“CARCINOMA GALL BLADDER”

DR AMOL KUMAR

DR HARI KISHAN

SEMINARSEMINAR

EpidemiologyEpidemiology-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 FactorsRisk 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

EtiologyEtiology

-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 featuresPathologic featuresCa gallbladder

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

1. Infiltrative

-Most common type

-causes thickning &

induration of gb wall

-difficult to distinguish

from a chronically

inflamed but benign gb

- Tumor to be disseminated

by cholicystectomy

2. Nodular

- More distinctive

- Early invasion

- Easier to control

surgically

4. Combined form

Ca gallbladder

3. Papillary

-polypoid appearance

-low invasiveness

-much batter prognosis

Histopathological classificationHistopathological classificationMALIGNENT EPITHELIAL TUMORS

(99%)MALIGNANT MESENCHYMAL

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

Activation of

protoncogenes

Cell Tumor

Inactivation of

tumour

separessor genes

TUMOUR BIOLOGYTUMOUR BIOLOGY

Gene mutation related to gall bladder carcinoma

P53 , K- ras, C-ergB-2 genes, nm23

PATTERN OF SPREADPATTERN OF SPREAD

Direct Lymphatic Haematogenous Iatrogenic

Direct spread to liver & other adjacent organ

Cystic Through small veins directly into the portal venous system

Leproscopic colistictomy

- Favourable factors for direct spread

Pericholedochal Via-large veins to the portal venous branch of segments IV & V of liver

FNAC

- Thin gall bladder wall

Posterosuperior Pancreaticoduodenal

- Narrow lamina propria

Superior mesenteric

- Only single muscle layer

Retroportal

Celiac

Interaortocaval nodes

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)

CLINICAL PRESENTATIONCLINICAL PRESENTATION

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.

INVESTIGATIONSINVESTIGATIONS

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

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

TNM Groupings by stage

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 MANAGEMENT

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.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.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

Management contd.Management contd.

Management contd.Management contd.Medical care

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

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

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