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Cancers of the Gallbladder and Biliary Ducts

Cancers of the Gallbladder and Biliary Ducts

Dr. Yee and his colleagues have offered a comprehensive
overview of the epidemiology, diagnosis, and therapy of both gallbladder
carcinoma and cholangiocarcinoma. They correctly note the infrequency of these
two neoplasms, with approximately 7,500 cases diagnosed in the United States
each year, two-thirds of which are gallbladder cancer. Unfortunately, neither
the incidence rate nor prognosis of these neoplasms has changed substantially
since biliary tumors were last reviewed in this journal[1]; the median 5-year
survival rate has remained at 5%. Some progress has been made, however, in our
understanding of the etiology of cancers of the biliary tract, and a body of
literature continues to emerge exploring the question of how best to approach
screening and prophylaxis in high-risk populations.

Risk Factors for Gallbladder Cancer

As Yee et al discuss, while its pathogenesis has yet to be fully delineated,
some risk factors for biliary tract carcinoma have been identified.
Cholelithiasis has been widely recognized as a factor that predisposes toward
its development, especially if the gallstones are symptomatic and large.[2]
"Porcelain gallbladder" or calcification of the gallbladder wall
predicts a high risk of concurrent or future gallbladder cancer. An anomalous
pancreaticobiliary ductal junction, a congenital defect most common among
Asians, is closely connected with gallbladder cancer; 15% to 40% of patients
with this anomaly go on to develop the malignancy.[3]

Other links have been made between gallbladder cancer and bacterial
infections of the biliary tract, most notably Salmonella typhi and,
intriguingly, bile-resistant Helicobacter spp. Some investigators have attempted
to identify biochemical changes in the composition of bile that may predispose
to metaplasia. Although early data suggested that patients with gallstones and
gallbladder cancer possess a higher biliary concentration of lithocholate—a
known carcinogen—than do patients with gallstones but no concomitant
malignancy, subsequent data have failed to confirm this.[4]

Whether one or more of these factors contributes to the striking geographic
and ethnic differences identified by Yee et al in gallbladder cancer incidence
rates is unclear, but the suggestions posited by preliminary data merit further
investigation. Less clear are the potential roles of estrogens and tobacco in
the etiology of gallbladder cancer. Some case-control and observational series
have identified them as risk factors, but the incidence of gallbladder cancer is
not higher than predicted among patients who have developed other more clearly
defined tobacco- and estrogen-associated tumors.[5]

Risk Factors for Cholangiocarcinoma

High-risk populations for cholangiocarcinoma have been identified as well.
Patients with gallstones are also at increased risk for cholangiocarconoma,
although less so than for gallbladder cancer. However, other patient populations
are at far greater risk. Notably, patients with primary sclerosing cholangitis
have a lifetime risk of at least 10% (some have reported this risk to exceed
30%). Patients with ulcerative colitis in the absence of primary sclerosing
cholangitis are at increased risk of developing cholangiocarcinoma as well, as
are those with rarer conditions, including Caroli’s disease, multiple biliary
papillomatosis, exposure to thorium dioxide (Thorotrast), and, in endemic
regions, infestation with the trematodes Clonorchis sinensis or Opisthorchis


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