J Ayub Med Coll Abbottabad 2009;21(1)

http://www.ayubmed.edu.pk/JAMC/PAST/21-94 1/Khairunnisa.pdf
GESTATIONAL TROPHOBLASTIC DISEASE: EXPERIENCE AT
NAWABSHAH HOSPITAL
Khairunnisa Nizam, Gulfareen Haider*, Nizamuddin Memon**, Ambreen Haider†
Department of Obstetrics and Gynaecology, Nawabshah Medical College Hospital, Nawabshah, *Department
of Obstetrics and
Gynaecology, Isra University Hospital, **Department of Radiology, †Department of Cardiology, Liaquat
University of Medical Health
Sciences Hospital, Hyderabad, Pakistan
Background: Gestational Trophoblastic Disease (GTD) is a heterogeneous group of diseases that
includes partial and complete hydatidiform mole, invasive mole, choriocarcinoma and placental site
trophoblastic tumour. The incidence of GTD varies in different parts of the world. The malignant
potential of this disease is higher in South East Asia in comparison to western countries. Objectives of
study were to determine the frequency, clinical presentation and management outcomes of GTD. This
retrospective, descriptive case series was conducted in the Department of Obstetric and Gynaecology
Nawabshah Medical College Hospital, from 1st Jan 2007 to 30th Dec 2007.
Methods: The case records
of all the gestational trophoblastic cases during study period were analysed regarding their history,
clinical examination, investigations, treatment and follow-up. The main outcomes were measured in
terms of duration, antecedent pregnancy, investigations, treatment and the follow-up.
Results: There
were a total of 1056 Obstetric admissions during the study period, which included 30 cases of
trophoblastic disease with a frequency of GTD was 28 per 1000 live births. Of these 30 cases, 21 (70%)
patients had hydatidiform mole, 7 (23.3%) patients had invasive disease and 2 (6.6%) patients had
choriocarcinoma. Twenty three patients (76.6%) received chemotherapy while 25 (83.3%) patients had
suction evacuation and 4 (13.3%) patients underwent hysterectomy. Among all patients, 29(96.7%)
fully recovered and 1 (3.3%) died because of extensive disease; metastasis extending up to brain.
Conclusion: Frequency of GTD was higher compared to national and international studies. The disease
was common in extremes of ages, low para and grand multiparous women. Hydatidiform mole was the
commonest type of trophoblastic disease in these patients. Most common presenting complaint was
bleeding per vagina followed by pain in lower abdomen.
Keywords: Gestational trophoblastic disease, Hydatidiform mole, Management

 Developmental anomaly of the placenta that converts the chorionic villi into a mass of clear fluid-filled
vesicles.
 Two types of moles:

a. Complete moles – neither an embryo nor an amniotic sac. It

is characterized by swelling and cystic formation of all
trophoblastic cells. No fetal blood is present. If an embryo
did develop, it was most likely only 1 to 2 mm in size and
died early on. A complete mole is highly associated with
the development of choriocarcinoma.

b. Partial mole – embryo (usually with multiple anomalies) and

amniotic sac. It is characterized by edema of a layer of the
trophoblastic villi with some of the villi forming normally.
Fetal blood may be present in the villi, and an embryo up
to the size of 9 weeks gestation may be present. Typically,
apartial mole has 69 chromosomes in which there are
three chromosomes for every one pair.

 Major cause of second trimester bleeding.

 Also called molar pregnancy or hydatidiform mole.

Pathophysiology

 Trophoblastic villi cells located in the outer ring of the blastocyst (the structure that develops via cell division
around 3 to 4 days after fertilization) rapidly increase in size, begin to deteriorate, and fill with fluid.
 The cells become edematous, appearing a grapelike clusters of vesicles.
 As a result, the embryo falls to develop past the early stages.

Causes

 Exact cause is unknown

 May be associated with poor maternal nutritional (specifically, an insufficient intake of protein and folic acid),
a defective ovum, chromosomal abnormalities, or hormonal imbalances.
 Preceding molar pregnancy in about 50% of patients with choriocarcinoma.
  Preceding spontaneous or induced abortion, ectopic pregnancy, or normal pregnancy in the remaining 50%
of patients.

Assessment findings

 Disproportionate enlargement of the uterus; possible grapelike clusters noted in the vagina on pelvic
examination.
 Excessive nausea and vomiting, abdominal cramping.
 Intermittent or continuous bright red or brownish vaginal bleeding
 Passage of tissue resembling grapelike clusters.
 Symptoms of gestational hypertension before 20 weeks’ gestation.
 Absence of fetal heart tones.

Test Results:

 Radioimmunoassay of human chorionic gonadotropin (hCG) levels reveals extremely elevated levels of
early pregnancy.
 Histologic examination may reveal the presence of vesicles.
 Ultrasonography performed after 3 months’ gestation reveals grapelike clusters rather than a fetus, an
absence of fetal skeleton, and evidence of a snowstorm-like pattern.
 Hemoglobin level, hematocrit, red blood cells (RBC) count, prothrombin time, partial thromboplastin time,
fibrinogen levels, and hepatic and renal function findings are all abnormal.
 White blood cells count and erythrocyte sedimentation rate are increased.

Treatment:

 Suction and curettage; if indicated.

 Weekly monitoring of beta-hCG levels until normal 3 consecutive weeks.
 Periodic follow-up for 1 to 2 years.
 Pelvic examinations and chest X-rays at regular intervals.
 Emotional support.
 Avoidance of pregnancy until hCG levels are normal (may take up to 1 year).

Nursing Interventions:

 Obtain baseline vital signs.

 Preoperatively observe the patient for signs of complications, such as hemorrhage, uterine infection, and
vaginal passage of vesicles.
 Save any expelled tissue for laboratory analysis.
 Prepare the patient physically and emotionally for surgery, if indicated.
 Postoperatively, monitor vital signs and fluid intake and output, and assess for signs of hemorrhage.
 Encourage the patient and her family to express their feelings.
 Offer emotional support, and help them through the grieving process.
 Help the patient and her family develops effective coping strategies, referring them to a mental health
professional, if needed.

Introduction

Background

Gestational trophoblastic disease (GTD) can be benign or malignant. Histologically, it is classified into hydatidiform
mole, invasive mole (chorioadenoma destruens), choriocarcinoma, and placental site trophoblastic tumor (PSTT).
Those that invade locally or metastasize are collectively known as gestational trophoblastic neoplasia (GTN).
Hydatidiform mole is the most common form of GTN. While invasive mole and choriocarcinoma are malignant, a
hydatidiform mole can behave in a malignant or benign fashion.
Histologic section of a complete hydatidiform mole stained with hematoxylin and eosin. Villi of different sizes
are present. The large villous in the center exhibits marked edema with a fluid-filled central cavity known as
cisterna. Marked proliferation of the trophoblasts is observed. The syncytiotrophoblasts stain purple, while
the cytotrophoblasts have a clear cytoplasm and bizarre nuclei. No fetal blood vessels are in the
mesenchyme of the villi.

[ CLOSE WINDOW ]

Histologic section of a complete hydatidiform mole stained with hematoxylin and eosin. Villi of different sizes
are present. The large villous in the center exhibits marked edema with a fluid-filled central cavity known as
cisterna. Marked proliferation of the trophoblasts is observed. The syncytiotrophoblasts stain purple, while
the cytotrophoblasts have a clear cytoplasm and bizarre nuclei. No fetal blood vessels are in the
mesenchyme of the villi.

No methods exist to accurately predict the clinical behavior of a hydatidiform mole by histopathology. The clinical
course is defined by the patient's serum human chorionic gonadotropin (hCG) curve after evacuation of the mole. In
80% of patients with a benign hydatidiform mole, serum hCG levels steadily drop to normal within 8-12 weeks after
evacuation of the molar pregnancy. In the other 20% of patients with a malignant hydatidiform mole, serum hCG
levels either rise or plateau.1,2

Pathophysiology

A hydatidiform mole is considered malignant when the serum hCG levels plateau or rise during the follow-up period
and an intervening pregnancy is excluded. This occurs in 15-20% of hydatidiform moles.1,2,3

A hydatidiform mole with a fetus or fetal tissue and a triploid karyotype is known as a partial or incomplete mole.
Partial moles also have malignant potential, but only 2-3% become malignant.4,5,6 Cases of partial hydatidiform moles
with lung metastasis have been reported and at least one case of choriocarcinoma on a biopsy from a vaginal
metastasis has been reported in a patient being observed for a partial hydatidiform mole.7,8

An invasive mole has the same histopathologic characteristics of a hydatidiform mole, but invasion of the
myometrium with necrosis and hemorrhage occurs or pulmonary metastases are present.

Histologically, choriocarcinomas have no villi, but they have sheets of trophoblasts and hemorrhage.
Choriocarcinomas are aneuploid and can be heterozygous depending on the type of pregnancy from which the
choriocarcinoma arose. If a hydatidiform mole preceded the choriocarcinoma, the chromosomes are of paternal
origin. Maternal and paternal chromosomes are present if a term pregnancy precedes the choriocarcinoma. Of
choriocarcinomas, 50% are preceded by a hydatidiform mole, 25% by an abortion, 3% by ectopic pregnancy, and the
other 22% by a full-term pregnancy.1 Choriocarcinoma has also been associated with ectopic pregnancy with a
theoretic incidence of 1 in 5333 ectopic pregnancies.9

Placental site trophoblastic tumor is a rare form of gestational trophoblastic neoplasia, with slightly more than 200
cases reported in the literature.10,11 In patients with PSTT, intermediate trophoblasts are found infiltrating the
myometrium without causing tissue destruction. The intermediate trophoblasts contain human placental lactogen
(hPL).12 These patients have persistent low levels of serum hCG (100-1000 mIU/mL). However, serum hCG levels as
high as 108,000 mIU/mL have been reported in patients with PSTT.13 The treatment of PSTT is hysterectomy with
ovarian conservation.14 If the tumor recurs or metastases are present at initial diagnosis, chemotherapy is
administered with variable results.15,16 Radiation therapy may provide local control.
The most frequent sites of metastases of malignant gestational trophoblastic neoplasia are the lungs, lower genital
tract, brain, liver, kidney, and gastrointestinal tract.

In this microphotograph of a choriocarcinoma metastatic to the brain, the neuropil is seen on the right and
the biphasic (2 cell populations) choriocarcinoma is seen to the left with hemorrhage at the left border of the
photograph (H&E stain).

Frequency

United States

Gestational trophoblastic neoplasia is diagnosed in 15-20% of patients with a complete hydatidiform mole and 2% of
partial hydatidiform moles. Lung metastases are found in 4-5% of patients with complete hydatidiform moles and
rarely in cases of partial hydatidiform moles.

Choriocarcinoma occurs in 1 out of 40 hydatidiform moles and in 1 out of 20,000-40,000 pregnancies.1,17

However,only 1 out of 160,000 term pregnancies is followed by a choriocarcinoma.18

International

The international rate of choriocarcinoma has been reported to be as high as 1 in 500-600 pregnancies in India to 1
in 50,000 pregnancies in Mexico, Paraguay, and Sweden.17,19,20 These differences are probably due to differences in
methodology (eg, identification of cases, accuracy of denominator).17,19

Mortality/Morbidity

Patients who have a malignant hydatidiform mole, an invasive mole, or a choriocarcinoma should undergo a
systematic search for metastases. Patients who have metastases are classified as high-risk or low-risk according to
the National Institutes of Health classification.2 The criteria for high-risk metastatic gestational trophoblastic neoplasia
include hepatic or brain metastasis, serum hCG levels greater than 40,000 mIU/mL prior to the initiation of
chemotherapy, duration of disease longer than 4 months, prior unsuccessful chemotherapy, and malignant
gestational trophoblastic neoplasia following a term pregnancy.

 Patients with malignant nonmetastatic or metastatic low-risk gestational trophoblastic neoplasia have an
almost 100% probability of cure with chemotherapy. The probability of cure after chemotherapy for patients
with metastatic high-risk gestational trophoblastic neoplasia is approximately 75%.21
 The probability of a late recurrence after the patient has been in remission (normal serum beta-hCG titers)
for 1 year is less than 1%.2,22

See Prognosis section for more information on recurrence rate.

Race

 Little information is available on international ethnic or racial differences of the incidence of choriocarcinoma.
 In the United States, African Americans have the highest incidence of choriocarcinoma and the lowest
survival rates.23

Sex

Gestational trophoblastic neoplasia affects women during their reproductive years. However, placental site
trophoblastic tumors have been diagnosed when patients were postmenopausal.

Age

The incidence of choriocarcinoma increases with age and is 5-15 times higher in women 40 years and older than in
younger women.19
Clinical

History

Most cases of gestational trophoblastic neoplasia are diagnosed when the serum hCG levels plateau or rise in
patients being observed after the diagnosis of hydatidiform mole. If metastases are present, signs and symptoms
associated with the metastatic disease, such as hemoptysis, abdominal pain, hematuria, and neurologic symptoms,
may be present.

Physical

 Metastasis to the lower genital tract present as purple to blue-black papules or nodules. These are
extremely vascular and might bleed profusely if biopsied.24
 Abdominal tenderness may be present if  liver or gastrointestinal metastases have occurred.
 Abdominal guarding and rebound tenderness may be present if a hemoperitoneum has occurred due to
bleeding from an abdominal metastasis. Bleeding from a metastasis could also result in signs and symptoms
of hemorrhagic shock.25,26
 Neurologic deficits, from lethargy to coma, can be encountered if brain metastasis has occurred.
 Jaundice may be present if liver metastasis causes biliary obstruction.

Causes

Why some hydatidiform moles become malignant and others do not is unknown. However, mounting evidence shows
different molecular profiles between nonmalignant and malignant gestational trophoblastic disease

Treatment

Medical Care

Patients with gestational trophoblastic disease (GTD) do not require medical therapy. Because 20% of patients with
hydatidiform mole develop malignant disease, such as persistent hydatidiform mole with or without metastasis, some
have suggested the use of a prophylactic dose of methotrexate in noncompliant patients.39,40 However, observing
patients with weekly serum hCG levels is preferable, and only patients with rising or plateauing titers, as occurs in
patients with gestational trophoblastic neoplasia (GTN), should be treated with chemotherapy.1

Patients with nonmetastatic GTN or metastatic low-risk GTN are treated with single-agent chemotherapy.41,42,43,44,45,46
Many in the United States prefer methotrexate. However, actinomycin D can be used in patients with poor liver
function. During treatment, the serum hCG levels are monitored every week. One additional course of chemotherapy
is administered after a normal serum hCG level. After 3-4 normal serum hCG levels, the levels are observed once per
month for 1 year. A switch from methotrexate to actinomycin D is made if the patient receiving methotrexate for
nonmetastatic or metastatic low-risk GTN develops rising or plateauing serum hCG levels.

A randomized clinical trial comparing 30 mg/m2 methotrexate given weekly to patients with low-risk GTN versus 1.25
mg/m2 of actinomycin D given every other week showed a higher complete response rate with actinomycin D.47

Patients with high-risk metastatic GTN are subdivided into 2 groups: those with a WHO score of less than 7 and
those with a score of 7 or higher and who are at high risk of therapy failure.

 Patients with a WHO score of less than 7 can be treated with single-agent chemotherapy (methotrexate or
actinomycin) because their chances of achieving a cure are high.48 AT least 1 additional course of
chemotherapy is administered after a normal serum hCG level is achieved.
 Patients with WHO scores of 7 or higher
o These patients are treated with a combination of etoposide, methotrexate, and actinomycin D
administered in the first week of a 2-week cycle and cyclophosphamide and vincristine (Oncovin)
administered in the second week.49,50,51,52 This is known as the EMA-CO regimen.
o Some substitute cisplatin and etoposide for cyclophosphamide and vincristine during the second
week. This is known as the EMA-CE regimen.53 Some reserve the EMA-CE regimen for patients in
whom EMA-CO fails.
o At least 2 additional courses of EMA-CO or EMA-CE are administered after a normal serum hCG
level.
o Patients with metastasis to the brain receive whole brain irradiation (3000 cGy) in combination with
chemotherapy.54,55,56 Corticosteroids (dexamethasone) with systemic effect are administered to
reduce brain edema. This is the most common approach in the United States.
o Early neurosurgical intervention for solitary lesions or stereotactic radiotherapy for multiple lesions
or solitary lesions in locations at high risk for surgical morbidity is used at the Charing Cross
Hospital in the United Kingdom and has been reported by physicians from Duke University in North
Carolina.57 At Charing Cross, neurosurgery is followed by moderate- and high-dose intravenous
 methotrexate and intrathecal methotrexate. However, intrathecal methotrexate is not routinely used
by others. A therapeutic level of methotrexate is achieved in the cerebrospinal fluid at doses of
methotrexate >600 mg/m2 given intravenously to patients with brain metastases.57
o In patients not receiving whole brain irradiation, the dose of methotrexate on day 1 of the EMA-CO
or EMA-CE regimen is increased to 1000 mg/m2. Instead of 4 doses of folinic acid, 8 doses are
given starting 24 hours after the methotrexate infusion. Patients with liver metastasis are
considered for liver irradiation (2000 cGy).58
 Patients with stage IV GTN are most often treated with multiagent chemotherapy, even when the WHO
score is less than 7, which is uncommon.
 After achieving 3-4 consecutive weekly normal serum hCG levels, patients with stage IV GTN are observed
with monthly serum hCG levels for 2 years. If the levels begin to rise during follow-up, the patient is
evaluated for possible intervening pregnancy, or persistent or recurrent disease.

Surgical Care

 A hysterectomy may be necessary in case of uncontrolled vaginal bleeding. Hysterectomy may reduce the
total number of chemotherapy cycles needed to achieve remission.36,37
 Uterine or hypogastric artery ligation or embolization of feeding vessels may be needed to control
hemorrhage. Hepatic artery embolization has been used successfully to control hemorrhage from hepatic
metastases.25
 A repeat D&C in the presence of persistent tissue on pelvic ultrasonography may reduce the number of
chemotherapy cycles needed to achieve remission.59
 Craniotomy may be needed to control bleeding and provide decompression.57,51
 Resection of solitary metastasis (eg, thoracotomy) or disease within the myometrium may help achieve a
remission.60,61,62

Consultations

A gynecologic oncologist experienced in managing GTN should be consulted.

Diet

No restrictions

Activity

No restrictions

Medication

The goals of pharmacotherapy are to reduce morbidity and to eradicate the neoplasm.

Antineoplastics

Gestational trophoblastic tumors are sensitive to many antineoplastic agents, especially those that act in the S phase
or the M phase of the cell cycle.

INTRODUCTION births.7 Common clinical presentations include

Gestational Trophoblastic Disease (GTD) is a
heterogeneous group of diseases that includes partial
and complete hydatidiform mole, invasive mole,
choriocarcinoma and placental site trophoblastic
tumour. In recent years, new entities like epithelioid
trophoblastic tumour have been added.1 The
incidence of GTD varies in different parts of the
world, for example, in Japan, the incidence is 2/1000
deliveries while in Malaysia, the incidence of molar
pregnancy and gestational trophoblastic neoplasia is
2.8/1000 and 1.59/1000 deliveries respectively.2,3
Meanwhile, in North America, its incidence is
reported up to 2.5/1000 pregnancies.4 Highest
incidence of 12.1/1000 deliveries is reported from
Turkey.5 The malignant potential of this disease is
higher in South East Asia where it is as high as 10–
15% in comparison to 2–4% in the western
countries.6
The exact incidence in Pakistan is not known
but only one study has reported it to be 0.68/1000
vaginal
bleeding in early trimester, uterus larger than
gestational
age and absence of foetal parts after 20 weeks of
gestation. Ultrasonography is a reliable non-invasive
tool for diagnosis of GTD in the clinical setting.
Since this group of disorders is now one of
the highly curable neoplasms, early diagnosis and
prompt treatment is necessary. The rates of GTD are
decreasing and survival has dramatically improved in
different parts of the world.8,9
In Pakistan, few studies have been
conducted in Lahore and Karachi to find out the
incidence of GTD, with an objective to compute the
epidemiological and clinical data in these areas.
The objective of this study was to find out
the frequency, common presentation, type of the
GTD, extent of the disease, treatment modalities and
the outcome in a cohort of local population.
PATIENTS AND METHODS
This retrospective, descriptive case review was
conducted at the Department of Gynaecology and
Obstetrics, Nawabshah Medical College Hospital,
from 1st Jan 2007 to 30th Dec 2007. The case
records
of all these patients who were admitted with
trophoblastic disease and neoplasm were analysed
retrospectively regarding the age, parity, signs and
symptoms, duration of previous treatment,
histopathology, investigations, type of trophoblastic
disease, type of surgical treatment, chemotherapy,
follow-up and mortality associated with this disease.
All those patients having trophoblastic disease with
J Ayub Med Coll Abbottabad 2009;21(1)
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elevated β-HCG, ultrasonic or histopathological
evidence of the disease were included in the study.
Brain metastasis was detected through CT Scanning
of the patients. Patients having irregular bleeding per
vagina without any evidence of trophoblastic disease
were excluded. Socioeconomic status of patient was
labelled as poor class if monthly income was up to
rupees 10,000 per months, middle class if income is
up to 20,000 per months and upper class if monthly
income was more than 20000 rupees per months.
Data was analyzed using SPSS version 11.0.
RESULTS
There were total 1056 Obstetrical admissions during
the study period which included 30 cases of GTD.
Hence, the frequency of GTD was 28 per 1000 live
births in this study.
Majority of the patients were of more than
of 38 year age 16 (53.3%) (Table-1). Out of these 30
patients, 15 (50%) were para one, while 12 (40%)
were para more than four (Table-2).
The most common presenting symptom was
bleeding per vaginum 11 (36.3%) followed by pain in
lower abdomen 7 (23.3%), passage of moles 5
(16.6%), hyperemesis gravidarum 4 (13.3%) and
dyspnoea in 3 (10.0%).
The antecedent pregnancy was hydatidiform
mole in 19 (63.3%) patients, abortion in 9 (30%) and
full term pregnancy in 2 (66.6%) patients.
The gestational period in 18 (60%) patients,
in which disease was diagnosed was between 2–5
months, in 9 (30%) patients, it was between 1–2
months, and in only 3 (10%) patients, it was more
than 5 months.
Hydatidiform mole was diagnosed in 21
(70%) patients, invasive mole in 7 (23.3%) and
choriocarcinoma in 2 (6.6%) patients. No patient had
placental site trophoblastic tumour.
Out of 30 patients, 29 underwent surgical
treatment. In 25 (83.3%) patients, suction evacuation
was done and 4 (13.3%) cases underwent
hysterectomy. Indication of hysterectomy was
emergency presentation with heavy bleeding.
Seven (23.3%) patients received no adjuvant
chemotherapy. Twenty three (76.6%) patients
received
chemotherapy. Among them 19 (82.6%) patients
received single drug therapy (methotrexate alternate
with folinic acid) and 4 (17.3%) received multiple drug
therapy (EMA-CO regime). Before starting
chemotherapy, opinion from oncologist in Atomic
energy department was taken regarding type and
dosage of chemotherapy. Chemotherapy was given
for
3–6 months. Among the 30 patients, 29 (96.7%) fully
recovered and 1 (3.3%) died because of extensive
disease (metastasising up to brain). Follow-up of the
patients was carried out by clinical examination and
investigations such as serum β-HCG level, ultrasound
examination and X-ray chest. Initially, it was carried
out monthly, then after every 3 months till the β-HCG
level was not detectable. In patients having benign
hydatidiform mole, the serum β-HCG level was
undetectable within 3 months period.
Table-1: Socio-demographic data
Parameters Number of Patients Percentage
Age
<20 10 33.1
21–38 4 13.31
>38 16 53.3
Parity
0–1 15 50
2–4 3 10
>4 12 40
Education
Illiterate 19 63.3
Primary 8 26.6
Middle 2 6.6
Graduation 1 3.33
Socioeconomic condition
Low 22 73.3
Middle 7 23.3
High 1 3.3
Table-2: Clinical presentation
Symptoms Number of Cases Percentage
Bleeding P/V 11 36.6
Pain in lower abdomen 7 23.3
Passage of moles 5 16.6
Hyperemesis gravidarum 4 13.3
Dyspnoea 3 10
Table-3: Type of gestational trophoblastic disease
Type of GTD Number of Cases Percentage
H. Mole 21 70
Invasive mole 7 23.3
Choriocarcinoma 2 6.6
DISCUSSION
Gestational Trophoblastic Disease (GTD) is
characterised by the secretion of a distinct tumour
marker, the β-HCG. This condition is curable even in
the presence of metastasis. The major
wellestablished
risk factors for the disease are advanced
maternal age and a past history of GTD.10
Frequency of GTD in our study is 28 per 1000 live
births, which is quite significant. This frequency is
also higher within our country if compared to
hospital based studies from Peshawar 11 and
Karachi.12 The reason for the high frequency of the
GTD in this study might be the fact that the hospital
is a major referral centre with large catchment area.
Another reason is that our patients had low
socioeconomic and poor educational status (73.3% of
patient had monthly income less than Rs. 10,000).
A Korean study proved this fact by
decreasing the rate of incidence from 4.4 (1960s) to
1.6 (1990s) with improvement in medical care and to
socioeconomic and educational changes.
J Ayub Med Coll Abbottabad 2009;21(1)
http://www.ayubmed.edu.pk/JAMC/PAST/21-96
1/Khairunnisa.pdf
Improvement in nutrition in another study
did not support the suggestion of protein deficiency
as an etiological factor.13
Another study conducted by Tham stated
that the high incidence in Asia is generally attributed
to low socioeconomic status and malnutrition.14
Maternal reproductive age is the most consistent risk
factor for hydatidiform mole in every region and
ethnic group. In this study, disease was more
common in the extreme of reproductive ages. It is
consistent with the findings of studies from
Singapore6 and Karachi12.
The available evidence suggests that
hydatidiform mole arises as a consequence of
defective ova.15 It is premature in young and post
mature in old ages. Antecedent pregnancy in invasive
mole was hydatidiform mole while in
choriocarcinoma both the patients had full-term
pregnancy one year back.
Vaginal bleeding was the most common
presenting symptom in this study and it is also
reported by other studies such as Kim16 and Zalel et
al17. Another study conducted by Moodley et al, have
also reported the same findings.2
The diagnosis of trophoblastic disease was
based on clinical and histopathological features, β-
HCG,
ultrasonography, especially by using high resolution
vaginal ultrasonography that could diagnose the
disease much earlier. Ultrasonography and serum β-
HCG are the sensitive detectors of trophoblastic
disease. These tests are simple, non invasive,
inexpensive and yield quick result. Ultrasonography
and Doppler imaging are helpful in diagnosing
gestational trophoblastic disease, in determining
whether invasive disease is present, in detecting
recurrent disease, and in following the effectiveness
of chemotherapy.18 Most of the patients in this study
were having hydatidiform mole while 29.9% were
having malignant trophoblastic disease in the form of
choriocarcinoma and invasive mole.
Choriocarcinoma is a potentially fatal disease but
current management protocol has turned the
prognosis highly favourable. Izhar19 from Peshawar
has also reported cure rate of 80%. Like other
studies,
in this study, majority of patients with molar
pregnancy were treated with suction curettage, i.e.
83.3% and only 4 patients needed hysterectomy;
seven had invasive mole and other had persistent
vaginal bleeding, which did not settle with
evacuation and chemotherapy. Patients with
malignant trophoblastic disease were treated with
multiple agent chemotherapy and those who had
increased serum β-HCG or those with persistent
bleeding per vagina, after evacuation, were treated
with single drug chemotherapy. The duration of
treatment ranged from 3–6 months with three doses
of chemotherapy till the serum β-HCG level was
undetectable.
Overall complete cure was achieved in
96.7% patients in this study. However, 1 patient
(3.3%) died during therapy. Main reasons of death in
this patient was extensive disease (metastasising up
to brain) and poor general health.
CONCLUSION
In this series, frequency of GTD was higher
compared to national and international literature. The
disease was common in extremes of ages, low para
and grand multiparous women. Hydatidiform mole
was the commonest type of trophoblastic disease in
these patients. Most common presenting complaint
was bleeding per vagina followed by pain in lower
abdomen. Patients with regular follow-up recovered
fully while mortality was associated with
complications, delay in recovery and receiving no
proper treatment. Proper management in the early
stages strongly influences the outcome of the
diseases. Hence, emphasis should be given to detect
the disease in its early stage to decrease the mortality
and morbidity from this condition.
REFERENCES
1. Cheung AN. Pathology of gestational trophoblastic
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2. Moodley M, Tunkyl K, Moodley J. Gestational
trophoblastic
syndrome: an audit of 112 patients. A South African
experience. Int J Gynecol Cancer 2003;13:234–9.
3. Sivanesaratnam V. Management of gestational
trophoblastic
disease in developing countries. Best Pract Res Clin
Obstet
Gynaecol 2003;17:925–42.
4. Lara FM, Alvarado AM, Candelaria M, Arce CS.
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Address for Correspondence:
Dr. Gulfareen Haider, B/No: 530-A, Block C, Unit 8
Latifabad, Hyderabad, Pakistan. Cell: +92-300-
9379794
Email: gfareen@yahoo.com