This Presentation gives summarized overview of Gall Bladder Carcinoma especially the management as per latest National Comprehensive Cancer Network(NCCN) Guidelines version 2.2013

1. Gall Bladder Carcinoma
Muhammad Haris Aslam Janjua
Resident, Surgical Unit I
SIMS/Services Hospital, Lahore

2. Case Summary
• A 40 Year old female presented to OPD SHL on 11th Jan 14, with pain in upper
abdomen for 15 days which was acute in onset, progressive, continuous,
constricting, moderate to severe, radiating to back side, aggravated by fatty meals
and relieved temporarily by medications.
• No h/o fever, vomiting, constipation/diarrhea ,weight loss
• Unremarkable medical and surgical history
• On examination: RHC was tender with Murphy sign +ve. Rest of examination
unremarkable.
• USG showed gall stones with no edema and thick GB wall.
• Serum amylase levels were 26, lipase levels were 11 and total bilirubin was 0.4 .
TLC was 11.0
• Patient was admitted and managed on lines of acute cholecystitis
• During her stay in the ward departmental USG showed cholelithiasis and multiple
enlarged lymph nodes in porta hepatis and peripancreatic area . Patient was sent
on leave and advised follow up after CT scan and CA 19-9 report.

3. Case Summary
• CT scan(17th Jan 14) showed multiple enlarged lymph nodes in porta
hepatis and both para-aortic planes and pleuropericardial recess. CA19-9
level (24th Jan 2014)were 15.68 (normal range less than 37)
• Patient was re-evaulated and was discharged on conservative treatment
• Patient again presented in ER on 7th Feb 14, with pain RHC and was
readmitted for workup
• Serum amylase was 60, total bilirubin was 0.7 ,TLC 10.0
• Repeat USG showed Multiple Gallstones with soft tissue density mass.
However wall is not thick and no pericholecystic fluid. CHD dilated upto
6mm but distal CBD and intrahepatic duct was not dilated . Multiple
enlarged lymph nodes in para aortic, celiac, peri pancreatic and porta
hepatic regions with liver slightly coarse in echo texture.
• Laparatomy was done on 13th Feb 14 and intraoperatively gall bladder
mass was seen infiltrating the liver and GB biopsy was taken, which
showed Poorly Differenciated adenocarcinoma.

4. Outline
• Relevent anatomy
• Introduction
• Epidemiology
• Etiology/Pathophysiology
• Presentation
• Workup
• Treatment
• Follow Up
• References

5. Relevant Anatomy
• Saccular structure located at the inferior surface of the
liver, at the division of the right and left lobes, just
below segments IV and V
• Composed of 4 areas: fundus, body, infundibulum, and
neck
• Approx. 7-10 cm long and about 2.5-3.5 cm wide
• Normally contains approx. 30-50 mL of fluid(max up to
300 mL)

6. Relevant Anatomy
Lymphatic Drainage
• Cystic Node
• pericholedochal nodes
• regional nodal basins (superior mesenteric,
retropancreatic, retroportal, and celiac)
• aortocaval nodes*( directly or indirectly)
*exposure of this region is a necessary step in the operative staging of gallbladder
cancer

7. Relevant Anatomy
Spread of GB cancer
• spreads via the lymphatic channels and venous
drainage
• Peritoneal metastasis common
• Due to adjacent location liver, bile duct, portal
vein, hepatic artery, duodenum, and transverse
colon involvement is common

8. Relevant Anatomy
Cystic Plate*
• It is reflection of the visceral peritoneum between the liver and the
gallbladder.
• Dissection between the gallbladder and the liver during
cholecystectomy divides the plane between the cystic plate and
the muscle layer of the gallbladder
*anatomic basis for the improved survival in patients undergoing liver
resection for T1b gallbladder cancer.

9. Introduction
• Gallbladder carcinoma was first described by Maximilian Stoll in
1777 and more than 200 years later it is still considered to be a
highly malignant disease with a poor survival rate
• G.B cancer is relatively uncommon but it is the 5th most common
GIT malignancy(worldwide)
• most frequent malignant tumor of the biliary tract
• 90 % Adenocarcinomas.
• Mucosal squamous metapalsia Squamous cell carcinoma

10. Introduction
Premalignant Lesions
• Adenomatous polyps
– Papillary adenomas grow as pedunculated, complex,
branching tumors projecting into the gallbladder lumen.
– Tubular adenomas arise as a flat, sessile neoplasm.
• Adenomyomatosis
– extensions of Rokitansky-Aschoff sinuses through the
muscular wall of the gallbladder
– USG reveals a thickened gallbladder wall with intramural
diverticula
– serial evaluation with USG is indicated to rule out
enlarging adenomatous polyps and gallbladder cancer

11. Epidemiology
• incidence of GC  1 to 23 per 100,000 worldwide
• over the last three decades there is decrease in incidence in
developed and increase in incidence in developing countries
• The highest incidence of gallbladder carcinoma is reported more
recently from the Indian-Subcontinent including India and Pakistan
(18-23/100,000)  mirror image of worldwide distribution of gall
stones
• A relatively rare malignancy worldwide but is the second
commonest gastrointestinal cancer in Pakistani women
• Most common cause of gastrointestinal cancer related mortality in
females in subcontinent.[17,18]

12. Epidemiology
• Rise in incidence of GC from Northern India and Southern Pakistan
over the past two decades
• Frequency of gallbladder cancer in Pakistan varies between 6-7%.
[13-15]
• Highest incidence is found in Chelians, American Indian and in parts
of Northern India where it accounts for 9% of all biliary tract
diseases.
• Female to male ratio is 3:1
• Peak incidence is in 7th decade of life.[2]

13. Etiology/Pathophysiology
• Gallstones are present in 60-90 % of GB cancer cases (World wide)
.[3][12].
– a small proportion of patients (1-3%) with gall stones developed G.B cancer
[16,17]
– inverse relationship between the incidence of GC and rate of cholecystectomy
– In pakistan 98-100 % of cases of GC have gall stone[18][19]
• Risk factors include
– Chronic inflamation and infection.
– Porcelain Gallbladder
– Typhoid carrier
– Adenomatous polyp (size of the polyp is strongest predictor of malignant
transformation)[3]
– Advanced age(>55 yr)
– Multiparity(>5)
– Presence of gallstone larger than 1[17]-3[18]cm.
– Anomalous pancreatobiliary junction
– Drugs :OCP, methyldopa

14. – Occupational exposure to rubber,cigrette smoking
– Bile acid composition.
– Diet: low fibre, low calories. High fine CHO, low protein
• A 2008 study found evidence that excess body weight
in women, specifically a 5 kg/m 2increase in the body-mass
index, is strongly associated with an increased
risk of gallbladder cancer.[4]
• Numerous studies have investigated genetic
abnormalities in gallbladder cancer and have shown
that approximately 39-59% of gallbladder cancers are
associated with the K-ras mutation, while more than
90% of them are associated with a p53 mutation.[5]

15. Presentation
• Usually asymptomatic at the time of diagnosis
• Symptoms if present are similar to benign
diseases such as cholecystitis or biliary colic.
• Jaundice and anorexia are late features
• Palpable mass is a late sign[2]
• Given this presentation, less than 50% of
gallbladder cancers are diagnosed preoperatively.
Many are diagnosed incidentally in gallbladders
removed for biliary colic or cholecystitis.

16. Work Up
• Laboratory studies are generally nonspecific for gallbladder
cancer.
• In the later stages, liver function enzyme levels may be slightly
elevated. These levels are generally not elevated in stages I
and II.
• An elevated bilirubin or alkaline phosphate level generally
indicates advanced or obstructive disease.
Tumour Marker Sensitivity Specificity
CA 19-9 * 79.4 % 79.5%
CEA 50 % 93%
*Found in 80% of the cases

17. Imaging studies
• Ultrasonography is a very useful tool in the workup of
gallbladder cancer. Polypoid lesions need to be at least 5
mm in size to be detected by ultrasonography. Cholesterol
polyps (benign) generally appear as pedunculated lesions
attached to the gallbladder wall.
• Ultrasonographic findings that indicate possible malignancy
– a thick gallbladder wall,
– vascular polyp,
– a mass projecting into the lumen or invading the wall, multiple
masses or a fixed mass in the gallbladder,
– a porcelain gallbladder, and an extracholecystic mass. Invasion
of the liver can also be seen on ultrasonograms.

18. This image demonstrates heterogeneous
thickening of the gallbladder wall (arrows). The
diagnosis was primary papillary adenocarcinoma of
the gallbladder.

19. • Computed tomography (CT) scanning and magnetic resonance
imaging (MRI) are useful in evaluating the extent of invasion and
resectability of gall bladder tumors. CT scan results suggestive of
gallbladder cancer include asymmetrical wall thickening or
gallbladder mass with or without invasion into the liver.
• CT scanning of the chest, abdomen, and pelvis is a common staging
modality that can determine the presence of distant metastases
and give reliable information about involvement of other organs
and vascular structures.
• Positron emission tomography (PET) scanning has a sensitivity of
75% and a specificity of 88% in gallbladder cancer but is not used
routinely.

20. Partially calcified gallbladder (arrow). At
laparotomy and histology,
an infiltrating adenocarcinoma of the
gallbladder was confirmed.
CT scan showing squamous cell
carcinoma of gall bladder showing Liver
metastasis

21. Diagnostic procedures
• Percutaneous CT scan – guided biopsy is avoided in patients
considered resectable based on preoperative imaging. Because of
the substantial risk of peritoneal seeding, percutaneous biopsy and
diagnostic cholecystectomy are not necessary in the patient
suspected of having gallbladder cancer. In these patients,
exploration with curative intent is planned based on preoperative
imaging alone.
• Percutaneous CT scan – guided biopsy is a useful diagnostic tool in
patients who appear to have a nonresectable tumor. Tissue
diagnosis is necessary for palliative treatment.
• Endoscopic ultrasonography with fine-needle aspiration Biopsy
can be used to evaluate for peripancreatic and periportal
lymphadenopathy.

22. Staging
• The American Joint Committee on Cancer (AJCC) has designated staging by the TNM (primary t umor, regional
lymph n odes, distant m etastasis) classification as follows [6]
• TNM Definitions
Primary tumor (T)
• TX - Primary tumor cannot be assessed
• T0 - No evidence of primary tumor
• Tis - Carcinoma in situ
• T1 - Tumor invades lamina propria or muscle layer . T1a - Tumor invades lamina propria
• T1b - Tumor invades the muscularis
• T2 - Tumor invades the perimuscular connective tissue; no extension beyond the serosa or into the liver
• T3 - Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or 1 other adjacent organ
or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts
• T4 - Tumor invades the main portal vein or hepatic artery or invades multiple extrahepatic organs or structures
Regional lymph nodes (N)
• NX - Regional lymph nodes cannot be assessed
• N0 - No regional lymph node metastasis
• N1 - Portal lymph node metastasis
• N2 - Distant lymph node metastasis such as periaortic, pericaval, superior mesenteric artery, or celiac artery
Distant metastasis (M)
• MX - Distant metastasis cannot be assessed
• M0 - No distant metastasis
• M1 - Distant metastasis

23. AJCC Stage Groupings
• Stage 0: Tis, N0, M0
• Stage I: T1 (a or b), N0, M0
• Stage II: T2, N0, M0
• Stage IIIA: T3, N0, M0
• Stage IIIB: T1 to T3, N1, M0
• Stage IVA: T4, N0 or N1, M0
• Stage IVB: Any T, N2, M0, OR Any T, any N, M1

24. In Our case......................
• T3 (liver involvement)
• N2 (para-aortic and celiac lymph node
involvement )
• M1(as paraaortic LN involvement is
considered sign of distant metastsis)
• i.e. Stage IVB

25. Non surgical Management
• Small gallbladder tumors are common and many can be safely followed
with serial ultrasonographic examination. It is generally thought that
polyps of less than 1 cm are safe to follow, although a study[7] has
recommended that polyps that are greater than or equal to 6 mm should
be considered for cholecystectomy.
• Chemotherapy is used in the adjuvant and palliative treatment of
gallbladder cancer. Phase II studies have shown that the use of single-agent
chemotherapy (with gemcitabine or 5-fluorouracil) in the palliative
setting can be beneficial.
• Combination chemotherapy also has been shown to be beneficial and is
usually based on gemcitabine, capecitabine, and 5-fluorouracil used in
combination with cis-platinum or oxaliplatinum. Fluoropyrimidine-based
chemoradiotherapy is commonly employed in the palliative and adjuvant
setting as well.

26. Surgical management
• Cholecystectomy recommended in
– polyps larger than 1 cm or with polyps in the setting of primary sclerosing
cholangitis
– porcelain gallbladder.[2]
• Diagnostic Laproscopy
– In order to exclude the presence of undetected intra-abdominal metastases
prior to curative laparotomy.
– Surgery is contraindicated in the presence of distant metastases.
• Exploratory Laparotomy
– The initial exploration focuses on the presence of metastatic disease that was
not detected by preoperative imaging and staging laparoscopy.(15%)
– In view of North american surgeons Biopsy-proven metastases in the celiac
nodes preclude resection.
– Aortocaval nodal metastases are considered distant metastatic disease.

27. STAGE TREATMENT
T1a Simple cholecystectomy
T1b or deeper Hepatic resection +
lymph node dissection
(portal , peripancreatic , and retroduodenal)+
Resection of liver segments
IVb and V +/-
extended liver resection
and/or bile duct resection

28. Intraoperative ultrasonography (IOUS)
• To evaluate the extent of involvement of the liver, as well as
the portal and intrahepatic vasculature.
• This information is especially useful when ligating the pedicle
to segment V and avoiding injury to the right anterior portal
pedicle or segment VIII pedicle. Extended right hepatectomy
may be necessary to achieve tumor clearance if the tumor
involves the right portal pedicles

29. A schematic drawing of the
extent of lymphadenectomy for
gallbladder cancer, especially
when the extrahepatic biliary
tree is resected.
Gallbladder tumors.
A schematic
drawing of the
extent of resection
of liver segments
IV-b and V for
gallbladder cancer.

30. • Surgical exploration
– will determine the need to resect other organs that may
be involved, such as the stomach, duodenum, and colon.
– It may be difficult to distinguish scar from malignancy. In
these cases, suspicious tissue should be treated as
malignancy in order to improve the chances of a margin-negative
resection.
– If tumor is suspected on the bile duct based on a previous
pathology report or operative exploration, the presence of
tumor on the right hepatic duct must be evaluated.
– Suspicion of tumorous involvement of the right hepatic
duct will require an extended right hepatectomy, excision
of the extrahepatic biliary tree, and Roux-en-Y
hepaticojejunostomy to the left hepatic duct.
• A recent study indicates that accurate staging requires
examination of at least 6 lymph nodes.

31. No standard adjuvant treatment protocol has been
defined for gall bladder cancer.
– A 2008 study found that only 20% of patients with gall
bladder cancer received adjuvant treatment.[9]
– In the report, no benefit from adjuvant therapy could
be demonstrated, but only a small number of patients
received this treatment.
– Generally, fluoropyrimidine-based chemoradiotherapy
or single-agent chemotherapy with fluoropyrimidines
or gemcitabine is used.[10]
– Because of the high cure rate with surgery alone for
T1N0 lesions, adjuvant therapy is not commonly
offered to these patients.

37. Complications
• The overall complication and morbidity rate is
approximately 25%.
• Complications are similar to those experienced
with cholecystectomy and include infection,
hematoma, and bile leaks.
• Complication rates are higher in patients
undergoing more extensive resections.
• Liver failure can occur following extended
hepatectomy, especially if jaundice is present
preoperatively.

38. PROGNOSIS [5][11]
STAGE 5 YEAR SURVIVAL RATE
T1b 100% especially with hepatectomy
T2 38% to 77% after extended
cholecystectomy
III and IV 25 % with extended resection
Unresectabe disease < 5% ( 1 year survival rate)
Patients with unresectable disease have a median survival of 2-4 months

39. Follow Up
• There are no data to support aggressive
surveillance following resection of gall bladder
cancer, because treatment of recurrences is
not generally effective. However, many
clinicians and patients prefer follow-up
imaging every 6 months.

40. References
1. D'Hondt M, Lapointe R, Benamira Z, Pottel H, Plasse M, Letourneau R, et al. Carcinoma of the
gallbladder: Patterns of presentation, prognostic factors and survival rate. An 11-year single centre
experience. Eur J Surg Oncol. Jun 2013;39(6):548-53
2. Bailey and Love edition 26th page 1116
3. Robins and cotrans pathologic basis of disease 7th edition
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systematic review and meta-analysis of prospective observational studies. Lancet. Feb 16
2008;371(9612):569-78.
5. Tumors of the gallbladder. In: Blumgart LH, ed. Surgery of the Liver, Biliary Tract, and Pancreas. 4th ed.
Philadelphia, Pa: Saunders Elsevier; 2007:764-81
6. American Joint Committee on Cancer. Gallbladder. In: AJCC Cancer Staging Manual. 6th ed. New York,
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7. Zielinski MD, Atwell TD, Davis PW, et al. Comparison of surgically resected polypoid lesions of the
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8. [Best Evidence] Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a
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9. Duffy A, Capanu M, Abou-Alfa GK, et al. Gallbladder cancer (GBC): 10-year experience at Memorial
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10. NCCN Clinical Practice Guidelines in Oncology™. Available at www.nccn.org.
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gallbladder adenocarcinoma. Anticancer Res. Feb 2009;29(2):685-91.
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carcinoma gallbladder patients. Pak J Surg 2005;21(1):19-22.

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