Clin J Gastroenterol (2012) 5:247–250 DOI 10.1007/s12328-012-0317-2
CLINICAL REVIEW
Long-term monitoring of gastric atrophy and intestinal metaplasia after Helicobacter pylori eradication Kazunari Murakami • Masaaki Kodama • Yoshihumi Nakagawa • Kazuhiro Mizukami Tadayoshi Okimoto • Toshio Fujioka
•
Received: 30 May 2012 / Accepted: 31 May 2012 / Published online: 17 June 2012 Ó Springer 2012
Abstract Improvements of atrophy and intestinal metaplasia which is seen after H. pylori eradication may be regarded as an important factor of gastric cancer prevention. Although many studies reported the alteration of gastric mucosa after H. pylori eradication, most of the results do not agree. Recently, two meta-analyses showed significant improvement of atrophy (one study showed improvement in both corpus and antrum, and the other showed improvement in corpus but not in antrum), whereas improvement of intestinal metaplasia was not shown in either corpus or antrum. However, one reason why conclusions are different is considered to be that the observation period after eradication was short, and another reason is considered to be that almost studies examined only two points in gastric mucosa for histological analysis. Further examination with a greater number of subjects and with longer follow up period should be required to clarify the mechanism of gastric injury and improvement of gastric mucosa, especially atrophy and intestinal metaplasia after H. pylori eradication. Keywords Helicobacter pylori Eradication Atrophy Intestinal metaplasia Prevention of gastric cancer
Introduction Gastric atrophy and intestinal metaplasia are known to be precancerous lesions of gastric cancer caused by Helicobacter
K. Murakami (&) M. Kodama Y. Nakagawa K. Mizukami T. Okimoto T. Fujioka Department of Gastroenterology, Faculty of Medicine, Oita University, Hasama-machi, Oita 879-5593, Japan e-mail: [email protected]
pylori infection. In Japan, H. pylori eradication frequently produces positive results in terms of improvement of atrophy, but negative results are frequently apparent in other countries [1–4]. In addition to differences in the prevalence of this condition in Japan and other countries, this may also be partly due to differences in medical insurance systems and diagnostic endoscopy techniques. Inhibition of gastric carcinogenesis by H. pylori eradication not only depends on improving chronic active inflammation, but also requires the improvement of atrophy and intestinal metaplasia, which are regarded as precancerous lesions. In this study, we review the reports about histological changes after H. pylori eradication, and describe our study of the changes during long-term monitoring after eradication [5].
Positive reports for improvement in atrophy and intestinal metaplasia after H. pylori eradication Ito et al. [6] monitored 22 cases of gastric atrophy for 5 years after H. pylori eradication, and found that atrophy and intestinal metaplasia scores decreased significantly in both the gastric corpus and antrum in patients in whom eradication was successful. After 5 years, they also observed a decrease in intestinal metaplasia assessed endoscopically by methylene blue staining. As intestinal metaplasia occurs sporadically on the gastric mucosa, surface diagnosis by methylene blue staining is regarded as useful. Watanabe et al. [7] performed biopsies of the greater curvature of the central antrum and the greater curvature of the upper gastric corpus at 6 and 30 weeks after H. pylori eradication in 171 patients with peptic ulcers in whom eradication had been successful and 34 in whom it was unsuccessful. Although scores for inflammation,
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activity and atrophy all improved significantly in patients in whom eradication was successful, there were no significant improvements in those for whom it had been unsuccessful. In China, Zhou et al. [8] divided 552 H. pylori-positive patients into an eradication group and a control group, and followed these for 5 years, finding that whereas intestinal metaplasia of the antrum decreased or did not progress in the eradication group, significant progression of intestinal metaplasia was evident in the H. pylori-positive group. There was no significant improvement in atrophy in either the antrum or corpus after H. pylori eradication. Toyokawa et al. [9] took biopsies from five sites (the antrum, gastric angle, and the lower, central, and upper corpus) in 241 patients at a mean of 101 months after H. pylori eradication, and evaluated these samples histologically according to the updated Sydney system. A comparison between samples from before eradication and 5 and 10 years after eradication showed that atrophy improved significantly after 10 years in all locations other than the antrum, but that there was no significant improvement in intestinal metaplasia at any location, even after 10 years. Vannella et al. [10] monitored 300 patients with gastric atrophy of the corpus (192 positive, 108 negative for H. pylori) for a mean 5.2 years after H. pyloripositive patients had undergone eradication. There was a higher rate of improvement in atrophy of the corpus (21.3 vs. 0.9 %, p \ 0.00001) in H. pylori-positive when compared with H. pylori-negative patients, with a 52 % rate of improvement at between 2 and 8 years of follow-up in particular. Factors predicting improvement in atrophy of the corpus were mild atrophy [hazard ratio (HR) 2.14], moderate to severe inflammation (HR 5.3), and absence of intestinal metaplasia (HR 2.4). With respect to gastric cancer after H. pylori eradication, in a randomized controlled trial (RCT) Wong et al. [11] found no significant differences in the prevalence of gastric cancer between patients who underwent eradication and those who did not, but considered that eradication significantly inhibited the onset of cancer in patients without precancerous lesions such as severe atrophy, intestinal metaplasia, and dysplasia. Vannella et al.’s finding of a higher rate of improvement of the gastric mucosa in patients without severe atrophy or intestinal metaplasia is also extremely interesting.
Negative reports for improvement in atrophy or intestinal metaplasia after H. pylori eradication Forbes et al. [12] carried out endoscopic observations of 54 patients with duodenal ulcer, 32 of whom had undergone H. pylori eradication successfully and 22 unsuccessfully, for a mean of 7.1 years. In patients for whom eradication
123
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was successful, infiltration of the antral mucosa by inflammatory cells and neutrophils declined and mucus production increased, but there was no difference in atrophy irrespective of H. pylori status, nor was there any significant difference in intestinal metaplasia between the two groups, or any changes in this condition over time. Satoh et al. [13] monitored 20 patients with gastric atrophy for a mean of 17 months after H. pylori eradication, and found no significant differences in the severity of atrophy according to the updated Sydney system in either the antrum or corpus before and after eradication, as well as no changes in intestinal metaplasia in the corpus and an increase in the antrum. A comparison by van der Hulst et al. [14] of changes in the gastric mucosa in 77 non-ulcer dyspepsia (NUD) patients before and 1 year after successful H. pylori eradication for CagA-positive and negative strains found that atrophy was significantly more severe in patients with CagA-positive strains when compared with negative strains. However, they found no significant changes in atrophy or intestinal metaplasia after eradication, irrespective of CagA status.
Factors affecting evaluation of histological changes in gastric mucosa One possible reason for this divergence of opinion is differences in monitoring periods. In most studies, monitoring was carried out for short periods ranging from 6 months to \2 years, and in comparisons of two points before and after eradication the interim course is unclear. Including our own study, to date, there have been seven reports of follow-up lasting over 5 years [5, 6, 8–10, 12, 15]. However, disagreement between their results is also apparent. In terms of sample size, Ohkusa et al. [16] and Sung et al. [17] investigated 115 and 295 patients, respectively, while Toyokawa et al. [9] also monitored 260 patients, and long-term monitoring of large numbers of patients will be required in the future. In many studies, few points within the stomach were monitored, with little evaluation of the entire stomach mucosa. The updated Sydney system is now widely used worldwide for evaluating gastritis, and this recommends assessment at five points; the greater curvature of the antrum, the lesser curvature, the lesser curvature of the gastric angle, the lesser curvature of the corpus, and the greater curvature of the corpus. One study [9] investigated five points, although slightly different from these. But so far there have been no reports other than our own study [5] on post-eradication assessment at all five points recommended in the updated Sydney system. In Japan, the East Asian CagA strain, which is more strongly associated with gastric cancer, accounts for almost
Clin J Gastroenterol (2012) 5:247–250
all CagA polymorphisms [18, 19], which is an H. pylori virulence factor. Atrophy is significantly more severe in infection with the East Asian CagA strain, as compared with the Western or CagA-negative strains [20–22]. In our department, we carried out an immunohistological investigation using antibodies that react specifically with East Asian CagA [22], and found that 30 of 254 H. pyloripositive patients were negative. These were considered to represent the Western CagA strain or CagA-negative strains. Histologically, level of activity, atrophy and intestinal metaplasia were severe in patients with East Asian CagA H. pylori, suggesting severe mucosal damage. Differences due to virulence factor polymorphism may also be a cause of the variations in reports of post-eradication changes in different countries.
Our study of post-eradication long-term histological investigation We carried out a comparative investigation of 30 patients who had successfully undergone H. pylori eradication and from whom yearly biopsies were taken from five points [greater curvature of the antrum (A2), lesser curvature of the antrum (A1) lesser curvature of the gastric angle (IA), lesser curvature of the central corpus (B1), and greater curvature of the upper corpus (B2)] over a 10-year period [5]. We scored the severity of mononuclear cell infiltration, neutrophil infiltration, atrophy, and intestinal metaplasia on a 4-grade scale according to the updated Sydney system (0, none; 1, mild; 2, moderate; 3, marked), and compared the results between two time points. Inflammation scores decreased significantly at all five points 6 months after H. pylori eradication (p \ 0.001), and subsequently there was also a tendency for decreases. Activity score was almost zero at 6 months after eradication (p \ 0.001), with no subsequent changes. During long-term monitoring, atrophy scores decreased significantly at A1 at 6 years after H. pylori eradication, and at B2 at 6 months after eradication. At the remaining three points, scores exhibited a significant decrease at 1 year after eradication. Atrophy scores all displayed a tendency to decrease at all points up to 10 years after eradication. Marked improvement of atrophy at the greater curvature of the corpus in the present study was confirmed. Long-term monitoring of intestinal metaplasia found intense fluctuations in intestinal metaplasia scores at A2, A1, IA and B2 over a 10-year period, but no significant changes. At B2, although there was a slight tendency for scores to decline, there were no significant decreases when compared with before H. pylori eradication. At B1, however, a declining tendency was evident from 6 months after
249
eradication, and from 6 years after eradication, the decrease in scores was significant. A maximum of 6 years was required for significant improvement in atrophy and intestinal metaplasia to become evident, and there was pronounced variation in intestinal metaplasia scores at different locations, with a significant decrease apparent only at the lesser curvature of the corpus. This suggests that long-term, comprehensive five-point assessment of the inside of the stomach is desirable.
Recent meta-analyses In recent years, two meta-analyses of gastric mucosal changes following H. pylori eradication have been published [3, 4]. In a meta-analysis of eight studies, Rokkas et al. [3] found that there was significant improvement in atrophy of the antrum, with an odds ratio of 0.554 (p = 0.004) and atrophy of the corpus, with an odds ratio of 0.209 (p = 0.001), but no significant changes in intestinal metaplasia of the antrum, with an odds ratio of 0.795 (p = 0.140) or the corpus, with an odds ratio of 0.891 (p = 0.506). In their meta-analysis, Wang et al. [4] finally compared histological scores before and after H. pylori eradication from 12 studies covering 2658 subjects of analysis. They found that there was significant improvement of atrophy in the corpus, but not in the antrum. Intestinal metaplasia improved in the antrum in only one of nine studies, and there was no report of marked improvement in intestinal metaplasia in the corpus. From these, recent meta-analyses of post-eradication course covered evaluation of only two points of the stomach, and found no changes in intestinal metaplasia.
Conclusion We described changes over time in gastric atrophy and intestinal metaplasia after H. pylori eradication. Despite the problem of differences between sites, atrophy can be considered to improve after eradication, but opinion is divided on intestinal metaplasia. As our own results have shown, however, long-term, comprehensive histological testing of the stomach enables the identification of points where even improvement of intestinal metaplasia occurs. This suggests that such changes in the background mucosa result in the inhibition of gastric cancer after H. pylori eradication. Conflict of interest of interest.
The authors declare that they have no conflict
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References 1. Ito M, Takata S, Tatsugami M, Wada Y, Imagawa S, Matsumoto Y, et al. Clinical prevention of gastric cancer by Helicobacter pylori eradication therapy: a systematic review. J Gastroenterol. 2009;44:365–71. 2. Murakami K, Kodama M, Sato R, Okimoto T, Watanabe K, Fujioka T. Helicobacter pylori eradication and associated changes in the gastric mucosa. Expert Rev Anti Infect Ther. 2005;3:757–64. 3. Rokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. The long-term impact of Helicobacter pylori eradication on gastric histology: a systematic review and meta-analysis. Helicobacter. 2007;12(Suppl 2):32–8. 4. Wang J, Xu L, Shi R, Huang X, Li SW, Huang Z, et al. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion. 2011;83:253–60. 5. Kodama M, Murakami K, Okimoto T, Sato R, Uchida M, Abe T, Shiota S, Nakagawa Y, Mizukami K, Fujioka T. Ten-year prospective follow-up of histological changes at 5 points on the gastric mucosa as recommended by the updated Sydney system after Helicobacter pylori eradication. J Gastroenterol. 2012; 47:394–403. 6. Ito M, Haruma K, Kamada T, Mihara M, Kim S, Kitadai Y, et al. Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis. Aliment Pharmacol Ther. 2002; 16:1449–56. 7. Watanabe H, Yamaguchi N, Kuwayama H, Sekine C, Uemura N, Kaise M, et al. Improvement in gastric histology following Helicobacter pylori eradication therapy in Japanese peptic ulcer patients. J Int Med Res. 2003;31:362–9. 8. Zhou L, Sung JJ, Lin S, Jin Z, Ding S, Huang X, et al. A five-year follow-up study on the pathological changes of gastric mucosa after H. pylori eradication. Chin Med J. 2003;116:11–4. 9. Toyokawa T, Suwaki K, Miyake Y, Nakatsu M, Ando M. Eradication of Helicobacter pylori infection improved gastric mucosal atrophy and prevented progression of intestinal metaplasia, especially in the elderly population: a long-term prospective cohort study. J Gastroenterol Hepatol. 2010;25:544–7. 10. Vannella L, Lahner E, Bordi C, Pilozzi E, Di Giulio E, Corleto VD, Osborn J, Delle Fave G, Annibale B. Reversal of atrophic body gastritis after H. pylori eradication at long-term follow-up. Dig Liver Dis. 2011;43:295–9. 11. Wong BC, Lam SK, Wong WM, et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291:187–94.
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Clin J Gastroenterol (2012) 5:247–250 12. Forbes GM, et al. Long-term follow-up of gastric histology after Helicobacter pylori eradication. J Gastroenterol Hepatol. 1996; 11:670–3. 13. Satoh K, et al. A follow-up study of atrophic gastritis and intestinal metaplasia after eradication of Helicobacter pylori. Helicobacter. 1998;3:236–40. 14. van der Hulst RW, van der Ende A, Dekker FW, Ten Kate FJ, Weel JF, Keller JJ, Kruizinga SP, Dankert J, Tytgat GN. Effect of Helicobacter pylori eradication on gastritis in relation to cagA: a prospective 1-year follow-up study. Gastroenterology. 1997;113: 25–30. 15. Lahner E, Bordi C, Cattaruzza MS, Iannoni C, Milione M, Delle Fave G, et al. Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection. Aliment Pharmacol Ther. 2005;22:471–81. 16. Ohkusa T, Fujiki K, Takashimizu I, Kumagai J, Tanizawa T, Eishi Y, Yokoyama T, Watanabe M. Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med. 2001;134:380–6. 17. Sung JJ, Chung SC, Ling TK, Yung MY, Cheng AF, Hosking SW, Li AK. One-year follow-up of duodenal ulcers after 1-wk triple therapy for Helicobacter pylori. Am J Gastroenterol. 1994; 89(2):199–202. 18. Yamaoka Y, Kodama T, Kashima K, Graham DY, Sepulveda AR. Variants of the 30 region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol. 1998;36(8):2258–63. 19. Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, Hatakeyama M. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci USA. 2002;99(22):14428–33. 20. Azuma T, Yamazaki S, Yamakawa A, Ohtani M, Muramatsu A, Suto H, Ito Y, Dojo M, Yamazaki Y, Kuriyama M, Keida Y, Higashi H, Hatakeyama M. Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. J Infect Dis. 2004;189(5):820–7. 21. Satomi S, Yamakawa A, Matsunaga S, Masaki R, Inagaki T, Okuda T, Suto H, Ito Y, Yamazaki Y, Kuriyama M, Keida Y, Kutsumi H, Azuma T. Relationship between the diversity of the cagA gene of Helicobacter pylori and gastric cancer in Okinawa, Japan. J Gastroenterol. 2006;41(7):668–73. 22. Abe T, Kodama M, Murakami K, Matsunari O, Mizukami K, Inoue K, et al. Impact of Helicobacter pylori CagA diversity on gastric mucosal damage: an immunohistochemical study of East Asian type CagA. J Gastroenterol Hepatol. 2011;26:688–93.
CLINICAL REVIEW
Long-term monitoring of gastric atrophy and intestinal metaplasia after Helicobacter pylori eradication Kazunari Murakami • Masaaki Kodama • Yoshihumi Nakagawa • Kazuhiro Mizukami Tadayoshi Okimoto • Toshio Fujioka
•
Received: 30 May 2012 / Accepted: 31 May 2012 / Published online: 17 June 2012 Ó Springer 2012
Abstract Improvements of atrophy and intestinal metaplasia which is seen after H. pylori eradication may be regarded as an important factor of gastric cancer prevention. Although many studies reported the alteration of gastric mucosa after H. pylori eradication, most of the results do not agree. Recently, two meta-analyses showed significant improvement of atrophy (one study showed improvement in both corpus and antrum, and the other showed improvement in corpus but not in antrum), whereas improvement of intestinal metaplasia was not shown in either corpus or antrum. However, one reason why conclusions are different is considered to be that the observation period after eradication was short, and another reason is considered to be that almost studies examined only two points in gastric mucosa for histological analysis. Further examination with a greater number of subjects and with longer follow up period should be required to clarify the mechanism of gastric injury and improvement of gastric mucosa, especially atrophy and intestinal metaplasia after H. pylori eradication. Keywords Helicobacter pylori Eradication Atrophy Intestinal metaplasia Prevention of gastric cancer
Introduction Gastric atrophy and intestinal metaplasia are known to be precancerous lesions of gastric cancer caused by Helicobacter
K. Murakami (&) M. Kodama Y. Nakagawa K. Mizukami T. Okimoto T. Fujioka Department of Gastroenterology, Faculty of Medicine, Oita University, Hasama-machi, Oita 879-5593, Japan e-mail: [email protected]
pylori infection. In Japan, H. pylori eradication frequently produces positive results in terms of improvement of atrophy, but negative results are frequently apparent in other countries [1–4]. In addition to differences in the prevalence of this condition in Japan and other countries, this may also be partly due to differences in medical insurance systems and diagnostic endoscopy techniques. Inhibition of gastric carcinogenesis by H. pylori eradication not only depends on improving chronic active inflammation, but also requires the improvement of atrophy and intestinal metaplasia, which are regarded as precancerous lesions. In this study, we review the reports about histological changes after H. pylori eradication, and describe our study of the changes during long-term monitoring after eradication [5].
Positive reports for improvement in atrophy and intestinal metaplasia after H. pylori eradication Ito et al. [6] monitored 22 cases of gastric atrophy for 5 years after H. pylori eradication, and found that atrophy and intestinal metaplasia scores decreased significantly in both the gastric corpus and antrum in patients in whom eradication was successful. After 5 years, they also observed a decrease in intestinal metaplasia assessed endoscopically by methylene blue staining. As intestinal metaplasia occurs sporadically on the gastric mucosa, surface diagnosis by methylene blue staining is regarded as useful. Watanabe et al. [7] performed biopsies of the greater curvature of the central antrum and the greater curvature of the upper gastric corpus at 6 and 30 weeks after H. pylori eradication in 171 patients with peptic ulcers in whom eradication had been successful and 34 in whom it was unsuccessful. Although scores for inflammation,
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activity and atrophy all improved significantly in patients in whom eradication was successful, there were no significant improvements in those for whom it had been unsuccessful. In China, Zhou et al. [8] divided 552 H. pylori-positive patients into an eradication group and a control group, and followed these for 5 years, finding that whereas intestinal metaplasia of the antrum decreased or did not progress in the eradication group, significant progression of intestinal metaplasia was evident in the H. pylori-positive group. There was no significant improvement in atrophy in either the antrum or corpus after H. pylori eradication. Toyokawa et al. [9] took biopsies from five sites (the antrum, gastric angle, and the lower, central, and upper corpus) in 241 patients at a mean of 101 months after H. pylori eradication, and evaluated these samples histologically according to the updated Sydney system. A comparison between samples from before eradication and 5 and 10 years after eradication showed that atrophy improved significantly after 10 years in all locations other than the antrum, but that there was no significant improvement in intestinal metaplasia at any location, even after 10 years. Vannella et al. [10] monitored 300 patients with gastric atrophy of the corpus (192 positive, 108 negative for H. pylori) for a mean 5.2 years after H. pyloripositive patients had undergone eradication. There was a higher rate of improvement in atrophy of the corpus (21.3 vs. 0.9 %, p \ 0.00001) in H. pylori-positive when compared with H. pylori-negative patients, with a 52 % rate of improvement at between 2 and 8 years of follow-up in particular. Factors predicting improvement in atrophy of the corpus were mild atrophy [hazard ratio (HR) 2.14], moderate to severe inflammation (HR 5.3), and absence of intestinal metaplasia (HR 2.4). With respect to gastric cancer after H. pylori eradication, in a randomized controlled trial (RCT) Wong et al. [11] found no significant differences in the prevalence of gastric cancer between patients who underwent eradication and those who did not, but considered that eradication significantly inhibited the onset of cancer in patients without precancerous lesions such as severe atrophy, intestinal metaplasia, and dysplasia. Vannella et al.’s finding of a higher rate of improvement of the gastric mucosa in patients without severe atrophy or intestinal metaplasia is also extremely interesting.
Negative reports for improvement in atrophy or intestinal metaplasia after H. pylori eradication Forbes et al. [12] carried out endoscopic observations of 54 patients with duodenal ulcer, 32 of whom had undergone H. pylori eradication successfully and 22 unsuccessfully, for a mean of 7.1 years. In patients for whom eradication
123
Clin J Gastroenterol (2012) 5:247–250
was successful, infiltration of the antral mucosa by inflammatory cells and neutrophils declined and mucus production increased, but there was no difference in atrophy irrespective of H. pylori status, nor was there any significant difference in intestinal metaplasia between the two groups, or any changes in this condition over time. Satoh et al. [13] monitored 20 patients with gastric atrophy for a mean of 17 months after H. pylori eradication, and found no significant differences in the severity of atrophy according to the updated Sydney system in either the antrum or corpus before and after eradication, as well as no changes in intestinal metaplasia in the corpus and an increase in the antrum. A comparison by van der Hulst et al. [14] of changes in the gastric mucosa in 77 non-ulcer dyspepsia (NUD) patients before and 1 year after successful H. pylori eradication for CagA-positive and negative strains found that atrophy was significantly more severe in patients with CagA-positive strains when compared with negative strains. However, they found no significant changes in atrophy or intestinal metaplasia after eradication, irrespective of CagA status.
Factors affecting evaluation of histological changes in gastric mucosa One possible reason for this divergence of opinion is differences in monitoring periods. In most studies, monitoring was carried out for short periods ranging from 6 months to \2 years, and in comparisons of two points before and after eradication the interim course is unclear. Including our own study, to date, there have been seven reports of follow-up lasting over 5 years [5, 6, 8–10, 12, 15]. However, disagreement between their results is also apparent. In terms of sample size, Ohkusa et al. [16] and Sung et al. [17] investigated 115 and 295 patients, respectively, while Toyokawa et al. [9] also monitored 260 patients, and long-term monitoring of large numbers of patients will be required in the future. In many studies, few points within the stomach were monitored, with little evaluation of the entire stomach mucosa. The updated Sydney system is now widely used worldwide for evaluating gastritis, and this recommends assessment at five points; the greater curvature of the antrum, the lesser curvature, the lesser curvature of the gastric angle, the lesser curvature of the corpus, and the greater curvature of the corpus. One study [9] investigated five points, although slightly different from these. But so far there have been no reports other than our own study [5] on post-eradication assessment at all five points recommended in the updated Sydney system. In Japan, the East Asian CagA strain, which is more strongly associated with gastric cancer, accounts for almost
Clin J Gastroenterol (2012) 5:247–250
all CagA polymorphisms [18, 19], which is an H. pylori virulence factor. Atrophy is significantly more severe in infection with the East Asian CagA strain, as compared with the Western or CagA-negative strains [20–22]. In our department, we carried out an immunohistological investigation using antibodies that react specifically with East Asian CagA [22], and found that 30 of 254 H. pyloripositive patients were negative. These were considered to represent the Western CagA strain or CagA-negative strains. Histologically, level of activity, atrophy and intestinal metaplasia were severe in patients with East Asian CagA H. pylori, suggesting severe mucosal damage. Differences due to virulence factor polymorphism may also be a cause of the variations in reports of post-eradication changes in different countries.
Our study of post-eradication long-term histological investigation We carried out a comparative investigation of 30 patients who had successfully undergone H. pylori eradication and from whom yearly biopsies were taken from five points [greater curvature of the antrum (A2), lesser curvature of the antrum (A1) lesser curvature of the gastric angle (IA), lesser curvature of the central corpus (B1), and greater curvature of the upper corpus (B2)] over a 10-year period [5]. We scored the severity of mononuclear cell infiltration, neutrophil infiltration, atrophy, and intestinal metaplasia on a 4-grade scale according to the updated Sydney system (0, none; 1, mild; 2, moderate; 3, marked), and compared the results between two time points. Inflammation scores decreased significantly at all five points 6 months after H. pylori eradication (p \ 0.001), and subsequently there was also a tendency for decreases. Activity score was almost zero at 6 months after eradication (p \ 0.001), with no subsequent changes. During long-term monitoring, atrophy scores decreased significantly at A1 at 6 years after H. pylori eradication, and at B2 at 6 months after eradication. At the remaining three points, scores exhibited a significant decrease at 1 year after eradication. Atrophy scores all displayed a tendency to decrease at all points up to 10 years after eradication. Marked improvement of atrophy at the greater curvature of the corpus in the present study was confirmed. Long-term monitoring of intestinal metaplasia found intense fluctuations in intestinal metaplasia scores at A2, A1, IA and B2 over a 10-year period, but no significant changes. At B2, although there was a slight tendency for scores to decline, there were no significant decreases when compared with before H. pylori eradication. At B1, however, a declining tendency was evident from 6 months after
249
eradication, and from 6 years after eradication, the decrease in scores was significant. A maximum of 6 years was required for significant improvement in atrophy and intestinal metaplasia to become evident, and there was pronounced variation in intestinal metaplasia scores at different locations, with a significant decrease apparent only at the lesser curvature of the corpus. This suggests that long-term, comprehensive five-point assessment of the inside of the stomach is desirable.
Recent meta-analyses In recent years, two meta-analyses of gastric mucosal changes following H. pylori eradication have been published [3, 4]. In a meta-analysis of eight studies, Rokkas et al. [3] found that there was significant improvement in atrophy of the antrum, with an odds ratio of 0.554 (p = 0.004) and atrophy of the corpus, with an odds ratio of 0.209 (p = 0.001), but no significant changes in intestinal metaplasia of the antrum, with an odds ratio of 0.795 (p = 0.140) or the corpus, with an odds ratio of 0.891 (p = 0.506). In their meta-analysis, Wang et al. [4] finally compared histological scores before and after H. pylori eradication from 12 studies covering 2658 subjects of analysis. They found that there was significant improvement of atrophy in the corpus, but not in the antrum. Intestinal metaplasia improved in the antrum in only one of nine studies, and there was no report of marked improvement in intestinal metaplasia in the corpus. From these, recent meta-analyses of post-eradication course covered evaluation of only two points of the stomach, and found no changes in intestinal metaplasia.
Conclusion We described changes over time in gastric atrophy and intestinal metaplasia after H. pylori eradication. Despite the problem of differences between sites, atrophy can be considered to improve after eradication, but opinion is divided on intestinal metaplasia. As our own results have shown, however, long-term, comprehensive histological testing of the stomach enables the identification of points where even improvement of intestinal metaplasia occurs. This suggests that such changes in the background mucosa result in the inhibition of gastric cancer after H. pylori eradication. Conflict of interest of interest.
The authors declare that they have no conflict
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