REVIEW

CURRENT
OPINION Aspects on gallbladder cancer in 2014
Åke Andrén-Sandberg a,b and Yang Deng a,b

Purpose of review
To discuss some key issues involved in the management of gallbladder cancer (GBC).
Recent findings
The decline in incidence and mortality of GBC began decades before the introduction of laparoscopic
surgery. In consecutive autopsies and in cases in which cholelithiasis was present, the incidence of
gallbladder carcinoma is 3–4%. A number of genetic alterations have been identified in the different
stages of GBC and they support the morphological evidence of two pathways by which tumors develop.
Some of these genetic changes are associated with particular risk factors. All management of GBC and all
comparisons of treatment results from different centers must be based on the stages.
Summary
Simple cholecystectomy is the adequate treatment for T1a GBC. Lymph node excision improved survival in
patients with T2 lesions. Radical en bloc resection of T2 tumors offers greater benefit over conventional
cholecystectomy alone in terms of greater long-term survival times. Provided that negative surgical margins
are secured, hepatectomy and lymph node resection can, therefore, be withheld in most cases in the
surgical treatment of pT2 GBC. With improvements in surgical and anesthetic techniques, aggressive
surgery has proven to be performed with safety.
Keywords
demography, gallbladder cancer, staging, surgery

INTRODUCTION DEMOGRAPHIC IMPLICATIONS FOR THE

Since the original description of carcinoma of the
gallbladder by Maxmillan de Stol in 1777, studies
have established a characteristic pattern of late diag-
nosis and ineffective treatment of this disease [1].
Gallbladder cancer (GBC) can be clinically obvious,
an unexpected finding at laparotomy, detected inci-
dentally on histological examination or may be
missed only to present with recurrence during fol-
low-up [2]. Although it is the most common cancer
of the biliary tree, gallbladder carcinoma remains
an uncommon disease. As a result, many clinicians
rarely encounter it and there is uncertainty regard-
ing proper management. Resection is the most effec-
tive and only potentially curative treatment. Early-
stage tumors are often curable with a proper resec-
tion; however, many patients present late in the
course of the disease when surgical intervention is
no longer effective. Although other treatment
modalities are used in patients with advanced dis-
ease, there are limited data on efficacy. In many
cases, the diagnosis is made after a cholecystectomy
has been performed and an incidental tumor is
identified in the specimen. In such cases, reopera-
tion and definitive resection is appropriate and
effective for patients with invasive lesions [3].
MANAGEMENT OF GALLBLADDER
CANCER
Unfortunately, most patients with symptoms of a
GBC have an uncurable cancer. Therefore, the inci-
dence of tumors at cholecystectomy for acute or
chronic cholecystitis is more interesting.
Incidental findings at cholecystectomy
Since the early 1970s, GBC incidence and mortality
rate have declined in the western world. Still,
women and older age groups continue to have the
highest risk for GBC, despite having greater declines.
The decline in the incidence and mortality of GBC
a
Department of Surgery, Karolinska Institutet, Karolinska University Hos-
pital, Huddinge, Stockholm, Sweden and bDepartment of Surgery, Ruijin
Hospital, Medical School of Shanghai Jiaotong University, Shanghai,
People’s Republic of China
Correspondence to Åke Andrén-Sandberg, MD, PhD, Professor of
Surgery, Section of Upper GI Surgery, K53, Department of Surgery,
Karolinska University Hospital, SE-141 86 Stockholm, Sweden. Tel: +46
70 222 15 77; e-mail: ake.andren-sandberg@karolinska.se
Curr Opin Gastroenterol 2014, 30:326–331
DOI:10.1097/MOG.0000000000000068

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 Aspects on gallbladder cancer in 2014 Andrén-Sandberg and Deng
KEY POINTS
! Gallbladder cancer steadily increases with age, women
are affected 2–5 times as often as men.
! Complete surgical resection offers the only chance
for cure.
! For in-situ and T1a tumors, a simple cholecystectomy
can be performed, resulting in a favorable 10-year
survival.
! For T1b and T2 tumors, an additional resection is
indicated, resulting in 5-year survival rates of 55–90%.
! For T3 tumors, only those patients without metastatic
disease will benefit from an additional resection.
began decades before the introduction of laparo-
scopic surgery, and apparently has stabilized in
the last decade. No temporal relationship existed
between laparoscopic rate and the incidence and
mortality rates of GBC in the USA [4].
Unexpected pathologic gallbladder findings
were found in 88 (2%) of 4317 cholecystectomy
specimens. GBC was detected in 24 specimens
(0.56%). A clinical diagnosis of empyema and
patient’s age over 60 years were two significant risk
factors for an unexpected GBC. About one-fourth of
patients with unexpected gallbladder findings
required further management [5].
In another retrospective review of 2890 final
pathology reports of processed gallbladder speci-
mens following cholecystectomy because of gall-
stones disease, 1994–2004, GBC was detected in
five specimens (0.17%), dysplasia in six (0.2%),
and secondaries to gallbladder in three (0.1%).
The median age of patients with GBC was 61 years
(range, 59–84 years). In all five patients, cancer was
isolated from thickened fibrotic wall on macro-
scopic appearance and spread through all layers of
the gallbladder wall. The percentage of thickened-
wall gallbladder in this study was 38% [6].
Autopsies
A total of 2395 consecutive autopsies was reviewed
and in cases in which cholelithiasis was present, the
incidence of gallbladder carcinoma was 3.4%. All
cases were in patients older than 60 years and all
were associated with cholelithiasis [7].
Chile
GBC is the first cause of death among Chilean
women and mortality has not improved in the last
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20 years. The GBC mortality trend was studied
from 1985 to 2002; risk differentials by age, sex,
geographic region, and accessibility to surgery were
analyzed. A total of 27 183 GBC deaths occurred,
1510 per year. The absolute number of deaths
increased by 65%, but standardized mortality rates
remained unchanged at 11.3 per 100 000. These
were higher among women than men (15.6 and
7.0, respectively, with a risk ratio of 2.2). Sex ratio
peaked at age 35–54 with a risk ratio of 4.1. Death
risk increased from North to South, peaking in
poorer areas, especially in places with rural popu-
lation and Mapuche ethnic admixture. Mortality
appears to correlate with the rate of people waiting
for gallbladder surgery, but not reaching statistical
significance [8].
Migrants
The changes of cancer incidence upon immigration
can be used as an estimator of environmental influ-
ence on cancer risk. Site-specific biliary cancers in
first-generation immigrants to Sweden were studied.
The nationwide Swedish Family-Cancer Database
was used to calculate standardized incidence ratios
(SIRs) in immigrants compared to native Swedes. A
total of 1428 cancers were identified in immigrants
whose median ages (years) at immigration were
27 for men and 26 for women, and whose median
diagnostic ages were 64 and 66, respectively. For
GBC, only women from the Indian subcontinent
(3.84) and Chile (2.34) had increased risk, whereas
some Northern European immigrants showed
decreased risks. The increase in GBC in Chileans
and Indians suggests that some persistent damage
was inflicted before emigration, characterization of
which will be a challenge for causative studies [9].
Mortality trends
Mortality data, abstracted from the WHO database,
for GBC (ICD-10: C23–C34) in 10 countries during
the period 1990–2006 were reviewed. The countries
were Japan, China (Hong Kong), and the Republic
of Korea (Asian countries); the United States of
America (USA); Australia; the United Kingdom
(UK); and Italy, Spain, France, and Germany (Euro-
pean countries). The world population was used for
age standardization. Among men, age-standardized
rates in Japan and the Republic of Korea were con-
siderably higher than the other countries studied.
Mortality rates in the Republic of Korea appeared to
have increased from the late 1990s but decreased in
Japan over the period. In contrast to the other Asian
countries, China (Hong Kong) showed lower rates
with a strong decreasing trend until the late 1990s.
www.co-gastroenterology.com 327
 Biliary tract
Mortality in the USA and Australia was relatively
low and showed slight decreasing trends. In Europe,
the UK had the lowest mortality rate during the
observation period, followed by Spain and France
which showed similar rates and trend. Although
both Italy and Germany showed the highest in
Europe, Germany had a decreasing trend, whereas
Italy did not change. Similar to men, age-standar-
dized mortality rates in women were the highest in
Japan and the Republic of Korea, showing increasing
and decreasing trends, respectively. Also in women,
the mortality rate in the UK was the lowest among
the European countries. Unlike mortality rates
for men, rates for women in China (Hong Kong)
continued to decrease throughout the observation
period. In Europe, all the five selected countries
including Italy showed a stronger decreasing trend
in rates compared with those observed for men [10].
MOLECULAR BIOLOGY
Risk factors for GBC development include a pathway
involving metaplasia or dysplasia or one in which
there is a preexisting adenoma. The former is the
more common and, because it is often not associ-
ated with a macroscopically recognizable lesion,
leads to the recommendation that all gallbladders
need to be examined microscopically. A number of
genetic alterations have been identified in the pre-
invasive and invasive stages of GBC, and they sup-
port the morphological evidence of there being two
pathways by which tumors develop. Some of these
genetic changes are associated with particular risk
factors. For example, cases with anomalous pancrea-
tobiliary ductal junction show a higher frequency of
K-ras mutations. Some changes are associated with
differences in prognosis. For example, cancers with-
out expression of p21 but with expression for p27
have a better prognosis, whereas those that express
c-erb-B2 have a worse one. Work has also been done
on identifying clinical, imaging, and other factors
which indicate that patients have a higher risk of
having GBC. This is particularly important in high-
incidence areas, in which GBC is a significant public
health problem [11].
Little difference between early and advanced
stages
There have been rather few data available about
the gene-expression profiles of GBC. In one study,
potential markers for GBC were identified, and the
genetic differences between early and advanced
GBCs were examined. Total RNA was extracted
from 17 gallbladder tissue specimens, including
six advanced GBCs, six early GBCs, and five normal
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control samples. When the GBC isolates were com-
pared to the normal control samples, 4682 genes
were identified, including 2270 that were over-
expressed genes and 2412 that were underexpressed
genes in the GBC. Nine overexpressed genes
(SERPINB5, BCL10, CD44, ARHGEF11, SERPINB2,
RELA, PAK4, PPARD, and BUB1B) and one under-
expressed gene (CAV2) were selected for real-time
PCR analysis. When the advanced GBC isolates were
compared with the early GBC isolates, only 12 genes
with greater than a 1.7-fold change in gene expres-
sion were identified. The close genetic similarity
found between the early and advanced GBCs may
help explain the poor prognosis of this disease, and
may be a sign of ‘advanced’ cancers already when
they are small [12].
STAGING
All final management of GBC and all comparisons of
treatment results from different centers must be
based on the stages, but unfortunately there are still
different staging system used around the world.
Anatomical implications for treatment
The gallbladder has unique anatomic features that
are conducive to direct invasion of surrounding
structures. The gallbladder wall consists of a mucosa,
a lamina propria, a smooth muscle layer, perimus-
cular connective tissue, and serosa without a sub-
mucosa. Also, no serosa exists at the attachment to
the liver and along the hepatic surface. The connec-
tive tissue is continuous with the interlobular con-
nective tissue of the liver. It is shown that direct
infiltration of gallbladder carcinoma into the adja-
cent liver segments is the most common type of
spread of this cancer. A macroscopic or microscopic
extension in the direction of the ductus cysticus is
rare. The thickness of liver parenchyma between the
neck of the gallbladder and the right hepatic duct is
only 1.6 " 0.7 mm, so that a recommended safety
distance of 2–3 cm cannot be reached without
anatomic liver resection when the gallbladder
carcinoma grows into the direction of the cystic
duct [13].
American Joint Committee on Cancer
A recent revision of the American Joint Committee
on Cancer (AJCC) staging for GBC (6th Edition)
involved some major changes. Most notably,
T2N0M0 tumors were moved from stage II to stage
IB; T3N1M0 tumors were moved from stage III to
stage IIB; and T4NxM0 (x ¼ any) tumors were moved
from stage IVA to stage III. In order to determine
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 Aspects on gallbladder cancer in 2014 Andrén-Sandberg and Deng
whether these changes were justified by data, an
analysis of the 10 705 cases of GBC collected
between 1989 and 1996 in the National Cancer
Database (NCDB) was performed. All patients had
more than 5 years’ follow-up. The staging according
to the 6th Edition provided no discrimination
between stage III and IV. Five-year survivals for stage
IIA, IIB, III, and IV (6th Edition) were 7, 9, 3, and 2%,
respectively. The data from the NCDB were used to
derive a proposed new staging system that builds
upon Edition 5 and had improved discrimination of
stage groups over previous editions. Changes in
staging systems should be justified by data. Multi-
center databases, including the NCDB, represent
important resources for verification of evidence-
based staging systems [14 ].
&&
TNM (tumor, nodes, metastases)
classification
No changes were made for tumors of the gallbladder
(excluding the inclusion of tumors of the cystic
duct) in 2010 [15].
(1) T1: gallbladder wall;
(2) T1a: lamina propria;
(3) T1b: muscle;
(4) T2: perimuscular connective tissue;
(5) T3: serosa, one organ, and liver;
(6) T4: portal vein, hepatic artery, or two or more
extrahepatic organs;
(7) N1: regional lymph node metastasis.
SURGERY
All attempts to treat GBC must be based on correct
staging.
Stage T1
To evaluate the efficacy of simple and extended
cholecystectomy for mucosa (T1a) or muscularis
(T1b) GBC, original studies on simple and extended
cholecystectomy for T1a or T1b GBC were searched
from MEDLINE (PubMed), Cochrane Library,
EMBase, and CancerLit. A total of 29 out of the
2312 potentially relevant publications met the eligi-
bility criteria. In most series, the treatment of choice
was simple cholecystectomy for T1a GBC patients
with a 5-year survival rate of 100%. Lymph node
metastasis was detected in 11% of the T1b GBC
patients and in 2% of the T1a GBC patients, which
was a statistically significant difference. Eight
patients (1%) with T1a GBC and 52 patients (9%)
with T1b GBC died of recurrent GBC, which is also a
significant difference. It was concluded that simple
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cholecystectomy represents adequate treatment
for T1a GBC. There is no definite evidence that
extended cholecystectomy is advantageous over
simple cholecystectomy for T1b GBC [16].
Recent large reviews of the NCDB and the
Surveillance, Epidemiology, and End Results (SEER)
Registry both reported that less than 10% of GBC fall
in the curable category, thus surgical management is
often more involved. T1b tumors invade the mus-
cular layer of the gallbladder. Some series support
simple cholecystectomy as sufficient management,
whereas others call for radical resection in these
cases. In one multicenter evaluation of 115 cases
of re-resection after prior cholecystectomy, 46% of
patients had residual disease in the re-resection
specimen on final histologic analysis. Current
recommendations from the National Comprehen-
sive Cancer Network support simple cholecystec-
tomy for T1a lesions and radical cholecystectomy
for T1b lesions [17].
Findings in the SEER database were also dis-
cussed. A total of 3209 patients with early-stage
GBC (12% Tis, 30% T1, and 58% T2) were identified.
On multivariate analysis, decreased survival was
noted among patients older than 60 years, among
patients with more advanced cancer, and among
patients with disease-positive lymph nodes, whereas
increased survival was observed among female
patients and among patients undergoing extended
surgical resection (ESR). The survival advantage of
ESR was seen only in patients with T2 lesions. On
multivariate analysis, patients with one to four
lymph nodes excised had a survival benefit over
those with no lymph node excised, and patients
with five or more lymph nodes excised had a sur-
vival benefit over patients with one to four lymph
nodes removed. Lymph node excision improved
survival in patients with T2 lesions. It was concluded
that ESR, lymph node excision, or both may
improve survival in certain patients with inciden-
tally discovered GBC [18].
Immediate re-resection
Incidental gallbladder carcinoma (IGBC) is the
carcinoma first detected by the pathologist. The
management of IGBC is difficult because no guide-
lines have been established. In 1997, one study
aimed to determine whether T1b IGBC actually
benefits from an immediate re-resection (IRR). All
the patients who had a re-resection in this study
were treated according to the effective guidelines in
Germany. No benefit was found for five of the 21
T1a patients who had an IRR, but 23 of the 72 T1b
patients who had an IRR experienced a significant
benefit. The rate of tumor recurrence was three
www.co-gastroenterology.com 329
 Biliary tract
times lower in the T1b group that underwent IRR
[19].
Stage T2
T2 tumors, which invade the perimuscular connec-
tive tissue, are best managed with en bloc resection of
the liver bed (Couinaud segments 4B and 5). It is
generally accepted that radical en bloc resection of T2
tumors offers greater benefit over conventional chol-
ecystectomy alone in terms of greater long-term sur-
vival times. In an assessment of 98 patients with
primary GBCs identified only after routine cholecys-
tectomy, 48 patients had T2 disease. The 5-year sur-
vival rate was 40% after cholecystectomy alone, but it
was 90% following more radical resection, including
the liver bed. In a separate analysis of 28 patients, the
survival rate was 59% at 5 years with radical resection
of the gallbladder liver bed versus 17% with chole-
cystectomy alone. Depth of subserosal invasion was
divided subjectively into three categories: invasion of
upper, middle, and lower thirds of the subserosal
layer. Relationships between subserosal subclassifica-
tion, histopathological factors, and prognosis were
examined. Subserosal layers were found to be signifi-
cantly thicker in portions with cancer invasion than
those without cancer invasion. Several other series
provide similar findings. It is currently advocated
that all patients with T2 GBCs who are fit and pro-
perly staged to exclude distant metastases be offered
radical cholecystectomy or re-resection of the liver
bed after an incidental finding of GBC following
cholecystectomy [17].
Lymph node dissection
The clinical indications for hepatectomy and extra-
hepatic bile duct resection (EBDR) for pT2 GBC
remain controversial, despite it being well known
that the most powerful predicting factor for survival
is nodal status. With respect to the surgical
procedures in one study, the 5-year survival rate
was 73% for the 51 patients with hepatectomy
and 87% for the 43 patients without hepatectomy.
In addition, the 5-year survival rate was 67% for the
11 patients with EBDR and 81% for the 83 patients
without EBDR. When restricting the patients to
those with pN1 disease, the 5-year survival rate of
the patients who received these procedures did
not surpass that of those who did not. It was con-
cluded that there is no positive therapeutic effect
in addition to providing surgical margins in hepa-
tectomy and EBDR in the surgical treatment of
pT2 GBC, whereas lymph node dissection is the
most effective procedure for improving survival.
Provided that negative surgical margins are secured,
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hepatectomy and EBDR can, therefore, be withheld
in most cases in the surgical treatment of pT2 GBC
[20].
Stage T3 and T4
T3 tumors perforate the serosa and directly invade
adjacent organs such as the liver, duodenum or
stomach, colon, pancreas, omentum, or extrahe-
patic bile ducts. As such, they are usually amenable
to radical resection; however, the morbidity from
these operations may be substantial. T4 tumors are
those that invade the main portal vein or hepatic
artery, and those that invade two or more extrahe-
patic organs or structures. T4 tumors are usually not
amenable to surgical resection or carry substantial
morbidity and mortality when approached surgic-
ally. Several series have focused on the outcomes in
patients with these locally advanced tumors and
arrive at different conclusions. A review of 724 cases
of GBC by the French Surgical Association showed
that 85% of cases were identified as T3 or T4, and
this group as a whole carried an overall survival time
of 2–8 months. The conclusion drawn from that
report was that little progress had been made in the
therapy of GBC over the previous decade [17].
Recent results have, however, significantly
improved because of a number of advances.
Improvements in radiologic staging including PET
now allow better selection of patients with disease
treatable by local regional resection. With improve-
ments in surgical and anesthetic techniques, aggres-
sive surgery has proven T3 and T4 tumors to be
resectable with safety and result in some long-term
survival [21,22].
CONCLUSION
There is still no breakthrough regarding the manage-
ment of GBC. Simple cholecystectomy is adequate
treatment for T1a GBC. Lymph node excision
improved survival in patients with T2 lesions.
Radical en bloc resection of T2 tumors offers greater
benefit over conventional cholecystectomy alone in
terms of greater long-term survival times. Provided
that negative surgical margins are secured, hepatec-
tomy and lymph node resection can, therefore, be
withheld in most cases in the surgical treatment of
pT2 GBC. Neoadjuvant and adjuvant therapy still
await improved results.
Acknowledgements
None.
Conflicts of interest
There are no conflicts of interest regarding this article for
either of the two authors.
Volume 30 ! Number 3 ! May 2014
 Aspects on gallbladder cancer in 2014 Andrén-Sandberg and Deng
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Shukla VK, Chauhan VS, Mishra RN, Basu S. Lifestyle, reproductive factors
and risk of gallbladder cancer. Singapore Med J 2008; 49:912–915.
2. Kapoor VK. Gallbladder cancer: a global perspective. J Surg Oncol 2006;
93:607–609.
3. Miller G, Jarnagin WR. Gallbladder carcinoma. Eur J Surg Oncol 2008;
34:306–312.
4. Le MD, Henson D, Young H, Albores-Saavedra J. Is gallbladder cancer
decreasing in view of increasing laparoscopic cholecystectomy? Ann Hepatol
2011; 10:306–314.
5. Lohsiriwat V, Vongjirad A, Lohsiriwat D. Value of routine histopathologic
examination of three common surgical specimens: appendix, gallbladder,
and hemorrhoid. World J Surg 2009; 33:2189–2193.
6. Bazoua G, Hamza N, Lazim T. Do we need histology for a normal-looking
gallbladder? J Hepatobiliary Pancreat Surg 2007; 14:564–568.
7. Mlinarić-Vrbica S, Vrbica Z. Correlation between cholelithiasis and gallblad-
der carcinoma in surgical and autopsy specimens. Coll Antropol 2009;
33:533–537.
8. Andia KM, Gederlini GA, Ferreccio RC. Gallbladder cancer: trend and
risk distribution in Chile. Rev Med Chil 2006; 134:565 – 574. [in
Spanish]..
9. Hemminki K, Mousavi SM, Brandt A, et al. Liver and gallbladder cancer in
immigrants to Sweden. Eur J Cancer 2010; 46:926–931.
10. Saika K, Matsuda T. Comparison of time trends in gallbladder cancer mortality
(1990–2006) between countries based using the WHO mortality database.
Jpn J Clin Oncol 2010; 40:374–375.
0267-1379 ! 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
11. Goldin RD, Roa JC. Gallbladder cancer: a morphological and molecular
update. Histopathology 2009; 55:218–229.
12. Kim JH, Kim HN, Lee KT, et al. Gene expression profiles in gallbladder cancer:
the close genetic similarity seen for early and advanced gallbladder cancers
may explain the poor prognosis. Tumour Biol 2008; 29:41–49.
13. Gore RM, Shelhamer RP. Biliary tract neoplasms: diagnosis and staging.
Cancer Imaging 2007; 7:S15–S23.
14. Koh CY, Demirjian AN, Chen WP, et al. Validation of revised American Joint
&& Committee on Cancer staging for gallbladder cancer based on a single
institution experience. Am Surg 2013; 79:1045–1049.
Staging is of outmost importance for being able to compare our treatment results;
this validates one of the important staging systems.
15. Tannapfel A, Wittekind C. The current TNM system for gastrointestinal tumors
part II. Pathologe 2010; 31:348–352. [in German]
16. Lee SE, Jang JY, Lim CS, et al. Systematic review on the surgical treatment for
T1 gallbladder cancer. World J Gastroenterol 2011; 17:174–180.
17. Zhu AX, Hong TS, Hezel AF, Kooby DA. Current management of gallbladder
carcinoma. Oncologist 2010; 15:168–181.
18. Downing SR, Cadogan KA, Ortega G, et al. Early-stage gallbladder cancer in
the Surveillance, Epidemiology, and End Results database: effect of extended
surgical resection. Arch Surg 2011; 146:734–738.
19. Goetze TO, Paolucci V. Immediate re-resection of T1 incidental gallbladder
carcinomas: a survival analysis of the German Registry. Surg Endosc 2008;
22:2462–2465.
20. Yokomizo H, Yamane T, Hirata T, et al. Surgical treatment of pT2 gallbladder
carcinoma: a reevaluation of the therapeutic effect of hepatectomy and
extrahepatic bile duct resection based on the long-term outcome. Ann Surg
Oncol 2007; 14:1366–1373.
21. Dai M, Fong Y, Lowy A. Treatment of T3 gallbladder cancer. J Gastrointest
Surg 2009; 13:2040–2042.
22. Jin LX, Pitt SC, Hall BL, Pitt HA. Aggressive surgical management of
gallbladder cancer: at what cost? Surgery 2013; 154:266–273. doi:
10.1016/j.surg.2013.04.022.
www.co-gastroenterology.com 331