Gallbladder cancer risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Overview

The most potent risk factor in the development of gallbladder carcinoma is gallstones. Other risk factors include Porcelain gallbladder, gallbladder polyps, Primary sclerosing cholangitis, chronic infection, pancreaticobiliary maljunction (PBM) and biliary cysts.

Risk factors

Common Risk Factors

Common risk factors in the development of gallbladder cancer include:

Gallstones: Gallstones are found in 70 to 90 percent of patients with gallbladder Cancer (GBC) and a history of gallstones appears to be one of the strongest risk factors for the development of GBC, With an 8.3x higher danger than the overall population.[1]In spite of the increased risk of GBC in patients with gallstones, the general occurrence of GBC in patients with cholelithiasis is only 0.5 percent.[2] The larger the stones are the higher the risk of gallbladder cancer in patients with gall stones. Patients with stones larger than 3 cm had a 10-fold higher chance of GBC in comparison with people with stones <1 cm.

Porcelain gallbladder: Porcelain gallbladder is characterized by intramural calcification of the gallbladder wall and it is a rare manifestation of chronic cholecystitis.In 95 % of the cases, the procelain gallbladder is associated with gallstones.The incidence of GBC in patients with a porcelain gallbladder levels about 2 to 3 percent and this increased risk can be restricted to patients with selective mucosal calcification.[3]

Gallbladder polyps: Around 5% of all adults have gallbladder polyps, These are the outgrowths of mucosa of the gallbladder which are found accidently on ultrasound.The classification of the gallbladder polyps are benign or malignant.Differentiating non-neoplastic from neoplastic polyps is important.[4]

Benign polyps Malignant polyps
Cholesterol polyps (60%) Adenocarcinoma (80%)
Adenomyomas (25%)
Inflammatory polyps (10%)
Adenomas (4%)
Miscellaneous (1%)

Leiomyomas, Fibromas, and Lipomas

Miscellaneous (20%)

Mucinous cystadenomas, Squamous cell carcinoma, and adenoacanthomas

Primary sclerosing cholangitis (PSC): PSC is a chronic inflamatory disease and is assosciated with increased risk of Gallbladder cancer (GBC).It is therefore advicesed that patients with PSC should undergo yearly gallbladder screening with ultrasound for the detection of any abnormal lesions.[5]

Chronic infection

Helicobacter: Exact mechanism is poorly understood but it is thought that gallbladder cancer may be related to the bacterial-induced degradation of bile acids.

Liver flukes: Liver flukes especially Clonorchis sinensis and Opisthorchis viverrini are related in the gallbladder cancer.[6]

Salmonella: Several reports and a meta-analysis of case-control and cohort studies advocate an association among chronic S. typhi carriage and increased hazard of GBC

Congenital biliary cysts: Biliary cysts are cystic dilatations in the bile ducts.They were originally coined as choledochal cysts .Biliary cysts are more frequently seen in Asian populations. An abnormal pancreaticobiliary duct junction is present in approximately 70 percent of patients with biliary cysts.Particularly cholangiocarcinoma is assciated with increased risk with biliary cysts.[7]

Pancreaticobiliary maljunction (PBM): It's a rare anatomical abnormality in which the pancreatic duct drains into the common bile duct, which results in a long common duct. PBM is due to failure of migration of embryological ducts into the duodenum.PDM has most commonly seen in Japanese population.[8]The abnormally long common channel may lead to reflux of pancreatic secretions into the biliary tree. This results in increased amylase levels in the bile, intraductal secretion and activation of proteolytic enzymes, changes in bile composition, and may be biliary epithelial damage, inflammation, ductal distension, and cyst formation. is the most common malignancy seen in patients with an anomalous pancreaticobiliary duct junction. is the most common malignancy seen in patients with an anomalous pancreaticobiliary duct junction. Gallbladder carcinoma is the most common malignancy seen in patients with a Pancreaticobiliary maljunction problem.[9]

Cigarette smoking: cigarette smoking is one the important risk factor in causing gallbladder cancer.

References

  1. Hsing AW, Gao YT, Han TQ, Rashid A, Sakoda LC, Wang BS, Shen MC, Zhang BH, Niwa S, Chen J, Fraumeni JF (2007). "Gallstones and the risk of biliary tract cancer: a population-based study in China". Br. J. Cancer. 97 (11): 1577–82. doi:10.1038/sj.bjc.6604047. PMC 2360257. PMID 18000509.
  2. Muszynska C, Lundgren L, Lindell G, Andersson R, Nilsson J, Sandström P, Andersson B (2017). "Predictors of incidental gallbladder cancer in patients undergoing cholecystectomy for benign gallbladder disease: Results from a population-based gallstone surgery registry". Surgery. 162 (2): 256–263. doi:10.1016/j.surg.2017.02.009. PMID 28400123.
  3. Khan ZS, Livingston EH, Huerta S (2011). "Reassessing the need for prophylactic surgery in patients with porcelain gallbladder: case series and systematic review of the literature". Arch Surg. 146 (10): 1143–7. doi:10.1001/archsurg.2011.257. PMID 22006872.
  4. Kanthan R, Senger JL, Ahmed S, Kanthan SC (2015). "Gallbladder Cancer in the 21st Century". J Oncol. 2015: 967472. doi:10.1155/2015/967472. PMC 4569807. PMID 26421012.
  5. Hundal R, Shaffer EA (2014). "Gallbladder cancer: epidemiology and outcome". Clin Epidemiol. 6: 99–109. doi:10.2147/CLEP.S37357. PMC 3952897. PMID 24634588.
  6. Hundal R, Shaffer EA (2014). "Gallbladder cancer: epidemiology and outcome". Clin Epidemiol. 6: 99–109. doi:10.2147/CLEP.S37357. PMC 3952897. PMID 24634588.
  7. Kanthan R, Senger JL, Ahmed S, Kanthan SC (2015). "Gallbladder Cancer in the 21st Century". J Oncol. 2015: 967472. doi:10.1155/2015/967472. PMC 4569807. PMID 26421012.
  8. Kaushik SP (2001). "Current perspectives in gallbladder carcinoma". J. Gastroenterol. Hepatol. 16 (8): 848–54. PMID 11555095.
  9. Hundal R, Shaffer EA (2014). "Gallbladder cancer: epidemiology and outcome". Clin Epidemiol. 6: 99–109. doi:10.2147/CLEP.S37357. PMC 3952897. PMID 24634588.


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