Search

Background: Gallbladder cancer has an unusual geographic and demographic distribution, suggesting many possible etiologies., Methods: A case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four patients with newly diagnosed, histologically confirmed gallbladder cancer were compared with 126 control subjects without stones and with 264 control subjects with cholelithiasis or choledocholithiasis without cancer. All study subjects underwent abdominal surgery. Study subjects were interviewed regarding demographic characteristics, medical history, family history, diet, and exposure to agents presumed to be risk factors for biliary cancer., Results: Virtually all subjects in Mexico were judged to be mestizos (i.e., persons of mixed ancestry) In contrast, race was a very strong risk factor for gallbladder cancer in Bolivia. Relative to mestizos who spoke neither language, the odds ratio (95% confidence interval [CI]) for cases versus control subjects without stones for those who spoke Aymara well was 15.9 (CI, 1.9-179), whereas it was 1.4 (CI, 0.2-8.2) for those who spoke Quechua well. An increased risk was also noted for elevated maximum body mass index (P = 0.03), family history of gallstones (odds ratio [OR] = 3.6 [CI, 1.3-11.4]), and physician-diagnosed typhoid (OR = 12.7 [CI, 1.5-598]). An increased risk was also seen with elevated maximum body mass index; compared with those with a body mass index less than 24 kg/m2, those with an index of 24-25 kg/m2, 26-28 kg/m2, and greater than 28 kg/m2 had odds ratios of 1.6 (CI, 0.4-7.6), 1.3 (CI, 0.3-5.6), and 2.6 (CI, 0.5-18.6), respectively (asymptotic test for trend, P = 0.03). Finally, a number of associations were noted with certain dietary and cooking habits., Conclusions: Patients with gallbladder cancer differed from control subjects in race, body mass, physician-diagnosed typhoid, and certain dietary patterns. These findings may provide useful clues to the pathogenesis of gallbladder cancer, but given the number of analyses performed, additional cases need to be studied.

Immunoreactivity for a panel of 15 monoclonal antibodies (MAbs), which are known to react with different gastrointestinal tumor antigens, was assessed in formalin-fixed paraffin-embedded sections that were prepared from cholecystectomy specimens obtained from Mexican patients. Each case was classified histologically into one of the following groups: (1) invasive adenocarcinoma (N = 21), (2) high-grade dysplasia (carcinoma in situ) (N = 2), (3) low-grade dysplasia (N = 4), hyperplasia (4) (N = 15), and (5) chronic cholecystitis (N = 10). Significant differences (P < 0.05) were identified among the five histopathologic groups in the proportion of epithelial cells demonstrating immunoreactivity with MAbs to Lewisb; Lewis(a); sialylated Lewis(a); sialylated Lewis(a) and Lewis(a); Y antigen; H antigen; X antigen; X-like antigen; 200-kDa protein of CEA; 180-, 160-, 50-, 40-kDa proteins of CEA; 30- to 37-kDa protein; and an undefined antigen identified by MAb 99-57, with invasive carcinoma more frequently being positive as compared to nonneoplastic (hyperplasia, chronic cholecystitis) epithelium. Significant differences were also observed among the five histopathologic groups (P < or = 0.0005) in the proportion of epithelial cells demonstrating immunoreactivity with MAbs to Y antigen and the 20- to 50-kDa glycoprotein. However, with these two antibodies immunoreactivity was more frequently found in nonneoplastic epithelium rather than in invasive carcinomas. No significant differences in immunoreactivity were detected among the different histologic groups with MAb to blood group B antigen, types 1 and 2. This study demonstrates that cellular antigens are both developed and lost during the process of neoplastic transformation in the gallbladder.(ABSTRACT TRUNCATED AT 250 WORDS)

The poor prognosis of gallbladder cancer and the presence of high-risk populations make the identification of a screening test for this disease very desirable. As part of an ongoing case-control study of gallbladder cancer being conducted in Mexico City, Mexico, and in La Paz, Bolivia, blood specimens were sought from all patients with cancer of the gallbladder and on controls of similar age and sex undergoing upper abdominal surgery. Each sample was analyzed for carcino-embryonic antigen (CEA) and CA 19-9. Using the specimens from Bolivia, a serum CEA cutoff of 4.0 ng/ml yielded a sensitivity of 50.0% and a specificity of 92.7%, while a serum CA 19-9 cutoff of 20.0 units/ml yielded a sensitivity of 79.4% and a specificity of 79.2%. Using ROC curve analysis, the latter was a much better test than the former (p less than 0.05). Using the tests in series or in parallel did not substantively improve the results. The specimens from Mexico were used for validation purposes, and yielded very similar results. In conclusion, serum CA 19-9 and CEA are fairly good tests for discriminating patients with gallbladder cancer from patients with gallstones and no cancer, the former being a better test than the latter. These tests may be useful in identifying disease recurrences. In addition, if a sufficiently high-risk population could be identified, this could potentially become a useful screening test for this serious disease, allowing early intervention. However, additional data are needed prior to recommending this clinically.

Gallbladder epithelium is unique among the gastrointestinal cell types because proteins and protein levels in the fluid bathing the luminal side of the cells (bile) are different from and can be compared with those in the fluid bathing the basal side (serum). To help identify cellular changes that occur during the development of gallbladder cancer, we obtained gallbladder tissue, serum, and bile specimens from 20 patients with invasive adenocarcinoma of the gallbladder, three with high-grade dysplasia (carcinoma in situ), six with low-grade dysplasia, 12 with hyperplasia, and 10 with acute or chronic cholecystitis. We obtained serum samples from 40 patients with invasive adenocarcinoma and bile samples from 29 of these patients; serum samples from three with high-grade dysplasia and bile specimens from two of these; serum and bile samples from five with low-grade dysplasia; serum or bile samples from 126 with metaplasia, hyperplasia, or cholecystitis, including serum samples from 121 and bile samples from 110; and serum and bile samples from eight with normal biliary tracts. The study was conducted in Mexico City, Mexico, and La Paz, Bolivia. We performed flow cytometric DNA analysis on gallbladder tissue specimens and measured levels of carcinoembryonic antigen (CEA) and CA 19-9 antigen in the serum and bile specimens. Analysis of the cell cycle compartments by flow cytometry revealed marked variations of the proliferation index for the different disease states (P less than .0001). The proliferation index increased with progression from cholecystitis to invasive adenocarcinoma. Of the bile and serum measurements, only serum CA 19-9 values were correlated with flow cytometry measurements (r = -.49, P = .005). Overall, the serum and bile measurements were in agreement (P less than .01). However, with the exception of the correlations among serum measurements for the patients with invasive adenocarcinoma, most of the correlations could be explained by differences in the disease state. In particular, the progression from normal tissue to invasive adenocarcinoma involved no change in bile CA 19-9 level and only a slight change in bile CEA level but much larger changes in serum CEA and CA 19-9 levels. It appears that the progression from normal tissue to invasive adenocarcinoma results in increased production of these antigens and often in loss of cell polarity as well, i.e., inability to prevent leakage of the antigens into the serum.