Carcinoma of the gallbladder is the most common malignancy of the extrahepatic biliary tract. It is slightly more common in women and occurs most frequently in the seventh decade of life. The incidence in the United States is 1 in 50,000. Only rarely is it discovered at a resectable stage, and the mean 5-year survival rate has remained unchanged at about 5% to 12% over the past many years. The most important risk factor associated with gallbladder carcinoma is gallstones (cholelithiasis), which are present in 95% of cases. Presumably, gallbladders containing stones or infectious agents develop cancer as a result of chronic inflammation, a known enabler of malignancy in several organs (Chapter 6). Carcinogenic derivatives of bile acids also are suspected to play a role. Primary sclerosing cholangitis is also a risk factor.
MORPHOLOGYCarcinomasofthegallbladdershowtwopatternsofgrowth:infiltrating andexophytic. Theinfiltratingpatternismorecommonandusuallyappearsasapoorlydefinedareaofdiffusewallthickeningandinduration.Theexophyticpatterngrowsintothelumenasanirregular,cauliflowermass,butatthesametimeinvadestheunderlyingwall(
Fig.16.42 ).Mostcarcinomasofthegallbladderareadenocarcinomas.About5%aresquamouscellcarcinomasorhaveadenosquamousdifferentiation.
Preoperative diagnosis of carcinoma of the gallbladder is the exception rather than the rule, occurring in fewer than 20% of patients. Presenting symptoms are insidious and typically indistinguishable from those associated with cholelithiasis: abdominal pain, jaundice, anorexia, nausea and vomiting. There is no satisfactory treatment of gall bladder cancer due to the advanced stage at the time of diagnosis. Only 10% are diagnosed at a stage that is early enough to attempt curative surgery.
SUMMARYGALLBLADDERDISEASES•Gallbladderdiseasesincludecholelithiasisandacuteandchroniccholecystitis,andgallbladdercancer.
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ABABFig. 16.42 Gallbladderadenocarcinoma.(A)Theopenedgallbladdercon-tainsalarge,exophytictumorthatvirtuallyfillsthelumen.(B)Microscopically,thetumorhasthesameappearanceasthatofintrahepaticcholangiocarcinoma.
GallstoneformationisacommonconditioninWesterncountries.Thegreatmajorityofthegallstonesarecholesterolstones.PigmentedstonescontainingbilirubinandcalciumaremostcommoninAsiancountries,duetothehigherincidenceofchronichemolyticdisordersandliverflukeinfestationsintheselocales.
Riskfactorsforthedevelopmentofcholesterolstonesareadvancingage,femalegender,estrogenuse,obesity,andheredity.
Cholecystitisalmostalwaysoccursinassociationwithcholelithiasis,althoughinabout10%ofcasesitoccursintheabsenceofgallstones.
Acutecalculouscholecystitisisthemostcommonreasonforemergencycholecystectomy.
Gallbladdercancerisalmostalwaysassociatedwithgallstones.Becauseoftheadvancedstageatdiagnosis,ithasaverypoorprognosis.
Mechanisms of Liver Injury and Repair
Gouw ASW, Clouston AD, Theise ND: Ductular reactions in human livers: diversity at the interface, Hepatology 54:2011, 1853. [A review of ductular reactions, the stem cell response of human livers in all liver diseases, that are related to mechanisms of regeneration, fibrogenesis, and neoplasia.]