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Kotelevets SM. Risks of anti- Helicobacter therapy and long-term therapy with antisecretory drugs. World J Gastroenterol 2025; 31:101933. [PMID: 39877710 PMCID: PMC11718649 DOI: 10.3748/wjg.v31.i4.101933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 11/08/2024] [Accepted: 12/06/2024] [Indexed: 12/30/2024] Open
Abstract
Helicobacter pylori (H. pylori) infection has a protective effect on gastroesophageal reflux disease (GERD). Both of these diseases have a very high incidence and prevalence. As a result, GERD often recurs after anti-Helicobacter therapy. The problem of effective treatment of H. pylori infection and GERD is that the main groups of drugs [proton pump inhibitors (PPIs) and potassium-competitive acid blockers] have the possibility of side effects with use. Such supposed side effects have no evidence in randomized controlled trials that comply with the principles of evidence-based medicine. Morphological changes in the gastric mucosa after long-term use of antisecretory drugs should be considered as compensatory mechanisms of sanogenesis. The greatest concern for doctors who treat patients with antisecretory drugs is the risk of gastric carcinogenesis. This article presents an analysis of morphological and pathophysiological changes that occur after long-term use of antisecretory drugs (PPIs). Hypertrophy (hyperplasia) of G cells, enterochromaffin-like cells and possible fundic gland polyps (hyperplasia) are compensatory mechanisms of sanogenesis during long-term treatment with PPIs. These mechanisms are of primary importance for rehabilitation and prevention of complications in patients with GERD, non-steroidal anti-inflammatory drugs-gastropathy and other diseases during long-term treatment with PPIs. Understanding the pathophysiological and morphological mechanisms of compensation and adaptation, the mechanisms of sanogenesis and carcinogenesis will increase the number of indications for long-term use of PPIs with a high level of efficiency and safety of treatment. In addition, understanding the pathophysiological and morphological mechanisms of compensation and adaptation, the mechanisms of sanogenesis will allow us to forecast the side effects of long-term use of potassium-competitive acid blockers.
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Affiliation(s)
- Sergey M Kotelevets
- Department of Therapy, North Caucasus State Academy, Cherkessk 369000, Russia
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Mamun TI, Younus S, Rahman MH. Gastric cancer-Epidemiology, modifiable and non-modifiable risk factors, challenges and opportunities: An updated review. Cancer Treat Res Commun 2024; 41:100845. [PMID: 39357127 DOI: 10.1016/j.ctarc.2024.100845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 08/27/2024] [Accepted: 09/20/2024] [Indexed: 10/04/2024]
Abstract
Gastric cancer represents a significant global health challenge due to its high mortality and incidence rates, particularly in Eastern Asia, Eastern Europe, and South America. This comprehensive review synthesizes the latest epidemiological data and explores both modifiable and non-modifiable risk factors associated with gastric cancer, aiming to delineate the multifactorial etiology of this disease. Modifiable risk factors include Helicobacter pylori infection, obesity, dietary habits, smoking and alcohol consumption, whereas nonmodifiable factors comprise genetic predispositions, age, family history and male gender. The interplay of these factors significantly impacts the risk and progression of gastric cancer, suggesting potential preventive strategies. The challenges in treating gastric cancer are considerable, largely because of the late-stage diagnosis and the heterogeneity of the disease, which complicate effective treatment regimens. Current treatment strategies involve a combination of surgery, chemotherapy, radiotherapy, and targeted therapies. The FLOT regimen (5-FU, Leucovorin, Oxaliplatin and Docetaxel) is now a standard for resectable cases in Europe and the US, showing superior survival and response rates over ECF and ECX regimens. For HER2-positive gastric cancer, trastuzumab combined with chemotherapy improves overall survival, as demonstrated by the ToGA trial. Additionally, immune checkpoint inhibitors like pembrolizumab and nivolumab offer promising results. However, the five-year survival rate remains low, underscoring the urgency for improved therapeutic approaches. Recent advancements in molecular biology and cancer genomics have begun to pave the way for personalized medicine in gastric cancer care, focusing on molecular targeted therapies and immunotherapy. This review also highlights the critical need for better screening methods that could facilitate early detection and treatment, potentially improving the prognosis. By integrating epidemiological insights with new therapeutic strategies, this article aims to thoroughly understand of gastric cancer's dynamics and outline a framework for future research and clinical management, advocating for a multidisciplinary approach to tackle this formidable disease.
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Affiliation(s)
- Tajul Islam Mamun
- Department of Epidemiology and Public Health, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
| | - Sabrina Younus
- Department of Pharmacy, University of Chittagong, Chattogram 4331, Bangladesh
| | - Md Hashibur Rahman
- Department of Physiology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh
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Wang Y, Wang Y, Han W, Han M, Liu X, Dai J, Dong Y, Sun T, Xu J. Intratumoral and fecal microbiota reveals microbial markers associated with gastric carcinogenesis. Front Cell Infect Microbiol 2024; 14:1397466. [PMID: 39355268 PMCID: PMC11442432 DOI: 10.3389/fcimb.2024.1397466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 08/28/2024] [Indexed: 10/03/2024] Open
Abstract
Background The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and reproducible diagnostic biomarkers for early GC are still lacking in multiple populations. Thus, this study aimed to characterize the gastrointestinal microbial communities involved in gastric carcinogenesis through a meta-analysis of multiple published and open datasets. Methods We analyzed 16S rRNA sequencing data from 1,642 gastric biopsy samples and 394 stool samples across 11 independent studies. VSEARCH, QIIME and R packages such as vegan, phyloseq, cooccur, and random forest were used for data processing and analysis. PICRUSt software was employed to predict functions. Results The α-diversity results indicated significant differences in the intratumoral microbiota of cancer patients compared to non-cancer patients, while no significant differences were observed in the fecal microbiota. Network analysis showed that the positive correlation with GC-enriched bacteria increased, and the positive correlation with GC-depleted bacteria decreased compared to healthy individuals. Functional analyses indicated that pathways related to carbohydrate metabolism were significantly enriched in GC, while biosynthesis of unsaturated fatty acids was diminished. Additionally, we investigated non-Helicobacter pylori (HP) commensals, which are crucial in both HP-negative and HP-positive GC. Random forest models, constructed using specific taxa associated with GC identified from the LEfSe analysis, revealed that the combination of Lactobacillus and Streptococcus included alone could effectively discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). This finding was also validated in an independent cohort (AUC = 0.7712). Conclusions This study examined the intratumoral and fecal microbiota of GC patients from a dual microecological perspective and identified Lactobacillus, Streptococcus, Roseburia, Faecalibacterium and Phascolarctobacterium as intratumoral and intestinal-specific co-differential bacteria. Furthermore, it confirmed the validity of the combination of Lactobacillus and Streptococcus as GC-specific microbial markers across multiple populations, which may aid in the early non-invasive diagnosis of GC.
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Affiliation(s)
- Yiwen Wang
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Yue Wang
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Wenjie Han
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Mengzhen Han
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Xiaolin Liu
- Department of Bioinformatics, Kanghui Biotechnology Co., Ltd., Shenyang, China
| | - Jianying Dai
- School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, China
| | - Yuesheng Dong
- School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, China
| | - Tao Sun
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Oncology Medicine, Key Laboratory of Liaoning Breast Cancer Research, Shenyang, Liaoning, China
- Department of Breast Medicine, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang, China
| | - Junnan Xu
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Breast Medicine, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang, China
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Sánchez-Quezada V, Velázquez-Guadarrama N, Mendoza-Elizalde S, Hernández-Iturriaga M, Landaverde PV, Loarca-Piña G. Bioaccessibility of bioactive compounds present in Persea americana Mill. seed ingredient during oral-gastric digestion with antibacterial capacity against Helicobacter pylori. JOURNAL OF ETHNOPHARMACOLOGY 2024; 331:118259. [PMID: 38685366 DOI: 10.1016/j.jep.2024.118259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 05/02/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE In ancient Mexican cultures, the Persea americana Mill seed has been used against gastrointestinal diseases, due to high concentrations of bioactive compounds. According to Traditional Mexican Medicine, P. americana seed aqueous infusion is used against roundworms, intestinal worms, parasites, and gastrointestinal problems, in a dose taken over three or four days. In addition, Mexican Society of Natural History indicates the traditional use of P. americana seed powder as an antiparasitic, and antibacterial. On the other hand, Helicobacter pylori infection is a factor associated with the development of gastric disease, peptic ulcers as well as some types of gastric lymphomas and gastric cancer in humans; in this way is necessary scientific evidence about P. americana seed effect in gastrointestinal disease. AIM OF THE STUDY The work aimed to evaluate bioactive compounds bioaccessibility and antimicrobial potential against Helicobacter pylori during oral-gastric digestion in vitro of food ingredient from Persea americana Mill. seed and elucidate the possible action mechanism using in silico tools. MATERIALS AND METHODS Initially, P. americana seed oil and aqueous extract of P. americana seed were obtained using ultrasound and maceration respectively, and the food ingredient from P. americana seed was obtained. The samples underwent oral-gastric digestions by the INFOGEST method, to continue identifying and quantifying the bioactive compounds by HPLC-DAD and GC-MS. The anti-Helicobacter pylori activity determination were used fourteen Helicobacter pylori clinical strains and reference strains by Susceptibility testing by Minimal Inhibition Concentration, Kinetics of Growth Inhibition of H. pylori, Urease Inhibitory Kinetic. Finally, to elucidate a possible action mechanism used in silico tools (Software AutoDock 4.2.6 and BioVia Discovery v.19.1.0.1.18287). RESULTS The lipophilic fraction of P. americana seed detected oleic acid, linoleic acid, and avocadenofuran compounds, and the phenolic fraction showed the presence of catechin, rutin, ellagic, and chlorogenic acid, among others. Phenolic compounds conformational changes during oral-gastric digestion due to mechanical and acid hydrolysis, while lipophilic compounds showed a 20% increase in the gastric phase. Persea americana Mill. seed ingredient (3.08 μg/mL) showed total in vitro inhibition of clinical and reference strains of H. pylori, likewise, the lipophilic fraction had a lower inhibition concentration (2.59 μg/mL) regardless of the strains. Among the mechanisms found in silico, inhibition of target proteins such as CagA, BabA, and MUC5 were observed, as virulence factors involving adherence and bacterial pathogenicity. CONCLUSIONS This research provides evidence that food ingredient from P. americana seed has antimicrobial in vitro potential against H. pylori clinical strains, through phenolic and mainly lipophilic compounds, opening new scientific evidence that supports the P. americana seed's traditional use.
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Affiliation(s)
- V Sánchez-Quezada
- Programa de Posgrado en Alimentos del Centro de la República (PROPAC), Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Querétaro, Mexico.
| | - N Velázquez-Guadarrama
- Unidad de Investigación en Enfermedades Infecciosas, Área de Genética Bacteriana, Hospital Infantil de México Federico Gómez, Mexico.
| | - S Mendoza-Elizalde
- Unidad de Investigación en Enfermedades Infecciosas, Área de Genética Bacteriana, Hospital Infantil de México Federico Gómez, Mexico.
| | - M Hernández-Iturriaga
- Programa de Posgrado en Alimentos del Centro de la República (PROPAC), Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Querétaro, Mexico.
| | - P Vázquez Landaverde
- Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA), Unidad Querétaro CICATA-IPN Querétaro, Mexico.
| | - G Loarca-Piña
- Programa de Posgrado en Alimentos del Centro de la República (PROPAC), Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Querétaro, Mexico.
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Cheung KS, Lyu T, Deng Z, Han S, Ni L, Wu J, Tan JT, Qin J, Ng HY, Leung WK, Seto WK. Vonoprazan Dual or Triple Therapy Versus Bismuth-Quadruple Therapy as First-Line Therapy for Helicobacter pylori Infection: A Three-Arm, Randomized Clinical Trial. Helicobacter 2024; 29:e13133. [PMID: 39244723 DOI: 10.1111/hel.13133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 08/16/2024] [Accepted: 08/20/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. METHODS This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance. RESULTS A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively. CONCLUSIONS VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection. TRIAL REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Tao Lyu
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Zijie Deng
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Shaowei Han
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Li Ni
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Juan Wu
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jing Tong Tan
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Jian Qin
- Department of Medicine, Yulin Traditional Chinese Medicine Hospital, Guangxi, China
| | - Ho Yu Ng
- School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Wai K Leung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
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Zhang X, Lai Y, Zhang L, Chen Z, Zhao J, Wang S, Li Z. Chitosan-modified molybdenum selenide mediated efficient killing of Helicobacter pylori and treatment of gastric cancer. Int J Biol Macromol 2024; 275:133599. [PMID: 38960263 DOI: 10.1016/j.ijbiomac.2024.133599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 06/09/2024] [Accepted: 06/29/2024] [Indexed: 07/05/2024]
Abstract
Helicobacter pylori (H. pylori) is one of the major causes of gastrointestinal diseases, including gastric cancer. However, the acidic environment of the stomach and H. pylori resistance severely impair the antimicrobial efficacy of oral drugs. Here, a biocompatible chitosan-modified molybdenum selenide (MoSe2@CS) was designed for the simultaneous photothermal treatment of H. pylori infection and gastric cancer. MoSe2@CS showed a photothermal conversion efficiency was as high as 45.7 %. In the H. pylori-infected mice model, MoSe2@CS displayed a high bacteriostasis ratio of 99.9 % upon near-infrared irradiation. The antimicrobial functionality was also proved by transcriptomic sequencing study, which showed that MoSe2@CS combined with NIR laser irradiation modulated the gene expression of a variety of H. pylori bioprocesses, including cell proliferation and inflammation-related pathways. Further gut flora analysis results indicated that MoSe2@CS mediated PTT of H. pylori did not affect the homeostasis of gut flora, which highlights its advantages over traditional antibiotic therapy. In addition, MoSe2@CS exhibited a good photothermal ablation effect and significantly inhibited gastric tumor growth in vitro and in vivo. The comprehensive application of MoSe2@CS in the PTT of H. pylori infection and gastric cancer provides a new avenue for the clinical treatment of H. pylori infection and related diseases.
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Affiliation(s)
- Xinyuan Zhang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, PR China; School of Materials and Chemistry, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, PR China
| | - Yongkang Lai
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, China; Department of Gastroenterology, Ganzhou People's Hospital Affiliated to Nanchang University, Ganzhou 341000, China
| | - Liang Zhang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, PR China; Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, China
| | - Zheng Chen
- School of Materials and Chemistry, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, PR China
| | - Jiulong Zhao
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, China.
| | - Shige Wang
- School of Materials and Chemistry, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, PR China.
| | - Zhaoshen Li
- School of Health Science and Engineering, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, PR China; Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, China.
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Zhao Z, Zhang R, Chen G, Nie M, Zhang F, Chen X, Lin J, Chen Z, Lin F, Wei C, Zheng Z, Ruan S, Huang B, Chen Y, Nie R. Anti-Helicobacter pylori Treatment in Patients With Gastric Cancer After Radical Gastrectomy. JAMA Netw Open 2024; 7:e243812. [PMID: 38546641 PMCID: PMC10979314 DOI: 10.1001/jamanetworkopen.2024.3812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 01/31/2024] [Indexed: 04/01/2024] Open
Abstract
Importance Whether anti-Helicobacter pylori treatment can provide survival benefits for patients with gastric cancer who are diagnosed with H pylori infection is an area with limited research. Objective To explore the potential survival benefits of anti-H pylori treatment after radical gastrectomy in patients with gastric cancer and presurgical confirmation of H pylori infection. Design, Setting, and Participants This retrospective cohort study was conducted using data from patients with gastric cancer treated between January 1, 2010, and December 31, 2018, and followed up for outcome ascertainment until May 19, 2021. Propensity score matching was performed in patients treated with or without anti-H pylori treatment. This study involved a single institute in a comprehensive cancer treatment and research center located in Guangzhou, Guangdong Province, China. The study included patients with gastric or esophagogastric junction adenocarcinoma who underwent curative gastrectomy with D2 lymphadenectomy and tested positive for H pylori infection. Data were analyzed from March to June 2023. Exposure Anti-H pylori treatment, which primarily includes triple therapy regimens consisting of amoxicillin, clarithromycin, and omeprazole for 14 days. Main Outcomes and Measures Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were analyzed by Kaplan-Meier method, log-rank test, and Cox proportional hazards regression model. Subgroup analysis based on crucial clinical information was also conducted. Results All 1293 patients (median [IQR] age, 59 [50-65] years; 860 [66.5%] male) were divided into 2 groups, with 125 patients in the anti-H pylori treatment group and 1168 patients in the non-anti-H pylori treatment group based on whether they received anti-H pylori treatment during the perioperative period and the follow-up. Survival analysis showed that the 5-year OS rates were 94.1% (95% CI, 89.3%-99.2%) in the anti-H pylori group and 73.8% (95% CI, 70.7%-77.0%) in the non-anti-H pylori group, and the hazard ratio (HR) of these 2 groups was 0.33 (95% CI, 0.18-0.60; P < .001). The survival benefit remained after propensity score matching (HR, 0.50; 95% CI, 0.26-0.99; P = .048). Multivariable analysis for OS and DFS further showed the survival benefit of anti-H pylori treatment, with HRs of 0.38 (95% CI, 0.17-0.87; P = .02) and 0.48 (95% CI, 0.28-0.83; P = .008), respectively. Among patients with TNM stage II/III disease who received adjuvant chemotherapy, anti-H pylori treatment was associated with survival benefits (OS: HR, 0.49; 95% CI, 0.24-0.99; P = .046), whereas among those who did not receive adjuvant chemotherapy, anti-H pylori treatment was not associated with survival benefits (OS: HR, 0.29; 95% CI, 0.04-2.08; P = .22). Conclusions and Relevance This cohort study indicates that anti-H pylori treatment may be associated with improved survival in patients with gastric cancer who have H pylori infections. The study reinforces the importance of including H pylori screening and treatment in the surgical treatment of these patients.
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Affiliation(s)
- Zhoukai Zhao
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ruopeng Zhang
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Guoming Chen
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Man Nie
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Feiyang Zhang
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaojiang Chen
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jun Lin
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zewei Chen
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Feizhi Lin
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chengzhi Wei
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ziqi Zheng
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shenghang Ruan
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Bowen Huang
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yingbo Chen
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Runcong Nie
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
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Angerilli V, Ghelardi F, Nappo F, Grillo F, Parente P, Lonardi S, Luchini C, Pietrantonio F, Ugolini C, Vanoli A, Fassan M. Claudin-18.2 testing and its impact in the therapeutic management of patients with gastric and gastroesophageal adenocarcinomas: A literature review with expert opinion. Pathol Res Pract 2024; 254:155145. [PMID: 38277741 DOI: 10.1016/j.prp.2024.155145] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 01/10/2024] [Accepted: 01/16/2024] [Indexed: 01/28/2024]
Abstract
Claudin-18.2 (CLDN18.2) is a member of the tight junction protein family and is a highly selective biomarker with frequent abnormal expression during the occurrence and development of various primary malignant tumors, including gastric cancer (GC) and esophago-gastric junction adenocarcinomas (EGJA). For these reasons, CLDN18.2 has been investigated as a therapeutic target for GC/EGJA malignancies. Recently, zolbetuximab has been proposed as a new standard of care for patients with CLDN18.2-positive, HER2-negative, locally advanced and metastatic GC/EGJA. The use of CLDN18 IHC assays to select patients who might benefit from anti-CLDN18.2 therapy is currently entering clinical practice. In this setting, pathologists play a central role in therapeutic decision-making. Accurate biomarker assessment is essential to ensure the best therapeutic option for patients. In the present review, we provide a comprehensive overview of available evidence on CLDN18.2 testing and its impact on the therapeutic management of patients with GC/EGJA, as well as some practical suggestions for CLDN18.2 staining interpretation and potential pitfalls in the real-world setting.
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Affiliation(s)
- Valentina Angerilli
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Filippo Ghelardi
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Floriana Nappo
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Federica Grillo
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Italy.
| | - Paola Parente
- Unit of Pathology, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
| | - Sara Lonardi
- Medical Oncology 3, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Filippo Pietrantonio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Clara Ugolini
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy
| | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy; Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy
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9
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Luzina EV, Lareva NV, Lazebnik LB, Dutova AA, Chartorizhskaya NN, Mutsolgova TB. <i>Helicobacter pylori</i> and herpes viruses co-infection in chronic gastritis. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:27-35. [DOI: 10.31146/1682-8658-ecg-220-12-27-35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Affiliation(s)
- E. V. Luzina
- Chita State Medical Academy of the Ministry of Health of Russia
| | - N. V. Lareva
- Chita State Medical Academy of the Ministry of Health of Russia
| | - L. B. Lazebnik
- A. I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - A. A. Dutova
- Chita State Medical Academy of the Ministry of Health of Russia
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10
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Iizuka C, Sue S, Onodera S, Ikeda A, Ikeda R, Goda Y, Irie K, Kaneko H, Maeda S. Risk assessment of metachronous gastric cancer after endoscopic submucosal dissection based on endoscopic intestinal metaplasia. JGH Open 2023; 7:783-789. [PMID: 38034056 PMCID: PMC10684977 DOI: 10.1002/jgh3.12989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/16/2023] [Indexed: 12/02/2023]
Abstract
Background and Aim The incidence of metachronous gastric cancer (MGC) after endoscopic treatment for early gastric cancer (EGC) is high, but a method of risk assessment for MGC based on endoscopic findings has not been established. In this study, we focused on endoscopic intestinal metaplasia (IM) and investigated the risk for MGC after endoscopic submucosal dissection (ESD) for EGC. Methods This retrospective observational study involved patients who underwent curative ESD for EGC from April 2015 to January 2021. We assessed endoscopic IM using the pretreatment endoscopic examination images. The severity of endoscopic IM was classified into four levels: 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Four different gastric areas were evaluated. We divided the patients into a low-score group and a high-score group, and compared the cumulative incidence of MGC. Results In total, 156 patients who met the inclusion criteria were followed up for at least 12 months after ESD, and MGC developed in 14 patients during a mean period oof 41.5 months. The endoscopic IM scores in the lesser curvature of the antrum, lesser curvature of the corpus, and greater curvature of the corpus were higher in patients with MGC than in those without MGC. In the corpus, the 5-year cumulative incidence of MGC was significantly higher in the high-score group than in the low-score group (29.8% vs 10.0%, P = 0.004). Conclusion The severity of endoscopic corpus IM was associated with MGC. Thus, patients with severe corpus IM at the time of ESD require careful examination and intensive follow-up.
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Affiliation(s)
- Chino Iizuka
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
| | - Soichiro Sue
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
| | - Sho Onodera
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
| | - Aya Ikeda
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
| | - Ryosuke Ikeda
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
| | - Yoshihiro Goda
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
| | - Kuniyasu Irie
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
| | - Hiroaki Kaneko
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
| | - Shin Maeda
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
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11
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Wang Y, Han W, Wang N, Han M, Ban M, Dai J, Dong Y, Sun T, Xu J. The role of microbiota in the development and treatment of gastric cancer. Front Oncol 2023; 13:1224669. [PMID: 37841431 PMCID: PMC10572359 DOI: 10.3389/fonc.2023.1224669] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 08/28/2023] [Indexed: 10/17/2023] Open
Abstract
The stomach was once considered a sterile organ until the discovery of Helicobacter pylori (HP). With the application of high-throughput sequencing technology and macrogenomics, researchers have identified fungi and fivemajor bacterial phyla within the stomachs of healthy individuals. These microbial communities exert regulatory influence over various physiological functions, including energy metabolism and immune responses. HP is a well-recognized risk factor for gastric cancer, significantly altering the stomach's native microecology. Currently, numerous studies are centered on the mechanisms by which HP contributes to gastric cancer development, primarily involving the CagA oncoprotein. However, aside from exogenous infections such as HP and EBV, certain endogenous dysbiosis can also lead to gastric cancer through multiple mechanisms. Additionally, gut microbiota and its metabolites significantly impact the development of gastric cancer. The role of microbial therapies, including diet, phages, probiotics and fecal microbiota transplantation, in treating gastric cancer should not be underestimated. This review aims to study the mechanisms involved in the roles of exogenous pathogen infection and endogenous microbiota dysbiosis in the development of gastric cancer. Also, we describe the application of microbiota therapy in the treatment and prognosis of gastric cancer.
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Affiliation(s)
- Yiwen Wang
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Wenjie Han
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Na Wang
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Mengzhen Han
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Meng Ban
- Department of Bioinformatics, Kanghui Biotechnology Co., Ltd., Shenyang, China
| | - Jianying Dai
- School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, China
| | - Yuesheng Dong
- School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, China
| | - Tao Sun
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Oncology Medicine, Key Laboratory of Liaoning Breast Cancer Research, Shenyang, Liaoning, China
| | - Junnan Xu
- Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
- Department of Oncology Medicine, Key Laboratory of Liaoning Breast Cancer Research, Shenyang, Liaoning, China
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12
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Livzan MA, Mozgovoi SI, Gaus OV, Shimanskaya AG, Kononov AV. Histopathological Evaluation of Gastric Mucosal Atrophy for Predicting Gastric Cancer Risk: Problems and Solutions. Diagnostics (Basel) 2023; 13:2478. [PMID: 37568841 PMCID: PMC10417051 DOI: 10.3390/diagnostics13152478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 07/19/2023] [Accepted: 07/24/2023] [Indexed: 08/13/2023] Open
Abstract
Patients suffering from chronic gastritis and developing gastric mucosa atrophy are at increased risk of the development of gastric cancer. The diagnosis of chronic atrophic gastritis (CAG) is a complex procedure involving a detailed history taking, a thorough physical examination and the use of laboratory and instrumental diagnostic methods among which the endoscopy of the upper digestive tract is the cornerstone because it allows the assessment of the topography of gastritis and identification of erosions and areas of intestinal metaplasia with the use of NBI endoscopy. However, the diagnosis of CAG requires morphological examination of the gastric mucosa. So, in addition to assessing macroscopic changes in the gastric mucosa, it is necessary to take biopsy specimens in accordance with the protocols for their morphological and immunohistochemical examination. In the absence of specific diagnostic stigmas of CAG, close cooperation between a clinician, endoscopist and pathologist is necessary. The article presents systematized data on the histopathological assessment of the gastric mucosa atrophy to predict the risk of gastric cancer.
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Affiliation(s)
- Maria A. Livzan
- Department of Internal Medicine and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia;
| | - Sergei I. Mozgovoi
- Department of Pathological Anatomy, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Olga V. Gaus
- Department of Internal Medicine and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia;
| | - Anna G. Shimanskaya
- Department of Pathological Anatomy, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Alexei V. Kononov
- Department of Pathological Anatomy, Omsk Sate Medical University, 644099 Omsk, Russia
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13
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Livzan MA, Gaus OV, Lisovskiy MA, Mozgovoi SI, Rubtsov VA, Parygina MN. Clinical supervision of chronic atrophic gastritis. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:148-155. [DOI: 10.31146/1682-8658-ecg-211-3-148-155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Patients with chronic gastritis (CG) with the development of atrophy of the gastric mucosa are at an increased risk of developing gastric cancer (GC). In the management of such patients, the development of high-grade dysplasia and invasive gastric cancer should be defined as adverse outcomes that must be prevented. To this end, patients with a diagnosis of «Chronic atrophic fundic/multifocal gastritis» are subject to dynamic dispensary observation to assess the achievement of target indicators, take into account information about changes in the diagnosis and concomitant diseases, emerging complications, as well as to enter data on ongoing therapeutic and preventive measures. This article presents the main aspects of prevention and dispensary monitoring of patients with an increased risk of gastric cancer.
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14
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Ng HY, Leung WK, Cheung KS. Antibiotic Resistance, Susceptibility Testing and Stewardship in Helicobacter pylori Infection. Int J Mol Sci 2023; 24:11708. [PMID: 37511471 PMCID: PMC10380565 DOI: 10.3390/ijms241411708] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/12/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
Despite the declining trend of Helicobacter pylori (H. pylori) prevalence around the globe, ongoing efforts are still needed to optimize current and future regimens in view of the increasing antibiotic resistance. The resistance of H. pylori to different antibiotics is caused by different molecular mechanisms, and advancements in sequencing technology have come a far way in broadening our understanding and in facilitating the testing of antibiotic susceptibility to H. pylori. In this literature review, we give an overview of the molecular mechanisms behind resistance, as well as discuss and compare different antibiotic susceptibility tests based on the latest research. We also discuss the principles of antibiotic stewardship and compare the performance of empirical therapies based on up-to-date resistance patterns and susceptibility-guided therapies in providing effective H. pylori treatment. Studies and clinical guidelines should ensure that the treatment being tested or recommended can reliably achieve a pre-agreed acceptable level of eradication rate and take into account the variations in antibiotic resistance across populations. Local, regional and international organizations must work together to establish routine antibiotic susceptibility surveillance programs and enforce antibiotic stewardship in the treatment of H. pylori, so that it can be managed in a sustainable and efficient manner.
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Affiliation(s)
- Ho-Yu Ng
- School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
| | - Wai K Leung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
| | - Ka-Shing Cheung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
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15
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Qin Y, Geng JX, Huang B. Clinical value of serum pepsinogen in the diagnosis and treatment of gastric diseases. World J Gastrointest Oncol 2023; 15:1174-1181. [PMID: 37546552 PMCID: PMC10401465 DOI: 10.4251/wjgo.v15.i7.1174] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/28/2023] [Accepted: 06/14/2023] [Indexed: 07/12/2023] Open
Abstract
Pepsinogen, secreted from the gastric mucosa, is the precursor of pepsin. It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity. The pepsinogen content that can enter the blood circulation through the capillaries of the gastric mucosa is approximately 1% and remains stable all the time. The pepsinogen content in serum will change with the pathological changes of gastric mucosa. Therefore, the level of pepsinogen in serum can play a role in serologic biopsy to reflect the function and morphology of different regions of gastric mucosa and serve as an indicator of gastric disease. This study conducts relevant research on serum pepsinogen 1, pepsinogen 2, and the ratio of pepsinogen 1 to pepsinogen 2, and reviews their important value in clinical diagnosis of Helicobacter pylori infection, gastric ulcer, and even gastric carcinoma, providing ideas for other researchers.
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Affiliation(s)
- Yuan Qin
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Jia-Xin Geng
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Biao Huang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
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16
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Shin WS, Xie F, Chen B, Yu P, Yu J, To KF, Kang W. Updated Epidemiology of Gastric Cancer in Asia: Decreased Incidence but Still a Big Challenge. Cancers (Basel) 2023; 15:cancers15092639. [PMID: 37174105 PMCID: PMC10177574 DOI: 10.3390/cancers15092639] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 05/02/2023] [Accepted: 05/02/2023] [Indexed: 05/15/2023] Open
Abstract
Despite the decline in incidence and mortality rates, gastric cancer (GC) is the fifth leading cause of cancer deaths worldwide. The incidence and mortality of GC are exceptionally high in Asia due to high H. pylori infection, dietary habits, smoking behaviors, and heavy alcohol consumption. In Asia, males are more susceptible to developing GC than females. Variations in H. pylori strains and prevalence rates may contribute to the differences in incidence and mortality rates across Asian countries. Large-scale H. pylori eradication was one of the effective ways to reduce GC incidences. Treatment methods and clinical trials have evolved, but the 5-year survival rate of advanced GC is still low. Efforts should be put towards large-scale screening and early diagnosis, precision medicine, and deep mechanism studies on the interplay of GC cells and microenvironments for dealing with peritoneal metastasis and prolonging patients' survival.
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Affiliation(s)
- Wing Sum Shin
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Fuda Xie
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China
- CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518000, China
| | - Bonan Chen
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China
- CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518000, China
| | - Peiyao Yu
- Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Jun Yu
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Ka Fai To
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Wei Kang
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong 999077, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 999077, China
- CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518000, China
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17
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Yang H, Mou Y, Hu B. Discussion on the common controversies of Helicobacter pylori infection. Helicobacter 2023; 28:e12938. [PMID: 36436202 DOI: 10.1111/hel.12938] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 11/02/2022] [Accepted: 11/03/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Helicobacter pylori ( H. pylori ) can persistently colonize on the gastric mucosa after infection and cause gastritis, atrophy, metaplasia, and even gastric cancer (GC). METHODS Therefore, the detection and eradication of H. pylori are the prerequisite. RESULTS Clinically, there are some controversial issues, such as why H. pylori infection is persistent, why it translocases along with the lesser curvature of the stomach, why there is oxyntic antralization, what the immunological characteristic of gastric chronic inflammation caused by H. pylori is, whether H. pylori infection is associated with extra-gastric diseases, whether chronic atrophic gastritis (CAG) is reversible, and what the potential problems are after H. pylori eradication. What are the possible answers? CONCLUSION In the review, we will discuss these issues from the attachment to eradication in detail.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Mou
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
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18
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Liu Y, Wen H, Wang Q, Du S. Research trends in endoscopic applications in early gastric cancer: A bibliometric analysis of studies published from 2012 to 2022. Front Oncol 2023; 13:1124498. [PMID: 37114137 PMCID: PMC10129370 DOI: 10.3389/fonc.2023.1124498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 03/13/2023] [Indexed: 04/29/2023] Open
Abstract
Background Endoscopy is the optimal method of diagnosing and treating early gastric cancer (EGC), and it is therefore important to keep up with the rapid development of endoscopic applications in EGC. This study utilized bibliometric analysis to describe the development, current research progress, hotspots, and emerging trends in this field. Methods We retrieved publications about endoscopic applications in EGC from 2012 to 2022 from Web of Science™ (Clarivate™, Philadelphia, PA, USA) Core Collection (WoSCC). We mainly used CiteSpace (version 6.1.R3) and VOSviewer (version 1.6.18) to perform the collaboration network analysis, co-cited analysis, co-occurrence analysis, cluster analysis, and burst detection. Results A total of 1,333 publications were included. Overall, both the number of publications and the average number of citations per document per year increased annually. Among the 52 countries/regions that were included, Japan contributed the most in terms of publications, citations, and H-index, followed by the Republic of Korea and China. The National Cancer Center, based in both Japan and the Republic of Korea, ranked first among institutions in terms of number of publications, citation impact, and the average number of citations. Yong Chan Lee was the most productive author, and Ichiro Oda had the highest citation impact. In terms of cited authors, Gotoda Takuji had both the highest citation impact and the highest centrality. Among journals, Surgical Endoscopy and Other Interventional Techniques had the most publications, and Gastric Cancer had the highest citation impact and H-index. Among all publications and cited references, a paper by Smyth E C et al., followed by one by Gotoda T et al., had the highest citation impact. Using keywords co-occurrence and cluster analysis, 1,652 author keywords were categorized into 26 clusters, and we then divided the clusters into six groups. The largest and newest clusters were endoscopic submucosal dissection and artificial intelligence (AI), respectively. Conclusions Over the last decade, research into endoscopic applications in EGC has gradually increased. Japan and the Republic of Korea have contributed the most, but research in this field in China, from an initially low base, is developing at a striking speed. However, a lack of collaboration among countries, institutions, and authors, is common, and this should be addressed in future. The main focus of research in this field (i.e., the largest cluster) is endoscopic submucosal dissection, and the topic at the frontier (i.e., the newest cluster) is AI. Future research should focus on the application of AI in endoscopy, and its implications for the clinical diagnosis and treatment of EGC.
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Affiliation(s)
- Yuan Liu
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Haolang Wen
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Qiao Wang
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Shiyu Du
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Shiyu Du,
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Abstract
BACKGROUND This study aimed to systematically analyze the association between long-term use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). METHODS We performed a systematic search of articles on the relationship between long-term use of PPIs and the risk of GC from PubMed and EMBASE. We calculated the pooled odds ratio of GC in PPI users compared to non-PPI users using random-effects models. RESULTS This meta-analysis included 18 studies from 20 different databases with 4348,905 patients enrolled. In the random effects model, we found that an increased risk of GC among PPI users (OR = 1.94; 95% CI [1.43, 2.64]). The long-term use of PPIs compared with histamine-2 receptor antagonist users did not increase the risk of GC (OR = 1.65; 95% CI [0.92, 2.97]). Stratified analysis showed that PPI users had a significantly increased risk of noncardia GC (OR = 2.53; 95% CI [2.03, 3.15]), but had a relatively small relationship with the risk of gastric cardia cancer. (OR = 1.79; 95% CI [1.06, 3.03]). With the extension of PPI use time, the estimated risk value decreases (<1 year: OR = 6.33, 95% CI [3.76, 10.65]; 1-3 years: OR = 1.82, 95% CI [1.30, 2.55]; >3 years: OR = 1.25, 95% CI [1.00, 1.56]). Despite Helicobacter pylori eradication, the long-term use of PPIs did not alter the increased risk of GC (OR = 2.29; 95% CI [1.57, 3.33]). CONCLUSION Our meta-analysis found that PPI use may be associated with an increased risk of GC. Further research on the causal relationship between these factors is necessary.
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Affiliation(s)
- Huiqin Gao
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Lunan Li
- Department of Gastroenterology, NO.2 People’s Hospital of Fuyang City, Fuyang, Anhui, China
| | - Ke Geng
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Changzheng Teng
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Yuanyuan Chen
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Fei Chu
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
| | - Yi Zhao
- Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China
- *Correspondence: Yi Zhao, Department of Gastroenterology, Guoyang County People’s Hospital, Guoyang Branch of Anhui Provincial Hospital, No. 189 Xiangyang Road, Guoyang 233600, Anhui, China (e-mail: )
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Yang H, Guan L, Hu B. Detection and Treatment of Helicobacter pylori: Problems and Advances. Gastroenterol Res Pract 2022; 2022:4710964. [PMID: 36317106 PMCID: PMC9617708 DOI: 10.1155/2022/4710964] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 09/28/2022] [Accepted: 10/12/2022] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection is chronic and etiologically linked to gastric cancer (GC) derived from gastric epithelium. The potential mechanism is complex, covering chronic inflammation, epithelial senescence, NF-κB activation, the cytotoxin-associated gene A protein translocation, and related abnormal signaling pathways. In clinical practice, the test-and-treat strategy, endoscopy-based strategy, and (family-based) screen-and-treat strategy are recommended to detect H. pylori and prevent GC. It has been demonstrated that the decreasing annual incidence of GC is largely attributable to the management of H. pylori. This study reviews the current clinical practice of H. pylori on the detection and eradication, alternative treatment strategies, and related problems and advances, and hopes to contribute to the better clinical management of H. pylori.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Liwen Guan
- Department of Gastroenterology, Sanya Central Hospital (Hainan Third People's Hospital), Sanya, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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21
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Bordin DS, Livzan MA, Osipenko MF, Mozgovoy SI, Andreyev DN, Maev IV. The key statements of the Maastricht VI consensus. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:5-21. [DOI: 10.31146/1682-8658-ecg-205-9-5-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
An analysis of the most important changes and provisions of the Maastricht VI consensus published in August 2022 is presented. 41 experts from 29 countries took part in the creation of the consensus. Recommendations have been developed in five areas: (1) indications for treatment and clinical associations of Helicobacter pylori (H. pylori) infection, (2) diagnosis, (3) treatment, (4) prevention of gastric cancer, (5) H. pylori and gastric microbiota -intestinal tract (GIT), taking into account the level of evidence and the strength of recommendations. Emphasis is placed on molecular testing, which is becoming an increasingly accessible research method in the world to identify both H. pylori itself and its sensitivity to antibiotics. The growing resistance of H. pylori strains to previously effective antibacterial agents requires a treatment strategy that implies the ability to determine the sensitivity of H. pylori to antibacterial agents both in the population and in a particular individual. The use of modern diagnostic tests expands the possibilities of individualization of therapy, since it allows determining not only the presence of H. pylori in the gastric mucosa, but also the sensitivity of the infection to antibacterial drugs. Along with individual approaches to treatment, the most effective empirical therapy regimens are given in case of impossibility to determine individual resistance to antibiotics. New data on the effectiveness and results of the use of primary and secondary preventive strategies for gastric cancer are presented. Given the important role of the entire microbiome of the gastrointestinal tract in the functioning of the body, the question of the interaction of H. pylori with other microorganisms is discussed. The critical issues of the near future are related to the global prevention of gastric cancer; the need to control antibiotic resistance, and the development of new methods of therapy and prevention of Helicobacter pylori infection.
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Affiliation(s)
- D. S. Bordin
- State Budgetary Institution of Healthcare of the city of Moscow “A. S. Loginov Moscow Clinical Scientific and Practical Center of the Department of Healthcare of the City of Moscow”; Federal State Budgetary Educational Institution of the Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation; Federal State Educational Establishment of Higher Education Tver State Medical University
| | - M. A. Livzan
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - M. F. Osipenko
- Federal State Educational Establishment of Higher Education Novosibirsk State Medical University of the Ministry of Health of the Russian Federation
| | - S. I. Mozgovoy
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - D. N. Andreyev
- Federal State Budgetary Educational Institution of the Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation
| | - I. V. Maev
- Federal State Budgetary Educational Institution of the Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation
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22
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Livzan MA, Gaus OV, Mozgovoi SI. Gastric cancer in a patient with chronic gastritis after <i>H. pylori</i> eradication: assessing the risks. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:22-28. [DOI: 10.31146/1682-8658-ecg-205-9-22-28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Stomach cancer occupies a leading position in oncological morbidity and mortality worldwide. Approximately 800,000 people die from stomach cancer every year. In two-thirds of patients gastric cancer is diagnosed at a late stage, when radical treatment becomes impossible. Helicobacter pylori (H. pylori) infection is considered as the main etiological factor for gastric cancer. To stratify the risk of developing gastric cancer an assessment of morphological changes in the gastric mucosa using the Operative Link for Gastritis Assessment of Atrophic Gastritis (OLGA) system is used. The stage of gastritis plays a key role in determining an individual’s risk of developing stomach cancer. H. pylori eradication therapy is an effective method for preventing gastric cancer. However not in all patients the elimination of the infection can prevent the development of gastric cancer in the future. It is extremely important to identify a group of people with ex-helicobacter gastritis, who have a high risk of developing stomach cancer, and to take timely preventive measures in them. The purpose of this publication is to summarize and systematize the currently available data on the risk of developing gastric cancer in patients with H. pylori-associated gastritis, including those after successful eradication.
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Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022; 71:gutjnl-2022-327745. [PMID: 35944925 DOI: 10.1136/gutjnl-2022-327745] [Citation(s) in RCA: 576] [Impact Index Per Article: 192.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/21/2022] [Indexed: 01/06/2023]
Abstract
Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.
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Affiliation(s)
- Peter Malfertheiner
- Medical Department 2, LMU, Munchen, Germany
- Department of Radiology, LMU, Munchen, Germany
| | - Francis Megraud
- INSERM U853 UMR BaRITOn, University of Bordeaux, Bordeaux, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
- Medical School, European University, Nicosia, Cyprus
| | - Javier P Gisbert
- Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Jyh-Ming Liou
- Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Christian Schulz
- Medical Department 2, LMU, Munchen, Germany
- Partner Site Munich, DZIF, Braunschweig, Germany
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy
| | - Richard H Hunt
- Medicine, McMaster University, Hamilton, Ontario, Canada
- Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Colm O'Morain
- Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy
- Veneto Tumor Registry (RTV), Padova, Italy
| | - Sebastian Suerbaum
- Partner Site Munich, DZIF, Braunschweig, Germany
- Max von Pettenkofer Institute, LMU, Munchen, Germany
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical School, Tochigi, Japan
| | - Emad M El-Omar
- Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
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24
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Png CW, Lee WJJ, Chua SJ, Zhu F, Yeoh KG, Zhang Y. Mucosal microbiome associates with progression to gastric cancer. Am J Cancer Res 2022; 12:48-58. [PMID: 34987633 PMCID: PMC8690935 DOI: 10.7150/thno.65302] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 09/09/2021] [Indexed: 12/22/2022] Open
Abstract
Background & Aims: Dysbiosis is associated with gastric cancer (GC) development. However, no longitudinal study was carried out to identify key bacteria that could predict for GC progression. Here, we aimed to investigate changes in bacterial metagenome prior to GC and develop a microbiome-based predictive model to accurately classify patients at risk of GC. Methods: Bacterial 16S rDNA was sequenced from 89 gastric antral biopsies obtained from 43 participants. This study was nested in a prospective, longitudinal study, whereby study participants underwent screening gastroscopy, with further 1-2 yearly surveillance gastroscopies for at least 5 years. Putative bacterial taxonomic and functional features associated with GC carcinogenesis were identified by comparing between controls, patients with gastric intestinal metaplasia (IM) and patients with early gastric neoplasia (EGN). Results: Patients with EGN had enrichment of Proteobacteria (in particular Proteus genus) and depletion of Bacteroidetes (in particular S24-7 family) in their gastric mucosa. Sequencing identified more patients with Helicobacter pylori compared to histopathological assessment, while H. pylori was also significantly enriched in EGN. Furthermore, a total of 261 functional features, attributing to 97 KEGG pathways were differentially abundant at baseline between patients who subsequent developed EGN (n = 13/39) and those who did not. At the same time, a constellation of six microbial taxonomic features present at baseline, provided the highest classifying power for subsequent EGN (AUC = 0.82). Conclusion: Our study highlights early microbial changes associated with GC carcinogenesis, suggesting a potential role for prospective microbiome surveillance for GC.
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Affiliation(s)
- Chin Wen Png
- Department of Microbiology & Immunology, and NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.,Immunology Programme, Life Science Institute, National University of Singapore, Singapore 117456, Singapore
| | - Wei Jie Jonathan Lee
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.,Division of Gastroenterology and Hepatology, National University Health System, Singapore 119074, Singapore.,Singapore Gastric Cancer Consortium, Singapore 119074, Singapore
| | - Shijia Joy Chua
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Feng Zhu
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | | | - Khay Guan Yeoh
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.,Division of Gastroenterology and Hepatology, National University Health System, Singapore 119074, Singapore.,Singapore Gastric Cancer Consortium, Singapore 119074, Singapore
| | - Yongliang Zhang
- Department of Microbiology & Immunology, and NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.,Immunology Programme, Life Science Institute, National University of Singapore, Singapore 117456, Singapore
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25
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The uninvited guests of our microbiome: Helicobacter pylori and Epstein-Barr virus and their role in gastric cancerogenesis. POSTEP HIG MED DOSW 2021. [DOI: 10.2478/ahem-2021-0008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
It is well established that human body is an ecosystem for numerous microorganisms: bacteria, fungi, eukaryotic parasites, and viruses. They form a “microbiome” that under conditions of homeostasis remains in a friendly mutual relationship with the host. However, the composition and diversity of this microbe community is dynamic and can be changed under the influence of environmental factors, such as diet, antibiotic therapy, lifestyle, and the host’s genotype and immunity. The result of gut microbiome dysbiosis can lead even to cancer. The aim of this review is the description of the healthy gastrointestinal microbiome and the role of two infectious agents: Gram-negative bacteria Helicobacter pylori and Epstein-Barr virus in the development of gastric cancer in terms of gut dysbiosis. H. pylori is the most important pathogen of gastric microbiome with clear impact on its diversity. Coinfection with Epstein-Barr virus causes chronic gastritis, and the inflammatory process is significantly increased. The process of carcinogenesis begins with chronic inflammation that causes atrophic gastritis, intestinal metaplasia, dysplasia, and finally cancer. It has been proven that chronic inflammatory infection caused by infectious agents increases the risk of stomach cancer. Molecular methods that are progressively used to explore the human microbiome provide hope that this knowledge will be used for future diagnoses and therapy in the state of its dysbiosis and in cases of gastric cancer.
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26
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Elucidated tumorigenic role of MAML1 and TWIST1 in gastric cancer is associated with Helicobacter pylori infection. Microb Pathog 2021; 162:105304. [PMID: 34818576 DOI: 10.1016/j.micpath.2021.105304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 11/12/2021] [Accepted: 11/18/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Epithelial-mesenchymal transition (EMT) has a fundamental role in tumor initiation, progression, and metastasis. Helicobacter pylori (HP) induces EMT and thus causes gastric cancer (GC) by deregulating multiple signaling pathways involved in EMT. TWIST1 and MAML1 have been confirmed to be critical inducers of EMT via diverse signaling pathways such as Notch signaling. This study aimed to investigate for the first time possible associations between TWIST1/MAML1 mRNA expression levels, HP infection, and clinicopathological characteristics in GC patients. METHOD TWIST1 and MAML1 mRNA expression levels were evaluated in tumoral and adjacent normal tissues in 73 GC patients using the quantitative reverse transcription PCR (RT-qPCR) method. PCR technique was also applied to examine the infection with HP in GC samples. RESULTS Upregulation of TWIST1 and MAML1 expression was observed in 35 (48%) and 34 (46.6%) of 73 tumor samples, respectively. Co-overexpression of these genes was found in 26 of 73 (35.6%) tumor samples; meanwhile, there was a significant positive correlation between MAML1 and TWIST1 mRNA expression levels (P < 0.001). MAML1 overexpression exhibited meaningful associations with advanced tumor stages (P = 0.006) and nodal metastases (P ˂ 0.001). 34 of 73 (46.6%) tumors tested positive for HP, and meanwhile, MAML1 expression was positively related with T (P = 0.05) and grade (P = 0.0001) in these HP-positive samples. Increased TWIST1 expression was correlated with patient sex (P = 0.035) and advanced tumor grade (P = 0.017) in HP-infected tumors. Furthermore, TWIST1 and MAML1 expression levels were inversely linked with histologic grade in HP-negative tumor samples (P = 0.021 and P = 0.048, respectively). CONCLUSION We propose TWIST1 and MAML1 as potential biomarkers of advanced-stage GC that determine the characteristics and aggressiveness of the disease. Based on accumulating evidence and our findings, they can be introduced as promising therapeutic targets to modify functional abnormalities in cells that promote GC progression. Moreover, HP may enhance GC growth and metastasis by disrupting TWIS1/MAML1 expression patterns and related pathways.
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Seo SI, Park CH, You SC, Kim JY, Lee KJ, Kim J, Kim Y, Yoo JJ, Seo WW, Lee HS, Shin WG. Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea. Gut 2021; 70:2066-2075. [PMID: 33975868 DOI: 10.1136/gutjnl-2020-323845] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 04/23/2021] [Accepted: 04/24/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The association between proton pump inhibitor (PPI) use and gastric cancer related to Helicobacter pylori eradication has not been fully investigated in geographical regions with high risk of gastric cancer. We aimed to evaluate the association between PPIs and gastric cancer in Korea. DESIGN This study analysed the original and common data model versions of the Korean National Health Insurance Service database from 2002 to 2013. We compared the incidence rates of gastric cancer after 1-year drug exposure, between new users of PPIs and other drugs excluding PPIs, by Cox proportional hazards model. We also analysed the incidence of gastric cancer among PPI users after H. pylori eradication. RESULTS The analysis included 11 741 patients in matched PPI and non-PPI cohorts after large-scale propensity score matching. During a median follow-up of 4.3 years, PPI use was associated with a 2.37-fold increased incidence of gastric cancer (PPI≥30 days vs non-PPI; 118/51 813 person-years vs 40/49 729 person-years; HR 2.37, 95% CI 1.56 to 3.68, p=0.001). The incidence rates of gastric cancer showed an increasing trend parallel to the duration of PPI use. In H. pylori-eradicated subjects, the incidence of gastric cancer was significantly associated with PPI use over 180 days compared with the non-PPI group (PPI≥180 days vs non-PPI; 30/12 470 person-years vs 9/7814 person-years; HR 2.22, 95% CI 1.05 to 4.67, p=0.036). CONCLUSION PPI use was associated with gastric cancer, regardless of H. pylori eradication status. Long-term PPIs should be used with caution in high-risk regions for gastric cancer.
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Affiliation(s)
- Seung In Seo
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, South Korea
| | - Seng Chan You
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Young Kim
- University Industry Foundation, Hallym University, Chuncheon, South Korea
| | - Kyung Joo Lee
- University Industry Foundation, Hallym University, Chuncheon, South Korea
| | - Jinseob Kim
- Department of Epidemiology, School of Public Health, Seoul National University, Seoul, South Korea
| | - Yerim Kim
- Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Jong Jin Yoo
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Won-Woo Seo
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Hyung Seok Lee
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
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Cullin N, Azevedo Antunes C, Straussman R, Stein-Thoeringer CK, Elinav E. Microbiome and cancer. Cancer Cell 2021; 39:1317-1341. [PMID: 34506740 DOI: 10.1016/j.ccell.2021.08.006] [Citation(s) in RCA: 290] [Impact Index Per Article: 72.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 08/05/2021] [Accepted: 08/13/2021] [Indexed: 12/14/2022]
Abstract
The human microbiome constitutes a complex multikingdom community that symbiotically interacts with the host across multiple body sites. Host-microbiome interactions impact multiple physiological processes and a variety of multifactorial disease conditions. In the past decade, microbiome communities have been suggested to influence the development, progression, metastasis formation, and treatment response of multiple cancer types. While causal evidence of microbial impacts on cancer biology is only beginning to be unraveled, enhanced molecular understanding of such cancer-modulating interactions and impacts on cancer treatment are considered of major scientific importance and clinical relevance. In this review, we describe the molecular pathogenic mechanisms shared throughout microbial niches that contribute to the initiation and progression of cancer. We highlight advances, limitations, challenges, and prospects in understanding how the microbiome may causally impact cancer and its treatment responsiveness, and how microorganisms or their secreted bioactive metabolites may be potentially harnessed and targeted as precision cancer therapeutics.
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Affiliation(s)
- Nyssa Cullin
- Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
| | - Camila Azevedo Antunes
- Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
| | - Ravid Straussman
- Department of Molecular Cell Biology, Weizmann Institute of Science, 234 Herzl Street, 7610001 Rehovot, Israel
| | - Christoph K Stein-Thoeringer
- Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
| | - Eran Elinav
- Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Department of Immunology, Weizmann Institute of Science, 234 Herzl Street, 7610001 Rehovot, Israel.
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29
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Kang S, Cho SJ. Proton Pump Inhibitors and Gastric Cancer. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Concerns have been raised regarding the long-term use of proton pump inhibitors (PPIs) as an important risk factor for gastric cancer in clinical practice. PPIs can cause hypergastrinemia at clinical doses, and hypergastrinemia has been reported to induce malignant neoplasms in the stomach in previous animal studies. In humans, the proliferation of enterochromaffin-like (ECL) cells induced by hypergastrinemia is suspected as a potential mechanism of gastric cancer. Meanwhile, persistent Helicobacter pylori (H. pylori) infection causes gastric atrophic change, which itself is a major cause of gastric cancer, and it can further increase the risk of gastric cancer by strengthening corpus atrophy through interaction with PPIs. Recent epidemiologic studies have reported an important link between long-term PPI intake and gastric cancer risk even after successful eradication of H. pylori. However, due to the methodological limitations of observational clinical studies, the causal relationship is still not clear, and a recent big data-based study reported that long-term PPI use was not related to gastric cancer incidence. Taken together, despite the potential detrimental effects of PPIs, it is currently difficult to draw a definite conclusion about its association with gastric cancer. To minimize the possibility of gastric cancer in H. pylori-infected patients or precancerous lesions in long-term PPI users, long-term PPI administration should be limited to the minimum effective dose, and antibacterial treatment for H. pylori should be considered.
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30
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Ng AKY, Ng PY, Ip A, Cheung KS, Siu CW. Association between proton pump inhibitors after percutaneous coronary intervention and risk of gastric cancer. BMJ Open Gastroenterol 2021; 8:e000719. [PMID: 34380699 PMCID: PMC8359470 DOI: 10.1136/bmjgast-2021-000719] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 07/17/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Previous studies showing an association between chronic use of proton pump inhibitor (PPI) and gastric cancer are limited by confounding by indication. This relationship has not been studied in patients receiving PPI for prophylaxis, such as those undergoing percutaneous coronary intervention (PCI). METHOD This was a retrospective cohort study including 14 hospitals under the Hospital Authority of Hong Kong between 1 January 2004 and 31 December 2017. Participants were patients who underwent first-ever PCI, were not on PPI prescription within 30 days before admission for PCI, had no known malignancy and survived for 365 days after PCI. Propensity score matching was used to balance baseline characteristics and other prescription patterns. The primary outcome was diagnosis of gastric cancer made >365 days after PCI as a time-to-first-event analysis. The secondary outcome was death from gastric cancer. RESULTS Among the 13 476 patients (6738 pairs) matched by propensity score, gastric cancer developed in 17 (0.25%) PPI users and 7 (0.10%) PPI non-users after a median follow-up of 7.1 years. PPI users had a higher risk of gastric cancer (HR 3.55; 95% CI 1.46 to 8.66, p=0.005) and death from gastric cancer (HR 4.18; 95% CI 1.09 to 16.08, p=0.037), compared with non-users. The association was duration-dependent and patients who took PPI for ≥365 days were at increased risk. CONCLUSIONS Chronic use of PPI was significantly associated with increased risk of gastric cancer and death from gastric cancer in patients for whom it was prescribed as prophylaxis. Physicians should judiciously assess the relevant risks and benefits of chronic PPI use before prescription.
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Affiliation(s)
| | - Pauline Yeung Ng
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - April Ip
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Chung-Wah Siu
- Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
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31
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Tseng CH. The Relationship between Diabetes Mellitus and Gastric Cancer and the Potential Benefits of Metformin: An Extensive Review of the Literature. Biomolecules 2021; 11:1022. [PMID: 34356646 PMCID: PMC8301937 DOI: 10.3390/biom11071022] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/02/2021] [Accepted: 07/08/2021] [Indexed: 12/14/2022] Open
Abstract
The objective of this review is to summarize the findings of published research that investigated the relationship between diabetes mellitus and gastric cancer (GCa) and the potential benefits of metformin on GCa. Related literature has been extensively reviewed, and findings from studies investigating the relationship between diabetes mellitus and GCa suggest that hyperglycemia, hyperinsulinemia and insulin resistance are closely related to the development of GCa. Although not supported by all, most observational studies suggest an increased risk of GCa in patients with type 2 diabetes mellitus, especially in women and in Asian populations. Incidence of second primary malignancy diagnosed after GCa is significantly higher in diabetes patients. Diabetes patients with GCa may have more complications after gastrectomy or chemotherapy and they may have a poorer prognosis than patients with GCa but without diabetes mellitus. However, glycemic control may improve in the diabetes patients with GCa after receiving gastrectomy, especially after procedures that bypass the duodenum and proximal jejunum, such as Roux-en-Y gastric bypass or Billroth II reconstruction. The potential links between diabetes mellitus and GCa may involve the interactions with shared risk factors (e.g., obesity, hyperglycemia, hyperinsulinemia, insulin resistance, high salt intake, smoking, etc.), Helicobacter pylori (HP) infection, medications (e.g., insulin, metformin, statins, aspirin, proton pump inhibitors, antibiotics, etc.) and comorbidities (e.g., hypertension, dyslipidemia, vascular complications, heart failure, renal failure, etc.). With regards to the potential benefits of metformin on GCa, results of most observational studies suggest a reduced risk of GCa associated with metformin use in patients with T2DM, which can be supported by evidence derived from many in vitro and animal studies. Metformin use may also reduce the risk of HP infection, an important risk factor of GCa. In patients with GCa, metformin users may have improved survival and reduced recurrence. More studies are required to clarify the pathological subtypes/anatomical sites of GCa associated with type 2 diabetes mellitus or prevented by metformin, to confirm whether GCa risk can also be increased in patients with type 1 diabetes mellitus and to explore the possible role of gastric microbiota in the development of GCa.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10051, Taiwan; ; Tel.: +886-2-2388-3578
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10051, Taiwan
- Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan 350, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan
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Cheung KS, Chung KL, Leung WK. Chemopreventive Effect of Metformin on Gastric Cancer Development. Gut Liver 2021; 16:147-156. [PMID: 34158423 PMCID: PMC8924804 DOI: 10.5009/gnl210132] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 04/17/2021] [Accepted: 05/12/2021] [Indexed: 12/24/2022] Open
Abstract
Although Helicobacterpylori infection is the most important causative factor for gastric cancer (GC), H. pylori eradication alone does not completely eliminate the GC risk. In addition to H. pylori eradication, other risk factors for GC should be identified and targeted. Diabetes mellitus (DM) confers a 20% increased risk of GC, which could be mediated via several biological mechanisms including the stimulation of cell proliferation via hyperinsulinemia and increased insulin-growth factor production, the promotion of angiogenesis, and DNA damage. With a current global prevalence of 9.3% and a predicted rise to 10.2% by 2030, DM could contribute substantially to the burden of GC cases worldwide. Emerging evidence showed that metformin possesses chemopreventive effects via both direct (e.g., adenosine monophosphate-activated protein kinase activation and subsequent inhibition of the mammalian target of rapamycin pathway) and indirect (e.g., modulation of the interaction between tumor cells and their microenvironment and gut microbiota) pathways. A recent meta-analysis of observational studies showed that metformin use was associated with 24% lower GC risk. However, many available observational studies related to metformin effects suffered from biases including the failure to adjust for the H. pylori infection status and serial glycemic control and time-related biases. Future prospective studies addressing these pitfalls are needed.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Kit Lam Chung
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
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Lyu T, Cheung KS, Ni L, Guo J, Mu P, Li Y, Yang Q, Yu X, Lyu Z, Wu J, Guo H, Leung WK, Seto WK. High prevalence and risk factors of multiple antibiotic resistance in patients who fail first-line Helicobacter pylori therapy in southern China: a municipality-wide, multicentre, prospective cohort study. J Antimicrob Chemother 2021; 75:3391-3394. [PMID: 32785699 DOI: 10.1093/jac/dkaa315] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 06/19/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND We aimed to study the prevalence of secondary antibiotic resistance of Helicobacter pylori in southern China and its risk factors, particularly geographical and socio-economic factors. METHODS This was a municipality-wide, multicentre, prospective cohort study involving five major hospitals. Patients aged ≥18 years who failed first-line bismuth-based quadruple anti-H. pylori therapy between September 2016 and February 2018 were recruited. Participants underwent upper gastrointestinal endoscopy with biopsy from the antrum and body for H. pylori culture and antimicrobial susceptibility testing for six antibiotics (clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline and furazolidone). Patients with failure of H. pylori culture were excluded. Participants completed a questionnaire profiling 22 potential risk factors of H. pylori infection and antibiotic resistance, including medical, social, household and birthplace factors. RESULTS A total of 1113 patients failed first-line therapy, with successful H. pylori culture in 791 (71.1%) [male = 433 (54.7%); median age = 43 years]. Secondary resistance rates of dual antibiotics (clarithromycin + metronidazole and levofloxacin + metronidazole) and triple antibiotics (clarithromycin + levofloxacin + metronidazole) were 34.0%, 38.7% and 17.8%, respectively. Risk factors for clarithromycin + metronidazole resistance were history of ≥2 courses of H. pylori therapies [adjusted OR (aOR) = 1.71; 95% CI = 1.17-2.54], ≥3 household members (aOR = 2.00; 95% CI = 1.07-3.90) and family history of gastric cancer (aOR = 1.85; 95% CI = 1.18-2.85). Risk factors for levofloxacin + metronidazole resistance were age ≥40 years (aOR = 1.94; 95% CI = 1.37-2.75), lower gross domestic product per capita (aOR = 0.29; 95% CI = 0.10-0.80) and higher number of doctors/10 000 population (aOR = 1.59; 95% CI = 1.07-2.39). A higher human development index was of borderline significance (aOR = 2.79; 95% CI = 0.97-8.70). CONCLUSIONS The rates of secondary resistance of H. pylori to multiple antibiotics were high in southern China. Certain population-level risk factors were associated with levofloxacin + metronidazole resistance.
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Affiliation(s)
- Tao Lyu
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Ka Shing Cheung
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,Department of Medicine, The University of Hong Kong, Hong Kong
| | - Li Ni
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jiaqi Guo
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Pei Mu
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Yinpeng Li
- Division of Gastroenterology, Shenzhen People's Hospital Longhua Branch, Shenzhen, China
| | - Qiu Yang
- Division of Gastroenterology, Shenzhen People's Hospital Longhua Branch, Shenzhen, China
| | - Xiqiu Yu
- Division of Gastroenterology, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
| | - Zhiwu Lyu
- Division of Gastroenterology, Baoan People's Hospital of Shenzhen (Group), Shenzhen, China
| | - Jianwei Wu
- Division of Gastroenterology, Baoan People's Hospital of Shenzhen (Group), Shenzhen, China
| | - Haijian Guo
- Division of Gastroenterology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,Department of Medicine, The University of Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,Department of Medicine, The University of Hong Kong, Hong Kong
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Snir Y, Leibovitzh H, Leibovici‐Weissman Y, Vilkin A, Cohen AD, Shochat T, Niv Y, Dotan I, Feldhamer I, Boltin D, Levi Z. Dose-dependent association of proton pump inhibitors use with gastric intestinal metaplasia among Helicobacter pylori-positive patients. United European Gastroenterol J 2021; 9:343-353. [PMID: 32962566 PMCID: PMC8259238 DOI: 10.1177/2050640620951403] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 07/23/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Gastric intestinal metaplasia is a pre-cancerous condition associated with multiple factors. OBJECTIVE We evaluated whether cumulative proton pump inhibitor dose is associated with the diagnosis of gastric intestinal metaplasia while controlling for multiple variables. METHODS We retrospectively identified patients who underwent upper endoscopy with gastric biopsy between 2005 and 2014. Covariate data retrieved included age, sex, ethnicity, smoking status, Helicobacter pylori status (based on clarithromycin-amoxicillin-proton pump inhibitor issued), cumulative proton pump inhibitor issued within 10 years (quartiles [PPI-Q1-4 ] of daily drug dose), anti-parietal cell antibodies, body mass index and comorbidity index. RESULTS Of the 14,147 included patients (median age 63.4 years; women 54.4%; Helicobacter pylori-positive 29.0%), 1244 (8.8%) had gastric intestinal metaplasia. Increasing age, Helicobacter pylori infection, smoking, anti-parietal cell antibodies and proton pump inhibitor use were all associated with the diagnosis of gastric intestinal metaplasia. Upper quartiles of cumulative proton pump inhibitor doses (PPI-Q4 and PPI-Q3 vs. PPI-Q1 ) were associated with the diagnosis of gastric intestinal metaplasia: adjusted odds ratios 1.32 (95% confidence interval [CI] 1.111.57) and 1.27 (95% CI 1.07-1.52), respectively, for the whole cohort (Ptotal 0.007, Ptrend 0.013), 1.69 (95% CI 1.23-2.33) and 1.40 (95% CI 1.04-1.89), respectively, for Helicobacter pylori-positive patients (Ptotal 0.004, Ptrend 0.005) and 1.21 (95% CI 0.98-1.49) and 1.20 (95% CI 0.96-1.49), respectively, for Helicobacter pylori-negative patients (Ptotal 0.288, Ptrend 0.018). Upper quartiles of proton pump inhibitor dose were associated with a 5-10-fold increased risk of low-grade dysplasia. CONCLUSIONS Among Helicobacter pylori-positive patients, proton pump inhibitor use appears to be associated with a dose-dependent increased likelihood of gastric intestinal metaplasia.
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Affiliation(s)
- Yifat Snir
- Division of GastroenterologyRabin Medical CenterPetah TikvaIsrael
| | - Haim Leibovitzh
- Division of GastroenterologyRabin Medical CenterPetah TikvaIsrael
| | | | - Alex Vilkin
- Division of GastroenterologyRabin Medical CenterPetah TikvaIsrael
| | - Arnon D. Cohen
- Department of Quality Measurements and ResearchClalit Health ServicesTel AvivIsrael
- Siaal Research Center for Family Medicine and Primary CareBenGurion University of the NegevBeer‐ShevaIsrael
| | - Tzippy Shochat
- Department of BiostatisticsRabin Medical CenterPetach TikvaIsrael
| | - Yaron Niv
- Division of GastroenterologyRabin Medical CenterPetah TikvaIsrael
- Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
| | - Iris Dotan
- Division of GastroenterologyRabin Medical CenterPetah TikvaIsrael
- Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
| | - Ilan Feldhamer
- Department of Quality Measurements and ResearchClalit Health ServicesTel AvivIsrael
| | - Doron Boltin
- Division of GastroenterologyRabin Medical CenterPetah TikvaIsrael
- Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
| | - Zohar Levi
- Division of GastroenterologyRabin Medical CenterPetah TikvaIsrael
- Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
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Li B, Cheung KS, Wong IYH, Leung WK, Law S. Nonaspirin nonsteroidal anti-inflammatory drugs and gastric cancer risk after Helicobacter pylori eradication: A territory-wide study. Cancer 2021; 127:1805-1815. [PMID: 33471380 DOI: 10.1002/cncr.33412] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 11/25/2020] [Accepted: 12/09/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Despite Helicobacter pylori (HP) eradication, individuals can still develop gastric cancer (GC). Prior studies have demonstrated that nonaspirin nonsteroidal anti-inflammatory drugs (NA-NSAIDs) reduce the risk of GC, but this may be caused by immortal time bias and failure to adjust for HP status. The objective of this study was to investigate whether NA-NSAIDs reduced the risk of GC in patients who undergo H. pylori eradication. METHODS Adult patients who had received clarithromycin-based triple therapy between 2003 and 2016 were identified from a territory-wide health care database. Exclusion criteria included prior GC or GC diagnosed <6 months after HP eradication, prior gastrectomy, gastric ulcer after HP eradication, and failure of triple therapy. Covariates included age, sex, prior peptic ulcer disease, other comorbidities, and concurrent medications (aspirin, proton pump inhibitors, statins, and metformin). To avoid immortal time bias, NA-NSAID use (≥90 days) was treated as a time-dependent variable in a multivariable Cox model (time-dependent analysis). Time-independent analysis was also performed. RESULTS During a median follow-up of 8.9 years (interquartile range, 5.4-12.6 years), 364 of 92,017 patients (0.4%) who underwent HP eradication developed GC. NA-NSAID use was associated with a significant reduction in the risk of GC in time-fixed analysis (adjusted hazard ratio [aHR], 0.65; 95% CI, 0.47-0.90), but not in time-dependent multivariable analysis (aHR, 1.35; 95% CI, 0.97-1.87). Time-dependent subgroup analyses also did not indicate any significant association between NA-NSAID use and either cardia GC (aHR, 0.75; 95% CI, 0.27-2.06) or noncardia GC (aHR, 1.28; 95% CI, 0.83-1.98). CONCLUSIONS NA-NSAID use was not associated with a reduced risk of GC among patients who underwent HP eradication. The chemopreventive effect of NA-NSAIDs observed in prior studies may have been confounded by immortal time bias.
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Affiliation(s)
- Bofei Li
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Ka Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Hong Kong, China
| | - Ian Yu-Hong Wong
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Wai Keung Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Simon Law
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
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Li B, Cheung KS, Wong IYH, Leung WK, Law S. Calcium channel blockers are associated with lower gastric cancer risk: A territory-wide study with propensity score analysis. Int J Cancer 2020; 148:2148-2157. [PMID: 33152125 DOI: 10.1002/ijc.33379] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 10/04/2020] [Accepted: 10/26/2020] [Indexed: 01/05/2023]
Abstract
Prior studies showed that calcium channel blockers (CCBs) could modify cancer risk, but data on gastric cancer (GC) are limited. We aimed to investigate whether CCBs could modify GC risk in Helicobacter pylori-eradicated patients. H pylori-infected patients with hypertension who are aged ≥50 and had received clarithromycin-based triple therapy between 2003 and 2016 were identified from a territory-wide healthcare database. Patients with eradication failure, GC diagnosed within 6 months after HP eradication, and gastric ulcer were excluded. Time-fixed Cox model with one-to-one propensity score matching was used to calculate hazard ratio (HR) of GC with CCBs. Sensitivity analysis using time-dependent multivariable Cox model in which CCB use was treated as time-varying covariate was also performed to address immortal time bias. 17 622 (29.6%) H pylori-eradicated patients with hypertension were included. During a median follow-up of 8.6 years, 105 (0.6%) developed GC. After PS matching, CCBs were associated with a lower GC risk (HR: 0.56; 95% CI: 0.32-0.97). Time-dependent analysis showed consistent result (aHR: 0.50; 95% CI: 0.33-0.75). A longer duration of CCB use was associated with even lower GC risk (adjusted HR [aHR]: 0.69; 95% CI: 0.61-0.79 for every 1-year increase in use). Long-acting CCBs (aHR: 0.47; 95% CI: 0.29-0.76) and dihydropyridines (aHR: 0.49; 95% CI: 0.32-0.73) conferred greater benefit than short-acting ones (aHR: 0.60; 95% CI: 0.36-1.03) and nondihydropyridines (aHR: 0.76; 95% CI: 0.24-2.48). The aHR was 0.57 (95% CI: 0.34-0.97) for noncardia and 0.59 (95% CI: 0.27-1.31) for cardia cancer. Use of CCBs was associated with lower risk of GC development in H pylori-eradicated patients, in a duration- and dose-response manner.
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Affiliation(s)
- Bofei Li
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong
| | - Ka Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Ian Yu-Hong Wong
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong
| | - Wai Keung Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong
| | - Simon Law
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong
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37
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Wu Y, Su T, Zhou X, Lu N, Li Z, Du Y. Awareness and attitudes regarding Helicobacter pylori infection in Chinese physicians and public population: A national cross-sectional survey. Helicobacter 2020; 25:e12705. [PMID: 32476197 DOI: 10.1111/hel.12705] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 05/03/2020] [Accepted: 05/06/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND There is a lack of reports on the awareness of Helicobacter pylori (H pylori) prevention and treatment in the general Chinese population. And whether the knowledge level will affect their action toward screening was unknown. This study aimed to conduct a national survey on the knowledge, attitudes, and practice regarding H pylori infection in Chinese physicians and the public. METHODS This was an Internet-based survey of the general Chinese population and Chinese physicians from different specialties, carried out from January to February 2019. Both surveys (general population's and physicians') included questions to assess the knowledge and attitudes toward H pylori and its action. RESULTS A total of 3211 people and 546 physicians were enrolled. In the population, the proportion of subjects who answered correctly to all questions about H pylori's infectivity was only 16%, and that for H pylori's harmfulness and that for H pylori preventive measures were 35% and 43.6%, respectively. In general, physicians had a better understanding of H pylori's harmfulness (83.9%) than the other population. The vast majority of the surveyed population (87.0%) and physicians (82.2%) supported a national H pylori screening plan to prevent gastric cancer. The support ratio paralleled with the overall knowledge level. Unexpectedly, gastroenterologists tend to have a relatively low support rate for H pylori screening than non-gastroenterologists (58.2% vs 84.2%, P < .001), which may be related to consideration of heavy medical burden (67.3%). CONCLUSIONS The general population in China has relatively insufficient awareness of H pylori, which is incompatible with the highly infectious status. More works on health education are needed to improve the knowledge of this gastric pathogen.
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Affiliation(s)
- You Wu
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Tun Su
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xianzhu Zhou
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Nonghua Lu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhaoshen Li
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Yiqi Du
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
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38
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Cho JH, Jin SY. Optimized diagnosis of Helicobacter pylori and tailored eradication therapy for preventing gastric cancer: a proposal for SHAKE strategy. Expert Rev Gastroenterol Hepatol 2020; 14:553-564. [PMID: 32410515 DOI: 10.1080/17474124.2020.1770594] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION To decrease gastric cancer-related mortality, the Korean National Cancer Screening Program provides biennial screening gastroscopy to all individuals aged >40 years. However, a test-and-treat strategy of Helicobacter pylori for preventing gastric cancer has not been established. AREAS COVERED In this review, we present up-to-date results of endoscopic findings of H. pylori gastritis, optimal sites for H. pylori detection, gastric cancer risk assessment using serum pepsinogen, tailored eradication based on the antimicrobial resistance against H. pylori, and post-eradication surveillance. EXPERT OPINION Here we propose approaches to H. pylori diagnosis and treatment for preventing gastric cancer, termed 'Screening for H. pylori in Korea and Eradication (SHAKE)' strategy. This strategy consists of the following: (1) optimized H. pylori diagnosis, (2) individualized management based on the H. pylori infection status, and (3) tailored eradication therapy. H. pylori gastritis can be diagnosed by endoscopic observation of the gastric mucosal pattern at the greater curvature of the corpus. Measurement of the serum pepsinogen I/II ratio is useful for assessing the risk of gastric cancer. As a first-line treatment, tailored eradication based on the results of molecular testing is effective in a country with a high rate of clarithromycin-resistant H. pylori.
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Affiliation(s)
- Jun-Hyung Cho
- Digestive Disease Center, Soonchunhyang University Hospital , Seoul, Korea
| | - So-Young Jin
- Department of Pathology, Soonchunhyang University Hospital , Seoul, Korea
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39
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Cheung KS, Chan EW, Wong AYS, Chen L, Seto WK, Wong ICK, Leung WK. Metformin Use and Gastric Cancer Risk in Diabetic Patients After Helicobacter pylori Eradication. J Natl Cancer Inst 2020; 111:484-489. [PMID: 30329127 DOI: 10.1093/jnci/djy144] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 06/11/2018] [Accepted: 07/17/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Although prior studies showed metformin could reduce gastric cancer (GC) risk in patients with diabetes mellitus, they failed to adjust for Helicobacter pylori infection and glycemic control. We aimed to investigate whether metformin reduced GC risk in H. pylori-eradicated diabetic patients and its association with glycemic control. METHODS This was a territory-wide cohort study using hospital registry database, recruiting all diabetic patients who were prescribed clarithromycin-based triple therapy for H. pylori infection from 2003 to 2012. Subjects were observed from H. pylori therapy prescription until GC diagnosis, death, or end of study (December 2015). Exclusion criteria included GC diagnosed within first year of H. pylori therapy, prior history of GC or gastrectomy, and failure of H. pylori eradication. The hazard ratio (HR) of GC with metformin (defined as at least 180-day use) was estimated by Cox model with propensity score adjustment for covariates (age, sex, comorbidities, medications [including insulin], and time-weighted average hemoglobin A1c [HbA1c]). All statistical tests were two-sided. RESULTS During a median follow-up of 7.1 years (IQR = 4.7-9.8), 37 (0.51%) of 7266 diabetic patients developed GC at a median age of 76.4 years (IQR = 64.8-81.5 years). Metformin use was associated with a reduced GC risk (adjusted HR = 0.49, 95% CI = 0.24 to 0.98). There was a trend towards a lower GC risk with increasing duration (Ptrend = .01) and dose of metformin (Ptrend = .02). HbA1c level was not an independent risk factor for GC. CONCLUSIONS Metformin use was associated with a lower GC risk among H. pylori-eradicated diabetic patients in a duration- and dose-response manner, which was independent of HbA1c level.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Esther W Chan
- Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Hong Kong
| | - Angel Y S Wong
- Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Hong Kong.,Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Lijia Chen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Wai Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ian C K Wong
- Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Hong Kong.,UCL School of Pharmacy, University College London, London, UK
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
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40
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Elsalem L, Jum'ah AA, Alfaqih MA, Aloudat O. The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives. Clin Exp Gastroenterol 2020; 13:151-185. [PMID: 32440192 PMCID: PMC7211962 DOI: 10.2147/ceg.s243337] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 04/13/2020] [Indexed: 12/24/2022] Open
Abstract
The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of "pharmacomicrobiomics" has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.
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Affiliation(s)
- Lina Elsalem
- Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Ahmad A Jum'ah
- Department of Conservative Dentistry, Faculty of Dentistry, Jordan University of Science and Technology, Irbid, Jordan
| | - Mahmoud A Alfaqih
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Osama Aloudat
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
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Laszkowska M, Oh A, Hur C. Screening for Upper Gastrointestinal Malignancies in the United States-Which Immigrant Groups Should Be Considered High-Risk? Gastroenterology 2020; 158:4-8. [PMID: 31614125 DOI: 10.1053/j.gastro.2019.09.047] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 09/14/2019] [Accepted: 09/23/2019] [Indexed: 02/07/2023]
Affiliation(s)
| | - Aaron Oh
- Columbia University, New York, New York
| | - Chin Hur
- Columbia University, New York, New York
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42
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Voynovan IN, Embutnieks YV, Mareeva DV, Kolbasnikov SV, Bordin DS. Helicobacter pylori as a risk factor for gastric cancer: the evidence and primary prevention strategy. ALMANAC OF CLINICAL MEDICINE 2019; 47:535-547. [DOI: 10.18786/2072-0505-2019-47-052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
Russia is a country with a high prevalence of Helicobacter pylori (HP) infection, a high incidence of gastric cancer, and its late diagnosis. HР infection has been recognized as the leading manageable risk factor for gastric cancer. Accurate diagnostic tests must be used to identify and control the effectiveness of HP eradication, and effective schemes must be implemented for HP eradication. The aim of this article was to analyze the latest consensus documents, systematic reviews and meta-analyzes that reflected the role of HP as a risk factor for the development of gastric cancer, as well as measures for the risk reduction. We describe in detail the diagnostic methods for HP infection, provide data on their use in the Russian Federation, and analyze the efficacy of eradication regimens. In all HPinfected individuals, HP leads to chronic inflammation in the gastric mucosa and launches a precancerous cascade (Correa's cascade). The risk of gastric cancer increases with severe atrophy, intestinal metaplasia and dysplasia. Primary prevention of gastric cancer is most effective if the eradication is performed before atrophic gastritis develops. The available consensus documents underline the importance of HP infection identification by accurate diagnostics at this stage of chronic gastritis. In Russia, the primary HP diagnosis is based on histology (37.7%), rapid urease test (29.2%), and serology (29.7%). HP stool antigen test (31.3%), 13C-urea breath test (23.4%) and the histological method (23.3%) are most often used to control eradication. Currently, the first line of eradication therapy is recommended as triple therapy with clarithromycin prescribed for 14 days. It is recommended to use double dose of proton pump inhibitors and bismuth to increase the effectiveness of this scheme. A 14-days triple regimen enhanced by bismuth has been recommended as the first-line therapy in the Russian Federation.
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Affiliation(s)
- I. N. Voynovan
- Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department
| | - Yu. V. Embutnieks
- Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department
| | - D. V. Mareeva
- Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department
| | | | - D. S. Bordin
- Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department;
Tver State Medical University;
A.I. Yevdokimov Moscow State University of
Medicine and Dentistry
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43
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Inoue M, Sawada N, Goto A, Shimazu T, Yamaji T, Iwasaki M, Tsugane S. High-Negative Anti–Helicobacter pylori IgG Antibody Titers and Long-Term Risk of Gastric Cancer: Results from a Large-Scale Population-Based Cohort Study in Japan. Cancer Epidemiol Biomarkers Prev 2019; 29:420-426. [DOI: 10.1158/1055-9965.epi-19-0993] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/04/2019] [Accepted: 12/03/2019] [Indexed: 01/11/2023] Open
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Cheung KS, Chan EW, Wong AYS, Chen L, Seto WK, Wong ICK, Leung WK. Statins Were Associated with a Reduced Gastric Cancer Risk in Patients with Eradicated Helicobacter Pylori Infection: A Territory-Wide Propensity Score Matched Study. Cancer Epidemiol Biomarkers Prev 2019; 29:493-499. [PMID: 31792089 DOI: 10.1158/1055-9965.epi-19-1044] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 10/08/2019] [Accepted: 11/25/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Individuals may still develop gastric cancer even after Helicobacter pylori eradication. We aimed to investigate statin effect on gastric cancer development in H. pylori-eradicated subjects. METHODS All adult subjects who were prescribed clarithromycin-based triple therapy between 2003 and 2012 were identified in this retrospective cohort study utilizing a territory-wide electronic healthcare database. Patients were observed from index date of H. pylori therapy, and censored at gastric cancer diagnosis, death, or December 2015 (study end date). Statin use was defined as ≥180-day use after index date. Exclusion criteria included gastric cancer diagnosed within the first year after index date, previous gastric cancer or gastrectomy, and H. pylori treatment failure. Subdistribution hazard ratio (SHR) of gastric cancer with statins was calculated by competing risk regression with propensity score (PS) analysis matching 19 variables (age, sex, comorbidities, and other drug usage, including proton pump inhibitors, nonsteroidal anti-inflammatory drugs, aspirin, cyclooxygenase-2 inhibitors, and metformin). RESULTS During a median follow-up of 7.6 years (interquartile range = 5.1-10.3), 169 (0.27%) of 63,605 patients developed gastric cancer at an incidence rate of 3.5 per 10,000 person-years. Among 22,870 PS-matched subjects, statins were associated with a lower gastric cancer risk (SHR = 0.34; 95% confidence interval, 0.19-0.61), in a duration- and dose-response manner (P trend < 0.05). CONCLUSIONS Statins were associated with a lower gastric cancer risk in a duration- and dose-response manner among H. pylori-eradicated patients. IMPACT This study provides evidence on the additional benefits of statins as chemopreventive agents against gastric cancer among H. pylori-eradicated patients.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Esther W Chan
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong
| | - Angel Y S Wong
- Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Lijia Chen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ian C K Wong
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.,UCL School of Pharmacy, University College London, London, United Kingdom
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
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45
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Cheung KS, Chan EW, Chen L, Seto WK, Wong ICK, Leung WK. Diabetes Increases Risk of Gastric Cancer After Helicobacter pylori Eradication: A Territory-Wide Study With Propensity Score Analysis. Diabetes Care 2019; 42:1769-1775. [PMID: 31296646 DOI: 10.2337/dc19-0437] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 06/21/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Whether diabetes mellitus (DM) increases risk of gastric cancer (GC) remains controversial because of inadequate adjustments for important risk factors, including Helicobacter pylori (HP) infection status, concomitant medication use, and cancer site. We investigated whether type 2 DM increased risk of GC in patients after they received treatment for HP infection. RESEARCH DESIGN AND METHODS This was a territory-wide cohort study of patients aged ≥45 years who had received clarithromycin-based triple therapy for HP infection between 2003 and 2012 in Hong Kong. Data were retrieved from a public electronic health database. Observation started from receipt of therapy for HP infection to GC diagnosis, death, or the end of the study (December 2015). Exclusion criteria included type 1 DM, GC diagnosed within the 1st year of HP therapy, prior GC or gastrectomy, and retreatment for HP infection. The adjusted hazard ratio (aHR) of GC with type 2 DM was calculated by using a Cox model that adjusted for 20 covariates (age, sex, comorbidities, and medications) through propensity score regression. RESULTS During a median follow-up of 7.1 years (interquartile range 4.8-9.3 years), 153 of 46,460 patients (0.33%) developed GC at a median age of 72.4 years. Type 2 DM was associated with an increased risk of GC (aHR 1.73 [95% CI 1.08-2.79]). Stratified analysis showed an increase in risk for cardia cancer only (aHR 3.40 [95% CI 1.45-7.97]) and in those with suboptimal DM control (time-weighted mean HbA1c ≥6.0% [42 mmol/mol]; aHR 1.68 [95% CI 1.07-2.63]). CONCLUSIONS Type 2 DM is associated with an increased risk of GC among patients in whom HP was eradicated, in particular gastric cardia cancer and in those with suboptimal DM control.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Esther W Chan
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong
| | - Lijia Chen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Wai Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ian C K Wong
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.,UCL School of Pharmacy, University College London, London, U.K
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
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46
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DNA methylation silencing of microRNA gene methylator in the precancerous background mucosa with and without gastric cancer: Analysis of the effects of H. pylori eradication and long-term aspirin use. Sci Rep 2019; 9:12559. [PMID: 31467363 PMCID: PMC6715663 DOI: 10.1038/s41598-019-49069-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs), such as miR-34c, miR-124a-3, miR-129-2, and miR-137, in the gastric mucosa with and without GC, i.e., in atrophic mucosal glands without intestinal metaplasia (non-IM) and intestinal metaplastic glands (IM). DNA was isolated from non-IM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in non-IM, but not in IM. miR-129-2 methylation in non-IM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either non-IM or IM, irrespective of H. pylori infection. miR-129-2 methylation in non-IM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective for improving methylation in IM than in non-IM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development. In addition, the effects of the interventions were not uniform for each miRNA gene.
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Abstract
The publication was prepared to systematize the data of the literature and our own research on the practice of effective eradication therapy of patients with HP-associated diseases. The most significant factors influencing the effective implementation of modern anti-Helicobacter therapy regimens should be adherence of physicians to the use of clinical guidelines, patient adherence to prescriptions and recommendations of specialists, as well as adherence to eradication treatment protocols.
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48
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Cheung KS, Leung WK, Seto WK. Application of Big Data analysis in gastrointestinal research. World J Gastroenterol 2019; 25:2990-3008. [PMID: 31293336 PMCID: PMC6603810 DOI: 10.3748/wjg.v25.i24.2990] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 04/14/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
Big Data, which are characterized by certain unique traits like volume, velocity and value, have revolutionized the research of multiple fields including medicine. Big Data in health care are defined as large datasets that are collected routinely or automatically, and stored electronically. With the rapidly expanding volume of health data collection, it is envisioned that the Big Data approach can improve not only individual health, but also the performance of health care systems. The application of Big Data analysis in the field of gastroenterology and hepatology research has also opened new research approaches. While it retains most of the advantages and avoids some of the disadvantages of traditional observational studies (case-control and prospective cohort studies), it allows for phenomapping of disease heterogeneity, enhancement of drug safety, as well as development of precision medicine, prediction models and personalized treatment. Unlike randomized controlled trials, it reflects the real-world situation and studies patients who are often under-represented in randomized controlled trials. However, residual and/or unmeasured confounding remains a major concern, which requires meticulous study design and various statistical adjustment methods. Other potential drawbacks include data validity, missing data, incomplete data capture due to the unavailability of diagnosis codes for certain clinical situations, and individual privacy. With continuous technological advances, some of the current limitations with Big Data may be further minimized. This review will illustrate the use of Big Data research on gastrointestinal and liver diseases using recently published examples.
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Affiliation(s)
- Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, Guangdong Province, China
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, Guangdong Province, China
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49
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Cheung KS, Leung WK. Long-term use of proton-pump inhibitors and risk of gastric cancer: a review of the current evidence. Therap Adv Gastroenterol 2019; 12:1756284819834511. [PMID: 30886648 PMCID: PMC6415482 DOI: 10.1177/1756284819834511] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 02/06/2019] [Indexed: 02/04/2023] Open
Abstract
Gastric cancer remains one of the leading cancers in the world with a high mortality, particularly in East Asia. Helicobacter pylori infection accounts for the majority of the noncardia gastric cancers by triggering gastric inflammation and subsequent neoplastic progression. Eradication of H. pylori can reduce, but not totally eliminate, subsequent risk of developing gastric cancer. Proton-pump inhibitors (PPIs) are one of the most widely prescribed medications worldwide. With their profound gastric-acid suppression, there are concerns about a possible carcinogenic role in gastric cancer, due to induced hypergastrinemia, gastric atrophy and bacterial overgrowth in the stomach. While randomized clinical trials to establish causality between long-term PPI use and gastric cancer are lacking, current evidence based on observational studies suggests PPIs are associated with an increased gastric cancer risk. However, opinions on causality remain divergent due to unmeasured and possible residual confounding in various studies. Our recent study has showed that even after H. pylori eradication, long-term PPI use is still associated with an increased risk of gastric cancer by more than twofold. Hence, long-term PPIs should be used judiciously after considering individual's risk-benefit profile, particularly among those with history of H. pylori infection. Further well-designed prospective studies are warranted to confirm the potential role of PPIs in gastric cancer according to baseline gastric histology and its interaction with other chemopreventive agents like aspirin, statins and metformin.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, The University of Hong Kong, Hong Kong
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50
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Mentis AFA, Dardiotis E. Helicobacter pylori Eradication for Metachronous Gastric Cancer: An Unsuitable Methodology Impeding Broader Clinical Usage. Front Oncol 2019; 9:90. [PMID: 30842937 PMCID: PMC6391328 DOI: 10.3389/fonc.2019.00090] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Accepted: 01/31/2019] [Indexed: 12/16/2022] Open
Affiliation(s)
- Alexios-Fotios A Mentis
- Public Health Laboratories, Hellenic Pasteur Institute, Athens, Greece.,Department of Microbiology, University Hospital of Larissa, University of Thessaly, Larissa, Greece
| | - Efthimios Dardiotis
- Department of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece
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