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Re: Dutta et al.—gallbladder cancer
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2003 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 98, No. 5, 2003 ISSN 0002-9270/03/$30.00
LETTERS TO THE EDITOR Re: Dutta et al.—Gallbladder Cancer
Response to Dr. Choudhuri
TO THE EDITOR: Typhoid carrier state has been implicated as an important etiological factor in gallbladder carcinogenesis by many investigators from all over the world. Dutta et al. (1) reported that 16% of patients with gallbladder cancer (GBC) were detected to be typhoid carriers, in contrast to 2.5% among controls (p ⫽ 0.01). The control arm (n ⫽ 80) comprised only gallstone patients without any evidence of GBC, whereas all cancer patients (n ⫽ 37) had coexisting gallstone disease. An apparently similar kind of study, published in the Proceedings of the Annual Meeting of the Indian Society of Gastroenterology (2) by the same authors, indicated that 74% (37 of 50) of GBC patients and 76% (84 of 114) of patients with gallstones were typhoid carriers in contrast to 29% (14 of 48) of healthy controls. The two publications by the same group seemed to have the same samples, used the same techniques (in-house ELISA for Vi antibody), but reported very different results. It would, therefore, be interesting to know whether normal healthy controls were included in the studies and the explanation for the observed differences in the respective results, particularly in reference to status of typhoid carrier state in GBC and gallstone disease. One study showed significant difference between these two groups (16% and 2.5%, respectively), whereas the other did not (74% and 76%, respectively). Could the authors please clarify?
TO THE EDITOR: We conducted a study on the prevalence of typhoid carrier state in patients with gallbladder cancer (CaGB) and compared it with that in patients with gallstones during the period March 1994 –July 1995. Data were collected from 49 patients with CaGB and 114 patients with gallstones who served as diseased controls. We presented our preliminary findings in the Annual Meeting of the Indian Society of Gastroenterology, which were reported in abstract form in the supplement issue of the Society’s journal (1). The study was subsequently published as a full article after a couple of peer reviews and modifications (2). The apparent differences between the results of the above two publications arise from two major differences between them. First, after the initial analysis of results, we realized that there was an unusually high typhoid carrier rate among healthy controls (29%). The only reported prevalence rate of typhoid carriers in India is 3.5% among food handlers (3). Thus, the positivity of 29% among the controls seemed unusually high, indicating a false positivity of the test, i.e., Vi antibody titers. This was possibly because we had taken 20 highly selected healthy controls (in whom the Widal test was negative and who had no past history of typhoid fever) to derive the Vi antibody titers and then used mean ⫹ 2 SD as the cutoff value for labeling a patient as a chronic carrier. We believed that using a cutoff from a population less likely to have been exposed to Salmonella typhi infection would be “oversensitive” and result in a high false-positivity rate. Thus, with mean ⫹ 2 SD as the cutoff value, the percentage of patients with CaGB and patients with gallstones having a typhoid carrier state actually turned out to be very high. Furthermore, it has been reported that typhoid carriers are known to have very high levels of Vi antibodies, whereas moderate amounts of Vi antibodies may be found in those recovering from a recent typhoid illness (4 – 6). To correct these two conceived shortcomings, we took the mean ⫹ 3 SD cutoff value derived from 39 healthy controls from the general population whose status regarding exposure to typhoid was not known. Second, gallstones are a recognized risk factor for CaGB. We wanted to primarily look for the role of Salmonella typhi carrier state in the etiopathogenesis of CaGB. Thus, we included only patients with CaGB with coexistent gallstones as cases and compared them with patients with gallstones alone to exclude gallstones as a confounding risk factor. Therefore, we excluded 13 patients who had CaGB but no gallstones. That was the reason why data from only 37 patients with CaGB were included in the final article. This point about the number of cases reduced from 50 to 37 had
Mahendra Kumar Singh, M.Sc. Gourdas Choudhuri, M.D., D.M. Department of Gastroenterology Sanjay Gandhi Post-Graduate Institute of Medical Sciences Lucknow, India
REFERENCES 1. Dutta U, Garg PK, Kumar R, et al. Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Am J Gastroenterol 2000;95:784 –7. 2. Dutta U, Garg PK, Tandon RK, et al. Gallstones and Salmonella typhi carrier state: Cofactors in the pathogenesis of carcinoma of the gallbladder (CaGB). Indian J Gastroenterol 1996; 15(suppl 1):A41 (abstract). Reprint requests and correspondence: Gourdas Choudhuri, M.D., D.M., Department of Gastroenterology, Sanjay Gandhi PostGraduate Institute of Medical Sciences, Lucknow 226014, India. Received Oct. 16, 2002; accepted Dec. 2, 2002.
Vol. 98, No. 5, 2003 ISSN 0002-9270/03/$30.00
LETTERS TO THE EDITOR Re: Dutta et al.—Gallbladder Cancer
Response to Dr. Choudhuri
TO THE EDITOR: Typhoid carrier state has been implicated as an important etiological factor in gallbladder carcinogenesis by many investigators from all over the world. Dutta et al. (1) reported that 16% of patients with gallbladder cancer (GBC) were detected to be typhoid carriers, in contrast to 2.5% among controls (p ⫽ 0.01). The control arm (n ⫽ 80) comprised only gallstone patients without any evidence of GBC, whereas all cancer patients (n ⫽ 37) had coexisting gallstone disease. An apparently similar kind of study, published in the Proceedings of the Annual Meeting of the Indian Society of Gastroenterology (2) by the same authors, indicated that 74% (37 of 50) of GBC patients and 76% (84 of 114) of patients with gallstones were typhoid carriers in contrast to 29% (14 of 48) of healthy controls. The two publications by the same group seemed to have the same samples, used the same techniques (in-house ELISA for Vi antibody), but reported very different results. It would, therefore, be interesting to know whether normal healthy controls were included in the studies and the explanation for the observed differences in the respective results, particularly in reference to status of typhoid carrier state in GBC and gallstone disease. One study showed significant difference between these two groups (16% and 2.5%, respectively), whereas the other did not (74% and 76%, respectively). Could the authors please clarify?
TO THE EDITOR: We conducted a study on the prevalence of typhoid carrier state in patients with gallbladder cancer (CaGB) and compared it with that in patients with gallstones during the period March 1994 –July 1995. Data were collected from 49 patients with CaGB and 114 patients with gallstones who served as diseased controls. We presented our preliminary findings in the Annual Meeting of the Indian Society of Gastroenterology, which were reported in abstract form in the supplement issue of the Society’s journal (1). The study was subsequently published as a full article after a couple of peer reviews and modifications (2). The apparent differences between the results of the above two publications arise from two major differences between them. First, after the initial analysis of results, we realized that there was an unusually high typhoid carrier rate among healthy controls (29%). The only reported prevalence rate of typhoid carriers in India is 3.5% among food handlers (3). Thus, the positivity of 29% among the controls seemed unusually high, indicating a false positivity of the test, i.e., Vi antibody titers. This was possibly because we had taken 20 highly selected healthy controls (in whom the Widal test was negative and who had no past history of typhoid fever) to derive the Vi antibody titers and then used mean ⫹ 2 SD as the cutoff value for labeling a patient as a chronic carrier. We believed that using a cutoff from a population less likely to have been exposed to Salmonella typhi infection would be “oversensitive” and result in a high false-positivity rate. Thus, with mean ⫹ 2 SD as the cutoff value, the percentage of patients with CaGB and patients with gallstones having a typhoid carrier state actually turned out to be very high. Furthermore, it has been reported that typhoid carriers are known to have very high levels of Vi antibodies, whereas moderate amounts of Vi antibodies may be found in those recovering from a recent typhoid illness (4 – 6). To correct these two conceived shortcomings, we took the mean ⫹ 3 SD cutoff value derived from 39 healthy controls from the general population whose status regarding exposure to typhoid was not known. Second, gallstones are a recognized risk factor for CaGB. We wanted to primarily look for the role of Salmonella typhi carrier state in the etiopathogenesis of CaGB. Thus, we included only patients with CaGB with coexistent gallstones as cases and compared them with patients with gallstones alone to exclude gallstones as a confounding risk factor. Therefore, we excluded 13 patients who had CaGB but no gallstones. That was the reason why data from only 37 patients with CaGB were included in the final article. This point about the number of cases reduced from 50 to 37 had
Mahendra Kumar Singh, M.Sc. Gourdas Choudhuri, M.D., D.M. Department of Gastroenterology Sanjay Gandhi Post-Graduate Institute of Medical Sciences Lucknow, India
REFERENCES 1. Dutta U, Garg PK, Kumar R, et al. Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Am J Gastroenterol 2000;95:784 –7. 2. Dutta U, Garg PK, Tandon RK, et al. Gallstones and Salmonella typhi carrier state: Cofactors in the pathogenesis of carcinoma of the gallbladder (CaGB). Indian J Gastroenterol 1996; 15(suppl 1):A41 (abstract). Reprint requests and correspondence: Gourdas Choudhuri, M.D., D.M., Department of Gastroenterology, Sanjay Gandhi PostGraduate Institute of Medical Sciences, Lucknow 226014, India. Received Oct. 16, 2002; accepted Dec. 2, 2002.