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SEMINAR

“CARCINOMA GALL BLADDER”

DR AMOL KUMAR
DR HARI KISHAN
Epidemiology
-The incidence of Gall Bladder cancer is extremely
variable by geographic regions & racial-ethinic groups
-Incidence
-Highest- Chileans, Northeastern Europeans, Israelies,
American Indian & Americans of Mexican origin
-Intermediate- Japan
-Lowest- Black Zimbabweans Black Americans
& the People of Spain & India
- Sex- M:F::1:2-6
- Age - incidence ↑ with age, reaching its maximum in
the seventh decade of life
Risk Factors
-Cholelithiasis usually cholesterol type stones
-Anomalous pancriaticobiliary duct junction
-Chronic typhoid infection
-Inflammatory bowel diseases
-Porcelain gallbladder
- Chemicals like methyldopa oral contraceptives
isoniazid chemicals used in rubber industry
- Gall bladder Polyps
Etiology
-It is likely to be the chronic inflammation that
predisposes to neoplasia, regardless of the
cause of inflammation
-A higher concentration of free radical oxidation
products and a higher conc. Of sec.bile acids
Pathologic features
Ca gallbladder

Fundus (60%) Body(30%) Neck(10%)

Ca gallbladder

1. Infiltrative 2. Nodular 3. Papillary 4. Combined form


-Most common type - More distinctive
-polypoid appearance
-causes thickning & - Early invasion
-low invasiveness
induration of gb wall - Easier to control
-much batter prognosis
-difficult to distinguish surgically

from a chronically
inflamed but benign gb
- Tumor to be disseminated
by cholicystectomy
Histopathological classification
MALIGNENT EPITHELIAL TUMORS MALIGNANT MESENCHYMAL
(99%) TUMORS
Adenocarcinoma Embryonal rhabdomyosarcoma
Well-differentiated Leiomyosarcoma
Papillary Malignant fibrous histiocytoma
Intestinal type Angiosarcoma
Pleomorphic giant cell Oat cell carcinoma
Poorly-differentiated, small cell
Signet ring cell
Clear cell
Colloid
With choriocarcinoma-like areas
Squamous
Adenosquamous
Oat cell carcinoma
TUMOUR BIOLOGY
Activation of
protoncogenes

Cell Tumor

Inactivation of
tumour
separessor genes

Gene mutation related to gall bladder carcinoma


P53 , K- ras, C-ergB-2 genes, nm23
PATTERN OF SPREAD
Direct Lymphatic Haematogenous Iatrogenic
Direct spread to liver Cystic Through small veins Leproscopic
& other adjacent directly into the portal colistictomy
organ venous system
- Favourable factors Pericholedochal Via-large veins to the FNAC
for direct spread portal venous branch
of segments IV & V
of liver
- Thin gall bladder Posterosuperior
wall Pancreaticoduodenal
- Narrow lamina Superior mesenteric
propria
- Only single muscle Retroportal
layer
Celiac
Interaortocaval nodes
CLINICAL PRESENTATION
History: The symptoms of gallbladder cancer overlap with the
symptoms of gallstones and biliary colic. Abdominal pain may be of a
more diffuse and persistent nature than the classic right upper quadrant
pain of gallstone disease. Jaundice, anorexia, and weight loss often
indicate more advanced disease.
Physical:
•Jaundice
•Palpable mass in the right upper quadrant (Courvoisier sign, if this is
due to a palpable gallbladder)
•Periumbilical lymphadenopathy (Sister Mary Joseph nodes)
•Left supraclavicular adenopathy (Virchow node)
•Pelvic seeding: Mass is palpated on digital rectal examination (Blumer
shelf)
INVESTIGATIONS
Lab Studies:
•Tumor marker CA 19-9 with 79.4% sensitivity & 79.2% specificity
-CA 19-9 may be significantly elevated in both
cholangiocarcinoma and gallbladder cancer.
-CA 19-9 tests may be helpful in the appropriate situation if the
clinical suspicion for gallbladder cancer is high.
•Liver function tests: Elevated alkaline phosphatase and bilirubin
levels are often found with more advanced disease.
•BUN, creatinine, UA: Assess renal function prior to performing an
enhanced CT scan.
•CBC: Anemia may be an indicator of more advanced disease.
IMAGING STUDIES
•Ultrasonography- is a standard initial study . A mass can be identified in 50-
75% of patients with gallbladder cancer. It also can delineate metastatic
lesions in the liver.
•Computed tomography- demonstrate tumor invasion outside of the gallbladder
and identify metastatic disease elsewhere in the abdomen or pelvis. Liver
invasion occurs in 60% of cases, and the combination of CT scan and US
provides accurate details of disease extension.
•Magnetic resonance imaging- useful in examining for disease extension into
other tissues or metastatic disease in the liver. It can provide details of the
vasculature for preoperative planning via magnetic resonance angiogram
(MRA) and bile duct passages via magnetic resonance cholangiogram
(MRCP).
•Cholangiography, via a percutaneous route, or endoscopic retrograde
cholangiography (ERCP) may establish the diagnosis of gallbladder cancer by
bile cytology.
•Endoscopic ultrasonography can be useful to assess regional
lymphadenopathy in conjunction with other studies.
•Angiography may confirm encasement of the portal vein or hepatic artery, and
assist in preoperative planning for definitive resection.
•A routine chest radiograph should also be obtained.
PROCEDURES
•ERCP can demonstrate the site of the obstruction by direct
retrograde dye injection, as well as excluding ampullary
pathology by endoscopic evaluation. Brush cytology, biopsy,
needle aspiration, and shave biopsies via ERCP can provide
material for histology. Palliative stenting to relieve biliary
obstruction can be performed at the time of the evaluation.
•Percutaneous transhepatic cholangiography (PTC) may
allow access to the proximal biliary tree that has become
obstructed by extensive tumor growth from the gallbladder.
Material for cytology can be obtained and drainage performed
as well.
•Other methods to obtain tissue include CT or ultrasound
needle aspiration, if a mass lesion is present, and endoscopic
ultrasonographic (EUS) fine-needle aspiration.
STAGING
The AJCC 6th edition guidelines follow the TNM system, with depth of tumor penetration and regional spread defined
pathologically . Survival is correlated directly with stage of disease.
Primary tumor
•Category 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 muscle layer
T2 - Tumor invades perimuscular connective tissue; no extension beyond serosa or into liver
T3 - Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ
or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts
T4 - Tumor invades main portal vein or hepatic artery or invades multiple extrahepatic organs or structures
Regional lymph node
•Category N
NX - Regional lymph nodes cannot be assessed
N0 - No metastases in regional lymph nodes
N1 - Metastases in regional lymph nodes
Distant metastases
•Category M
MX - Presence of metastases cannot be assessed
M0 - No distant metastases
M1 - Distant metastases
TNM Groupings by stage
Stage 0 Tis N0 M0
Stage IA - T1 N0 M0
Stage IB - T2 N0 M0
Stage IIA - T3 N0 M0
Stage IIB - T1 N1 M0
T2N1M0
T3N1M0
Stage III - T4 any N M0
Stage IV - any T any N M1
MANAGEMENT
Surgical Medical

- Surgical-
T1diseases-
1. Most often presents after the gall bladder has already been removed by simple
colecystectomy for presumed gall stone disease.
2. Reviewed pathologic findings to ensure that margins are negative
3. Particular attention is paid to the cystic duct margin
-ve - no other therapy
- Margin <
+ve – common bile duct excision & biliary reconstruction
4. 5 years survival rate is 85% to 100%
Management contd.
T2 diseases-

- 2 reasons to perform more extensive surgery in T2 disease


1. The plane i.e., generally taken between the liver and gall bladder is
subserosal and may violate T2 tumor along the liver interphase
2. T2 tumour are associated with a high incidence of regional nodal
metastasis
3. Therefore most reasonable primary operation is radicle
colecystectomy
4. This includes – a wedge resesction of the gall bladder bed and
lymph node of hepatico duodenal ligament
5. 5 yrs survival after radical colecystectomy is 80-90% as compared
to 40% 5 yrs survival with simple colecystectomy
Management contd.

T3 T4 diseases (advance tumour) -


- Recently the literature absunds with review of radical surgery for
advanced disease and many centre reports long term survivous
after aggressive surgical management
- In Japan they report a 63.6% 5 yrs survival for Japanese Biliary
Surgical Society Stage II and 44.4% 5 yrs survival for stage III
disease after extended colecystectomy
- This stage combined represent AJCC stage III
Management contd.
Management contd.
Management contd.
Laproscopically discovered gall bladder cancer
- Standard technique for treatment of symptomatic gall stone disease
is laproscopic colecystectomy
- With the proliferation of laproscopic cholecyetectomy a new
scenario now encountered namely gb cancer discovered at or after
laproscopic chlecystectomy
- M/m –is re exploration & complete excision of laproscopically
Discovered GB carcinoma
Medical care
Management contd.
Radiotherapy
1-the role of adjuvant radiation the therapy is to control microscopic residual
deposits of carcinoma in tumour bed and regional lymph node
2-palliation in unresectable diseases
The role of RT for carcinoma gall bladder is unclear but data support the following
statements
Radiotherapy has been delivered in a variety of situations including after curative
resection with close or positive microscopic margins gross macroscopic residual
disease and palliative debulking with bypass
-Post op RT increases survival in T2 and advance carcinoma

-Chemotherapy
-CT – 5FU – based CT is usually given in conjunction with concurrent RT both in
the adjuvent and palliative settings
-Adriamycin, mitomycin cisplatin can have some role in management of Ca GB
PALLIATIVE MANAGEMENT
-The goal of palliation
-Relieve of pain, jaundice and bowel obstruction
-Prolongation of life
-Decisions on palliative treatment should take into account
the short survival of patients with non resectable gall
bladder cancer. Therefore all palliation treatment should be
simple as possible
PROPHYLACTIC CHOLECYSTECTOMY
-GB polyps > 10 mm size
-Porcelain GB
-High risk situation that serum CA 19-9 elevation and bile
cytology helpful in making a pre operative diagnosis of
carcinoma GB

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