Correspondence
Helicobacter pylori Infection and the Development of Gastric Cancer
N Engl J Med 2002; 346:65-67January 3, 2002
- Article
To the Editor:
Uemura et al. (Sept. 13 issue)1 make an important contribution to our understanding of the complications of Helicobacter pylori infection, but I have a question regarding the ethics of their study. The authors enrolled 1526 patients, of whom 1246 had H. pylori infection. Of the H. pylori–positive patients, 297 had gastric ulcers and 275 had duodenal ulcers. Hence, 572 patients had a condition for which treatment to eradicate the H. pylori infection is indicated. The remaining H. pylori–positive patients had gastric polyps and nonulcer dyspepsia, conditions for which eradication treatment is not currently indicated.
Eradication treatment was administered to 253 patients, but the authors do not specify whether these patients were among the 572 who had gastric ulcers or duodenal ulcers. Assuming that they were, there remained at least 319 patients who had a clinical indication for eradication therapy yet did not receive this treatment. More important, it appears that these remaining patients were not offered this therapy.
No gastric cancer developed after the eradication of H. pylori in the 253 infected patients who received this treatment. Therefore, at least 319 patients were exposed to an increased risk of gastric cancer even though they had an indication for eradication therapy that, if successful, would have eliminated the risk.
1 ReferencesRobert P. Blankfield, M.D.
Berea Health Center, Berea, OH 44017
rblankmd@aol.com 1
Uemura N ,Okamoto S ,Yamamoto S , et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001;345:784-789
Full Text | Web of Science | Medline
To the Editor:
Uemura et al. reported that corpus-predominant gastritis is a strong risk factor for gastric cancer in patients with H. pylori infection. They state that the updated Sydney system was used for classification, but at least five biopsy specimens are required in the Sydney system1; in their study, only two biopsy specimens from each patient were used. Is there evidence that such sampling is sufficient to diagnose corpus-predominant gastritis correctly?
The prevalence of corpus-predominant gastritis was relatively high in the study population. Although this finding may reflect a genetic predisposition in the Japanese population,2 it may also be related to long-term therapy with proton-pump inhibitors. Indeed, such therapy is associated with corpus-predominant gastritis in H. pylori–infected patients. Although it is uncertain whether the use of proton-pump inhibitors leads to atrophic gastritis,3,4 it is clearly associated with epithelial-cell hyperproliferation in the gastric body,5 which is a precancerous change.
Assuming that all 253 patients with H. pylori infection who received eradication therapy had gastric or duodenal ulcers, the remaining 319 patients with ulcers had ongoing infection. Were these patients treated with proton-pump inhibitors? If not, in how many patients did complications, such as bleeding, perforation, or stenosis, develop? What are the possible implications of therapy with proton-pump inhibitors with respect to the findings?
5 ReferencesAngelo Zullo, M.D.
Cesare Hassan, M.D.
Sergio Morini, M.D.
Nuovo Regina Margherita Hospital, 00153 Rome, Italy
zullo@tiscalinet.it 1
Dixon MF ,Genta RM ,Yardley JH ,Correa P . Classification and grading of gastritis: the updated Sydney System. Am J Surg Pathol 1996;20:1161-1181
CrossRef | Web of Science | Medline2
Schlemper RJ ,van der Werf SDJ ,Vandenbroucke JP ,Biemond I ,Lamers CBHW . Seroepidemiology of gastritis in Japanese and Dutch working populations: evidence for the development of atrophic gastritis that is not related to Helicobacter pylori. Gut 1995;37:199-204
CrossRef | Web of Science | Medline3
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;334:1018-1022
Full Text | Web of Science | Medline4
Genta RM . Acid suppression and gastric atrophy: sifting fact from fiction. Gut 1998;43:Suppl 1:S35-S38
CrossRef | Web of Science | Medline5
Berstad AE ,Hatlebakk JG ,Maartmann-Moe H ,Berstad A ,Brandt-zaeg P . Helicobacter pylori gastritis and epithelial cell proliferation in patients with reflux oesophagitis after treatment with lansoprazole. Gut 1997;41:740-747
CrossRef | Web of Science | Medline
To the Editor:
Several aspects of the study by Uemura et al. raise questions, and clarifications are needed before the authors' conclusion that gastric cancer develops only in H. pylori–infected persons can be accepted. First, was the study truly “blind”? No details are given regarding the endoscopists' knowledge of the patients' clinical history. Second, the reported incidence of H. pylori infection in patients with duodenal or gastric ulcers — 100 percent — is far higher than that generally reported, even in the Japanese population.1 Is there an explanation? Third, where were the cancers located? Previous studies have found no association between H. pylori infection and cancer of the gastric cardia.2,3 Because of the important public health implications of the report, these issues should be addressed.
3 ReferencesRamy Eid, M.D.
Steven F. Moss, M.D.
Rhode Island Hospital, Providence, RI 02903-1912
steven_moss_md@brown.edu 1
Sugiyama T ,Nishikawa K ,Komatsu Y , et al. Attributable risk of H. pylori in peptic ulcer disease: does declining prevalence of infection in general population explain increasing frequency of non-H. pylori ulcers? Dig Dis Sci 2001;46:307-310
CrossRef | Web of Science | Medline2
Helicobacter and Cancer Collaborative Group
CrossRef | Web of Science | Medline3
Huang JQ ,Sridhar S ,Chen Y ,Hunt RH . Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology 1998;114:1169-1179
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Uemura replies:
To the Editor: In response to Blankfield: I believe that the absence of H. pylori eradication therapy in our study was ethically acceptable. The medical insurance system in Japan — unlike that in the United States — did not cover the expenses of H. pylori eradication until very recently. In November 2000, the National Health Insurance System began to cover such expenses for patients with H. pylori–associated peptic ulcer. Before this time (when our study was conducted), patients had to bear all expenses, not only of anti–H. pylori agents but also of endoscopy and laboratory tests. In our observational study, the 253 of the 1246 infected patients who received eradication therapy selected that treatment of their own free will, whereas the other patients did not want to bear the expenses of such treatment. Fortunately, patients in Japan are no longer faced with this decision.
As Zullo et al. point out, no previous reports have shown that only two biopsy specimens are sufficient for the assessment of the degree of neutrophilic infiltration related to H. pylori infection. Unlike intestinal metaplasia or gastric mucosal atrophy, inflammation in the gastric mucosa is generally relatively uniform. The inflammation in the greater curvature of the antrum is the most advanced, and that in the greater curvature of the upper corpus the least advanced.1 We believe that the use of two biopsy specimens was sufficient.
The high incidence of corpus-predominant gastritis reflects a typical difference in gastric disease between Western and Japanese populations. When gastritis due to duodenal ulcer is excluded, the most prevalent gastritis associated with H. pylori infection in the West is the antrum-predominant type, whereas in Japan it is the corpus-predominant type.1,2 Our finding that the incidence of cancer was higher in patients with corpus-predominant gastritis than in those with antrum-predominant gastritis may be consistent with the finding that gastric cancer is more prevalent in Japan than in the West. Our data on the location of histologic gastritis were obtained during the entry period, when patients with peptic ulcer had yet to receive antiulcer agents such as proton-pump inhibitors. None of our patients underwent surgery for gastric hemorrhage, perforation, or stenosis.
In response to Eid and Moss: our patients underwent periodic endoscopic examinations for the early detection of cancer. The endoscopists examined each patient without knowledge of his or her clinical history. Although cases of H. pylori–negative peptic ulcer have been reported in Japan, most have been associated with treatment with nonsteroidal antiinflammatory drugs.3 We excluded eight patients with ulcers who did not have H. pylori infection because they had received such treatment. We detected gastric cancer in 36 patients; 3 had cancer of the cardia. We found no instances of cancer of the esophagus or esophagogastric junction or of adenocarcinoma in association with Barrett's esophagus, each of which is remotely associated with H. pylori infection.
3 ReferencesNaomi Uemura, M.D.
Kure Kyosai Hospital, Kure 737-8505, Japan
n-uemura@mua.biglobe. ne. jp 1
Sipponen P ,Stolte M . Clinical impact of routine biopsies of the gastric antrum and body. Endoscopy 1997;29:671-678
CrossRef | Web of Science | Medline2
Tabata H ,Fuchigami T ,Kobayashi H , et al. Helicobacter pylori and mucosal atrophy in patients with gastric cancer: a special study regarding the methods for detecting Helicobacter pylori. Dig Dis Sci 1999;44:2027-2034
CrossRef | Web of Science | Medline3
Sugiyama T ,Nishikawa K ,Komatsu Y , et al. Attributable risk of H. pylori in peptic ulcer disease: does declining prevalence of infection in general population explain increasing frequency of non-H. pylori ulcers? Dig Dis Sci 2001;46:307-310
CrossRef | Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
Xuemei Zhang, Rong Zhong, Zhi Zhang, Juxiang Yuan, Li Liu, Yan Wang, Susan Kadlubar, Fumin Feng, Xiaoping Miao. (2011) Interaction of Cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer. Molecular Carcinogenesis 50:11, 876-883
CrossRef2
Jung Hoon Lee, Nayoung Kim, Jae Il Chung, Kyung Phil Kang, Sang Hyup Lee, Young Soo Park, Jin-Hyeok Hwang, Jin-Wook Kim, Sook-Hyang Jeong, Dong Ho Lee, Hyun Chae Jung, In Sung Song. (2008) Long-term Follow up of Helicobacter pylori IgG Serology After Eradication and Reinfection Rate of H. pylori in South Korea. Helicobacter 13:4, 288-294
CrossRef3
Ji Youn Yoo, Nayoung Kim, Young Soo Park, Jin-Hyeok Hwang, Jin-Wook Kim, Sook Hyang Jeong, Hye Seung Lee, Cheeyoung Choe, Dong Ho Lee, Hyun Chae Jung, In Sung Song. (2007) Detection Rate of Helicobacter pylori Against a Background of Atrophic Gastritis and/or Intestinal Metaplasia. Journal of Clinical Gastroenterology 41:8, 751-755
CrossRef4
Hae Yeon Kang, Nayoung Kim, Young Soo Park, Jin-Hyeok Hwang, Jin-Wook Kim, Sook Hyang Jeong, Dong Ho Lee, Hyun Chae Jung, In Sung Song. (2006) Progression of Atrophic Gastritis and Intestinal Metaplasia Drives Helicobacter pylori Out of the Gastric Mucosa. Digestive Diseases and Sciences 51:12, 2310-2315
CrossRef
