Gallbladder Cancer

Definition and PathogenesisTop

The most common gallbladder cancer is adenocarcinoma originating in the epithelium of the gallbladder mucosa.

Risk factors: Cholelithiasis (long-lasting gallstones >3 cm; cholelithiasis is present in ~80% of cancer cases; cancer is diagnosed in ~1% of gallbladders removed due to cholelithiasis), biliary cysts, gallbladder polyps sized >1 cm, primary sclerosing cholangitis, familial polyposis syndromes.

Clinical Features and Natural HistoryTop

Symptoms are nonspecific and usually appear late (the lesion is often unresectable at diagnosis). The most common symptom is blunt pain in the right subcostal area, radiating rightwards to the spine and interscapular area; jaundice and pruritus (due to tumor infiltrating the bile duct; this worsens the prognosis); nausea and vomiting; loss of appetite, weight loss; tumor palpable in the right upper abdominal quadrant.

DiagnosisTop

Diagnostic Tests

1. Laboratory tests: Elevated serum activity of alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), bilirubin concentration, activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (in advanced disease with liver infiltration and metastatic lesions); elevated concentration of carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9.

2. Imaging: Ultrasonography may show a thickened gallbladder wall, tumor in the gallbladder lumen (polyps <1 cm in diameter are rarely cancerous) or in the adjacent liver parenchyma. Endoscopic ultrasonography (EUS) allows for determination of the depth of cancer infiltration and assessment of regional lymph node involvement. Computed tomography (CT) visualizes lesions similar to those seen on ultrasonography and allows for assessment of the topography of lesions, regional lymph nodes, and liver infiltration. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) can reveal midbiliary obstruction, which indicates their infiltration by cancer.

Diagnostic Criteria

Preliminary diagnosis is based on the results of imaging. Many gallbladder polyps >1 cm in diameter are neoplastic, often malignant. As it is difficult to distinguish cancer from adenoma on the basis of cytologic examination of fine-needle biopsy material, lesions arising from the gallbladder wall and having a diameter >1 cm are an indication for cholecystectomy.

TreatmentTop

1. Intent-of-cure treatment: Surgical treatment (radical surgery is possible only early in the disease): open cholecystectomy (gallbladder removal with a wide liver margin [~2 cm] and removal of regional lymph nodes). If a non–locally advanced gallbladder cancer is diagnosed incidentally on histologic examination performed after laparoscopic cholecystectomy, open reoperation is not warranted as long as the margins are negative and the lesion has not invaded the perimuscular connective tissue (<T2).

2. Palliative treatment: Endoscopic drainage of the bile ducts with endobiliary stenting is performed to reduce the symptoms of cholestasis. Systemic treatment is also used (see Cholangiocarcinoma).

PrognosisTop

Average overall survival is ~6 months. Postoperative 5-year survival depends on the clinical stage and ranges from >90% in stage I to 15% in stage III (according to the tumor, node, metastasis [TNM] classification).