Murdani Abdullah, Abdul Aziz Rani, Ari F Syam, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia
Hiroyuki Ohtsuka, Tadashi Sato, Masayuki A Fujino, First Department of Medicine, Yamanashi Medical University, 4-4-37 Takeda, Kofu, Yamanashi 400-8510, Japan
Author contributions: Abdullah M, Ohtsuka H, Rani AA, Sato T, Syam AF, and Fujino MA contributed equally to this work.
Correspondence to: Murdani Abdullah, MD, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine University of Indonesia, Cipto Mangunkusumo Hospital, Jalan Diponegoro No. 71, Jakarta 10430, Indonesia. email@example.com
Telephone: +62-21-3153957 Fax: +62-21-3142454
Received: August 5, 2009 Revised: August 31, 2009
Accepted: September 7, 2009
Published online: October 21, 2009
AIM: To compare the effects of Helicobacter pylori (H pylori) infection on gastropathy between Indonesian and Japanese patients.
METHODS: Biopsy specimens were obtained during upper gastrointestinal endoscopy from 167 subjects (125 Indonesians and 42 Japanese) with uninvestigated symptoms of dyspepsia. The specimens were analyzed for the presence of H pylori using urease analysis, histopathology, and cell culture. The grade and activity of gastritis was assessed using the updated Sydney system.
RESULTS: The percentages of Indonesian and Japanese patients who were H pylori-positive at the antrum or body of the stomach were similar (68% and 59.5%, respectively; P = 0.316). Of those who were H pylori-positive, more Japanese patients than Indonesian patients had high levels of polymorphonuclear cells (P = 0.001), mononuclear cells (P = 0.013), glandular atrophy (P = 0.000), and intestinal metaplasia (P = 0.011) in both the antrum and body of the stomach.
CONCLUSION: The grade of gastritis and prevalence of mucosal atrophy and intestinal metaplasia were higher in Japanese patients. The difference between Indonesian and Japanese patients was significant.
© 2009 The WJG Press and Baishideng. All rights reserved.
Key words: Helicobacter pylori; Gastritis; Gastric cancer; Intestinal metaplasia; Atrophy
Peer reviewer: Dr. Philip Abraham, Professor, Consultant Gastroenterologist & Hepatologist, P. D. Hinduja National Hospital & Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai 400016, India
Abdullah M, Ohtsuka H, Rani AA, Sato T, Syam AF, Fujino MA. Helicobacter pylori infection and gastropathy: A comparison between Indonesian and Japanese patients. World J Gastroenterol 2009; 15(39): 4928-4931 Available from: URL: http://www.wjgnet.com/1007-9327/15/4928.asp DOI: http://dx.doi.org/10.3748/wjg.15.4928
There is abundant evidence of an association between Helicobacter pylori (H pylori) chronic infection and gastric cancer[1-5]. Some population-based studies show that high levels of H pylori infection are not necessarily accompanied by high mortality from gastric cancer, the so-called African[6-8] and Asian enigmas.
Indonesia and Japan have a similar prevalence of H pylori infection, but the incidence of gastric cancer is much higher in Japan than Indonesia. We conducted this cross-sectional study to compare the effects of H pylori infection on gastropathy between Indonesian and Japanese patients.
We consider the old concept of a cascade of mucosal changes that develop from acute/chronic gastritis to atrophic gastritis with intestinal metaplasia, and finally to dysplasia and gastric cancer, as proposed by P. Correa before the discovery of H pylori in the stomach. This is relevant because a difference in the pattern of H pylori-associated gastritis may explain the difference in the incidence of gastric cancer between Indonesia and Japan.
MATERIALS AND METHODS
Selection of patients
Patients were eligible to participate in the study if they were aged 18 years or older and had experienced uninvestigated symptoms of dyspepsia for at least 3 mo before enrollment. We defined dyspepsia as epigastric pain or discomfort perceived to originate in the upper gastrointestinal tract, including heartburn, acid regurgitation, excessive belching, abdominal bloating, nausea, a perception of abnormal or slow digestion, and early satiety[12,13]. Patients who experienced only heartburn and/or regurgitation were considered to have gastroesophageal reflux disease and were excluded. We also excluded patients who underwent upper gastrointestinal endoscopy and/or barium radiography less than 6 mo before the study or underwent these procedures on more than two separate occasions within the preceding 10 years, and patients who received eradication therapy for H pylori less than 6 mo before the study. We excluded patients who had undergone gastric surgery and those who had a documented history of ulcer disease, esophagitis, irritable bowel syndrome, or clinically significant abnormal results on laboratory analyses. None of the patients who enrolled in the study received treatment with nonsteroidal anti-inflammatory drugs, aspirin (> 325 mg/d), antibiotics, H2-receptor antagonists, proton pump inhibitors, misoprostol, sucralfate, prokinetic agents, or a bismuth compound within 14 d of the study.
From 1998 to 1999, 42 Japanese patients at Yamanashi Medical University Hospital, Koufu and 125 Indonesian patients at Metropolitan Medical Centre Hospital, Jakarta were diagnosed as having dyspepsia and were consecutively enrolled in the study. Informed consents were obtained from all of the patients. This study was reviewed and approved by the ethics committee of Faculty of Medicine University of Indonesia, who approved the protocol.
Intervention and measurements
All patients underwent an upper gastrointestinal endoscopy procedure to identify lesions and to obtain biopsy specimens from the antrum and body of the stomach. The grade and activity of gastritis was assessed using the updated Sydney system. The presence of H pylori in Indonesian patients was determined using histopathology, culture, and rapid urease test (RUT)[15,16]. The presence of H pylori in Japanese patients was determined using urease analysis, histopathology, cell culture, and RUT.
SPSS for Windows version 14 software (SPSS Inc., Chicago, Illinois) was used to analyze data. The prevalence of H pylori, polymorphonuclear cells, mononuclear cells, glandular atrophy, and intestinal metaplasia in the antrum and body of the stomach was analyzed using the c2 test or Fisher’s exact test, as appropriate.
Baseline characteristics of patients
We studied 125 Indonesian patients and 42 Japanese patients (males, 49.7%; females, 50.3%), of whom 110 (65.9%) tested positive for H pylori at the antrum and/or body of the stomach. The percentages of Indonesian and Japanese patients who were H pylori-positive at the antrum or body of the stomach were similar (68% and 59.5%, respectively; P = 0.316). The percentage of Japanese patients (52.4%) positive for H pylori at the antrum of the stomach was similar to that of Indonesian patients (68%) (P = 0 .068) but more Japanese patients were positive for H pylori at the body of the stomach (47.6%) than Indonesian patients (4%) (P < 0 .000) (Table 1).
Comparison of the effects of H pylori infection on gastropathy in Indonesian and Japanese patients who were positive for H pylori at the antrum and/or body of the stomach
Of patients who were H pylori-positive at the antrum and/or body of the stomach, more Japanese patients had high numbers of polymorphonuclear cells (P = 0.001) and mononuclear cells (P = 0.013), glandular atrophy (P = 0.000), and intestinal metaplasia (P = 0.011) than Indonesian patients (Table 2).
The development of gastric cancer is a long process and caused by many factors. Although H pylori is an important risk factor for gastric cancer, it is not the only factor that is involved in the etiology of gastric cancer. The association between gastric cancer and H pylori infection should be considered from the perspective of the multi-agent compound etiological theory. The H pylori infection rate is very high both in Indonesian and Japanese populations. The reason why Indonesians with H pylori infection do not develop gastric cancer to the same extent as their Japanese counterparts remains unknown.
The limitation of this study was that samples were obtained from a hospital population. Consequently, the results may not represent the community. However, this is the first study in which the effects of H pylori infection on gastropathy between Indonesian and Japanese patients were compared.
This study showed that the grade and activity of gastritis was higher among Japanese H pylori-positive patients. The prevalence of mucosal atrophy was also greater in Japanese H pylori-positive patients than in Indonesians. In addition, more Japanese H pylori-positive patients had severe atrophic gastritis and intestinal metaplasia than Indonesians. The difference between those two groups was significant statistically.
Japanese H pylori-positive patients had higher grade and activity of gastritis than Indonesian H pylori-positive patients. This finding was consistent with the study by Kang et al which observed differences in gastritis among Chinese, Malays, and Indians. This indicates that risk factors other than H pylori, such as genetic factors, are associated with the development of gastric cancer in Japanese patients. Moreover, atrophic gastritis in Japanese subjects originating from autoimmune gastritis may explain the high grade and activity of gastritis in these patients.
Another important risk factor is a dietary factor because this affects the rate of development of gastric cancer[19,20]. Japanese dietary habits such as high consumption of nitrite-rich, salty pickled vegetables and dried fish, and alcohol, are associated with atrophic gastritis and gastric cancer[21-24]. A low consumption of fresh fruit and raw vegetables may increase this risk. Such dietary habits may act in synergy with H pylori in causing gastric cancer. Migrants to countries with low gastric cancer rates have a diminished risk of gastric cancer.
In conclusion, although the prevalence of H pylori infection was similar in Indonesian and Japanese patients, the grade and activity of gastritis was higher in Japanese H pylori-positive patients. Moreover, the prevalence of mucosal atrophy and intestinal metaplasia was also higher in Japanese group. The difference between Indonesian and Japanese H pylori-positive patients was found to be significant. That difference may be responsible for the disparity in the incidence of gastric cancer in Indonesia and Japan. Further studies will be needed.
Although Helicobacter pylori (H pylori) has been classified as a class Ⅰ (or definite) carcinogen by WHO, the controversy as to why only a minority of infected patients develop distal adenocarcinoma still remains. Moreover, in Asian countries such as Indonesia, Japan, China, and Thailand, where the H pylori infection rates are similar, there is a significant difference regarding the outcome of gastric cancer. In the present study, the authors evaluated the transformation of gastric mucosa that is induced by H pylori infection prior to gastric cancer. The authors also compared the transformation between Indonesian and Japanese patients, the two countries that represent an “Asian paradox”.
Innovations and breakthroughs
By means of this study, the authors revealed that there was a significant difference in the grade and activity of gastritis and the prevalence of mucosal atrophy and intestinal metaplasia between Indonesian and Japanese H pylori-positive patients. These findings may be responsible for the difference in the incidence of gastric cancer in Indonesia and Japan.
This study indicates that there is a difference in host response between Indonesian and Japanese patients regarding H pylori infection.
The study is a good idea. Patients were enrolled consecutively with no selection bias. There was no difference in patients’ clinical features. The endoscopic features were assessed using OMED Database of Digestive Endoscopy. The histological differences were assessed using the Updated Sydney System by two observers with good interobserver degree of agreement.
1 Infection with Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum 1994; 61: 177-240 PubMed
2 Wang TC, Fox JG. Helicobacter pylori and gastric cancer: Koch’s postulates fulfilled? Gastroenterology 1998; 115: 780-783 PubMed
3 Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001; 345: 784-789 PubMed
4 Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC. Gastric cancer originating from bone marrow-derived cells. Science 2004; 306: 1568-1571 PubMed
5 Eslick GD. Helicobacter pylori infection causes gastric cancer? A review of the epidemiological, meta-analytic, and experimental evidence. World J Gastroenterol 2006; 12: 2991-2999 PubMed
6 Holcombe C. Helicobacter pylori: the African enigma. Gut 1992; 33: 429-431 PubMed
7 Lunet N, Barros H. Helicobacter pylori infection and gastric cancer: facing the enigmas. Int J Cancer 2003; 106: 953-960 PubMed
8 Tokudome S, Kuriki K, Suzuki S, Akasaka S, Kosaka H, Ishikawa H, Yoshimura T, Azuma T, Duc Van D, Cong Khan N, Sriamporn S, Wiangnon S, Soeripto, Triningsih FE, Moore MA. Re: helicobacter pylori infection and gastric cancer: facing the enigmas. Int J Cancer 2004; 112: 166-167; author reply 168-169 PubMed
9 Singh K, Ghoshal UC. Causal role of Helicobacter pylori infection in gastric cancer: an Asian enigma. World J Gastroenterol 2006; 12: 1346-1351 PubMed
10 Xiao SD. Seroepidemiology of H pylori infection and gastric cancer in western pacific area. J Gastroenterol Hepatol 2000; 15: H24 DOI
11 Correa P. A human model of gastric carcinogenesis. Cancer Res 1988; 48: 3554-3560 PubMed
12 Chiba N. Definitions of dyspepsia: time for a reappraisal. Eur J Surg Suppl 1998; 14-23 PubMed
13 Veldhuyzen van Zanten SJ, Flook N, Chiba N, Armstrong D, Barkun A, Bradette M, Thomson A, Bursey F, Blackshaw P, Frail D, Sinclair P. An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori. Canadian Dyspepsia Working Group. CMAJ 2000; 162: S3-S23 PubMed
14 Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996; 20: 1161-1181 PubMed
15 Blecker U, Lanciers S, Hauser B, Vandenplas Y. Diagnosis of Helicobacter pylori infection in adults and children by using the Malakit Helicobacter pylori, a commercially available enzyme-linked immunosorbent assay. J Clin Microbiol 1993; 31: 1770-1773 PubMed
16 Lage AP, Godfroid E, Fauconnier A, Burette A, Butzler JP, Bollen A, Glupczynski Y. Diagnosis of Helicobacter pylori infection by PCR: comparison with other invasive techniques and detection of cagA gene in gastric biopsy specimens. J Clin Microbiol 1995; 33: 2752-2756 PubMed
17 Xue FB, Xu YY, Wan Y, Pan BR, Ren J, Fan DM. Association of H pylori infection with gastric carcinoma: a Meta analysis. World J Gastroenterol 2001; 7: 801-804 PubMed
18 Kang JY, Wee A, Math MV, Guan R, Tay HH, Yap I, Sutherland IH. Helicobacter pylori and gastritis in patients with peptic ulcer and non-ulcer dyspepsia: ethnic differences in Singapore. Gut 1990; 31: 850-853 PubMed
19 Kato I, Tominaga S, Ito Y, Kobayashi S, Yoshii Y, Matsuura A, Kameya A, Kano T, Ikari A. A prospective study of atrophic gastritis and stomach cancer risk. Jpn J Cancer Res 1992; 83: 1137-1142 PubMed
20 Nomura A, Yamakawa H, Ishidate T, Kamiyama S, Masuda H, Stemmermann GN, Heilburn LK, Hankin JH. Intestinal metaplasia in Japan: association with diet. J Natl Cancer Inst 1982; 68: 401-405 PubMed
21 Tsugane S, Sasazuki S, Kobayashi M, Sasaki S. Salt and salted food intake and subsequent risk of gastric cancer among middle-aged Japanese men and women. Br J Cancer 2004; 90: 128-134 PubMed
22 Uppal R, Lateef SK, Korsten MA, Paronetto F, Lieber CS. Chronic alcoholic gastritis. Roles of alcohol and Helicobacter pylori. Arch Intern Med 1991; 151: 760-764 PubMed
23 Mahjub H, Sadri GH. Association between alcohol consumption and gastric cancer: a meta-analysis. J Res Health Sci 2007; 7: 63-72
24 Abdullah M, Kitahara F, Sato T, Kojima Y, Rani AA, Fujino MA. Lifestyle factors influencing serum pepsinogen levels in healthy Japanese: a prospective study. Ind J Gastroenterol Hepatol Dig Endos 2003; 4 : 6-10
25 Tsugane S, Sasazuki S. Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer 2007; 10: 75-83 PubMed
26 Haenszel W, Kurihara M. Studies of Japanese migrants. I. Mortality from cancer and other diseases among Japanese in the United States. J Natl Cancer Inst 1968; 40: 43-68 PubMed
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