Fundic gland polyps and gynecological malignancies

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Letters to the Editor

Reprint requests and correspondence: Pankaj Singh, 76-04 270th Street, New Hyde Park, NY 11040. Received Nov. 6, 2000; accepted Jan. 8, 2001.

Response to Drs. Singh et al. TO THE EDITOR: We are deeply thankful for the interest and comments made by Singh and colleagues. We believe there was a mistake in the reading and analysis of our study, because we did not conclude that bacterial infection in cirrhotics is not dependent on the etiology. Our findings state clearly that bacterial infections are more frequent in alcoholic cirrhotics than in nonalcoholics (p ⫽ 0.02). Although it was not reported in our study, of 78 alcoholic cirrhotics with infection, 66 (84.7%) were drinking actively up to the moment of diagnosis of infection, and nine (11.5%) were abstinent. Information could not be confirmed for three (3.8%) patients. Dr. Singh and colleagues rightly state that acute exposure to ethanol impairs the immune system (1–3). However, it is still unclear whether such alterations in the immune system are reversible following the discontinuation of the chronic use of alcohol and how long it take for this to occur. Despite the fact that active alcoholism may be a predisposing factor for the acquisition of infections, many other factors are also responsible for the higher prevalence of bacterial infection in cirrhotics. Heitor Rosa, M.D. Ame´rico O. Silve´rio, M.D. Rafael F. Perini, M.D. Claudia Barruda, M.D. Department of Gastroenterology and Hepatology Federal University of Goia´s School of Medicine Goiaˆnia, Brazil

REFERENCES 1. Mirland B, Mirland J. Reduced Fc receptor function in human monocytes exposed to ethanol in vitro. Alcohol 1984;19:211–7. 2. Bode C, Kugler V, Bode JC. Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J Hepatol 1987;4:8 –14. 3. Singhal PC, Reddy K, Ding G, et al. Ethanol induced macrophage apoptosis: The role of TGF-␤. J Immunol 1991;162: 3031– 6.

Reprint requests and correspondence: Heitor Rosa, M.D., Federal University of Goia´s, School of Medicine, Rua 126, n. 21, Setor Sul, Goiaˆnia, GO 74093-080, Brazil. Received Dec. 26, 2000; accepted Jan. 8, 2001.

AJG – Vol. 96, No. 5, 2001

Re: Sørensen et al.: Low Dose Aspirin TO THE EDITOR: Dr. Sorensen and his group (1), in a retrospective analysis of low dose aspirin at the level of 150 mg/day, note the risk of upper GI bleeding with the low dose aspirin and other nonsteroidal drugs is high, at a rate ratio of 5.6, whereas the rate ratio is 2.6 in users of noncoated low dose aspirin as well as coated low dose aspirin. This study done retrospectively suggests that prophylactic low dose aspirin carries an increased risk of GI bleeding irrespective of whether it is coated or uncoated. I am pleased to note that the authors comment on a need to analyze the risk/benefit effect of low dose aspirin in any prophylactic treatment program, but retrospective study is never as convincing as a prospective study that is yet to be done with significant numbers of patients. In addition, dosing of 81 mg/day in coated or uncoated form is more commonly used in the United States and bears a dose-related phenomenon with GI toxicity (D. Petroski, unpublished data, May 10, 1993). Also, the type of coated aspirin studied was not mentioned (various products are available to physicians and the public for supervised or unsupervised use). Some suggest that enteric coating is not protective at a low dose (2). In summary, let us further analyze low dose prophylactic aspirin by establishing a good large prospective study and find the most effective and safest lowest dose aspirin needed. Let us not count out properly formulated enteric coating as an added safety feature just yet. Donald Petroski, M.D. MCP Hahnemann University School of Medicine Philadelphia, Pennsylvania

REFERENCES 1. Sørensen HT, Mellekjær L, Blott WJ, et al. Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin. Am J Gastroenterol 2000;95:2218 –24. 2. Kelly JP, Kaufman D, Jurgelon JM, et al. Risk of aspirinassociated major upper gastrointestinal bleeding with entericcoated or buffered product. Lancet 1996;348:1413– 6. Reprint requests and correspondence: Donald Petroski, M.D., Brachfeld Medical Associates, 218C Sunset Road, Willingboro, NJ 08046-1192. Received Oct. 16, 2000; accepted Jan. 8, 2001.

Fundic Gland Polyps and Gynecological Malignancies TO THE EDITOR: We read with interest the article by McGarrity et al. that appeared in a recent issue (1). The authors report the occurrence of a giant polyp of the prox-

AJG – May, 2001

imal stomach in a patient of a known kindred (2) of attenuated familial adenomatous polyposis (AFAP). Moreover, they found in their patient an association with endometrial and ovarian adenocarcinomas. As a group of pathologists deeply engaged in the pathology of fundic gland polyps (FGPs), we have, for a long time, studied the clinical associations of these polyps, whose etiology is still unknown more than 20 years since their first description (3). The really intriguing clinicopathological aspect of FGPs is that polyps with identical histology may arise in very different clinical settings. They have been described both in a sporadic form, predominantly in females during perimenopausal age (4, 5), and in a syndromic form, associated with FAP–Gardner’s syndrome (6). Patients with syndromic polyps usually have them discovered in the second to third decades of life, without gender prevalence, probably because of screening examination programs for FAP families. Unfortunately, this apparently easy clinical distinction between patients with sporadic and syndromic FGPs is blurred in patients with attenuated variants of FAP (AFAP). These patients share molecular defects on the proximal or distal ends of the APC gene, in a position different from that of classic FAP (7, 8). The AFAP patients are discovered at a later age than FAP patients; family history for colon cancer may not be so impressive relative to FAP patients; colonic adenomas are sparse (1–50, never ⬎100), with predilection for the right colon; colon cancer develops later (mean ⫽ 55 yr); and paradoxically, FGP prevalence is near 100%. Recently, Aprile et al. described a new association between FGPs and Zollinger-Allison syndrome (9, 10). Some years ago, studying a case series of sporadic FGPs (all of our patients had a negative family history of colon cancer, and 17% of them were also examined with colonoscopy) (11), we saw two cases that impressed us because of their unexpected gynecological malignancies. The two patients, both with a negative family history for colon cancer and negative colonoscopy, had a truly unexpected association between FGPs and serous ovarian cystoadenocarcinoma (12). No molecular studies were performed, unfortunately, and in our discussion we ruled out on clinical grounds alone an association with FAP or AFAP. After more experience with the possible variations in phenotype of AFAP patients, we would now be more cautious with our conclusions. In fact, the initial impression of Lynch et al. (13) was that the AFAP would be a variant of hereditary nonpolyposis colon cancer. In conclusion, the report by McGarrity et al. shows a truly original association, coupled with molecular analysis, between AFAP-associated FGPs and gynecological malignancy. Moreover, their article sheds new light on our old clinicopathological observation. We would now rewrite our old statement: “From the practical standpoint, we would recommend a cautious approach to every patient with FGPs,

Letters to the Editor

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with a series of clinico-instrumental examinations to rule out an associated malignancy, even outside the GI tract” (12). Paolo Declich, M.D. Monica Porcellati, M.D. Stefano Bellone, M.D. Luciana Ambrosiani, M.D. Enrico Tavani, M.D. Roberta Grassini, M.T. Service of Pathology Rho Hospital Rho, Italy

REFERENCES 1. McGarrity TJ, Ruggiero FM, Chey WY, et al. Giant fundic polyp complicating attenuated familial adenomatous polyposis. Am J Gastroenterol 2000;95:1824 – 8. 2. Lynch HT, Smyrk TC, Watson P. Hereditary flat adenoma syndrome: A variant of familial adenomatous polyposis? Dis Colon Rectum 1992;35:411–21. 3. Declich P, Ambrosiani L, Grassini R, et al. Fundic gland polyps: A still elusive entity on the eve of the year 2000. Pol J Pathol 2000;51:3– 8. 4. Elster K, Eidt H, Ottenjann R, et al. Dru¨senko¨rperzysten, eine polypoide la¨sion der magenschleimhaut. Dtsch Med Wochenschr 1977;102:183–7. 5. Lee RG, Burt RW. The histopathology of fundic gland polyps of the stomach. Am J Clin Pathol 1986;86:498 –503. 6. Watanabe H, Enjoji M, Yao T, et al. Gastric lesions in familial adenomatosis coli: Their incidence and histologic analysis. Hum Pathol 1978;9:269 – 83. 7. Lynch HT, Smyrk T, McGinn T, et al. Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP. Cancer 1995 76: 2427–33. 8. Gardner RJ, Kool D, Edkins E, et al. The clinical correlates of a 3⬘ truncating mutation (codons 1982-1983) in the adenomatous polyposis coli gene. Gastroenterology 1997;113:326 –31. 9. Aprile MR, Azzoni C, Gibril F, et al. Intramucosal cysts in the gastric body of patients with Zollinger-Ellison syndrome. Hum Pathol 2000;31:140 – 8. 10. Declich P, Bellone S, Ambrosiani L, et al. Fundic gland polyps: Do they arise as a by-product of hypergastrinemia in patients with Zollinger-Ellison syndrome? Hum Pathol 2000; 31:889 –90. 11. Declich P, Isimbaldi G, Sironi M, et al. Sporadic fundic gland polyps: An immunohistochemical study of their antigenic profile. Pathol Res Pract 1996;192:808 –15. 12. Declich P, Di Bella C, Assi A. Sporadic fundic gland polyps associated with serous papillary ovarian cystoadenocarcinomas: A report of two cases. Med Biol Environ 1995;23:93– 6. 13. Lynch HT, Smyrk TC, Lanspa SJ, et al. Flat adenomas in a cancer-prone kindred. J Natl Cancer Inst 1988;80:278 – 82.

Reprint requests and correspondence: Paolo Declich, M.D., Service of Pathology, Rho Hospital, Corso Europa 250, I-20017 Rho, Italy. Received Dec. 6, 2000; accepted Dec. 14, 2000.