Gallbladder cancers: associated conditions, histological types, prognosis, and prevention

Eur J Gastroenterol Hepatol. 2014 May;26(5):562-9. doi: 10.1097/MEG.0000000000000074.


Introduction: Gallbladder cancer has a poor prognosis, with a reported 5-year survival of 5%. The prognosis improves when an R0 resection is feasible, but an early diagnosis is rare. The aim of the present study is to analyze the different conditions associated with gallbladder carcinomas and to report the main prognostic factors for these tumors to enable prevention.

Materials and methods: From 1986 to 2012, 75 patients were found to have gallbladder cancer during the study of 2942 patients affected by biliary tract diseases; 34 of these patients had gallbladder and gallstones, and had been subjected to bile analysis. Pancreatobiliary reflux was studied by biliary trypsin and C-Ki-ras genes were analyzed in 11 cases.

Results: Gallstones were found in 72 of 75 gallbladder cancer patients; in particular, large gallstones were associated with 88.88% of squamous-cell carcinoma, 68.2% of adenocarcinoma, and never with papillary adenocarcinoma. Pancreatobiliary reflux was associated with papillary adenocarcinoma in 100% of cases, but seldom with squamous cell carcinoma. C-Ki-ras mutations were found in 100% of patients with papillary carcinoma.

Discussion and conclusion: R0 resection in in-situ cancer has the best prognosis. Preventive cholecystectomy should be performed in high-risk patients (gallstones larger 3 cm; adenomatous polyps>1 cm; pancreatobiliary reflux, porcelain gallbladder, segmental adenomyomatosis, xanthogranulomatous cholecystitis). The histological stratification of gallbladder cancer should be carried out before starting further studies because squamous-cell carcinoma, adenocarcinoma, and papillary carcinoma are associated with different risk factors and genetic mutations and have different responsiveness to chemotherapies.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Bile Reflux / epidemiology
  • Carcinoma* / epidemiology
  • Carcinoma* / genetics
  • Carcinoma* / pathology
  • Carcinoma* / prevention & control
  • Carcinoma* / therapy
  • Cholecystectomy
  • Female
  • Gallbladder Neoplasms* / epidemiology
  • Gallbladder Neoplasms* / genetics
  • Gallbladder Neoplasms* / pathology
  • Gallbladder Neoplasms* / prevention & control
  • Gallbladder Neoplasms* / therapy
  • Gallstones / epidemiology
  • Genetic Predisposition to Disease
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Mutation
  • Patient Selection
  • Precision Medicine
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome
  • ras Proteins / genetics


  • Antineoplastic Agents
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins