- Email: [email protected]
Lack of effect of acid suppression therapy on gastric atrophy
242
CORRESPONDENCE
6. Dixon M, Genta R, Yardley JH, et al. Classification and grading of gastritis, the updated Sydney system. Am J Surg Pathol 1996;20: 1161–1181.
Editorss Note: Due to tight production deadlines, Dr. Lundell was unable to reply to the letter from Drs. Stolte and Meining.
Lack of Effect of Acid Suppression Therapy on Gastric Atrophy Dear Sir: Several points in the interesting study by Lundell et al.1 published recently are unclear. Perhaps the authors could clarify these points by their answers to the following questions. Many studies show that treatment with proton pump inhibitors,2,3 but also with H2-receptor antagonists and antacids,4 as well as vagotomy5 leads to aggravation of H. pylori gastritis of the corpus mucosa. It is all the more surprising to learn from Lundell’s study that, despite 3 years of treatment with omeprazole, the corpus gastritis remained unchanged compared with baseline and compared with the group of patients undergoing fundoplication. However, in the Materials and Methods section the authors state that the patients had been taking omeprazole before the start of the study. This means that the baseline histological inflammatory parameters of the corpus mucosa might already have been changed by the prior omeprazole treatment. This prompts the question: are histological data available for the omeprazole patient group before the start of the omeprazole treatment? Patients in the fundoplication group were also treated preoperatively with omeprazole. Are the relevant data before the first use of omeprazole available for this patient group as well? Was treatment with omeprazole discontinued before fundoplication and the preoperative biopsy-based diagnosis of gastritis, and if so, how much time elapsed between discontinuation and the harvesting of biopsy material for the histological classification and grading of gastritis? If the fundoplication had been performed in the absence of an interruption of the prior omeprazole treatment, we would have expected postoperative improvement in H. pylori gastritis parameters after discontinuation of omeprazole. Because this was not observed, the question must be asked whether postoperative use of proton pump inhibitors, H2-receptor antagonists, or antacids was excluded in this group of patients. Because the use of proton pump inhibitors can readily be established histologically on the basis of hypertrophy of parietal cells,6 we ask whether the authors also searched for such hypertrophy. This also applies to the omeprazole group, because, conversely, it ought to be established whether patient compliance had been good. Gastritis was graded in accordance with the Sydney system. In the Results section, however, information is provided only on intestinal metaplasia, atrophy, and changes in ‘‘inflammation.’’ It is not quite clear what exactly is meant by inflammation. The authors provide no data on the activity of the gastritis. Why? After all, granulocytes are the source of the reactive oxygen metabolites, the free radicals, that cause the damage to the surface epithelium, possibly leading to necrosis, and can have a mutagenic effect.7 Furthermore, an evaluation of gastritis on the basis of the Sydney system always requires biopsies from both the corpus and the antrum. The literature unequivocally shows that H. pylori is eliminated from the antrum in a high percentage of patients receiving proton pump inhibitor treatment,2,3,8 but it remains uncertain whether the density
GASTROENTEROLOGY Vol. 118, No. 1
of H. pylori colonization in the corpus increases. On the basis of their 3-year results, can the authors provide us with a definitive answer to this question? We miss comparative statements about the changes in the parameters of H. pylori gastritis in the antrum. Previous studies investigating this point have shown that the frequently demonstrable elimination of H. pylori results in considerable improvement in antral gastritis.2,3,8 Since most gastric carcinomas develop in the antrum, it might be speculated that this effect of proton pump inhibitor treatment might have a preventive effect on carcinogenesis. Such an effect is not to be expected from fundoplication with continued presence of H. pylori in the antrum. Would it be possible for the authors to provide data on the changes in the antral gastritis? In the Discussion, the authors reported on 11 H. pylori–negative patients with moderate-to-severe gastritis, but do not classify this gastritis. Did these patients have autoimmune or chemical gastritis? Or did they perhaps have H. pylori gastritis with focal elimination of H. pylori during omeprazole treatment? It is known that evaluation of H. pylori in biopsy specimens obtained from patients receiving proton pump inhibitors treatment is unreliable. Were additional methods of diagnosing H. pylori used? In an earlier study by Kuipers et al.,9 atrophic corpus gastritis occurred after 5 years of treatment with omeprazole. Because the histological examinations were done by one and the same pathologist in both the Kuipers study and the present study, it would be important to learn whether there were any differences in the grading of atrophy between the omeprazole group in the Kuipers study and that in the present study after 3 years. Because the histological evaluation for the Kuipers study was done several years before that for the present study, could it be that the pathologist’s grading of the atrophy might have changed under the influence of recent relevant critical publications? MANFRED STOLTE, M.D. Institut fu¨r Pathologie Klinikum Bayreuth Bayreuth, Germany ALEXANDER MEINING, M.D. Medical Department II Technical University of Munich Munich, Germany 1. Lundell L, Miettinen P, Myrvold HE, et al. Lack of effect of acid suppression therapy on gastric atrophy. Gastroenterology 1999; 117:319–326. 2. Solcia E, Villani L, Fiocca R, et al. Effect of eradication of Helicobacter pylori on gastritis in duodenal ulcer patients. Scand J Gastroenterol 1994;29(suppl 201):28–34. 3. Solte M, Meining A, Schmitz JM, et al. Changes in Helicobacter pylori–induced gastritis in the antrum and corpus during 12 months of treatment with omeprazole and lansoprazole in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1998; 12:247–253. 4. Meining A, Bosseckert H, Caspary WF, et al. H2-receptor antagonists and antacids have an aggravating effect on Helicobacter pylori gastritis in duodenal ulcer patients. Aliment Pharmacol Ther 1997;11:729–734. 5. Jonsson K, Stro¨m M, Bodemar G, et al. Histological changes in the gastroduodenal mucosa after long-term medical treatment with
January 2000
cimetidine or parietal cell vagotomy in patients with juxtapyloric ulcer disease. Scand J Gastroenterol 1988;23:433–441. 6. Stolte M, Bethke B. Elimination of Helicobacter pylori under treatment with omeprazole. Z Gastroenterol 1990;28:271–274. 7. Davies GR, Banatvala N, Collins CE, et al. Relationship between infective load of Helicobacter pylori and reactive oxygen metabolite production in antral mucosa. Scand J Gastroenterol 1994;29:419–424.
CORRESPONDENCE
243
8. Graham DY, Genta R, Evans DG, et al. Helicobacter pylori does not migrate from the antrum to the corpus in response to omeprazole. Am J Gastroenterol 1996;91:2120–2134. 9. Kuipers EJ, Lundell L, Klinkenberg-Knol EC, et al. Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. N Engl J Med 1996;304: 1018–1022.
Image of the Month Answer Answer to the Image of the Month Question (page 6): The barium esophagogram (see Question) showed a filling defect located eccentrically within the distal esophagus (large arrow), lying superior to an esophageal stricture. A barium tablet was seen abutting the defect superiorly (arrowhead). Contiguity with the esophageal wall could not be excluded, and its location, away from the most dependent portion of the esophagus (directly adjacent to the stricture), argued against the possibility of a foreign body. The patient denied history of impaction, and the history of weight loss and progressive dysphagia favored a malignant lesion. Both benign and malignant lesions of the esophagus may present as large polypoid lesions on an esophagogram. The benign lesions include leiomyomas, lipomas, fibrovascular polyps, and hamartomas. The classification of a malignant lesion with this presentation remains controversial, although all seem to share an epithelial origin. The terms most commonly used include carcinosarcoma, pseudosarcoma, and spindle cell carcinoma. Esophagogastroduodenoscopy surprisingly revealed a small plastic pig lodged over an esophageal stricture (left figure). The pig was removed endoscopically without complications (right figure) and with resolution of symptoms. Repeat endoscopy with dilation of the stricture was subsequently performed. The patient has done well but still cannot remember ever swallowing the plastic pig. For submission instructions, please see the Gastroenterology website (http://www.gastrojournal.org).
CORRESPONDENCE
6. Dixon M, Genta R, Yardley JH, et al. Classification and grading of gastritis, the updated Sydney system. Am J Surg Pathol 1996;20: 1161–1181.
Editorss Note: Due to tight production deadlines, Dr. Lundell was unable to reply to the letter from Drs. Stolte and Meining.
Lack of Effect of Acid Suppression Therapy on Gastric Atrophy Dear Sir: Several points in the interesting study by Lundell et al.1 published recently are unclear. Perhaps the authors could clarify these points by their answers to the following questions. Many studies show that treatment with proton pump inhibitors,2,3 but also with H2-receptor antagonists and antacids,4 as well as vagotomy5 leads to aggravation of H. pylori gastritis of the corpus mucosa. It is all the more surprising to learn from Lundell’s study that, despite 3 years of treatment with omeprazole, the corpus gastritis remained unchanged compared with baseline and compared with the group of patients undergoing fundoplication. However, in the Materials and Methods section the authors state that the patients had been taking omeprazole before the start of the study. This means that the baseline histological inflammatory parameters of the corpus mucosa might already have been changed by the prior omeprazole treatment. This prompts the question: are histological data available for the omeprazole patient group before the start of the omeprazole treatment? Patients in the fundoplication group were also treated preoperatively with omeprazole. Are the relevant data before the first use of omeprazole available for this patient group as well? Was treatment with omeprazole discontinued before fundoplication and the preoperative biopsy-based diagnosis of gastritis, and if so, how much time elapsed between discontinuation and the harvesting of biopsy material for the histological classification and grading of gastritis? If the fundoplication had been performed in the absence of an interruption of the prior omeprazole treatment, we would have expected postoperative improvement in H. pylori gastritis parameters after discontinuation of omeprazole. Because this was not observed, the question must be asked whether postoperative use of proton pump inhibitors, H2-receptor antagonists, or antacids was excluded in this group of patients. Because the use of proton pump inhibitors can readily be established histologically on the basis of hypertrophy of parietal cells,6 we ask whether the authors also searched for such hypertrophy. This also applies to the omeprazole group, because, conversely, it ought to be established whether patient compliance had been good. Gastritis was graded in accordance with the Sydney system. In the Results section, however, information is provided only on intestinal metaplasia, atrophy, and changes in ‘‘inflammation.’’ It is not quite clear what exactly is meant by inflammation. The authors provide no data on the activity of the gastritis. Why? After all, granulocytes are the source of the reactive oxygen metabolites, the free radicals, that cause the damage to the surface epithelium, possibly leading to necrosis, and can have a mutagenic effect.7 Furthermore, an evaluation of gastritis on the basis of the Sydney system always requires biopsies from both the corpus and the antrum. The literature unequivocally shows that H. pylori is eliminated from the antrum in a high percentage of patients receiving proton pump inhibitor treatment,2,3,8 but it remains uncertain whether the density
GASTROENTEROLOGY Vol. 118, No. 1
of H. pylori colonization in the corpus increases. On the basis of their 3-year results, can the authors provide us with a definitive answer to this question? We miss comparative statements about the changes in the parameters of H. pylori gastritis in the antrum. Previous studies investigating this point have shown that the frequently demonstrable elimination of H. pylori results in considerable improvement in antral gastritis.2,3,8 Since most gastric carcinomas develop in the antrum, it might be speculated that this effect of proton pump inhibitor treatment might have a preventive effect on carcinogenesis. Such an effect is not to be expected from fundoplication with continued presence of H. pylori in the antrum. Would it be possible for the authors to provide data on the changes in the antral gastritis? In the Discussion, the authors reported on 11 H. pylori–negative patients with moderate-to-severe gastritis, but do not classify this gastritis. Did these patients have autoimmune or chemical gastritis? Or did they perhaps have H. pylori gastritis with focal elimination of H. pylori during omeprazole treatment? It is known that evaluation of H. pylori in biopsy specimens obtained from patients receiving proton pump inhibitors treatment is unreliable. Were additional methods of diagnosing H. pylori used? In an earlier study by Kuipers et al.,9 atrophic corpus gastritis occurred after 5 years of treatment with omeprazole. Because the histological examinations were done by one and the same pathologist in both the Kuipers study and the present study, it would be important to learn whether there were any differences in the grading of atrophy between the omeprazole group in the Kuipers study and that in the present study after 3 years. Because the histological evaluation for the Kuipers study was done several years before that for the present study, could it be that the pathologist’s grading of the atrophy might have changed under the influence of recent relevant critical publications? MANFRED STOLTE, M.D. Institut fu¨r Pathologie Klinikum Bayreuth Bayreuth, Germany ALEXANDER MEINING, M.D. Medical Department II Technical University of Munich Munich, Germany 1. Lundell L, Miettinen P, Myrvold HE, et al. Lack of effect of acid suppression therapy on gastric atrophy. Gastroenterology 1999; 117:319–326. 2. Solcia E, Villani L, Fiocca R, et al. Effect of eradication of Helicobacter pylori on gastritis in duodenal ulcer patients. Scand J Gastroenterol 1994;29(suppl 201):28–34. 3. Solte M, Meining A, Schmitz JM, et al. Changes in Helicobacter pylori–induced gastritis in the antrum and corpus during 12 months of treatment with omeprazole and lansoprazole in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1998; 12:247–253. 4. Meining A, Bosseckert H, Caspary WF, et al. H2-receptor antagonists and antacids have an aggravating effect on Helicobacter pylori gastritis in duodenal ulcer patients. Aliment Pharmacol Ther 1997;11:729–734. 5. Jonsson K, Stro¨m M, Bodemar G, et al. Histological changes in the gastroduodenal mucosa after long-term medical treatment with
January 2000
cimetidine or parietal cell vagotomy in patients with juxtapyloric ulcer disease. Scand J Gastroenterol 1988;23:433–441. 6. Stolte M, Bethke B. Elimination of Helicobacter pylori under treatment with omeprazole. Z Gastroenterol 1990;28:271–274. 7. Davies GR, Banatvala N, Collins CE, et al. Relationship between infective load of Helicobacter pylori and reactive oxygen metabolite production in antral mucosa. Scand J Gastroenterol 1994;29:419–424.
CORRESPONDENCE
243
8. Graham DY, Genta R, Evans DG, et al. Helicobacter pylori does not migrate from the antrum to the corpus in response to omeprazole. Am J Gastroenterol 1996;91:2120–2134. 9. Kuipers EJ, Lundell L, Klinkenberg-Knol EC, et al. Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. N Engl J Med 1996;304: 1018–1022.
Image of the Month Answer Answer to the Image of the Month Question (page 6): The barium esophagogram (see Question) showed a filling defect located eccentrically within the distal esophagus (large arrow), lying superior to an esophageal stricture. A barium tablet was seen abutting the defect superiorly (arrowhead). Contiguity with the esophageal wall could not be excluded, and its location, away from the most dependent portion of the esophagus (directly adjacent to the stricture), argued against the possibility of a foreign body. The patient denied history of impaction, and the history of weight loss and progressive dysphagia favored a malignant lesion. Both benign and malignant lesions of the esophagus may present as large polypoid lesions on an esophagogram. The benign lesions include leiomyomas, lipomas, fibrovascular polyps, and hamartomas. The classification of a malignant lesion with this presentation remains controversial, although all seem to share an epithelial origin. The terms most commonly used include carcinosarcoma, pseudosarcoma, and spindle cell carcinoma. Esophagogastroduodenoscopy surprisingly revealed a small plastic pig lodged over an esophageal stricture (left figure). The pig was removed endoscopically without complications (right figure) and with resolution of symptoms. Repeat endoscopy with dilation of the stricture was subsequently performed. The patient has done well but still cannot remember ever swallowing the plastic pig. For submission instructions, please see the Gastroenterology website (http://www.gastrojournal.org).