).This study evaluates the necessity of
dissecting the internerve tissue during axillary dissection in breast cancer surgery by reviewing the lymph node
yield and metastasis rate in this tissue. This is a prospective non-randomized study, conducted on 50 female
patients, who underwent axillary lymphadenectomy for breast cancer. The internerve tissue was excised
separately after a routine axillary dissection.Twenty eight ( 56% ) of the 50 internerve specimens contained
lymph nodes; the internerve nodes were positive for carcinoma in 5 patients ( 10%). In those 5 patients,
metastasis was also found in some other axillary lymph nodes. There was no incidence of isolated metastasis in
the internerve tissue nodes in absence of metastatic disease to other lymph nodes in the axilla.There is a
significant incidence of lymph nodes ( 56% ) and axillary node metastases ( 10% ) in the tissue lying between
the long thoracic and thoracodorsal nerves. Therefore, meticulous dissection and excision of this internerve
tissue is strongly recommended in order to optimize decision making regarding adjuvant treatment and
outcome in women with operable breast cancer. Key Words:Breast cancer - Axillary lymphadenectomy -
Internerve tissue.
Cell line studies

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PMID: 22895066

Antagonism between curcumin and the topoisomerase II inhibitor etoposide: A study of

DNA damage, cell cycle regulation and death pathways.

Saleh EM; El-Awady RA; Eissa NA; Abdel-Rahman WM

The use of combinations of chemotherapy and natural products has recently emerged as a new method of
cancer therapy, relying on the capacity of certain natural compounds to trigger cell death with low doses of
chemotherapeutic agents and few side effects. The current study aims to evaluate the modulatory effects of
curcumin (CUR), Nigella sativa (NS) and taurine on etoposide (ETP) cytotoxicity in a panel of cancer cell lines
and to identify their underlying mechanisms. CUR alone showed potent antitumor activity, but surprisingly, its
interaction with ETP was antagonistic in four out of five cancer cell lines. Neither taurine nor Nigella sativa
affect the sensitivity of cancer cells to ETP. Examination of the DNA damage response machinery (DDR)
showed that both ETP and CUR elicited DNA double-strand breaks (DSB) and evoked γ-H2AX foci formation at
doses as low as 1 µg/ml. Cell cycle analysis revealed S phase arrest after ETP or CUR application, whereas co-
treatment with ETP and CUR led to increased arrest of the cell cycle in S phase (MCF-7 cells) or the
accumulation of cells in G 2/M phases (HCT116, and HeLa cells). Furthermore, cotreatment with ETP and CUR
resulted in modulation of the level of DNA damage induction and repair compared with either agent alone.
Electron microscopic examination demonstrated that different modalities of cell death occurred with each
treatment. CUR alone induced autophagy, apoptosis and necrosis, whereas ETP alone or in combination with
CUR led to apoptosis and necrosis. Conclusions: Cotreatment with ETP and CUR resulted in an antagonistic
interaction. This antagonism is related, in part, to the enhanced arrest of tumor cells in both S and G 2/M
phases, which prevents the cells from entering M-phase with damaged DNA and, consequently, prevents cell
death from occurring. This arrest allows time for the cells to repair DNA damage so that cell cycle -arrested
cells can eventually resume cell cycle progression and continue their physiological program.
PMID: 21812646

Antioxidant and anticarcinogenic effects of methanolic extract and volatile oil of fennel
seeds (Foeniculum vulgare).

Mohamad RH; El-Bastawesy AM; Abdel-Monem MG; Noor AM; Al-Mehdar HA; Sharawy SM; El-
Merzabani MM

The present study evaluated the efficacy of fennel seed methanolic extract (FSME) for its antioxidant,
cytotoxic, and antitumor activities and for its capacity to serve as a nontoxic radioprotector in Swiss albino
mice. We also assessed the natural antioxidant compounds of FSME for use in industrial application. Cytotoxic
activity of FSME was evaluated in a mouse model of Ehrlich ascites carcinoma (EAC) and on different types of
human cell lines in vitro. The safety and optimum dose of FSME were determined. FSME, 100 mg/kg, was
injected intraperitoneally into mice bearing EAC before the mice were exposed to three 2-Gy doses of gamma
irradiation. After 30 days, mice were fasted for 18 hours and then sacrificed to observe the lifespan of EAC-
bearing hosts. Malondialdehyde (MDA), catalase activity, glutathione content, and total protein in serum, liver
tissue, and ascitic fluid were determined. Iron, total iron-binding capacity, transferrin, and ferritin were also
evaluated in serum. The data showed the presence of different types of compounds in FSME, such as
flavonoids, terpenoids, alkaloids, phenols, and sterols; estragole (71.099%) was the predominant alcohol, gallic
acid was the phenolic compound (18.895%), and L-limonene was the most prevalent monoterpene
hydrocarbon (11.967%). The mean±standard deviation 50% inhibitory concentrations were 50±0.03 μg/mL for
the MCF7 breast cancer cell line and 48±022 μg/mL for the Hepg-2 liver cancer cell line. The significant
increase in MDA levels and the significant decrease in catalase activity and glutathione content in liver and
tumor tissue in mice bearing EAC were ameliorated after FSME administration. In contrast, total protein
content was increased in ascitic fluid. Serum iron was inversely proportional to the levels of ferritin and
transferrin and total iron-binding capacity. Administration of FSME before irradiation exerted a cytoprotective
effect against gamma irradiation, as manifested by a restoration of the MDA level, catalase activity, and GSH
content to near-normal levels. In conclusion, FSME may have remarkable anticancer potential against a breast
cancer cell line (MCF7) and liver cancer cell line (Hepg-2). It also showed strong free radical-scavenging activity

95
(100%). Thus, FSME may reduce oxidative stress and protect mouse cells from damage caused by reactive
oxygen species. In addition, it could be used as a safe, effective, and easily accessible source of natural
antioxidants to improve the oxidative stability of fatty foods during storage. FSME also exhibited an antitumor
effect by modulating lipid peroxidation and augmenting the antioxidant defense system in EAC-bearing mice
with or without exposure to radiation.
PMID: 18382799

Apoptosis is the most efficient death-pathway in tumor cells after topoisomerase II

inhibition.

El-Awady RA; Ali MM; Saleh EM; Ghaleb FM

To compare the efficiency of apoptosis and other modes of cell death in killing tumor cells after the induction
of DNA damage by topoisomerase inhibitors like etoposide.This study was carried out in the Tumor Biology
Department, National Cancer Institute, Cairo University, Cairo, Egypt, from September 2005 to August 2007.
The breast cancer MCF7, the cervix carcinoma, human cervical adenocarcinoma Hela, and the brain tumor
U251 cell lines were exposed to etoposide. Apoptosis was detected using the flow cytometry and the DNA
ladder formation methods. Cell viability was determined by a colorimetric assay, and the residual DNA double-
strand breaks dsb were measured by gel electrophoresis.The Hela cells were the most, the MCF7's were
moderately, whereas the U251's were the least sensitive to etoposide. Apoptosis was detected only in Hela
cells whereas the other 2 cell lines showed a very low level of apoptosis only 3% increase above the control
cells. At equitoxic drug concentrations namely IC50, the Hela cells showed the lowest amount of non-repaired
DNA dsb, and the MCF7's showed the highest amount, whereas the U251 cells showed a moderate
amount.These results indicate that although other modes of cell death exist, apoptosis is the most efficient
and requires lower drug concentrations and fewer numbers of non-repaired dsb to give the same killing effect.
Clinically, this means that tumors that can execute apoptosis may require lower doses of topoisomerase
inhibitors than those that lost the ability to exercise apoptosis.
PMID: 16353081

Contribution of nitric oxide and epidermal growth factor receptor in anti-metastatic

potential of paclitaxel in human liver cancer cell (HebG2).

Sayed-Ahmad MM; Mohamad MA

Paclitaxel is a general antineoplastic drug used against different types of experimental and human tumors.
Several anti-cancer drugs have been shown to stimulate nitric oxide (NO) production, which has been shown
to affect many aspects of tumor biology.This study was initiated to determine if paclitaxel stimulates NO
production in HebG2 cells, and if so, whether NO interferes with the metastatic potential of HebG2 cells and
contributes to paclitaxel cytotoxicity. In addition, we sought to determine the relationship between NO
production and the expression of epidermal growth factor receptor (EGFR) and matrix metaloproteinases
(MMPs) in HebG2 cells.The effects of paclitaxel (0.1-1000 nM) on surviving fraction, NO production and the
expression of EGFR, MMP-2 and MMP-9 were studied in human liver cancer cells (HebG2).Paclitaxel resulted in
a significant dose dependent decrease in the surviving fraction of HebG2 cells. A 62% and 86% decrease in the
surviving fraction was attained at 10nM and 100 nM paclitaxel, respectively. Paclitaxel produced a significant
increase in NO production, starting from 1 nM. A 64% and 111% increase in NO production was attained after
exposure to 10nM and 100 nM of paclitaxel, respectively. In all of the HebG2 cells treated with paclitaxel (1.0-
1000 nM) mRNA specific for EGFR, MMP-2 and MMP-9 were undetectable. However, untreated HebG2 cells
and those treated with paclitaxel (0.1 nM) expressed mRNA specific for these markers.This study suggests that:
(1) increased production of NO may contribute to paclitaxel's cytotoxicity against HebG2 cells, (2) paclitaxel
may inhibit tumor metastasis via inhibition of the expression of EGFR and MMPs and (3) an inverse correlation
exist between NO production and expression of EGFR and MMPs.
PMID: 18301452

96
 Effect of differentiating agents on interferon-gamma (INF-gamma) level in leukemic cells
propagated ex-vivo.

El-Houseini ME; Amer IR; Hussein TD

Leukemia is a type of cancer that starts in the bone marrow. The anticancer drugs used in the treatment of
patients suffering from the disease have many side effects due to their toxicity. This fact has prompted
researchers to search for other agents instead of, or in combination with, these anticancer drugs.
Differentiating agents (DAs) including Na-Butyrate (NaBu), trans-retinoic acid (TRA), dibutyryl- cAMP (Bu-
cAMP) and many others have been used for this purpose.In this investigation, we studied 120 patients with
acute myeloid leukemia (AML),presenting to the Oncology Institute of Tanta, Egypt. We studied the effect of
some differentiating agents (DAs)mainly Na-Butyrate (Na-Bu., 1mM), trans-retinoic acid (TRA, l micro M) and
dibutyryl-cAMP (Bu-cAMP, lmM) on the morphology of leukemia cells propagated ex-vivo for 3 and 6 days. We
also studied the level of interferon- gamma and its release in the conditioned media of the leukemic cells
compared to normal leukocytes.The results revealed that DAs enhanced the conversion of the immature
granulocytes into mature ones clearly at 6 days of treatment when we used the agents in combination. The
results also showed that statistically significant elevation (p<0.001) of interferon- gamma level was found to be
in the conditioned media of the treated leukemic cells (3 and 6 days) using the previously mentioned agents
alone or in combination; that could reach almost the level in the cultured media of normal leukocytes.In
conclusion, this work could highlight the possibility of using DAs as a novel complementary therapy in the
management of acute myeloid leukemia (AML) via the activation of the immune surveillance of patients
suffering from AML through raising the interferon- gamma level. Further work is recommended to use DAs in
clinical trials with and without conventional anticancer drugs for the management of patient with AML.
PMID: 2126646

Evaluation of in-vitro effects of recombinant human alpha 2 interferon on bilharzial

urinary bladder cancer cells.

Khaled HM; Attia MM; Nabawi AR

Using two different agar based double-layer culture assays, 16 bilharzial urinary bladder carcinoma samples
were evaluated for the in-vitro effects of 1 hour's exposure to alpha 2 interferon at 3-log concentrations. Ten
of these tumor samples were evaluable for drug sensitivity testing. In the liquid top layer dye exclusion assay,
40%, 60%, and 60% of the 10 tested tumor samples were sensitive to alpha 2 interferon 100, 1,000, and 10,000
units/ml respectively, and 25%, 25%, and 63% of 8 tumor cell suspensions were sensitive to the above drug
concentrations when the human tumor colony forming assay was performed. Comparing both assays in 24
different drug measurements, there was a 71% concordance rate. All of the 7 discordant measurements were
sensitive in the dye exclusion and resistant in the clonogenic assays. Thus, bilharzial bladder cancer cells are
relatively sensitive to the in-vitro effect of alpha 2 interferon, especially of higher concentrations, and a phase
II clinical trial deserves consideration.
PMID: 20803320

Expression of RAD51, BRCA1 and P53 does not correlate with cellular radiosensitivity of
normal human fibroblasts.

Saleh EM; El-Awady RA

To evaluate the potential role of key DNA repair proteins in the sensitivity of normal human fibroblasts to
ionising radiations.Radiosensitivity of six human fibroblast strains established from skin biopsies of women
who had undergone conservative breast surgery and received a curative breast conserving radiotherapy was
measured by colony-formation assay. The expression level of RAD51, BRCA1 and p53 proteins were studied
using western blot analysis.The six fibroblast strains represent a typical spectrum of normal human

97
radiosensitivity with the surviving fraction measured for a dose of 3.5 Gy (SF3.5) ranging from 0.21 to 0.40. We
found that these differences in cell survival did not correlate with the expression of RAD51, BRCA1 nor p53 in
the tested normal human fibroblast strains.We conclude that measurement of protein expression of the three
tested genes (RAD51, BRCA1 and p53) did not reflect sensitivity of normal fibroblasts to IR.
PMID: 8249181

Hyperthermic potentiation of cisplatin cytotoxicity on solid Ehrlich carcinoma.

Osman A el-M ; Ahmed MM; Khayyal MT; el-Merzabani MM

Hyperthermia produces marked effects on many biochemical parameters of tumor cells and has been reported
to potentiate the effect of many drugs. We therefore evaluated the possible synergistic effect between
hyperthermia and cisplatin against solid Ehrlich carcinoma. The study was based on the measurement of some
biologic characteristics in tumor tissues, namely: DNA, RNA, and protein content and their rate of synthesis as
parameters for nuclear damage; total lipids and cholesterol as parameters for membrane damage; acid-
phosphatase and acid-ribonuclease as parameters for lysosomal damage; and tumor volume as a direct
parameter for tumor growth.Treatment of solid Ehrlich carcinoma by hyperthermia at 43 degrees C for 30 min
for 3 successive days produced a 41.5% decrease in tumor volume, as well as a significant decrease in nucleic
acids, protein contents and their rate of synthesis, in total lipids and cholesterol, and in acid-phosphatase and
acid-ribonuclease. Chemotherapeutic management of the tumor by 5 mg/kg x 3 of cisplatin alone showed a
continuous increase in tumor volume but at a lower rate than that of the untreated control. However, when
cisplatin was given 1 h prior to hyperthermia, the tumor volume was significantly decreased by 82.6%.The
effects observed on all the investigated parameter were intensified when cisplatin was combined with
hyperthermia. The results obtained suggest that hyperthermia may enhance the penetration of cisplatin to its
target site inside the tumor cells due to a membrane-damaging effect. The enhanced lethality of cisplatin on
tumor cells may also be due to the inhibition of DNA repair processes by hyperthermia.
PMID: 22939736

Induction and repair of DNA double-strand breaks using constant-field gel electrophoresis
and apoptosis as predictive markers for sensitivity of cancer cells to cisplatin.

Saleh EM; El-Awady RA; Anis N; El-Sharkawy N

This study was designed to evaluate some parameters that may play a role in the prediction of cancer cells
sensitivity to cisplatin (CIS). Sensitivity, induction and repair of DNA double-strand breaks (DSB), cell cycle
regulation and induction of apoptosis were measured in four cancer cell lines with different sensitivities to CIS.
Using a sulphorhodamine-B assay, the cervical carcinoma cells (HeLa) were found to be the most sensitive to
CIS followed by breast carcinoma cells (MCF-7) and liver carcinoma cells (HepG2). Colon carcinoma HCT116
cells were the most resistant. As measured by constant-field gel electrophoresis (CFGE), DSB induction, but not
residual DSB exhibited a significant correlation with the sensitivity of cells to CIS. Flow cytometric DNA ploidy
analysis revealed that 67% of HeLa cells and 10% of MCF-7 cells shift to sub-G1 phase after incubation with CIS.
Additionally, CIS induced the arrest of MCF-7 cells in S-phase and the arrest of HepG2 and HCT116 cells in both
S phase and G2/M phase. Determination of the Fas-L level and Caspase-9 activity indicated that CIS-induced
apoptosis results from the mitochondrial (intrinsic) pathway. These results, if confirmed using clinical samples,
indicate that the induction of DNA DSB as measured by CFGE and the induction of apoptosis should be
considered, along with other predictive markers, in future clinical trials to develop predictive assays for
platinum -based therapy.
PMID: 16508680

98
Misrejoined , residual double strand DNA breaks and radiosensitivity in human tumor cell
lines.

Saleh EM; El-Awady RA

The aim of the present study is to investigate whether differences between tumor cells in radiosensitivity are
related to misrejoined- or residual DNA-double strand breaks.An assay that allows measurement of absolute
induction frequencies for DNA double strand breaks (DSBs) in defined regions in the genome, and that
quantitates rejoining of correct DNA ends has been used to study repair of DSBs in three human tumor cell
lines. DNA double-strand breaks (DSBs) were measured within a 3.5-Mbp Not 1 fragment on chromosome X of
human tumor cell lines with different radiosensitivities. Correct rejoining of DSBs was measured by
hybridization of single-copy DNA probe to Not 1 restriction fragments separated according to size by pulsed
field gel electrophoresis (PFGE). Induction of DSBs is quantified from the decrease in the intensity of the
hybridizing restriction fragment and an accumulation of a smear below the band. Rejoining of DSBs results in
reconstitution of the intact restriction fragment only if correct DNA ends are joined. By comparing results from
this technique with results from a conventional electrophoresis technique (FDR assay) that detects all rejoining
events, it was possible to quantitate the misrejoining frequency after 50Gy of X irradiation. Residual breaks
were measured 24h after irradiation.In terms of clonogenic assay, squamous cell carcinoma cell line (4451)
was the most radiosensitive, followed by the breast carcinoma cell line (BB) while the bladder carcinoma cell
line (RT112) was the most radioresistant. Twenty-four hours after irradiation, 4451 cell line accumulated the
highest level of residual (non-repairable) DSB followed by BB and then RT112 cell line, which showed the
lowest level of residual DSB. This was the same rank as in the radiosensitivity assay. Regarding DSB
misrejoining, RT112 cell line showed the highest percent of incorrectly repaired DSB, which does not agree
with the results of the radiosensitivity assay.From our data, it could be concluded that residual (non
repairable) DSB is more important in terms of radiosensitivity than incorrectly repaired DSB.
PMID: 10623482

Propionyl-L-carnitine as potential protective agent against adriamycin-induced

impairment of fatty acid beta-oxidation in isolated heart mitochondria.

Sayed-Ahmed MM; Shouman SA; Rezk BM; Khalifa MH; Osman AM; El-Merzabani MM

Propionyl-L-carnitine (PLC), a natural short-chain derivative of L-carnitine, has been tested in this study as a
potential protective agent against adriamycin (ADR)-induced cardiotoxicity in isolated rat heart myocytes and
mitochondria. In cardiac myocytes, ADR (0.5 mM) caused a significant (70%) inhibition of palmitate oxidation,
whereas, PLC (5 mM) induced a significant (49%) stimulation. Addition of PLC to ADR-incubated myocytes
induced 79% reversal of ADR-induced inhibition of palmitate oxidation. In isolated rat heart mitochondria, ADR
produced concentration-dependent inhibition of both palmitoyl-CoA and palmitoyl-carnitine oxidation, while
PLC caused a more than 2.5-fold increase in both substrates. Preincubation of mitochondria with 5 mM PLC
caused complete reversal of ADR-induced inhibition in the oxidation of both substrates. Also ADR induced
concentration-dependent inhibition of CPT I which is parallel to the inhibition of its substrate palmitoyl-CoA. In
rat heart slices, ADR induced a significant (65%) decrease in adenosine triphosphate (ATP) and this effect is
reduced to 17% only by PLC. Results of this study revealed that ADR induced its cardiotoxicity by inhibition of
CPT I and beta-oxidation of long-chain fatty acids with the consequent depletion of ATP in cardiac tissues, and
that PLC can be used as a protective agent against ADR-induced cardiotoxicity.
PMID: 22730303

99
 Radiation-induced double-strand breaks require ATM but not Artemis for homologous
recombination during S-phase.

Köcher S; Rieckmann T; Rohaly G; Mansour WY; Dikomey E; Dornreiter I; Dahm-Daphi J

Double-strand breaks (DSBs) are repaired by two distinct pathways, non-homologous end joining (NHEJ) and
homologous recombination (HR). The endonuclease Artemis and the PIK kinase Ataxia-Telangiectasia Mutated
(ATM), mutated in prominent human radiosensitivity syndromes, are essential for repairing a subset of DSBs
via NHEJ in G1 and HR in G2. Both proteins have been implicated in DNA end resection, a mandatory step
preceding homology search and strand pairing in HR. Here, we show that during S-phase Artemis but not ATM
is dispensable for HR of radiation-induced DSBs. In replicating AT cells, numerous Rad51 foci form gradually,
indicating a Rad51 recruitment process that is independent of ATM-mediated end resection. Those DSBs
decorated with Rad51 persisted through S- and G2-phase indicating incomplete HR resulting in unrepaired
DSBs and a pronounced G2 arrest. We demonstrate that in AT cells loading of Rad51 depends on functional
ATR/Chk1. The ATR-dependent checkpoint response is most likely activated when the replication fork
encounters radiation-induced single-strand breaks leading to generation of long stretches of single-stranded
DNA. Together, these results provide new insight into the role of ATM for initiation and completion of HR
during S- and G2-phase. The DSB repair defect during S-phase significantly contributes to the radiosensitivity of
AT cells.
PMID: 10208759

Reversal of doxorubicin-induced cardiac metabolic damage by L-carnitine.

Sayed-Ahmed MM; Shaarawy S; Shouman SA; Osman AM

Biopharmacological evaluations of the protective effects of L-carnitine (a naturally occurring quaternary

ammonium compound) against doxorubicin-induced metabolic damage were carried out in isolated cardiac
myocytes and in isolated rat heart mitochondria. Perfusion of the heart with DOX (0.5 mM) caused a significant
70% inhibition of palmitate oxidation in cardiac myocytes, while L-carnitine (5 mM) perfusion caused
stimulation which accounted for 37%. Perfusion of the heart with L-carnitine after 10-min perfusion with DOX
(0.5 mM) caused 88% reversal of DOX-induced inhibition of palmitate oxidation in cardiac cells. In rat heart
mitochondria, DOX has no effect on either palmitate oxidation or acyl-CoA synthetase activity, whereas
Enoximone (c-AMP-dependent phosphodiesterase inhibitor), caused a significant inhibition of palmitate
oxidation and acyl-CoA activity (40 and 27%, respectively). The oxidation of palmitoyl-CoA, an index of
carnitine palmitoyltransferse reaction was significantly inhibited by DOX as a function of DOX concentration.
Preincubation of mitochondria with L-carnitine caused reversal of DOX-induced inhibition of palmitoyl-CoA
oxidation depending on the concentration of L-carnitine. Moreover, L-carnitine treatment did not interfere
with the cytotoxic effect of doxorubicin against the growth of solid Ehrlich carcinoma. The findings of this
study may suggest that inhibition of fatty acid oxidation in the heart is at least a part of doxorubicin
cardiotoxicity and that L-carnitine can be used to prevent the doxorubcin-induced cardiac metabolic damage
without interfering with its antitumour activities.

GIT Cancer Studies

PMID: 17671536

A comparative study of rectal and colonic carcinoma: demographic, pathologic and TNM
staging analysis.

El-Bolkainy TN; Sakr MA; Nouh AA; El-Din NH

The aim is to determine the relative frequency of rectal carcinoma in a large recent surgical series. In addition,

100
rectal carcinoma is compared with colonic carcinoma with regard to demographic data, histological types and
TNM stages.A retrospective pathologic study was conducted on 215 patients with colorectal carcinomas, all
treated by radical surgery during the years 2003-2005. Tumors of unfavorable histology included: Mucinous
carcinoma, signet-ring carcinoma and undifferentiated carcinoma. For tumor staging, the international TNM
staging system was adopted.The mean age was 51 years and male to female ratio was 1.1. Rectal tumors
contributed only 27% of cases, contrary to much higher previous reports from Egypt. Tumors of unfavorable
histology constituted 24.2% of cases. Patients presented at advanced stages (78.6% stages II and III) with
46.5% lymph node metastases. Patients with rectal carcinomas were younger, with more risk of suboptimal
distal surgical margins.Egyptian patients with rectal carcinoma are younger than those with colonic carcinoma.
Otherwise, patients with rectal carcinoma are similar to colonic carcinoma with regard to sex distribution,
histological types and TNM stages.
PMID: 22617715

Clinical Value of Circulating Lipocalins and Insulin-Like Growth Factor Axis in Pancreatic
Cancer Diagnosis.

El-Mesallamy HO; Hamdy NM; Zaghloul AS; Sallam AM

OBJECTIVES: Early diagnosis of pancreatic cancer (PC) in diabetic patients is difficult owing to late presentation
of symptoms. Hence, finding a marker to identify cancer stage early would be useful to improve survival. We
aimed to determine levels of serum retinol binding protein 4 (RBP-4), neutrophil gelatinase-associated
lipocalin (NGAL), insulin-like growth factor I (IGF-I), and its binding protein 3 (IGFBP-3) in patients with PC with
preexisting type 2 diabetes. Moreover, we assessed their clinical usefulness in PC diagnosis and their
association with tumor severity. METHODS: Twenty-three patients with PC, 32 diabetic patients, and 20
healthy controls were examined. Preoperative and postoperative samples were obtained from 15 patients
with PC. Serum insulin, cancer antigen (CA 19-9), RBP-4, NGAL, IGF-I, and IGFBP-3 levels were estimated by
enzyme-linked immunosorbent assay. RESULTS: Significant elevation in the levels of RBP-4 (60.1 [46.3-71.4]
ng/mL), NGAL (142 [80-235] ng/mL), and IGF-I (174 [9.3] ng/mL) together with significant reduction in the level
of IGFBP-3 (3669 [299] ng/mL) was found in patients with PC. Moreover, RBP-4 and NGAL levels were reduced
in postoperative samples compared with preoperative ones. Receiver operating characteristic curve analysis
revealed that they can distinguish PC from non-PC cases with significant area under the curve. CONCLUSIONS:
Retinol binding protein 4, NGAL, IGF-I, and IGFBP-3 are associated with PC in type 2 diabetic patients. They
could be useful in distinguishing PC from non-PC cases when used in combination or with cancer antigen.
PMID: 19034345

Clinicopathologic and prognostic significance of overexpression of her-2/neu and p53

oncoproteins in gastric carcinoma using tissue microarray.

Ismail HM; Moneer M; El-Baradie M; Khorshid O; Touny A

The aim of the study was to verify the frequency of the immunohistochemical overexpression of her-2/neu and
p53 in gastric carcinoma and their relation to the other clinico-pathological features and the impact on survival
rates.A total of 93 patients of gastric carcinoma, who had a potential curative surgery in the period from 2001-
2007 and with representative paraffin blocks, and sufficient follow-up data were included in this study. They
were arrayed and evaluated for protein marker overexpression using tissue microarray (TMA). Patients, tumor
and treatment characteristics were collected from the patients' files. The possible prognostic significance of
p53 and her-2/neu over expression and different clinico-pathological features on survival rates were
explored.Twenty four (25.8%) cases were her-2/neu and p53 positive. None of the examined clinico-pathologic
factors had a significant relation to her-2/neu overexpression. p53 was overexpressed in intestinal type, 14/34
(41.2%), more than in diffuse type, 10/59 (16.9%), (p= 0.01). There was no relation between the
overexpression of p53 and her-2/neu. The median survival period was 17.7 months. The survival rates at 12
months were 64.2%, 52.2%, 55.6% and 45.0% for overall (OS), local control (LC), metastasis free survival (MFS)
and disease free survival (DFS) rates, respectively. Patients with advanced stages had a significantly lower OS
and MFS. Age above 57 years was associated with significantly lower OS, LC, MFS and DFS. Patients who
received radiotherapy had significantly higher OS, LC, MFS and DFS. None of the survival rates had been

101
affected by the overexpression of p53, or her-2/neu.Although, this study failed to show any prognostic effect
of p53 and her-2/neu on survival rates, we may suggest that p53 overexpression may play a role in the
pathogenesis of intestinal gastric adenocarcinoma. It could also demonstrate the significantly improved
survival rates with adjuvant chemoradiation. Also, TMA is a useful technique for rapid identification of protein
expression profiles using minimal samples from archived tissues.
PMID: 18839030

Clinico-Pathological and Prognostic Significance of p53, Bcl-2 and Her-2/neu Protein

Markers in Colorectal Cancer Using Tissue Microarray.

Ismail HM; El-Baradie M; Moneer M; Khorshid O; Touny A

Background: The prognostic role of her-2/neu has been established in breast cancer but remains controversial
in colorectal cancer (CRC). Widespread genetic mutations in colorectal carcinogenesis exist on chromosome
17. Her- 2/neu gene and the tumor suppressor gene p53 are both located on this chromosome. Bcl-2 protein
prolongs survival of a variety of cells by blocking apoptosis. The aim of this study is to evaluate the relationship
between the overexpression of p53, bcl-2 and her-2/neu protein markers and the clinico-pathologic
characteristics of CRC, and their influence on survival rates. Patients and Methods: One hundred and four
cases of CRC had paraffin blocks with representative tissue, and sufficient follow-up data. They were arrayed
and evaluated for protein marker expression using tissue microarray (TMA). Results: Ten (9.6%), 35 (33.7%)
and 27 (26%) of the patients were her-2/neu, p53 and bcl-2 positive, respectively. None of the examined
clinico-pathologic factors had a significant relation with her-2/neu overexpression. Patients with +ve bcl-2 had
a significantly higher mean age (52.4-/+13.3years) compared to 45.4-/+14.4 years for bcl-2 negative patients,
p=0.03. Positive p53 was overexpressed in 20/44 (45.5%), 6/17 (35%), 9/43 (21%) cases of the colon, recto-
sigmoid, and rectal sites, respectively, p=0.05. For the whole population, p53 overexpression had a significantly
lower disease-free survival (DFS). For patients with Dukes' stage B, overexpression of p53 protein had a
significant reduced overall survival (OS) p=0.04, metastasis free survival (MFS) p=0.004, and DFS p=0.01 rates.
Expression of bcl-2 had a significantly better MFS p=0.001, while her-2/neu overexpression worsened the OS
rate significantly, p=0.04. Conclusion: This study recommends the application of TMA technique for its
economic importance and reliable quick throughput. The results from this study also suggest that
overexpression of p53, bcl-2, and her-2/neu protein markers appear to be useful in selecting a group of CRC
patients with a worse prognosis and constitute potential candidates for adjuvant therapy. Key Words: Her-
2/neu , p53 , Bcl-2 , Colorectal cancer , Tissue microarray , Prognostic factors.
PMID: 15385053

Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients.

Bahnassy AA; Zekri AR; El-Houssini S; El-Shehaby AM; Mahmoud MR; Abdallah S; El-Serafi M

Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been
shown to be of prognostic significance in colorectal cancer.The expression of cyclin D1, cyclin A, histone H3
and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using
immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated
semi quantitatively by determining the staining index of the studied proteins.There was a significant
correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6%) and
between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large,
poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply
invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were
associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent
prognostic factors in colorectal cancer patients.Loss of cell cycle checkpoints control is common in colorectal
cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients.
Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could
be considered important therapeutic targets.

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PMID: 23060297

Evaluation of Noninvasive Versus Invasive Techniques for the Diagnosis of Helicobacter

pylori Infection.

Alam El-Din HM; Hashem AG; Ragab YM; Hussein IL; Mohamed DB; Mohamed EC

BACKGROUND:: Helicobacter pylori is one of the most common bacterial strains causing chronic infections,
affecting over one half of the world's population. There is increasing interest in noninvasive methods for
diagnosing H. pylori infection. The aim of the study was to evaluate 3 different noninvasive methods of
diagnosis: the stool antigen test (HpSA), the serum antibody test, and the stool-polymerase chain reaction
(PCR) test as against invasive methods based on histopathologic diagnosis. MATERIALS AND METHODS::
Gastric biopsies were obtained during endoscopy. Sections were stained with hematoxylin and eosin and
Giemsa stain. Serum samples were tested for H. pylori antibody using an enzyme-linked immnunosorbent
assay kit for the semiquantitative determination of IgG antibodies; stool samples were tested for H. pylori
antigen using polyclonal enzyme-linked immnunosorbent assay kits. DNA samples from stool specimens were
extracted, followed by PCR for the detection of H. pylori UreA. RESULTS:: The results revealed that 18/19
(94.7%) patients were positive for H. pylori infection as detected by Giemsa stain, and 84.2% were positive on
the basis of hematoxylin and eosin stain, with a sensitivity and specificity of 88.9% and 100%, respectively.
Diagnosis by noninvasive methods, including the serum antibody test, revealed a sensitivity and positive
predictive value of 88.9% and 94.2%, respectively, whereas the stool antigen test recorded a sensitivity and
positive predictive value of 72.2% and 92.9%, respectively. The stool-PCR test recorded a sensitivity of 72.2%
and specificity of 100%. CONCLUSIONS:: Among the noninvasive methods for diagnosis of H. pylori infection,
the 3 methods used in this study recorded promising results, including good sensitivity, which was the highest
in the serum antibody test, whereas the stool-PCR test recorded excellent specificity.
PMID: 16508676

Gastrointestinal stromal tumor (GIST)'s surgical treatment, NCI experience.

El-Zohairy M; Khalil el-SA; Fakhr I; El-Shahawy M; Gouda I

To review the clinical presentation, surgical management, and prognostic factors for gastrointestinal stromal
tumors.A prospective study which was carried out between January 2002 and March 2004 on thirty-three
patients with gastrointestinal stromal tumor (GIST) at the National Cancer Institute, Cairo University. All
patients were evaluated preoperatively and underwent exploratory laparotomy with a curative intent, they
were followed up for period ranging between 14-35 months.Among the 33 patients there were 17 males and
16 females. The mean age of patients was 52.8 years. Clinical findings included gastrointestinal bleeding
(42.4%), palpable mass (33.3%) and abdominal pain (24.3%). The stomach was the most common site of origin
of the disease (39.4%), followed by the colorectal region (24.2%). Tumors were high grade in 63.6% of patients
and low-grade in 36.4% of patients. Complete resection of all gross disease was accomplished in 26 patients
(78.7%), among whom, multiple adjacent organ resection was required in 6 patients (22.2 %) and metastatic
disease was identified in the liver in 3 patients at the time of exploratory surgery of these one could be
resected. Immunohistochemical staining for CD117 was positive in 88.9% of patients. The median follow-up
period was 20 months (range, 14-35 months). The overall median survival in this study was 25 months, and the
cumulative survival at 30 months was 46.9%. Unfavorable prognostic factors were incomplete resection and,
high-grade histological features (p<0.05). None of the patients received adjuvant or palliative chemotherapy.
Twenty six patients (78.8%) are alive free of disease. Of the 7 patients with incomplete resections or biopsy
only; 4 patients (12.1%) are alive with disease and 3 patients died.Surgical resection, including en bloc
resection of locally advanced tumors, remains the only curative treatment. Overall survival is significantly
affected by high-grade tumors and positive resection margin.
PMID: 19847285

103
 Gastrointestinal stromal tumors (GIST) of the stomach: retrospective experience with
surgical resection at the National Cancer Institute.

Naguib SF; Zaghloul AS; El Marakby H

Gastric GISTs account for more than half of all gastrointestinal stromal tumors and represent less than 5% of all
gastric tumors. The peak age for harboring GIST of the stomach is around 60 years and a slight male
preponderance is reported. These tumors are identified by expression of CD117 or CD34 antigen. Symptoms at
presentation usually include bleeding, abdominal pain or abdominal mass. Endoscopically, they typically
appear as a submucosal mass with or without ulceration and on CT scans an extragastric mass is usually seen.
Complete surgical resection provides the only chance for cure, with only 1-2 cm free margins needed.
However, local recurrence and/or metastases supervene in almost half the patients treated with surgery
alone, even when no gross residual is left. Thereby imatinib mesylate was advocated as an adjuvant to surgery,
which appears to have improved disease-free and overall survival.The aim of this work was to assess clinico-
pathological features of gastrointestinal stromal tumors (GIST) of the stomach and to appraise the results of
treatment by surgery in patients treated at the National Cancer Institute (NCI) of Cairo between January 2002
and December 2007.Nineteen patients with histologically and immuno-histochemically proven GIST of the
stomach were treated by surgery at the NCI during the 6-year study period. Preoperative assessment included
detailed history, clinical examination, full laboratory tests, endoscopy, abdominal ultrasound and CT. General
medical assessment included chest X-ray, ECG and echocardiography.The patients' age ranged from 26 to 77
years with a median of 51 years. Obvious male/female preponderance was noticed (68.4% to 31.6%). Tumors
were located at the upper 1/3 in 42.1%, at the middle 1/3 in 31.6% and at the lower 1/3 in 26.3%. The most
common clinical presentation was related to bleeding (hematemesis, melena or anaemia) and was seen in
63.2%. No tumors were labeled as very low or low risk while there were 52.6% intermediate risk and 47.4%
high risk. Wedge resection was carried out in 15.8%, partial gastrectomy in 37.8%, total gastrectomy in 5.2%,
extended gastric resection in 21.1% and only biopsy in 5.2%. Lymphadenectomy was carried out in 5/19
patients to reveal negative lymph nodes in all five. Complications occurred in 73.7% of patients and only 1 case
of early postoperative mortality was recorded. Two patients were lost to follow-up. The remaining 16 patients
were followed-up for a period ranging from 6-34 months with a mean of 19.5+/-5.6 months and they were all
alive by the end of the study, 10 were free of disease and 6 showed disease recurrence.Gastric GIST can
present with vague and non specific clinical picture. Therefore, thorough clinical and radiological evaluation
and preoperative endoscopy and biopsy are essential to reach the diagnosis and to assess the risk for
metastasis. The clinical outcome of these tumors is influenced by completeness of tumor extirpation while
avoiding tumor rupture, and by the tumor malignant potential. Accordingly for tumors with adverse factors,
multimodal therapy with adjuvant imatinib or one of its successors should be considered in order to improve
overall and disease-free survival.
PMID: 15716997

Ileocecal interpositional graft for gastric replacement after total gastrectomy.

Attia A; El-Shazly S; El-Shafiey M; Zaher A

The aim of this study is to evaluate the technique of ileocecal segment interpositional graft after total
gastrectomy for gastric cancer with assessment of its advantages and disadvantages.This is a prospective study
carried out at the National Cancer Institute, Cairo University. Twenty four patients with gastric carcinoma were
identified from December 1998 to February 2003. All of them were submitted to surgery after preoperative
clinical, radiological and endoscopic diagnosis. Total gastrectomy with ileocecal interpositional graft were done
(19 subdiaphragmatic reconstruction and 5 intrathoracic reconstruction). Patients were followed up for at
least 12 months for postoperative morbidity, body weight, reflux and dumping symptoms. Gastrografin
swallow, barium swallow, upper GIT endoscopy were routinely done in all patients and pouch emptying time
by Tc-99m sulpher colloid was done in 11 patients only.Perioperative mortality was 8.3% (2/24). No patient
reported reflux symptoms or showed endoscopic findings of reflux esophagitis in the subdiaphragmatic
reconstruction group and mild reflux was noted in only one patient in the intrathoracic reconstruction group.
No patient reported dumping symptoms. Emptying time showed good capacity as a reservoir of food.
Postoperative decrease in body weight averaged less than 10% of preoperative weight.Ileocecal interposition

104
graft after total gastrectomy has the advantages of preventing reflux esophagitis and providing functional
replacement of the stomach as a reservoir for ingested food. It can be done with acceptable morbidity and
mortality. It is simpler than some of the pouch reconstructions and deserves more attention.
PMID: 17671533

Locally advanced rectal carcinoma: preoperative radiotherapy versus postoperative

chemoradiation, 10-year follow-up results of a randomized clinical study.

Taher AN; El-Baradie MM; Nasr AM; Khorshid O; Morsi A; Hamza MR; Mokhtar N; Ezzat S

A prospective study was designed to randomize locally advanced rectal carcinoma patients between either
preoperative radiotherapy (+/- postoperative chemotherapy) or postoperative adjuvant chemoradiation. Two
end points were evaluated, local recurrence and survival, aiming at defining prognostic parameters that can
help in the choice of the optimum treatment modality.This is a prospective randomized clinical study including
patients with locally advanced low rectal cancer treated at the National Cancer Institute (NCI), Cairo University,
during the period from December 1994 to January 1999. Fifty patients with previously untreated rectal cancer
were randomized into two groups, Group I: Subjected to surgery followed by radiation therapy (50Gy/5 weeks,
2Gy/fraction, 5 days/week) plus chemotherapy and Group II, subjected to preoperative radiotherapy
(46Gy/4.5 weeks, 2Gy/ fraction, 5 days/week) followed by surgery +/- postoperative chemotherapy.
Chemotherapy in the concomitant setting was given in the form of Leucovorin in a dose of 300mg/m2 as a
short i.v. infusion followed by 5-FU in a dose of 350mg/m2 as a 6 hour i.v. infusion, whereas adjuvant
chemotherapy consisted of 5- FU as 600mg/m2 short i.v. infusion weekly for 48 weeks, in addition to
levamisole tablets.The long-term treatment end results obtained showed that group I patients had a slightly
higher 10-year overall survival (OS) rate when compared to group II patients (63% versus 60%, p=0.698). The
corresponding figures for the 10-year disease-free survival (DFS) were 65% and 66%, respectively, p=0.816.
Although the 10- year local failure rate (persistent/relapsed disease) was higher for the preoperative group, it
was not of statistical significance, (30% Vs. 8%, p=0.057). On the other hand, the 10-year distant metastasis
free survival was higher in the preoperative group (88% Vs. 72%), yet this difference did not reach statistical
significance (p=0.16). The rate of acute radiation reactions was higher in the postoperative group, with no
increase in the operative complications in the preoperative group. Moreover, none of the 50 patients had
grade 3 or more late radiation/surgical squealae. There were no grade 3 or 4 chemotherapy related
toxicities.This work showed equal results for DFS and OS rates between preoperative and postoperative
radiation therapy with the same acceptable acute and late radiation toxicity. High dose preoperative
irradiation did not cause any significant increase in acute or late radiation induced reactions, delay in wound
healing or increased postoperative morbidity when compared to postoperative adjuvant radiochemotherapy.
Duke' s stage and response to preoperative irradiation proved to be of significance regarding DFS, while
compliance to systemic therapy was of significance regarding both OS and DFS.
PMID: 21552057

Modified pseudocontinent perineal colostomy: a special technique.

Nassar OA

Innovative techniques created to restore gastrointestinal perineal continuity after abdominoperineal resection
in patients with anorectal cancer include pseudocontinent perineal colostomy, in which the colon is pulled to
the perineum and wrapped with a sleeve of stretched colon segment to act as a new sphincter.We
investigated perineal reconstruction with a modified pseudocontinent perineal colostomy
technique.Prospective cohort study.Tertiary care university hospital in Egypt.Patients with T2 or T3 anorectal
cancer invading the sphincter who underwent Miles abdominoperineal resection and immediate total pelvic
reconstruction between 2003 and 2007.Reconstruction consisted of a vertical rectus abdominis myocutaneous
flap with modified perineal colostomy pulled through the flap to add the high-pressure zone of the flap to that
of the colostomy and to create a persistent new anorectal angle.Early and late complications were recorded.
Functional results were evaluated at regular intervals by questionnaire, physical examination, and balloon
manometry. Continence was graded according to Kirwan. Satisfaction with continence was assessed by
questionnaire.A total of 14 patients (3 women) were included. Tumors were adenocarcinoma (n = 11),

105
squamous-cell carcinoma (n = 2), and melanoma (n = 1). Complete (R0) resection was achieved in all patients
without perioperative deaths, major postoperative morbidity, or conversion to permanent iliac colostomy.
Early postoperative complications (perineal wound infection, flap dehiscence, and partial perineal stoma
necrosis) occurred in the first 4 patients. Late complications occurred in 7 patients, with mucosal prolapse in 3,
stomal stricture in 4, and tumor recurrence in 1. Fecal continence progressed consistently with time, and by
the end of the first year 8 patients (57%) had complete continence (grade A), 5 (36%) were continent with
minor soiling (grade C), and 1 (7%) still had major soiling (grade D). After 6 months, 9 patients (64%) were
satisfied with continence; after 1 year, 13 patients (93%) were satisfied. Regular enemas were necessary
during the first year to improve soiling, and 8 patients (57%) were not in need after that. At 37 months median
follow-up, 8 of 9 evaluable patients (89%) were satisfied with continence (grade A) without regular
enemas.This was a preliminary observational study with no control group.Total orthotopic pelvic
reconstruction with autologous tissue transposition to rebuild the principle anorectal continence elements is
feasible with minor complications, and is oncologically safe. This new technique offered high continence
satisfaction independent of regular enemas and electrical stimulation.
PMID: 20164007

Percutaneous endoscopic gastrostomy (PEG) in cancer patients; technique, indications and

complications.

Rabie AS

Enteral feeding is the preferred method of nutritional support in malnourished patients with inadequate oral
intake but with intact gastrointestinal tract. In cancer patients, adequate nutrition plays an important role in
the success of the treatment and hence the overall prognosis. Percutaneous endoscopic gastrostomy proved
to be an effective means for providing enteral nutrition with easy technique, less hospital stay and cost with
less morbidity and mortality.It is a prospective study on 40 cancer patients with different indications for PEG
which is done by pull technique under local anesthesia and sedation over a period of 12 months with a follow
up period of 60 days.The procedure was successful in 38 patients (95%), 22 patients (55%) with esophageal
cancer, 16 cases (40%) with head and neck cancer, and 2 cases (5%) for gastric decompression due to
prepyloric gastric cancer. Mortality rate was 2.5% (1 case) due to leakage and peritonitis, and morbidity
occurred in 6 cases (15%) due to port infection and minor leakage managed by dressing and systemic
antibiotics.PEG is an easy procedure for providing enteral nutrition for cancer patients and associated with
fewer rates of morbidity and mortality compared to gastrostomy procedures.
PMID: 21443094

Role of KLF6 tumor suppressor gene mutations in the development of colorectal

carcinoma in an Egyptian population.

Wahab AH; Kassem AM; Matter S; El Deen AF; Helmy AS; Ismaeil MM; Zakaria MS

Colorectal cancer is one of the common cancers of the gastrointestinal tract in Egypt. It is characterized by a
relatively earlier onset compared to that in the western world. Studying genetic alterations involved in
colorectal cancer progression may help in identifying molecular biomarkers that can be used for early
detection.We analyzed DNA isolated from 83 cases including 38 colorectal carcinomas, 23 polyps (16 of which
were adenomatous) and 22 cases with inflammatory bowel disease (IBD). Mutations at KLF6 tumor suppressor
gene (exon 1-4) were examined by PCR-SSCP silver staining technique followed by direct sequencing. 10p15
LOH was analyzed using KLF6 M1, KLF6 M2 and KLF6 M4 markers by microsatellite assay.KLF6 mutations were
found in 45%, 27% and 26% of colorectal carcinoma, ulcerative colitis and polyp cases, respectively. Most of
the mutations detected were located at exon 2. The majority of mutations found in KLF6 were missense
mutation and their type and locations were different from those previously described in the western
population. The frequencies of LOH at the three markers examined were 29%, 36%, and 52% for colorectal
carcinomas, IBD, and polyp cases, respectively. LOH was detected in mutant KLF6 as well as wild type. No
significant association was found between genetic alterations examined with different clinicopathological
factors.Our data highlights for the first time an association of KLF6 gene in colorectal cancer in an Egyptian
population. Detecting mutational sites different from those in western population is a characteristic feature in

106
our study which may be related to environmental and/or genetic factors that have to be further identified.

PMID: 22429319

Signet-ring cell adenocarcinoma of rectum with breast metastases diagnosed on FNA

cytology: case report and literature review.

Shaaban H; Kapila K; Mostafa EK; Amanguno H; Hebbar GH; Francis I

PMID: 16116497

Sphincter sparing procedures: is it a standard for management of low rectal cancer.

Khalil el-SA; El-Zohairy M; El-Shahawy M

The purpose of this study is to determine whether the type of operation, sphincter sparing procedures (SSP) or
abdomino-perineal resection (APR) for primary adenocarcinoma of the rectum at or below the peritoneal
reflection affects survival and recurrence after curative surgery.A prospective controlled study of seventy nine
patients with low rectal carcinoma was done between January 1999 and March 2003. Two types of operations
were done; SSP (43 patients) including a low anterior resection with either double-stapling technique (DST)
(18) or hand-sewn colorectal anastomosis (HSA) (25), and APR (36 patients). The outcome factors evaluated
were operative time, intraoperative blood loss, mortality, morbidity, disease-free survival and tumor
recurrence. Patients have been followed-up for a minimum of 12 months (mean time 32 months).Out of 43
patients who underwent SSP, there was one mortality, and 7 morbidities. Anastomotic leakage occurred in 4
cases; one patient needed colostomy. In APR group, no mortalities and 6 morbidities were found. Morbidity
was similar in both groups. The local recurrence rates for SSP and APR were 13.8% and 22.2%, respectively (p =
0.540), and the distant metastases rates were 11.1% and 8.3%, respectively (p = 1.000). Two-year disease-free
survival rates for SSP and APR patients were 73.3% and 66.7%, respectively (p = 0.121). Intraoperative blood
loss was significantly lower in SSP groups.Sphincter saving procedures can be performed to all patients with
rectal carcinoma regardless of the site of the lesion so long the distal and lateral margins are clear. Survival and
the risk of local recurrence are similar to that obtained by standard abdomino-perineal resection. Unlike
abdomino-perineal resection, sphincter saving procedures preserve the continence and give accepted good
quality of life.
PMID: 20424651

Study of endothelin-1 and vascular endothelial growth factor in patients with cancer
colon.

Abdel-Gawad IA; Hassanein HM; Bahgat NA; Abdel Sattar MA; El-Sissy AH; Altaweel MA; Helal AM

The levels of endothelin-1 and VEGF were evaluated in the sera of newly diagnosed patients with cancer colon
and were compared with the routinely used tumor markers; CEA and CA19.9. Their relations with some
prognostic factors of cancer colon were also investigated.The study included 48 patients with cancer colon and
20 apparently healthy volunteers as a control group. Patients were 23 males and 25 females with age range
from 18 to 71 years (mean = 47 +/- 1.8). Both serum and plasma samples were obtained from patients and
controls.Six percent of patients had grade 1 tumors, 77 % had grade 2 and 17 % had grade 3 disease. As regard
to the stage, 52 % of patients were stage II, 35.5 % were stage III, while 12.5 % were stage IV. Liver metastasis
was present in 12.5 %, while 35 % showed lymph node metastasis. The VEGF, endothelin-1, CA19.9 and CEA
were significantly higher in the cancer colon patients than in control groups (p-value < 0.001,0.006, < 0.001
and <0.001; respectively). Plasma level of endothelin-1 and serum level of VEGF showed significantly higher
levels in advanced stages of the disease (p value < 0.001) and in presence of liver metastasis (p value <0.00l
and 0.002 respectively), while VEGF showed significant result when compared with the grade (p value = 0.032).
In this study, when comparing the levels of plasma endothelin-1 and serum VEGF between the metastatic,

107
non-metastatic liver patients of the cancer colon group and the control group, the comparison was statistically
significant for both markers (p < 0.001). Endothelin-1 and VEGF showed significant positive correlation (r=0.77
and p-value < 0.0001). Serum VEGF and CA19.9 showed good sensitivities which were not different (97.9 %
and 87.5 % ,respectively), while there was no significant difference between VEGF, CA19.9 and CEA with
respect to specificities (100 %, 90 % and 100 % respectively).Both endothelin-1 and VEGF may be used for early
detection of liver metastasis in cancer colon and VEGF may be used as a potential new marker for the
diagnosis of cancer colon. Further studies with larger number of patients are recommended to establish the
value of VEGF and endothelin- 1 as potential diagnostic and prognostic markers for cancer colon. KEY WORDS:
Cancer colon - VEGF - Endothelin-1 - Angiogenesis.
PMID: 20652953

The prognostic value of c-Kit, K-ras codon 12, and p53 codon 72 mutations in Egyptian
patients with stage II colorectal cancer.

El-Serafi MM; Bahnassy AA; Ali NM; Eid SM; Kamel MM; Abdel-Hamid NA; Zekri AR

The prognosis for patients with colorectal cancer (CRC) depends mainly on standard clinicopathologic factors.
However, patients with similar disease characteristics exhibit various outcomes, especially in stage II.
Therefore, the identification of molecular prognostic markers is needed to predict patient outcomes.The
authors assessed the prognostic value of c-Kit (also called cluster of differentiation 117 [CD117] or KIT),
cyclooxygenase-2 (COX-2), tumor protein 53 (p53), and Kirsten rat sarcoma viral oncogene homolog (K-ras)
aberrations in 90 patients with stage II CRC using immunohistochemistry and molecular techniques. The results
were correlated with standard clinicopathologic prognostic factors, overall survival (OS), and disease-free
survival (DFS).COX2 and c-Kit overexpression was detected in 54.6% and 59.3% of patients, respectively.
Overexpression of p53 was detected in 47 patients, including 29 who had mutations, and a unique mutation
pattern was detected with 3 hotspots at codons 72, 245, and 273. Overexpression of ras was detected in 44
patients, including 37 who had mutations. On multivariate analysis, c-Kit overexpression, p53 codon 72
mutations, perforation, and performance status were independent prognostic factors for DFS (P=.054, P=.015,
P<.0001, and P=.043, respectively); whereas codon 12 K-ras mutation, performance status, and perforation
were independent prognostic factors for OS (P=.033, P=.006, and P<.0001, respectively).The current results
provide evidence for the prognostic value of c-Kit overexpression in patients with stage II CRC. The high p53
mutation rate and the unique hotspot in codon 72 have not been reported previously in CRC. This may be
related to environmental or racial features that are unique to the studied population.

Leukemia Studies

PMID: 11106820

A simple strategy for breakpoint fragment determination in chronic myeloid leukemia.

Kamel AM; Shaker HM; GadAllah FH; Hamza MR; Mansour O; El Hattab OH; Moussa HS

Molecular characterization is considered a part of the routine work-up of chronic myeloid leukemia (CML)
cases. Southern blot analysis using the universal BCR (UBCR) probe on BglII-digested DNA samples is the most
commonly used technique, while employing the human 3' bcr probe (PR-1) is usually considered a
complementary tool. In this study, we tried to develop a simple and economic strategy for molecular
characterization of CML using the 3' probe as it has been shown to be the one capable of locating the
breakpoint site. Seventy-eight cases of CML were studied. Molecular analysis was performed using the
Southern blot technique. DNA was digested with Bam HI, BglII, EcoRI, and XbaI. Hybridization was performed
using the human 3' bcr (PR-1) probe. BamHI and BglII could differentiate fragment 1 (F1) showing
rearrangement (R) with Bam HI and germline configuration (G) with BglII; F2/3 showing R with both, and F4
showing R with BamHI and G with BglII. F2/3 cases were further divided by HindIII enzyme into F2 showing (G)
and F3 showing (R). Fragment 0 showed G with both, but R with EcoRI and/or XbaI, while 3' deletion gave G
with all four enzymes. Our results showed a relative incidence of 6.4% for F0, 20.5% for F1, 32.1% for F2, 19.2%

108
for F3, 15.4% for F4, and 6.4% for 3' deletion. Sixty cases were evaluated clinically and hematologically and
were followed up for disease evolution and survival. They included 32 cases in early chronic phase, 24 in late
chronic phase, two in acceleration, and two in blastic crisis. No significant correlation was encountered
between the breakpoint site and any of the clinical and hematological data except those patients with 3'
deletion who showed a very short survival. The study emphasizes Southern blotting as the method of choice
for molecular characterization of CML and offers a simple and economic strategy for diagnosis and
determination of breakpoint fragment.
PMID: 22180424

Acute myeloid leukemia developing in patients with autoimmune diseases.

Ramadan SM; Fouad TM; Summa V; Hasan SKh; Lo-Coco F

Therapy-related acute myeloid leukemia is an unfortunate complication of cancer treatment, particularly for
patients with highly curable primary malignancies and favorable life expectancy. The risk of developing
therapy-related acute myeloid leukemia also applies to patients with non-malignant conditions, such as
autoimmune diseases treated with cytotoxic and/or immunosuppressive agents. There is considerable
evidence to suggest that there is an increased occurrence of hematologic malignancies in patients with
autoimmune diseases compared to the general population, with a further increase in risk after exposure to
cytotoxic therapies. Unfortunately, studies have failed to reveal a clear correlation between leukemia
development and exposure to individual agents used for the treatment of autoimmune diseases. Given the
dismal outcome of secondary acute myeloid leukemia and the wide range of available agents for treatment of
autoimmune diseases, an increased awareness of this risk and further investigation into the pathogenetic
mechanisms of acute leukemia in autoimmune disease patients are warranted. This article will review the data
available on the development of acute myeloid leukemia in patients with autoimmune diseases. Possible
leukemogeneic mechanisms in these patients, as well as evidence supporting the association of their primary
immunosuppressive status and their exposure to specific therapies, will also be reviewed. This review also
supports the idea that it may be misleading to label leukemias that develop in patients with autoimmune
diseases who are exposed to cytotoxic agents as 'therapy-related leukemias'. A better understanding of the
molecular defects in autoimmune disease patients who develop acute leukemia will lead to a better
understanding of the association between these two diseases entities.
PMID: 18839034

AML1/ETO Fusion Gene in de novo Pediatric Acute Myeloid Leukemia: Clinical Significance
and Prognostic Implications.

Abdel Rahman H; Farrag SA; El-Attar IA

The characterization of leukemia-associated chromosome translocations has contributed relevant insights into
our understanding of leukemia pathogenesis and has provided new specific tumor markers essential in
prognostic assessment and minimal residual disease studies. The aim of this work is to study the frequency of
AML1/ETO fusion gene in a series of Egyptian childhood AML cases. The clinical significance and prognostic
implications of this aberration, including CR rate, duration of first CR, extramedullary leukemia (EML), and
survival are investigated as well. Peripheral blood and/or bone marrow mononuclear cells were available for
analysis from 78 children, all newly diagnosed with AML. AML1/ ETO fusion transcript was detected by the
reverse transcriptase- polymerase chain reaction (RT-PCR) technique. Patients with de novo AML were treated
by 2 courses of induction chemotherapy, followed by 4 courses of consolidation treatment if the patient
achieved complete remission (CR). The marrow status was evaluated after each course in order to check bone
marrow cellularity and presence of blasts. Patients with less than 5% blasts by the end of the second course of
ADE passed to consolidation chemotherapy. Patients with more than 5% blasts by the end of the second
course of ADE were excluded from the study. The AML1/ETO fusion transcript was detected by a singleround
RT-PCR reaction and was found to be expressed in 15 out of 78 cases (19.2%). AML1/ETO positive patients
were 7 girls and 8 boys, with ages ranging from 5 to 15 years. Seven cases (46.67%) belonged to FAB subtype
M1, 7 (46.67%) M2, while only one case (6.67%) belonged to M5a subtype. Their total leukocytic counts
ranged from 7.1 to 183.0 x 109/l with a median of 21.0 x 109/l. Their hemoglobin concentrations ranged from

109
4.8 to 10.3g/dl with a median of 7.4g/dl, while their platelet counts ranged from 6.0 to 96.0 x 109/l with a
median of 25.5 x 109/l. Lymph nodes were enlarged in 8/15 cases (53.34%), hepatomegly was observed in
4/15 cases (26.67%), splenomegaly in 8/15 cases (53.34%), purpura in 6/15 cases (40%), while pallor was
observed in all fifteen cases.Extramedullary leukemia occurred in 4/15 cases (26.67%). As regards the fate of
the positive cases, thirteen cases (86.67%) attained complete remission (CR) following induction
chemotherapy. Two patients (13.33%) died during induction in active disease. Eight patients were in complete
continuous remission (CCR), four patients (26.67%) relapsed and died during relapse, and one patient (6.67%)
died in complete remission due to severe neutropenia and infection. On comparing the AML1/ETO fusion gene
status with overall survival, no significant difference was found between AML1/ETO positive and negative
cases. Likewise, no difference could be found between positive and negative cases as regards disease-free
survival (p=0.354). In conclusion, we report a frequency of 19.2% of AML1/ETO fusion gene in our newly
diagnosed pediatric AML cases. Positive cases showed good response to induction therapy, as well as high
complete remission rates, which are features of good prognosis. Key Words: Pediatric acute myeloid leukemia
, AML1/ETO fusion gene , RT-PCR , Clinical outcome , Prognostic significance.
PMID: 20601973

Bcl-2 protein expression in egyptian acute myeloid leukemia.

El-Shakankiry NH; El-Sayed GM; El-Maghraby S; Moneer MM

The primary cause of treatment failure in acute myeloid leukemia (AML) is the emergence of both resistant
disease and early relapse. The bcl-2 gene encodes a 26-kDa protein that promotes cell survival by blocking
programmed cell death (apoptosis). In the present study, bcl-2 protein expression was evaluated in newly
diagnosed AML patients and correlated with the induction of remission and overall survival (OS), in an attempt
to define patients who might benefit from modified therapeutic strategies.Pretreatment cellular bcl-2 protein
expression was measured in bone marrow samples obtained from 68 patients of newly diagnosed acute
myeloid leukemia and 10 healthy controls by western blotting.The mean bcl-2 protein expression was
significantly higher in patients (0.686+/-0.592) compared to controls (0.313+/-0.016) (p=0.002). The overall
survival for patients with mean bcl-2 expression of less, and more than or equal to 0.315, was 67% and 56%,
respectively, with no significant difference between the two groups (p=0.86).Even though we did not observe a
significant difference in overall survival between patients with high and low levels of bcl-2, modulation of this
protein might still be considered as an option for enhancing the effectiveness of conventional chemotherapy.
KEY WORDS: Acute myeloid leukemia (AML) - Bcl-2 - prognosis - Western blot.
PMID: 22220257

Clinical features and treatment outcome of acute promyelocytic leukemia patients treated
at cairo national cancer institute in egypt.

Khorshid O; Diaa A; Moaty MA; Fatah RA; Dessouki IE; Hamid MA; Noshokaty EE; Saied GE; Fouad
TM; Ramadan SM

The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic
leukemia (APL) treated at National Cancer Institute (NCI-Cairo), in Egypt from January 2007 to January 2011.
The median age at presentation was 29 years. Bleeding was the most common presenting symptom (79%).
Most patients had an intermediate risk Sanz score (49%) and 34% had a high risk score. The median follow-up
time was 36 months. All evaluable patients were treated for induction with the simultaneous administration of
all-trans retinoic acid (ATRA) and an anthracycline. The original AIDA treatment protocol was modified due to
resource limitations at the NCI-Cairo by replacing of idarubicin with daunorubicin or doxorubicin in most of the
cases and the inclusion of cytarabine during the consolidation phase only in pediatric patients. All patients who
achieved molecular complete remission after consolidation received two-year maintenance treatment with
low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. Five
patients died before treatment initiation due to bleeding, three died during induction chemotherapy due to
infectious complications (n=2) and bleeding (n=1) and one patient died during consolidation therapy due to
infection. The main therapeutic complications during the induction phase were febrile neutropenia (42%),
bleeding (18%) and differentiation syndrome (11%). All patients achieved molecular CR at end of consolidation

110
therapy at a median time of 100 days. The 3-year OS was 89%. Two patients relapsed at 13 and 24 months,
respectively. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity
during consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin) may be
a valid treatment option for APL in developing countries. In spite of the increased incidence of high and
intermediate risk disease in our cohort, we reported an acceptable CR rate, toxicity and OS.
PMID: 20029466

Clinical significance of immunophenotypic markers in pediatric T-cell acute lymphoblastic

leukemia.

Sidhom I; Shaaban K; Soliman S; Ezzat S; El-Anwar W; Hamdy N; Yassin D; Salem S; Hassanein H; Mansour MT

Cell-marker profiling has led to conflicting conclusions about its prognostic significance in T-ALL.To investigate
the prevalence of the expression of CD34, CD10 and myeloid associated antigens (CD13/ CD33) in childhood T-
ALL and to relate their presence to initial clinical and biologic features and early response to therapy.This study
included 67 consecutive patients with newly diagnosed T-ALL recruited from the Children's Cancer Hospital in
Egypt during the time period from July 2007 to June 2008. Immunophenotypic markers and minimal residual
disease (MRD) were studied by five-color flow cytometry.The frequency of CD34 was 34.9% , CD10 33.3% ,
while CD13/CD33 was 18.8%. No significant association was encountered between CD34, CD10 or myeloid
antigen positivity and the presenting clinical features as age, sex, TLC and CNS leukemia. Only CD10(+)
expression had significant association with initial CNS involvement (p=0.039). CD34 and CD13/CD33 expression
was significantly associated with T-cell maturation stages (p<0.05). No relationship was observed for age, TLC,
gender, NCI risk or CNS involvement with early response to therapy illustrated by BM as well as MRD day 15
and day 42. CD34(+), CD13/CD33(+) and early T-cell stage had high MRD levels on day 15 that was statistically
highly significant (p<0.01), but CD10(+) had statistically significant lower MRD level on day 15 (p=0.049).
However, only CD34 retained its significance at an MRD cut-off level of 0.01%.CD34, CD10, CD13/CD33
expression, as well as T-cell maturation stages, may have prognostic significance in pediatric T-ALL as they have
a significant impact on early clearance of leukemic cells detected by MRD day 15.
PMID: 16508681

Comparison of variable number tandem repeat and short tandem repeat genetic markers
for qualitative and quantitative chimerism analysis post allogeneic stem cell
transplantation.

Mossallam GI; Smith AG; McFarland C

Analysis of donor chimerism has become a routine procedure for the documentation of engraftment after
allogeneic hematopoietic stem cell transplantation. Quantitative analysis of chimerism kinetics has been
shown to predict graft failure or relapse. In this study, we compared the use of variable number tandem
repeats (VNTR) and short tandem repeats (STR) as polymorphic genetic markers in chimerism analysis. This
study included qualitative and quantitative assessment of both techniques to assess informative yield and
sensitivity.We analyzed 206 samples representing 40 transplant recipients and their HLA-identical sibling
donors. A panel of six VNTR loci, 15 STR loci and 1 sex chromosome locus was used. Amplified VNTR products
were visualized in an ethidium bromide-stained gel. STR loci were amplified using fluorescent primers, and the
products were analyzed by capillary electrophoresis.VNTR and STR analysis gave comparable qualitative results
in the majority of cases. The incidence of mixed chimerism (MC) by STR analysis was 45% compared to 32% in
cases evaluated by VNTR analysis. STR markers were more informative; several informative loci could be
identified in all patients. Unique alleles for both patient and donor could be identified in all patients by STR
versus 32/40 by VNTR analysis. The STR markers were also more sensitive in the detection of chimerism. The
size of VNTR alleles and differences between the size of donor and recipient VNTR alleles affected the
sensitivity of detection. With both techniques, quantitative assessment of chimerism showed some
discrepancies between the estimated and the calculated percentage of donor DNA. Discordance between the
two estimates was observed in 8/19 patients with MC. However, sequential monitoring of the relative band
intensity of VNTR alleles offered some insight into the direction of change in engraftment over time.The higher
yield of informative loci with STR and the automated measurement of amplified STR 103 products offered the

111
advantages of more rapid and accurate quantitative assessment of chimerism. The choice between these two
techniques depends on the need for quantitative or qualitative information, the availability of equipment, and
the cost.
PMID: 19034338

Correlation of karyotype and immunophenotype in childhood acute lymphoblastic

leukemia; experience at the National Cancer Institute, Cairo University, Egypt.

Hamouda F; El-Sissy AH; Radwan AK; Hussein H; Gadallah FH; Al-Sharkawy N; Sedhom E; Ebeid E; Salem SI

To identify chromosomal pattern among the major immunophenotypic subgroups in Egyptian children with
ALL, and its correlation with clinical presentation and disease free survival.Cytogenetic and immunophenotypic
analysis were done for all patients. Patients received ALL-PNCI-III/98 chemotherapy protocol used at NCI, Cairo
University.The frequency of pseudodiploidy and normal karyotype in the whole group was 42.9% and 33.3%
respectively. The frequency of pseudodiploidy was 36.8% in CALLA positive early pre B, 30.7% in pre B cases,
71.4% in T cell cases and 100% in mature B cell cases. At 12 months, DFS was 50% for pseudodiploid group
having pre B phenotype, compared to 16.6% for pseudodiploid group with CALLA positive early pre B ALL.
Sixteen percent of the studied cases showed T cell phenotype, 71.4% of them showed pseudodiploid
karyotype, all of them had high risk features. Hyperdiploidy was found in 31.5% of CALLA positive early pre B
cases and was associated with favorable prognostic features and DFS of 66.6% at 12 months. Hyperdiploidy of
>50 chromosome represented 62.5% of hyperdipoid cases, 80% of them were CALLA positive early pre B ALL
carrying good risk features. Fifty percent of normal karyotypic patients showed pre B phenotype, while 42.8%
showed CALLA positive early pre B ALL. Their age, TLC, DFS, were almost comparable.CALLA early pre B
phenotype has a positive impact on chromosomal pattern having best outcome among patients with
hyperdiploidy. The Pseudodiploid karyotype carries a better outcome with pre B phenotype.
PMID: 19034340

Cost and outcome of treatment of adults with acute myeloid leukemia at the National
Cancer Institute-Egypt.

El-Zawahry HM; Zeeneldin AA; Samra MA; Mattar MM; El-Gammal MM; Abd El-Samee A; Darwish T

Despite important advances in the therapy of acute myeloid leukemia (AML), the majority of patients die of
their disease, unless bone marrow transplantation (BMT) is done. Infection and hemorrhage are still the major
causes of mortality in AML patients. Progress in therapy and supportive care has led to gradual improvement
in the overall results, but further improvements are still needed.The aim of this study is to identify the
outcome and costs of adult AML patients treated with conventional chemotherapy (CCT) at the National
Cancer Institute (NCI), Cairo University during the time period from April 1999 to January 2002. Clinical,
laboratory characteristics were all recorded. Data regarding different types of therapies given for these
patients including response, outcome and costs were also collected.The median age of 82 identified AML
patients was 34 years. The complete remission (CR) rate after induction with CCT was 52% (42/82 patients)
with a median CR duration of 9 months. Twenty-eight percent of patients who achieved CR subsequently
relapsed. By January 2003, fifty-eight patients were dead (70.7%). Infections were the major mortality cause,
followed by disease progression then bleeding (65% , 28% and 7% respectively). The median treatment cost
per patient was 33158 Egyptian Pounds (LE). It was higher for patients who achieved CR compared to those
who relapsed and/or died. Drugs contributed by 78 % to the total treatment cost, while hospitalization,
investigations and blood-component therapy contributed by 6%, 7% and 8% respectively.Outcome of patients
with AML treated at NCI- Cairo University can be enhanced by improvement of supportive therapy; mainly
infection control and expanding BMT programs to accommodate all eligible patients.
PMID: 23082469

112
 Cytokine profiling as a prognostic markers in chronic myeloid leukemia patients.

Singer MK; Assem M; Abdel Ghaffar AB; Morcos NY

Chronic myeloid leukemia (CML) accounts for 20% of all adult leukemias worldwide. Most Egyptian patients
are diagnosed in the chronic phase and progress to the accelerated or blastic phase, which is related with
decreased survival. Various pro-inflammatory cytokines are involved in the pathogenesis of chronic leukemia
but their prognostic significance is unknown. The aim of the current study is to determine the validity of TNF-
alpha, IL-6, IL-18 and CRP levels as prognostic markers in CML patients. These parameters were monitored
with clinical routine tests in 25 CML patients besides ten healthy control subjects at National Cancer Institute,
Cairo, Egypt. IL-6 and IL-18 levels before hydroxyurea treatment were significantly higher in all patients
compared to controls (P<0.001 for both levels). At hematological remission, significant reductions were
observed for IL-6 (P<0.001), IL-18 (P<0.001) and CRP (P<0.001) whereas reduction in the levels of TNF were
non-significant. Moreover, an inverse correlation was observed between both of TNF (P<0.05) and CRP
(p<0.01) on one side and megakaryocytic dysplasia on the other side. These findings offer evidence that TNF
may have potential prognostic role in megakaryocytic dysplasia detection.
PMID: 22771839

Defining the Role of Sirolimus in the Management of Graft-versus-Host Disease: From

Prophylaxis to Treatment.

Abouelnasr A; Roy J; Cohen S; Kiss T; Lachance S

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic
hematopoietic stem cell transplantation (HSCT). Measures developed that have significantly reduced GVHD
were also frequently associated with an increased risk of relapse. GVHD and graft-versus-tumor (GVT) effects
are tightly linked, and balance between both reactions is difficult to achieve. To have an impact on the
outcome and quality of life after HSCT, improvements in current strategies to prevent and treat GVHD while
preserving the GVT effect are clearly needed. Sirolimus (rapamycin) is a lipophilic macrocytic lactone with
immunosuppressive, antitumor, and antiviral properties. Because of its multiple modes of activities, it is being
increasingly used in the management of GVHD. This review aims to summarize its mechanisms of action and
potential advantages over other immunosuppressors and to analyze the most relevant studies investigating its
role in both prevention and treatment of GVHD.
PMID: 20029468

Detection of anti-asparaginase antibodies during therapy with E.coli asparaginase in

children with newly diagnosed acute lymphoblastic leukemia and lymphoma.

Ebeid EN; Kamel MM; Ali BA

Asparaginase is an effective antileukemic agent which is included in most front-line protocols for pediatric
acute lymphoblastic leukemia (ALL) worldwide. Since asparaginase is a bacterial protein, it may induce
formation of antibodies. The reported frequency of anti-asparaginase antibodies is highly variable: antibodies
have been reported in as many as 79% of adults and as many as 70% of children after intravenous or
intramuscular administration of E.coli asparaginase.The aim of this study was to determine if the presence of
antibodies during induction and continuation phases in newly diagnosed children with ALL and lymphoblastic
lymphoma during therapy with E.coli asparaginase, had any correlation with various factors such as: age,
gender, hypersensitivity reactions, response to therapy and Event Free Survival (EFS).Between the period from
March 2005 to May 2007, sixty-four children who attended the Menia outpatient pediatric oncology clinic, or
were admitted to the inpatient department of the Menia oncology center, were enrolled in the study. Forty
children had newly diagnosed ALL and 24 had lymphoblastic lymphoma. Patients were 48 males (75%) and 16
females (25%) with a male:female ratio 3:1. Their ages ranged from 3.5 to 17 years with mean age of 9.6 years.
All patients received asparaginase therapy according to the St. Jude Total XIII protocol, in a dose of 10,000
IU/m(2)/dose, intramuscularly for 6-9 doses during the induction phase and another 6-9 doses during

113
continuation phase according to disease status.Forty one patients achieved complete remission, 9 had partial
remission, and 14 were lost to followup at different intervals of treatment. Antiasparaginase antibodies were
detected in 36 patients (56%) out of 64 patients, and 37 patients (60%) out of 62 patients who were treated
with asparaginase at day 8 and day 27 of induction phase respectively. Moreover, 33 patients (61%) out of 54
patients, and 41 patients (83%) out of 50 patients had positive antiasparaginase antibodies at week 10 and
week 21 of continuation phase respectively. The 2-year EFS of the whole group was 50%. There was no
statistically significant relation between positivity of antiasparaginase antibodies and the following: age,
gender, hypersensitivity reaction, response to therapy and EFS.The presence of antiasparaginase antibodies
was unrelated to age, gender, hypersensitivity reaction, response to therapy and event free survival of newly
diagnosed children with acute lymphoblastic leukemia and lymphoblastic lymphoma.
PMID: 17671537

Glutathione S-transferase GSTM1 and GSTT1 polymorphisms in adult acute myeloid

leukemia; its impact on toxicity and response to chemotherapy.

Mossallam GI; Abdel Hamid TM; Samra MA

Heterogeneity in patient' s response to chemotherapy is consistently observed across populations.

Pharmacogenomics, the study of inherited differences in drug disposition and effects, is emerging as a tool to
predict efficacy and toxicity of drugs. Glutathione S-transferases (GST) are involved in the metabolism and
detoxification of environmental carcinogens and some classes of chemotherapeutics. Polymorphism of GSTM1
and GSTT1, in the form of homozygous deletion, is encountered in varying frequencies in normal population. It
has been associated with altered response and toxicity from cytotoxic chemotherapy. In this study, we
investigated the impact of these polymorphisms on response and side effects of chemotherapy in adult acute
myeloid leukaemia (AML) patients. Correlations between these genetic polymorphisms and other prognostic
factors were also investigated.We genotyped GSTM1 and GSTT1 in 98 adult AML patients using multiplex PCR.
Induction therapy included Doxorubicin and Cytosine arabinoside (3+7) regimen. Treatment outcomes were
compared in those with or without GSTM1 and GSTT1 genes.The frequencies of GSTM1 null and GSTT1 null
genotypes were 56% and 14%, respectively. Six percent (6%) were double null. The rate of toxic death during
induction was 3/7 (43%) and 17/56 (30%) in GSTT1 null and GSTT1 present patients, respectively, p=0.67. This
constituted 75% and 42% of total deaths in each group, respectively, p=0.31. Differences were not statistically
significant. On the other hand, the rate of complete remission (CR) in patients with GSTM1 present compared
to those with GSTM1 null genotype was 12/27 (48%) versus 23/36 (64%), p=0.21. GSTT1 null genotype was
significantly associated with lymphoid marker (mainly CD7) expression (p=0.03), known with its adverse effect
on prognosis. Overall survival and disease-free survival were similar in patients with and without the genes. No
significant associations were encountered between GST genotypes and treatment outcomes.Our data suggest
possible association, though not significant, between GSTT1 null genotype and toxic death during induction
and between GSTM1 present genotype and lower rate of CR. Studies on larger numbers are needed focusing
on selection of anticancer agents to avoid adverse reactions and therapeutic failure, with special emphasis on
drug toxicity and dose adjustment.
PMID: 18724311

Hematopoietic stem cell transplantation in Egypt.

Mahmoud H; El-Haddad A; Fahmy O; El-Emary M; Nassar A; Abdel-Mooti M; Sobhy A; Sultan A

Hematopoietic SCT is now an established treatment modality with definitive indications for many
hematological disorders. However, this line of treatment requires tremendous resources, and it becomes
increasingly difficult for transplanters practicing in the developing world to reconcile the difference between
what is possible and what is available. On the basis of 18 years of experience and more than 1300 transplants,
this article will focus on special issues, which we think are important for hematopoietic SCT practices in
developing countries, taking the program in Egypt as an example that may be applicable to other countries in
the developing world. The SCT program in Egypt started in 1989 on a narrow scale. In 1997, the transplant rate
increased dramatically with the opening of the SCT unit at the Nasser Institute. Our team is registered in the
Center for International Blood and Marrow Transplant Research. The total number of transplants performed

114
till June 2007 is 1362; 80% of the cases are allogeneic and 20% autologous. There are seven other centers in
Egypt performing mainly autologous transplants.

PMID: 2761288

Immunological phenotypic pattern of acute lymphoblastic leukaemia in Egypt.

Kamel AM; Assem MM; Jaffe ES; Magrath I; Aboul Enein MI; Hindawy DS

We have performed immunophenotyping studies on 186 untreated cases of acute lymphoblastic leukemia
(ALL) in an Egyptian population, using panels of monoclonal antibodies (mAb) and an avidin-biotin-
immunoperoxidase detection system. Sixty-two of these cases were tested with a panel of mAb directed
against the T-cell markers CD2, CD4, CD8, B-cell markers CD20, kappa and lambda, the common ALL antigen
(common ALLa) and class II HLA antigens. The remaining 124 cases were also tested with additional markers of
T- and B-cell precursors, namely CD7 and CD19. The common leukocyte antigen, T200, was used to exclude
nonhemopoietic neoplasms. Cases that remained unclassifiable were further tested with a wider panel of T-
cell markers, including CD1, CD2, CD3 and CD5. In some cases multiple mAb directed against the same antigens
were used. The relative frequencies of common ALL and B ALL were calculated from the total number of cases
and were found to be 39.2% and 3.2%, respectively. The proportions of T-cell and null leukemias were
calculated from the better characterized subgroup of 124 cases, and were found to be 50% and 4.8%,
respectively. In our series, the age distribution of common ALL revealed a peak at 2-5 yr, but this was partially
obscured in the entire series by the high proportion of T-cell cases, which had an age peak between 4 and 12
yr of age. Our results demonstrate marked differences in the phenotypic pattern of ALL in Egypt compared to
Western Countries, the predominant finding being a relative excess of T-cell ALL and a paucity of common ALL
cases. At present it is not clear whether this results from an increased incidence of T-cell ALL or a decreased
incidence of common ALL.
PMID: 15568034

Impact of CD34 subsets on engraftment kinetics in allogeneic peripheral blood stem cell
transplantation.

Kamel AM; El-Sharkawy N; Mahmoud HK; Khalaf MR; El Haddad A; Fahmy O; El Fattah RA; Sayed D

Our objective was to evaluate, probably for the first time, the impact of CD34 subsets on engraftment kinetics
in allogeneic PBSC transplantation (PBSCT). PBSC graft components were analyzed in 62 cases for the absolute
count/kg of total CD34+ and the following subsets: DR- and +, CD71+/-, CD38+/-, CD33+/- and CD61+/-. Time
to ANC >0.5 and >1 x 10(9)/l and platelets >20 and >50 x 10(9)/l was reported. The median value for each
parameter was used to discriminate rapid from slow engraftment. Four parameters showed significant
predictive power of early neutrophil engraftment, namely CD34+ /DR- (P = 0.002), CD34+/38- (P = 0.02),
CD34+/CD61- (P = 0.04) and total CD34+ cell dose (P = 0.04). Four parameters showed significant predictive
power of early platelet engraftment, namely CD34+/CD61+ (P = 0.02), CD34+ /CD38- and total CD34+ cell dose
(P = 0.04) and CD34+ /CD71- (P = 0.05). Comparing patients who received > to those who received < the
threshold dose(s), only CD34+ /CD38- lost its significance for neutrophil engraftment; and only CD34+ /CD61+
retained its significance for platelet engraftment (P = 0.03); furthermore, the former group required
significantly fewer platelet transfusions (P = 0.018). We concluded that in allogeneic PBSCT, the best predictor
of early neutrophil engraftment is the absolute CD34+ /DR- and for early platelet engraftment is the absolute
CD34+ /CD61+ cell dose.
PMID: 22853046

115
Insulin-like growth factor system in egyptian children with acute lymphoblastic leukemia.

Zakhary NI; Boshra SA; El-Sawalhi MM; Fahim AT; Ebeid EN

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) have been reported to play an important
role in tumor proliferation. This study aimed to investigate the validity of measuring IGFs and specific IGFBPs in
the serum of Egyptian children with acute lymphoblastic leukemia (ALL) as additional markers in diagnosis and
follow-up of the disease. IGF-I, IGF-II, IGFBP-2, and IGFBP-3 were determined in the sera of 33 ALL patients at
time of diagnosis and after an intensification phase of chemotherapy (IPC) that lasts about 6 months as well as
in 15 healthy children as a control group using enzyme-linked immunosorbent assay (ELISA) technique. At time
of diagnosis, serum IGF-I, IGF-II, and IGFBP-3 were significantly lower than those in the control group. After
IPC, serum IGF-I and IGF-II returned to their normal levels, while serum IGFBP-3 was still decreased. On the
other hand, serum IGFBP-2 was significantly higher than those in the control group at diagnosis, but returned
to normal value after IPC. In conclusion, the changes in IGF system could be useful to support diagnosis and
follow-up of children with ALL.
PMID: 15284589

Outcome and prognostic factors of acute lymphoblastic leukemia in children at the

National Cancer Institute, Egypt.

Hussein H; Sidhom I; Naga SA; Amin M; Ebied E; Khairy A; Kamel A; El-Sharkawy N

To improve survival of children with acute lymphoblastic leukemia (ALL) in the authors' institute and to define
significant prognostic factors.This study included 154 children with newly diagnosed ALL below the age of 18
years during the period August 1, 1998, to December 31, 2000. All patients were treated according to the NCI,
Cairo, Egypt, treatment protocol modified from study XIII for high-risk ALL of St. Jude Children's Research
Hospital.B-cell precursor phenotype was encountered in 73.4% of patients, T-cell in 26.6%. According to
NCI/Rome criteria for risk classification, 58.4% of patients were in the high-risk group (90% of T-lineage
compared with 47% of B-lineage ALL, P < 0.001). Nine patients (5.8%) died during induction and 10 patients
(6.5%) failed to achieve remission. With a median follow-up of 43 months, the 3-year disease-free survival and
its probability at 5 years were 80 +/- 3.6% and 75.3 +/- 4%, respectively; the 3-year event-free survival and its
probability at 5 years were 69 +/- 3.8% and 65.2 +/- 4%, respectively. B-cell precursor ALL had 5-year
probabilities of disease-free survival and event-free survival of 80.5 +/- 4% and 71.8 +/- 4.5% compared with
60.2 +/- 8.6% and 46.7 +/- 8% for T-cell, respectively (P < 0.01, log-rank test). Prognostic factors that had a
statistically significant unfavorable impact on survival by univariate analysis were age 10 years or more, central
nervous system involvement, T-lineage phenotype, high-risk group, DNA index less than 1.16, and slow early
response to treatment. By multivariate analysis, central nervous system involvement, high-risk group, and slow
early response to treatment still had prognostic significance. Risk classification demonstrated prognostic
significance for B-lineage but not T-lineage ALL.This treatment protocol was effective in improving ALL survival
among patients at the authors' institute compared with previous trials, although the outcome remains lower
than that in more industrialized countries. Prognostic factors defined in this study were similar to those
identified by other cooperative groups.
PMID: 17671532

p15 (INK4B) and E-cadherin CpG island methylation is frequent in Egyptian acute myeloid
leukemia.

El-Shakankiry NH; Mossallam GI

Hypermethylation within the promoters of selected genes is an epigenetic pathway that appears to be
especially common in all types of human haematopoeitic neoplasms. It is usually associated with inactivation
of the involved genes, and can be reversed using demethylating agents. The aim of this study is to evaluate the
frequency of p15 and E-cadherin promoter methylation in Egyptian acute myeloid leukemia (AML) patients in
an attempt to identify a subset of patients who might be candidates for demethylating agents as a form of

116
targeted therapy either as a primary or as an adjunct to current standard induction and post-remission
regimens.In the present work we have studied tumor-associated aberrant p15 and E-cadherin promotor
methylation in 59 newly diagnosed acute myeloid leukemia (AML) patients using methylation specific
PCR.Aberrant p15 promoter methylation was detected in 49% (29/59) of the patients. In 4 of these patients,
no DNA could be amplified by the p15 unmethylated reaction showing a complete methylation of both alleles
in the examined region. In the remaining 25 cases both methylated and unmethylated DNA could be amplified.
Aberrant methylation of E-cadherin was detected in 63% (37/59) of the cases. In all of these cases both the
methylated and the unmethylated alleles were amplified denoting partial methylation of the examined region.
Concomitant methylation of p15 and E-cadherin was detected in 40% (23/59) of all the cases tested, while in
27% (16/59) of the cases both genes were not methylated.These results demonstrate that p15 and E-cadherin
promoter methylation are frequent events in Egyptian AML and provide an impetus for larger studies to define
the extent and pattern of methylation in the various subgroups of AML. Methylation studies, therefore,
represent a novel additional tool to define the subset of patients who might benefit from demethylating
agents,thus providing the molecular basis for targeted therapeutic approaches and better designing of risk-
adapted therapy.
PMID: 15218412

Parvovirus B19 infection as a cause of anemia in pediatric acute lymphoblastic leukemia

patients during maintenance chemotherapy.

El-Mahallawy HA; Mansour T; El-Din SE; Hafez M; Abd-el-Latif S

Persistent parvovirus B19 tends to occur in immunocom-promised patients and manifests as pure red cell
aplasia and chronic anemia. This study aimed to detect the contribution of parvovirus B19 infection to anemia
in children with acute lymphoblastic leukemia (ALL) receiving chemotherapy.Two groups of ALL patients were
studied during maintenance chemotherapy: 50 patients with persistent anemia (ie, extending for >2 weeks)
and 34 patients without anemia (controls). Serum parvovirus B19 IgG and IgM were investigated by an
enzyme-linked immunosorbent assay, and the virus DNA was sought in bone marrow cells by a nested
polymerase chain reaction assay.Parvovirus B19 DNA was detected in 11 of the 50 (22%) ALL children with
anemia, 4 of whom were also IgM positive. In addition, IgM positivity was observed in nine (18%) other
children who were negative for parvovirus B19 DNA. The children without anemia were found to be
significantly different than those with anemia in terms of parvovirus B19 DNA positivity and DNA + IgM
positivity (P = 0.03 and 0.01, respectively). IgG was found to be positive in a total of 19 (38%) cases, with B19
DNA present in 6 of them.These findings indicate the high frequency of parvovirus B19 in anemia in children
with ALL and the importance of testing for its DNA in the bone marrow cells together with IgG and IgM
antibodies in the serum of immunocompromised patients. It is important to consider parvovirus B19 infections
as a cause of anemia and suppressed erythropoiesis in children with ALL who are receiving ongoing treatment.
PMID: 10467322

Peripheral blood vs bone marrow as a source for allogeneic hematopoietic stem cell
transplantation.

Mahmoud H; Fahmy O; Kamel A; Kamel M; El-Haddad A; El-Kadi D

In this randomized prospective study, we included 30 patients with different hematological diseases (acute
myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome or
severe aplastic anemia) to compare peripheral blood stem cells (PBSC) (15 patients; mean age 23) and bone
marrow (BM) (15 patients; mean age 21.8) as a source for allogeneic transplantation regarding the tempo of
hematopoietic recovery and the incidence of acute graft-versus-host disease (GVHD). In the BM group, the
median nucleated cell count harvested was 1.3 x 10(10), while in the PBSC group, the aphereses contained a
median of 4.4 x 10(6) CD34+/kg recipient weight. PBSC transplantation (PBSCT) was associated with faster
hematopoietic reconstitution measured as absolute neutrophil count (ANC) >0.5 x 10(9)/l (log-rank P value
<0.0018) and platelet count >25 x 10(9)/l (log-rank P value <0.0098). Seven patients (46.7%) in the BM group vs
only one patient (6.7%) in the PBSC group developed acute GVHD (P = 0.013). Therefore, we conclude that
PBSCT is associated with faster hematopoietic recovery and the incidence of acute GVHD does not exceed that

117
seen with BMT.

PMID: 16799654

P-gp expression and Rh 123 efflux assay have no impact on survival in Egyptian pediatric
acute lymphoblastic leukemia patients.

Kamel AM; El-Sharkawy N; Yassin D; Shaaban K; Hussein H; Sidhom I; Abo El-Naga S; Ameen M; El-
Hattab O; Aly El-Din NH

In a previous work we have studied MDR status in terms of P-glycoprotein (P-gp) expression and Rhodamine
123 efflux assay in Egyptian acute leukemia patients. We have reported results comparable to the literature as
regards ANLL both in pediatric and adult cases. However, higher figures were encountered for the functional
assay in ALL. As our ALL cases especially in pediatric age group show worse prognosis compared to literature,
we hypothesized that the higher percentage of cases with positive Rh123 efflux assay might be a contributing
factor.A total of 108 cases were studied including 80 ALL and 28 ANLL. ALL cases included 48 male and 32
female with an age range of 6m to 18 yrs and a median of 7 yrs. ANLL cases included 18 male and 10 female
with an age range of 6m to 18 yrs and a median of 8 yrs. P-gp expression was evaluated using 4E3 and UIC2
mAb, analyzed by Coulter XL flow cytometer and expressed as a ratio at a cut off of >or= 1.1 and/or >or= 5%
positive cells. For the evaluation of MDR function Rh123 efflux assay using cyclosporine as a blocker and
expressed as a ratio at a cutoff of >or= 1.1 and/or >or= 10% positive cells was performed. MDR expression and
function were correlated to age, Hb, TLC, CD34 expression, immunophenotype and DNA index in ALL, FAB
subtypes in ANLL as well as to CR, DFS and EFS in ALL.In ALL, P-gp expression was encountered in 26.4% of
cases. Positive Rh efflux was reported in 61.5%. No correlation was encountered between neither expression
nor functional assay with age, Hb, TLC, CD34 expression or immunophenotype. CR was achieved in 89.8%;
neither P-gp expression nor Rh123 efflux had an impact on CR except for Rh123 efflux in T-ALL where a cutoff
of 1.25 could predict CR at a total accuracy of 70.6%. DFS was 92.3% while EFS was 72.2% for the whole group.
No significant difference was encountered neither between cases expressing or lacking P-gp nor between
cases with negative or positive Rh123 efflux assay. In ANLL P-gp expression was encountered in 47.6% of cases,
while positive Rh123 efflux assay was encountered in 75% of cases. No correlation as encountered between
neither expression nor Rh123 efflux assay and neither age, Hb, TLC, CD34 expression nor FAB subtypes.Neither
P-gp expression nor Rh123 efflux assay has any impact on survival in pediatric ALL. Rh123 ratio of 1.25 is
predictive of CR in TALL.
PMID: 1697005

Phenotypic analysis of T-cell acute lymphoblastic leukemia in Egypt.

Kamel AM; Ghaleb FM; Assem MM; Hindawy DS; Jaffe ES; Magrath IT

Leukemic cells from 46 T ALL cases were studied with a wide panel of mAb reacting with T cells using an
immunoperoxidase technique. The cases included 15 adults (16 years or over) and 31 children (less than 16
years). The mAb used in the panel were: CD1, (T6), CD2 (T11, X11, D66, clone 2), CD3 (T3/Leu4), CD4,
(T4/Leu3a), CD5 (Leu1, T1, A50, I73D9), CD7 (Leu9, I21), CD8 (T8/Leu2a) and HNK1. Based on their reactivity
with the mAb panel all cases were assigned to one of the intrathymic differentiation compartments. Among
the adults, five cases were assigned to compartment I, six to compartment II and four to compartment III. The
pediatric cases included eight in compartment I, eighteen in compartment II and five in compartment III.
Fifteen L1 cases studied included four in compartment I, seven in compartment II and four in compartment III;
while thirty L2 cases showed nine in compartment I, sixteen in compartment II and five cases in compartment
III. The most frequently observed CD groups among T ALL cells were CD5 (100% and 88.9% in children and
adults respectively), CD7 (93.1% and 84.6%) and CD2 (76.7% and 76.9%). The most frequently reactive mAb in
our series was Leu1 (81.8% followed by I21 (71.1%) and Leu9 (68.9%). The most frequently reactive
combination of two mAb was Leu1/I21 (100%) followed by Leu1/T11 (97.4%). Five of the 46 cases reacted with
HNK1, suggesting an origin from the natural killer (NK) subset. Our results indicate that in T-cell ALL in Egypt
the surface phenotype is similar to that of intermediate or late thymocytes in more than 66% of cases. CD5,

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CD7 and CD2 were the most frequently detected antigens. Studies of the association between T-cell
phenotype and socioeconomic status are warranted.

PMID: 16353080

Prevalence of anti human herpes virus-6 IgG and its receptor in acute leukemia
(membrane cofactor protein: MCP, CD46).

Assem MM; Gad WH; El-Sharkawy NM; El-Rouby MN; Ghaleb FM; Tarek H; Kamel AM

CD46 is a membrane cofactor protein, which acts as a cofactor for factor I proteolytic cleavage of C3, so it
protects the cells expressing it on their surface from autologous complement attack. It has been recently
described as a receptor for HHV-6. Also, it has been shown to be highly expressed on malignant cells as
compared to normal cells, thus playing a major role by which these cells, either cells of haematological
malignancy or cells of other body cancers, can protect themselves against complement attack so they can
survive and metastasize.This study has been done to detect the seroprevalence of HHV-6 among 47 Egyptian
adult cases of acute leukemia using the anti-HHV-6 IgG ELISA serological technique. CD46 receptor expression
and immunophenotyping technique were performed using FCM. Twenty nine of the cases were ANLL, while 18
were ALL cases. Sixteen age- and sex-matched control cases were also studied for both anti-HHV-6 IgG and
CD46 receptor expression.HHV-6 IgG antibodies were encountered in 29 (100%), 14 (77.8%) and 12 (75%) of
the ANLL, ALL and the control group, cases, respectively. CD46 expression was encountered in 21 (72.4%) of
the ANLL cases and in 10 (55.6%) of the ALL cases. Concordance between HHV- 6 seropositivity and CD46
expression was encountered in 31 cases (29 positive and 2 negative). Disconcordance was encountered in 16
cases with 14 showing HHV-6 IgG seropositivity with no CD46 expression and 2 showing the reverse.The lack of
significant correlation between CD46 expression and seropositivity would exclude CD46 expression as a cause
of contracting HHV-6 infection in leukemic patients.
PMID: 19203726

Prognostic utility of routine chimerism testing at 2 to 6 months after allogeneic

hematopoietic cell transplantation.

Mossallam GI; Kamel AM; Storer B; Martin PJ

The utility of routine chimerism analysis as a prognostic indicator of subsequent outcomes after allogeneic
hematopoietic cell transplantation (HCT) with myeloablative conditioning regimens remains controversial. To
address this controversy, routine chimerism test results at 2 to 6 months after HCT with myeloablative
conditioning regimens were evaluated for association with subsequent risk of chronic graft-versus-host disease
(GVHD), nonrelapse mortality (NRM), relapse, and overall mortality. Only 70 of 1304 patients (5%) had < 95%
donor-derived cells in the marrow. Low donor chimerism in the marrow occurred more often in patients with
low-risk diseases compared with those with higher-risk diseases and was significantly associated with a
reduced risk of chronic GVHD. Among 673 patients evaluated, 164 (24%) had < 85% donor-derived T cells in
the blood. Low donor T cell chimerism was more frequent in patients with low-risk diseases compared with
those with higher-risk diseases, in those who received conditioning with busulfan compared with those who
received conditioning with total body irradiation, and in those with lower-grade acute GVHD. Low donor T cell
chimerism in the blood was significantly associated with a reduced risk of chronic GVHD but not with a
reduced risk of relapse, NRM, or overall mortality. Routine testing of chimerism in the marrow and blood at 2
to 6 months after HCT with myeloablative conditioning regimens may be helpful in documenting engraftment
in clinical trials, but provides only limited prognostic information in clinical practice.
PMID: 15589744

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 Risk factors for cytomegalovirus, hepatitis B and C virus reactivation after bone marrow
transplantation.

Zekri AR; Mohamed WS; Samra MA; Sherif GM; El-Shehaby AM; El-Sayed MH

To derive guidelines for a safer bone marrow transplantation (BMT) policy, we have to study pre-BMT risk
factors that may be associated with an increased post-BMT death. Among those factors, the importance of
pre-BMT viral hepatitis markers in BMT donors and recipients remains unsettled. In the present study, we have
determined the effect of prior donor and recipient cytomegalovirus (CMV), hepatitis B virus (HBV), and
hepatitis C virus (HCV) exposure on the incidence of those viral infections after bone marrow transplantation
(BMT). The study included 63 patients presented to the BMT unit; 28 of them underwent transplantation and
35 were not transplanted. All serum markers of CMV, HBV, and HCV infections were monitored using ELISA
technique, as well as PCR-DNA for CMV, HBV and HCV RT-PCR techniques for HCV. The incidence of active CMV
and HCV was 11/28 (39%) and 6/28 (21%) in post-BMT recipients compared to 2/35 (6%) and 2/35 (6%) in the
35 untransplanted patients (P=0.00003 and P=0.05). Whereas active HBV infection was non significantly
(P=0.13) higher 3/28 (11%) in the BMT patients in comparison to 1/35 (3%) in untransplanted patients. Ten out
of the 19 (53%) of the CMV-seropositive recipients developed CMV reactivation compared to 1/9 (11%) of the
CMV-seronegative recipients who developed CMV seroconversion. In addition, 3/8 (38%) of the HBV-
seropositive recipients developed HBV reactivation in comparison to 0/20 of the HBV-seronegative recipients.
Moreover, 5/13 (39%) of the HCV-seropositive recipients developed HCV reactivation in comparison to 1/16
(6%) of the HCV-seronegative recipients who developed HCV seroconversion. In conclusion, previous exposure
to CMV, HBV, and HCV infections in the recipients of BMT patients were found to influence the risk of
developing those viral infections.
PMID: 23082480

Role of TNF-alpha as a survival prognostic marker in chronic lymphocytic leukemia

patients.

Singer MK; Assem M; Abdel Ghaffar AB; Morcos NY

Pro-inflammatory cytokines play a central role in the pathogenesis of chronic leukemia. This pilot study
assesses the potential value of measuring TNF-alpha, IL-6, IL-18 and CRP levels as prognostic markers for
disease monitoring in CLL patient. These parameters were evaluated in 45 CLL patients and 25 healthy control
subjects IL-6 on contraire to the other cytokines, was significantly higher (P<0.05) in patients compared to
controls. At hematological remission, only CRP was significantly reduced (P<0.005). IL-6 is inversely correlated
with Hb (P<0.05). In the meantime, IL-18 is correlated to splenomegaly, and CRP (P<0.05; for both). TNF-alpha
level in non-survived patients was significantly higher than both survived patients (P<0.05), and controls
(P<0.01). In conclusion, TNF-alpha can be potentially used as a survival prognostic factor in CLL.
PMID: 8704694

Schistosomiasis as a predisposing factor to veno-occlusive disease of the liver following

allogeneic bone marrow transplantation.

Mahmoud HK

Among 89 allogeneic bone marrow transplant recipients, veno-occlusive disease of the liver (VOD) was
diagnosed in 10 patients (11.2%). All cases (n = 5) with schistosomal hepatic periportal fibrosis detected by
pretransplant ultrasonography, developed severe fatal VOD in spite of normal initial liver functions and
absence of portal hypertension. The incidence of VOD among patients without previous schistosomal contact
was 5.95% (5/84). The relative risk to develop VOD was calculated to be 16.8-fold higher in patients with
previous schistosomiasis. Schistosomal hepatic periportal fibrosis may thus be added to the known risk factors
predisposing to the development of VOD in allogeneic transplant recipients.

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PMID: 16883441

Seroprevalence of herpes simplex virus types 1 and 2, Epstein-Barr virus, and

cytomegalovirus in children with acute lymphoblastic leukemia in Egypt.

Loutfy SA; Alam El-Din HM; Ibrahim MF; Hafez MM

Viral infection, especially caused by herpes viruses, is now recognized as an important cause of morbidity and
mortality in immunocompromised cancer patients. This study aimed at studying seroprevalence of 3 herpes
viruses Herpes simplex virus types 1 and 2 (HSV 1 and 2), Epstein-Barr virus (EBV), and cytomegalovirus (CMV)
in children with acute lymphoblastic leukemia (ALL).We conducted this study on 68 newly diagnosed pediatric
patients with ALL presented to the Pediatric Oncology Service of National Cancer Institute, Cairo University,
Egypt from November 2001 to June 2003. We used enzyme-linked immunosorbent assay in detecting HSV 1
and 2, CMV, EBV antibodies of both types immunoglobulin (Ig) M and IgG detection of DNA for both CMV and
EBV by polymerase chain reaction was carried out.High seroprevalence of HSV-1 and 2, CMV and EBV IgG
antibodies in both leukemic children and their control was observed (69%, 100%, 83%) and (80%, 100%, 95%).
Significantly higher percentage of HSV-1 and 2 IgM or reactivated infection was found among leukemic
children 17/68 (25%) compared with normal control 0%. Analysis showed that prevalence of HSV 1 and 2 IgG
increased from 18/33 (54%) in children <5 years to 11/13 (77%) in children >10 years, and reactivation of HSV-
1 and 2 increased with increasing age from 1/33 (3%) in children <5 years to 4/13 (30%) in children >10 year.
This was in contrast to seroprevalence of CMV and EBV IgG which were 100% and 83% in children <5 years. No
difference in seroprevalence was found among both gender, and no difference was found in leukemic patients
with granulocytopenia.The data show a higher exposure to HSV-1 and 2 both primary infections and
reactivation among ALL children. Therefore, acyclovir prophylaxis could be highly effective for seropositive
leukemic patients who are undergoing induction chemotherapy.
PMID: 19034339

Synergistic effect of methyltetrahydrofolate reductase (MTHFR) C677T and A1298C

polymorphism as risk modifiers of pediatric acute lymphoblastic leukemia.

Kamel AM; Moussa HS; Ebid GT; Bu RR; Bhatia KG

ALL is the most common pediatric cancer. The causes of the majority of pediatric acute leukemia are unknown
and are likely to involve an interaction between genetic and environmental factors. Therefore, unfavourable
gene-environmental interactions might be involved in the genesis of ALL. The aim of this work was to evaluate,
in a case-control study, whether the common polymorphisms in 5, 10-methylenetetrahydrofolate reductase
(MTHFR) namely (C677T and A1298C) and methionine synthase (MS) (A2756G) genes may play a role in
altering susceptibility to pediatric ALL as individual genes and in combination.DNA of 88 ALL patients (age < or
= 18 years) and 311 healthy control subjects was analyzed for the polymorphisms of MTHFR and MS genes
using PCR-RFLP method.The frequencies of the wild types of MTHFR 677CC, MTHFR 1298AA and MS 2756AA,
the homozygous genotypes of MTHFR 677TT, MTHFR 1298CC and MS 2756GG and heterozygous genotypes of
MTHFR 677CT and MS 2756AG showed no statistically significant differences between patients and controls.
The frequency of the MTHFR 1298AC heterozygous genotype was 25% among patients compared to 45.0%
among controls; the difference was found to be statistically significant (p value =0.001, O.R=0.382 & 95%
C.I=0.222-0.658). The frequency of the MTHFR1298AC heterozygous genotype plus 1298CC homozygous
genotype was 34% among patients compared to 54.3% among controls and the difference was statistically
significant (p value =0.001). A synergistic effect of 677CT and1298AC (CTAC) was observed, (p value=0.002)
with 3.65 fold protection (OR 0.273 & 95% C.I=0.155-0.9) compared to 2.6 folds for MTHFR 1298AC alone. This
protective effect of CTAC polymorphism was abolished when combined with MS 2756AA or AG.The present
study provided further evidence for the protective role of MTHFR 1298AC mutant alleles in acute
lymphoblastic leukemia in children (2.6 fold protection). This suggests that folate and methionine metabolism
play an important role in the pathogenesis of pediatric ALL. In contrast to the main bulk of literature, we did
not find any protective role of either MTHFR C677T or MS A2756G polymorphisms. This may reflect the ethnic
variation in both the polymorphism frequencies, variation in plasma level of folate, in addition to the possible
role of gene-environment interaction mainly dietary availability of folate. The synergistic effect of MTHFR

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1298AC and 677CT and its abolishment by MS 2756AA or AG further emphasizes that the interaction of genes,
rather than the polymorphism in any single one, determines risk susceptibility to disease.

PMID: 21863068

The Clinical Implications of Methylated p15 and p73 Genes in Adult Acute Lymphoblastic
Leukemia.

Abd El-Hamid TM; Mossallam GI; Sherisher MA

Aberrant methylation of promoterassociated CpG islands is an epigenetic modification of DNA which is

associated with gene silencing. It plays an important role in the leukemia pathogenesis. This phenomenon is
frequently observed in acute lymphoblastic leukemia (ALL) and results in the functional inactivation of its
associated genes. The aim of this study is to investigate the frequency and the prognostic impact of p15 and
p73 genes methylation in adult acute lymphoblastic leukemia patients.Methylation-specific polymerase chain
reaction (PCR) was used to analyze methylation of the p15 and p73 genes in 51 newly diagnosed adult ALL
patients.The methylation frequencies of p15 and p73 genes at diagnosis were 41.2% and 27.5% respectively,
while concomitant methylation was detected in 14% of the patients. Concomitant methylation of p15 and p73
genes was associated with significant lower rate of CR compared to patients without methylation (57% versus
90%), p=0.008. Overall survival (OS) was not affected by p15 methylation, but was poorer with p73
methylation and the difference was near significant (p=0.059). For patients without meyhylation, the survival
benefit was significant when compared to patients with p15, p73 or both genes methylation (p=0.047). The
leukemia free survival was not affected by the methylation status of single gene p15 or p73, but tended to be
worse in patients with methylated p15, p73 or both genes when compared to patients without methylation
(p=0.08).Aberrant p73 promoter methylation is a potential prognostic factor in adult ALL patients. P15
methylation is frequent in Egyptian adult ALL patients, its concomitant methylation with p73 is of poor
prognostic significance. Identification of these molecular targets improve risk assessment and selection of
appropriate therapy. KEY WORDS: Methyaltion - p15 - p73 - Adult acute lymphoblastic leukemia.
PMID: 21415865

The Prognostic Significance of Combined Expression of ZAP-70 and CD38 in Chronic

Lymphocytic Leukemia.

Assem M; Abdel Hamid T; Kohla S; Arsanyos S

Following gene expression profiling which compared the two well established prognostic markers in CLL, ZAP-
70 and CD38 with unmutated and mutated IgVH, ZAP-70 has emerged as the most promising surrogate marker
for the IgVH mutation status. CD38 expression has also been suggested as a surrogate marker for the IgVH
mutation status.We aimed to investigate the impact of ZAP-70 and CD38 expressions as well as their combined
expressions on the treatment outcome and survival of our CLL patients.This study included 50 CLL patients as
well as10 normal volunteers as a control group. All patients were subjected to complete work up and
immunophenotyping to confirm the diagnosis. ZAP-70 and CD38 expressions were studied in (CD19+, CD5+) B
cells. Results were expressed as percent expression and mean flourecent index (MFI). Results were correlated
to the treatment outcome and survival as well as to other prognostic markers of CLL including TLC, Hb level,
platelets count, modified Rai staging at diagnosis, P53 and BCL 2.A significant association was found between
ZAP-70 percent expression and the diffuse pattern of bone marrow infiltration (p<0.002) as well as the P53
percent expression (p=0.005). A Significant increase in serum levels of LDH and B2M in ZAP-70 positive as
compared to negative groups was detected (p=0.049 and 0.007 respectively). A higher number of non-
responding patients was reported in the ZAP70 positive as compared to ZAP70 negative group (p<0.001). ZAP-
70 percent expression was significantly associated with shorter time to disease progression (TDP) and shorter
overall survival (p=0.025 and 0.029 respectively). A significant increase in serum levels of B2M in CD38 percent
positive as compared to negative group was encountered (p=0.045). CD38-MFI showed a significant
associations to advanced modified Rai staging at diagnosis (p=0.019) and to higher serum levels of both LDH
and B2M (p=0.03 and 0.05 respectively). CD38, either expressed as a percentage or as MFI, showed a
significant association with the non-responders (p=0.034 and 0.006 respectively). There was a significant

122
inverse relation between CD38 expression and time to disease progression (p=0.033) while no significant
relation was encountered with overall survival (p=0.197). Combined expression of both markers, ZAP-70+
/CD38+ was reported in 5 patients (10%) while ZAP-70- /CD38- expression was encountered in 24 patients
(48%). Patients with either ZAP-70+ or CD38+ represented 42% of the cases (21 patients).There were
significant differences between the three groups and the initial response to chemotherapy (p=<0.001) and the
pattern of bone morrow infiltration (p=0.015), while no significant relation was found with age, sex, modified
Rai staging at diagnosis or BCL2 percent expression. Patients with combined expression of ZAP-70 and CD38
had significantly shorter TDP and overall survival (p<0.001 and 0.03 respectively).ZAP-70 is one of the most
important prognostic markers in CLL, it appears to be more predictive of disease progression and poor
outcome than CD38 expression. Semi quantification of the CD38 antigen by flowcytometry greatly improves
the prognostic value of its expression. The combination of ZAP-70 and CD38 increases the prognostic power of
either alone. KEY WORDS: CLL - Prognostic factors - ZAP 70 and CD38.
PMID: 20424654

The Role of Type I Insulin Like Growth Factor Receptor (IGF-IR) in Adult and Childhood
Acute Lymphoblastic Leukemia.

Kamel MM; Hammam AA; Elhoseiny SM; Mokhles A; Mohsen E

Type 1 insulin like growth factor receptor (IGF-IR) is over expressed in many tumors including hematological
cancers. It is a critical signaling molecule for tumor cell proliferation and survival. Data suggest that IGF-IR
antibodies can effectively and specifically inhibit cancer cell growth in vitro and in vivo. Blockage of IGF-IR
expression could be a promising therapeutic approach for the management of cancer patients.To characterize
the expression pattern of IGF-IR gene in malignant lymphoblasts of children and adults suffering from ALL in
relation to clinical features at diagnosis.The expression of IGF-IR was analyzed in 60 patients with ALL, 30
childhood ALL (16 newly diagnosed and 14 in complete remission) and 30 adulthood ALL (15 newly diagnosed
and 15 in complete remission) together with 20 normal age and sex matched healthy controls using a Real-
Time Quantitative Reverse- Transcriptase Polymerase Chain Reaction (RTQ-PCR) to assess the possible relation,
association or correlation between IGF-IR expression and ALL clinical and laboratory features at diagnosis.IGF-
IR was expressed in all 60 patients with ALL; the expression levels of IGF-IR were significantly higher in newly
diagnosed patients than in patients in complete remission (CR) and controls (p < 0.001). There were no
statistically significant differences in the expression of IGF-IR between patients with different clinical and
laboratory features.IGF-1R seems to play a crucial role in patients with ALL since it is expressed in all ALL cases
(adulthood and childhood). Therefore, new therapeutic agents targeting IGF-1R may provide a better chance
for those patients. KEY WORDS: IGF-IR - Adult ALL - Childhood ALL - RTPCRT - Prognosis.
PMID: 20029467

ZAP-70 as a possible prognostic factor in childhood acute lymphoblastic leukemia.

Ebeid E; Kamel M; Moussa H; Galal U

Zeta-chain-associated protein (ZAP- 70) is a 70kD adaptor protein that acts quickly after T cell activation to
propagate signal. The role of ZAP-70 in Tcell function is well established, and in the previous years, this
molecule was considered to be T-cell specific. More recent data have documented a role of ZAP-70 in B cells.
Interest in ZAP-70 has grown since it has been shown, through gene expression profiling, that it is expressed in
a subset of cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).The aim of this study
was to investigate the expression of ZAP-70 in leukemic blasts of 50 newly diagnosed patients of B-lineage
acute lymphoblastic leukemia (ALL), and to assess the correlation between ZAP-70 expression and various
prognostic factors and outcome.This study included 50 pediatric patients with newly diagnosed B-lineage ALL.
They were 28 males (56% ) and 22 females (44% ) presented to the Pediatric Oncology Department, National
Cancer Institute, Cairo University, during the period from 2005 to 2007. The age range was 2 to 17 years with a
mean of 8.58+/-5.8 years and median 8 years. All patients were subjected at presentation to a full clinical
history and physical examination. Patients diagnosed with ALL were enrolled on St. Jude Total XV protocol:
standard risk and low risk according to results of primary investigation. Immunophenotyping was done using
monoclonal antibodies which were analyzed on Coulter XL (Panel included CD1, CD2, CD3, CD4, CD5, CD7, CD8,

123
CD10, CD19, CD22, Cytoplasmic m, anti k, anti l, CD13, CD33, anti classII MHC and TdT). Cases were considered
ZAP-70 positive when exhibiting a ZAP/GAPDH (Glyceraldehyde- 3-phosphate dehydrogenase) ratio >or=
0.13.The study revealed expression of ZAP-70 in 5/50 cases (10% ). There was no statistically significant
relation between ZAP-70 expression and the following: age, Total Leukocytic Count, hepatomegaly and
splenomegaly. There was a correlation however between ZAP-70- expression and sex. Four patients died of
disease progression: one patient with positive ZAP-70 expression and 3 patients with negative ZAP-70
expression. Fifteen patients (30% ) relapsed after achieving complete remission (CR) and 3 patients (6% ) did
not achieve CR. Four patients of those who relapsed had positive ZAP-70 expression. The 2.5 years DFS was
73.1% for negative ZAP-70 cases while it was 20% in positive ZAP-70 cases. There was a statistically significant
difference between 2.5-year DFS and ZAP-70 expression (p=0.048). The Overall Survival at 2.5-years for
negative ZAP-70 cases was 93.3% while it was 80% for positive ZAP-70 cases with p-value =0.27.Our results
show that in B-Lineage ALL, ZAP-70 expression correlates with a worse DFS and an increased relapse rate.
Furthermore, these results raise the need of prospective trials to evaluate the possibility of designing new
compounds targeting this protein.
Liver cancer studies

PMID: 17102821

A panel of molecular markers in hepatitis C virus-related hepatocellular carcinoma.

Elgendy SM; Hessien M; Elsherbiny MM; Abd El-Salam IM; El-Attar IA; El-Asser Ael-B

Hepatocellular carcinoma is triggered by many factors including infection with hepatitis C virus. The molecular
basis, however, of the development of HCV-related HCC remains unknown.This work was designated to
compare the circulating levels of some molecular markers between HCV-infected and HCV-free HCC
patients.We investigated 77 of HCC patients admitted to the National Cancer Institute, Cairo during the period
2002-2003. The plasma circulating levels of bcl-2, transforming growth factor beta 1 (TGF-beta1), vascular
endothelial growth factor (VEGF) and beta2-microglobulin (beta2- MG) were investigated in HCV related HCC
patients (n=40) compared to both HCV-free HCC patients (n=37) and a group of healthy subjects (n=20).
Additionally, the LOH at the mannose 6-phosphate/insulin like growth factor-II receptor (M6P/IGFIIr) was
investigated.The result did not predict a significant role of HCV infection on the circulating bcl-2 protein. In
both HCC and HCC/HCV groups a limited number of patients had high levels of bcl-2. TGF-beta1 level increased
particularly, but insignificantly in HCC associated with HCV infection. A similar pattern was obtained in the
levels of beta2-MG, however the difference between HCC and HCC/HCV patients was significant (p=0.001). The
infection with HCV was associated with a high incidence of LOH at M6P/IGFIIr site compared to HCV-free
patients. Although the level of serum VEGF was significantly higher in all HCC patients than in healthy control,
no significant difference, however was observed between HCV infected and HCV-free groups.In HCC patients,
HCV infection did not exclusively affect the levels of both bcl-2 and VEGF. TGF-beta1, beta2-MG and the LOH at
M6P/IGFIIr, however were higher in presence of HCV infection.
PMID: 21475468

Assessment of the Proliferative Marker Ki-67 and p53 Protein Expression in HBV- and HCV-
related Hepatocellular Carcinoma Cases in Egypt.

Mohamed WS; Omar MM; Khayri TM; Fakhr IM

Chronic HBV and HCV infections are the major risk factors for the development of HCC through a multistep
pathway that involves viral and non-viral dependent pathophysiological steps. Hepatic expression of the
nuclear proliferative marker ki-67 and the p53 oncoprotein were found to be associated with poor outcome.
So, the present study was done to evaluate the changes in expression of Ki-67 and p53 oncoprotein, and to
determine p53 gene mutation in HBV/HCV-related HCC Egyptian patients.Eight HBV-and 22 HCV-positive HCC
cases have been examined for the presence of p53 mutation by immunohistochemistry (IHC) and single-strand
conformation polymorphism (SSCP), followed by direct DNA sequencing. HCV were genotyped by LiPA-II.Our

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results have shown that the proliferative marker ki-67 LI and p53 were highly expressed and significantly
related to tumor grade in the Egyptian HCC cases (p<0.05). Also, p53 mutation was found in 16 HCC cases by
IHC and in 14 HCC cases by SSCP, only 11 patients showed p53 mutation by sequencing. The highest mutation
rate was scored for exon 7 (7 mutations) at codon 249; 4 out of 8 (50%) of HBV-related HCC cases and 3 out of
22 (13.6%) of HCV-related HCC cases, followed by exon 5 (3 mutations) at codons 133, 146, 176 in HCV-related
HCC cases, then exon 8 at codon 275 in HCV-related HCC cases. The concordance between the IHC and
sequencing analysis was 69%.The present study demonstrates the association between the proliferative
marker ki-67 and p53 expression with the tumor grade of Egyptian HBV/HCV-related HCC cases. Our results
also support the hypothesis that p53 mutations are rather a late event in the carcinogenesis. Also, they
suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the viral
infection.
PMID: 21781333

Characterization of chronic HCV infection-induced apoptosis.

Zekri AR; Bahnassy AA; Hafez MM; Hassan ZK; Kamel M; Loutfy SA; Sherif GM; El-Zayadi AR; Daoud SS

To understand the complex and largely not well-understood apoptotic pathway and immune system evasion
mechanisms in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and HCV associated chronic
hepatitis (CH), we studied the expression patterns of a number of pro-apoptotic and anti-apoptotic genes (Fas,
FasL, Bcl-2, Bcl-xL and Bak) in HepG2 cell line harboring HCV- genotype-4 replication. For confirmation, we also
assessed the expression levels of the same group of genes in clinical samples obtained from 35 HCC and 34 CH
patients.Viral replication was assessed in the tissue culture medium by RT-PCR, quantitative Real-Time PCR
(qRT-PCR); detection of HCV core protein by western blot and inhibition of HCV replication with siRNA. The
expression level of Fas, FasL, Bcl-2, Bcl-xL and Bak was assessed by immunohistochemistry and RT-PCR
whereas caspases 3, 8 and 9 were assessed by colorimetric assay kits up to 135 days post infection.There was a
consistent increase in apoptotic activity for the first 4 weeks post-CV infection followed by a consistent
decrease up to the end of the experiment. The concordance between the changes in the expression levels of
Fas, FasL, Bcl-2, Bcl-xL and Bak in vitro and in situ was statistically significant (p < 0.05). Fas was highly
expressed at early stages of infection in cell lines and in normal control liver tissues followed by a dramatic
reduction post-HCV infection and an increase in the expression level of FasL post HCV infection. The effect of
HCV infection on other apoptotic proteins started very early post-infection, suggesting that hepatitis C
modulating apoptosis by modulating intracellular pro-apoptotic signals.Chronic HCV infection differently
modulates the apoptotic machinery during the course of infection, where the virus induces apoptosis early in
the course of infection, and as the disease progresses apoptosis is modulated. This study could open a new
opportunity for understanding the various signaling of apoptosis and in the developing a targeted therapy to
inhibit viral persistence and HCC development.
PMID: 19347802

Crucial issues of hepatic artery reconstruction in living donor liver transplantation: our
experience with 133 cases at Dar El-Fouad Hospital, Egypt.

Amin AA; Kamel R; Hatata Y; Attia H; Marawan I; Hosney A; El-Malt O; Tanaka K

Hepatic artery (HA) reconstruction is a crucial step in living donor liver transplantation (LDLT). However, many
important aspects specific to this challenging step are still inadequately documented. From August 2001
through March 2007, we performed a total of 133 cases of LDLT at Dar El-Fouad Hospital. The magnifying
loupe was used for performing microanastomoses in the first 31 cases, and the operating microscope was used
for 98 cases. There were 128 adult and five pediatric patients. One hundred twenty-five patients received right
lobe grafts, and seven patients received left lobe grafts. One patient died intraoperatively and was excluded
from analysis. Arterial complications occurred in four patients of the first group (4/30, 13%) in the form of
early thrombosis. One patient underwent successful interventional thromboembolectomy, two patients
underwent surgical reexploration with revision of anastomoses; these three patients survived. The fourth
patient died from fulminant liver failure. Regarding the second group, all arterial anastomoses were patent
after reconstruction. Signal problems occurred in the form of intraoperative intermittent flow and

125
postoperative no diastole phenomenon. Our overall arterial complication rate was 4.5%; however, we lost only
one patient due to HA thrombosis (0.8%). Microsurgical reconstruction of the HA carries its own challenges.
The use of operating microscope reduces the risk of complications, and aggressive interference including
salvage surgery maximizes the success of HA reconstruction.
PMID: 19858727

Disease progression from chronic hepatitis C to cirrhosis and hepatocellular carcinoma is

associated with repression of interferon regulatory factor-1.

Zekri AR; Moharram RA; Mohamed WS; Bahnassy AA; Alam El-Din HM; Abo-Shadi MM; Zayed NA; El-
Magzangy H; Abdel-Aziz AO; Esmat G

Infection with hepatitis C virus (HCV) frequently results in a persistent infection, suggesting that it has evolved
efficient mechanism(s) for blocking the host cell's innate antiviral response. The immune response to virus
infection results in activation or direct induction of the interferon regulatory factors (IRFs), which are a family
of proteins involved in the regulation of interferon (IFN) and IFN inducible genes. IRF-3 and IRF-7 have been
shown to play an essential role in virus-dependent signaling, whereas IRF-1 is critical for proper IFN-dependent
gene expression. This study has been performed to show the expression profile of IRF-1, IRF-3, and IRF-7 in
Egyptian patients with HCV-related liver diseases and hepatocellular carcinoma (HCC).This study included 90
patients, who were positive for HCV infection by reverse transcription PCR, divided into three groups: group I
(Gr I) included 30 patients with chronic hepatitis C, group II (Gr II) included 30 patients with liver cirrhosis in
addition to group III (Gr III) of 30 patients with HCC. Reverse transcription PCR analysis was performed to
determine the expression profile of IRF-1, IRF-3, and IRF-7 genes extracted from the peripheral blood
mononuclear cells of those patients.IRF-1expression was significantly higher (P<0.001) in patients of Gr I
(86.6%) compared with those in Gr II (46.7%) and Gr III (36.7%), whereas IRF-3 expression was significantly
higher (P<0.005) among patients of Gr II (73.3%) in comparison with that in Gr I (50%) and Gr III (36.7%). In
contrast, although expression of IRF-7 was higher in Gr II than in the other groups, there was no statistically
significant difference (P > 0.05).Alterations in IRFs expression might be considered as markers associated with
a higher risk of cirrhosis in patients with chronic HCV infection. Expression of IRF-1 and IRF-3 were more
prevalent in patients with chronic HCV and cirrhosis, respectively, in comparison with HCC patients. Thus, IRF-1
could be nominated as one of the tumor suppressor factors and could aid in the early detection of HCC.
PMID: 18959789

Genetic profile of Egyptian hepatocellular-carcinoma associated with hepatitis C virus

Genotype 4 by 15 K cDNA microarray: preliminary study.

Zekri AR; Hafez MM; Bahnassy AA; Hassan ZK; Mansour T; Kamal MM; Khaled HM

Hepatocellular carcinoma (HCC) is a preventable disease rather than a curable one, since there is no well-
documented effective treatment modality until now, making the molecular study of this disease
mandatory.We studied gene expression profile of 17 Egyptian HCC patients associated with HCV genotype-4
infection by c-DNA microarray. Out of the 15,660 studied genes, 446 were differentially expressed; 180 of
them were up regulated and 134 were down regulated. Seventeen genes out of the 180 up-regulated genes
are involved in 28 different pathways. Protein phosphatase 3 (PPP3R1) is involved in 10 different pathways
followed by fibroblast growth factor receptor 1 (FGFR1), Cas-Br-M ecotropic retroviral transforming sequence
b (CBLB), spleen tyrosine kinase (SYK) involved in three pathways; bone morphogenetic protein 8a (BMP8A),
laminin alpha 3 (LAMA3), cell division cycle 23 (CDC23) involved in 2 pathways and NOTCH4 which regulate
Notch signaling pathway. On the other hand, 25 out of the 134 down-regulated genes are involved in 20
different pathways. Integrin alpha V alpha polypeptide antigen CD51 (ITGVA) is involved in 4 pathways
followed by lymphotoxin alpha (TNF superfamily, member 1) (LTA) involved in 3 pathways and alpha-2-
macroglobulin (A2M), phosphorylase kinase alpha 2-liver (PHKA2) and MAGI1 membrane associated guanylate
kinase 1 (MAGI1) involved in 2 pathways. In addition, 22 genes showed significantly differential expression
between HCC cases with cirrhosis and without cirrhosis. Confirmation analysis was performed on subsets of
these genes by RT-PCR, including some up-regulated genes such as CDK4, Bax, NOTCH4 and some down-

126
regulated genes such as ISGF3G, TNF, and VISA.This is the first preliminary study on gene expression profile in
Egyptian HCC patients associated with HCV-Genotype-4 using the cDNA microarray. The identified genes could
provide a new gate for prognostic and diagnostic markers for HCC associated with HCV. They could also be
used to identify candidate genes for molecular target therapy.
PMID: 10628830

Hepatitis C virus genotyping in relation to neu-oncoprotein overexpression and the

development of hepatocellular carcinoma.

Zekri AR; Bahnassy AA; Shaarawy SM; Mansour OA; Maduar MA; Khaled HM; El-Ahmadi O

The distribution of hepatitis C virus (HCV) genotypes among Egyptian patients positive for anti-HCV was
determined and their influence, when combined with neu-oncoprotein overexpression, on the development of
hepatocellular carcinoma (HCC) was examined. The study groups included asymptomatic carriers (ASC) and
patients with chronic active hepatitis (CAH) and HCC. HCV genomes were detected in the sera of 27 ASC, 29
CAH and 33 HCC patients known to have HCV infection defined by EIA and recombinant immunoblotting
techniques (Inno-LiA) as well as by reverse transcriptase (RT)-PCR. The HCV genotype was determined by a
reverse hybridisation technique (Inno-LiPA I and II), whereas neu-overexpression was detected by the
Oncogene Science EIA Kit. Eighty-nine patients were eligible for HCV genotyping; 75 patients (84.3%) were
infected with a single genotype, including 1a in 11 patients (12.4%), 1b in 2 patients (2.2%) and 2a in 10
patients (11.2%). Genotype 4 (a or c+d) was detected in 51 patients (57.3%) and only one patient had
genotype 10a (1.2%). Fourteen patients (15.7%) showed mixed infection; eight of them had 1a+4 (a or c+d)
and four had 2a+4 (a or c+d); the remaining two cases had 1a+2a and 1b+2a. The results revealed an increased
incidence of genotype 4 in CAH and HCC patients in comparison with ASC. There was also a significant
overexpression of neu-oncoprotein in CAH and HCC patients compared with ASC, which was significantly
associated with subtype 4 infection. The results suggest that infection with subtype 1a and 4 HCV may be
considered a risk factor for the induction of neu-overexpression and subsequent development of HCC.
PMID: 16246194

Hepatitis C virus-NS3P in relation to p53, p21waf, mdm2, p21-ras and c-erbB2 in

hepatocarcinogenesis.

Bahnassi AA; Zekri AR; El-Houssini S; Mokhtar NM; Abdel-Aziz AO; Sherif GM; El-Mishad AM; Khaled HM

The non-structural protein 3 (NS3P) of hepatitis C virus (HCV) genome was linked to the neoplastic
transformation of normal hepatocytes in chronically infected patients. However, the exact mechanisms
involved in this process are unidentified yet, especially in the Egyptian population where the commonest type
is genotype 4.We investigated 32 HCV reverse transcriptase-polymerase chain reaction (RT-PCR) positive
hepatocellular carcinoma (HCC) cases and 18 morphologically normal hepatic tissues distant to tumors (MNT)
for the correlation between HCV-NS3P, p53, p21(waf), mdm2, p21ras and c-erbB2 and DNA content by
immunohistochemistry and image analysis.The NS3P expression was lower in HCC (65.6%) than in MNT
(94.4%) patients. The expression level of studied genes in HCC was: p53 (56.25%), p21(waf) (43.7%), mdm2
(59.4%), p21-ras (73.3%) and c-erbB2 (75%). Whereas in MNT, it was 22.2, 61.1, 44.4, 41.2 and 77.8%,
respectively. The NS3P expression showed a significant correlation with the presence of cirrhosis, chronic
active hepatitis (CAH) and tumor grade (P < 0.05). c-erbB2 overexpression and p21(waf) loss were higher in
MNT than in HCC patients, however, this did not reach a statistically significant level. There was a statistically
significant correlation between NS3P, c-erbB2 and p21(waf) (P < 0.01). There was also a significant correlation
between p21(waf) loss and CAH (P = 0.01) as well as between mdm2, c-erbB2 and cirrhosis (P = 0.025 and
0.001) in HCC cases. There was a statistically significant difference in the ploidy status between HCC and MNT,
but there was no significant relationship between the ploidy status and other clinicopathological features.The
carcinogenic effect of NS3P is probably exerted at an early stage of HCC possibly through a pathway involving
c-erbB2 and p21(waf) alterations. In contrast, p53, p21ras and mdm2 alterations are late events in
hepatocarcinogenesis and are usually associated with an aggressive phenotype.

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PMID: 18689276

Impact of SEN virus on immunoblot INNO-LIA HCV reactivity pattern and disease outcome
in Egyptian hepatocellular carcinoma patients.

Alam El-Din HM; Abo-Shadi MA; Helal A

Recently, a novel virus designated SEN virus (SENV), which is thought to be related to posttransfusion
hepatitis, was discovered. The aim of the present study was to investigate the prevalence and clinical
significance of 2 SENV variants (SENV-D and SENV-H) in patients with hepatocellular carcinoma (HCC) and
healthy adults. Also, to investigate the possible effect of SEN virus on the humoral immune response against
different proteins of HCV through analyzing reactivity patterns of the confirmatory INNO-LIA HCV Ab III update
in relation to SEN viremia. We investigated SEN virus infection in 41 patients with HCC (25 males and 16
females) and twenty healthy blood donors (12 males and 8 females). All samples were taken from the National
Cancer Institute, Cairo University. We used semi nested polymerase chain reaction (PCR) amplification to
detect SENV-D and SENV-H strains in serum. All patients were tested against HCV antibody by ELISA and HCV
viremia by RT-PCR. Furthermore, nineteen patients positive for HCV antibody by EIA (10 positive for SEN DNA
and 9 non viremic for SEN) were confirmed in the immunoblot assay. SENV DNA was detected in 68 % (28 of
41) of patients with HCC and in 64 % (21 of 33) HCV-related HCC, in comparison to 5% (1 of 20) healthy blood
donor populations. The blood biochemical parameters, and performance status did not differ significantly
between the SENV DNA-positive and- negative patients. However, the overall survival rate was 50 % after two
years follow up in SENV DNA-positive and 14 % in SENV DNA-negative HCC patients. Reactivity to NS5 and E2
were less (22 % and 44 % of cases) in SENV negative cases, than in SENV positive cases (70 % and 80 % of
cases, respectively). In conclusion, SENV DNA seems to be highly prevalent among Egyptian HCC patients.
Cross reactivity between SENV proteins and HCV NS5, E2 or the increased immune response in SENV positive
cases and consequently the increased reactivity to HCV NS5 and E2 proteins could not be ruled out. Although
there was no apparent effect of SENV on biochemical tests, survival rates of SENV DNA-positive HCC patients
were higher thannegative cases, which might be due to other factors affecting survival in our Egyptian HCC
patients.
PMID: 22776841

Laparoscopy with laparoscopic ultrasound for pretreatment staging of hepatic focal

lesions: A prospective study.

Soliman HO; Gad ZS; Mahmoud AM; Farahat AM; Abdelrazek NM; Gareer WY

The need for accurate intrahepatic staging is crucial for patients with primary or secondary hepatic
malignancies. Currently available data indicate that laparoscopy with laparoscopic ultrasound provides
information similar to that obtained by intraoperative ultrasound and that it is able to identify small
intrahepatic lesions not diagnosed by preoperative conventional imaging techniques.To determine the role of
preoperative laparoscopy and laparoscopic ultrasonography in patients with potentially resectable hepatic
focal lesion or candidate for radiofrequency ablation based on preoperative imaging.From March 2004 to
March 2007, 55 patients with potentially resectable hepatic focal lesions were candidates for exploratory
laparotomy based on preoperative abdominal ultrasonography and triphasic spiral CT. All cases were then
reevaluated prior to surgery using laparoscopy and laparoscopic ultrasound. All these procedures were
performed within a time period of no more than 4 weeks. The data obtained were compared to those
obtained by the preoperative conventional imaging studies as regards the presence of satellites,
subcentimetric lesions, newly discovered deep parynchymatous lesions, liver condition, portal vein
thrombosis, nodal metastases, ascites, peritoneal implants, size and site of the primary lesion.After performing
ultrasound-guided laparoscopy, fourteen patients proved to be unfit for surgical resection or ablation, seven
patients showed newly discovered focal lesions, five patients proved to have satellites around the tumor and
peritoneal deposits, one patient had ascites and one patient had been falsely diagnosed as HCC, proved to
have had a liver abscess.Preoperative laparoscopy and laparoscopic ultrasonography as an adjunct to
preoperative imaging techniques provide more accurate staging for patients with potentially resectable
hepatic focal lesions.

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PMID: 15918183

Mismatch repair genes (hMLH1, hPMS1, hPMS2, GTBP/hMSH6, hMSH2) in the

pathogenesis of hepatocellular carcinoma.

Zekri AR; Sabry GM; Bahnassy AA; Shalaby KA; Abdel-Wahabh SA; Zakaria S

DNA mismatch repair (MMR) is an important mechanism for maintaining fidelity of genomic DNA.
Abnormalities in one or more MMR genes are implicated in the development of many cancers. We
investigated the role of expression of MMR genes (hMLH1, hPMS1, hPMS2, GTBP/hMSH6, hMSH2) in
hepatocellular carcinogenesis.We evaluated the expression level of MMR genes in 33 hepatocellular carcinoma
(HCC) cases using the multiplex reverse transcription (RT) PCR assays, as well as in 16 cases of normal adjacent
hepatic tissues. beta-actin gene was used as an internal control and calibrator for quantification of gene
expression.Out of the 33 studied cases, 25 were HCV positive and 30 (90.9%) showed reduced expression in
one or more of the studied MMR genes. Reduced expression was found in hMSH2 (71.9%), hMLH1 (53.3%),
GTBP (51.1%), hPMS2 (33.3%) and hPMS1 (6%). A significant correlation was found between reduced
expression of hPMS2 (P = 0.0069) and GTBP (P = 0.0034), hPMS2 and non-cirrhosis (P = 0.0197), hMLH1 and
high grade. On the other hand, 57.1%, 50%, 20%, 18.8%, and 6% of the normal tissues distant to tumors
showed reduced expression of hMSH2, hMLH1, GTBP, hPMS2, and hPMS1 respectively. Multivariate analysis
revealed a significant correlation between the expression level of hMSH2 (P = 0.008), hMLH1 (P = 0.001) and
GTBP (P = 0.032) and HCC, between hPMS2, GTBP and HCV-associated HCC (P<0.001, 0.002).Reduced
expression of MMR genes seems to play an important role in HCV-associated HCC. hPMS2 is likely involved at
an early stage of hepatocarcinogenesis since it was detected in normal adjacent tissues. Reduced expression of
hPMS2 provides a growth advantage and stimulates proliferation which encourages malignant transformation
in non-cirrhotic HCV-infected patients via acquisition of more genetic damages.
PMID: 15912149

Multidisciplinary treatment in children with non-metastatic hepatoblastoma: treatment

results at the National Cancer Institute, Cairo University.

Zamzam MA; Elmalt O; Aboul Kassem H; Nouh A; El-Basmy A

The aim of this study is to evaluate our experience at the NCI, Cairo University in the management of non-
metastetic hepatoblastoma (HB). Also to improve survival of children with HB and reduce the operative
morbidity and mortality by using preoperative chemotherapy.After biopsy and assessment of the extent of
disease, all patients were treated with a 6-hour continuous intravenous infusion of cisplatin (PLA) 90mg/m2 on
day one followed by doxorubicin (DO) 20mg/m2 per day administered as 1- hour infusion on days 2,3 and 4.
After four courses of preoperative chemotherapy, patients were reassessed. Whenever possible, the primary
tumor was resected and the treatment was completed with two more courses of chemotherapy.Twenty
children with HB were registered between January 1999 and December 2000, the median age at diagnosis was
12 months (range, 40 days to 11 years). All the 20 patients had received preoperative chemotherapy (PLADO).
Fifteen patients (75%) showed partial response with tumor shrinkage and serial decrease of serum alpha-
fetoprotein levels. Sixteen patients underwent surgery, fourteen of them had complete resection of the
primary tumor (87.5%). The median duration of followup was 26 months (range 1-55 months). The three year
disease-free survival was 68.4% and event-free survival was 65%.We can advocate the use of PLADO
chemotherapy and delayed surgery to be the standard treatment for children with HB. Other treatment
programs should be measured against this standard.
PMID: 21371325

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 Occult HBV infection among Egyptian hepatocellular carcinoma patients.

Hassan ZK; Hafez MM; Mansor TM; Zekri AR

Occult HBV infection accelerates the progression of liver fibrosis, cirrhosis, and finally leading to hepatocellular
carcinoma (HCC). This study analyzed the occult HBV-genotypes in HCC patients.To achieve our objective,
matched serum and tissue samples were collected from 40 HCC patients. Three sets of primers were used for
the HBV-DNA detection by nested-PCR, which cover the HBV-genome; Core, Surface and X genes. Genotyping
system based on PCR using type-specific primers was applied on HBV-DNA positive samples.Intrahepatic occult
HBV-DNA was detected in 62.5%, whereas; Serum occult HBV-DNA were detected in only 22.5% of HCC
patients. In patients' positive for both anti-HBs and anti-HBc, 10% had occult HBV in serum. In serologically
negative HCV patients, 63% had intrahepatic HBV-DNA, and 21% had HBV-DNA in serum samples. HBV-
genotype D (32%) and B (24%) attributed predominantly to intrahepatic HBV infections in HCC patients,
whereas HBV-genotype A (4%) and C (8%) infections were the least observed.This is the first study to show the
genotypes of occult HBV infection in HCC Patients. We suggest that B or D may influence the outcome of HBV
infection which may lead to the development of HCC.
PMID: 17237848

p53 mutation in HCV-genotype-4 associated hepatocellular carcinoma in Egyptian

patients.

Zekri AR; Bahnassy AA; Madbouly MS; Asaad NY; El-Shehaby AM; Alam El Din HM

HCV-associated hepatocellular carcinoma (HCC) is a common neoplasm in Egypt where genotype-4 is

prevalent. In the present study the incidence and pattern of p53 mutations was assessed in relation to HCV-
genotype- 4 in Egyptian HCC patients. We investigated 25 HCV positive HCCs for p53 mutations/overexpression
in relation to HCV-NS3 by immunohistochemistry, SSCP and sequencing. Genotyping was done using LiPA-II
and TRUGENE 5' NC' sequencing kit. Results were correlated to standard clinicopathologic prognostic factors
for HCC. Thirteen cases showed p53 overexpression, and 10 showed p53 mutation (13 mutations) by
sequencing (72% concordance). The highest mutation rate was in exons 6 and 7 (30%) followed by exons 5 and
8 (20%). Mutations included 3 transitions, 5 transversions, 3 deletions, and 2 insertions. All exon 7 mutations
were at codon 249 specific for AFB1 (AGG-->AGT, Arg-->Ser) and codon 248 specific for vinyl chloride
contamination (CGG-->TGG, Arg-->Trp). Other mutations reported are novel. Immunostaining for HCV NS3 was
detected in 19 cases independent of p53 mutation. p53 aberrations were significantly associated with poor
prognostic factors for HCC. However, no specific pattern for p53 mutations was observed in HCV genotype 4-
associated HCC and no significant relation between p53 mutations, HCV-NS3 expressions or any HCV sub-
genotype-4 sequence.
PMID: 18053271

Prevalence of transfusion transmitted virus (TTV) genotypes among HCC patients in

Qaluobia governorate.

Hafez MM; Shaarawy SM; Hassan AA; Salim RF; Abd El Salam FM; Ali AE

Transfusion Transmitted virus (TTV) is a novel single-stranded DNA virus that was identified in patients with
post-transfusion hepatitis of non-A-G type. Clinical significance of TTV infection was analyzed in Egyptian
hepatocellular carcinoma (HCC) patients. The present study attempted to clarify these issues in Egypt,
particularly in Qaluobia governorate, a country known for its high endemicity of liver disease and hepatotropic
viruses.TTV are determined in the serum of 60 samples obtained from HCC and liver cirrhosis (LC) patients and
30 healthy individuals. TTV DNA is amplified by nested-PCR with TTV-specific mixed primers derived from the
conserved open reading frame 1 (ORF1) region followed by digestion with restriction enzyme. Using the
enzymes HaeIII, DraI, EcoRI and PstI, we are able to distinguish between the four TTV genotypes.The positive
rate of TTV detection was 46.7%, 40% and 36.7% among HCC, LC patients and healthy individuals respectively.
The more prevalence genotype was detected in the positive serum samples was genotype 1 (35.7%) in HCC

130
patients, (50%) in LC and (63.3%) in healthy individuals, Genotype 5 (21.4%), (25.5%) and (18.2%) in HCC, LC
and healthy individuals respectively.This study indicates that TTV is commonly present in adult patients with
HCC and LC as well as healthy individuals. The most prevalence TTV genotype is genotype 1. It seems that the
infection neither contribute to the severity of liver disease no to the causation of HCC.
PMID: 21701780

Serum levels of β-catenin as a potential marker for genotype 4/hepatitis C-associated

hepatocellular carcinoma.

Zekri AR; Bahnassy AA; Alam El-Din HM; Morsy HM; Shaarawy S; Moharram NZ; Daoud SS

The global rising incidence of hepatocellular carcinoma (HCC), which parallels the increase of hepatitis C virus
(HCV) prevalence, has sparked a renewed interest in discovering additional HCC serum markers. In this study,
we investigated the clinical use of serum E-cadherin, ICAM, MMP-2, VEGF, OPN and β-catenin as potential
diagnostic makers for HCV/genotype 4-associated HCC. Twenty cases of healthy subjects, 11 cases with
asymptomatic HCV/genotype 4 carriers (ASC), 28 chronic hepatitis (CH) cases and 32 patients with HCC were
enrolled in this study. Serum levels of proteins were measured by a sandwich-enzyme-linked (ELISA) assay. The
diagnostic accuracy of each candidate marker was evaluated using receiver-operating characteristic (ROC)
curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). We
demonstrated that serum β-catenin levels were significantly elevated in patients with HCC compared to those
with CH, ASC and healthy controls. Among the six studied markers, β-catenin was also found to be the only
marker that can significantly discriminate between patients with HCC and those with CH; therefore, β-catenin
could be considered as a potential marker for early diagnosis of HCV-associated HCC in patients infected with
HCV genotype 4.
PMID: 21801719

The role of cyclins and cyclin dependent kinases in development and progression of
hepatitis C virus-genotype 4-associated hepatitis and hepatocellular carcinoma.

Bahnassy AA; Zekri AR; Loutfy SA; Mohamed WS; Moneim AA; Salem SE; Sheta MM; Omar A; Al-
Zawahry H

Altered cell cycle regulatory genes expression contributes to HCV-associated liver disease. We sought to assess
the role of cyclins and cyclin dependent kinases (CDKs) in HCV-associated CH and HCC. Aberrant expression of
cyclins A, E, D1, CDK2 and CDK4 was assessed by immunohistochemistry and differential PCR in HCV-associated
CH and HCC with pericarcinomatous foci (PCF). S phase fraction (SPF) was determined by flow cytometry.
Results were correlated with overall survival (OS) in HCC patients. In HCC, cyclins A, E, D1, CDK2 and CDK4
protein overexpression was detected in 52.8%, 52.8%, 69%, 47% and 58% compared to 36.1%, 33%, 56%,
27.8%, 55.6% for CH and 36.1%, 27%, 30.6%, 27%, 50% for PCF. Gene amplification was detected in 38.9%,
33% 66%, 33%, 44% of HCC compared to 27.8%, 25%, 44%, 27.8%, 36% in CH and 25%, 22.2%, 38.9%, 27%,
33% in PCF. A significant difference was reported between HCC, CH, NHT regarding cyclins A, E, D1, CDK2
(p=0.007, p=0.002, p=0.047, p=0.002) protein expression (ADD) and cyclin D1 amplification (p=0.009). Cyclins
A, E, CDK2 expression was associated with fibrosis in CH (p=0.004, p=0.02, p=0.012). Reduced OS was (ADD)
associated with cyclin D1 and cyclin A, grade, stage and metastasis (p=0.001, p=0.02, p=0.018, p=0.01,
p=0.001). CONCLUSIONS: Increased cyclins A, E, D1, CDK2 and CDK4 expression is important for HCV-
associated CH and HCC. Cyclin D1 and cyclin A are prognostic biomarkers associated with reduced OS in HCC.
Cyclin D1 aberration could identify high risk groups of CH patients prone to develop HCC.

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 Lung Cancer and Mesothelioma

PMID: 21802939

A double-blind, randomised, placebo-controlled phase III intergroup study of gefitinib in

patients with advanced NSCLC, non-progressing after first line platinum-based
chemotherapy (EORTC 08021/ILCP 01/03).

Gaafar RM; Surmont VF; Scagliotti GV; Van Klaveren RJ; Papamichael D; Welch JJ; Hasan B; Torri V;
van Meerbeeck JP;

EORTC study 08021/ILCP 01/03 evaluated the role of consolidation gefitinib, an oral tyrosine kinase inhibitor
(TKI), administered in patients with advanced non-small cell lung cancer (NSCLC), not progressing following
standard 1st-line chemotherapy.Patients with advanced NSCLC, not-progressing after four cycles of platinum-
based chemotherapy, were randomised to receive either gefitinib 250mg/d or matched placebo until
progression or unacceptable toxicity. The primary end-point was overall survival (OS). Secondary end-points
were progression-free survival (PFS) and toxicity. The study was powered to detect a 28% increase in OS from a
median of 11-14.1months (HR=0.78) and planned to randomise 598 patients to observe 514 deaths.After
inclusion of 173 patients, the trial was prematurely closed due to low accrual. Baseline characteristics for
gefitinib (n=86) and placebo (n=87) arms were well balanced. After a median follow up of 41months, the
difference in median OS in the gefitinib and placebo arms was not statistically significant (10.9 and 9.4months,
HR 0.83 [95% confidence interval (95% CI) 0.60-1.15]; p=0.2). The difference in median PFS significantly
favoured gefitinib (4.1 and 2.9months, HR=0.61, [95% CI 0.45, 0.83]), p=0.0015). Adverse events reported in
more than 10% of patients were rash (47% with gefitinib versus 13% with placebo) and diarrhoea (34% with
gefitinib versus13% with placebo).Despite its premature closure, this trial confirms previous evidence that
consolidation gefitinib is safe and improves PFS. However, no difference in OS was observed in this study
(NCT00091156).
PMID: 17305675

A new catheter technique for thoracic subarachnoid neurolysis in advanced lung cancer
patients.

El-Sayed GG

Subarachnoid neurolytic block (dorsal rhizotomy) was carried out in patients suffering from severe pain
unresponsive to analgesic therapy. An intrathecal catheter technique was performed in 20 patients with lung
cancer. Visual analog scale (VAS) for pain, patient satisfaction, and complications were recorded at 24 hours, 1
week, and 1, 2, and 3 months after procedure. VAS and patient satisfaction significantly decreased at
measured time points (P < 0.05). Duration of procedure was 20.3 +/- 6.4 minutes; no significant complications
were reported. This new intrathecal catheter technique for dorsal rhizotomy in advanced lung cancer patients
was an easily performed, effective, and safe technique in this setting.
PMID: 22504106

Aberrant expression of cell cycle regulatory genes predicts overall and disease free
survival in malignant pleural mesothelioma patients.

Bahnassy AA; Zekri AR; Abou-Bakr AA; El-Deftar MM; El-Bastawisy A; Sakr MA; El-Sherif GM; Gaafar RM

Malignant pleural mesothelioma (MPM) is a highly aggressive disease with a generally poor prognosis. Since
escape from cell cycle checkpoint control is common in several solid tumors, the present study was performed

132
to evaluate the role of some cell cycle regulatory genes in the development and progression of MPM.Aberrant
expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP), p53, mdm2 and Rb was assessed in 55 MPM cases
from Egypt using immunohistochemistry and PCR techniques. Results were correlated with clinico-pathological
prognostic factors, overall and disease free survival (OS&DFS).Altered expression of p14(ARF), p16(INK4A),
p21(waf), p27(KIP1), Rb, p53 and mdm2 proteins was detected in 50.9%, 54.5%, 53.3%, 61.8%, 53.3%, 58.2%,
and 50.8% of cases, respectively. SV40 infection significantly correlated with p14(ARF), 16(INK4A), p27(kip1)
and Rb aberrations (p=0.014, p=0.02, p=0.01, p=-0.01). Asbestos exposure significantly correlated with p53,
p21(waf) and mdm2 aberrations (p=0.001, p=0.03, p=0.02). On multivariate analysis PS ≥ 2, p27(KIP1) and Rb
aberrations were independent prognostic factors for OS (p=0.016, p=0.011, p=0.003) whereas on tumor
recurrence, p27(KIP1) and Rb aberrations were independent prognostic factors for DFS (p=0.002, p=0.03,
p=0.01).MPM is a complex disease characterized by multiple genetic aberrations; some of them involve cell
cycle regulatory genes. p14(ARF), p16(INK4A), Rb and p27(KIP1) seem to be involved in SV40-associated MPM
whereas mdm2, p53 and p21(WAF) are related to asbestos exposure. In addition to recurrence and PS, only
p27(KIP1)and Rb could be used as molecular prognostic markers in MPM.
PMID: 16116501

Acetyl-L-carnitine modulates bleomycin-induced oxidative stress and energy depletion in

lung tissues.

Sayed-Ahmed MM; Mansour HH; Gharib OA; Hafez HF

The usefulness of Bleomycin (BLM) as an important antineoplastic drug is usually limited to the development
of dose and time-dependent interstitial pneumonitis and pulmonary fibrosis. This study has been initiated to
investigate the possible protective effects of acetyl-L-carnitine (AC) against BLM-induced lung toxicity at an
early stage of its development.A total of 40 male Sprague-Dawley rats weighing from 200-250 g each, were
divided into 4 groups of 10 animals each. The first group received a daily i.p. injection of normal saline (0.5
ml/200 gm body weight) for 5 consecutive days and served as a control. Animals in the second, third and
fourth groups were daily injected intraperitoneally (i.p.) with BLM (15 mg/kg body weight), AC (250 mg/kg
body weight) and AC (250 mg/kg) 2 hrs before BLM (15 mg/kg) each for 5 consecutive days,
respectively.Treatment of rats with BLM (15 mg/kg) resulted in a significant 3.4 and 2.9 folds increase in
malondialdehyde (MDA) and nitric oxide (NO) production in lung tissue, respectively and a significant 39%,
35%, 54% and 44% decrease in reduced glutathione (GSH), superoxide dismutase (SOD), glutathione
peroxidase (GSHPx) and adenosine triphosphate (ATP), respectively as compared to the control group.
Treatment of rats with AC did not lead to any significant change in the mentioned biochemical parameters in
the lung tissue. Administration of AC two hours before BLM attenuated BLM-induced increase in MDA and NO
and the decrease in GSH, SOD, GSHPx and ATP in lung tissue.The present data suggests that the protective
effect of AC against BLM-induced acute lung injury could be, at least in part, due to its free radical scavenging
properties with the consequent improvement in mitochondrial function and ATP production.
PMID: 20672705

Analysis of the effect of radiotherapy on malignant pleural mesothelioma when given on

adjuvant or palliative basis.

El Hossieny HA; Aboulkasem F; Abdel Rahman M

This retrospective study was designed to evaluate the response and survival of malignant pleural
mesothelioma to radiotherapy when delivered with surgery and chemotherapy and when delivered alone or
with chemotherapy.A study for 110 patients with malignant pleural mesothelioma who presented to
radiotherapy department, National Cancer Institute, Cairo and received radiation therapy in the period
fromJanuary 1999 to July 2007.Forty-six patients (41.8%) received trimodality therapy (surgery & adjuvant or
neoadjuvant chemotherapy & adjuvant radiotherapy), while bimodality therapy (chemotherapy &
radiotherapy) in 38 patients (34.5%), while 26 patients (23.6%) received single modality therapy (palliative
radiotherapy), 22 patients (20%) developed local recurrence, 22 patients (20%) developed distant metastases
months, 14 patients (12.7%) developed local disease progression, 25 patients (22.7%) are still alive and free of
disease at time of reporting. The median survival for all patients was 16 months, while 12 and 18 months

133
overall survival were 63.6% & 31.8% respectively while median survival for stage II, III, IV patients was 16.5,
12.5 and 8 months respectively.Multimodality approach involving surgery, chemotherapy and radiotherapy
have been evaluated and proved its superiority in improving survival, especially in stages II.
PMID: 21503009

Bronchoplasty for primary broncho-pulmonary tumors.

Abdel Rahman AR

Parenchyma-sparing procedures are widely used in patients with low-grade malignancies of the airway when
anatomically suited lesions exist. This study was conducted to evaluate the short-term and the long-term
results of bronchoplastic procedures for patients with centrally located primary bronchopulmonary
tumors.Between 2000 and 2009, 36 patients with primary lung tumors required bronchoplasty were
retrospectively analyzed. Preoperative assessment included computed tomography (CT) of the chest,
bronchoscopy, and spirometry. Pre operative diagnosis was acheived by bronchoscopy for all patients,
mediastinoscopy was done for patients with primary lung cancer. Neo adjuvant chemotherapy was given for 6
patients with non small cell lung cancer (NSCLC).We had 15 males and 21 female, the mean age was 37 years
and the mean hospital stay was 7.2 days. Operative procedures performed were:Sleeve lobectomy in 30
patients (13 right, 17 left), partial sleeve right pneumonectomy in 3 and bronchial resection with
reanastomosis in 3 (2 left, 1 right). Twelve patients (33.3%) suffered post-operative problems. There was one
operative related mortality. Post operative pathology revealed: 27 patients with typical carcinoid, 2 with
atypical carcinoid, 4 with squamous cell carcinoma, 2 with adenocarcinoma and one with hamartoma.
Pathological TNM staging revealed: 17 patients with stage IA, 11 with IB, 5 with IIA and 2 with stage IIIA.
Follow-up data were available for all patients except two. Two patients died with disseminated disease 1.5
year and 2 years after surgery. The patient with hamartoma developed local recurrence 5 years later and re-
excision was done. One patient with lung cancer developed bone metastases and was alive with disease, while
the remaining 30 patients were alive and disease free. The overall 5 years survival was 83.3%.Bronchoplastic
resections achieve local control and long-term survival comparable to the standard resections in patients with
carcinoid tumor and NSCLC in anatomically suited lesions. KEY WORDS: Bronchoplasty - Primary - Lung -
Tumors.
PMID: 21132036

Delayed bronchial stump dehiscence following trimodality treatment for malignant

pleural mesothelioma.

Abdel Rahman AR; Gaafar RM; Zayed SB; Elhoseiny HM

Post pneumonectomy bronchopleural fistula represents the most serious complication in thoracic surgery.
Delayed fistula following tri modality treatment for mesothelioma is a serious problem regarding diagnosis and
treatment. Surgical repair of the bronchial stump through a lateral thoracotomy is a dangerous attempt due to
mediastinal fibrothorax and the risk of pulmonary artery stump damage.Between 2002 and 2007, 85 extra
pleural pneumonectomies for mesothelioma were performed. Only 58 patients completed the assigned tri
modality treatment, five of them developed delayed bronchial stump dehiscence. The interval between
primary surgery and stump dehiscence ranged from 6 months to 2 years.There were 4 right and one left sided
fistulae. We had 4 males and one female, the mean age was 41 years. Bronchial stump was stapled in 3
patients and hand sewn closure was used in the remaining 2. By bronchoscopy, no stump recurrence was
observed, but all patients with stapled bronchus had longer remaining stump. Empyema was present in all
patients. All complicated patients received 2 field post operative radiotherapy with mediastinal dose of 40-45
Grays. The initial treatment consisted of tube thoracostomy followed by exploration through the previous
thoracotomy incision with thorough curettage and wash of the infected space and removal of any exposed
infected mesh. Bronchial stump was identified and re sutured. Re enforcement of the bronchial stump was
done. Three patients required mechanical ventilation and 2 of them died. Surgery was successful in the
remaining 3 patients.Delayed bronchial stump dehiscence is liable to develop especially for right sided lesions.
Prophylactic augmentation of right sided stumps with vascularised muscle flap, shielding of pathology proven
negative stumps during radiotherapy and improvement of radiation techniques may improve the dose

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distribution. KEY WORDS: Delayed - Bronchial - Stump - Fistula - Tri modality - Mesothelioma.

PMID: 22776843

Diagnostic value of p53 and ki67 immunostaining for distinguishing benign from malignant
serous effusions.

Hafez NH; Tahoun NS

The differentiation of benign mesothelial cells from malignant tumor cells, primary, or metastatic, in serous
effusions based on cytomorphologic features alone can be problematic.This study was conducted to evaluate
the utility of p53 and ki67 immunocytochemical markers in differentiating benign from malignant tumor cells
in serous effusions.Archival Papanicolaou-stained smears of 91 pleural and peritoneal effusions were retrieved
from Cytology Unit, Pathology Department, NCI, Cairo University between 2008 and 2010. Forty-one cases
were positive for malignant cells and 50 cases were benign based on cytomorphologic features. Cases having
doubt were excluded from the study. The slides were destained and subjected to immunocytochemical
staining for p53 and ki67. Histologic sections of colonic carcinoma and tonsillar tissue were used as positive
control for p53 and ki67, respectively. Smears having >5% positively stained nuclei for p53 were taken as
positive and labeling index ⩾10% of ki67 was considered positive. Frequencies of the individual
immunocytochemical stains; p53 and ki67, in benign and malignant effusion as well as the combination of both
stains were calculated.p53 immunostaining showed nuclear positivity in 31 out of 41 malignant effusions
(75.6%) and in 3 out of 50 benign effusions (6%), p<0.005. p53 had 75.6% sensitivity, 94% specificity, 91.2%
PPV, and 82.5% NPV. ki67 immunostaining was positive in 30 out of 41 malignant effusions (73.2%) and in 17
out of 50 benign effusions (34%), p<0.05. ki67 had 73.2% sensitivity, 66% specificity, 63.8% PPV, and 75% NPV.
Cases were then analyzed for combined immunoprofile of p53 and ki67. Among the 24 cases that coexpressed
both antigens, 22 cases (91.7%) were malignant. Thirty two out of 34 cases (94.1%) that showed negative
results for both antigens were benign. For the cases that showed p53 immunostaining only, 9 out of 10 cases
(90%) were malignant. Fifteen out of 23 cases (65.2%) that showed ki67 immunostaining were benign.Benign
and malignant effusions showed significantly different staining pattern for p53 and ki67. When used
individually, p53 immunostaining can truly diagnose 75.6% and 94% of the malignant and benign cases,
respectively. ki67 immunostaining can correctly identify 73.2% and 66% of the malignant and benign cases,
respectively. When used in combination, 91.7% of p53 and ki67 positive cases were malignant while 94% of
p53 and ki67 negative cases were benign. Hence they could be used when the cytomorphology fails to provide
a definitive diagnosis.
PMID: 15950794

Epidemic of mesothelioma in Egypt.

Gaafar RM; Eldin NH

Asbestos has been recognized in Egypt since a long time as ancient Egyptians were using it in mummification.
Mesothelioma in Egypt is mainly attributed to environmental origin with a high incidence of women and young
adults affected. The incidence of mesothelioma is rising in Egypt. Epidemiological data for 635 malignant
mesothelioma (MM) patients over 4 years in the third Millennium were collected from the National Cancer
Institute (NCI), Cairo University and Abbassia Chest hospital. This number is more than four times the number
diagnosed in the previous 11 years at NCI. A clinicopathological study was done for 100 malignant pleural
mesothelioma (MPM) patients and showed that asbestos exposure and SV40 positivity were evident in 67%
and 60% of cases, respectively. The median survival was 14.3 months and the 1 and 2 year survival rates were
60% and 27%, respectively. Evaluation of p53 and pRb immunohistochemically showed that pRb alteration was
related to poor survival. Other biological prognostic factors such as EGFR, HER-2, glutathione S transferase
(GST) and MDR were evaluated in 50 cases. Overexpression of EGFR was correlated with lack of clinical benefit
and poor survival. GST potentiated the effect of EGFR on survival. The use of EGFR inhibitors may have a role in
the treatment of MM. Asbestos in Cairo is a silent killer and measures toward eliminating it entirely or at least
strictly controlling human contact with this dangerous carcinogen have to be taken in order to combat the

135
coming epidemic of mesothelioma in Egypt.
PMID: 17610473

Evaluation of simian virus-40 as a biological prognostic factor in Egyptian patients with

malignant pleural mesothelioma.

Zekri AR; Bahnassy AA; Mohamed WS; Hassan N; Abdel-Rahman AR; El-Kassem FA; Gaafar R

The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an
etiological role for SV40. However, exact pathogenetic mechanisms and possible prognostic value are not
clear. The purpose of the present paper was to investigate 40 Egyptian MPM patients for the presence of SV40
DNA, altered Rb expression and p53 gene status using immunohistochemistry and molecular techniques. The
relation between SV40, asbestos exposure, Rb, p53 and their contribution to the overall survival (OS) were also
assessed. SV40 DNA was detected in 20/40 patients and asbestos exposure in 31 patients; 18 of them were
SV40 positive. Altered p53 and Rb expression were detected in 57.5% and 52.5%, respectively, with no p53
mutation. Univariate analysis showed a significant correlation between OS and stage (P = 0.03), performance
status (P = 0.04), p53 overexpression (P = 0.05), asbestos exposure (P = 0.002) and SV40 (P = 0.001).
Multivariate analysis showed that when SV40 and asbestos exposure were considered together, only
combined positivity of both was an independent prognostic factor affecting the OS (P = 0.001). SV40 and
asbestos exposure are common in Egyptian MPM, denoting a possible etiological role and a synergistic effect
for both agents. Combined positivity for SV40 and asbestos exposure is an independent prognostic factor in
MPM, having a detrimental effect on OS.
PMID: 15716991

Gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer:
National Cancer Institute Cairo experience.

Gaafar RM; Hamza R; Khaled HM; Elserafi M; Mansour O; Karim NA; Abdelmoneim D; Elattar I;
Soliman S

The aim of the present study is to document the antitumor activity of the combination of gemcitabine and
cisplatin for the treatment of advanced NSCLC, asses the nature and severity of the side effects and elicit the
impact of the combination chemotherapy on progression free survival and overall survival.From August 1997
to August 2001, we conducted a phase II study of gemcitabine and cisplatin in 60 chemonaive patients (21
stage IIIB and 39 stage IV). For the first 34 cases, gemcitabine was given at a dose of 1,000 mg/m2 IV on days 1,
8 and 15 with cisplatin 100 mg/m2 on day 15, every 28 days. In the following 26 patients, the regimen was
modified to gemcitabine 1,250 mg/m2 days 1 and 8 and cisplatin 80 mg/m2 day 1, every 21 days.Patients
included 53 males and 7 females [median age, 52 years (range, 28-69)]. Twenty-nine had adenocarcinoma, 18
large-cell carcinoma and 13 squamous-cell carcinoma. Thirty-one patients had a performance status (PS) of 2
and 22 presented with weight loss. All patients were evaluable for response. Three patients achieved a
complete response (CR) and 22 had partial response (PR), giving an overall response of 41.7%, with a median
duration of 10 months (range, 4-46 months). The time to progression (TTP) was 8 months (range, 2-46
months), with a median overall survival of 9 months (range, 2-46 months). The one-year survival rate was
30.3% for the entire study population, 44% for responders, and statistically improved in patients with a PS of I
and those with no weight loss. A total of 255 cycles were administered (median, four cycles/patient).
Myelosuppression was significant (but manageable) with grade 3/4 neutropenia in 32.6% of cases, anemia in
18.6% and thrombocytopenia in 20.4%. Nonhematologic toxicity was limited to grade 3/4 nausea and vomiting
in 28.8% of cases and impaired liver enzymes in 13.6%.Inspite of the relatively poor prognostic characteristics
in the study population, gemcitabine and cisplatin, was an effective combination with tolerable, manageable
toxicity in advanced NSCLC.
PMID: 22263061

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Optimizing the use of epidermal growth factor receptor inhibitors in advanced non-small-
lung cancer (NSCLC).

Shash E; Peccatori FA; Azim HA

Lung cancer is the leading cause of cancer-related death in US and Europe. Treatment with a platinum-based
chemotherapy remains the standard of care, however with modest effect on quality of life and overall survival
which seldom reaches 1 year. Recently, several classes of targeted agents have emerged showing promising
results. In particular, agents targeting the epidermal growth factor receptor (EGFR) showed impressive clinical
activity both in the first line and salvage settings. However, it is evident that these drugs are not effective in all
patients. Putting into consideration the very high cost of these agents, there is an urgent need to provide
reliable tools to identify those patients that would derive the maximum benefit from these drugs. Several
predictive biomarkers were developed to identify those patients who would derive the maximal benefit of
these drugs. In this review we will discuss the recent updates on the role of EGFR inhibitors in the treatment of
advanced NSCLC and the role of predictive bio-markers in patient selection.
PMID: 18301454

Pleural mesothelioma: diagnostic problems and evaluation of prognostic factors.

Ismail HM; Nouh MA; Abulkheir IL; Abd El-Rahman Ael-R; Tawfik HN

Malignant pleural mesothelioma (MPM) in Egypt is mainly attributed to an environmental origin i.e exposure
to asbestos, with a high incidence in women and young adults. Immunohistochemistry and ultrastructural
features aid in the diagnosis. The p27Kip1 is a kinase inhibitor protein acting as a cell cycle regulator and a
putative tumor suppressor gene playing a critical role in the pathogenesis of several human neoplasms.A
clinicopathologic, immunohistochemical and ultrastructural study of mesothelioma in Egyptian patients, with
identification of different prognostic factors.Sixty-one cases of MPM were collected from the department of
pathology at the NCI, Cairo. Cases were stained by monoclonal antibodies against CK5/6, calretinin, vimentin,
CD15, CEA and p27.More than half (57.4%) of the patients were residents in endemic areas; 50.8% were of
epithelioid type. CK5/6 was positive in 45 (73.8%) cases, 39 (63.9%) cases were positive for vimentin, 49
(80.3%) cases were positive for calretinin. One case showed a focal weak positive reaction to CD15. None of
the cases stained for CEA. There was a statistically significant relation between p27 expression and the
histopathologic type (p=0.02) between overall survival and age (p=0.01), histopathologic type (p=0.02) and
stage (p=0.006).MPM is an increasing disaster in Egypt which is underestimated and neglected. A panel of
immunohistochemical markers should be used for proper evaluation. p27 has proven to be a potential biologic
prognostic marker for mesothelioma and more studies as regard its significance are recommended on a larger
number.
PMID: 18640302

Prevalence and pattern of lymph node metastasis in malignant pleural mesothelioma.

Abdel Rahman AR; Gaafar RM; Baki HA; El Hosieny HM; Aboulkasem F; Farahat EG; Nouh AM;
Mansour KA

The incidence and pattern of nodal metastases in mesothelioma are not well understood. This study was
conducted to evaluate the prevalence and pattern of nodal metastasis in mesothelioma patients.The study
included 53 patients with mesothelioma. The first 37 patients (group I) underwent combined modality
treatment without preoperative mediastinoscopy. The second group included 16 patients (group II) with
pretreatment mediastinoscopy.A total of 18 patients had positive lymph nodes, 12 in group I and 6 in group II;
of the latter, 4 had positive mediastinoscopy and 2 had positive nodes on final pathology. Postoperatively, a
mean of 14 nodes were dissected (range, 5 to 34). In the post-pleuropneumonectomy group, 6 of 14 patients
had positive hilar node metastases in addition to positive mediastinal lymph nodes. One patient had positive
hilar nodes only. Of the 49 patients operated on, only 7 had no lung invasion by pathologic evaluation, and
none had positive hilar nodes. The mechanism of spread of the disease to hilar nodes may be through lung

137
invasion and not due to direct spread from the pleura. This observation raises the possibility that mediastinal
nodes should be considered the primary station in patients with mesothelioma, whereas hilar node metastasis
necessitated lung invasion first.The pattern of nodal metastases may be different from that of lung cancer, and
multicenter studies are needed to evaluate this observation.
PMID: 19463624

Primary yolk sac tumor of the lung.

Abdel Rahman AR; Ebied EN; Nouh MA; Gal AA; Mansour KA

Yolk-sac tumor mimics the yolk sac of the embryo, and the presence of alpha fetoprotein in the tumor cells is
highly characteristic. We present an 18-year-old boy with primary pulmonary yolk-sac tumor diagnosed
postoperatively. A computed tomographic scan revealed a huge intrathoracic soft tissue mass 20 x 25 cm
occupying most of the left hemithorax. Two trials of computed tomographic-guided needle biopsy were
nonconclusive. A left upper lobectomy was performed with a complete tumor resection. Postoperatively, the
patient's alpha fetoprotein (AFP) was 10,512 IU/mL with gradual decline under chemotherapy. The patient is
alive 10 months after surgery and is disease free.
PMID: 19093231

Serum levels of epidermal growth factor and HER-2 neu in non small-cell lung cancer:
prognostic correlation.

Abdel Salam I; Gaballa HE; Abdel Wahab N

Lung cancer is still a leading cause of cancer related mortality all over the world with the majority of cases are
discovered at a late stage. Various panels of molecular prognostic markers are being studied to map the
association of these markers with response and survival. The aim of this study is to study levels of epidermal
growth factor receptor (EGFR), HER-2 neu in both serum and bronchoalveolar lavage (BAL) in patients with non
small-cell lung cancer (NSCLC), correlate their levels with clinical, pathological characters as well as prognosis.
A total of 30 patients with pathologically proven NSCLC were enrolled in this study in addition to ten normal
controls subjects and ten cases with benign pulmonary diseases as broncheicatsis, chronic obstructive
pulmonary disease. Results revealed significantly increased levels of EGFR and HER-2 neu in both serum and
bronco-alveolar lavage compared with controls. The levels were significantly higher in those with stages III, IV
compared with I, II, and in those with higher grades of the tumor. There was no statistically significant
correlation with performance status or survival. In conclusion, serum measurement of these markers is a
promising noninvasive technique which needs correlation with other methods of determination, measurement
at different chronological points during disease evolution to explore its full potential. Standardization of
techniques for determination of EGFR and HER-2 neu over-expression must become a priority in future studies
that should also include larger number of patients, conducted in a prospective manner together with
comparisons of various methods and correlation of protein expression with gene copy numbers.
PMID: 20424652

Soluble mesothelin-related protein in malignant pleural mesothelioma.

Azim HA; Gaafar R; Abdel Salam I; El-Guindy S; Elattar I; Ashmawy A; Khorshid O

Building-up evidence suggests that soluble mesothelinrelated protein (SMRP) carries a diagnostic and a
prognostic value in malignant pleural mesothelioma (MPM). Egypt suffers endemic asbestosis and thus this
study was conducted to evaluate the sensitivity and specificity of SMRP in patients with MPM and to correlate
this marker with known clinicopathological prognostic factors.During the period from January 2006 till March
2008, Serum samples were obtained from MPM patients presenting to the Egyptian National Cancer Institute,
Cairo University. Serum samples were provided from patients with breast cancer and from healthy individuals
to function as controls. The SMRP was assayed using the ELISA technique and correlations were made with
different clinico-pathological prognostic parameters.83 patients (50 MPM and 33 breast cancer) as well as 22

138
healthy individuals were enrolled in this study. Serum SMRP levels were not different between patients with
breast cancer and healthy controls (p > 0.05). However, there was a significant difference between MPM
patients and the other two groups (p < 0.0001). ROC analysis showed an AUC = 0.765 for differentiating
between the controls and MPM with a best statistical cut-off of 7.22nM/L (sensitivity = 66 % , specificity = 70.9
% ). The mean SMRP concentrations were significantly higher in patients with advanced disease (p = 0.038),
poor performance status (p = 0.017) and high alkaline phosphatase (p = 0.015). The mean SMRP
concentrations were also higher in males, elderly patients, asbestos-exposed patients, epithelioid subtypes
and patients with high platelet and leucocytic counts. However, these differences did not reach statistical
significanceThis study confirms that SMRP is of considerable sensitivity and specificity in Egyptian patients with
MPM. Higher levels are frequently seen in patients with high tumor burden, which could be helpful in
monitoring response to therapy. KEY WORDS: Malignant pleural mesothelioma (MPM) - Soluble mesothelin
related protein (SMRP)- Sensitivity - Specificity - Asbestos.
PMID: 17034953

Targeted therapy in advanced non-small cell lung cancer (NSCLC): where do we stand?

Azim HA; Ganti AK

Cytotoxic chemotherapy has helped improve the outcomes in patients with advanced non-small cell lung
cancer (NSCLC), but we seem to have reached a plateau with respect to the benefit obtained. Also, a large
subset of elderly patients and those with a poor performance status cannot tolerate these drugs at
recommended doses. There is a growing need to incorporate newer drugs with different mechanisms of action
and better safety profile. The epidermal growth factor receptor family (EGFR) and vascular endothelial growth
factor (VEGF) have been identified as potential targets and agents acting specifically against these targets have
been developed with the hope of improving outcomes. Although recent data with the small molecule EGFR
tyrosine kinase inhibitors have been disappointing, there have been instances of dramatic responses thereby
raising questions about the ideal patient to whom these drugs should be administered. Cetuximab, the anti-
EGFR antibody has shown promising results. Bevacizumab, the anti-VEGF antibody was the first drug to
demonstrate a survival benefit in first line treatment when added to chemotherapy. This review will briefly
discuss the important trials using these targeted agents in advanced NSCLC.
PMID: 18809226

Third generation triplet cytotoxic chemotherapy in advanced non-small cell lung cancer: a
systematic overview.

Azim HA; Elattar I; Loberiza FR; Azim H; Mok T; Ganti AK

Previous meta-analysis on three drugs combination for treatment of advanced non-small cell lung cancer
(NSCLC) did not demonstrate an improvement in survival, however many of the trials included in this meta-
analysis used older and less effective cytotoxic drugs. We conducted this analysis to compare the relative
efficacy of third generation triplet therapy with that of standard double therapy in the treatment of advanced
NSCLC.A MEDLINE search was performed using the search terms "lung cancer" and "randomized trials". Trials
not utilizing a third generation cytotoxic chemotherapeutic agent (paclitaxel, docetaxel, vinorelbine,
gemcitabine) were excluded. Pooled odds ratios (OR) for the objective response and toxicity rates were
calculated using the Mantel-Haenszel estimate. Pooled median ratios for median survival were calculated
using the weighted sum of the log-ratio of median ratios of individual study.We analyzed six randomized
comparative trials involving 1932 patients. Patients receiving triplet therapy had a significantly higher response
rate (OR: 1.33; 95% CI, 1.50-2.23; P<0.001). Incidence of grade III/IV hematological toxicity was higher with
triplet therapy. Non-hematological toxicities, with the exception of neuropathy, were similar. Median survival
of triplet therapy was not significantly different from doublet (MR: 1.10; 95% CI: 0.91-1.35; P=0.059).
Conclusions: Triplet therapy with third generation cytotoxic drugs is associated with higher tumor response
rate at the expense of increased toxicity. Although triplet therapy had a better overall survival compared to
doublet therapy, this did not reach statistical significance.

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PMID: 20347505

Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma.

Gaafar R; Bahnassy A; Abdelsalam I; Kamel MM; Helal A; Abdel-Hamid A; Eldin NA; Mokhtar N

Malignant pleural mesothelioma (MPM) is an asbestos related aggressive tumor. Asbestos causes genetic
modifications and cell signaling events that favor resistance to chemotherapy. A variety of receptor tyrosine
kinases have been identified to play a central role in various aspects of tumorigenesis. Epidermal growth factor
receptor (EGFR) is overexpressed in a variety of epithelial malignancies including lung cancer in which EGFR
aberrations not only predict response to EGFR tyrosine kinase inhibitors but also indicate tumor progression.
However in MPM, the role of EGFR is less clear. This study was designed to identify serum and tissue EGFR
levels in patients with MPM and to evaluate the relationship between serum and tissue EGFR levels and
clinicao-pathological prognostic factors and survival.We investigated 71 cases of MPM for EGFR expression in
tissue. Serum EGFR was assessed in 40 out of those 71 cases and 20 healthy subjects as a control. Pre-
treatment serum EGFR levels were measured using quantitative enzyme-linked immunosorbent assay. Tissue
EGFR protein overexpression was assessed by immunohistochemistry and gene amplification was assessed by
the chromogen in situ hybridization (CISH) technique. Results were correlated with the clinical-pathological
factors of the patients and overall survival (OS).Out of the 71 patients included in the study, 19 had undergone
extrapleural pneumonectomy. As for the rest of the patients, 46 received chemotherapy while 6 had only best
supportive care. EGFR immuno-reactivity was detected in 74.6% of the cases, 37 (52.1%) cases were positive
for EGFR gene amplification by CISH, 31 of them revealed moderate to high (++, +++) EGFR immuno-reactivity.
Elevated serum EGFR >2.5 ng/ml (the median concentration of EGFR in MPM) was reported in 45% of the
cases. The overall response rate (RR) for the 46 treated patients who received chemotherapy was 24.1%. After
a median follow up of 29 months, the median overall survival (OS) was 10 months. Elevated serum and tissue
EGFR is significantly associated with advanced disease stage. However neither EGFR overexpression in tissues
nor high serum levels were associated with survival rates.EGFR expression is a common feature in MPM
patients. High pre-treatment levels of serum EGFR are associated with advanced stage but not with reduced
OS. Detailed mutational analysis of EGFR on a larger number of patients is still needed to clarify the exact role
of EGFR in MPM patients.
PMID: 17264756

Treatment options for relapsed small-cell lung cancer.

Azim HA; Ganti AK

Small-cell lung cancer is a chemo-sensitive disease with a response rate ranging from 70 to 90% for first-line
treatment; however, relapses are very common and as a result long-term survival is poor. Chemotherapy has
demonstrated a benefit over the best supportive care, even in patients who have relapsed after initial
treatment with a platinum-based regimen. Agents currently being used in salvage therapy include topotecan,
cyclophosphamide, doxorubicin and vincristine regimen. In the last 5 years, several drugs have shown promise
in initial evaluation; however, randomized phase III trials would be needed to answer this question. Our
understanding of the biology of small-cell lung cancer has improved dramatically over the past few years and
this has translated into the developments of new therapeutic targets for this disease. Agents affecting several
targets, including bcl-2, matrix metalloproteinases, epidermal growth factors and angiogenesis, are being
studied currently and have the potential to change the treatment paradigms of this otherwise fatal
malignancy. This review focuses on the various current and future options, including cytoxic and targeted
agents, for salvage therapy in patients with this disease.
Lymphoma studies

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PMID: 10643541

A randomized EPOCH vs. CHOP front-line therapy for aggressive non-Hodgkin's lymphoma
patients: long-term results.

Khaled HM; Zekri ZK; Mokhtar N; Ali NM; Darwish T; Elattar I; Gaafar R; Moawad MS

The value of continuous-infusion chemotherapy (EPOCH) vs. the standard CHOP combination was evaluated in
78 patients with previously untreated aggressive non-Hodgkin's lymphoma in a randomized phase III clinical
trial.The EPOCH regimen given to 38 patients consisted of the drugs etoposide (50 mg/m2), vincristine (0.4
mg/m2), and doxorubicin (10 mg/m2), all given in a continuous infusion on days 1-4. Cyclophosphamide (750
mg/m2) was administered on day 6 as i.v. bolus, while prednisone was given orally 60 mg/m2 on days 1-6.
Courses were repeated every three weeks. CHOP was given to 40 patients as routinely prescribed.Forty-eight
patients were males and thirty were females. Their ages ranged from 19-75 years (median 45 years). Forty-
three (55%) had grade 2 and thirty-five (45%) had grade 3 pathologic subtype. Nine patients (12%) presented
with stage I, fourteen (18%) with stage II, forty (51%) with stage III, and fifteen (19%) with stage IV disease. The
different clinico-pathologic characteristics, including international index categories, were comparable in the
two groups. The number of courses given ranged between 3 and 9 (median 6) for both the EPOCH and CHOP
regimens. Complete remission (CR) was achieved in 19 (50%), and 27 (67%) of the 38 and 40 patients for both
the EPOCH and CHOP combinations, respectively. After a median observation time of 27 months, the four-year
overall and failure-free survival rates were 42% and 30% for the EPOCH and 71% and 54% for the CHOP
regimen (P = 0.006 and 0.1 for the overall and FFS rates, respectively). Toxicities were comparable and were
mostly of grades 1 and 2, except for hair loss, hematologic toxicities, and infectious episodes which were more
common in the EPOCH group. In the EPOCH group, overall survival rates were 55% vs. 22% (P < 0.04) at four
years for the low-risk (2 prognostic factors) and high-risk (> 2 factors) groups, respectively.Thus, it may be
concluded that continuous-infusion (EPOCH) chemotherapy did not improve treatment outcome over that of
the CHOP regimen for aggressive non-Hodgkin's lymphoma patients.
PMID: 21132031

CA 125, a New Prognostic Marker for Aggressive NHL.

Abd El Gawad IA; Shafik HE

CA 125 was evaluated in the sera of patients with aggressive NHL, together with LDH and β2m, in a trial to
assess its value in the diagnosis and follow-up, and to compare it to some prognostic factors.The study
included 78 newly diagnosed patients with diffuse large B cell non-Hodgkin's lymphoma (DLBCL), with age
range 18-60 years, and a WHO performance status of 0, I or II, in addition to twenty apparently healthy
controls. All patients received CHOP regimen for 6 cycles.The levels of CA 125 and LDH were significantly
higher in DLBCL compared to the control group (p-value = 0.031 and = 0.009, respectively). Cutoff levels used
were 20U/ml, 310 U/L, and 2mg/l for CA125, LDH and β2m, respectively. CA125 serum level was high in 55%,
LDH level in 72%, and β2m level in 62% of patients. As regards the stage, CA 125 was elevated in 17%, 52%,
80%, and 100% of patients in stage I, II, III, and IV, respectively. CA 125 was elevated in 81.3% of patients with
bulky disease, in 83.3% presenting with involvement of more than 1 extranodal site, and in 90% presenting
with effusion. The highest levels of CA125, LDH, and β2m were observed in stage IV, and lowest in stage I (p-
value<0.001, 0.005, and 0.154, respectively). There was also a significant positive correlation between CA 125
and LDH (p-value <0.001). CA 125 showed specificity of 80% with 95% CI (56- 94), and LDH showed sensitivity
of 72% with 95% CI (60-81). Complete response to treatment was achieved in 71.8% of our patients. Survival at
24 months was 78.2%. There was a statistically significant increase in survival in patients with CA125<20U/ml,
patients with LDH<310U/L, and patients with β2m<2mg/l (p-value = 0.006, 0.025, and 0.042, respectively). A
shorter disease-free survival was associated with increased CA 125 (p<0.001).CA125 was found to correlate
with stage, tumor bulk, involvement of more than 1 extranodal site, and presence of effusion. Elevated levels
of CA 125 and LDH were found to predict decreased survival. Initial measurement of CA125 may, therefore,
provide valuable prognostic information. KEY WORDS: CA125 - LDH - β2m, NHL - DLBCL.

141
PMID: 22099932

Clinical prognostic factors of diffuse large B cell non-Hodgkin lymphoma: A retrospective

study.

Abdelhamid T; Samra M; Ramadan H; Mehessin M; Mokhtar N

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL in Egypt. It represents about 49%
of NHL presenting to the National Cancer Institute (NCI), Cairo University. CHOP regimen is the standard
treatment used for NHL since the 1970s with only 30-40% overall survival. Recently, integration of Rituximab
became a standard of care for patients with DLBCL. However, its widespread use in developing countries is still
limited by the lack of financial coverage. Clinical prognostic factors, as well as the pathological markers, are
mandatory to individualize treatment.The aim of the study was to evaluate the clinical risk stratification
models including the age adjusted International prognostic index (aaIPI), patients profile and dose intensity
(DI) of Cyclophosphamide and Doxorubicin as effective tools for predicting the outcome and prognosis of our
DLBCL patients treated with first line CHOP regimen.This retrospective study included 224 patients with diffuse
large B cell lymphoma who were treated with 3-8 cycles of CHOP regimen at the Medical Oncology
Department, NCI, Cairo University during the time period from 1999 to 2006.One hundred and seventy-eight
patients (79.5%) achieved CR after the CHOP regimen with an observation period of 51months. The median
survival time was 12months. The OS and DFS at 2years were 82% and 68.8%, respectively. The univariate
analysis of predictive factors for response to treatment showed that the CR rate was significantly affected by
aa-IPI and its elements (performance status, stage & LDH), extranodal lesions and DI of Cyclophosphamide and
Doxorubicin. The CR rate was 96.9%, 91.2%, 73.9% and 55.6% in cases with aa-IPI 0, 1, 2 and 3, respectively
(p<0.001) and it was 82.4%, 81.9% versus 50% in cases with no extranodal site, one extranodal site and two
extranodal sites, respectively (p=0.01). As regard DI of Cyclophosphamide, with DI below or equal to the
median (249mg/m(2)/week) the CR rate was 69%, while with DI above the median the CR rate was 87.7%
(p=0.001). For Doxorubicin, the CR rate was 72.3% with DI below or equal to the median (16.5mg/m(2)/week),
however, it was 86.6% with DI above the median (p=0.008). The OS rate was significantly affected by aa-IPI as
it was 89.8% in cases of aa-IPI 0+1 versus 75.8% in those of aa-IPI 2+3 (p=0.03). DI of Cyclophosphamide and
Doxorubicin significantly influenced the OS. The OS rate was 74% with DI of Doxorubicin below or equal to the
median versus 96% in cases with DI above the median (p=0.02). For Cyclophosphamide the OS rate was 72.7%
with DI below or equal to the median versus 96.3% in cases with DI above the median (p=0.01). The tumor bulk
(with a median tumor size of 5cm) affected the OS, which was 91.23% versus 86.8% in the tumor bulk less than
and more than or equal to the median, respectively (p=0.05). By multivariate analysis of predictive factors for
response to treatment, the CR rate was significantly affected by the number of extranodal sites and the clinical
staging of diffuse large B cell lymphoma. However, OS rate was strongly associated with the bulk of the tumor
and the clinical staging of diffuse large B cell lymphoma.DI of Cyclophosphamide and Doxorubicin is important
in the future treatment regimen plan for DLBCL especially in high risk cases. In addition to aa-IPI and its
elements, extra nodal sites and bulk of the tumor proved to be significant predictors and prognostic factors for
DLBCL treatment outcome.
PMID: 17102814

Clinico-pathological features and outcome of management of pediatric gastrointestinal

lymphoma.

Morsi A; Abd El-Ghani Ael-G; El-Shafiey M; Fawzy M; Ismail H; Monir M

The purpose of this study is to evaluate pediatric GIT lymphomas as regards clinico-pathological features,
controversies in surgical treatment, role of chemotherapy and the prognostic features.This study included
forty three patients with pediatric GIT Non-Hodgkin's lymphoma collected over 7 years at the NCI Cairo
University between January 1997 and December 2003. The data of every patient included: Age, sex, presenting
symptoms and signs, preoperative investigations, extent of the disease at diagnosis and the type of resection
performed, histopathological examination, details of chemotherapy and state at follow up. Overall and disease
free survival were calculated and correlated with all parameters.The study included 30 boys and 13 girls with
median age 5.00 years (range: 0.4:17). The lesions were located in the small intestine (n=15), the large

142
intestine (n=14), the ileocecal region (n=10), stomach (n=2), and multifocally (n=2). Burkitt's lymphoma was
the commonest histological type (n=24). The majority were stage IIE and IIIE (22 and 17 respectively).
Exploration was done in thirty nine patients (complete resections were done in 23 cases, incomplete
resections (debulking) were done in 14 cases and in 2 cases only lymph node biopsies were done). All patients
received a sort of systemic chemotherapy. The median follow up duration was 44 months (range 4- 116
months). The only parameters that had significantly affected the overall survival were localized disease,
complete resection, earlier stage and response to chemotherapy with p values, (0.005, 0.001, 0.005 and
<0.001 respectively). As regards the disease free survival the only significant factor was localized disease
(p=0.035).The extent of disease at presentation is the most important prognostic factor in pediatric GIT
lymphoma. Surgery still plays an important role such as complete resection in localized disease, management
of complicated disease and diagnostic biopsy. There is no value of debulking and surgery is not advised for
gastric lesions. Chemotherapy represents a cornerstone in the treatment and offers an excellent chance for
long term, disease free survival.
PMID: 16353079

De novo nodal diffuse large B-cell lymphoma: identification of biologic prognostic factors.

Abd El-Hameed A

Diffuse large B-cell Lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma (NHL).
Although combination chemotherapy has improved the outcome, long-term cure is now possible for
approximately 50% of all patients, making the search for parameters identifying patients at high risk
particularly needed. The presence of bcl-2 gene rearrangement in de novo DLBCL suggests a possible follicle
center cell origin and perhaps a distinct clinical behavior. This study investigated the frequency and prognostic
significance of t(14;18) translocation and bcl-2 protein overexpression in a cohort of patients with de novo
nodal DLBCL who where uniformly evaluated and treated.A total of 40 patients with de novo nodal DLBCL
treated at National Cancer Institute (NCI), Cairo University were investigated. Formalin? fixed, paraffin-
embedded sections were analyzed for: 1) bcl-2 gene rearrangement including major break point region (mbr)
and minor cluster region (mcr) by polymerase chain reaction (PCR), and 2) bcl-2 protein expression by
immunohistochemistry using Dako 124 clone. Results were correlated with the clinical features and
subsequent clinical course.Bcl-2 gene rearrangement was detected in 8 cases (20%), 2 cases at mbr, and 6
cases at mcr. Bcl-2 protein (>10%) was expressed in 24 cases (60%), irrespective of the presence of t(14;18)
translocation. The t(14;18), and bcl-2 protein overexpression were more frequently associated with failure to
achieve a complete response to therapy (p=0.008, and 0.04, respectively). DLBCL patients with t(14;18), and
bcl-2 protein expression had a significantly reduced 5-year disease free survival (p=0.04, and 0.01,
respectively).The t(14;18) translocation, and bcl-2 protein expression define a group of DLBCL patients with a
poor prognosis, and could be used to tailor treatment, and to identify candidates for therapeutic approaches.
Geographic differences in t(14;18) may be related to the difference in distribution of bcl-2 breakpoints.
PMID: 19190690

ERCC1 Expression in Diffuse Large B-Cell Lymphoma Patients Treated with a Cisplatin-
Based Regimen : A Brief Communication.

Azim HA; Pruneri G; Raviele PR; Steffanoni S; Martinelli G; Peccatori FA

There is growing interest in defining biomarkers that could predict response to different chemotherapeutic
agents. Excision repair cross complement 1 (ERCC1) enzyme has been shown to predict benefit of cisplatin in
different types of cancer. As cisplatin-based regimens are frequently used in the salvage treatment of diffuse
large B-cell lymphomas (DLBCL), a small pilot study was conducted to determine whether ERCC1 is expressed
in this disease or not. Out of seven patients examined, only one had a 25% ERCC1 expression, which could
represent a tumour truly expressing this marker. However, expression was not able to predict response to
treatment. It remains unclear whether ERCC1 could serve as a predictive marker for cisplatin in this disease
requiring further studies. Key Words : ERCC1 -Large B-cell lymphoma -Cisplatin resistance.

143
PMID: 19847278

Evaluation of bone marrow in 143 lymphomas: the relative frequency and pattern of
involvement, secondary myelopathies, pitfalls and diagnostic validity.

El Bolkainy TM; Abo Deif WS; Gouda HM; Mokhtar NM

The aim of the present study is to assess the frequency of bone marrow (BM) involvement by both bone
marrow aspirate and biopsy (BMA and BMB, respectively) procedures in established cases of lymphomas at
initial presentation, and to study the relative frequency of marrow disease in relation to lymphoma types,
patterns of infiltration and the 2ry associated changes, as well as the diagnostic challenges. Moreover, the
diagnostic validity of BMA is tested taking the results of the BMB as the true test results, in order to determine
the role of each procedure in the diagnostic approach of marrow infiltration.This is a retrospective study
carried out on 143 nonconsecutive Egyptian patients with lymphomas obtained from a private series during
the years 2005 to 2008. Criteria of inclusion included the availability of full medical records and material
(medical and pathological), patient consent, nodal disease with no therapy prior to BM sampling, except in 7
patients who had another 2nd BMB following therapy. BMA and BMB were performed as part of the routine
workup for diagnosis and staging of lymphoma. The patients had a male to female sex ratio of 2.6:1 and a wide
age range from 4 to 74 years.In the present series, 64 cases out of the 143 lymphoma patients studied (44.8%)
had a BM disease. Involvement was mostly bilateral (80%). Patients older than 40 years showed higher
incidence of bone marrow involvement. There was complete concordance (100%) between both diagnostic
procedures in the detection of 76 marrow disease-free lymphoma patients. BMA showed no false positive
results and a low rate of deference that makes of it an ideal screening test. Three deferred smears of CLL for
BMB diagnosis were all positive for involvement. However, in a total number of 64 BMB positive patients,
aspirates could only identify lymphoma involvement in 42 lymphoma patients and missed 22 patients with a
BM disease, with an overall sensitivity rate of 65.6%. BMB had a high diagnostic viability and is an easily
applied reproducible procedure for diagnosis of BM involvement based on a more detailed informative
analysis of both architectural and individual cytomorphologic changes.The relatively high level of BM
involvement in Egyptian lymphoma patients was directly proportional to high-risk factors. The diagnostic
validity of BMB is higher than that of BMA. However, BMA serves as a good positive test in screening
lymphomas for marrow disease. A negative BMA does not exclude involvement. Thus, smears should be taken
as a complimentary procedure.
PMID: 19672286

Evaluation of MIB-1 and p53 overexpression as risk factors in large cell non-Hodgkin
lymphoma in adults.

El-Bolkainy TN; El-Bolkainy MN; Khaled HM; Mokhtar NM; Eissa SS; Gouda HM; El-Hattab OH

Improvement of current results of therapy for large cell non-Hodgkin lymphoma patients can be achieved by
optimization of initial treatment or application of risk-adapted therapy. The international prognostic index (
IPI), introduced to identify high-risk patients, was recently criticized because it was based on clinical risk
factors only, ignoring important tumor molecular risk factors and it fails to identify a sector of high-risk
patients, who ultimately relapse.The aim of this study is to evaluate the value of two tumor biomarkers:MIB-1
and p53 as potential risk factors in diffuse large cell lymphoma. MIB-1 measures tumor cell proliferation,
whereas p53 is related to tumor progression and response to chemotherapy.The study was done on 69 adult
patients with diffuse large cell NHL ( 58 B-phenotype and 11 T-phenotype). Clinical risk assessment was
determined by the IPI and patients with a score of 3 or more were considered high-risk. Expression of MIB-1
and p53 was determined by immunohistochemistry and nuclear staining was quantitated by image analysis.
Immunoexpression was considered high for MIB-1 nuclear count 50% and p53 counts 20%. Evaluation included
both response to chemotherapy ( mostly CHOP), as well as 2- year overall survival analysis.The IPI was the only
clinical variable which had a significant impact on survival. Overexpression of both MIB-1 and p53 was
associated with poor response to treatment, as well as unfavorable survival. Combined risk factor analysis
revealed that only MIB-1 was an independent variable. MIB-1 could also identify some high-risk patients
previously categorized in the IPI lowrisk group.MIB-1 is an independent biologic risk factor for large cell NHL. In

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order to optimize risk assessment of these patients, it is recommended to construct a new prognostic index by
adding MIB-1 overexpression to the other clinical factors of standard IPI. This may allow better identification of
high-risk patients and help to guide planning of effective initial treatment. Key Words:NHL - MIB-1 - p53 -
CHOP - Risk factors.
PMID: 18986555

Flow cytometric immunophenotyping (FCI) of lymphoma: correlation with histopathology

and immunohistochemistry.

El-Sayed AM; El-Borai MH; Bahnassy AA; El-Gerzawi SM

To evaluate the role of flow cytometric immunophenotyping (FCI) in diagnosis and characterization of
lymphoma tissue specimens from Egyptian patients.FCI using 2 and 3 color staining approaches, was
performed on 50 fresh lymph nodes specimen from Cairo NCI patients with suspected lymphoma presenting
with either localized or generalized lymphadenopathy.FCI results were correlated with histopathologic as well
as immunophenotypic[by immunohistochemistry (IHC)] findings.By FCI, cases were diagnosed as follows:
9(18%) reactive hyperplasia (RH), 32(64%) B-cell non-Hodgkin's lymphoma (B-NHL) [24 diffuse large (DLBCL), 2
follicular, 3 small lymphocytic, 2 mantle cell lymphoma and a case of T cell rich B cell lymphoma], 3 (6%) T cell
NHL [2 peripheral T cell lymphoma and a case of anaplastic large cell lymphoma], 2(4%) Hodgkin's lymphoma
(HL) while 4 (8%) were non-lymphomatous tumors (NLT). Light chain restriction (LCR) was detected in the 32
FCI diagnosed B-NHL. The overall concordance between FCI versus histopathology and IHC was 88%. The
sensitivity and specificity of FCI in diagnosis of NHL was 94.9% and 100% respectively; in HL they were 40% and
100% respectively and in NLT, both sensitivity and specificity were 100% while for RH were 100% and 89.1%
respectively.FCI is a sensitive and specific method in diagnosis and classification of NHL as well as in detection
of monoclonality. False negative results could be due to the presence of heterogeneous populations of
lymphocytes in special types of lymphoma.
PMID: 23082489

Genetic profiling of non-Hodgkin's lymphoma with or without hepatitis C virus infection.

Zekri AR; Ahmed H; Ismail M; El-Nashar AT; El-Mokadem T; Hassan A

Hepatitis C virus (HCV) which is one of the endemic viral infections in Egypt is not only hepatotropic, but also a
lymphotropic virus and has many extrahepatic manifestations as mixed cryoglobulinemia and non-Hodgkin's
lymphoma. We studied gene expression profile of 20 B-cell non-Hodgkin's lymphoma with HCV infection and
20 B-cell non-Hodgkin's lymphoma without HCV infection as a control group by c-DNA microarray. Out of the
15,500 studied genes, more than 1000 genes were differentially expressed; either upregulated or
downregulated. We found that HCV may rescue B lymphocytes from apoptosis possibly through causing
suppression of CASP1 and CASP4 and causing overexpression of the anti-apoptotic BCL2 gene. Also, HCV was
associated with overexpression of the genes related to myeloid/lymphoid leukemia and B lymphoma as
MLLT3, BAL, influences the overexpression of transcription regulator genes as TATA box binding protein (TBP)
and may influence the overexpression of some immunoglobulin genes as immunoglobulin superfamily
containing leucine gene in B cells resulting in overproduction of immunoglobulins in B-lymphocyte disorders.
Moreover HCV was associated with reduced expression of MHC class II molecules in B lymphocytes, and
therefore inhibition of antigen processing and presentation through downregulation of different MHC class II
molecules genes. We conclude that the upregulated and the downregulated genes identified through the
studied expression profiles of NHL with HCV infection may shed light on the mechanisms of HCV
lymphomagenesis.
PMID: 15912152

Hepatitis C virus and its genotypes and Helicobacter pylori in pediatric non-Hodgkin's
lymphoma: could there be a possible etiologic role?

145
 El-Mahallawy HA; Bahgat N; El-Din HM; Farag SA; Nouh A; El-Attar I

It has been recently hypothe-sized that Helicobacter pylori (H. pylori) and Hepatitis C virus (HCV) might be
involved in the pathogenesis of malignant non-Hodgkin's lymphoma (NHL). However, most of the studies were
carried out on adult patients. On the basis of this observation, we sought to determine the prevalence of these
infections in pediatric NHL patients at National Cancer Institute (NCI) and whether there is any clinical or
histopathologic picture linked to the presence of these infectious agents.The study was performed on 119
pediatric NHL patients, either as new or relapse cases, at the hematology out patient clinic of NCI from January
2002 to July 2003. Thirty apparently healthy children were studied as the control. We searched for H. pylori
IgG antibodies using an enzyme immuno-assay (EIA) procedure. HCV was investigated by EIA to detect its
antibodies, reverse transcriptase polymerase chain reaction (RT-PCR) for the presence of its RNA and viral
sequencing for the determination of the viral genotype.Antibodies for H. pylori were detected in 51/119
(43.2%) and in none of the control group, p<or= 0.001, whereas HCV antibodies were found in 21/119 (17.6%)
of the NHL patients and in one of the controls (3.3%), p<or= 0.001. HCV RNA was detected in 18/21 (85.7%)
anti-HCV positive patients analyzed, but was negative in the anti-HCV positive control. Viral genotype most
frequently encountered was genotype 4; a mixed genotype of 1+4 was detected in four patients and only one
patient showed genotype 1. No specific histological subtype, extra-nodal presentation, nor stage of disease
was related to H. pylori or HCV positivity. Older age was significantly related to H. pylori positive NHL patients.
A positive correlation between the presence of H. pylori antibodies and a complaint of vomiting and diarrhea
was observed in our patients, p<or= 0.001.We report a high prevalence of HCV and H. pylori infections in
paediatric NHL patients at NCI. Concerning the hypothesis of their pathogenetic role in lymphomagenesis, it is
still unclear whether these agents have a direct role in malignant transformation in pediatric lymphoma
because a typical NHL clinico-histological feature associated with HCV and H. pylori is lacking.
PMID: 15724387

Hepatitis C Virus and related changes in immunological parameters in non Hodgkin's

lymphoma patients.

el-Din HM; Attia MA; Hamza MR; Khaled HM; Thoraya MA; Eisa SA

Viral hepatitis is a common and important problem in immunocompromised cancer patients. The present
study was conducted to investigate changes in some cellular and humoral immunological parameters as a
consequence of HCV infection in non Hodgkin's lymphoma patients (NHL). The study included 40 NHL patients:
20 anti-HCV antibody positive (Gr. I ), and 20 anti-HCV antibody negative (Gr.II ). In addition, forty non-cancer
controls (NCCs) were included: 20 of them were anti-HCV antibody positive (Gr. III) and 20 anti-HCV antibody
negative (Gr. IV). The studied immunological parameters included serum levels of interleukin-1 (IL-1),
interleukin-2 (IL-2), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors (s-TNFr) measured by
ELISA, as well as assessment of T and B lymphocyte subsets by PAP immunostaining method. Mean IL-1 level
(pg/ml) was significantly higher in Gr. 1 (14 +/- 6) and Gr. III (20 +/- 12) as compared to those in Gr. II (7 +/- 5)
and Gr. IV (9 +/- 6). Mean IL-2 level (pg/ml) was also significantly higher in Gr. I (132 +/- 101) and Gr. III (135 +/-
59) compared to those in Gr. II (36 +/- 29) and Gr. IV (31 +/- 48). On the other hand, level of IL-6 showed no
significant difference between groups. The mean level of sTNF-r, (ng/ml) was only significantly higher in Gr. I
(2.9 +/- 1.7) when compared to that in Gr. IV (1.9 +/- 2.2). In group IV, the average percentage of CD3 (70 +/-
4%) and CD4 (44 +/- 5%) were significantly higher than in those of Gr. I (CD3 = 51 +/- 11%, CD4 = 30 +/- 12%),
Gr. II (CD3 = 52 +/- 7%, CD4 = 30 +/- 8%), and Gr. III (CD3 = 52 +/- 9%, CD4 = 26 +/- 8%). From all the above
immunological and virological features two main tips could be inferred: (1) HCV leads a mild course of
infection in NCCs evidenced by normal ALT level in all but 20% of subjects, normal IL-6, sTNF-r, lower counts of
CD4+ T cells and hence a mild hepatocellular injury, and (2) In the immunocompromised NHL patients the virus
leads potentially more aggressive course as evidenced by higher viremia, as well as significant elevation in
sTNF-r, and CD8+ depression.
PMID: 19644357

146
 Immunohistochemical detection of hepatitis C virus (genotype 4) in B-cell NHL in an
Egyptian population: correlation with serum HCV-RNA.

Gouda I; Nada O; Ezzat S; Eldaly M; Loffredo C; Taylor C; Abdel-Hamid M

Retrospective evaluation of hepatitis C virus (HCV) prevalence in lymphoma tissues has important applications
in clarifying the contribution of viral factors to the pathogenesis. Trials for detection of HCV at the cellular level
in lymphoma tissues are, so far, minimal with unsatisfactory results. We aimed to study the detection and
localization of HCV in the tissues of B-cell non-Hodgkin lymphoma (NHL) patients.We performed
immunohistochemistry to detect the HCV nonstructural 3 protein in paraffin-embedded tissue specimens of B-
cell NHL patients, in 39 serum HCV-RNA positive samples and 35 serum HCV-RNA negative samples as controls.
The serum analysis was carried out for HCV antibodies using enzyme-linked immunoassay and for HCV-RNA
using reverse transcription-polymerase chain reaction. Reverse transcription-polymerase chain reaction was
used to detect the HCV-RNA in tissues in immunohistochemically positive cases. We correlated the results with
the clinicopathologic characteristics of the patients.A diffuse cytoplasmic immunohistochemical staining for
HCV in the lymphoid cells was detected in 8 of 39 serum positive cases (20.5%), all of which were genotype 4,
which is the most prevalent HCV genotype in Egypt. Only 2 out of 35 serum negative control samples showed
positive staining and in 1 of them HCV-RNA was detected in tissue. No significant correlation was detected
between HCV positive cases and the clinicopathologic features of the patients.Immunohistochemical detection
of HCV proteins in lymphoma tissues supports a potential role of viral replication in lymphomagenesis. The low
number of cases showing expression of viral proteins may represent a low viral load in lymphoid tissue and/or
restriction of HCV protein expression to certain subtypes of B-cell NHL. Immunohistochemistry can be used as
a complementary tool for specific HCV detection in the paraffin-embedded material of lymphoma tissues not
suitable for RNA analysis.
PMID: 16116502

Intercellular adhesion molecule-1(ICAM-1), CD44s expression and serum level of sICAM-1

in disseminated non-Hodgkin's lymphoma: correlation with overall survival.

Aboul-Enein M; El-Sayed GM; El-Maghraby S; Abd-Elatif NA; Abd Elwahab GA; Elbasmy AA

Uncontrolled growth, invasion and distant spread are the characteristics of neoplastic cells. Changes in
adhesion molecule expression, such as loss of expression, de novo expression or functional alterations, can be
observed in each of these steps. The aim of the present work was to study the expression of two adhesion
molecules [standard CD44 (CD44s) and intercellular adhesion molecule-1 (ICAM-1)] and the soluble form of
ICAM-1(sICAM-1) in adult disseminated non-Hodgkin's lymphoma (D-NHL) and to correlate the findings with
overall survival.The expression of CD44s and ICAM-1 adhesion molecules and the level of sICAM-1 were
studied in 34 cases of (D-NHL). They included: 13 cases of lymphoblastic lymphoma (LBL), 5 cases of Burkitt's
lymphoma (BL), one case of diffuse large cell lymphoma (DLCL), 14 cases of small lymphocytic lymphoma (SLL),
one case of mantle cell lymphoma (MCL). Ten apparently healthy individuals were taken as a control group.
CD44s expression was evaluated by direct immunofluoresence, ICAM-1 by immunoperoxidase on cyto-preps
and serum level of sICAM-1 by ELISA.ICAM-1 was positive in 6/34 cases (17.6%) of D-NHL. ICAM-1 was
expressed in 2/15 (13.3%) of low-grade NHL and 4/19 (21%) of high-grade lymphoma with no significant
difference between the two groups (p=0.6). CD44s was expressed in 13/34 cases (38.2%) of D-NHL; in 4/15
(26.6%) of low grade NHL and 9/19 (47.3%) of high grade lymphoma with no significant difference between the
two groups (p=0.2). The serum levels of sICAM-1 were elevated in all patients with D-NHL compared to healthy
controls with a statistically significant difference (p <0.001), (median 1160 ng/ml, range from 150 to 2500
ng/ml, and 375 ng/ml, range from 270 to 620 ng/ml, respectively). The median of sICAM-1 in patients with
high-grade D-NHL was significantly (p=0.006) lower than that of those with low-grade D-NHL (median 890
ng/ml, range from 150 to 1540 ng/ml and 1440 ng/ml, range from 380 to 2500 ng/ml respectively). The
median follow-up duration for all patients was 18 months. No statistical significant difference was achieved
(p=0.8) on comparing overall survival pattern between D-NHL lymphoma patients with positive or negative
expression of ICAM-1 or sCD44 expression. Also, no statistically significant difference (p=0.9) was found

147
between patients with sICAM (above and below 600 ng/ml) at 18 months from diagnosis.There is a marked
heterogeneity in cell adhesion molecule (CAM) expression in NHL and this may correlate with degree of
differentiation of malignant lymphocytes. However the exact significance of these findings will require
functional studies to determine the role of these CAMs in each subtype of NHL.
PMID: 18565897

Intracranial Rosai-Dorfman disease with relapsing spinal lesions.

Raslan O; Ketonen LM; Fuller GN; Schellingerhout D

PMID: 2254118

Late tissue reactions after single-fraction sequential half-body irradiation (HBI) in patients
with non-Hodgkin's lymphomas.

Awwad HK; el Badawy S; el Ghamrawy K; el Mongy M; Rizk S

Lung and hepatic toxicities constituted the main radiation-related damage after half-body irradiation (HBI)
used as the treatment for patients with non-Hodgkin's lymphomas (NHL). Liver damage was mostly transient
after a single dose of 8 Gy and could be well monitored by serum enzyme levels. A dose-response relationship
could be shown for lung damage in the single dose range of 6.25-9.25 Gy, but the relationship did not reach
statistical significance. A significant dose-rate effect could be shown. Mediastinal involvement by lymphoma
seemed to increase the risk of pneumonitis. In a radical setting half-body irradiation is recommended to be
used at a low dose-rate or as a multifraction irradiation in order to reduce the risk of liver and lung toxicities.
PMID: 1743630

Pediatric non-Hodgkin's lymphoma abdominal presentations: a comparative study

between two treatment regimens at the National Cancer Institute Cairo.

Abdel Hadi SS; el Taneer OM; Hussein MH; el Haddad A; el Badawi S; Mokhtar N; Hamza MR; el Mawla NG

Abdominal presentations of pediatric NHL are rarely amenable to complete surgical resection. Chemotherapy
is the hallmark of treatment for pediatric NHL. Treatment of various types of this disease including intra-
abdominal NHL in children with various protocols have not exceeded 54 per cent two-year disease-free
survival. We have attempted to study and compare the effects of two treatment regimen upon two groups of
previously untreated children up to the age of 16 years who presented to the Pediatric Oncology Unit at the
NCI. The first group included 18 children who presented between 1983 and 1985 and were treated by a
modified St Jude regimen: while the second group of patients was comprised of 19 children who presented
between 1985 and 1987 and were treated by a multi-national protocol: the MCP 842. The two groups will be
compared with respect to various patient characteristics, response to therapy and their two-year disease-free
survival as well as overall survival.
PMID: 1743631

Prolonged disease-free survival in pediatric non-Hodgkin's lymphoma using ifosfamide-

containing combination chemotherapy.

Gad-el-Mawla N; Hamza MR; Abdel-Hadi S; el-Tannir O; Hussein MH; el-Haddad A; Adde M; Magrath I

Pediatric non-Hodgkin's lymphoma (NHL) constitutes 16 per cent of pediatric malignancies reported to the
National Cancer Institute (NCI) in Cairo. The adopted treatment for these cases was, from 1982 to July 1985, a
modified St Jude's regimen consisting of: vincristine, cyclophosphamide, adriamycin, prednisone and
intrathecal methotrexate for the first 6 weeks for induction, followed by cranial irradiation for cranial
prophylaxis. Patients in remission received maintenance therapy for 18 months. Of 32 patients complete
remission (CR) was achieved in 24 patients (75 per cent); partial remission (PR) in one patient (3 per cent); five

148
patients showed no response (15 per cent) while two patients died during the induction phase. At 60+ months
follow-up, 60 per cent of cases are still alive, disease-free, and overall survival is 66 per cent. A new protocol
was adopted in 1985, consisting of alternating cycles: A and B, for 4-8 cycles. Cycle A: cyclophosphamide, high
dose ara-C, adriamycin, and vincristine. Cycle B: ifosfamide, methotrexate, VP 16, with intrathecal
methotrexate. The response in 39 cases is: CR in 31 cases (82 per cent); PR in four cases (10 per cent); no
response in three cases (8 per cent). At 60+ months, the disease-free survival is 60 per cent, and overall
survival 80 per cent. This new protocol has the advantage of: short duration of therapy and so better patient
compliance, no maintenance therapy or cranial irradiation with its sequelae in the future. Moreover, it has a
better overall survival.
PMID: 19190689

Review article composite lymphoma.

Mokhtar NM

Background : Composite lymphoma (CL) is a rare disease that has been identified in recent literature. The term
composite lymphoma was first proposed to denote the occurrence of more than one lymphoma in a single
patient; however, the present accepted definition is the occurrence of 2 or more distinct lymphoma types in a
single anatomic site. The condition could be concurrent or sequential. Unlike disease progression or
transformation in lymphoma, CL should include two distinct clones proven by morphological and laboratory
tests. Pathogenesis : No single definite mechanism has been suggested to explain the pathogenesis of the
different types of CL. The etiology is variable, complex and differs according to the types of lymphomas
involved. Several theories were proposed including clonal selection with additional mutational accumulation,
genomic instability with genetic predisposition, common precursor cell and the aid of a viral factor, mostly
EBV. Diagnosis : The morphologic criteria must be confirmed by one or more tests including
immunohistochemistry, flow cytometry, gene rearrangement by PCR, cytogenetics, FISH, in-situ hybridization,
DNA sequencing and cDNA microarray . Results are more accurate using the laser capture microdissection
method. Many combinations of CL are reported, including : Multiple B-cell lymphomas; B-cell and T-cell
lymphomas; NHL and HL; or complex B-cell, T-cell and HL cases. Conclusion : Due to the great advancement in
molecular characterization of lymphoma, CL is being increasingly identified. It must be carefully diagnosed,
because the multiple disease entities may have entirely different natural histories, prognosis and treatment
modalities. Also, careful study of such cases may clarify the possible pathogenic mechanisms of the
interrelationship of clonal evolution in lymphoma. Key Words : Composite lymphoma -EBV.
PMID: 20029465

Risk adapted combined modality treatment in children with Hodgkin's disease: NCI, Cairo.

El-Badawy S; Aboulnaga S; Abou Gabal A; Mokhless A; Zamzam M; Sidhom I; Ebeid E; Hussein H

The objective of this study is to maximize the chance of cure while minimizing surgery, radiotherapy and
chemotherapy as much as possible to avoid late effects and toxicity of combined modality treatment in
children with Hodgkin's disease.One hundred twenty-one (121) children under the age of 18 years with a
histopathologic diagnosis of Hodgkin's disease were enrolled into this study. Patients were stratified according
to stage into 3 risk groups: low (Stages: I, II A), intermediate (Stages: II B, III A) and high risk group (Stages: III B,
IV). Oral Etoposide was used in this study instead of procarbazine in the management of boys with HD to
reduce the gonadotoxic effects of procarbazine. Two cycles of OPPA for females and E-OPA for males were
effective induction treatment for children with all stages of HD and stage-tailored chemotherapy (2, 4, 6 cycles
of OPPA, E-OPA/ COPP) was sufficient to eradicate occult microfoci. Involved field radiotherapy was given in
doses of 30, 25, 20 Gy, depending on the extent of initial chemotherapy and risk status. Staging laparotomy
was performed in 30 patients out of the 121 patients, 24 of them underwent splenectomy. Patients who
received whole neck radiotherapy were submitted to thyroid U/S and thyroid hormonal profile. Only 3
adolescent patients did semen analysis.The overall and disease-free survival rates at 6 years were 95.3% and
86.1% (95% CI), respectively (entire group), 96.1% , 92.3% (95% CI) for low risk, 96.1% , 80.7% (95% CI) for
intermediate risk and 93.3% , 80% (95% CI) for high risk patients. During the followup period all patients had
normal thyroid functions.In children with HD, only low dose involved field radiotherapy with reduced doses is

149
needed,if a risk-dependent chemotherapy is given. In this series the strategy of selective laparotomy and
restrictive splenectomy is very useful in the context of combined modality treatment, in which laparotomy was
omitted if both abdominal U/S and CT were negative.

PMID: 21257861

Rosai-Dorfman disease in neuroradiology: imaging findings in a series of 10 patients.

Raslan OA; Schellingerhout D; Fuller GN; Ketonen LM

Rosai-Dorfman disease is a rare disorder characterized histologically by lymphatic sinus dilatation due to
histiocyte proliferation. Our goal was to describe the CT, MRI, and (18)F-FDG (FDG) PET findings in a series of
patients with this diagnosis.We retrospectively reviewed the imaging studies of 10 patients with pathologically
confirmed Rosai-Dorfman disease who were treated in our institution between January 2004 and December
2007.We found the following areas of general involvement: three intracranial, seven head and neck, and three
spinal, with some patients having more than one site. Specific sites of involvement included the following:
intracranial meninges, n = 2; pituitary, n = 2; lacrimal gland, n = 1; paranasal sinus, n = 3; neck lymph nodes, n =
6; salivary gland, n = 3; tonsil, n = 1; skin, n = 1; spinal meninges, n = 2; vertebral body, n = 1; and thymus, n = 1.
The MRI characteristics of the involved areas were generally T1 isointense, T2 isointense, diffusion isointense
to gray matter, and intensely enhancing with gadolinium chelate contrast agents. CT images generally showed
the lesions were hyperdense to gray matter and intensely enhancing. FDG PET showed variable uptake, with
nodal and lacrimal disease generally being FDG avid and other sites not.Rosai-Dorfman disease has a protean
imaging appearance but most frequently presents as neck lymphadenopathy. The disease is frequently
multifocal, and a diagnosis in one area should prompt suspicion that other sites may be involved also.
PMID: 8630905

The investigation of Epstein-Barr viral sequences in 41 cases of Burkitt's lymphoma from

Egypt: epidemiologic correlations.

Anwar N; Kingma DW; Bloch AR; Mourad M; Raffeld M; Franklin J; Magrath I; el Bolkainy N; Jaffe ES

Epstein-Barr virus (EBV) is associated with many human neoplasms, including Burkitt's lymphoma (BL).
Endemic BL in central Africa is more often EBV-associated than BL in the United States, where seroconversion
for EBV occurs somewhat later than in Africa. Therefore, the EBV association rate in BL may correlate more
with the socioeconomic status of the population studied, which influences the age of EBV seroconversion, than
with such factors as malaria, which may relate to the overall higher incidence rate in endemic regions.Forty-
one patients with BL in Egypt, which differs both climatically and racially from central African countries (i.e.,
Kenya, Uganda) where BL is endemic, were analyzed. All biopsies were evaluated for EBV-encoded RNAs
(EBER1) by RNA in situ hybridization, analyzed for p53 protein expression using the monoclonal antibody D07,
and immunophenotyped using a panel of monoclonal antibodies that included L26 (CD20), Leu 22 (CD43), and
A6 (CD45RO). Twelve cases were evaluable for EBV subtype by polymerase chain reaction with EBV-specific
primers.The median age at diagnosis was 9 years (range, 2-22 years). The biopsy site was extranodal in 29
patients and nodal in 12 patients. All 41 cases were documented as B-cell neoplasms. A hybridization signal for
EBER1 RNA was identified in greater than 95% of the neoplastic cells in 30 of 41 cases (73%), whereas no signal
was observed in 11 cases (27%). Epstein-Barr virus subtype 1 was found in 10 patients, subtype 2 in two
patients. Immunostaining for p53 was observed in greater than 5% of the neoplastic cells in 9 of 37 cases
(24%). No significant correlation was observed between EBV positivity and sex, biopsy site, or p53
immunostaining.The prevalence of EBV in BL from Egypt is slightly lower than in BL in endemic regions, but
significantly higher than in sporadic BL. Epstein-Barr virus positivity probably reflects the socioeconomic status
of the patient population, and age at seroconversion. The prevalence of EBV subtype 1 suggests that
immunodeficiency does not play a role in Egyptian Burkitt's lymphoma, in contrast to endemic Burkitt's
lymphoma, in which holoendemic malaria is thought to contribute to immunodeficiency, a higher incidence
rate, and the observed prevalence of subtype 2.

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PMID: 14597354

The potential palliative role and possible immune modulatory effects of low-dose total
body irradiation in relapsed or chemo-resistant non-Hodgkin's lymphoma.

Safwat A; Bayoumy Y; El-Sharkawy N; Shaaban K; Mansour O; Kamel A

In a group of 35 patients with relapsed and/or chemo-resistant non-Hodgkin's lymphoma (NHL), low-dose total
body irradiation (LTBI) (+involved-field radiotherapy to bulky sites) achieved a complete remission rate of 29%,
2-years progression-free survival of 32% and a median progression-free survival of 12 months. The 2-year
survival was 42% and the median survival was 17 months. Immuno-staining and flow cytometry of peripheral
blood in 14 patients showed that LTBI leads to a significant increase in the percentage of CD4+ cells with a
consequent significant increase in the CD4+/CD8+ ratio. High lymphocytic percent and a high percentage of
CD4+ cells before LTBI were significantly correlated with longer response duration and overall survival. These
data may suggest that the palliative potential of LTBI should be investigated as an alternative to chemotherapy
in NHL patients. The pre-treatment percentage of lymphocytes and CD4+ cells may be used as predictors for
response to LTBI.
PMID: 21863071

Treatment Outcome of Pediatric Patients with Mature B Cell Lymphoma Receiving Fab
LMB96 Protocol at the National Cancer Institute, Cairo University.

Abd El-Rahman H; Bedair RM

Lymphomas are the third most common malignant tumor in the pediatric age group after leukemia and brain
tumors. Outcome has improved remarkably over the past decade because of improvements in imaging and
staging systems that more accurately reflect the clinical behavior, and the development of risk adapted
multiagent chemotherapeutic regimens. The aim of this work is to study the outcome, Overall Survival (OS)
and Event Free Survival (EFS) of patients receiving FAB LMB96 protocol applied for treatment of mature B cell
lymphoma.This is a retrospective study analyzing the data of 103 newly diagnosed pediatric NHL [Burkitt's
lymphoma÷leukemia, Diffuse Large B Cell Lymphoma (DLBCL)] who received LMB96 protocol at Department of
Pediatric Oncology, National Cancer Institute, Cairo University, during the time period from 1st of January
2006 to the end of December 2008. A total of 103 patients were included in the study, and were followedup
till 31st December 2009.This study included were 80 males (77.7%) and 23 females (22.3%), their mean age
was 6.55±3.9 years ranged from 2 to 16 years. Abdominal presentation was the most common clinical
presentation seen in 85 patients (82.5%) followed by thoracic mass in 27 patients (26.2%) and cervical mass in
22 patients (21.4%). CNS involvement occurred in 16 patients (15.5%) while bone marrow infiltration occurred
in 18 patients (17.5%). The most common pathological subtype was Burkitt's lymphoma seen in 83 patients
(80.6%) followed by DLBCL in 12 patients (11.7%). Stage III was the most commonly seen; detected in 65
patients (63.1%). The commonest treatment group seen was group B in 80 patients (77.7%) followed by group
C in 19 patients (18.4%) then group A in 4 patients (3.9%).Complete remission for the whole group of patients
was achieved in 72 patients (70%), relapses and disease progression occurred in 9 patients (8.7%) and stable
disease in 1 patient (1%). Death due to septicemia occurred in 13 patients (12.6%). There were 8 patients
(7.7%) who discontinued treatment.FAB LMB96 protocol is well tolerated, giving results close to the
international literature for both group A and B patients, while it seems toxic for group C patients. KEY WORDS:
NHL- FAB LMB96- Pediatric- Lymphoma.
PMID: 17974155

151
Viral genomes and antigen detection of hepatitis B and C viruses in involved lymph nodes
of Egyptian non-Hodgkin's lymphoma patients.

El-Sayed GM; Mohamed WS; Nouh MA; Moneer MM; El-Mahallawy HA

Several studies have suggested an association between Hepatitis C and B viruses (HCV and HBV) and non-
Hodgkin's lymphoma (NHL). In the present study we have searched for viral genomes and antigens in the
malignant lymphoma tissues as well as their seroprevalence. Antibodies against Hepatitis C as well as HCV RNA
and hepatitis B surface antigen (HBsAg) were determined for 29 newly diagnosed non-Hodgkin's lymphoma
patients using an enzyme linked immunosorbent assay (ELISA), as well as RT-PCR and compared with 36
apparently healthy individuals as a control group for viral markers. Immunohistochemical staining (IHC) was
performed on paraffin embedded tissues for the NS3 of HCV and for HBsAg of HBV using the
immunoperoxidase technique. Paraffin embedded lymph nodes (LN) were studied for the presence of viral
sequences. Ten non-metastatic lymph nodes (LN) from cancer cases other than NHL were used as a control for
IHC and molecular studies. HCV was significantly more encountered in patients with NHL when compared to
controls for both antibodies (27.6% versus 8.3% of serum controls; p = 0.04), and antigens studied by IHC in
the involved LN (41% versus 10% of tissue controls; p = 0.06). Although HBsAg positivity was not different in
NHL patients when compared to controls (6.9% and 2.7%); yet it was significantly more encountered in LN of
NHL patients (p = 0.04). HBV-DNA was detected in 27.5% of patient's samples and none of the controls. In
conclusion, overall our findings confirm the presence of HBV and HCV antigens and viral sequences in the
involved LNs of NHL patients, except for HCV RNA which perhaps necessitates fresh and not paraffin
embedded tissues. These results strengthen the assumption that these viruses may be involved in the
development of NHL.

Miscellaneous studies

PMID: 21132029

A Comparative Dosimetric Study of Adjuvant 3D Conformal Radiotherapy for Operable

Stomach Cancer Versus AP-PA Conventional Radiotherapy in NCI-Cairo.

El-Hossiny HA; Diab NA; El-Taher MM

This study was to compare this multiplefield conformal technique to the AP-PA technique with respect to
target volume coverage and dose to normal tissues.Seventeen patients with stages II-III denocarcinoma of the
stomach were treated with adjuvant postoperative chemoradiotherapy presented to radiotherapy department
in National Cancer Institute, Cairo in period between February 2009 to March 2010 using 3D conformal
radiotherapy technique that consisted of a monoisocentric arrangement employing 4-6 radiation fields. For
each patient, a second radiotherapy treatment plan was done using an antroposterior (AP-PA) fields, the two
techniques were then compared using dose volume histogram (DVH) analysis.Comparing different DVHs, it
was found that the planning target volume (PTV) was adequately covered in both (3D & 2D) plans while the
left kidney and spinal cord demonstrate lower radiation doses on using the conformal technique. The liver
doses is higher in the 3D tecq, but still well below liver tolerance.Both 3D conformal radiotherapy and AP-PA
conventional techniques doses are within range of normal tissues tolerance. Regarding the left kidney and
spinal cord the 3D conformal radiotherapy is superior than the AP-PA conventional techniques but with higher
doses to the liver in the 3D conformal radiotherapy compared to the AP-PA conventional techniques. KEY
WORDS: Dosimetric study in cancer stomach.
PMID: 12132778

152
 A prospective study on fungal infection in children with cancer.

el-Mahallawy HA; Attia I; Ali-el-Din NH; Salem AE; Abo-el-Naga S

A prospective study was conducted in 1999 at the National Cancer Institute, Cairo University, to estimate the
incidence, morbidity and mortality of fungal infections along with the evaluation of risk factors influencing
outcome of infections among paediatric cancer patients. Of 1917 infectious episodes, the fungal infection rate
as documented both clinically and microbiologically was 3.7% (70 cases). Fungal pathogens isolated were
yeasts in 55 patients (78.6%) and moulds in 15 patients (21.11%). Among yeasts, Candida parapsilosis was the
commonest, followed by C. tropicalis. Pneumonia was the most common fungal infection (n = 25, 35.7%),
followed by fungaemia (n = 18, 25.7%). The overall mortality rate was 40% (n = 28), with an infection-related
mortality of 28.5% (n = 20). Risk factors that accompanied mortality were relapsing or recurrent disease,
profound neutropenia, ADE (Ara-C, daunorubocin and etoposide) protocol of chemotherapy, C. tropicalis
isolated and fungaemia as a site of infection. Early use of empirical antifungal therapy (day 4) was not
associated with a better outcome. In the light of the poor outcome of patients with fungaemia and fungal
pneumonia, every effort should be made to prevent these infections in paediatric cancer patients.
PMID: 21671364

Antibiotic resistance is associated with longer bacteremic episodes and worse outcome in
febrile neutropenic children with cancer.

El-Mahallawy HA; El-Wakil M; Moneer MM; Shalaby L

With the increasing emergence of multiresistant pathogens, better understanding of these infections is
necessary. The aim of the present study was to evaluate the risk factors associated with isolating a
multiresistant organism (MRO) from a positive blood culture in pediatric cancer patients with febrile
neutropenia (F&N), and to study its impact on clinical course and outcome of febrile episodes.The association
between MRO with underlying malignancy, age, disease status, hospitalization during episode, absolute
neutrophil count, absolute monocyte count, clinical foci of infection, and pathogens isolated was assessed in
bacteremic pediatric cancer patients. The MRO phenotype was defined as diminished susceptibility to ≥3 of
the broad spectrum antibody classes.Among 239 episodes of blood stream infections (BSI), Gram-positive, and
Gram-negative organisms were detected in 180 (75%), and 59(25%) episodes, respectively; with 38% of
isolates showing multiresistance (n = 92). Significant risk factors (P < 0.05) for MRO were hospitalization, Gram-
negative organisms, presence of clinical focus of infection, reduced ANC, prolonged duration of neutropenia,
and previous intake of antibiotics. Of the episodes with prolonged duration of fever extending for more than 7
days 62% (64|93) were associated with a multiresistant phenotype, while it accompanied 72% (18|25) of the
cases with an unfavorable outcome; P-value <0.001.Isolation of MRO is more likely to be associated with a
prolonged course and an unfavorable outcome. Continuous multidisciplinary surveillance of BSI is warranted
to develop strategies for antimicrobial resistance control.
PMID: 15724392

Application of refractory fragment amplification system for detection of Egyptian variant

of Familial Mediterranean Fever.

Zekri AR; el-Bassuoni MA; Hammad OM; Sakr MA; Ibrahim AA

Until recently, the diagnosis of familial Mediterranean fever (FMF) was, based on clinical manifestations,
ethnicity, family history and response to colchicines. The aim of this study is to evaluate the use of polymerase
chain reaction (PCR) for diagnosis of FMF and to detect the prevalence of the most common MEFV gene (FMF
gene) mutations, M694V and V726A in FMF Egyptian patients. From January 2002 to December 2002, twenty
patients with FMF as well as 10 healthy subjects with no symptoms suggestive of FMF were enrolled in this
study. All patients were subjected to PCR for MEEV gene mutations detection. Fifteen patients (75%) have age
of onset of FMF less than 20 years. Five patients (25%) had past history of appendicectomy or laparotomy. The
clinical features of patients during attacks were fever (100%), abdominal pain (95%), arthritis (55%), pleurisy

153
(40%) and no skin rash or pericarditis. The M694V mutation was detected in 20 patients (100%) and V726A
mutation in 17 patients (85%). No false positive or false negative results were obtained by using the three sets
of primers for each sample, indicating a sensitivity and specificity of 100% of this assay.
PMID: 8591181

Automated medical records technology at the National Cancer Institute-Egypt: a case

study in technology transfer.

El Hattab O; Dayhoff RE

The National Cancer Institute-Cairo, Egypt (NCI) has adopted three different approaches to the automated
medical record. These approaches are: the use of an integrated hospital information system, a document
scanning system, and an imaging system. This paper discusses each of these approaches with regard to its
benefits, technology-implemented and technology-related issues, and the social and cultural differences
between implementations in developed and developing countries.
PMID: 19459752

Camel milk as an adjuvant therapy for the treatment of type 1 diabetes: verification of a
traditional ethnomedical practice.

Mohamad RH; Zekry ZK; Al-Mehdar HA; Salama O; El-Shaieb SE; El-Basmy AA; Al-said MG; Sharawy SM

There is a traditional belief in the Middle East that regular consumption of camel milk may aid in prevention
and control of diabetes. The aim of this work was to evaluate the efficacy of camel milk as an adjuvant therapy
in young type 1 diabetics. This 16-week randomized study enrolled 54 type 1 diabetic patients (average age 20
years) selected from those attending the outpatient diabetes clinic of the Menofia University Hospital,
affiliated with Egypt's National Cancer Institute. Subjects were randomly divided into two groups of 27
patients: one received usual management (diet, exercise, and insulin), whereas the other received 500 mL of
camel milk daily in addition to standard management. A control group of 10 healthy subjects was also
assessed. The following parameters were evaluated at baseline and at 4 and 16 weeks: hemoglobin A1c
(HbA1c), human C-peptide, lipid profile, serum insulin, anti-insulin antibodies, creatinine clearance, albumin in
24-hour urine, body mass index, and Diabetes Quality of Life score. The following parameters were
significantly different between the usual-management group versus the camel milk group after 16 weeks:
fasting blood sugar (227.2 +/- 17.7 vs. 98.9 +/- 16.2 mg/dL), HbA1c (9.59 +/- 2.05[%] vs. 7.16 +/- 1.84[%]),
serum anti-insulin antibodies (26.20 +/- 7.69 vs. 20.92 +/- 5.45 microU/mL), urinary albumin excretion (25.17
+/- 5.43 vs. 14.54 +/- 5.62 mg/dL/24 hours), daily insulin dose (48.1 +/- 6.95 vs. 23 +/- 4.05 units), and body
mass index (18.43 +/- 3.59 vs. 24.3 +/- 2.95 kg/m(2)). Most notably, C-peptide levels were markedly higher in
the camel milk group (0.28 +/- 0.6 vs. 2.30 +/- 0.51 pmol/mL). These results suggest that, as an adjunct to
standard management, daily ingestion of camel milk can aid metabolic control in young type 1 diabetics, at
least in part by boosting endogenous insulin secretion.
PMID: 18341198

Cancer magnitude, challenges and control in the Eastern Mediterranean region.

Omar S; Alieldin NH; Khatib OM

Cancer is increasingly recognized as a major and growing health concern in the Eastern Mediterranean Region
(EMR). This report outlines the current burden of cancer in the Region and the challenges faced by the
countries; these are mainly lack of national cancer surveillance, lack of a model of integrated care for
noncommunicable disease prevention in general and cancer in particular, inadequate national capacity-
building and lack of programme sustainability. Strategies for cancer prevention, control and care in the Region
are discussed, such as: the formulation of evidence-based policies, mobilization and appropriate allocation of
resources, active participation of all stakeholders, government commitment to legislation, education and
international collaboration.

154
PMID: 22834638

Characterization of Mycobacterium tuberculosis isolated from cancer patients with

suspected tuberculosis infection in Egypt: identification, prevalence, risk factors and
resistance pattern.

El-Sharif A; Afifi S; El-Dahshan R; Rafeh N; Eissa S

Clin Microbiol Infect 2012; 18: E438-E445 ABSTRACT: Data are sparse on Mycobacterium tuberculosis infection
among patients with cancer in Egypt. We sought to detect the presence of tuberculosis (TB) disease among
patients with malignant conditions and suspected TB and to study the main risk factors. Also, we compared
different diagnostic procedures and detected the antimicrobial susceptibility of M. tuberculosis isolates against
rifampin and isoniazid. One hundred patients were included in this study, all of them had malignant conditions
and were suspected by the clinicians of having TB. Identification of M. tuberculosis in different specimens was
performed by smear microscopy, followed by Lowenstein-Jensen medium and Mycobacterium growth
indicator tube (MGIT) cultures and artus(®) real-time PCR. In addition, an indirect MGIT anti-TB susceptibility
test was carried out against rifampin and isoniazid. A total of 76% of studied cases were found to be TB
positive. The frequencies of TB-positive cases in the bronchogenic, haematological and solid tumour
malignancy groups were 21%, 25% and 30%, respectively. Significant differences between pulmonary and
extrapulmonary TB in different malignancy groups were recorded. Real-time PCR showed the highest overall
diagnostic efficiency. Multidrug-resistance of M. tuberculosis to both rifampin and isoniazid was detected in
28.6% of examined isolates. Infection in cancer patients with TB was significantly more often recorded among
elderly patients and those suffering from poverty. Pulmonary TB is more common than extrapulmonary TB in
patients with malignancy. Real-time PCR is the most accurate and rapid method for TB diagnosis. MGIT-
rifampin resistance may be used as a reliable marker for detection of multidrug-resistant TB. Diagnosis and
instituting treatment course for active or latent TB infection are crucial before starting anticancer therapy.
PMID: 17671526

Chest wall resection and reconstruction: analysis of 11 cases after methylmethacrylate

reconstruction.

Fouad FA

Patients with extensive resection of the chest wall, followed by reconstruction with methylmethacrylate and
double prolene mesh in the form of "sandwich" prosthesis. Substitutes were assessed prospectively as chest
wall defects continue to present a complicated treatment scenario for thoracic and reconstructive surgeons.To
evaluate the results of eleven patients who underwent chest wall resection and reconstruction.Eleven patients
were prospectively reviewed who underwent chest wall resection and reconstruction at National Cancer
Institute Cairo University. Among them, 7 were male and 4 female. The mean age was 34.5 (SDV +/- 19.8)
years. The indications for resection were primary chest wall tumor in 7 patients (63.7%), recurrence of breast
cancer 2 (18.2%), lung cancer with invasion of chest wall 1 (9.1%) and pleuroblastoma 1 (9.1%).The mean
number of rib resected was 4.18 +/- 1.16 ribs (3-6). Concomitant resection was done in 6 patients; including
lung resection 2, partial resection of diaphragm 2, lateral clavicle with forequarter amputation 1 and partial
sternectomy 1. All patients underwent skeletal reconstruction (SR) with methylmethacrylate and double
prolene mesh in the form of"sandwich" prosthesis. Simultaneous SR and soft tissue reconstruction (STR) were
performed in 7 patients 63.7%. Five patients (45.5%) developed postoperative complications with no
perioperative mortality. Follow-up was carried out for a mean period of 18.7 months (11-36). Three patients
developed relapse (27.3%), local recurrence in two cases and bone metastases in one case.Chest wall resection
followed immediately by reconstruction utilizing synthetic mesh with a filler of methylmethacrylate with or
without local or pedicled muscle flaps can be performed as a safe, effective one-stage surgical procedure for
major chest wall defects which prevents paradoxical movement of chest wall and overcomes deformity.
PMID: 2758567

155
Childhood non-Hodgkin's lymphoma in Egypt: preliminary results of treatment with a new
ifosfamide-containing regimen.

Gad-el-Mawla N; Hussein MH; Abdel-Hadi S; el-Taneer O; Adde M; Magrath I

Pediatric non-Hodgkin's lymphoma (NHL) constitutes 16% of pediatric malignancies reported to the National
Cancer Institute (NCI) in Cairo. Since July 1985, we have treated 39 previously untreated pediatric NHL cases
younger than 16 years of age (mean, 7.6 years) with a new protocol consisting of alternating cycles: regimen A
comprised cyclophosphamide, high-dose ara-C, Adriamycin and vincristine; regimen B consisted of ifosfamide,
methotrexate and VP16, with intrathecal methotrexate. Diagnoses included 20 abdominal masses, 16
peripheral lymphadenopathies and 6 bony lesions. Histopathology according to the working formulation
revealed 21 cases of small non-cleaved lymphoma, 6 lymphoblastic, 5 large-cell and 7 unclassified diffuse
lymphomas. Responses were complete in 31 cases (82%) and partial in 4 cases (10%), and no response was
obtained in 4 cases (8%). Overall survival was 82% in limited disease and 60% in extensive disease at 28+
months. This short-term ifosfamide-containing regimen proved its efficacy, with results matching those of
other regimens used in the United States and Europe.
PMID: 15603994

Clinical and microbiologic determinants of serious bloodstream infections in Egyptian

pediatric cancer patients: a one-year study.

El-Mahallawy H; Sidhom I; El-Din NH; Zamzam M; El-Lamie MM

Bloodstream infections (BSI) remain a major cause of morbidity and death in patients undergoing treatment
for cancer. However, all recent epidemiological and therapeutic studies underline the absolute need for
knowledge of the factors governing the infections in each center. The aim of this study is to identify the factors
affecting BSI in the pediatric service of the National Cancer Institute (NCI) at Cairo University. More tailored
policies for the treatment of patients with febrile neutropenia following chemotherapy can then be
created.Over a 12-month period, all children with cancer and fever, with or without neutropenia, who were
admitted to the NCI for empirical therapy of febrile episodes and who had a microbiologically confirmed
bloodstream infection were studied retrospectively.A total of 328 BSI occurred in 1135 febrile episodes in
pediatric cancer patients at the NCI in one year. Gram-positive bacteria were isolated in 168 episodes (51.2%)
and 61.9% of the total isolates (either single or mixed), Gram-negative in 97 (29.6%), and mixed infections in
45 (13.7%). The common causative agents of bloodstream infections in this study were coagulase-negative
staphylococci (16.2%), Staphylococcus aureus (13.4%), Streptococcus spp. (12.1%) followed by Acinetobacter
spp. (6.7%) and Pseudomonas spp. (5.5%). Fungemia was encountered in 18 episodes, being mixed in nine of
them. A more serious BSI in terms of a prolonged episode was encountered in 30.2% of the episodes and was
significantly associated with patients being hospitalized, having intensified chemotherapy, polymicrobial and
fungal infection, lower respiratory tract infections and persistent neutropenia at day seven.In a large
population of children, common clinical and laboratory risk factors were identified that can help predict more
serious BSI. These results encourage the possibility of a more selective management strategy for these
children.
PMID: 19214976

156
 Clinical implications of icaA and icaD genes in coagulase negative staphylococci and
Staphylococcus aureus bacteremia in febrile neutropenic pediatric cancer patients.

El-Mahallawy HA; Loutfy SA; El-Wakil M; El-Al AK; Morcos H

Staphylococci are the most frequently isolated organisms from blood cultures of febrile neutropenic (FN)
cancer patients. We aimed to define the nature of these isolates by studying the prevalence of icaA and icaD
genes in coagulase-negative staphylococci (CoNS) and Staphylococcus aureus isolates in relation to clinical and
microbiological features.Fifty-five CoNS and S. aureus isolates from blood cultures of FN pediatric patients
receiving chemotherapy were tested for slime production using Congo red agar plate test (CRA test), and for
the presence of icaA and icaD genes by PCR.Of the CoNS isolates, eight were positive for ica genes, and three
were slime positive/ica negative. A total of 11 (24.4%) cases of CoNS bacteremia were either ica genes or CRA
test positive. There was a concordance between ica genes and CRA test positivity (P < 0.001). S. aureus isolates
exhibited icaA and icaD genes more than CoNS isolates (P = 0.03). Vancomycin was significantly more
prescribed in episodes of ica-positive cases (P = 0.029).The results of the present study support the hypothesis
that the ica genes are important virulence markers for clinically significant CoNS isolates, indicating their ability
to produce slime. This could be used to assign a group with higher risk FN. On the other hand, absence of these
genes may permit, along with other clinical criteria, the consideration of a low-risk FN episode and allow for
safe early discharge.
PMID: 15716999

Clinical significance of vascular endothelial growth factor (VEGF) in sera of patients with
pediatric malignancies.

El-Houseini ME; Abdel-Azim SA; El-Desouky GI; Abdel-Hady S; El-Hamad MF; Kamel AM

Angiogenesis is essential for solid tumor growth. It is induced by tumor cells through stimulatory angiogenic
peptides, one such peptide is vascular endothelial growth factor (VEGF).The ultimate aim of the work is to
investigate the possible role of VEGF as an early biomolecule involved in the progression of pediatric malignant
tumors with high metastatic potential.Forty-five pediatric patients were studied. They included four groups
with malignant solid tumors suffering from Ewing's sarcoma, osteosarcoma, neuroblastoma and
rhabdomyosarcoma. In addition, a healthy control group including fifteen age and sex matched children was
included in the study. Serum VEGF levels were determined by ELISA technique.The level of VEGF was
significantly higher in all types of solid tumors compared to normal healthy children. The mean values obtained
for patients and controls were 429.44 +/- 258.55 pg/ml and 79.36 +/- 63.81 pg/ml, respectively. No significant
difference was detected in the level of VEGF among males and females. Also, no statistically significant
difference was detected among the different types of malignant tumors. However, a marked significant
difference was elucidated between metastatic and non-metastatic cancer patients, the values recorded were
753.33 +/- 173.64 pg/ml and 267.5 +/- 75.54 pg/ml, respectively (p < 0.001). Furthermore the results showed
that 207 pg/ml of serum level of VEGF is the optimal cut-off value (mean +/- 2 SD of control) with sensitivity of
87% and specificity of 100%. Using the receiver operating characteristic (ROC) curve analysis,the area under
the curve (0.917) indicated the validity of using serum VEGF level in the diagnosis of all different types of
pediatric malignant solid tumors with high potentiality to metastasis.VEGF is an angiogenic stimulatory
peptide. Its serum level could be a reliable marker in assessing pediatric malignancies with high metastatic
potentials.
PMID: 16508683

157
 Community respiratory viruses as a cause of lower respiratory tract infections following
suppressive chemotherapy in cancer patients.

El-Mahallawy HA; Ibrahim MH; Shalaby L; Kandil A

Community respiratory viruses are an important cause of respiratory disease in the immunocompromised
patients with cancer. To evaluate the occurrence and clinical significance of respiratory virus infections in
hospitalized cancer patients at National Cancer Institute, Cairo University, during anticancer treatment, we
studied cases that developed episodes of lower respiratory tract infections (LRTI).Thirty patients with LRTI
were studied clinically, radiologically, and microbiologically. Sputum cultures were done and an
immunofluorescence search for IgM antibodies of influenza A and B, parainfluenza serotypes 1, 2 and 3,
adenovirus, respiratory syncytial virus, Legionella pneumophila, Coxiella burnettii, Chlamydia pneumoniae, and
Mycoplasma pneumoniae were performed on serum samples of patients.The main presenting symptom was
cough and expectoration. Hematologic malignancy was the underlying disease in 86.6% of cases. Blood
cultures were positive in 11 patients (36.6%) only. Sputum cultures revealed a bacterial pathogen in 13 cases
and fungi in 3; whereas viral and atypical bacterial IgM antibodies were detected in 13 and 4 patients;
respectively. Influenza virus was the commonest virus detected, being of type B in 4 cases, type A in one case
and mixed A and B in another 5 cases; followed by RSV in 5 patients. Taken together, bacteria were identified
as a single cause of LRTI in 10 cases, viruses in 6, fungi in 3 and mixed causes in 7. Still, there were 4
undiagnosed cases.This study showed that respiratory viruses are common in LRTI, either as a single cause or
mixed with bacterial pathogens, in hospitalized cancer patients receiving chemotherapy. Diagnostic tests for
respiratory viruses should be incorporated in the routine diagnostic study of patients with hematologic
malignancies. Also, it must be emphasized that early CT chest is crucial as a base-line prior to initiation of anti-
fungal or anti-viral therapy. In cancer patients with a febrile episode and LRTI, tailored therapy is
recommended according to the clinical findings of the patient.
PMID: 20927224

Comparison of dosimetric characteristics of Siemens virtual and physical wedges for

ONCOR linear accelerator.

Attalla EM; Abo-Elenein HS; Ammar H; El-Desoky I

Dosimetric properties of virtual wedge (VW) and physical wedge (PW) in 6- and 10-MV photon beams from a
Siemens ONCOR linear accelerator, including wedge factors, depth doses, dose profiles, peripheral doses, are
compared. While there is a great difference in absolute values of wedge factors, VW factors (VWFs) and PW
factors (PWFs) have a similar trend as a function of field size. PWFs have stronger depth dependence than VWF
due to beam hardening in PW fields. VW dose profiles in the wedge direction, in general, match very well with
those of PW, except in the toe area of large wedge angles with large field sizes. Dose profiles in the nonwedge
direction show a significant reduction in PW fields due to off-axis beam softening and oblique filtration. PW
fields have significantly higher peripheral doses than open and VW fields. VW fields have similar surface doses
as the open fields, while PW fields have lower surface doses. Surface doses for both VW and PW increase with
field size and slightly with wedge angle. For VW fields with wedge angles 45° and less, the initial gap up to 3 cm
is dosimetrically acceptable when compared to dose profiles of PW. VW fields in general use less monitor units
than PW fields.
PMID: 19173711

Consensus siRNA for inhibition of HCV genotype-4 replication.

Zekri AR; Bahnassy AA; El-Din HM; Salama HM

HCV is circulating as a heterogeneous group of quasispecies. It has been addressed that siRNA can inhibit HCV
replication in-vitro using HCV clone and/or replicon which have only one genotype. The current study was
conducted to assess whether siRNA can inhibit different HCV genotypes with many quasispecies and to assess
whether consensus siRNA have the same effect as regular siRNA.We generated two chemically synthesized

158
consensus siRNAs (Z3 and Z5) which cover most known HCV genotype sequences and quasispecies using
Ambium system. Highly positive HCV patient's serum with nine quasispecies was transfected in-vitro to Huh-7
cell line which supports HCV genotype-4 replication. siRNA (Z3&Z5) were transfected according to Qiagen
Porta-lipid technique and subsequently cultured for eight days. HCV replication was monitored by RT-PCR for
detection of plus and minus strands. Real-time PCR was used for quantification of HCV, whereas detection of
the viral core protein was performed by western blot.HCV RNA levels decreased 18-fold (P = 0.001) and 25-fold
(P = 0.0005) in cells transfected with Z3 and Z5, respectively, on Day 2 post transfection and continued for Day
3 by Z3 and Day 7 by Z5. Reduction of core protein expression was reported at Day 2 post Z3 siRNA
transfection and at Day 1 post Z5 siRNA, which was persistent for Day 4 for the former and for Day 6 for the
latter.Consensus siRNA could be used as a new molecular target therapy to effectively inhibit HCV replication
in the presence of more than one HCV quasispecies.
PMID: 16425355

Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver disease

progression.

Zekri AR; Ashour MS; Hassan A; Alam El-Din HM; El-Shehaby AM; Abu-Shady MA

To observe the imbalance between T helper cell Th1 and Th2 cytokines in several chronic hepatitis disease at
different stages of disease progression.We measured the cytokine levels of Th1 (IL-2 and IL-2R), Th2 (IL-10) and
the pro-inflammatory cytokines (IL-6 and IL-6R and TNF and TNF-RI and II) by the ELISA technique in the sera of
33 hepatocellular carcinoma (HCC) patients and 20 chronic liver disease (CLD) patients. In addition, 20
asymptomatic hepatitis C virus carriers and 20 healthy subjects negative for hepatitis C virus(HCV) markers
served as controls.Anti-HCV antibodies were found to be positive in 94% of HCC cases and 75% of CLD cases.
On the other hand, HCV viremia was detected using RT-PCR in 67% of HCC cases and 65% of CLD cases. HBsAg
was positive in 9% of HCC cases and 30% of CLD cases. Also bilharzial-Ab was positive in 55% of HCC cases, 65%
of CLD cases and in 70% of asymptomatic carriers (ASC). HCC patients had significantly higher values of IL-2R,
TNF-RII (P<0.001), and TNF-RI (P>0.05), but lower TNFalpha (P<0.001) and IL-6 (P = 0.032) in comparison to
ASC. But, in comparison to non-cancer controls, HCC patients had higher values of IL-2R, IL-6R, TNF-RI and TNF-
RII, but lower TNF-alpha (P<0.001). CLD patients had higher IL-2R, TNF-RI, and TNF-RII (P<0.001) than ASC. But,
in comparison to non-cancer controls, CLD patients had higher values of IL-2R, TNF-RI and TNF-RII, but lower
TNF-alpha (P<0.001). IL-10 was higher (though not significantly) in HCC and CLD patients than in symptomatic
carriers and non-cancer controls.Liver disease progression from CLD to HCC due to HCV genotype-4 infection is
associated with an imbalance between Th1 and Th2 cytokines. IL-2R, TNF-RI, and TNF-RII could be used as
potential markers.
PMID: 17786720

Detection of simian virus 40 DNA sequences in Egyptian patients with different

hematological malignancies.

Zekri AR; Mohamed W; Bahnassy A; Refat L; Khaled M; Shalaby S; Hafez M

SV40 DNA sequences have been detected in non-Hodgkin's lymphoma patients. A link between SV40 and NHL
is biologically plausible since SV40 causes hematological malignancies in laboratory rodents. We investigated
266 Egyptian cases of hematological malignancies (158 NHL, 54 HD, 26 ALL, 13 AML, 8 CLL, 7 CML) and 34
subjects as a control for detection of SV40 DNA using nested PCR. SV40 DNA sequences were found in (53.8%)
of NHL, (29.6%) of HD and in (40.7%) of different types of leukemia cases. Frequency of SV40 DNA sequences
was higher in NHL patients compared with those with the other tumors and control group (p < 0.05). The
highest frequency was in Burkitt's lymphoma followed by diffuse large B-cell lymphoma. The present study
suggests that SV40 is significantly associated with non-Hodgkin's lymphoma and most probably acts as a
cofactor in the pathogenesis of these tumors. This could lead to new diagnostic, therapeutic, and preventive
approaches.
PMID: 15959548

159
 Dexmedetomidine vs. propofol for short-term sedation of postoperative mechanically
ventilated patients.

Elbaradie S; El Mahalawy FH; Solyman AH

Propofol is often used for sedation in the intensive care unit. The aim of this study was to compare the efficacy
and endocrine response of propofol vs. the new alpha2-agonist dexmedetomidine for sedation in surgical
intensive care patients who need postoperative short-term ventilation.Our work is a randomized clinical study
conducted on sixty adult patients who required postoperative short term ventilation and sedation. The
patients were allocated randomly, to receive IV infusion of either dexmedetomidine 0.2-0.5 microg/kg/h or
propofol 0.5-1 mg/kg/h. Hemodynamic parameters, Ramsay sedation score, extubation time and serum
cortisol and interleukin-6 (IL-6) levels were measured.Ramsay sedation score was 4.1+/-1 and 4+/-0.9 for
propofol and dexmedetomidine, respectively, (p=0.59.) Total fentanyl dose in the propofol group was 75+/-15
microg compared to 15+/-10.5 microg in the dexmedetomidine group, (p=0.0045). Patients who received
dexmedetomidine infusion had significantly lower heart rates compared to patients who received propofol
infusion, (p=0.041). Pre-infusion serum concentrations of IL-6 were comparable in both groups, while the 24 h
post-infusion levels were insignificantly decreased in both groups compared to pre-infusion level, (p=0.36).
There were no intergroup differences in serum cortisol concentrations (p=0.231).Dexmedetomidine and
propofol are safe sedative drugs for postoperative mechanichally ventilated patients. Patients were easily
aroused to co-operate without showing signs of irritations with less fentanyl analgesia in the
dexmedetomidine group. Dexmedetomidine and propofol do not inhibit adrenal function, but they may
influence the inflammatory response.
PMID: 8897161

Diverse patterns of recognition of hepatitis C virus core and nonstructural antigens by

antibodies present in Egyptian cancer patients and blood donors.

Attia MA; Zekri AR; Goudsmit J; Boom R; Khaled HM; Mansour MT; de Wolf F; el-Din HM; Sol CJ

Serum samples from 429 cancer patients, 82 unpaid blood donors, and 74 paid blood donors were tested for
hepatitis C virus (HCV) markers in two commercially available enzyme immunoassays (EIAs). A total of 229 of
429 (53.4%) cancer patients were positive by the two EIAs. A total of 34 of 156 (21.8%) of the blood donors
were positive by the EIAs, with a higher prevalence among paid blood donors (20/74; 27%) compared with that
among the unpaid blood donors (14 of 82; 17%). EIA-positive sera were tested for confirmation of the results
in an immunoblot assay (LiaTek) in which reactivities to four synthetic peptides representing the HCV core
protein and two synthetic peptides representing nonstructural proteins 4 and 5 were measured. Of 243 first
and/or second EIA-positive samples from cancer patients, 188 (77.2%) were confirmed to be positive in the
synthetic peptide immunoblot. A total of 33 of 35 (94.3%) blood donor samples were confirmed to be positive.
A great diversity in reactivity patterns was seen. However, all sera from the group of paid blood donors were
exclusively reactive to core peptides 1 and 2. A subset of LiaTek assay-positive samples were tested by the
four-antigen RIBA-2 assay. The sera from the paid blood donors were all nonreactive. A subset of the LiaTek-
positive sera was analyzed for the presence of the HCV genome by reverse transcriptase-PCR. Eleven of the 20
serum samples with reactivity to LiaTek core peptides 1 and 2 only were HCV reverse transcriptase-PCR
positive, as were the majority of the sera with other reactivity patterns by the LiaTek assay. The results confirm
the very high prevalence of HCV infection in Egypt. Furthermore, the results indicate that there is circulating in
Egypt, particularly in the group of blood donors paid for their donation, an HCV variant which elicits an
immune response that is not detected by the RIBA-2 assay.
PMID: 20084794

Dosimetry study comparing NCS report-2 versus IAEA report TRS-398 for high energy
photon beams.

Attalla EM; Khaled NE; Abou-Elenein HS; Elsayed AA

160
In this work a dosimetry study is presented in which the results of absorbed dose data determined under
reference condition according to the IAEA TRS-398 protocol and the NCS report-2 are compared. The IAEA TRS-
398 protocol for absorbed dose calibration is based on ionization chamber having an absorbed dose to water
calibration factor N(D,W), while the NCS-2 report for absorbed dose calibration is based on an ionization
chamber having an air- kerma calibration factor N(K). This study shows that the absorbed dose calculated with
the IAEA TRS-398 formalisms is higher than that calculated with the NCS Report-2 formalism within a range of
0.4 to 0.9% in a cobalt-60 beam, and from 0.2 to 1.1% for photon beams of 6, 8 and 18 MV. The chambers
used are PTW 30001, 30004, and NE-2571, which have calibration factors N(K) and N(D,W) traceable to the
BIPM (Bureau International des Poids et Mesures).
PMID: 17366527

Early hospital discharge versus continued hospitalization in febrile pediatric cancer

patients with prolonged neutropenia: A randomized, prospective study.

Ahmed N; El-Mahallawy HA; Ahmed IA; Nassif S; El-Beshlawy A; El-Haddad A

Hospitalization with single or multi-agent antibiotic therapy has been the standard of care for treatment of
febrile neutropenia in cancer patients. We hypothesized that an empiric antibiotic regimen that is effective
and that can be administered once-daily will allow for improved hospital utilization by early transition to
outpatient care.Febrile pediatric cancer patients with anticipated prolonged neutropenia were randomized
between a regimen of once-daily ceftriaxone plus amikacin (C + A) and imipenem monotherapy (control).
Afebrile patients on C + A satisfying "Early Discharge Criteria" at 72 hr continued treatment as outpatients. We
compared the outcome, adverse events, duration of hospitalization, and cost between both groups.A
prospective randomized controlled clinical trial was conducted on 129 febrile episodes in pediatric cancer
patients with prolonged neutropenia. No adverse events were seen in 32 children (84% of study arm) treated
on an outpatient basis. We found a statistically significant difference between the duration of hospitalization
of the C + A group [median 5 days] and control [median 9 days](P < 0.001), per episode antibiotic cost (P <
0.001) and total episode cost (P < 0.001). There was no statistically significant difference in the response to
treatment at 72 hr or after necessary antimicrobial modifications.We conclude that pediatric febrile cancer
patients initially considered at risk for sepsis due to prolonged neutropenia can be re-evaluated at 72 hr for
outpatient therapy. The convenience, low incidence of adverse effects, and cost benefit of the once-daily
regimen of C + A may be particularly useful to reduce the overall treatment costs and duration of
hospitalization.
PMID: 19058953

Effect of magnetic resonance myelography on the target volume in craniospinal irradiation

in children.

Nazmy MS; Attalla EM; Refeat A

To examine the potential role of magnetic resonance myelography (MRM) in defining the clinical target
volume for the spinal field in craniospinal irradiation in children.Of the 42 patients for whom magnetic
resonance imaging (MRI) of the spine was carried out, 12 patients had MRM. The width of the cerebrospinal
fluid (CSF) with any lateral extension at different levels was measured from the coronal MRM. The clinical
target volume was defined using MRM and the conformal field surface area was compared with the direct
conventional field. The inferior border of the thecal sac was determined from MRI spine of 42 patients.Coronal
MRM showed variation in the width of the CSF at different levels. The maximum width was 2.9 cm (level of
C2). In the same case, the width of the CSF at the level of D8 was 1.7 cm. The mean surface area of the
conventional field that covered the CSF was 190.6 cm(2), as compared with 150.5 cm(2) using conformal field,
with an 18.5% reduction in the irradiated surface area. The thecal sac ended at S2 in 40.4% of the patients,
whereas it ended above and below this level in 28.6 and 31%, respectively.Implementation of coronal MRM
during the treatment planning will improve target definition and lead to a more conformal field. Planning
systems with the ability to fuse MRM with reconstructed coronal computed tomography are highly desirable.
The use of MRI is highly recommended to individualise the lower border of the spinal field in craniospinal
irradiation.

161
PMID: 7525763

Egypt: status of cancer pain and palliative care.

Tawfik MO
PMID: 14966830

Epidemiologic profile of symptomatic gastroenteritis in pediatric oncology patients

receiving chemotherapy.

El-Mahallawy HA; El-Din NH; Salah F; El-Arousy M; El-Naga SA

Patients with cancer who receive intensive chemotherapeutic regimens are subject to profound
immunosuppression and are susceptible to an extended array of pathogens.The infectious causes of
symptomatic gastroenteritis as evidenced by diarrhea +/- fever, vomiting, and abdominal colic in children
following chemotherapy were prospectively monitored at National Cancer Institute, Cairo University.A total of
104 diarrhea episodes were recorded in our institution during a 10-month period, of which an infectious cause
was detected in 74 (71.1%). Bacterial and fungal pathogens were isolated in culture from 41 (39.4%) and 24
(23.1%), respectively, while Clostridia difficile (C. difficile) and Cryptosporidium parvum (C. parvum) were
detected in 15 (14.4%) and 10 (9.6%) of 104 diarrhea episodes following chemotherapy, respectively. Mixed
infections were found in 24 of the patients; whereas, no cause was demonstrable in 30. Hospital acquired and
mixed infections were the worst as regards morbidity (P = 0.004 and 0.02) and mortality (P = 0.007 and <0.001)
of the infectious episode regardless the cause, respectively. On multivariate analysis, C. difficile was associated
with the highest mortality rate (OR = 0.04, 95% CI = 0.01-0.19), followed by fungal pathogens (OR = 0.20, 95%
CI = 0.05-0.74) and bacterial infections (OR = 0.20, 95% CI = 0.05-0.79).Infectious gastroenteritis is an
important cause of morbidity and mortality in hospitalized pediatric cancer patients receiving intensified
protocols of chemotherapy.
PMID: 12515905

Evaluation of blood units with isolated anti HBC for the presence of HBV DNA.

Zekri AR; Awlia AA; El Mahalawi H; Ismail EF; Mabrouk GM

We screened blood donors in one center in Saudi Arabia for a safety transfusion. We found that among 5043
blood donors negative for HCV and HIV, the incidence of HBsAg positivity was 2.97%. When antiHBc antibody
was measured (HBcIg) in HBsAg negative donors, we observed that 21.47% were positive indicating previous
exposure to hepatitis B virus. The HBcIg positive blood was further screened for HBsAb and the specimens
were found to be reactive in 81.54%. Based on these data blood transfusion was permissible from donors who
showed HBsAg negativity, HBcIg positive and HBsAb reactive blood. In order to ensure safety transfusion an
aliquot of specimens (n = 80) was further analyzed for HBV DNA by PCR. We found only one specimen positive
with incidence of 1.25%. So we recommended restricting transfusion from the previously mentioned donors to
emergencies.
PMID: 22099934

Evaluation of nuclear unrest and p53 immunostaining in Wilms' tumor.

Salama A; Kamel A

Nuclear unrest is a term applied to Wilms' tumors (WT) that show nuclear abnormalities close to anaplasia but
without abnormal mitoses. p53 is claimed to be associated with anaplasia and poor prognosis. This study was
undertaken to evaluate the clinical significance of nuclear unrest and p53 immunostaining in Wilms'
tumor.This is a retrospective study of 63 patients who presented at NCI with Wilms' tumors, and underwent
preoperative chemotherapy followed by nephrectomy. Histopathologic assessment and p53
immunohistochemistry were done.WT with nuclear unrest grade III closely resembled anaplastic tumors and

162
both of them (group 1) constituted 19% of cases. Group 1 constituted 29% of cases showing blastema
dominant morphology compared to 9.4% of cases without blastema dominant morphology with significant
statistical difference (p=0.047). Almost 83% of cases that achieved 1st complete remission were stages I, II and
III, while 17% were stages IV and V with significant statistical difference (p<0.001). Stage affected the 3-year
relapse-free-survival (RFS) significantly (p=0.014) as it was more in stages I, II and III than in stages IV and V
(75.4% versus 50%). Blastema dominant morphology and high risk state significantly lowered the 3-year overall
survival (OS) into 54.8% in comparison to 80.9% for cases with non-blastema dominant morphology (p=0.042).
Regarding p53 immunohistochemistry, group 1 tumors showed positive p53 more than group 2 with significant
statistical difference (p=0.014). p53 Positive immunostaining was significantly associated with high risk
nephroblastoma (p=0.004).Tumor stage and blastema dominant morphology are potent prognostic factors.
p53 is linked to blastema dominant morphology. WT with nuclear unrest grade III closely resembles anaplastic
WT. It may be appropriate to group tumors with nuclear unrest grade III with anaplastic histology regarding
treatment stratification.
PMID: 17127630

Evaluation of pan-fungal PCR assay and Aspergillus antigen detection in the diagnosis of
invasive fungal infections in high risk paediatric cancer patients.

El-Mahallawy HA; Shaker HH; Ali Helmy H; Mostafa T; Razak Abo-Sedah A

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal
infection. As the early diagnosis of invasive fungal infection (IFI) is difficult, these infections are still associated
with high morbidity and mortality. Recently, Pan-fungal polymerase chain reaction (PCR) has been a promising
aid in rapid, early diagnosis of IFI. During the past few years, increasing numbers of suspected IFIs were
encountered at our institution in patients with prolonged neutropenia after intensified immunosuppressive
chemotherapy. The aim of this study was to investigate the diagnostic utility of both the aspergillus
galactomannan (GM) antigen and the pan-fungal PCR assay in the diagnosis of IFI in high risk febrile
neutropenic paediatric cancer patients. During one year period, 91 febrile neutropenic (FN) paediatric cases at
high risk for developing IFI while receiving chemotherapy were investigated at National Cancer Institute, Egypt.
These patients were subjected to clinical evaluation, chest CT scan, conventional blood cultures for bacterial
and fungal pathogens, aspergillus GM antigen detection and PCR assay utilizing pan-fungal primers. Of the 91
FN episodes, 15 were proven IFI; whereas 27 cases were either probable (n=13) or possible IFI (n=14), and 49
were unlikely to be IFI episodes. Based on positive results for proven/probable IFI and compared to culture
results, Pan-fungal PCR showed sensitivity, specificity, positive and negative predictive values of 75%, 92%,
84% and 87%; respectively. Aspergillus antigen test showed a sensitivity of 79%, specificity of 61%, positive
and negative predictive values of 54% and 83%; respectively. A negative PCR in the proven and probable cases
was closely related to previous antifungal therapy for a prior history of IFI. In patients at high risk for IFI,
neither the sensitivity, nor specificity of the GM test was sufficient. The results of PCR assay was reasonably
specific but not very sensitive and had a chance of missing the diagnosis of IFI. The PCR assay seems a
promising test for objectively defining IFI, but is not recommended as the only tool for diagnosing IFI.
Combining microscopy, culture, and PCR may improve the diagnostic outcome.
PMID: 20664339

Evaluation of posteromedial transdiscal superior hypogastric block after failure of the

classic approach.

Nabil D; Eissa AA

The iliac crest and L5 transverse process are potential barriers to proper needle placement in superior
hypogastric plexus block (SHPB) for pelvic cancer pain. Several investigators report successful SHPB using a
paramedian transdiscal approach. Another new single puncture approach, posteromedian transdiscal, has
been described which can be performed with the patient in either lateral or prone position.Twenty-two
patients were included in the study. Visual analog score, daily morphine consumption, duration of the
procedure, side effects, and Quality of Life Questionnaire-C30 were recorded.The duration of the procedure
was 21.4 ± 6.5 minutes. The mean visual analog score, daily morphine consumption, and Quality of Life

163
Questionnaire-C30 score were significantly decreased. There was no neural injury, headache, discitis, or disc
herniation.The posteromedian transdiscal approach to SHPB for cancer pain proved to be safe and reliable
compared with the classic technique. No nerve or disc-related complications were noted.
PMID: 19054267

Expression of pro- and anti-inflammatory cytokines in relation to apoptotic genes in

Egyptian liver disease patients associated with HCV-genotype-4.

Zekri AR; Bahnassy AA; Abdel-Wahab SA; Khafagy MM; Loutfy SA; Radwan H; Shaarawy SM

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide strongly linked to hepatitis C
virus (HCV) infection. However, the exact pathogenetic mechanisms are still unclear.We assessed the
expression of apoptosis genes (GSK3-B, AKT-1, Bcl-2), inflammatory cytokines (TNFalpha, TNF-RI, TNF-RII, IL-6,
IL-6R), anti-inflammatory IL-10, CRP and alphaFP by reverse transcription-polymerase chain reaction (RT-PCR)
in 33 HCC, 25 chronic hepatitis and 16 asymptomatic HCV carrier positive for HCV subjects. Also, pooled
normal liver tissues and HepG2 cells were used as controls.Hepatocellular carcinoma and liver disease (LD)
showed reduced expression of GSK-3beta, TNFalpha, TNF-R I, TNF-RII, IL-10 and overexpression of IL-6R and
CRP with no significant difference between the two groups. AFP was expressed in HCC only (33%). AKT, BCL2
and IL-6 showed normal, reduced and overexpression in studied patients with a significant difference between
AFP, AKT overexpression (67% and 30%), BCL2 overexpression (49% and 10%) and reduced IL-6 in between
HCC and LD. The morphologically normal tissues adjacent to tumors showed aberrant expression of AKT, IL-6,
CRP, TNFalpha and TNFRI. A significant relation was observed between cirrhosis and GSK-3beta, AKT and IL-6
(P = 0.0018, P = 0.018, P = 0.0001; respectively).Aberrant expressions of AKT, GSK3-B, and BCL2 are common
events in HCV-associated LD and HCC. AKT, GSK3-B and IL-6 are significantly associated with cirrhosis and could
be used as biomarkers for both early detection and molecular target therapy for the prevention of HCC
development. TNFRII, GSK3-B and s-AFP could be used as prognostic factors that can predict the clinical
outcome of HCC patients.
PMID: 22588434

Fasting among Muslim cancer patients during the holy month of Ramadan.

Zeeneldin AA; Taha FM

Muslims constitute more than 20% of the world's population and have a significant share of its cancer cases.
Many Muslim cancer patients witness the fasting month of Ramadan but we do not know which individuals
elect to fast.Cross-sectional study conducted among Muslim cancer patients at the National Cancer Institute
(NCI), Egypt, during Ramadan, Hijri 1430 (the month of fasting) August-September 2009.One-hundred and two
patients being treated at the NCI were interviewed. The most common diagnoses were breast cancer (31%),
acute leukemia (24%), colorectal cancer (7%), non-Hodgkin lymphoma (5%), bladder cancer (4%), lung cancer
(4%), and laryngeal cancer (4%). The two sexes were equally represented and so were metastatic and
nonmetastatic diseases. The outpatient:inpatient ratio was 3:1. Treatments being received by these patients
included chemotherapy, radiotherapy, hormonal therapy, and nonspecific therapy in 42%, 31%, 10%, and 17%,
respectively. Other concomitant diseases were present in 22% of the patients.While 40% of patients did not
fast at all during Ramadan, 36% and 24% were partial and complete fasters, respectively. Female patients,
those with performance status (PS) 0 to 1, those whose disease was a nonmetastatic solid tumor, and those
receiving non-intravenous chemotherapy as outpatients were more likely to be fasting than their
corresponding counterparts. Being a female, having PS 0 to 1, and receiving treatment as an outpatient were
the only factors that were significant on multivariate analysis. Only 46% of patients sought the treating
oncologist advice on whether they could fast.Most cancer patients fast during Ramadan, but only half of them
discuss the issue with their oncologists. We hope that our study stimulates more research on this topic.
PMID: 17300723

164
 Genetic distance and heterogenecity between quasispecies is a critical predictor to IFN
response in Egyptian patients with HCV genotype-4.

Zekri AR; El-Din HM; Bahnassy AA; Khaled MM; Omar A; Fouad I; El-Hefnewi M; Thakeb F; El-Awady M

HCV is one of the major health problems in Egypt, where it is highly prevalent. Genotype 4 is the most
common genotype of HCV and its response to treatment is still a controversy.HCV genotype 4 quasispecies
diversity within the 5' untranslated region (5'UTR) was studied in a series of 22 native Egyptian patients with
chronic hepatitis C virus with no previous treatment who satisfied all NIH criteria for combined treatment of
pegylated IFN and ribavirine and was correlated with the outcome of treatment. The study also included 7
control patients with no antiviral treatment. HCV sequencing was done using the TRUGENE HCV 5-NC
genotyping kit.At the 48th week of treatment, 15 patients (68%) showed virological response. Whereas HCV-
RNA was still detected in 7 patients (32%) in this period; of those, 6 experienced a partial virological response
followed by viral breakthrough during treatment. Only one patient did not show any virological or chemical
response. The four females included in this study were all responders. There was a significant correlation
between the response rate and lower fibrosis (p = 0.026) as well as the total number of mutation spots
(including all the insertions, deletions, transitions and transversions) (p = 0.007, p = 0.035).Patients who
responded to interferon treatment had statistically significant less number in both transitions (p = 0.007) and
the genetic distances between the quasispecies (p = 0.035). So, viral genetic complexity and variability may
play a role in the response to IFN treatment. The consensus alignment of all three groups revealed no
characteristic pattern among the three groups. However, the G to A transitions at 160 was observed among
non responders who need further study to confirm this observation.
PMID: 22099961

Geometrical uncertainty margins in 3D conformal radiotherapy in the pediatric age group.

Eldebawy E; Attalla E; Eldesoky I; Zaghloul MS

To evaluate set-up variation of pediatric patients undergoing 3D conformal radiotherapy (3DCRT) using
electronic portal image device (EPID), in an effort to evaluate the adequacy of the planning target volume
(PTV) margin employed for the 3DCRT treatment of pediatric patients.Set-up data was collected from 48
pediatric patients treated with 3DCRTfor head and neck (31 patients), abdomino-pelvic (9 patients) and chest
(8 patients) sites during the period between September 2008 and February 2009. A total of 358 images
obtained by EPID were analyzed. The mean (M) and standard deviation (SD) for systematic and random errors
were calculated and the results were analyzed.All images were studied in anterior and lateral portals. The
systematic errors along longitudinal, lateral and vertical directions in all patients showed an M equal to 1.9,
1.6, and 1.6mm with SD of 1.8, 1.4, and 1.8mm, respectively; (head and neck cases: M equal to 1.5, 1.2, and
1.6mm with SD 1.4, 1.2, and 1.8mm; chest cases: M equal to 2.5, 1.8, and 0.8mm with SD 2.7, 1.7, and 1.2mm,
abdomino-pelvic cases: M equal to 2.9, 2.8 and 2.3mm with SD 1.6, 1.2, and 2.3mm). Similarly, the random
errors for all patients showed SD of 1.9, 1.6, and 1.8mm, respectively (head and neck cases: SD 1.7, 1.3, and
1.5mm; chest cases: SD 1.2, 1.9, and 2.5mm; abdomino-pelvic cases SD 2.5, 2, and 2.4mm, respectively). Using
Van Herk's formula the suggested (PTV) margin around the clinical target volume (CTV) of 5.5mm appears to
be adequate.The ranges of set-up errors are site specific and depends on many factors.
PMID: 12078799

Giant mediastinal chordoma.

Rahman AM; Farahat IG; Ali WA; Mansour KA

A chordoma is a slow-growing tumor representing about 5% of all malignant bone tumors. Mediastinal
chordoma is very rare. We report a giant thoracic chordoma in a 32-year-old woman who presented with chest
pain, progressive dyspnea, and cough. Open biopsy confirmed a definitive preoperative diagnosis, and
complete surgical excision of the tumor was accomplished.

165
PMID: 17631684

Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and
chronic active HBV infection.

Zekri AR; Hafez MM; Mohamed NI; Hassan ZK; El-Sayed MH; Khaled MM; Mansour T

There are eight genotypes of hepatitis B virus (A-H) and subgenotypes are recognized. Genotyping can be
accomplished based on a partial sequence of HBV genome such as the pre-S or S gene. Several methods have
been developed and used for HBV genotyping. This study was undertaken to determine the HBV genotypes in
Egyptian pediatric cancer patients with acute and chronic liver disease.HBV genotypes were determined in 22
patients who had acute forms of liver disease (AH) and in 48 patients with chronic active hepatitis (CAH). A
type-specific primer based the nested-PCR method was employed in the HBV genotyping.This study showed
that HBV infections in pediatric cancer patients are attributed predominantly to viral genotypes D and B that
constituted 37.1% and 25.7%, respectively of the total infections. In addition, there was a relatively high
prevalence of mixed infections of 15.7% among the studied group especially mixed A/D genotype infections.
Genotype D was found significantly more often in patients with CAH than in patients with AH [23/48(47.9%) v
3/22 (13.6%)].These findings show the distribution of HBV A-D genotypes in pediatric cancer Egyptian patients.
Furthermore, our results indicate a markedly high prevalence of mixed A/D genotype infections in subjects
with CAH and a possible association of mixed infections with the severity of liver diseases.
PMID: 11261753

Hepatitis C virus genotyping versus serotyping in Egyptian patients.

Zekri AR; Bahnassy AA; Ramadan AS; El-Bassuoni M; Badran A; Madwar MA

The RNA genome of hepatitis C virus (HCV) displays extensive sequence variation. In this study, serotyping and
genotyping techniques were applied to assess this variability by comparing the performance of the serotyping
assay with a panel of well-characterized HCV strains isolated from chronic active hepatitis (CAH) patients.60
serum samples from CAH patients were analyzed. All isolates were genotyped by a line probe assay and the
results of genotyping and serotyping were evaluated.The overall sensitivity of the serotyping and genotyping
techniques was 81.16% with a concordance of 73.3%. Type 4 was detected in 73.3% of cases and it was highly
heterogeneous.Type 4 HCV is the most prevalent type in Egyptian CAH patients and there is a high
concordance between the results of serotyping and genotyping techniques.
PMID: 16508682

Hepatocyte growth factor as a tumor marker in the serum of patients with prostate
cancer.

Hashem M; Essam T

Prostate cancer is a leading cause of death among men worldwide; it is invasive and metastasizes to different
organs. Metastatic spread of this type of cancer is the greatest barrier to achieve cure. The present study is
carried out to study the serum levels of hepatocyte growth factor (HGF) in patients with prostate cancer in
relation to stage and grade and to evaluate its diagnostic and prognostic clinical validity as a tumor marker.The
study included 47 patients with prostate cancer and 15 apparently healthy men as a control group. The
patients were divided into two groups, including 27 patients with localized prostate cancer (group I) and 20
patients with metastatic prostate cancer (group II). Detection of serum levels of HGF and prostate specific
antigen (PSA) was carried out by an enzyme immunoassay.The serum levels of HGF and PSA were significantly
increased in groups I and II as compared to the control group and were highest in group II. The best cut-off
value for HGF was 663.8 pg/ml with 83% and 93.3% sensitivity and specificity, and was 4.4 ng/ml for PSA with a
sensitivity and specificity of 85.1% and 100%; respectively; with positive and negative predictive values of
97.5%, 63.6% and 100%, 68.2%; respectively. Combining PSA and HGF was more accurate in distinguishing
between patients with metastatic disease and those with localized disease than either marker alone with a

166
sensitivity of 98.1% (p<0.05).HGF is elevated in the serum of patients with carcinoma of the prostate and this
elevation is related to the stage of malignancy and is independent of age. These results imply that HGF may be
an important serum marker for prostate cancer.
PMID: 16892095

How to write an oncology manuscript.

Gaafar R

Publications may represent accomplishment in academic medicine, primary documentation of research data,
evidence of expertise through writing an authoritative review paper or book chapter or a major determinant in
achieving academic promotion and career development. Editors and reviewers appreciate receiving
manuscripts that are easy to read and edit. Much of the information in journals instructions to authors is
designed to accomplish that goal in ways that meet each journal's particular editorial needs. The CONsolidated
Standards of Reporting Trial (CONSORT) statement is an important research tool that takes an evidence-based
approach to improve the quality of reports of randomized trials. The guidance that follows provides a general
background and rationale for preparing oncology manuscripts for any journal. Many of these guidelines are
based on feedback provided by actual peer reviewers. Even before you start writing, it is good practice to
review the typical sections of a manuscript The text of observational and experimental articles is usually (but
not necessarily) divided into sections with the headings Introduction, Methods, Results, and Discussion. This
so-called "IMRAD". The abstract of the manuscript is usually divided into background, purpose, patients and
methods, results and conclusion. The section on patients and methods of an oncology manuscript should
include the eligibility criteria for the patients, study design, treatment plan, baseline and treatment
assessments and statistical analysis. The results include data on patient characteristics, tumor response, time
to event measures, toxicity and dose administration. The conclusion must address the primary objective of the
study. Authors will be able to address up front many issues regarding content, organization, presentation, and
formatting, thereby increasing the likelihood of successful publication of their papers in peer-reviewed
journals.
PMID: 15693850

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53,

p21, mdm2, C-erbB2 and impact on survival.

Bahnassy AA; Zekri AR; Abdallah S; El-Shehaby AM; Sherif GM

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2,
p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC
were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation
polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to
determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of
tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and
60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of
tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40%
each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2,
c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf).
Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent
pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the
p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are
independent prognostic markers.
PMID: 17576388

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 Immunomodulators, sFas and Fas-L as potential noninvasive predictors of IFN treatment
in patients with HCV genotype-4.

Zekri AR; Haleem HA; Esmat GE; Bahnassy AA; El-Din HM; Hafez MM; Sharaby AF; Sharaf H; Zakaria MS

Recent studies have indicated that cytokines can be used as markers for disease progression in hepatitis C virus
(HCV)-infected patients, therefore this study was conducted to determine the influence of pegylated IFN vs
standard IFN on interleukin-2 receptor (IL-2R), IL-6R, IL-8, TNFR-I, TNFR-II, sFas, and sFas-L in Egyptian patients
with chronic hepatitis C genotype 4, as no previous studies have been performed on this genotype. We also
aim at establishing a possible relationship between these cytokines and the response to INF to determine
whether they can be used as noninvasive markers for the response to INF therapy and as monitors for the
outcome of treatment. Thirty-eight patients with chronic HCV hepatitis were investigated for the serum levels
of the previously mentioned cytokines in a randomized opened controlled trial (22 patients treated with
pegylated IFN and 16 patients treated with standard IFN). Cytokine levels were measured by ELISA at 0, 1 and
12 months of IFN therapy. There was marked increase in the serum levels of IL-2R and IL-6R in nonresponders
to pegylated interferon, IL-8, TNFR-I and II were significantly higher in nonresponders to standard interferon
but were also high in responders of pegylated interferon. sFas and sFas-L showed high levels among
responders to pegylated interferon but the standard interferon was again less effective in this regard. Serum
levels of TNFR-II, sFas and sFas-L have the potential to be used as serological markers for response to
pegylated IFN therapy, and IL-8 is a predictor for nonresponse. Moreover, TNFR-I and II have the potential to
be used as markers of response to standard IFN treatment. The persistent correlation between sFas and TNFR-
II may elaborate the possible role of pegylated IFN in the induction of apoptosis as a possible new mechanism
of viral clearance during treatment with pegylated interferon treatment.
PMID: 20424659

Limb sparing surgical resection of groin sarcoma. Surgical approach and reconstructive
options.

El-Sherbiny M

The aim of this study is to evaluate limb sparing surgical resection and reconstructive options in a group of
patients having soft tissue sarcoma of the groin and nearly most of them were previously subjected elsewhere
to some sort of mismanagement.Between 2001 and 2006, 14 patients having soft tissue sarcoma of the groin
presented to National Cancer Institute with some sort of mismanagement elsewhere. Preoperative
reevaluation included CT chest, MRI or MRA, Doppler US and angiography in some selected patients. According
to the Enneking staging system, 9 patients had stage II, 4 had stage IIA and 1 patient had stage III. Limb sparing
resection was done including wide resection of the tumor enbloc with the pubic bone or its rami and involved
femoral vessels and nerve. Abdominal wall defect was reconstructed by mesh, skin defect was reconstructed
by local myocutaneous flaps and vascular replacement was done by vascular prosthesis.The mean follow-up
period was 31 months (range 25-53 months). Surgical margins were negative in 13 patients and
microscopically positive in one patient. Femoral nerve was resected in 3 cases. Pubic bone resection was done
in all patients. Vascular resection and prothetic replacement were done in 2 cases. Ten cases required
myocutaneous flap reconstruction of skin defect, 2 cases required muscle flap only. All mobilized flaps showed
no failure. Complications included seroma in all cases, superficial stitch gaping in 3 cases, wound breakdown
and deep infection occurred in one case and chronic lymphedema in 5 cases. Limb sparing function according
to MSTS functional score ranged from 92 % to 97 %. The 2 year local control rate was 92.8 % and the 2 years
survival rate was 85.7 %.Patients having groin sarcoma with some sort of improper management may still have
a chance of successful limb sparing surgical resection with a curative intent and achievement of good
functional results. This requires proper preoperative reevaluation of the extension of the tumor and vascular
involvement, wide retroperitoneal exposure to maximize tumor resection, vascular replacement if ileofemoral
vessels are involved and local myocutaneous flap transfer to minimize the problems of wound healing and
subsequent infection. KEY WORDS: Groin sarcoma - Limb salvage - Groin defect reconstruction.

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PMID: 20424655

Limb-sparing surgery with vascular reconstruction for extremity soft tissue sarcomas:
surgical, oncological and functional outcomes.

El-Zohairy MA; El-Samadoni A; El-Sherbieny ME; Anwar H

The indications of limb-sparing surgery (LSS) for extremity soft tissue sarcoma (ESTS) can be extended by
excision with simultaneous reconstruction of major blood vessels without adding significant risk.From January
2005 to January 2009, 12 patients with (ESTS) underwent LSS with major vascular reconstruction. Patients with
metastatic disease and those with cardiopulmonary restraints were excluded. Arterial repair was mandatory
whilst venous repair was selective according to selected protocol. Data were collected regarding the method
of treatment, complications and tumor recurrence.All tumors could be resected without amputation. In spite
of the large tumor size 10 (83.3 %) patients were resected with negative margins. Vascular complications
occurred in eight patients: 4 cases of DVT, edema in 3 patients and one patient developed secondary
hemorrhage that ended up by limb amputation. Nonvascular complications occurred in nine patients: Partial
necrosis of the flap (n =2), wound infection (n =3), Wound dehiscence (n =2) hematoma (n =1) and seroma (n
=1). The 2-year overall survival rates were 53.9 %. Cumulative local recurrence free survival was 64.2 %.
Cumulative distant metastasis-free survival was 58.3 %. Survival was significantly longer for surgical margin >
10mm (p < 0.027). During a median follow-up period of 20 months, 4 (33.3 %) developed local recurrence and
6 (50 %) developed Distant metastases.Limb-sparing surgery with vascular reconstruction for extremity soft
tissue sarcomas achieves good local control and functional results in the majority of extremity sarcomas for
which amputation is infrequently indicated. KEY WORDS: Extremity Ssarcoma - Limb - Sparing surgery -
Vascular reconstruction.
PMID: 20029475

Long term behavior of pedicled vascularized fibular grafts in reconstruction of middle and
distal tibia after resection of malignant bone tumors.

El-Sherbiny M

The aim of this study was to evaluate the long term behavior of pedicled vascualrized fibula graft in
reconstruction of middle and distal tibia defects following malignant tumor resection with particular emphasis
on success in limb salvage and the specific late related complications.Between 1997 and 2006, 16 patients
having malignant bone tumors of the middle tibia (10 cases) and distal tibia (6 cases) were candidate for wide
resection of their tumors and reconstruction of the bony defect by ipsilateral vascularized pedicled fibular graft
based on the peroneal vessels. There were 9 males and 7 females with a mean age of 13 years at time of
surgery (range 11-23 years). Mean follow up period was 52 months (range 32 -110 months). Fixation was done
by cast in 14 cases and by plate and screws in 2 patients. According to the Enneking staging system (1), 9
patients had stage IIB and 7 had stage IIA. Bony union and hypertrophy were assessed radio graphically on
regular basis. Hypertrophy was estimated in a percentage. Functional limb results were also reported
according to MSTS functional scores [2].The mean length of bony gap bridged was 14 cm (range of 11.0-16.0
cm) and the mean length of fibula harvested was 15.5 cm (range 12-17 cm). Ninety seven percent of patients
(15 cases) healed primarily at a mean time of 4.8 months (range 3.5-6 months). Hypertrophy was evident in all
patients and ranged from 60 to 210% (mean 91% ). Increase in size of the hypertrophied fibula beyond the
recipient bone was noticed in three cases (18.7% ) and we relate this to weight-bearing forces and not to the
size of the recipient bone. The mean time of the fibula to double its size (10 cases) was 21 months (range 18-
31 months). Young patients developed full hypertrophy earlier than older patients. Complication rate was low.
One patient had non union at the proximal end of the fibulotibial junction and two patients had stress fracture
of the fibula.Long term follow-up of pedicled vascularized fibula in reconstruction of bony defects of the
middle or distal tibia after bone tumor resection showed that it is a useful tool in the limb salvage procedure. It
is a short procedure, inexpensive, with low rate of late complications. It has a good outcome regarding the
union, hypertrophy and the functional outcome.
PMID: 19896236

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 Lung cancer in the pregnant woman: to treat or not to treat, that is the question.

Azim HA; Peccatori FA; Pavlidis N

Lung cancer in pregnancy is a rare situation; however, it is increasingly reported in the past two decades. The
association might be more encountered in the coming years due to the rising trends of cigarette smoking
among young women and tendency to delay pregnancy to later in life. We performed a literature search
without any date or language restriction and identified 44 cases diagnosed and/or treated for lung cancer
during the course of pregnancy. Patients had poor post-partum outcome with less than one-forth alive at 1
year following delivery. There was a high incidence of metastases to the products of conception reaching 26%.
Eight patients were treated with systemic therapies during the course of gestation with normal fetal outcome
and no evidence of fetal or placental metastases. Counseling of these patients is very important. Apart from
the clinical conflict they pose, some ethical aspects should be taken in consideration. The poor maternal
prognosis should be discussed and the patient's autonomy should be respected to decide whether she wants
to keep the pregnancy or not.
PMID: 20571600

Multidisciplinary approach to wilms' tumor: a retrospective analytical study of 53

patients.

Naguib SF; El Haddad A; El Badawy SA; Zaghloul AS

The aim of this work was to assess the epidemiologic aspects, clinico-pathological features and the results of
multidisciplinary treatment of Wilms' tumor (WT) in pediatric patients treated at the National Cancer Institute
(NCI), Cairo University, between January 2002 and December 2004.This study included 53 patients, all under
the age of 16 years, with previously untreated WT. Initial evaluation of all patients comprised laboratory
investigations and radiological assessment which included chest X-ray and CT, abdomino-pelvic
ultrasonography and CT. Doppler study of the renal vein and vena cava and bone scan were done when
needed. Neoadjuvant chemotherapy was given to patients suffering from poor general condition, extensive
tumor thrombus in the renal vein, irresectable and bilateral (stage V) nephroblastoma. Otherwise, up-front
nephrectomy was the standard therapeutic approach in this study.The age of the patients ranged from 2 to
108 months with a mean of 39.9 months (+/-22.56). Males and females were almost equal in number (50.9%
and 49.1% respectively). Tumors were located in the left kidney in 52.8%, right kidney in 41.5% and bilaterally
in only 5.7% of the cases. An abdominal mass was the most common clinical presentation (77.4%). Favorable
histology was found in 86.3% while unfavorable histology was elicited in 13.7% of the cases. Congenital
anomalies were recorded in 4 patients. Stage I and III were the most common (29.4% each), followed by stage
II and IV (17.7% each), and finally by stage V (5.9%). Neoadjuvant chemotherapy was given to 27 cases while
up-front nephrectomy was undertaken in 26 cases. Intra-operative spillage occurred in 12% of patients who
had preoperative chemotherapy and 31% of those who had upfront nephrectomy. Postoperative abdominal
radiotherapy was given to 32 patients. Twenty five patients underwent renal bed irradiation only, while in the
other 7 whole abdominal irradiation was used. Additional chest bath (1200 cGy) was given to 7 patients.
Complete remission (CR) was achieved in 74%, while death during neoadjuvant therapy took place in 4% of the
cases. Disease progression during treatment was noticed in 8%. These patients were all treated with radio- and
chemotherapy. Fatal outcome supervened in 75% of these, whereas in 25%, CR could be accomplished.
Relapse after remission occurred in 14%. A 2nd CR could be achieved in 28.5% with a survival rate of 21.4%.
Patients who relapsed >12 months after 1st CR had a 14 month-survival rate of 37.5% compared to 0% in those
who relapsed <12 months after 1st CR. Disease-free survival (DFS) at 2 years was 82.4%, while overall survival
(OAS) at 2 years was 78.9%. Therapy-related complications were mainly related to chemotherapy in 49% of
patients and surgery in 5.9%.Tight communication between the surgical, the medical and the radiation
oncologists, together with the pathologist, is indispensable for better management of WT patients. Regional
lymph node biopsy and accurate marking of residual disease are essential components of surgical treatment
and heroic surgical attempts are unnecessary. Neoadjuvant chemotherapy, which is still a fertile source of
debate, could possibly help to avoid excessive post-operative radiotherapy and its potential complications.
Tumor stage and age of patient were found to affect the results of treatment of Wilms' tumor; but the only
statistically significant determinant of prognosis was histologic differentiation. Finally, further studies including

170
molecular markers are needed to augment therapy for the blastemal predominance subtype or for favorable
histology associated with loss of heterozygosity (LOA) at chromosomes 1p and 16q aiming at improved
survival. KEY WORDS: Wilms' tumor - Nephroblastoma.
PMID: 21503006

Multimodality treatment for non melanoma skin cancer: a prospective study done on 120
egyptian patients.

Mebed AH; Soliman HO; Gad ZS; Abdel Hay RM

Multiple currently accepted treatments for non melanoma skin cancer (NMSC) are now available.To present
multimodality treatment for NMSCs and to report any side effects or recurrence during three years follow-up
period.This is a prospective study including 120 patients with NMSCs. Patients were subjected to different
treatment modalities with follow-up for three years.103 Patients (85.8%) were treated by surgery with or
without post operative radiotherapy, 8 patients (5%) received only radiation therapy, 7 patients (5.8%) treated
by shave excision followed by medical treatment (intralesional interferon for 3 months, systemic retinoids and
cyclo-oxygenase inhibitor for 6 months), and 2 patients (1.7%) escaped the treatment. All patients treated by
shave excision followed by medical treatment showed complete healing of all lesions 6 months after
completing the course of treatment.Alternatives to the surgical management of NMSC may be preferred under
certain circumstances. KEY WORDS: BCC - Interferon - Retinoids - SCC.
PMID: 22099962

Nephron-sparing surgery for renal tumors.

Ezzat Ael H; Helmy A; Ibrahim AH

To report National Cancer Institute (NCI) experience in managing various benign and malignant renal tumors
with nephron sparing surgery (NSS), and to assess its safety and feasibility.Literature review for NSS, and
reviewing of the patients records who underwent NSS between the period from January-2000 to December-
2009 at NCI-Cairo University was done. Tumor related characteristics, indication for NSS, operative techniques,
postoperative complications, full histopathological data, and follow up results were reviewed.The total
number of patients was 15. Median age at surgery was 32 years (range from 1.5 to 65 years). Five patients had
bilateral tumors. The mean radiologic tumor size was 4.7±5.2cm. All patients had normal preoperative kidney
functions. Six patients had an absolute indication for NSS, while 6 patients had a relative indication, and 3
patients were elective. All 5 patients with bilateral tumors underwent bilateral simultaneous surgery. Cold
ischemia was used in 7 patients, 1 patient was exposed to warm ischemia. Manual compression was used in 2
patients, and no vascular control was applied in 5 patients. Complications were encountered in 2 patients, one
of them had urinary leakage which needed reoperation, and the other had subcutaneous hematoma which
was treated conservatively. Histopathological analysis revealed Wilm's tumor (7 patients), angiomyolipoma (4
patients), renal cell carcinoma (RCC) (3 patients), and Hydatid cyst (1 patient). All patients had negative
surgical margin. For patients with Wilm's tumor, the median follow up was 24.4 months (range from 5 to 94
months), two patients had local recurrence, and 1 patient had distant metastasis. For patients with RCC, The
median follow up was 14.7 months (range from 5 to 33 months) with no local recurrence or distant metastasis.
All patients had normal kidney functions during postoperative and follow up periods.NSS is a feasible safe
procedure that could be done with acceptable complications. It provides a good solution for patients with
bilateral benign tumors and early localized RCC.
PMID: 15912151

171
 Neuromuscular efficacy and histamine-release hemodynamic changes produced by
rocuronium versus atracurium: a comparative study.

Elbradie S

Rocuronium and atracurium are muscle relaxants used for short-and intermediate-duration surgical
procedures. This study compares rocuronium and atracurium with regard to neuromuscular efficacy,
hemodynamic changes, and their effects on plasma histamine concentration.Sixty adult patients scheduled for
general surgical operations lasting less than 120 minutes were clinically randomized to receive either 0.6mg/kg
rocuronium (group-1, n=30) or 0.5mg/kg atracurium (group-2, n=30). Twitch response to a course of four
electrical stimulations, baseline heart rate, and mean blood pressure were monitored, as well as histamine
levels through venous blood samples.The onset time of neuromuscular block was 54+/-22 seconds in the
rocuronium group, vs. 94+/-26 seconds in atracurium group (p=0.001). The clinical duration of the intubating
dose was 34+/-6.9 minutes in the rocuronium group, vs. 45+/-7.1 minutes in atracurium group (p<0.001).
Tracheas were intubated in less than 90 seconds from the time of the injection of the muscle relaxant in only
20 of the 30 patients in the atracurium group, but in all 30 patients in the rocuronium group (p=0.005).
Atracurium, but not rocuronium, produced significant reduction of mean arterial blood pressure and increased
heart rate at all times. Atracurium resulted in a significant increase in plasma histamine concentrations at one
and three minutes of 232% and 149% (as percentage changes from control values, p<0.01). This corresponded
significantly with the decrease in mean arterial blood pressure and the increase in heart rate (p<0.01).
Rocuronium did not result in significant changes in plasma histamine concentrations. Further, 62+/-10% of the
patients in the atracurium group, and none of rocuronium group, had clinical signs of histamine
release.Rocuronium provides more suitable conditions for rapid tracheal intubation than atracurium, is
associated with a shorter clinical duration, has less effect on mean arterial blood pressure and heart rate, and
has less histamine releasing potency when compared to atracurium.
PMID: 11604832

New millennium hospital management information system: experience of the National

Cancer Institute--Cairo University.

El Hattab E

The National Cancer Institute-Cairo University (NCI) is a leading cancer center in the Middle East and Africa. It
serves more than 15,000 new cases and more than 250,000 patient visit every year. The implementation of its
Hospital Management Information System was completed and the system was operational in 1992. Although
different modules were added to the HMIS, the core of the system has never been changed or updated. NCI
evaluated its current system. NCI also evaluated the modern tools in databases and programming. NCI came to
the conclusion that a new HMIS need to be installed. The needs of NCI staff were analyzed with consideration
to budget issues and the limitations of a developing country. Different hardware, networking and software
issues had to be considered in the updating. Arabization and customization were main factors in decision
making.
PMID: 17102816

Normal tissue radiosensitivity: prediction on deterministic or stochastic basis?

Awwad HK

For the same standardized physical radiation dose there is considerable variation, among different patients, of
the magnitude of early and late normal tissue reactions. Technical and clinical factors account for about one
third only of these variations. Genetic or epigenetic differences between patients account for the greater
proportion of interpatient radiosensitivity differences. Attempts have been made to correlate differences in
the tissue radiosensitivity with the in vitro radiosensitivity of fibroblasts or lymphocytes as well as with other
biological cellular processes related to cell death (mainly DNA repair and chromosomal aberrations). Apart
from some genetic diseases such as ataxia telangiectasia, there were positive results in some studies that

172
could not be reproduced in others. It is now realized that for normal tissue radiation-induced morbidity (a) cell
kill is not the only factor, (b) interaction with a large number of gene products, such as IL-2, IL-6, TGF-beta, is
involved, and (c) radiosensitivity differences can reflect genetic differences. Polymorphism in a wide range of
genes can now be demonstrated and analyzed as a source of variations in the radiation response. cDNA
microarray procedures can also allow simultaneous measurement, in the same sample, of thousands of genes
and thus avoiding basing the investigation on a restricted number of genes. Preliminary results could show
retrospectively a correlation between late normal tissue reactions and expression of certain genes. Using cDNA
microarray before radiotherapy to predict the occurrence of serious late reactions is still under consideration.
Theoretically, an efficient predictor procedure may serve in (a) detection of hypersensitive patients before
submitting them to highly toxic radiotherapy regimes such as whole body irradiation, (b) detection of
hypersensitive patients in clinical situations where radiotherapy can be effectively replaced by other
modalities, and (c) selection of patients for elaborate radiotherapy techniques involving dose escalation to
high levels.
PMID: 21448029

Optimizing pain care delivery in outpatient facilities: experience in NCI, Cairo, Egypt.

Hameed KA

As a result of increasing waiting lists of patients attending National Cancer Institute of Cairo, we are faced to
provide high-quality pain care service through our outpatient pain clinic. The program description presented
here shows the capacity of a 24 hours/7 days outpatient cancer pain management service to provide rapidly
accessible, high-quality care to patients with complex pain and palliative care symptom burdens. In addition,
this model avoids inpatient hospital admissions. Pain clinics of cancer are committed to helping patients and
families identify and implement the treatments necessary to achieve optimum functional ability and the best
possible quality of life. These clinics also help to communicate and work with the family physician, surgeon,
and other physicians associated with patient treatment. Cancer pain is complex in its causes, and affects all
parts of the body. It involves the tissues, body systems , and the mind. Being multidimensional, it is never
adequately addressed with unidimensional treatment. Pain management must extend beyond physical
approaches to include the psychological, social, and even spiritual aspects of the patient. Effective integrated
treatment fosters self awareness and teaches appropriate and effective self care. With time, complex issues
are managed, pain is reduced, and the patient moves toward peak physical and psychological functioning.
These goals can be achieved by providing the highest quality pain management services. Patients attending the
clinic get treated medically for their physical ailments. Their emotional and psychological problems also need
to be attended with an atmosphere of love and care. The mission of the highest quality service is to obtain
customer satisfaction with reduction of cost in a multidisciplinary (or better interdisciplinary) approach. This
can be reached by proper identification of the customers either internal or external, assessing their needs, and
implementing plans for their satisfaction. In addition, monitoring the improvement of such plans is an integral
part of the quality process. Importantly, the facility provides comprehensive care with professionals available
24 hours/7 days. On-call teams assigned to manage pain and other treatment modalities comprises of staff
supervised by the primary cancer clinicians; this arrangement facilitates reaching this goal. This study will
illustrate our experience through 25 years, trying to provide the highest care of patients with cancer pain on an
outpatient basis.
PMID: 19034341

Overdose problem associated with treatment planning software for high energy photons
in response of Panama's accident.

Attalla EM; Lotayef MM; Khalil EM; El-Hosiny HA; Nazmy MS

The purpose of this study was to quantify dose distribution errors by comparing actual dose measurements
with the calculated values done by the software. To evaluate the outcome of radiation overexposure related to
Panama's accident and in response to ensure that the treatment planning systems (T.P.S.) are being operated
in accordance with the appropriate quality assurance programme, we studied the central axis and pripheral
depth dose data using complex field shaped with blocks to quantify dose distribution errors.Multidata T.P.S.

173
software versions 2.35 and 2.40 and Helax T.P.S. software version 5.1 B were assesed. The calculated data of
the software treatment planning systems were verified by comparing these data with the actual dose
measurements for open and blocked high energy photon fields (Co-60, 6MV & 18MV photons).Close calculated
and measured results were obtained for the 2-D (Multidata) and 3-D treatment planning (TMS Helax). These
results were correct within 1 to 2% for open fields and 0.5 to 2.5% for peripheral blocked fields. Discrepancies
between calculated and measured data ranged between 13. to 36% along the central axis of complex blocked
fields when normalisation point was selected at the Dmax, when the normalisation point was selected near or
under the blocks, the variation between the calculated and the measured data was up to 500% difference.The
present results emphasize the importance of the proper selection of the normalization point in the radiation
field, as this facilitates detection of aberrant dose distribution (over exposure or under exposure).
PMID: 19847279

Palliative spleen irradiation: can we standardize its technique?

Nazmy MS; Radwan A; Mokhtar M

To explore the pattern of practice of palliative splenic irradiation (PSI) at the National Cancer Institute (NCI),
Cairo University.The medical records of patients referred for PSI during the time period from 1990 to 2005
were retrospectively reviewed. We compared the three most common planning techniques (two parallel
opposing, single direct field, anterior and lateral fields).Eighteen patients who received PSI were identified.
Thirteen patients were diagnosed as CML and 5 as CLL. The mean age of the patients was 44 (+/-16) years and
the majority were men (60%). Spleen enlargement was documented in all cases. The single direct anterior field
was the most commonly used technique. The dose per fraction ranged from 25 cGy to 100 cGy. The total dose
ranged from 125 cGy to 1200 cGy and the median was 200 cGy (mean 327 cGy). There was no significant
difference between CML and CLL patients regarding the dose level. Three out of 5 CLL patients and only one
out of 13 CML patients received re-irradiation. All patients showed subjective improvement regarding pain and
swelling. There was a significant increase in the hemoglobin level and a significant decrease in the WBC count.
The single direct field shows variations in the dose from 56 to 102%; however, it is the simplest and the best
regarding the dose to the surrounding normal tissues especially the kidney and the liver.PSI has a significant
palliative benefit. Although the most widely accepted technique is the 2 parallel opposing anterior-posterior
fields, single anterior field is also considered as a suitable option. Higher doses are needed for CLL patients
compared to CML patients.
PMID: 20601967

Paravertebral neurogenic tumors with intraspinal extension: preoperative evaluation and

surgical approach.

Hussein HA; Goda HA

To achieve adequate excision of paravertebral neurogenic tumors with intra spinal extension, safe
decompression of spinal cord and preservation of spine stability.From Nov. 2000 till July 2009 sixteen patients
of paravertebral neurogenic tumors with intraspinal extension (dumbbell tumors) were operated upon by
combined team work of surgical oncology and neurosurgery at the National Cancer Institute and at Kasr- Al
Einy Hospitals, Cairo University. All patients had CT with guided biopsy and MRI to evaluate extent of tumor
bone invasion, intraspinal component, to decide surgical approach and the need for spine fixation. Patients
were referred postoperatively to I.C.U for stabilization of general condition. Follow-up with radiology was done
for a period from 3-36 month.The group of patients were 9 males and 7 females with age range 1.5-47 year, 8
patients had tumors in post. Mediastinum, 7 in the retroperitoneal space and one in the cervicothoracic inlet.
Benign schwannoma were diagnosed in 5 cases, malignant schwannoma in 3, neurofibromatosis in one case,
neuroblastoma in 3 cases, ganglioneuroblastoma in 2 cases and ganglioneuroma in 2 cases. Anterior
transthoracic resection through posterolateral thoracotomy was used in 6 cases, anterior transabdominal
resection was done in 6 cases through midline or transverse incisions. Combined anterior and posterior
approach was used in 3 cases while Posterior approach was done in one case using medial para scapular
incision. Delivery of the tumor was done in 8 cases, widening of the intervertebral foramina in 3 cases,
costotransversectomy with lateral laminectomy in 3 cases while posterior laminectomy and total

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vertebrectomy was done in one case. We fixed the spine in 3 cases using Z-plate and screws, lateral plates and
screws with either iliac crest or isobone graft. All cord compression manifestations improved postoperatively
with perfect spine stability. Morbidity was detected in 3 cases in the form of (graft and plate infection in
posterior approach case, and limited spine mobility in 2 cases) while mortality of local and distant recurrence
within 16-19 month was registered in 3 cases.Para vertebral neurogenic tumors with intra spinal extension
could be diagnosed and evaluated with very high accuracy using C-T in adjunct with MRI. C-T guided biopsy can
select patients with pathological diagnosis that could be sensitive to pre operative chemotherapy and/or
radiotherapy to facilitate surgery. Adequate surgical resection is feasible in a combined team work with
different surgical approaches and possible spine fixation. KEY WORDS: Para vertebral - Neurogenic tumors -
Intra spinal extension - Surgical approach.
PMID: 20571598

Pediatric Non Metastatic Non Rhabdomyosarcoma Soft Tissue Sarcomas (NRSTSS): Five
Years Experience from NCI-Egypt.

El-Haddad AM; Ibrahim MF; El-Wakil MA; El-Bolkainy TN; Farahat IG

Evaluation of demographic, pathological, and clinical patterns in addition to treatment outcome of pediatric
NRSTS patients treated at the NCI, Egypt.21 pediatric patients of NRSTS between 2001 and 2006 were
included. Clinical and pathological diagnosis and subtyping verification were done. Patients' cohort formed of 3
treatment groups. (1) Patients who underwent complete surgical resection with no adjuvant therapies. (2)
Patients who received chemotherapy and complete surgical resection, and group (3) Patients with localized
unrersectable tumors for whom systemic chemotherapy only was given. Demographic, clinicopathological
variables, and treatment modalities were statistically evaluated and compared with the outcome.Tumors of
unknown histiogenesis followed by MPNST and myxofibrosarcoma were the most frequent tumor subtypes.
Low tumor grade was in favor of better outcome. With a median follow up of 2-years; respectively 100% and
81.1% of patients who had complete surgical resection of a localized disease with or without chemotherapy
entered in CR (p=0.01). Local failure rate was 27.2% among CR patients (n=17). Two patients suffered local
recurrance and one had distant disease metastasis.Complete surgical resection with or without chemotherapy
is the mainstay of therapy for localized NRSTS. Tumor grade and surgical resection of NRSTS are 2 important
predictors of prognosis. KEY WORDS: Nonrhabdomyosarcoma - Soft tissue sarcoma - Pediatric.
PMID: 20029476

Pedicled gastrocnemius flap: clinical application in limb sparing surgical resection of

sarcoma around the knee region and popliteal fossa.

El-Sherbiny M

To highlight on the versatility of superiorly based pedicled gastrocnemius muscle flap in the limb-sparing
surgery for bone or soft tissue sarcoma around the knee and popliteal fossa.A total of 30 patients with
localized bone or soft tissue sarcoma around the knee and popliteal fossa were treated with limb-salvage
procedure. The study included 5 cases with bone sarcoma of the distal femur, 15 cases having bone sarcoma of
proximal tibia and 10 cases having soft tissue sarcoma around the knee region and popliteal fossa. Routine
preoperative staging studies were done for every patient and included local plain radiography, local MRI,
isotopic bone scan and CT chest. Local MRA or angiography was done in selected cases. According to the
Enneking staging system, 19 patients had stage IIB and 11 had stage IIA. Patients having bone sarcoma of the
proximal tibia were subjected to wide resection, endoprosthetic reconstruction and reconstruction of the
extensor mechanism by the medial gastrocnemius muscle flap. Patients having bone sarcoma of the distal
femur were subjected to wide resection, endo prosthetic reconstruction and coverage of the prosthesis and
rebalance of the patellar tendon by the medial gastrocnemius flap. Patients having soft tissue sarcoma were
subjected to wide resection and soft tissue coverage with either medial or lateral myocutaneous
gastrocnemius flap or muscle flap with grafting. Limb function was evaluated according to MSTS functional
scores. Adjuvant chemotherapy or radiotherapy was given according to nationally-agreed protocols.There
were 18 males and 12 females with a mean age of 29 years at the time of surgery (range 11-44 years). The
mean follow-up period was 52 months (range 25-72 months). Resection with a negative bony and soft tissue

175
margins could be achieved in all cases. A total of 30 flaps were used and included medial gastrocnemius
muscle flaps in 21 cases (15 cases had proximal tibia endoprothesis, 5 cases had distal femur endoprothesis, 2
cases had soft tissue sarcoma infiltrating the chin of tibia), myocutaneous gastrocnemius flaps in 8 cases
having soft tissue sarcoma (5 had medial head flap and 3 cases lateral head flap). Flap survival was 100&. The
success rate of limb salvage was 96.6% with high score functional results according to MSTS functional scores.
The area of the skin island harvested in cases of myocutaneous flaps ranged from 11 to 18cm in length and
from 5 to 8cm in width and all these cases required grafting of the donor site. Complications included partial
wound dehiscence in one case, revision of the prosthesis in one case, amputation due to local recurrence in
one case and significant extension lag in 2 cases.The unique vascularization of the gastrocnemius muscle (one
pedicle to each head), the size of the muscle belly, the fact that it is situated in the dissection field and that its
transfer does not affect the function of the spared limb too adversely, makes it particularly suitable for limb
sparing procedures for sarcoma in the region of the knee and popliteal fossa. The medial head is the
workhorse muscle flap for soft tissue coverage of knee endoprothesis and reconstruction of extensor
mechanism. This decreases the rate of complications and improves the functional outcome. Reconstruction of
the soft issue defect improves wound healing, protects exposed deep structures and subsequently prevents
wound problems, delays adjuvant therapy and secondary amputation.
PMID: 20172169

Pedunculated endocardial left ventricular fibroma presenting with cerebral and bilateral
peripheral embolization.

Darwazah AK; Shoeb J; Eissa SS

Left ventricular fibroma is a rare benign tumour of the heart. We present the case of a 24-year-old man with
left hemiplegia and bilateral popliteal artery occlusion associated with left ventricular mass. The patient
underwent successful excision of a pedunculated mass attached to the trabeculae of left ventricular cavity.
Histopathologic examination confirmed the presence of fibroma associated with septic thrombus. The
association of fibroma and embolization is rare.
PMID: 2522918

Pharmacokinetics of etanidazole (SR-2508) in bladder and cervical cancer: evidence of

diffusion from urine.

Awwad HK; el Badawy S; abd el Baki H; Zaghloul M; el Moneim Osman A; Akoush H; Fairchild K

Following an IV infusion of 2.0 g/m2 of Etanidazole, the mean tumor concentration 40 min after injection was
126 micrograms/g in bladder cancer and 65 micrograms/g in cervical cancer. The tumor/plasma concentration
ratio was 1.88 in bladder and 0.85 in cervical cancer. This high tumor concentration in bladder cancer could be
accounted for by diffusion from a highly concentrated urine. This renders bladder cancer a suitable clinical
model for testing this sensitizer.
PMID: 15959552

Pleurodesis as a palliative treatment of advanced lung cancer with malignant pleural

effusion.

Mourad IA; Abdel Rahman AR; Aziz SA; Saber NM; Fouad FA

This study was conducted to evaluate the success rate of management of advanced. Lung cancer patients with
malignant pleural effusion comparing talc powder with tetracycline for pleurodesis.We report 60 patients with
lung cancer associated with malignant pleural effusion treated in the department of surgery NCI, Cairo
University, between January. 1998 and February, 2003. Patients were Divided Into Three Groups: Group I:
Pleurodesis using tetracycline (20 patients). Group II: Pleurodesis using talc slurry (20 patients). Group III:
Pleurodesis using talc insufflation (20 patients). Good response to pleurodesis is defined as no pleural fluid re-
accumulation or minimal pleural fluid re-accumulation not causing symptoms or requiring further aspiration

176
for one month.There were 34 males and 26 females, mean age was 54 years with range of 42-66 years, right
sided effusion was present in 32 patients (53%) and left sided in 28 patients (47%). Pathological subtypes were
adenocarcinoma in 32 patients, squamous cell carcinoma in 18 and undifferentiated carcinoma in 10 patients.
In group I, 12 patients (60%) showed good response to intrapleural tetracycline, 15 patients (75%) responded
in group II, while 17 patients (85%) showed good response in group III. Post pleurodesis complications
included, fever, chest pain and empyema.It is concluded from this study that thoracoscopic talc insufflation
was an effective, easy and low cost method for producing pleurodesis in patients with recurrent malignant
pleural effusion and proved to be better than talc slurry and tetracycline.
PMID: 16353076

Posterior mediastinal tumors: outcome of surgery.

Abdel Rahman AR; Sedera MA; Mourad IA; Aziz SA; Saber TK; Alsakary MA

The incidence of posterior mediastinal tumors relative to all tumors of the mediastinum is 23% to 30%. The
posterior mediastinum is a potential space along each side of the vertebral column and adjacent proximal
portion of the ribs. Primary tumors of posterior mediastinum are usually neurogenic. The aim of this study was
to evaluate different surgical approaches used for the resection of posterior mediastinal tumors, and to assess
morbidity, mortality and patients' survival.Between January 2001 and January 2004, 30 patients with posterior
mediastinal tumors were included. CT scan of the chest and CT guided biopsy were done for all patients;
whereas MRI was done for suspected intraspinal extension. Posterolateral thoracotomy was the approach
used in most of the patients. The Akwari approach was used in most of the patients with Dumbbell
tumors.Neurogenic tumors constituted 67% of cases, being neuroblastoma in 60%. The non neurogenic tumors
included a heterogenous group of rare tumors (n=10). Dumbbell tumors were found in 10 patients.
Neuroblastoma was the commonest tumor to cause intraspinal extension (40%). Wide local excision was done
in 13 patients; whereas extended resection was done in the remaining 17 patients. The mean intra-operative
blood loss was 800cc and the mean hospital stay was 12 days. The size of the resected tumor ranged from 3 X
4 cm to 30 X 22 cm, 80% of tumors were malignant. Morbidity in relation to the procedures developed in 8
patients (atelectasis, meningitis, paraplegia, Horner syndrome and mild wound sepsis in 4, 1, 1, 1 and 1 of the
patients; respectively). One postoperative mortality, due to meningitis was recorded. The overall survival by
the end of three years was 87.7% with a mean survival of 30.4 months. The overall disease free survival was
55.9% with a mean disease free survival of 26.2 months.Posterior mediastinal tumors may reach large size
before becoming symptomatic. Complete surgical excision (including adjacent invaded organs) mainly by open
technique should be the rule for these patients as there is survival benefit. Great care should be taken when
dealing with Dumbbell tumors.
PMID: 20979645

Presence of human herpes virus 6 (HHV6) in pediatric lymphomas: impact on clinical

course and association with cytomegalovirus infection.

Loutfy SA; Fawzy M; El-Wakil M; Moneer MM

Activation of herpes virus 6 (HHV6) has seen in Hodgkin's and non-Hodgkin's Lymphoma (HL&NHL) as a result
of lymphoma associated immunosuppression. Multiple studies have suggested an association between both
HHV6 and cytomegalovirus CMV for development of CMV disease affecting the pathogenesis of lymphoma.
Therefore, this study investigated the frequency of HHV6, its impact on clinical manifestations of lymphoma
and its possible association with risk for development of CMV infection in pediatric lymphoma
patients.Presence of HHV6 DNA and CMV DNA was investigated by PCR assay in both WBC's and plasma
samples from 50 patients diagnosed with HL or NHL. CMV antibody titer was also determined in sera obtained
from each patient. Twenty apparently healthy siblings were used as a control group.In a study group of 50
patients diagnosed with HL or NHL, 23/50 (46%) were found to be positive for herpes virus DNA (HHV6 or
CMV) in WBC's or plasma by PCR assay and this was significantly higher than its presence in the pediatric
control group 2/20 (10%) (p = 0.005). Ten out of these 23 (43%) were found to have active CMV infection. Fifty
six percent of patients with CMV infection were found among NHL cases with B- subtype. The presence of both
herpes viruses DNA was significantly associated with more frequent episodes of febrile neutropenia (median 3

177
episodes), absolute neutrophil count (< 0.8), lymphocytes (< 0.5), and low hemoglobin level (< 9.1), (p <
0.05).The presence of HHV6 can be considered as a predicting indicator of cellular immunosuppression
preceding the onset of CMV infection which may result in a severe outcome among pediatric lymphoma
patients.
PMID: 21475447

Presence of simian virus 40 DNA sequences in egyptian patients with lymphoproliferative

disorders.

Mohamed WS; Samra MA; Fawzy MA

Although no definite risk factors have emerged for the different hematological malignancies, a viral cause has
been postulated. Several studies have detected SV40 DNA sequences in tumor tissues obtained from non-
Hodgkin's lymphoma patients. A link between SV40 and NHL is biologically plausible because SV40 causes
hematological malignancies in laboratory rodents.We investigated 266 Egyptian cases of different
hematological malignancies, for the presence of SV40 DNA using multiplex nested PCR technique. These cases
consisted of 158 non-Hodgkin's lymphoma (NHL), 54 Hodgkin's disease(HD), 26 acute lymphocytic leukemia
(ALL), 13 acute myeloid leukemia (AML), 8 chronic lymphoblastic leukemia (CLL), 7 chronic myeloid leukemia
(CML), in addition to 34 subjects of control group.Our results have shown that SV40 DNA sequences were
found in 53.8% of non-Hodgkin lymphoma patients, 29.6% of Hodgkin's disease patients, and 40.7% of
different types of leukemia cases. Frequency of SV40 DNA sequences was higher in NHL patients compared to
the other tumor cases. Also, frequency of SV40 DNA sequences was significantly higher (p<0.05) in NHL
patients than in the control group. Regarding the different histological types of non-Hodgkin's lymphoma,
SV40 DNA sequences were detected frequently in diffuse large B-cell lymphoma and in follicular
lymphoma.The present study suggests that SV40 DNA virus is significantly associated with non-Hodgkin's
lymphoma and might have a role in the development of these hematological malignancies. Polyomavirus SV40
may act as a cofactor in the pathogenesis of these tumors and this could lead to new diagnostic, therapeutic,
and preventive approaches.
PMID: 22776813

Prevalence of bone marrow necrosis in Egyptian cancer patients referring to the National
Cancer Institute.

Elgamal BM; Rashed RA; Raslan HN

Bone marrow necrosis is a relatively rare entity which has been associated with a poor prognosis. It is most
commonly found in patients with neoplastic disorders and severe infections.The study comprised examination
of 5043 bone marrow biopsy specimens performed at the National Cancer Institute, Cairo University, over
7years period (March 2004-March 2011). It included 5years retrospective (2867 archived samples) and 2years
prospective (2176 samples).Bone marrow necrosis was diagnosed in fifteen out of 5043 examined specimens
with a percentage of 0.3% and ranged from mild to massive according to semiquantitative estimation.
Prognosis of all patients was poor with survival not exceeding 6months from the date of marrow necrosis
diagnosis.In Egyptian patients, bone marrow necrosis in association with malignancy is a rare disorder which is
accompanied by a poor outcome.
PMID: 21458039

Primary repair of rectovaginal fistulas complicating pelvic surgery by gracilis

myocutaneous flap.

Nassar OA

Complex rectovaginal fistulas repair are extremely challenging. Various surgical options have been suggested;
nevertheless, none had been universally accepted as the procedure of choice. This prospective study discusses
a novel surgical technique using gracilis myocutaneous flap interposition.Eleven patients had fistulas post-

178
resection of pelvic malignancy (n=10) and rectal endometriosis (n=1). Primary treatment was pelvic resection;
nevertheless, 6 cases had adjuvant chemo-irradiation, 2 cases had post-operative irradiation and 2 patients
had chemotherapy only. Fistulas mean diameter was 2±0.24 cm (1-3) and 8 patients (72.7%) had their fistulas
in the middle vaginal third. Repair was wide debridement of fistulas margins followed by gracilis
myocutaneous flap interposition with synchronous diverting stomas. Success was defined as healing of fistula
after stomal closure.Five patients were repaired by single gracilis myocutaneous flaps, 2 cases by simple
gracilis muscle and 4 cases by double gracilis myocutaneous flaps. Patients had a mean follow-up time of
34.8±5.03 months (12-67) and all patients had definitive healing of their fistulas (100%). Median time to stoma
closure was 2 months (1-5). Four women (36.4%) had at least one early postoperative complications including
temporary leak (n=3), vaginal sepsis (n=1), partial skin paddle necrosis (n=1) and donor limb deep venous
thrombosis (n=1). Late morbidities were seen in 3 cases (27.3%) including vaginal stricture, anorectal
anastomotic stricture and anastomotic tumor recurrence.Rectovaginal septum repair requires adequate
debridement of necrotic devascularized tissues, tissue transposition and reconstruction of vaginal wall. Gracilis
myocutaneous flaps are ideal for this issue.
PMID: 18839029

Professor Hassan K. Awwad; The Father of Radiation Oncology and Radiobiology in Egypt
and the Arab World, His Good Deeds Last Forever and Inspire us for the Future.

Zaghloul MS; El-Badawi SA; Abd Elbaky H

Our most respected professor Hassan K. Awwad passed away on January 5th, 2007, at the age of 81. He was
considered as the father of radiotherapy in Egypt. He was always named "The Professor", as he was the
founder of the radiotherapy departments at the National Cancer Institute, Cairo University&Faculty of
Medicine, Alexandria University. He also shared in developing NEMROCK (Kasr El Aini Center of Radiation
Oncology and Nuclear Medicine), the place where he graduated and worked during his early years of
experience. He, together with professor Reda Hamza, dean of NCI, Cairo at that time, had initiated 7 oncology
centers all over Egypt, from Aswan in the South to Dammietta and Damanhour in the North. These 7 centers
were developed by the Ministry of Health. Prof. Awwad and Prof. Hamza were responsible for facility providing
and plans. They chose all the necessary equipment, tools and personnel. These centers were in action since
1988 and are currently taking care of the oncology patients in a wide area of the country. Prof. Awwad
graduated from the Faculty of medicine, Cairo University, in 1949. He had his Medical Doctorate (MD) in
Radiotherapy from Alexandria University in 1956. The International Atomic Energy Agency (IAEA) awarded him
fellowships in France (Institute Gustave Rossy) to gain experience in brachytherapy in 1956 and 1971, England
1956, 1959. Another fellowship was awarded to Prof Awwad in Harvard University (Peter Bent Brigham
Hospital) in radiobiology and radiotherapy during the years 1964-1965. He personally and with other members
of the National Cancer Institute gave much of their efforts and time to teach, train and guide young
radiotherapists, biologists, physicists and radiation therapists through direct on-hand teaching and training as
well as holding training courses for radiation oncologists, physicists and technologists. He insisted to ensure its
regularity 4 times yearly. These courses trained a lot of personnel from all over Egypt, Sudan, Libya, Palastine,
Iraq, Uganda, Nigeria and other countries. He himself had many teaching missions in different Arab countries
(Saudi Arabia, Kuwait and others) for the sake of groups of his students that could not come to Egypt. He
served as the head of the Department of Radiation Oncology for more than 15 years (1970-1985), full time
Professor in Radiation Oncology and Radiobiology (1985-2007), Professor of Radiotherapy, Alexandria
University (1954-1970), Chief of the Department of Nuclear Medicine, Medical Research Institute, University of
Alexandria (1963-1964), Chief of the Radiotherapy Unit in the Heliopolis Hospital, Ministry of Public Health,
1985-2007. He was co-founder of the Egyptian Society of Cancer and acted as vice present and head of the
scientific committee of the society. He shared the activities of many Egyptian, Arab and international scientific
societies. His activities in these societies were great. Prof. Awwad had direct contact with his students that
never ended, even after some of them left to work in other places in USA, Canada, Europe or Arab Countries.
His students' specialty varied between radiobiology, pharmacology, biochemistry, tumor biology, radiation
oncology, medical oncology and surgical oncology. Prof. Awwad had more than 100 published articles on
hypoxia and hypoxic cell radiosensitizers, biology of growth of human tumors, biology and clinical models of
the time factor in external beam radiotherapy, biology and mathematical models of time factor in
brachytherapy, radioactive dynamic cancer studies of plasma protein metabolism, radioactive dynamic factor
studies of blood disorders and lymphoma, radiation damage of DNA and normal tissues,head and neck cancer,

179
bladder cancer, breast cancer, cervical cancer and development and optimization of clinical radiotherapy. He
had continuous cooperation and collaboration with many of the great scientists and clinicians in Holland,
France, United Kingdom, USA and Japan. He continued to exchange ideas with these great people all through
his life and till the last moments of his extended fruitful life. Prof. Awwad wrote many books for a wide
diversity of readers, for the lay people in Arabic, for radiographers, young oncologist, and the highly
experienced radiation oncologists and radiobiologists. His book "Radiation Oncology: Radiobiological and
Physiobiological Perspectives" was a real translation of radiobiology language to the oncologist and at the
same time translation of the oncologist language to the biologist. This book ended with establishing a common
language for both teams. In addition, it led other books in these specialties to communicate with the same
language. The good news is that Prof. Awwad had completed the second edition of this book just before
passing away. This second edition is really a totally new book coping with the advancement of knowledge
reached till the end of 2006. We are sure that this book with all other good deeds performed by Prof. Awwad,
will keep his memory in Egypt as well as elsewhere in the whole world.
PMID: 17147725

Radiofrequency treatment in Egypt.

Tawfik MO
PMID: 21503003

Reconstruction of large full thickness chest wall defects following resection of malignant
tumors.

Khalil el-SA; El-Zohairy MA; Bukhari M

Full-thickness chest wall resection is the well-established treatment for primary or metastatic chest wall
tumors. Adequate surgery with large resections is always needed to achieve a radical resection in healthy
tissues, leading to optimal local control of the disease. The purpose of this study is to present our experience
in chest wall reconstruction after major tumor resection.Between January 2006 and January 2010, 18
consecutive patients who underwent major chest wall resections for primary or metastatic chest wall tumors
were studied. All had resection of at least three ribs and immediate reconstruction. Surgical procedures, extent
of the resection, resulting defects and postoperative morbidity and mortality were discussed.Surgical
indications included primary, recurrent and metastatic chest wall neoplasms, sarcoma and recurrent breast
cancer were the most frequent diagnoses. Resection of 3 ribs was performed in 8 patients, while resection of
more than 3 ribs was performed in 10 patients. Resection of sternum and adjacent costal cartilages was
performed in one patient, right chest wall resections were performed in 7 patients while left chest wall
resections were performed in 10 patients. Immediate repair of the defects was performed in all cases, all
patient had placement of prosthesis either polypropylene or polytetrafluroethylene, 3 patients had
methylacrylate in addition to the prosthesis. Coverage was achieved using myocutaneous flaps in 7 patients.
Mechanical ventilation was needed in 11 patients with a mean duration of ventilation 2.2±1.8 days (range
between 1- 6 days). No 30-days mortality was recorded. Four patients 22.2% developed complications, 2
patients need prolonged mechanical ventilation for respiratory insufficiency and 2 patients had partial flap
necrosis and wound infection. Mean hospital stay was 10.1±3.2 days.Immediate reconstruction of large full
thickness chest wall defects following resection of malignant tumors should be performed in all cases. Our
series proved that reconstruction can be performed safely with no recorded mortality and low morbidity.
Polypropylene mesh or polytetrafluroethylene (PTFE) were used with equal results, myocutaneous flaps were
used efficiently for soft tissue coverage if needed. KEY WORDS: Tumor of chest wall - Massive chest-wall defect
- Musculocutaneous flap - Prosthesis.
PMID: 20571595

180
 Reconstruction of the proximal humerus after wide resection of tumors: comparison of
three reconstructive options.

El-Sherbiny M

Assessment of the functional results and complications of three bone reconstructive procedures after
resection of primary tumors of the proximal humerus.Between 2000 and 2008, 32 patients having primary
malignant, aggressive benign or metastatic tumors of the proximal humerous were selected for limb sparing
surgery. Preoperative evaluation included CT chest, MRI. Limb sparing surgical resection was done including
intraarticular or extraarticular wide resection of the tumor. Bone defect was reconstructed with fusion
shoulder using free vascularized fibular graft (FFFG) in 11 patients and pedicled lateral scapular crest graft
(PLSCG) in 8 patients and mobile shoulder reconstruction using proximal humerus prosthesis in 13 patients.
Those patients were followed-up at regular interval to detect bone union and complications related to bone
flaps or prosthesis. Functional results were assessed for every patient after one year postoperatively.The
median age of the patients was 21 years and the follow-up period ranged from 19 months to 92 months.
Postoperative resection margins were negative in all cases. The mean length of the resected humerus was
13cm. The mean operative time for prosthesis cases was 3.5 hours and that for FVFG was 6.5 hours and was 5
hours for PLSCG cases. The mean time of bone union proximally and distally for FVFG and PLSCG was 4.2 and
5.5 months accordingly. At 1 year follow-up, the functional results for the three reconstructive procedures
were nearly the same with a mean functional score for FVFG cases was 73%, for PLSCG cases was 68% and was
71% for prosthesis cases. Hand and elbow functions were preserved in all types of reconstruction. The range of
shoulder abduction and flexion was grossly limited with prosthesis cases while it showed marked improvement
with fusion by FVFG and PLSCG. Complications for prosthesis cases were one case proximal migration and one
case posterior sublaxation. Complications of bone flaps were nonunion of one end in 2 cases of PLSCG and one
case of FVFG. Limb shortening was seen in 32 cases with PLSCG.Summarizing our experience in this small
study, we can state that, limb sparing surgical resection of tumors of the proximal humerus is effective in local
tumor control and preserving hand and elbow movements. MSTS functional score of the limb after
reconstruction and shoulder fusion with FVFG or PLSCG is nearly the same as mobile shoulder reconstruction
with endoprosthesis. Shoulder range of movement was grossly limited with prosthesis replacement while a
wider range of movement was obtained with shoulder fusion. Pedicled lateral scapular crest graft is able to
bridge defects only up to 12cm whereas the fibula can replace a longer defect. Selection between those
reconstructive options should be individualized and is based on the age, the length of defect, the type of
resection, intraarticular or extraarticular, preservation of deltoid and axillary nerve, the prognosis of the
tumor. KEY WORDS: Proximal humerus tumors - Reconstruction - Limb salvage.
PMID: 8668646

Regulation of glucose utilization by inhibition of mitochondrial fatty acid uptake in cardiac

cells.

Sharawi S; Mohamoud EM; Nada M; Hendrickson SC; Abdel-Aleem S

In order to investigate the mechanism by which fatty acid oxidation inhibitors regulate cardiac metabolism, the
effects of 2-tetradecylglycidic acid (2-TDGA), and 2-bromopalmitic acid (2-BPA) on the oxidation of [1-
14C]palmitate, [1-14C]octanoate and [U-14C]glucose were studied in isolated rat myocytes. Fifty per cent
inhibition of palmitate oxidation was achieved at 20 microM 2-TDGA and 60 microM 2-BPA. Octanoate
oxidation was also inhibited by 2-BPA. In contrast to their effect on palmitate oxidation, fatty acid inhibitors
significantly stimulated the oxidation of glucose in a concentration-dependent manner. Moreover, the
oxidation of [2-14C]pyruvate was increased two-fold by these compounds. The rate of uptake of [U-14C]-2-
deoxyglucose was also stimulated two-fold by these inhibitors. These studies suggest that the stimulation of
glucose utilization via the inhibition of fatty acid oxidation may be mediated through the stimulation of both
glucose transport and the oxidation of pyruvate by the pyruvate dehydrogenase complex.
PMID: 16508677

181
 Rhabdomyosarcoma in childhood: a retrospective analysis of 190 patients treated at a
single institution.

Shouman T; El-Kest I; Zaza K; Ezzat M; William H; Ezzat I

The study goal was to retrospectively review the treatment results of childhood rhabdomyosarcoma and
identify prognostic factors that affect treatment outcome.The records of 190 patients with childhood
rhabdomyosarcoma treated between January 1991 and December 1999 were reviewed. The data were
analyzed for clinico-epidemiological factors and the impact of potential prognostic factors on failure-free
survival. Factors evaluated were age, gender, histology type, primary site, tumor size, Intergroup
Rhabdomyosarcoma Study (IRS) group, surgical procedure, and the use of radiation treatment.The 5-year
actuarial FFS and OS were 40% and 50%, respectively. The only significant prognostic factors as estimated by
univariate analysis were histology type (p=0.01), primary site (p=0.002), tumor size (p=0.049), IRS-group
(p=0.003), surgical procedure (p=0.002), and radiation treatment (p=0.001). Multivariate analysis showed that
histology type (p=0.02), primary site, and IRS-group (p=0.02) were the only independent prognostic
factors.This analysis demonstrates that failure-free survival for rhabdomyosarcoma is dependent on several
factors at the time of initial diagnosis, including histologic subtype, primary site and disease group. Our
treatment results were inferior compared to IRS-studies as the patients during this period were treated on
individual bases and not standardized protocol.
PMID: 3509536

Round cell neoplasms of children: value of electron microscopy in their diagnosis.

Aboul Ela F; Ananieva L; Nayera A; Kawther A

PMID: 16799659

Ru106 brachytherapy for management of choroidal melanoma: do we need to adjust total

dose according to the new NIST calibration measurement?

Lotayef MM; Othman IS; Shelil AE; Kerima H

To detect the need of adjusting the apical total dose according to the new NIST calibration measurement
introduced by BEBIG Isotopen und Medizintechnik GmbH for the treatment of choroidal melanoma. As the
total radiation dose should not be individualized depending on errors pf previous calibration but can be
applicable if based on a radiosensitivity test that was able to predict the final response of tumor to radiation
for each particular patient.Twenty patients with choroidal melanomas were treated between November 2002
and July 2004 at "Suzanne Mubarak Eye Tumor Centre", National Eye centre Rod-EL Farag, Cairo, Egypt. The
prescribed dose was calculated according to the new NISTcalibrated dosimetry introduced by BEBIG, but
without dose modification by using a conversion factor F(type,z) from the ASMW calibrated measurement to
the NIST calibrated measurement that have been calculated depending on the plaque type and the distance z
from the inner concave plaque surface along the central axis. For the treatment of choroidal melanoma in this
study the apical dose ranged from 9000-10400cGy with a mean of 9855 +/- 385.After a follow up period from
12-28 months (median of 19 months) there was a local control rate of 100 % and the three years actuarial
disease specific survival was 95% as only one patient died of liver metastases. Fourteen patients had a best
corrected pre-treatment visual acuity of better than 6/60 in the affected eye. At the last follow up available,
useful visual acuity of>0.5 was preserved in 7 of the patients.Recalculation of the apical total dose (mostly
increasing of the total dose) according to the conversion factor F(type,z), suggested by BEBIG after the new
NIST calibration measurement, does not seem to have an effect on both local control and survival, in this
study.
PMID: 20422130

182
SEN virus infection in Egyptian patients undergoing maintenance hemodialysis: prevalence
and clinical importance.

Loutfy SA; Hafez MM; Massoud WA; Fotuh NA; Moneer MM; Zaghloul HS

SEN virus (SENV) is assumed to be responsible for post-transfusion non-A to -E hepatitis. Phylogenetic analysis
of SENV has shown 9 different strains. Two strains, SENV-H and SENV-D, were described as possible candidates
for post-transfusion hepatitis. This study examined the prevalence of SENV infection and its clinical importance
for patients undergoing hemodialysis.Serum samples were obtained from 63 long-term hemodialysis patients,
and examined for SENV-H and SENV-D viremia by polymerase chain reaction. Serum samples were also
obtained from 20 patients with chronic kidney diseases (CKD) who were not undergoing hemodialysis and
from 20 apparently healthy blood donors to act as controls. For SENV screening, a primer pair was used for the
conserved ORF1 region among all SENV genotypes from A to I.SENV infection was significantly more frequent
among hemodialysis patients (33/63; 52.4%) and those with CKD (10/20; 50.0%) than among the control
participants (2/20; 10.0%) [p = 0.003]. Twenty three of 33 hemodialysis patients had SENV-H or -D, 61% of
whom were positive for SENV-H only, 4% were positive for SENV-D only, and 36% were positive for both SENV-
H and SENV-D. SENV infection was not associated with age, sex, amount or duration of hemodialysis, or liver
function test results. Elevated alanine aminotransferase was significantly associated with HCV viremia, but not
with SENV infection.Egyptian hemodialysis patients and those with CKD are at higher risk for SENV
transmission. SENV-H is more prevalent than SENV-D.
PMID: 19034343

Shielding for scattered radiation to the testis during pelvic radiotherapy: is it worth?

Nazmy MS; El-Taher MM; Attalla EM; El-Hosiny HA; Lotayef MM

To assess the value of external shielding of the testis during pelvic radiotherapy.Nineteen patients, receiving
radiotherapy to the pelvis with the lower border of the field at the obturator foramen, were randomly
selected. A 5 half value layer cerrobent shield was positioned at the inferior border of the field. The dose to
the testis was measured with and without the shield. Observations were made regarding the reflex cremaster
contraction and phantom measurements were done at different distances from the perineum.The mean
radiation dose to the testis for patients receiving treatment with no shield was 7.4cGy (1.3) and it was 5.7cGy
(-/+2.5) for patients with external shield, this difference was statistically significant by the paired t test
p<0.0001. This accounted for a 22 % decrease in the dose received by the testis. The position of the testis with
the contraction of the cremaster muscle and the dartos fascia after manipulation of the testis during diodes
placement changed up to 3.5 cm (mean 1.5). Phantom measurements showed 37% increase in the dose with
2cm change in the position of the testis to the pelvic direction.External shield at the inferior border of the
pelvic field is a simple, easy reproducible, convenient shielding method. Clam-shell scrotal shield is not free of
drawbacks, but still its benefits overweigh its harms and should be used with caution.
PMID: 16788341

Superior hypogastric block: transdiscal versus classic posterior approach in pelvic cancer
pain.

Gamal G; Helaly M; Labib YM

The classic posterior approach of superior hypogastric block has several technical difficulties. The transdiscal
approach is a novel and easier approach for superior hypogastric which overcome these technical
difficulties.Thirty patients were randomly allocated to two groups: The transdiscal group and the classic group;
visual analog scale pain scores, daily morphine consumption, duration of the procedure and side effects were
recorded.The duration of the procedure was significantly decreased in the transdiscal group (24.4+/-5.6 min)
compared to the classic group (57.9+/-9.8 min). There were no significant differences between the 2 groups in

183
daily morphine consumption and VAS pain scores. There was no discitis, disc rupture, or herniation in the
transdiscal group.The transdiscal approach for superior hypogastric plexus block in pelvic cancer pain is easier,
safer, and more effective with less side effects than the classic approach.
PMID: 15959547

Surgical management for giant cell tumor of bones.

Khalil el SA; Younis A; Aziz SA; El Shahawy M

To evaluate the different surgical techniques used in the treatment of giant cell tumor of bone and their effect
on the rate of local recurrence.This is a prospective study of fifty-two patients with giant cell tumor (GCT) of
the bones treated at the National Cancer Institute, Cairo University between 1998 and 2002. All patients were
evaluated by clinical examination, plain X-ray, CT scan and MRI (in some cases). Biopsy was taken in all cases to
confirm the diagnosis and to define the grade of the tumor. All patients underwent surgical treatment
including curettage, curettage combined with cryosurgery and bone cement or bone graft, bone resection and
amputation. Selection of the surgical technique was based on site and size of the lesion, soft tissue
involvement (intra- or extra-compartmental), tumor grade and if recurrent or not. Patients were followed up
for a minimum of twenty-four months.Out of 52 patients 14 patients were males and 38 patients were
females, (male to female ratio was (1: 2.7). The age of our patients ranged from 13 to 71 years, with a mean
age of 32.9 years. Based on Enneking's staging system, 40 patients (77%) were stage IA, 9 patients (17%) were
stage IB & 3 were stage IIB. Histopathological examination of all cases revealed giant cell tumor of borderline
malignancy. Curettage alone was done in 4 patients, curettage and bone cement in 7 patients, curettage,
cryosurgery and bone graft in 4 patients, curettage, cryosurgery and bone cement in 18 patients, resection in
16 patients and amputation in 3 patients. There were no mortalities among our cases. Local recurrence was
highest in cases treated with curettage only (50%), lowest in cases treated with curettage and cryosurgery with
bone cement (16.6%).The main primary treatment of GCT is surgery; the type of which depends on
preoperative evaluation, which includes clinical evaluation that involves the site and size of the tumor in
relation to surrounding structures, together with plain X-ray, CT scan and/or MRI as indicated, and tissue
biopsy to define tumor grade. Curettage alone results in high rate of local recurrence. On the other hand,
curettage and adjuvant cryosurgery using bone cement or bone grafts give low rate of local recurrence.
Resection is recommended for stages IB and IIB, extremely large lesions, and in cases where resection results
in no significant morbidity as proximal fibula and flat bones. Amputation is preserved for massive recurrences
and malignant transformation.
PMID: 16353082

Survivin expression in colorectal adenocarcinoma using tissue microarray.

Abd El-Hameed A

The additional prognostic information closely related to tumor cell biology is essential for the identification of
patients with poor prognosis. Survivin, an identified inhibitor of apoptosis, is unique for its expression in
human malignancies but not in normal adult cells. This study examined the expression, and potential
prognostic value of survivin in colorectal adenocarcinoma (CRC) on tissue microarray (TMA) sections. Analysis
of large numbers of tissue samples, improved tissue salvage, cost reduction, ease of interpretation, and
significant time saving were realized by using the arrays.Two-hundred and eighty cases of colorectal
adenocarcinoma were arrayed. Immunohistochemical stains of TMA sections were performed for survivin, bcl-
2, and p53. Cases were followed up for 5 years.Survivin was detected in 147 of 230 cases (63.9%). No
expression of survivin was observed in normal tissues. There was no correlation between survivin
immunoreactivity and age, sex, tumor site, tumor size, histopathologic subtype, tumor grade and clinical stage
(p >0.05). Prevalence of survivin expression was significantly higher in bcl-2 positive than in bcl-2 negative
cases (88.1% versus 42.1%, p <0.0001), but was not associated with p53 (p=0.09). The 5-year disease free
survival (DFS) for patients with survivin positive colorectal adenocarcinoma was significantly lower than that
for patients with survivin negative tumors (46% versus 68.7%, p=0.001).Survivin expression in colorectal
adenocarcinoma provides an important prognostic parameter and targeted antagonists of survivin may be
beneficial as apoptosis-based therapy for colon cancer.

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PMID: 18525325

Systemic nonhormonal management of advanced prostate cancer and its likely impact on
patients' survival and quality of life.

Azim HA; Mok T

Prostate cancer is a hormonal sensitive disease with a response rate ranging from 80 to 90%; however, the
majority of patients develop hormone resistance resulting in poor long term survival. Chemotherapy has
demonstrated a benefit over steroids in improving the quality of life in the hormone refractory phase.
Furthermore, the introduction of docetaxel succeeded in improving the survival of these patients in first-line
therapy. Second-line treatment following docetaxel is challenging with no agent classified as standard in this
setting. In the last 5 years, several drugs have shown promising results in initial evaluation. However,
randomized phase III trials would be needed to answer this question. The majority of patients develop bone
metastasis and the use of bisphosphonates has yielded encouraging results. Our understanding of the biology
of hormone refractory prostate cancer has improved dramatically over the past few years and has translated
into the developments of new therapeutic targets for this disease. Agents affecting several targets, including
calcitriol, endotheline-1, bcl-2, and angiogenesis, are being studied currently and have the potential to change
the treatment paradigms of this otherwise fatal disease. This review focuses on current and potential
treatment options, including cytotoxic agents, bisphosphonates, and targeted agents, for patients with
hormone refractory prostate cancer and the impact of these options on survival and quality of life.
PMID: 20075715

Targeting DNA double-strand break repair: is it the right way for sensitizing cells to 5-
fluorouracil?

El-Awady RA; Saleh EM; Dahm-Daphi J

Inhibition of the repair of 5-fluorouracil (FU)-induced DNA lesions may improve the response of many tumors
to this anticancer agent. Despite the identified associations between DNA strand breaks and the lethality of
thymidylate synthase inhibitors, the role of DNA double-strand break (DSB) repair pathways in a cellular
response to 5-FU treatment has not been studied yet. Isogenic cell lines defective (irs1SF), wild type (AA8), or
reconstituted (1SFK8) in the DSB repair protein XRCC3 were used to investigate the effect of defective DSB
repair on the overall sensitivity of cells to 5-FU and to see how targeting DSB repair may affect other cellular
responses to 5-FU. Treatment with 5-FU resulted in (i) similar induction of DSB in both cell lines as indicated by
the formation of gamma-H2AX (a marker for DSB). The repair of these breaks was complete in AA8 but not in
irs1SF cells. (ii) Concentration-dependent reduction in the survival of both cell lines. The AA8 cells were six
times more sensitive to 5-FU than the irs1SF cells. (iii) An earlier and more prolonged G(1)/S phase arrest in
AA8 compared with the irs1SF cells. (iv) Induction of apoptosis as indicated by sub-G(1) cells and caspase-3
activity in AA8 but not in irs1SF cells. XRCC3 complementation of irs1SF cells restored the wild-type phenotype.
This result shows that targeting DSB repair is not always associated with increased sensitivity to DNA damaging
agents such as 5-FU because it may affect other cellular responses such as cell cycle regulation and induction
of apoptosis.
PMID: 21442386

Teaching oncology to medical students is a must: the Egyptian NCI step on the road.

Gaafar R; Shash E; El-Haddad A; Hady SA

PMID: 17356388

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 The diagnostic value of C-reactive protein, interleukin-8, and monocyte chemotactic
protein in risk stratification of febrile neutropenic children with hematologic malignancies.

El-Maghraby SM; Moneer MM; Ismail MM; Shalaby LM; El-Mahallawy HA

Recent advances in febrile neutropenia have highlighted the value of risk stratification especially that it can
have important implications in terms of management. We aimed to identify a serum marker that may help to
stratify febrile neutropenic pediatric patients treated for hematologic malignancies at the time of first
evaluation. Thus, C-reactive protein (CRP), interleukin-8 (IL-8), and monocyte chemotactic protein-1-alpha
(MCP-1-alpha) were evaluated for their predictive and diagnostic relevance in febrile episodes of cancer
patients.Within 24 hours of fever, CRP, IL-8, and MCP-1 serum levels were measured and the levels of these
markers were related to the clinical findings of the patients. For this purpose, we collected and analyzed
clinical data of 85 fever episodes occurring in 76 patients with hematologic malignancies, presenting to the
Department of Pediatric Oncology, National Cancer Institute, Cairo University, during a 6-month
period.Neutropenic children with febrile episodes were classified into 2 groups, a group with unexplainable
fever (group I, n=26) and another group with either blood culture positive, and/or fever periods with a
documented clinical sepsis and/or local infection (group II, n=59). Clinically, local sites of infection were
encountered in 39 cases (45.9%), whereas a positive blood culture was detected in 20 cases. CRP, IL-8, and
MCP-1 levels were significantly lower in group I versus group II (P value <0.001). There were overlaps of values
between groups. CRP > or =90 mg/L was significantly associated with chemotherapy-related neutropenia and
fever owing to bacteremia (P=0.038). The sensitivity, specificity, negative and positive predictive values of CRP,
MCP-1, and IL-8 were (70%, 73%, 51%, and 85%), (64%, 92%, 53%, and 95%), and (71%, 77%, 54%, and 88%),
respectively. Combining 2 or 3 markers improved the diagnostic performance of these test, as 78% of group II
had elevated 2 or 3 markers versus 16% of the group with no evident infection.Low levels of CRP, MCP-1, and
IL-8 could identify patients with unexplainable fever; whereas, high levels of these markers were of help in the
diagnosis of infectious episodes. A model combining more than 1 marker is recommended in the assessment
of febrile neutropenia.
PMID: 19828004

The First Children's Cancer Hospital, Egypt International Scientific Conference.

Zaghloul MS

A wide gathering of scientists, clinicians, pharmacists and nurses specialized in pediatric oncology practice met
to celebrate the second anniversary of Children's Cancer Hospital, Egypt (CCHE). The celebration was in the
form of high-brow teaching lectures and reports presented by international experts in the fields of pediatric
CNS tumors, solid tumors (neuroblastoma, nephroblastoma, soft tissue and bone tumors, lymphoma, leukemia
and pediatric oncology nursing. The conference extends its activities to hospital management, clinical
pharmacy and telemedicine. Furthermore, CCHE experts presented the efforts performed to establish a state-
of-the-art pediatric oncology hospital equipped with all needed facilities to raise the standard of care to the
highest levels.
PMID: 10790282

The immunobiology of low-dose total-body irradiation: more questions than answers.

Safwat A

Low-dose total-body irradiation (TBI) is used in the treatment of chronic lymphocytic leukemia and low-grade
non-Hodgkin's lymphoma. The usual practice is to give very low individual fractions (0.1 to 0.25 Gy) several
times a week, to a total dose of 1.5 to 2 Gy. Despite this low dose, low-dose TBI can induce long-term
remissions in the majority of patients. Immune enhancement, rather than direct radiation cell killing, is one of
the suggested mechanisms by which low-dose TBI can exert its effect. Data from animal experiments have

186
shown that low-dose TBI could enhance the immune response through (1) augmenting the proliferative
reactive response of the T cells to mitogenic stimulation; (2) altering cytokine release, particularly the
activation of interferon gamma and Il2 production; (3) increasing the expression of Il2 receptors on the T-cell
surface; (4) facilitating signal transduction in T lymphocytes; (5) increasing splenic catecholamine content and
lowering the serum corticosterone level; and (6) eliminating a particularly radiosensitive subset of the
suppressor T cells. Data for humans, though scarce, suggest that at least some of these mechanisms occur in
patients treated with low-dose TBI. Whether these immunomodulatory effects are responsible for the clinical
outcome is not yet clear. Much is still unknown about the immunobiology of low-dose TBI, its clinical potential,
and the possible synergism with chemotherapy, biological response modifiers, or immunotherapy. This lack of
comprehensive knowledge hampers the optimal and widespread use of this intriguing and potentially useful
treatment modality in clinical practice.
PMID: 19847284

The role of surgical management in pediatric germ cell tumors (GCTs), NCI case series.

Fakhr IM; Khalil el-SA; El-Baradie TS; Shaalan MA; Shalaby LM; Nassif SL; Farahat IG

To review the experience of a tertiary referral center in pediatric germ cell tumors (GCTs) in the last 8 years
and to investigate the impact of surgery and site of disease on prognosis.We retrospectively analyzed the
cases of pediatric germ cell tumors at National Cancer Institute over an 8 years period. Data concerning
diagnosis, surgery and medical decisions were reviewed and analyzed for all patients. A total of 34 children
with (GCTS) were found, with a mean age, at presentation, of 6.7 years and a follow-up period ranging from 3-
52 months. One patient with benign GCT was excluded during analysis of the results.Among the 34 patients,
there were 14 males and 20 females with mean age of 6.7 years (range: 9 months-15 years), with male to
female ratio 1:1.4. All patients were symptomatic at presentation, most commonly with abdominal swelling
(18 patients; 52.9%). Anatomic distribution of GCTs according to sex organ involvement was either gonadal in
21 patients (61.8%) or extragonadal in 13 patients (38.2%). All patients had surgery either in the form of
curative resection or biopsy after formal exploration and evidence of irresectability. No significant surgical
morbidity or mortality were encountered in our patients. Yolk sac tumor and malignant teratoma were the
commonest histologic subtypes in our series. Metastatic disease was encountered in nine out of 33 patients
(27.2%). Adjuvant chemotherapy was administered in 28 out of 33 patients (84.8%), following surgery,
including all patients with extragonadal disease. Our patients were followed-up to 52 months. Twenty-two
patients (66.7%) had no recurrence while two patients (6.1%) died from disease. Pelvic extragonadal site was
the worst site regarding resectability. Complete surgical resection showed better disease free survival, while
those with irresectable disease had comparable overall survival while none could be rendered disease free
with chemotherapy.The initial surgical approach to malignant GCTs at all sites should be complete resection
when possible; the morbidity of extensive surgical resection should be weighed carefully against the good
tumor control with chemotherapy. Surgical staging does not preclude preservation of fertility, which should
always be considered in this young age. The site of primary disease plays a role in the prognosis of pediatric
germ cell tumors with the extragonadal pelvic tumors being the worst regarding resectability. Good tumor
response can be achieved with surgery and chemotherapy even for advanced stage and metastatic disease.
PMID: 16799651

The use of tensor fascia lata pedicled flap in reconstructing full thickness abdominal wall
defects and groin defects following tumor ablation.

Rifaat MA; Abdel Gawad WS

The tensor fascia lata is a versatile flap with many uses in reconstructive plastic surgery. As a pedicled flap its
reach to the lower abdomen and groin made it an attractive option for reconstructing soft tissue defects after
tumor ablation. However, debate exists on the safe dimension of the flap, as distal tip necrosis is common.
Also, the adequacy of the fascia lata as a sole substitute for abdominal wall muscles has been disputable. The
aim of the current study is to report our experience and clinical observations with this flap in reconstructing
those challenging defects and to discuss the possible options to minimize the latter disputable issues.From
April 2001 to April 2004, 12 pedicled TFL flaps were used to reconstruct 5 central abdominal wall full thickness

187
defects and 6 groin soft tissue defects following tumor resection. In one case, bilateral flaps were used to
reconstruct a large central abdominal wall defect. There were 4 males and 7 females. Their age ranged from 19
to 60. From the abdominal wall defects group, all repairs were enforced primarily with a prolene mesh except
for one patient who was the first in this study. Patients presenting with groin defects required coverage of
exposed vessels following tumor resection. All patients in the current study underwent immediate
reconstruction.The resulting soft tissue defects in this study were due to resection of 4 abdominal wall
desmoid tumors, a colonic carcinoma infiltrating the abdominal wall, 4 primary groin soft tissue sarcomas, a
metastatic SCC of the leg to groin nodes, and a primary SCC of the groin. The size of the flaps used ranged from
20 x 10 cm to 31 x 18 cm. All flaps survived. However, distal flap necrosis occurred in 4 cases. Three of those
cases developed in flaps reconstructing abdominal wall defects, and one case developed in a flap used to cover
a groin defect. In the former 3 cases, the flap was simply transposed without complete islanding of the flap. In
the latter case, a very large flap was harvested beyond the safe limits with its distal edge just above the knee.
In addition, wound dehiscence of the flap occurred in 2 other cases from the groin 132 group. Nevertheless, all
the wounds healed spontaneously with repeated dressings. Out of the 5 cases that underwent abdominal wall
reconstruction, one case developed ventral hernia, in which bilateral TFL flaps were used without mesh
enforcement. There was minimal donor site morbidity in the form of partial skin graft loss in 2 cases. The
average follow up period in this study ranged from 6 months to 2 years. Only one patient died of distant
metastasis of a SCC of the groin skin, 8 months postoperatively and another 2 patients with abdominal
desmoid tumors developed local recurrence.The tensor fascia lata flap is a reliable and a versatile flap, with
minimal donor site morbidity. Problems with the flap's vascularity of its distal part should not be encountered,
if the flap is harvested within the safe limits and properly designed and the edges comfortably insetted to the
defect. A pedicled flap would be appropriate for lower abdominal wall defects, and is better islanded to
achieve extra mobilization and allow a tension free closure, while for groin defects, simple flap transposition
should be enough. Nevertheless, reconstruction for full thickness abdominal wall defects by this flap is a static
reconstruction. We therefore strongly recommend enforcing the repair with a synthetic mesh primarily to
minimize the incidence of ventral hernia. However, further studies with larger number of cases are needed to
confirm this observation.
PMID: 16116496

Total skin electron therapy: a modified technique for small room linear accelerator.

Shouman T; El-Taher Z

Development of a technique for treating whole-body skin using linear accelerator with electron beam energy
of 6-MeV at a short treatment distance.The 6 MeV high dose rate total skin electron irradiation mode on a
linear accelerator was used. Beam profiles and percentage depth doses in the patient plane were measured
for different beam angulations.At a treatment distance (SSD) of 292 cm and using acrylic scatterer-degrader
4mm thick, the beam penetration was calculated so that the 80% dose lied at 1.6 cm for the single beam and
only 6 mm for the clinical beam. A uniform vertical profile was obtained by using 3 beams for each treatment
position with gantry angles of 700, 900 and 1100.We could implement a modified stanford technique for total
skin electron beam irradiation at a short treatment distance. Using an acrylic scatterer-degrader and three
beam angulations we could produce a uniform beam in the treatment plane.
PMID: 20015593

Treatment of the pregnant mother with cancer: a systematic review on the use of
cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part I: Solid
tumors.

Azim HA; Peccatori FA; Pavlidis N

The association of cancer and pregnancy is increasingly encountered nowadays in clinical practice. Due to the
relative rarity of the situation, it lacks a systematized approach. Different systemic therapies are used in
managing cancer with uncertainty regarding the potential hazards they could pose on the pregnancy and/or
the fetus. We have performed a systematic review of literature to identify all reports addressing cancer
patients who were exposed to any of the known systemic therapies during the course of the pregnancy. The

188
results were discussed in two parts; part I addresses pregnant patients with solid tumors while part I for those
with hematological malignancies. In part I, we identified different solid tumors diagnosed and treated during
the course of pregnancy. Breast cancer was the most commonly treated followed by ovarian cancer. Other
tumors were treated as well including lung cancer, cervical cancer, sarcoma and melanomas. It is important to
acknowledge the intent of therapy (palliative vs. curative) and the patients has to be properly counseled to
reach an informed decision. We aim to provide a more robust consensus on how to approach these cases and
provide a higher degree of evidence to support the safety of applying certain management strategies over the
other.
PMID: 20018452

Treatment of the pregnant mother with cancer: a systematic review on the use of
cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part II:
Hematological tumors.

Azim HA; Pavlidis N; Peccatori FA

Managing pregnant patients with hematological tumors pose even more conflicts compared to solid tumors.
Unlike the majority of solid tumors, hematological malignancies are potentially curable; hence it is important
to deliver the best treatment options available, which sometimes could be too aggressive to deliver during
pregnancy. In part II, we report the results of women with hematological malignancies treated with systemic
therapies during the course of pregnancy. Lymphoma, acute leukemia and chronic myeloid leukemia were the
most commonly treated. We discuss the safety of the different regimens reported and propose alternatives to
standardized approaches in case they pose significant risk to the pregnancy and/or the fetus.
PMID: 15648068

TRUGENE sequencing versus INNO-LiPA for sub-genotyping of HCV genotype-4.

Zekri AR; El-Din HM; Bahnassy AA; El-Shehabi AM; El-Leethy H; Omar A; Khaled HM

Hepatitis C virus genotypes and subtypes determination is an important factor for understanding the
epidemiology of the virus, in the pre-treatment evaluation of the patients and in defining better treatment
strategies. In the present study, we compared two commercially available assays for HCV genotyping: the
reverse hybridization based Innogenetics INNO-LiPA HCV II and the direct sequencing by TRUGENE assay. The
study included 31 HCV-RNA positive Egyptian patients; 18 patients with chronic active hepatitis, 8 with HCC,
and 5 with cirrhosis. Using the TRUGENE genotyping test, all the samples had genotype 4 (100%) and subtyped
as 4a in 18/31(58%), 4c in 10/31 (32%), 4e in 1/31 (3%), 4a/c in 1/31 (3%), and 4g in 1/31 (3%). Using the
INNO-LiPA assay, 30 samples had genotype 4 (97%), and 1 sample had genotype 1e (3%). One sample showed
mixed infection with type 4f and type 1. Only six samples were subtypable by INNO-LiPA, three were genotype
4c/d, and the other three were 4f, 4e, and 1e. Seven samples gave reactivity in the INNO-LiPA of lines 5, 6, 16,
17, 18, which are considered untypable by the interpretation chart but considered to be a rare HCV genotype 4
by the manufacturer. At the genotype level, there was a 97% concordance between TRUGENE sequencing and
INNO-LiPA, but at the subtype level the concordance rate was 3% only. We conclude that the TRUGENE
genotyping assay is a reliable test for HCV genotyping for the detection of major types and subtypes detection,
while INNO-LiPA is a good test at the genotype level but unreliable for subtyping especially in the Egyptian
population. This is mainly due to the high diversity of genotype 4, which is the most prevalent genotype in
Egypt.
PMID: 15025835

Use of transdermal fentanyl without prior opioid stabilization in patients with cancer pain.

Tawfik MO; Bryuzgin V; Kourteva G;

To determine the safety and efficacy of transdermal fentanyl for pain relief in cancer patients and to compare
the effects on patients according to whether they had previously received strong opioids, weak opioids or non-

189
opioid analgesia.Cancer patients requiring strong analgesia were recruited into an open-label, multicentre
study, conducted in eight countries. Patients received transdermal fentanyl treatment for 28 days. Pain
severity, overall satisfaction with pain control, convenience of use of patches and treatment preferences were
recorded daily.Of the 292 participants, 135 had previously received a strong opioid, 84 had previously received
a weak opioid and 73 had received no regular opioids. Thirty-eight patients did not complete the study, mainly
due to adverse events. For all groups the proportion of patients with 'good to excellent' pain control increased
after transdermal fentanyl treatment. Transdermal fentanyl was well tolerated, with the most common
treatment-related adverse events being nausea, vomiting and constipation. The percentage of strong-opioid-
tolerant patients with constipation decreased following transdermal fentanyl treatment and increased slightly
in the strong-opioid-naïve groups. Most patients rated the convenience of the patches as 'good to excellent',
and most preferred transdermal fentanyl to their previous therapy.Transdermal fentanyl is an effective and
well-tolerated treatment for cancer-related pain for patients regardless of whether they have previously
received opioids. Previous guidelines have often advocated initial dose finding with short-acting opioids but
this study demonstrates that such a complex titration and conversion schedule may not be necessary,and that
treatment may be initiated directly with long-acting formulations such as transdermal fentanyl when previous
analgesic therapy fails to provide adequate relief.
PMID: 17237846

Vaginal reconstruction using the ileocecal segment after resection of pelvic malignancy.

Abd El-Aziz S

This prospective study was carried out at the National Cancer Institute, Cairo University. The aim of this study
is to evaluate the use of the ileocecal segment as a vaginal substitute in young female patients undergoing
vaginal resection for malignant pelvic tumors.The study included eleven patients with different pelvic
malignancies undergoing vaginal resection as a part of surgical treatment. The ileocecal segment, based on the
ileo-colic artery, was used for vaginal reconstruction in all cases. Five cases had cervical carcinoma that
underwent extended Wertheims operation. Three cases had urinary bladder cancer that underwent anterior
pelvic excentration. Two cases had endometrial carcinoma, and one case had ovarian tumor. In 2 cases the
terminal ileum was used, in addition, for ureteric replacement in one case, and as a bladder substitute in the
other case. Their ages ranged from 39 to 47 years, with a mean age of 42 years. Primary reconstruction was
done in 9 cases, while secondary reconstruction was performed in 2 cases.An average of one hour was
consumed in addition to the time of the original operation. Mucous discharge, as an early post operative
complication was recognized only in 2 cases (18%). Late complications, in the form of inspissated mucous
secretion, were encountered only in 3 cases (27%). Sexual function was satisfactory in most of the cases (10
cases) (90.9%).The ileo-coecal segment, although not the ideal, is an excellent substitute for vaginal
reconstruction, with minimal post operative complications and satisfactory sexual function.
PMID: 17362327

Vaginal reconstruction with a greater omentum-pedicled graft combined with a vicryl

mesh after anterior pelvic exenteration. Surgical approach with long-term follow-up.

Elaffandi AH; Khalil HH; Aboul Kassem HA; El Sherbiny M; El Gemeie EH

Resection of anterior vaginal wall that occurs with some cases of anterior pelvic exenteration leaves the
patient with a small and narrow vagina. This affects their sexual life leading to major psychologic problems,
especially in young women. The aim of this study is to evaluate a new technique of vaginal reconstruction
following anterior pelvic exenteration with clinical and cytohistologic follow-up. Between March 2002 and
November 2004, ten sexually active female patients underwent vaginal reconstruction after radical cystectomy
that required en bloc removal of the anterior vaginal wall, with a pedicle graft of greater omentum combined
with a vicryl mesh. The mean age of the patients was 38 years. The mean operative time of the reconstructive
procedure was 50 min. There were no complications regarding the reconstructive procedure. On follow-up,
the neovagina accepted two fingers easily and showed a pink-colored smooth lining. Seven patients reported
successful attempts of sexual intercourse. It was concluded that reconstruction of vagina after anterior pelvic
exenteration in sexually active women can be done safely with the use of vicryl mesh combined with a

190
pedicled omental graft. It is a simple, reliable, and not time-consuming technique. The long-term follow-up
was very beneficial in detection of complete healing, postoperative infections, and hormonal activity of the
graft and recurrence of malignancy.
PMID: 8176938

Wilms' tumor: long-term results from a single institution.

Zaghloul MS; Hussein MH; el Koutbey M

One-hundred-twelve children with pathological diagnosis of Wilms' tumor were treated during the period
1979-1989. They were postoperatively staged as follows: stage I, 25 patients; stage II, 27 patients; stage III, 48
patients; and stage IV, 9 patients. Three patients were preoperatively classified as stage V. The National Wilms'
Tumor Study (NWTS) staging system was used. Except for Stage V patients, the treatment regimen consisted of
nephrectomy followed by radiotherapy and/or chemotherapy according to stage of disease and pathology.
Stage I, II, and III patients with favorable histology enjoyed 94 +/- 6%, 86 +/- 8%, and 71 +/- 8% 10-year
actuarial survival, respectively. Stage IV patients and those in stages I, II, and III with unfavorable histology had
a 10-year actuarial survival of 36 +/- 8%. Univariate analyses proved that NWTS stages affected the 10-year
actuarial disease-free survival rates but not the overall survival rates. The histopathology significantly affected
the disease-free survival and the overall survival rates both in the whole group of patients and in each stage
when considered separately. The same histopathology also affected the incidence of development of distant
relapse but not the local recurrence rate. On the other hand, massive tumor rupture at surgery increased the
incidence of local relapse but not of distant metastasis and did not affect the overall survival rates. The
presence of residuum after surgery had nearly the same effect as tumor rupture on the local recurrence. It also
did not increase significantly the distant relapse incidence, but it affected significantly the overall survival.
Retroperitoneal lymph node involvement had a similar effect. It increased the incidence of local relapse and
decreased the 10-year overall survival rate but it had a borderline effect on development of distant metastasis
(P = 0.06). The age at diagnosis had also a borderline effect on disease-free survival but it had not effect, of
statistical significance, on the overall survival.

Gynecological Cancers
PMID: 16799653

Cytoreductive surgery for advanced epithelial tumors of the ovary: technical

considerations and outcome.

Khalil el-SA; Fakhr I; Younis A; El-Shahawy M; Adel I

To study the role of cytoreductive surgery in the management of advanced epithelial tumors of the ovary and
its effect on survival.A prospective study of fifty eight female patients presenting with stage III and VI epithelial
ovarian tumors attending the National Cancer Institute, Cairo University during the period from January 2003
to of December 2004. All patients were evaluated clinically, radiologically (including plain chest-X-ray and
abdomino-pelvic ultrasound and/or CT), laboratory work up and CA-125. Abdominal exploration under general
anesthesia with intent of maximum surgical cytoreduction was performed for all patients. Patients were
followed up during the period of the study by history and physical examination, CA-125 measurement and
abdomino-pelvic ultrasound or CT.Our study included 58 female patients with advanced epithelial tumors of
the ovary. Their age ranged from 18 to 73 years with a mean age of 49 years. Pathological distribution of the
lesions were borderline malignancy in 5 patients (8.6%) and malignant in 53 patients (91.4%). According to
FIGO classification there were 46 patients stage III (79%) and 12 patients stage VI disease (21%). Eighteen
patients (31%) had surgery prior to admission to NCI. Cytoreductive surgery was done for 51 patients (88%),
while 7 patients (12%) had exploration and biopsy only, one of whom had palliative colostomy for large bowel
obstruction. Intraoperative surgical complications were encountered in 5 patients (8.6%), all were managed
intraoperatively. We had no early postoperative mortalities and 8 postoperative morbidities (13.7%). All
patients were referred for chemotherapy. Thirteen patients (22.4%) had local recurrence within the follow up
period of the study which was between 8-24 months. One patient died from locally advanced disease and the
rest of the patients were explored and lesions were surgically resected.Surgery remains a major line of therapy

191
in ovarian cancer including advanced lesions. Extensive procedures to maintain a R0 result are crucial to reach
a satisfactory local disease control. The NCI, as well as all tertiary cancer centers, has an important role in
providing this quality of surgery especially in advanced cases. Chemotherapy remains the hope to ameliorate
the survival especially in advanced cases. The close coordination between surgery and chemotherapy in the
form of Intra- Peritoneal Hyperthermic Chemotherapy (IPHC) represents a hope for patients with advanced
disease and should be introduced and established in all major cancer centers.
PMID: 22776814

Laparoscopic hysterectomy in the treatment of endometrial cancer: NCI experience.

Soliman HO; Elsebaie HI; Gad ZS; Iskandar SS; Gareer WY

The standard treatment for women with endometrial cancer is total abdominal hysterectomy and pelvic
lymphadenectomy for surgical staging. Total laparoscopic radical hysterectomy (TLH) is an alternative
approach providing surgical and patient related advantages to laparoscopy.Twenty female patients with early
stage endometrial cancer were operated upon by TLH and pelvic lymphadenectomy, aiming to assess the
safety and efficacy of TLH.The mean operative time was 296.8min conversion to laparotomy was done in one
patient due to bleeding from the uterine vessels. The mean blood loss was 517.5cc. The uterus was removed
transvaginally in 18 patients (90%) and via a small Pfannenstiel incision in two patients (10%). The mean
number of pelvic lymph nodes retrieval was 21.2. Postoperative bleeding occurred in one patient (5%) which
necessitated exploration. One patient (5%) suffered a pulmonary embolism. Four patients (20%) developed
pyrexia, and one patient (5%) suffered from a chest infection. One patient (5%) had wound infection. The
mean hospital stay was 4.5days (range 3-10).TLH with pelvic lymphadenectomy is a safe and effective
approach in the treatment of early endometrial carcinoma.
PMID: 21298536

Needle oophoropexy: a new simple technique for ovarian transposition prior to pelvic
irradiation.

Gareer W; Gad Z; Gareer H

Irradiation of the pelvis in the treatment of cancers will result in ovarian failure unless the ovaries are shielded
adequately. To protect the ovaries, an oophoropexy may be performed. Our aim was to evaluate the
feasibility, morbidity, and efficacy of laparoscopic ovarian transposition using a simple percutaneous needle
technique.Fifteen patients (ten with rectal cancer and five with Hodgkin's disease) underwent the new
laparoscopic oophoropexy technique. Laparoscopic releasing of the ovary was performed by cutting the utero-
ovarian ligament followed by placing the ovaries on the anterior abdominal wall. A percutaneous straight
needle was introduced through a 2-mm skin incision at the site of fixation. Repositioning of the ovaries was
done on an outpatient basis without the need for readmission to the operating theatre.The technique was
effective, reliable, and simple with no morbidities. Repositioning was performed simply in the outpatient clinic.
At follow-up, 11 patients had evidence of ovarian function.Percutaneous needle transposition of the ovaries is
a simple, effective, reliable, and easy-to-perform technique. It has short learning curve and can be done by less
experienced laparoscopic surgeons.
PMID: 21860468

Outcome and prognostic factors of uterine sarcoma in 59 patients: single institutional

results.

Nassar OA; Abdul Moaty SB; Khalil el-SA; El-Taher MM; El Najjar M

Uterine corpus sarcomas are rare heterogeneous tumors characterized by rapid progression and poor
response to treatment. This series investigated treatment options, relapse pattern, survival and prognostic
factors.A total of 59 patients were treated in the National Cancer Institute, Cairo University, (2000-2007).
Leiomyosarcoma accounted for 42.2% followed by carcinosarcoma (35.5%) and endometrial stromal sarcoma

192
(18.6%). 40.7% had FIGO stage I disease, 30.5% were II, 16.9% were III and 11.9% were IV. Surgery was the
primary line of treatment for all cases with total abdominal hysterectomy and bilateral salpingoophorectomy
in 88% of cases and 12% had less extensive surgery. Twenty-four (40.7%) patients had surgery alone, 24
(40.7%) had surgery and radiotherapy, 7 (11.9%) had surgery and chemo-irradiation and 4 (6.7%) had surgery
and chemotherapy.After 27.4 months mean follow-up (range: 2-69), relapses were detected in 32 patients
(59.2%) including 19 (59%) systemic metastases. Stage, adjuvant irradiation, tumor size, myometrial invasion,
vascular and cervix invasion were significant factors in univariate analysis; nevertheless, multivariate
prognostic factors were only stage (p=0.04) and adjuvant irradiation (p=0.01). 5-year cumulative disease free
survival for stage I was 63.6%, 41.2% for stage II, 10% for stage III and 0% in stage IV. Neither extent of surgery,
chemotherapy, histologic type or grade had significant effect on survival. Adjuvant radiotherapy offered 62%
2-year cumulative overall survival versus 22% for surgery alone and surgery with chemotherapy. Salvage
surgery for isolated relapses was performed for 9/32 recurrent patients (28%) including 5 lung
metastatectomies and 4 local pelvic resections. Mean survival after pulmonary resections was 7.4 months (6-
14).Diagnosis of uterine sarcoma is in itself a poor prognostic factor. Complete cytoreductive surgery and
adjuvant radiotherapy is essential for local control, provided tumor is limited to the uterus. Adjuvant
irradiation showed survival benefit. KEY WORDS: Uterine cancer - Uterine sarcoma - Uterine sarcoma
treatment - Sarcoma irradiation - Sarcoma prognosis.
PMID: 11121641

Prognostic implication of apoptosis and angiogenesis in cervical uteri cancer.

Zaghloul MS; El Naggar M; El Deeb A; Khaled H; Mokhtar N

A retrospective study was performed to investigate the relationship between spontaneous apoptosis and
angiogenesis uterine cervix squamous cell carcinoma patients. The prognostic value of each (and both) of
these biologic parameters was also tested.The pathologic materials of 40 cervical uteri squamous cell
carcinoma patients were examined and immunohistochemically stained to determine the tumor angiogenesis
(tumor microvascular score), using factor VIII-related antigen, and their tumor apoptotic index (AI), using the
TdT-mediated dUTP nick end-labeling (TUNEL) method. Three patients were Stage I, 18 were Stage II, 15 were
Stage III, and 4 were Stage IV (FIGO classification). All patients were treated with radical radiotherapy and all
had follow-up for more than 2 years.The mean AI was 15.1 +/- 12.8, with a median of 8.3. The mean tumor
microvascular score was 39.7 +/- 14.4, with a median of 3 8. The patients' age and tumor grade did not seem
to significantly affect the prognosis. On the other hand, AI and angiogenesis (tumor microvascular score) were
of high prognostic significance. The 3-year disease-free survival (DFS) rate for the patients having AI above the
median was 78% (confidence interval [CI] 69-87%), compared to 32% (CI 22-42%) for those having AI below the
median. The DFS was 18% (CI 9-27%) for patients having an angiogenesis score above the median, while it was
86% (CI 78-94%) for those patients having a score below the median.Determination of both tumor
microvascular score and AI can identify patients with the best prognosis of 100% DFS (with low angiogenesis
score and high AI). Women with a high score and low AI had the worst prognosis (DFS = 3%, CI 1-5%).
Moreover, high AI can compensate partially for the aggressive behavior of tumors showing a high rate of
angiogenesis.
PMID: 17671528

The correlation between FHIT, P53 and MMR genes in human papillomavirus-associated
cervical carcinoma.

Bahnassy AA; Zekri AR; Madbouly MS; El-Naggar M; El-Khelany ZF; El-Merzebany MM

High risk human papillomavirus (HR-HPV) types have been closely associated with cervical carcinoma.
However, other genetic events are likely to be required, in addition to HPV infection, for the development of
cervical cancer. We investigated 20 human cervical carcinomas and 15 normal cervical tissues for the
correlation between aberrant expression of the FHIT, p53 and MMR genes and their prognostic impact.The
expression of p53, FHIT and MMR genes (hMSH2, hMLH1,GTBP/hMSH6,hPMS2, hPMS1) was assessed in
relation to HPV infection by immunohistochemistry and PCR. HPV-16 and 18 DNA were detected in 95% and
25%, HPV m-RNA in 90% and 10% of cases; respectively. Homozygous deletion (HZD) and reduced FHIT protein

193
was detected in 40% and 65% of cases, respectively; 25% of which showed abnormal gene transcripts.
Reduced MMR gene expression was found in 19 cases. hMSH2 and hMLH1 showed the highest frequency (80%
and 70%, respectively). p53 overexpression was present in 50% of cases with a single mutation in exon 7.
There was a significant relation between FHIT aberrations, HPV-16 RNA, reduced hMLH-1 and hMSH- 2
expression; between reduced expression of hMSH-2 and p53 overexpression, GTPB-6, as well as between
GTPB-6 and hMLH-1. Aberrant expression of p53, FHIT, hMLH1and GTPB-6 was significantly associated with
recurrence.Aberrations involving MMR genes, FHIT and p53 are frequent in HPV-associated cervical carcinoma
with a significant correlation between them. However, only the FHIT, p53, hMLH1 and GTPB6 aberrations
could be used as predictors of tumor recurrences.
PMID: 17521451

The possible role of cell cycle regulators in multistep process of HPV-associated cervical
carcinoma.

Bahnassy AA; Zekri AR; Saleh M; Lotayef M; Moneir M; Shawki O

Human papillomavirus (HPV) 16 and 18 are associated with cervical carcinogenesis through an interaction
between HPV oncogenic proteins and cell cycle regulatory genes. However, the exact pathogenetic
mechanisms are not determined yet.We investigated 43 invasive squamous cell carcinoma (ISCC), 38 CIN III, 11
CINII and 18 CINI for cyclin D1, cyclin E, CDK4, p53, mdm-2, p21(waf), p27, p16(INK4A), Rb and Ki-67
aberrations using immunohistochemistry and molecular techniques. Twenty samples of normal cervical tissues
(NCT) were taken as a control.There was a significant increase in the expression of Ki-67, cyclin E, CDK4,
p16(INK4A), Rb (p= 0.003, 0.001, 0.001, 0.01) and a significant decrease in p27(KIP1) from NCT to ISCC (p =
0.003). Increased cyclin D1, p21(waf), p53, mdm-2 expression, homozygous deletion (HZD) and promoter
methylation (PM) of the Rb were detected in CINIII and ISCC only. On univariate analysis; tumor size,
differentiation, lymph node status, FIGO stage, Ki-67, cyclin D1, p53 and p27(KIP1) are significantly associated
with reduced overall survival (OS) while on multivariate analysis; only FIGO stage, Ki-67, cyclin D1, p53 and
p27(KIP1) were significant.1) Aberrations involving p27(KIP1), cyclin E, CDK4, p16(INK4A) are considered early
events in HPV 16 and 18-associated cervical carcinoma, whereas cyclin D1 and p53 pathway abnormalities are
considered late events. 2) Immunohistochemical tests for p16(INK4A) and cyclin E, could help in early diagnosis
of cervical carcinoma. 3) Only FIGO stage p53, cyclin D1, p27(KIP1) and Ki-67 are independent prognostic
factors that might help in predicting outcome of cervical cancer patients.
PMID: 18301453

The role of cyclins and cyclins inhibitors in the multistep process of HPV-associated
cervical carcinoma.

Bahnassy AA; Zekri AR; Alam El-Din HM; Aboubakr AA; Kamel K; El-Sabah MT; Mokhtar NM

Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is possibly
achieved through an interaction between HPV oncogenic proteins and some cell cycle regulatory genes.
However, the exact pathogenetic mechanisms are not well defined yet.We investigated 110 subjects (43
invasive squamous cell carcinoma (ISCC), 38 CIN III, 11 CIN II, 18 CIN I) confirmed to be positive for HPV16
and/or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin D1, cyclin E,
CDK4, cyclin inhibitors (p21 (waf), p27, p16 (INK4A)) and Ki-67 using immunohistochemistry and differential
PCR techniques.There was a significant increase in the expression of Ki-67, cyclin E, CDK4, p16 (INK4A)
(p=0.003, 0.001, 0.001) and a significant decrease in p27 (Kip1) from NCT to ISCC (p=0.003). There was a
significant correlation between altered expression of p27 (KIP1) and p16(INK4A) (p<0.001), cyclin D1 and CDK4
(p=0.001), cyclin E and p27 (Kip1) (p=0.011) in all studied groups. In ISCC, there was significant relationship
between standard clinicopathological prognostic factors and high Ki-67 index , increased cyclin D1 and cyclin E,
reduced p27 (Kip1) and p21 (waf).1) Aberrations involving p27 (KIP1), cyclin E, CDK4 and p16 (INK4A) are
considered early events in HPV 16 and 18-associated cervical carcinogenesis (CINI & II), whereas cyclin D1
aberrations are late events (CINIII & ISCC) 2) Immunohistochemical tests for p16 (INK4A) and cyclin E could
help in early diagnosis of cervical carcinoma 3) Only FIGO stage, cyclin D1, p27 (Kip1) and Ki-67 are
independent prognostic factors that might help in predicting outcome of cervical cancer patients.

194
PMID: 21863069

Trachelectomy: a review of 15 cases.

El-Zohairy MA

To determine the indications and complications of removal of the retained cervical stump
(trachelectomy).Retrospective review of the records of 15 cases of removal of the retained cervical stump
performed at the Department of Surgical Oncology NCI Cairo University and Nasser Institute Cairo between
January 2005 and December 2009.Fifteen patients were identified with a mean age of 43.1±8.4 years. The
indications for subtotal hysterectomy were uterine fibroids, 7 (46.7%), abnormal bleeding, 5 (33.3%), and
ovarian mass, 3 (20%) cases. Route of trachelectomy was abdominal in all cases. The indications for
trachelectomy were cervical malignancy in 8 (53.3%), residual tumor at the hysterectomy specimen in 3 (20%),
and persistent bleeding in 2 (13.3%) cases. The most common concomitant procedures with the trachelectomy
were pelvic lymphadenectomy in 11 (73.3%), and oophorectomy in 10 (66.6%) cases. There were no
postoperative mortalities. The most common complications were wound infection, 4 (26.6%), and urinary tract
infection, 3 (20%). The mean estimated blood loss was 341.0± 82.3ml. Hospital stay was 7.9±5.1 days. The
most common histological diagnosis was squamous carcinoma 9 cases (60%). The median follow-up period
was 16 months.Subtotal hysterectomy carries the risk of developing a stump cancer. Patient agreement is
mandatory. Subtotal hysterectomy should be avoided whenever possible in populations with restricted access
to screening programs for cancer of the uterine cervix. KEY WORDS: Trachelectomy - Cervical stump.

195
 Appendix-1: Publications by Departments

Anesthesia:

PMID #:21178606, 17305675, 15959548, 7525763, 20664339, 15912151, 21448029, 17147725,

16788341, 15025835

Biology

PMID #:17102822, 12033498, 14502848, 22530140, 15469721, 10706382, 10706383, 19459743,

20586027, 17102820, 11418321, 22570651, 10493959, 19593673, 22527932, 22866165, 22929918,
17192687, 21557333, 10778762, 20571596, 15717000, 22295218, 16263653, 12913081, 22895066,
21812646, 18382799, 16353081, 18301452, 20803320, 8249181, 22939736, 16508680, 22730303,
23060297, 21443094, 22853046, 15589744, 16883441, 17102821, 21475468, 21781333, 19858727,
18959789, 10628830, 18689276, 15918183, 21371325, 17237848, 18053271, 21701780, 17610473,
19093231, 23082489, 15724387, 19644357, 15724392, 19459752, 15716999, 19173711, 16425355,
17786720, 8897161, 12515905, 19054267, 17300723, 17631684, 11261753, 16508682, 17576388,
20979645, 21475447, 8668646, 20422130, 20075715, 15648068

Clinical Pathology

PMID #:16799657, 16353083, 22897908, 17496933, 20424651, 11106820, 20601973, 16508681,

19034338, 23082469, 17671537, 2761288, 17671532, 15218412, 16799654, 1697005, 16353080,
19203726, 19034339, 21415865, 20424654, 21132031, 15912152, 16116502, 17974155, 12132778,
21671364, 22834638, 15603994, 19214976, 16508683, 17127630, 22776813, 17356388,

Dental

PMID #:2246587, 21863076, 21863077

Epidemiology

PMID #:10792158, 16430058, 8591181, 11604832

Medical Oncology

PMID #:10908847, 16018940, 2054316, 11301380, 2706136, 10526537, 15610858, 8905036,

11173945, 11693804, 21552959, 18312930, 16892094, 1797193, 22929919, 17671530, 2347057,
22570674, 11917941, 19652667, 19282568, 1390313, 2126646, 20652953, 22180424, 22220257,
19034340, 22771839, 18724311, 15568034, 10467322, 8704694, 21863068, 21802939, 15950794,
15716991, 22263061, 20424652, 17034953, 18809226, 20347505, 17264756, 10643541, 22099932,
19190690, 1743631, 2758567, 22588434, 16892095, 19896236, 18525325, 21442386, 20015593,
20018452

Nuclear Medicine

PMID #:18228210, 20601971, 18228214

Pathology

PMID #:3383943, 19034337, 3147281, 19171060, 21860467, 20571594, 22099965, 22776815,

22553813, 22099935, 21863073, 21199580, 19847283, 10752778, 21860469, 22929921, 17671536,
19034345, 18839030, 15385053, 22429319, 23082480, 16246194, 21801719, 22504106, 22776843,
18301454, 16353079, 19847278, 19672286, 18986555, 19190689, 8630905, 22099934, 15693850,
20172169, 3509536, 16353082, 17671528, 17521451, 18301453

196
Pediatric Oncology

PMID #:22099936, 21503005, 21863070, 18839034, 20029466, 20029468, 15284589, 20029467,

15912149, 1743630, 21863071, 17366527, 14966830, 20571598

Pharmacology

PMID #:11589785, 11529691, 8082409, 15347908, 11419959, 10623482, 10208759, 16116501

Radio-diagnosis

PMID #:20601970, 20571599, 19190691, 21860470, 18565897, 21257861

Radiotherapy

PMID #:8040027, 7646934, 7631026, 21353794, 20354750, 20624129, 16430078, 17671529,

8616767, 21554043, 16414487, 1612951, 20084724, 22716492, 15729596, 20029473, 16508679,
11870530, 11669328, 22776812, 22227539, 20029474, 16508678, 15959551, 21132030, 16799658,
17671533, 20672705, 2254118, 20029465, 14597354, 21132029, 20927224, 20084794, 19058953,
22099961, 17102816, 19034341, 19847279, 2522918, 18839029, 16508677, 16799659, 19034343,
19828004, 10790282, 16116496, 8176938, 11121641

Surgery

PMID #:20571597, 21492915, 15716994, 16536777, 21503002, 21503004, 22776840, 19652671,

21132032, 21132035, 20601969, 11917950, 17237855, 16456769, 20601966, 17671535, 18301456,
15716996, 19190695, 19847286, 15912146, 15716993, 22099963, 3507426, 21508824, 15959545,
20601968, 20424656, 19652672, 17237850, 22185515, 17102819, 14965588, 15751939, 14734470,
22099933, 22776816, 17671531, 17496938, 17671527, 21415863, 18301457, 22776844, 17496937,
16799652, 22236813, 17102817, 19672288, 22617715, 16508676, 19847285, 15716997, 21552057,
20164007, 16116497, 19347802, 22776841, 21503009, 21132036, 18640302, 19463624, 17102814,
18341198, 17671526, 12078799, 20424659, 20424655, 20029475, 20571600, 21503006, 22099962,
20601967, 20029476, 15959552, 16353076, 21458039, 21503003, 20571595, 15959547, 19847284,
16799651, 17237846, 17362327, 16799653, 22776814, 21298536, 21860468, 21863069

197