Gall Bladder Carcinoma

GALL BLADDER
CARCINOMA
Dr.Mohsin Khan
Resident surgeon,GRMC,Gwalior

Outline
 Relevent anatomy
 Introduction
 Epidemiology
 Etiology/Pathophysiology
 Presentation
 Workup
 Treatment
 Follow Up

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)

Relevant Anatomy
Lymphatic Drainage
*exposure of this region is a necessary step in the operative staging of
gallbladder cancer

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

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.

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

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

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.

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%.
 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.

Etiology/Pathophysiology
 Gallstones are present in 60-90 % of GB cancer cases (World wide)
 a small proportion of patients (1-3%) with gall stones developed G.B cancer
 inverse relationship between the incidence of GC and rate of cholecystectomy
 In pakistan 98-100 % of cases of GC have gall stone
 Risk factors include
 Chronic inflamation and infection.
 Porcelain Gallbladder
 Typhoid carrier
 Adenomatous polyp (size of the polyp is strongest predictor of malignant
transformation)
 Advanced age(>55 yr)
 Multiparity(>5)
 Presence of gallstone larger than 1-3cm.
 Anomalous pancreatobiliary junction
 Drugs :OCP, methyldopa
 Occupational exposure to rubber,cigrette smoking
 Bile acid composition.
 Diet: low fibre, low calories. High fine CHO, low protein

 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.

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
 Given this presentation, less than 50% of
gallbladder cancers are diagnosed
preoperatively. Many are diagnosed
incidentally in gallbladders removed for biliary
colic or cholecystitis.

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.
TumourMarker Sensitivity Specificity
CA 19-9 * 79.4 % 79.5%
CEA 50 % 93%
*Found in 80% of the cases

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.

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

 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.

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

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.

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]
 TNMDefinitions
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

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

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
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.

Surgical management
 Cholecystectomy recommended in
 polyps larger than 1 cm or with polyps in the setting of primary sclerosing
cholangitis
 porcelain gallbladder.
 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.

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

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

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.

 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.

No standard adjuvant treatment protocol has
been defined for gall bladder cancer.
 Generally, fluoropyrimidine-based
chemoradiotherapy or single-agent chemotherapy
with fluoropyrimidines or gemcitabine is used.
 Because of the high cure rate with surgery alone
for T1N0 lesions, adjuvant therapy is not
commonly offered to these patients.

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.

STAGE 5 YEARSURVIVAL 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
PROGNOSIS [5][11]

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.

Gall Bladder Carcinoma

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