Diagnosis

Gallbladder cancer

Etiology

Cause/Pathophysiology [rtu]

1. Chronic inflammation (or toxins and direct injury) --> DNA mutations (K-ras, TP53, CDKN2a, c-erb-b2)

   • Cholesterol gallstones (most common)

   • Primary sclerosing cholangitis

   • Ulcerative colitis

   • Crohns disease

   • Liver parasite

   • Chronic Salmonella typhi/paratyphi infection

   • Helicobacter infection

   • Extrinsic carcinogens:

     • Medications: methyldopa, isoniazid

     • Work exposure: methylcellulose, radon

     • Lifestyle: cigarette smoking, obesity, high carbohydrate intake

2. Polyps --> dysplasia --> invasive gallbladder cancer (usually adenocarcinoma)

3. Other rare types: squamous, adenosquamous, and neuroendocrine tumors

4. Grim prognosis with 5 year survival rate 38% [m49] due to: [rtu]

   • Aggressive tumor biology

   • Complex anatomical location

   • Advanced stage at diagnosis

Risk factors [rtu]

• Woman

• Gallstones

• Porcelain gallbladder (gallbladder calcification)

• Choledochal cysts

• Gallbladder polyps

• Occupational chemical exposure

• Estrogens

• Anomalous pancreatobiliary duct junction

• Hereditary syndromes with an increased incidence of gallbladder cancer: Gardner syndrome, neurofibromatosis type I, and hereditary nonpolyposis colon cancer.

Epidemiology

Incidence per 100.000 [fq5]

Approach

• Blood test: CA 19-9 (elevated), CEA (not specific for gallbladder cancer), liver function tests

• Ultrasound abdomen

• CT abdomen

• MR abdomen

• MRCP

• ERCP

• PTC

Classification [rtu]

• T1: Tumor invades lamina propria or muscular layer

  • T1a: Tumor invades lamina propria

  • T1b: Tumor invades muscle layer

• T2: Tumor invades the perimuscular connective tissue

  • T2a: Tumor invades the perimuscular connective tissue on the peritoneal side, without the involvement of the serosa (visceral peritoneum)

  • T2b: Tumor invades the perimuscular connective tissue on the hepatic side, with no extension 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 main portal vein or hepatic artery or invades 2 or more extrahepatic organs or structures

• N (regional lymph nodes)

  • NX: Regional lymph nodes cannot be assessed

  • N0: No regional lymph node metastasis

  • N1: Metastases to 1 to 3 regional lymph nodes

  • N2: Metastases to ≥4 or more regional lymph nodes

• M (distant metastasis)

  • M0: No distant metastasis

  • M1: Distant metastasis [3]

Treatment

1. Early-stage disease (a minority of patients): [rtu][m49]

   • T1a tumors (incidentally detected): Tumors confined to the mucosa require only a cholecystectomy

   • T1b, T2, and T3 tumors: En-bloc resection of the gallbladder including resection of the adjacent segments 4b and 5 with adequate surgical margins + portal lymphadenectomy + adjuvant radiotherapy to control microscopic residual deposits of carcinoma in the tumor bed and regional lymph nodes

   • Extended hepatic (beyond segments 4b and 5) and biliary resections increase morbidity and mortality without any survival benefit

2. Neoadjuvant chemotherapy: Some patients may have an adequate response that allows for subsequent resection

3. Unresectable disease due to locally advanced and metastatic disease:

   Palliation with radiation therapy and/or chemotherapy

Differential diagnoses

Acalculous cholecystitis, Ampullary carcinoma, Benign bile duct tumor, Bile duct stricture, Biliary obstruction, Carcinoma of the ampulla of Vater, Cholangiocarcinoma, Cholangitis, Cholecystitis, Choledochal cysts, Choledocholithiasis, Cholelithiasis, Gallbladder mucocele, Gallbladder volvulus, Gastrinoma, Glucagonoma, Hepatocellular carcinoma, Insulinoma, Liver abscess, Pancreatic cancer, Primary biliary cirrhosis, Primary sclerosing cholangitis, VIPoma