Gallbladder cancer is an aggressive malignancy with a generally poor prognosis. Described for the first time in two autopsy cases by Stoll and his colleagues in 1777, it is the most common malignant tumor of the biliary tract and the sixth most common gastrointestinal cancer.1,2 Complete surgical resection provides the only hope of long-term cure and survival. Despite an increasing number of patients diagnosed incidentally, most patients are found with advanced disease when potentially curative treatment is not feasible and palliative therapy is the only option.3
EPIDEMIOLOGY AND MORTALITY
One of the features of the global pattern incidence of gallbladder cancer is the variation on the basis of geography and ethnicity. Though it is common in the Indian Subcontinent (India, Pakistan), South America (Chile, Bolivia), East Asia (Korea, Japan), and Central Europe (Slovakia, Poland, Czech Republic), it is relatively infrequent in other parts of Europe, North America, and Australia/NewZealand.3 Crude incidence rates for females range from 1.45 per 100,000 in United States to 25.3 per 100,000 in Chile.4 However, regional variations in the same country are also notable—in Argentina a markedly higher incidence is found in the North (Province of Salta) with 6.7 per 100,000 population than in other provinces.5 Certain ethnic groups such as Hispanics, American Indian Natives, Mexican Indian Natives, and Chilean Mapuche Indians are identified as high-risk groups for gallbladder cancer.4 There are multiple potential heterogeneous factors of both genetic and environmental origins. For instance, Hispanic Americans without direct lineage from indigenous New World ancestors do not appear to be at high risk for gallbladder cancer.6 Gallbladder cancer is the leading cause of cancer death among women in Chile and the highest mortality rates were reported in the Araucanía region (35 per 100,000 population).7
INCIDENCE AND RISK FACTORS
The incidence is three times higher among women than men, making gallbladder cancer one of the few non-reproductive-organ-related cancers having a female predominant distribution. Recent findings raise the possibility that gallbladder carcinogenesis may have estrogen- or progesterone-mediated features.3 The mean age at diagnosis falls in the sixth or seventh decade, with exceedingly rare presentations in persons younger than 30 years.8 The strongest risk factors for gallbladder cancer include cholelithiasis, obesity, anomalous pancreatobiliary junction, mucosal microcalcifications, and gallbladder polyps.9 The most relevant associated feature is comorbid gallstones present in 60% to 80%.3 The relative risk of developing carcinoma of the gallbladder has been estimated at between 2 and 24 times higher than in patients without cholelithiasis depending on the study population involved.1 The strong association between gallstone formation and neoplasia appears to be the principal determinant of risk factors such as female gender, increased age, fecundity, and obesity. Other risk factors, related to chronic inflammatory processes, such as porcelain gallbladder, chronic cholecystitis, or pancreatobiliary maljunction share etiologic mechanisms similar to ...