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Sugimoto M, Murata M, Yamaoka Y. Chemoprevention of gastric cancer development after Helicobacter pylori eradication therapy in an East Asian population: Meta-analysis. World J Gastroenterol 2020; 26:1820-1840. [PMID: 32351296 PMCID: PMC7183870 DOI: 10.3748/wjg.v26.i15.1820] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 03/15/2020] [Accepted: 04/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is a risk factor for gastric cancer (GC), especially in East Asian populations. Most East Asian populations infected with H. pylori are at higher risk for GC than H. pylori-positive European and United States populations. H. pylori eradication therapy reduces gastric cancer risk in patients after endoscopic and operative resection for GC, as well as in non-GC patients with atrophic gastritis. AIM To clarify the chemopreventive effects of H. pylori eradication therapy in an East Asian population with a high incidence of GC. METHODS PubMed and the Cochrane library were searched for randomized control trials (RCTs) and cohort studies published in English up to March 2019. Subgroup analyses were conducted with regard to study designs (i.e., RCTs or cohort studies), country where the study was conducted (i.e., Japan, China, and South Korea), and observation periods (i.e., ≤ 5 years and > 5 years). The heterogeneity and publication bias were also measured. RESULTS For non-GC patients with atrophic gastritis and patients after resection for GC, 4 and 4 RCTs and 12 and 18 cohort studies were included, respectively. In RCTs, the median incidence of GC for the untreated control groups and the treatment groups was 272.7 (180.4-322.4) and 162.3 (72.5-588.2) per 100000 person-years in non-GC cases with atrophic gastritis and 1790.7 (406.5-2941.2) and 1126.2 (678.7-1223.1) per 100000 person-years in cases of after resection for GC. Compared with non-treated H. pylori-positive controls, the eradication groups had a significantly reduced risk of GC, with a relative risk of 0.67 [95% confidence interval (CI): 0.47-0.96] for non-GC patients with atrophic gastritis and 0.51 (0.36-0.73) for patients after resection for GC in the RCTs, and 0.39 (0.30-0.51) for patients with gastritis and 0.54 (0.44-0.67) for patients after resection in cohort studies. CONCLUSION In the East Asian population with a high risk of GC, H. pylori eradication effectively reduced the risk of GC, irrespective of past history of previous cancer.
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Affiliation(s)
- Mitsushige Sugimoto
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Sinjuku, Tokyo 1600023, Japan
| | - Masaki Murata
- Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto 6128555, Japan
| | - Yoshio Yamaoka
- Department of Gastroenterology, Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Oita 8795593, Japan
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Li L, Yu C. Helicobacter pylori Infection following Endoscopic Resection of Early Gastric Cancer. BIOMED RESEARCH INTERNATIONAL 2019; 2019:9824964. [PMID: 31737682 PMCID: PMC6816031 DOI: 10.1155/2019/9824964] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 07/29/2019] [Accepted: 08/20/2019] [Indexed: 12/14/2022]
Abstract
The role of Helicobacter pylori (H. pylori) infection in patients following endoscopic resection of early gastric cancer (EGC) remains unclear. This article presents a review of literature published in the past 15 years. H. pylori-mediated persistent methylation levels are associated with the development of metachronous gastric cancer. The methylation of certain specific genes can be used to identify patients with a high risk of metachronous gastric cancer even after H. pylori eradication. H. pylori eradication after endoscopic resection should be performed as early as possible for eradication success and prevention of metachronous precancerous lesions. Although whether the eradication of H. pylori could prevent the development of metachronous cancer after endoscopic resection is controversial, several meta-analyses concluded that H. pylori eradication could reduce the incidence of metachronous gastric cancer significantly. In addition, H. pylori eradication in gastric cancer survivors after endoscopic resection could reduce healthcare cost and save lives in a cost-effective way. Taken together, H. pylori eradication after endoscopic resection of EGC is recommended as prevention for metachronous precancerous lesions and metachronous gastric cancer.
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Affiliation(s)
- Lan Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Sugano K. Effect of Helicobacter pylori eradication on the incidence of gastric cancer: a systematic review and meta-analysis. Gastric Cancer 2019; 22:435-445. [PMID: 30206731 DOI: 10.1007/s10120-018-0876-0] [Citation(s) in RCA: 127] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 09/04/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is considered to be the most important risk factor for gastric cancer (GC). The International Agency for Research on Cancer reported that H. pylori eradication could reduce the risk of developing GC. Several clinical studies have investigated this relationship as well; however, their results are inconsistent owing to the varied inclusion criteria. To address the effect of H. pylori eradication on GC incidence, we conducted a comprehensive meta-analysis with several subgroup analyses to resolve these inconsistencies. METHODS We searched MEDLINE and Ichushi-Web to identify randomized control trial and cohort study articles (English or Japanese) through December 2016. Manual searches were also conducted to identify unlisted references in these databases. Eligible studies reported GC incidence as an outcome, with comparisons between H. pylori eradication and control groups. Subgroup analyses were conducted by country, conditions at baseline, and follow-up periods. RESULTS We selected 28 studies among 1583 references in the databases and 4 studies by manual searches. The H. pylori eradication group showed significantly lower risk of GC [odds ratio (OR) 0.46; 95% confidence interval 0.39-0.55]. The subgroup analyses indicated that the beneficial effect of eradication was greater in Japan (OR 0.39; 95% CI 0.31-0.49), particularly among those with benign conditions (OR 0.32; 95% CI 0.19-0.54), although none of them was statistically significant. However, reduction of gastric cancer after eradication was significantly greater (p = 0.01) in the groups with long-term (5 years or longer) follow-up (OR 0.32; 95% CI 0.24-0.43) as compared to those with shorter follow-up (less than 5 years) (OR 0.55; 95% CI 0.41-0.72). CONCLUSION Real world data showed that large-scale eradication therapy has been performed mostly for benign conditions in Japan. Since eradication effects in preventing gastric cancer are conceivably greater there, GC incidence may decline faster in Japan than expected from the previous meta-analyses data which were based on multi-national, mixed populations with differing screening quality and disease progression.
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Affiliation(s)
- Kentaro Sugano
- Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
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Xiao S, Li S, Zhou L, Jiang W, Liu J. Helicobacter pylori status and risks of metachronous recurrence after endoscopic resection of early gastric cancer: a systematic review and meta-analysis. J Gastroenterol 2019; 54:226-237. [PMID: 30251121 DOI: 10.1007/s00535-018-1513-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 09/13/2018] [Indexed: 02/07/2023]
Abstract
The impact of different Helicobacter pylori (H. pylori) status (H. pylori negative, H. pylori eradication and H. pylori persistence) on the development of metachronous gastric lesions after endoscopic resection of early gastric cancer is not well defined. Thus, a systematic review and meta-analysis was performed to investigate this relationship. Two authors independently searched the electronic databases (Pubmed, Embase, the Cochrane Library and Web of Science) through March 2018, without language restriction. Pooled risk ratio for metachronous gastric lesions with regard to H. pylori status was calculated using fixed- or random-effects models, and heterogeneity and publication bias were also measured. 20 eligible studies were finally identified in systematic review, and 17 out of 20 studies were further included in meta-analysis. H. pylori eradication was associated with overall 50% lower odds of metachronous events (RR = 0.50; 95 % CI 0.41-0.61). Pooled risk ratios for metachronous gastric neoplasm were 0.85 (95 % CI 0.43-1.68) between H. pylori-eradicated and -negative patients, and 0.63 (95 % CI 0.35-1.12) between H. pylori-negative and -persistent patients, respectively. In conclusion, based on the best available evidence, eradication of H. pylori can provide protection against secondary gastric neoplasm, and this quantitative benefit seemed greater than among asymptomatic individuals. Metachronous risk seems comparable between H. pylori-eradicated and -negative population, or between H. pylori-negative and -persistent patients.
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Affiliation(s)
- Shiyu Xiao
- Department of Gastroenterology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Sizhu Li
- Department of Gastroenterology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Liya Zhou
- Department of Gastroenterology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China.
| | - Wenjun Jiang
- Department of Gastroenterology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Jinzhe Liu
- Department of Gastroenterology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
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Fischbach W, Malfertheiner P. Helicobacter Pylori Infection. DEUTSCHES ARZTEBLATT INTERNATIONAL 2018; 115:429-436. [PMID: 29999489 PMCID: PMC6056709 DOI: 10.3238/arztebl.2018.0429] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 10/11/2017] [Accepted: 05/02/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Infection with Helicobacter pylori (H. pylori) is a major pathogenic factor for gastroduodenal ulcer disease and gastric carcinoma, as well as for other types of gastric and extragastric disease. As a result of changing epidemiologic conditions (e.g., immigration), changing resistance patterns with therapeutic implications, and new knowledge relating to the indications for pathogen eradication, the medical management of H. pylori is a dynamic process in need of periodic reassessment. METHODS This review is based on pertinent publications retrieved by a selective search in PubMed and the Cochrane Database, with particular attention to three international consensus reports and the updated German S2k guideline. RESULTS H. pylori is now dealt with as an infection, whether or not the infected individual has symptoms or suffers from and H.-pylori-induced illness. H.-pylori-associated dyspepsia and functional dyspepsia are distinct entities that can only be diagnosed when competing elements in the differential diagnosis have been ruled out. H. pylori can be detected with noninvasive methods (13C-urea breathing test, stool antigen detection) and with invasive methods (histology, culture, rapid urease test). An important consideration for treatment is that primary clarithromycin resistance is common in many groups of patients; in Germany, its prevalence is now 10.9%. Primary treatment can be with either standard triple therapy (clarithromycin and amoxicillin or metronidazole) or bismuth-containing quadruple therapy. Treatment for 10 to 14 days is more likely to eradicate the pathogen than treatment for 7 days. When H. pylori infection is initially diagnosed in a patient over age 50, gastritis risk stratification should be performed by means of endoscopic biopsy and histologic examination. CONCLUSION The new, clinically relevant developments that are presented and commented upon in this review now enable evidence-based management of H. pylori infection.
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Affiliation(s)
- Wolfgang Fischbach
- Department II, Gastroenterology and Oncology, Klinikum Aschaffenburg – Alzenau GmbH, Academic Teaching Hospital of the University of Würzburg
| | - Peter Malfertheiner
- Clinic for Gastroenterology, Hepatology, and Infectious Diseases, University Clinic Magdeburg
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Abe S, Oda I, Minagawa T, Sekiguchi M, Nonaka S, Suzuki H, Yoshinaga S, Bhatt A, Saito Y. Metachronous Gastric Cancer Following Curative Endoscopic Resection of Early Gastric Cancer. Clin Endosc 2017; 51:253-259. [PMID: 28920420 PMCID: PMC5997077 DOI: 10.5946/ce.2017.104] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Accepted: 07/27/2017] [Indexed: 12/13/2022] Open
Abstract
This review article summarizes knowledge about metachronous gastric cancer (MGC) occurring after curative endoscopic resection (ER) of early gastric cancer (EGC), treatment outcomes of patients who developed MGC, and efficacy of Helicobacter pylori eradication to prevent MGC. The incidence of MGC following curative ER increases over time and is higher than in patients undergoing gastrectomy. Increasing age and multifocal EGC are independent risk factors for developing MGC. An MGC following curative ER is usually a small (<20 mm) and differentiated intramucosal cancer. Most MGC lesions are found at an early stage on semiannual or annual surveillance endoscopy and are successfully treated by further ER, with excellent long-term outcomes. Eradication of H. pylori may reduce the risk of MGC following ER of EGC, but further prospective studies with long-term outcomes are required. Surveillance endoscopy following gastric ER should be continued indefinitely, due to the risk of MGC even after successful H. pylori eradication. Risk stratification and tailored endoscopic surveillance schedules need to be developed.
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Affiliation(s)
- Seiichiro Abe
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | | | - Masau Sekiguchi
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Satoru Nonaka
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Haruhisa Suzuki
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | | | - Amit Bhatt
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland, OH, USA
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
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Maehata Y, Nakamura S, Esaki M, Ikeda F, Moriyama T, Hida R, Washio E, Umeno J, Hirahashi M, Kitazono T, Matsumoto T. Characteristics of Primary and Metachronous Gastric Cancers Discovered after Helicobacter pylori Eradication: A Multicenter Propensity Score-Matched Study. Gut Liver 2017; 11:628-634. [PMID: 28395508 PMCID: PMC5593324 DOI: 10.5009/gnl16357] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 09/08/2016] [Accepted: 11/09/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND/AIMS Gastric cancers develop even after successful Helicobacter pylori eradication. We aimed to clarify the characteristics of early gastric cancers discovered after H. pylori eradication. METHODS A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dissection were included. After matching the propensity score, we retrospectively investigated the clinicopathological features of 192 patients, including 96 patients who had undergone successful H. pylori eradication (Hp-eradicated group) and 96 patients who had active H. pylori infection (Hp-positive group). RESULTS In the Hp-eradicated group, early gastric cancers were discovered 1 to 15 years (median, 4.1 years) after H. pylori eradication. Compared with Hp-positive patients, Hp-eradicated patients showed a more frequently depressed configuration (81% vs 53%, respectively, p<0.0001) and a higher trend toward submucosal invasion (18% vs 8%, respectively, p=0.051). A multivariable analysis revealed the macroscopic depressed type to be characteristics of early gastric cancers after H. pylori eradication. Among patients in the Hp-eradicated group, metachronous cancers showed less frequent depressed lesions (68% vs 84%, respectively, p=0.049) and smaller tumor sizes (median, 11 mm vs 14 mm, respectively, p=0.014) than primary cancers. CONCLUSIONS Early gastric cancers after H. pylori eradication are characterized by a depressed configuration. Careful follow-up endoscopies are necessary after H. pylori eradication.
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Affiliation(s)
- Yuji Maehata
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan
| | - Shotaro Nakamura
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka,
Japan
| | - Motohiro Esaki
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan
| | - Fumie Ikeda
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan
| | - Tomohiko Moriyama
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan
| | - Risa Hida
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan
| | - Ema Washio
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan
| | - Minako Hirahashi
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka,
Japan
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Rokkas T, Rokka A, Portincasa P. A systematic review and meta-analysis of the role of Helicobacter pylori eradication in preventing gastric cancer. Ann Gastroenterol 2017; 30:414-423. [PMID: 28655977 PMCID: PMC5479993 DOI: 10.20524/aog.2017.0144] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 03/04/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Increasing evidence has suggested that Helicobacter pylori (H. pylori) eradication might prevent the development of gastric cancer (GC). This systematic review and meta-analysis aimed to better explore the role of H. pylori eradication in preventing GC, with particular reference to patients with precancerous lesions at baseline histology. METHODS Searches for human studies were performed through October 2016 and risk ratios (RRs), were obtained. Heterogeneity between studies was estimated using the Cochran Q test and I2 values, whereas the possibility of publication bias was estimated with funnel plots. Additionally, we performed subgroup and sensitivity analyses. RESULTS In 26 studies suitable for meta-analysis (10 randomized controlled trials and 16 cohort studies) 52,363 subjects were included. The risk of GC among patients in whom H. pylori was successfully eradicated was significantly lower than that among controls: pooled RRs [95% CI] 0.56 [0.48-0.66], Z= -7.27, P=0.00001. This finding applied separately for randomized controlled trials (0.65 [0.51-0.84], Z= -3.33, P=0.0009) and for cohort studies (0.51 [0.42-0.62], Z= -6.63, P=0.00001). Concerning H. pylori eradication in patients with precancerous lesions, subgroup analyses showed that patients with non-atrophic or atrophic gastritis benefited from H. pylori eradication for the risk of GC development, whereas those with intestinal metaplasia or dysplasia did not. CONCLUSION H. pylori eradication is associated with a significantly lower risk of GC; this finding has significant implications for the prevention of this cancer. The benefit is maximized when H. pylori eradication is applied at early stages of the infection.
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Affiliation(s)
- Theodore Rokkas
- Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece (Theodore Rokkas)
| | - Androniki Rokka
- Department of Internal Medicine, “Aldo Moro” University, Bari Medical School, Bari, Italy (Androniki Rokka, Piero Pontincasa)
| | - Piero Portincasa
- Department of Internal Medicine, “Aldo Moro” University, Bari Medical School, Bari, Italy (Androniki Rokka, Piero Pontincasa)
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Kobayashi M, Sato Y, Terai S. Endoscopic surveillance of gastric cancers after Helicobacter pylori eradication. World J Gastroenterol 2015; 21:10553-62. [PMID: 26457015 PMCID: PMC4588077 DOI: 10.3748/wjg.v21.i37.10553] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/05/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
The incidence and mortality of gastric cancer remains high in East Asian countries. Current data suggest that Helicobacter pylori (H. pylori) eradication might be more effective for preventing gastric cancer in young people before they develop atrophic gastritis and intestinal metaplasia. However, the long-term effect of H. pylori eradication on metachronous cancer prevention after endoscopic resection (ER) of early gastric cancer remains controversial, with some discordance between results published for Japanese and Korean studies. The detection ability of synchronous lesions before ER and eradication of H. pylori directly influences these results. After eradication, some gastric cancers are more difficult to diagnose by endoscopy because of morphologic changes that lead to a flat or depressed appearance. Narrow-band imaging with magnifying endoscopy (NBI-ME) is expected to be useful for identifying metachronous cancers. However, some gastric cancers after eradication show a "gastritis-like" appearance under NBI-ME. The gastritis-like appearance correlates with the histological surface differentiation of the cancer tubules and superficial non-neoplastic epithelium atop or interspersed with the cancer. Till date, it remains unclear whether H. pylori eradication could prevent progression of gastric cancer. Until we can establish more useful endoscopic examination methodologies, regular endoscopic surveillance of high-risk groups is expected to be the most beneficial approach for detection.
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Bang CS, Baik GH, Shin IS, Kim JB, Suk KT, Yoon JH, Kim YS, Kim DJ. Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer. J Korean Med Sci 2015; 30:749-756. [PMID: 26028928 PMCID: PMC4444476 DOI: 10.3346/jkms.2015.30.6.749] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Accepted: 02/03/2015] [Indexed: 12/12/2022] Open
Abstract
Controversies persist regarding the effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer (EGC). The aim of this study was to assess the efficacy of Helicobacter pylori eradication after endoscopic resection of EGC for the prevention of metachronous gastric cancer. A systematic literature review and meta-analysis were conducted using the core databases PubMed, EMBASE, and the Cochrane Library. The rates of development of metachronous gastric cancer between the Helicobacter pylori eradication group vs. the non-eradication group were extracted and analyzed using risk ratios (RRs). A random effect model was applied. The methodological quality of the enrolled studies was assessed by the Risk of Bias table and by the Newcastle-Ottawa Scale. Publication bias was evaluated through the funnel plot with trim and fill method, Egger's test, and by the rank correlation test. Ten studies (2 randomized and 8 non-randomized/5,914 patients with EGC or dysplasia) were identified and analyzed. Overall, the Helicobacter pylori eradication group showed a RR of 0.467 (95% CI: 0.362-0.602, P < 0.001) for the development of metachronous gastric cancer after endoscopic resection of EGC. Subgroup analyses showed consistent results. Publication bias was not detected. Helicobacter pylori eradication after endoscopic resection of EGC reduces the occurrence of metachronous gastric cancer.
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Affiliation(s)
- Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - In Soo Shin
- College of Education, Jeonju University, Jeonju, Korea
| | - Jin Bong Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Jai Hoon Yoon
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Yeon Soo Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
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11
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Jung DH, Kim JH, Chung HS, Park JC, Shin SK, Lee SK, Lee YC. Helicobacter pylori Eradication on the Prevention of Metachronous Lesions after Endoscopic Resection of Gastric Neoplasm: A Meta-Analysis. PLoS One 2015; 10:e0124725. [PMID: 25915048 PMCID: PMC4411104 DOI: 10.1371/journal.pone.0124725] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Accepted: 03/04/2015] [Indexed: 12/24/2022] Open
Abstract
Background There is controversy about the effect of Helicobacter pylori (H. pylori) eradication on the prevention of metachronous gastric cancer after endoscopic resection (ER). Aims The aim of this study was to systematically evaluate the effect of H. pylori eradication on the prevention of metachronous gastric lesions after ER of gastric neoplasms. Methods We performed a systematic search of PubMed, EMBASE, the Cochrane Library, and MEDLINE that encompassed studies through April 2014. Our meta-analysis consisted of 10 studies, which included 5881 patients who underwent ER of gastric neoplasms. Results When we compared the incidence of metachronous lesions between H. pylori-eradicated and non-eradicated groups, H. pylori eradication significantly lowered the risk of metachronous lesions after ER of gastric neoplasms (five studies, OR = 0.392, 95% CI 0.259 – 0.593, P < 0.001). When we compared H. pylori-eradicated and persistent groups, again, H. pylori eradication significantly lowered the incidence of metachronous lesions after ER of gastric neoplasms (six studies, OR = 0.468, 95% CI 0.326 – 0.673, P < 0.001). There was no obvious heterogeneity across the analyzed studies. Conclusions This meta-analysis suggests a preventive role for H. pylori eradication for metachronous gastric lesions after ER of gastric neoplasms. Thus, H. pylori eradication should be considered if H. pylori infection is confirmed during ER.
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Affiliation(s)
- Da Hyun Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Soo Chung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Chul Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Kwan Shin
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Kil Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- * E-mail:
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12
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Dzinic SH, Chen K, Thakur A, Kaplun A, Daniel Bonfil R, Li X, Liu J, Margarida Bernardo M, Saliganan A, Back JB, Yano H, Schalk DL, Tomaszewski EN, Beydoun AS, Dyson G, Mujagic A, Krass D, Dean I, Mi QS, Heath E, Sakr W, Lum LG, Sheng S. Maspin expression in prostate tumor elicits host anti-tumor immunity. Oncotarget 2014; 5:11225-36. [PMID: 25373490 PMCID: PMC4294340 DOI: 10.18632/oncotarget.2615] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2014] [Accepted: 10/21/2014] [Indexed: 12/13/2022] Open
Abstract
The goal of the current study is to examine the biological effects of epithelial-specific tumor suppressor maspin on tumor host immune response. Accumulated evidence demonstrates an anti-tumor effect of maspin on tumor growth, invasion and metastasis. The molecular mechanism underlying these biological functions of maspin is thought to be through histone deacetylase inhibition, key to the maintenance of differentiated epithelial phenotype. Since tumor-driven stromal reactivities co-evolve in tumor progression and metastasis, it is not surprising that maspin expression in tumor cells inhibits extracellular matrix degradation, increases fibrosis and blocks hypoxia-induced angiogenesis. Using the athymic nude mouse model capable of supporting the growth and progression of xenogeneic human prostate cancer cells, we further demonstrate that maspin expression in tumor cells elicits neutrophil- and B cells-dependent host tumor immunogenicity. Specifically, mice bearing maspin-expressing tumors exhibited increased systemic and intratumoral neutrophil maturation, activation and antibody-dependent cytotoxicity, and decreased peritumoral lymphangiogenesis. These results reveal a novel biological function of maspin in directing host immunity towards tumor elimination that helps explain the significant reduction of xenograft tumor incidence in vivo and the clinical correlation of maspin with better prognosis of several types of cancer. Taken together, our data raised the possibility for novel maspin-based cancer immunotherapies.
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Affiliation(s)
- Sijana H. Dzinic
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - Kang Chen
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan
- Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan
- Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan
- Department of Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Detroit, Michigan
- Mucosal Immunology Studies Team, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland
| | - Archana Thakur
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan
| | - Alexander Kaplun
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Current address: BIOBASE Corporation, Beverly, Massachusetts
| | - R. Daniel Bonfil
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Urology, Wayne State University School of Medicine, Detroit, Michigan
| | - Xiaohua Li
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - Jason Liu
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - M. Margarida Bernardo
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - Allen Saliganan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Urology, Wayne State University School of Medicine, Detroit, Michigan
| | - Jessica B. Back
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan
| | - Hiroshi Yano
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan
| | - Dana L. Schalk
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan
| | - Elyse N. Tomaszewski
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan
| | - Ahmed S. Beydoun
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - Gregory Dyson
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan
| | - Adelina Mujagic
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - David Krass
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - Ivory Dean
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - Qing-Sheng Mi
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan
- Henry Ford Health Systems, Detroit, Michigan
| | - Elisabeth Heath
- Department of Urology, Wayne State University School of Medicine, Detroit, Michigan
- Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - Wael Sakr
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
| | - Lawrence G. Lum
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan
- Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan
- Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan
| | - Shijie Sheng
- Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan
- Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan
- Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan
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Mitsunaga A, Tagata T, Hamano T, Teramoto H, Kan M, Mitsunaga Y, Tobari M, Shirato I, Shirato M, Yoshida S, Shimada M, Nishino T. Metachronous early gastric cancer over a period of 13 years after eradication of Helicobacter pylori. Clin J Gastroenterol 2014; 7:490-5. [PMID: 25491907 PMCID: PMC4261136 DOI: 10.1007/s12328-014-0536-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Accepted: 10/21/2014] [Indexed: 12/30/2022]
Abstract
Stomach cancer can occur during chronic inflammation from Helicobacter pylori (HP) infection, and its occurrence can be suppressed by eradication of HP. However, the effects of suppressing stomach cancer by HP eradication are limited, and the cancer is known to recur even after eradication of this infection. Here, we report the case of a 56-year-old male patient with gastric cancer who, although undergoing HP eradication after treatment of early gastric cancer with endoscopy, experienced five metachronous cancer recurrences over a period of 13 years. Whether observation of patients who undergo eradication of HP due to peptic ulcers or chronic gastritis and patients who undergo eradication after endoscopic treatment for early gastric cancer should be performed at the same interval is an issue that must be addressed in the future. The appropriate observation period for each patient must be established while considering the burdens to the patient and from the medical economic perspective.
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Affiliation(s)
- Atsushi Mitsunaga
- Department of Endoscopy, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo, Chiba, 276-8524, Japan,
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14
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Shiotani A, Haruma K, Graham DY. Metachronous gastric cancer after successful Helicobacter pylori eradication. World J Gastroenterol 2014; 20:11552-11559. [PMID: 25206262 PMCID: PMC4155348 DOI: 10.3748/wjg.v20.i33.11552] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 12/30/2013] [Accepted: 05/28/2014] [Indexed: 02/06/2023] Open
Abstract
The high incidence of gastric cancer in Japan initially resulted in establishment of a country-wide gastric cancer screening program to detect early and treatable cancers. In 2013 countrywide Helicobacter pylori (H. pylori) eradication was approved coupled with endoscopy to assess for the presence of chronic gastritis. Current data support the notion that cure of the infection in those with non-atrophic gastritis will prevent development of gastric cancer. However, while progression to more severe damage is halted in those who have already developed, atrophic gastritis/gastric atrophy remain at risk for subsequent development of gastric cancer. That risk is directly related to the extent and severity of atrophic gastritis. Methods to stratify cancer risk include those based on endoscopic assessment of the atrophic border, histologic grading, and non-invasive methods based on serologic testing of pepsinogen levels. Continued surveillance is required because those with atrophic gastritis/gastric atrophy retain considerable gastric cancer risk even after H. pylori eradication. Those who have already experienced a resectable early gastric cancer are among those at highest risk as metachronous lesions are frequent even after H. pylori eradication. We review the role of H. pylori and effect of H. pylori eradication indicating the incidence and the predictive factors on development of metachronous cancer after endoscopic therapy of early gastric cancer. Studies to refine risk markers to stratify for risk, surveillance methods, intervals, and duration after successful H. pylori eradication, and whether adjuvant therapy would change risk are needed.
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Rollan A, Arab JP, Camargo MC, Candia R, Harris P, Ferreccio C, Rabkin CS, Gana JC, Cortés P, Herrero R, Durán L, García A, Toledo C, Espino A, Lustig N, Sarfatis A, Figueroa C, Torres J, Riquelme A. Management of Helicobacter pylori infection in Latin America: a Delphi technique-based consensus. World J Gastroenterol 2014; 20:10969-83. [PMID: 25152601 PMCID: PMC4138478 DOI: 10.3748/wjg.v20.i31.10969] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Revised: 03/21/2014] [Accepted: 05/23/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To optimize diagnosis and treatment guidelines for this geographic region, a panel of gastroenterologists, epidemiologists, and basic scientists carried out a structured evaluation of available literature. METHODS Relevant questions were distributed among the experts, who generated draft statements for consideration by the entire panel. A modified three-round Delphi technique method was used to reach consensus. Critical input was also obtained from representatives of the concerned medical community. The quality of the evidence and level of recommendation supporting each statement was graded according to United States Preventive Services Task Force criteria. RESULTS A group of ten experts was established. The survey included 15 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 50% in the first round, 73.3% in the second round and 100% in the third round. Main consensus recommendations included: (1) when available, urea breath and stool antigen test (HpSA) should be used for non-invasive diagnosis; (2) detect and eradicate Helicobacter pylori (H. pylori) in all gastroscopy patients to decrease risk of peptic ulcer disease, prevent o retard progression in patients with preneoplastic lesions, and to prevent recurrence in patients treated for gastric cancer; (3) further investigate implementation issues and health outcomes of H. pylori eradication for primary prevention of gastric cancer in high-risk populations; (4) prescribe standard 14-d triple therapy or sequential therapy for first-line treatment; (5) routinely assess eradication success post-treatment in clinical settings; and (6) select second- and third-line therapies according to antibiotic susceptibility testing. CONCLUSION These achievable steps toward better region-specific management can be expected to improve clinical health outcomes.
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