Epidemiology

Most common malignancy of the biliary system.

􀂄 5th most common tumor of the GI tract

􀂄 Most common in the seventh or eighth decades

of life.

􀂄 Females to males: 3-4:1

􀂄 1.2 cases per 100,000

􀂄 Highest rates in Native Americans and South

Americans, Polish and North Indians

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Pathology

Dysplasia to invasive carcinoma takes over 15 years.

􀂄 Macroscopically is divided into papillary, tubular or

nodular. Papillary less invasion to the liver and lymph

nodes.

􀂄 Most carcinomas are adenocarcinomas 80-95%, and

can be papillary, tubular, mucinous or signet cells.

􀂄 Less common types include: anaplasic (2-7%),

squamous cell (1-6%), and adenosquamous (1-4%).

Carcinoid, small-cell, malignant melanoma, lymphoma

and sarcomas are particularly rare.

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Genetics

K-ras mutations in 39-59%. Increases to 50-

83% in patients with abnormal

pancreaticobiliary duct junction.

􀂄 P53 abnormalities are seen in 35-92% of GB

cancers.(S. Misra et al, Eur J Surg Oncol 26, 2000).

􀂄 Over-expression of p53 is associated with grade,

stage and presence of gallstones.

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Clinical Presentation

Symptoms Proportion of patients

RUQ pain 82%

Weight loss 72%

Anorexia 74%

Nausea and vomiting 68%

RUQ mass 65%

Jaundice 44%

Abdominal distention 30%

Pruritus 20%

Hematemesis 2%

Melena 1%

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Diagnosis

Only 8-10% are diagnosed preoperatively.

􀂄 Diagnosis is often challenging, no signs and

symptoms specific to gallbladder cancer.

􀂄 Most are incidental discovery during the OR.

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Diagnosis

Ultrasonography: 80% accurate; part of the

initial assessment. Demonstrates polypoidal

mass without acoustic shadow with localized

thickening. Loss of GB/liver interface found in

advance cancer.

Limitation in diagnosis of involved nodes and

staging of the disease

􀂄 Endoscopic ultrasound improves diagnosis of

GB cancer and predicts depth of tumor.

Helpful for differential diagnosis of polypoid

lesions.

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Diagnosis

CT Scan accurately detects GB abnormalities

and the extent of disease, direct infiltration into

adjacent tissues or vessels, nodal or distant

metastasis.

􀂄 MRI: tumors are hypodense in T1 images and

hyperdense in T2 images. Particularly useful for

visualizing invasion of the hepatoduodenal

ligament, portal vein encasement and lymph

node involvement.

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Diagnosis

Selective angiography is very accurate for

detection of vessel encasement or

neovascularization.

􀂄 ERCP is helpful in planning surgery, because it

can show tumor growth in the intrahepatic ducts

or CBD.

􀂄 HIDA can show CBD obstruction or cystic duct

obstruction (rare in GB cancer).

􀂄 FNA ultrasound or CT guided most frequently

used for preop cytodiagnosis, has a sensitivity of

88%.

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Diagnosis

Laparoscopy and biopsy are extremely useful for

assessment of peritoneal metastasis, extend of

the disease and suitability of surgery in patients

with locally advanced disease.

􀂄 Markers as CA 19-9 >20U/ml have 79.4%

sensitivity and 79.2% specific. CEA >4mcg/L

is 93% specific but only 50% sensitive.

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Staging UICC/AJCC TNM

Primary tumor

Tx Primary tumor cannot be assessed.

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1a Tumor invade lamina propria

Tib tumor invadesmuscle layer

T2 Tumor invades perimuscular connective tissue, no extension beyong serosa or into

liver.

T3 Tumor perforates serosa or directly invades the liver or other adjacent organs or

structure (stomach, duodenum, colon, pancreas, omentum, extrhepatic bile ducrs)

T4 Tumor invades main portal vein or hepatic artery or invades two or more extrahepatic

organs or structures.

Regional Nodes

Nx Regional nodes cannot be assessed

N0 No regional lymph no metastasis

N1 Regional Lymph nodes metastasis

Distant metastasis

Mx distant metastasis cannot be assessed

M0 no distant metastasis

M1 distant metastasis

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Stage UICC/AJCC TNM

Staging group

Stage 0 Tis N0m0

Stage IA T1N0M0

Stage IB T2N0M0

Stage IIA T3N0M0

Stage IIB T1,T2,T3 N1M0

Stage III T4 Any N M0

Satge IV Any T Any N M1

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Staging

Nevin’s classification:

􀂄 Stage I: mucosa only (45% 2yr survival)

􀂄 Stage II: muscularis (15%)

􀂄 Stage III: all layers (4%)

􀂄 Stage IV: lymph nodes (2%)

􀂄 Stage V: liver invasion, adjacent organs, distant

metastasis

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Histology 2yr surv. Median surv.

Adenocarcinoma 14% 4 months

Papillary variant 47% 20 months

Mucinous Variant 12% 4 months

Squamous cell 9% 4 months

Adenosquamous 8% 3 months

Undifferentiated 0% 2 months

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The only potentially curative therapy

􀂄 Surgical options:

􀂄 Simple cholecystectomy

􀂄 Radical or extended cholecystectomy

􀂄 Radical cholecystectomy with liver resection(segemental or

lobar)

􀂄 Radical cholecystectomy with extensive lymph-node

dissection

􀂄 Radical cholecystectomy with bile duct resection or

pancreaticoduodenectomy

􀂄 Bilio-enteric bypass

􀂄 Resection of port sites after laparoscopic cholecystectomy

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Stage I: simple cholecystectomy

􀂄 Stage II: radical cholecystectomy (2-5cm wedge

resection of GB fossa and regional lymph node

dissection

􀂄 Stage III and above: controversial ( liver resection or

palliative bilioenteric bypass vs adjuvant

chemo/radiotherapy)

􀂄 If GB cancer is suspected during laparoscopic

cholecystectomy, recommend convertion to open

procedure.

􀂄 GB cancer suspected before surgery, laparoscopic

cholecystectomy should not be considered.

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Surgical management

80-96% 5yr survival for T1 lesions with simple

cholecystectomy.

􀂄 15% lymph node metastasis in T1b lesions.

87% 10 yr survival with simple

cholecystectomy.(T. Wakai et al, Br J Surg 88, 2001).

􀂄 30-40% 5 yr survival for T2 lesions treated with

simple cholecystectomy(D.L.Barlett, et al, Ann Surg 224, 1996)

􀂄 80-90% 5yr survival for T2 and T3 lesions

treated with radical cholecystectomy.(Y.shirai et al, Ann

Surg 215, 1992).

􀂄 Re-exploration reveals residual tumor in 40-76%

of cases

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Surgical management

Palliation for advance GB cancer:

􀂄 Segment II duct bilio-enteric bypass

􀂄 Endoscopic stenting

􀂄 Radiological stenting

􀂄 Duodenal or intestinal bypass for gastric outlet or

intestinal obstruction.

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Radiotherapy

􀂄 Stage IV tumors treated with resection and

radiotherapy, 3yr survival of 10%.(Todoroki et al, World J

surg 15, 1991).

􀂄 Tumor control is rarely achieved by radiotherapy

alone.

􀂄 Brachytherapy via percutaneous transhepatic

approach is used for palliation of obstructive

jaundice due to bile duct obstruction.

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Chemotherapy

34% response rate and 7 months response

duration with intra-arterial infusion of 5-FU and

mitomycin c.(Misra, et al, Reg Cancer Treat 5 ,1992).

􀂄 61% response rate with Gemcitabine and

Cisplatinum. Needs further studying.

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