|
1
|
Kak M. Rebamipide in gastric mucosal protection and healing: An Asian perspective. World J Gastrointest Pharmacol Ther 2025; 16:101753. [PMID: 40094150 PMCID: PMC11907339 DOI: 10.4292/wjgpt.v16.i1.101753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/05/2024] [Accepted: 01/02/2025] [Indexed: 03/03/2025] Open
Abstract
This review emphasizes the exemplary safety and efficacy of rebamipide in the treatment of gastric ulcers and other mucosa-related disorders, positioning it as a viable candidate for inclusion in treatment guidelines across India and globally. An in-depth literature review of rebamipide was carried out on PubMed and Google Scholar. Rebamipide has a multifaceted mechanism of action, including prostaglandin synthesis, scavenging free radicals, and enhancing mucin production, leading to enhanced mucosal protection and ulcer healing. Rebamipide serves as a highly effective and safe treatment option for gastric ulcers and gastroesophageal reflux disease. The efficacy of this drug in treating ulcers often surpasses that of routinely used agents such as pantoprazole, sucralfate, misoprostol, famotidine, lansoprazole, and esomeprazole. This superiority of rebamipide can be attributed to the low rate of adverse events associated with it and its mild side effects, contributing to its widespread adoption across Southeast Asia and Russia. This popularity extends to its application beyond gastrointestinal ailments. Notably, it has been successfully employed in the treatment of ophthalmological, oncological, and bone regeneration-related issues. Rebamipide's exemplary safety and efficacy in treating gastric ulcers and other mucosa-related disorders support its potential for inclusion in treatment guidelines, not only in India but also globally.
Collapse
Affiliation(s)
- Manish Kak
- Department of Gastroenterology, Manipal Hospital, Ghaziabad 201002, Uttar Pradesh, India
| |
Collapse
|
|
2
|
Li M, Jin X, Zhou X, Lou G, Ji F, Wang L, Jin H, Huang X, Zhao J, Bao H, Huang L, Shi C, Jin B, Lu H, Lyu B. Effectiveness and safety of a newly designed self-assembling gel in the treatment of endoscopic submucosal dissection-induced gastric ulcer: A multicenter randomized controlled trial. Front Pharmacol 2022; 13:1002381. [DOI: 10.3389/fphar.2022.1002381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 11/18/2022] [Indexed: 12/03/2022] Open
Abstract
Objectives: To evaluate the effectiveness and safety of a newly designed self-assembling gel in treating ESD-induced gastric ulcers in patients.Methods: This open-label, multicenter, randomized controlled trial enrolled patients who underwent ESD between September 2020 and May 2021. Patients were randomized (1:1) to receive the gel (applied to cover the entire ulcer bed under endoscopic guidance immediately after ESD; gel group) or not (control group). The primary outcome was the ulcer healing rate at 28 days. And the secondary outcomes were the delayed bleeding, changes in the ulcer stage, and adverse events.Results: Finally, 125 patients (mean age, 63.7 years; 70 [56.0%] males) were enrolled. The ulcer healing rate was higher in the gel group than in the control group at 28 days (96.9 ± 4.1% vs. 94.7 ± 5.0%; p = 0.001). The ulcer reduction rate at 28 days differed significantly (p < 0.001) between ulcers with majority gel coverage (99.8%), ulcers with minority gel coverage (96.2%), and ulcers with no gel coverage (98.0%). Delayed bleeding was found in 1/63 gel-treated patients (1.6%) versus 5/62 controls (8.1%). A1-stage ulcers were found in 16/63 patients in the gel group versus 44/62 patients in the control group (25.4% vs. 71.0%, p < 0.001) at 3–5 days.Conclusion: The newly developed self-assembling gel was safe and effective in accelerating gastric ulcer healing in patients after ESD.Clinical Trial Registration: UMIN Clinical Trials Registry System (registration number, ChiCTR2100052935).
Collapse
|
|
3
|
Osadchuk MA, Osadchuk AM. Erosive and ulcerative lesions of the digestive tract: optimization of diagnosis and management tactics. TERAPEVT ARKH 2022; 94:271-276. [PMID: 36286751 DOI: 10.26442/00403660.2022.02.201376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 03/29/2022] [Indexed: 11/22/2022]
Abstract
Erosive and ulcerative lesions of the digestive tract are one of the most pressing problems in the clinic of internal diseases due to the extremely widespread prevalence, the presence of severe complications, often fatal, diagnostic difficulties due to the presence of a large number of asymptomatic pathologies and difficulties in the rational choice of therapy. Particularly noteworthy is the data that during the global pandemic of Covid-19 infection, it is capable, quite often, of causing the development of erosive and ulcerative lesions of the gastrointestinal tract. In this regard, it seems important to use drugs that can not only prevent the occurrence of erosive and ulcerative lesions and strictures throughout the gastrointestinal tract, but also effectively achieve epithelialization of injuries to the mucous membrane of the oral cavity, esophagus, stomach, small and large intestine. One of them is Rebamipid-CZ, which has a fairly high safety and efficacy profile. It seems important to consider the issues of optimizing the prevention and treatment of erosive and ulcerative lesions of various parts of the gastrointestinal tract of various etiologies, taking into account the possibility of using rebamipide both as part of complex therapy and in isolation.
Collapse
|
|
4
|
Liu X, Acree WE, Abraham MH. Descriptors for some Compounds with Pharmacological Activity; Calculation of Properties. Int J Pharm 2022; 617:121597. [PMID: 35181462 DOI: 10.1016/j.ijpharm.2022.121597] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/05/2022] [Accepted: 02/13/2022] [Indexed: 11/29/2022]
Abstract
Abraham model solute descriptors have been determined for nisoldipine, nizatidine, loratadine, zonisamide, oxaprozin, rebamipide, domperidone, temozolomide, 'florfenicol', florfenicol A, dapsone, chrysin, benorilate, β-lapachone, and Ipriflavone based on published partition coefficients, molar solubilities and gas chromatographic retention indices. The calculated solute descriptors, combined with our previously published Abraham model correlations, are used to predict several important physicochemical and biological properties, such as air-water, air-blood, air-lung, air-fat, air-skin, water-lipid, water-membrane and water-skin partition coefficients, as well as permeation from water through skin.
Collapse
Affiliation(s)
- Xiangli Liu
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK
| | - William E Acree
- Department of Chemistry, 1155 Union Circle Drive #305070, University of North Texas, Denton, TX, 76203-5017, USA.
| | - Michael H Abraham
- Department of Chemistry, University College London, London WC1H 0AJ, UK, BD7 1DP, UK
| |
Collapse
|
|
5
|
Serum Gastrin and Pepsinogen Levels after Administration of Acid Secretion Inhibitors for Ulcers due to Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer. Gastroenterol Res Pract 2022; 2022:2830227. [PMID: 35126509 PMCID: PMC8816605 DOI: 10.1155/2022/2830227] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 01/11/2022] [Indexed: 11/18/2022] Open
Abstract
Acid secretion inhibitors, such as proton pump inhibitors (PPIs) and potassium competitive acid blockers (PCABs), are used to treat ulcers after endoscopic submucosal dissection (ESD) for early gastric cancer. These drugs can influence serum gastrin and pepsinogen (PG) levels; however, their definite effects remain unclear. This open-label, randomized study investigated the effect of acid secretion inhibitors on the serum gastrin and pepsinogen levels. In total, 76 patients were enrolled in the study. They underwent gastric ESD and received a PPI (n = 21) or PCAB (n = 55). Changes in the serum gastrin and PG levels before and 4 weeks after administration were examined. Patient factors associated with the alteration of serum PG or gastrin levels were identified. The median serum levels of gastrin, PGI, and PGII before the administration of the acid secretion inhibitors were 110.5 pg/mL, 36.4 ng/mL, and 8.9 ng/mL, respectively; after administration, the levels increased to 300 pg/mL, 64.7 ng/mL, and 15.8 ng/mL, respectively (P < 0.01). Univariate analysis revealed that PCABs led to a more significant increase in the serum gastrin and PG levels as compared to PPIs. Furthermore, the PG levels were significantly increased in patients with previous Helicobacter pylori infections than in those with current infections. In conclusion, the serum gastrin and PG levels increased after the use of acid secretion inhibitors. This elevation was affected by the type of drug used, whereas the elevation in PGs was affected by the patient's background as well.
Collapse
|
|
6
|
Rebamipide with Proton Pump Inhibitors (PPIs) versus PPIs Alone for the Treatment of Endoscopic Submucosal Dissection-Induced Ulcers: A Meta-analysis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:7196782. [PMID: 33062694 PMCID: PMC7539128 DOI: 10.1155/2020/7196782] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 08/24/2020] [Indexed: 11/18/2022]
Abstract
Objective To contrast the effect of rebamipide with proton pump inhibitors (PPIs) versus PPIs alone for the treatment of endoscopic submucosal dissection (ESD-) induced ulcers. Methods PubMed, Embase, the Cochrane library, the WanFang database, and China National Knowledge Infrastructure (CNKI) were searched to identify studies that met the inclusion criteria. Results Nine randomized controlled trials (RCTs) were recognized, including 1170 patients. In general, rebamipide plus PPIs acted better than PPIs alone against ESD-induced ulcers at four weeks (RR = 1.42, 95% CI: 1.13-1.78, P = 0.003) but showed no significant differences at eight weeks (RR = 1.03, 95% CI: 0.97-1.10, P = 0.315). The use of rebamipide plus PPIs was superior to PPIs alone for ESD-induced ulcers greater than 20 mm in size (20-40 mm: RR = 1.98, 95% CI: 1.22-3.23, P = 0.006; >40 mm: RR = 5.14, 95% CI: 1.49-17.74, P = 0.010). In addition, rebamipide plus PPI therapy was discovered to be significantly more effective than PPIs alone for lower ESD-induced ulcers (RR = 1.82, 95% CI: 1.04-3.20, P = 0.037). There were no significant differences between the treatment groups with the ulcer reduction rate. Conclusion Evidences now available show rebamipide plus PPIs is practical for protecting against ESD-induced ulcers at four weeks but not at eight weeks, especially large ulcers (>20 mm). However, we still need more high-quality RCTs in the future to supplement our conclusions.
Collapse
|
|
7
|
A Multicenter, Randomized, Controlled Trial of Rebamipide Plus Lansoprazole for the Treatment of Postendoscopic Submucosal Dissection Ulcers. Clin Transl Gastroenterol 2020; 10:e00008. [PMID: 30702488 PMCID: PMC6369969 DOI: 10.14309/ctg.0000000000000008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
To evaluate the healing efficacy of rebamipide and lansoprazole combination therapy with lansoprazole alone for endoscopic submucosal dissection (ESD)–induced ulcers and clarify the ulcer healing-associated factors.
Collapse
|
|
8
|
Ha ES, Lee SK, Jeong JS, Sim WY, Yang JI, Kim JS, Kim MS. Solvent effect and solubility modeling of rebamipide in twelve solvents at different temperatures. J Mol Liq 2019. [DOI: 10.1016/j.molliq.2019.111041] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
|
|
9
|
Risk of post-stroke pneumonia with proton pump inhibitors, H2 receptor antagonists and mucoprotective agents: A retrospective nationwide cohort study. PLoS One 2019; 14:e0216750. [PMID: 31067267 PMCID: PMC6505944 DOI: 10.1371/journal.pone.0216750] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 04/27/2019] [Indexed: 01/16/2023] Open
Abstract
Stroke patients are at high risk of developing pneumonia, which is major cause of post-stroke mortality. Proton pump inhibitors and H2 receptor antagonists are anti-ulcer drugs, which may predispose to the development of pneumonia by suppression of the gastric acid with bactericidal activity. Unlike proton pump inhibitors and H2 receptor antagonists, mucoprotective agents have gastroprotective effects with no or less anti-acid property. We aimed to investigate effects of the acid-suppressive medications (proton pump inhibitors and H2 receptor antagonists) and mucoprotective agents on risk for post-stroke pneumonia using the National Health Insurance Service-National Sample Cohort in Korea. This retrospective cohort study included 8,319 patients with acute ischemic stroke. Use of proton pump inhibitors, H2 receptor antagonists, and mucoprotective agents (rebamipide, teprenone, irsogladine, ecabet, polaprezinc, sofalcone, sucralfate, and misoprostol) after stroke were determined based on the prescription records, which were treated as time-dependent variables. Primary outcome was the development of post-stroke pneumonia. During the mean follow-up period of 3.95 years after stroke, 2,035 (24.5%) patients had pneumonia. In the multivariate time-dependent Cox regression analyses (adjusted hazard ratio [95% confidence interval]), there was significantly increased risk for pneumonia with use of proton pump inhibitors (1.56 [1.24–1.96]) and H2 receptor antagonists (1.40 [1.25–1.58]). In contrast to the proton pump inhibitors and H2 receptor antagonists, use of mucoprotective agents did not significantly increase the risk for pneumonia (0.89 [0.78–1.01]). In conclusion, the treatment with proton pump inhibitors and H2 receptor antagonists was associated with increased risk for pneumonia in stroke patients. Clinicians should use caution in prescribing the acid-suppressive medications for the stroke patients at great risk for pneumonia.
Collapse
|
|
10
|
Kim EH, Park SW, Nam E, Lee JG, Park CH. Comparative efficacy of various anti-ulcer medications after gastric endoscopic submucosal dissection: a systematic review and network meta-analysis. Surg Endosc 2019; 33:1271-1283. [PMID: 30167955 DOI: 10.1007/s00464-018-6409-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 08/24/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The comparative efficacy of various anti-ulcer medications after gastric endoscopic submucosal dissection (ESD) has not been fully evaluated. Recently, vonoprazan, a novel potassium-competitive acid blocker, has also been used in ulcer treatment after ESD. METHODS We searched for all relevant randomized controlled trials examining the efficacy of anti-ulcer medications after gastric ESD, published through October 2017. Healing of iatrogenic ulcers was investigated at 4-8 weeks after ESD. A network meta-analysis was performed to calculate the network estimates. RESULTS Twenty-one studies with 2005 patients were included. Concerning the comparative efficacy for ulcer healing at 4 weeks after ESD, no network inconsistency was identified (Cochran's Q-test, df = 10, P = 0.13; I2 = 34%). A combination therapy of proton-pump inhibitor (PPI) and muco-protective agent was superior to PPI alone [risk ratio (RR) (95% confidence interval, CI) 1.69 (1.20-2.39)]. The combination therapy of PPI and muco-protective agents tended to be superior to vonoprazan [RR (95% CI) 1.98 (0.99-3.94)]. There was no difference of ulcer healing effect between PPI and vonoprazan [RR (95% CI) PPI vs. vonoprazan, 1.17 (0.64-2.12)]. Concerning the ulcer healing rate at 8 weeks after ESD, however, vonoprazan was superior to PPI [RR (95% CI) 1.27 (1.03-1.56)]. Additionally, vonoprazan tended to be superior to the combination therapy of PPI and muco-protective agent [RR (95% CI) 1.20 (0.96-1.51)]. CONCLUSIONS A combination therapy of PPI and muco-protective agent was superior to PPI alone for ulcer healing at 4 weeks after ESD. In the ulcer healing effect at 8 weeks after ESD, vonoprazan was superior to PPI.
Collapse
Affiliation(s)
- Eun Hye Kim
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Se Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwasung, Republic of Korea
| | - Eunwoo Nam
- Biostatistical Consulting and Research Lab, Medical Research Coordinating Center, Hanyang University, Seoul, Republic of Korea
| | - Jae Gon Lee
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea.
| |
Collapse
|
|
11
|
Pittayanon R, Martel M, Barkun A. Role of mucoprotective agents in endoscopic submucosal dissection-derived ulcers: A systematic review. J Gastroenterol Hepatol 2018; 33:1948-1955. [PMID: 29870582 DOI: 10.1111/jgh.14305] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 05/21/2018] [Accepted: 05/27/2018] [Indexed: 12/09/2022]
Abstract
BACKGROUND Currently, it is still unclear whether adding a mucoprotective agent to a proton pump inhibitor (PPI) results in better outcomes compared with using a PPI alone in patients with post-gastric endoscopic submucosal dissection (ESD) ulcers. This study aimed to examine the efficacy of PPI alone versus combination treatment in healing of post-gastric ESD ulcers, as well as on delayed bleeding and amount of blood transfused. METHODS A systematic search of MEDLINE, EMBASE, Cochrane, and ISI Web of knowledge databases, up until May 2017, for randomized trials comparing PPI alone versus PPI plus a mucoprotective drug in achieving ulcer healing in patients undergoing gastric ESD was performed. The primary outcome is scarring stage on endoscopic assessment at 4 or 8 weeks after gastric ESD. RESULTS From an initial 3071 citations, eight articles (n = 953 lesions from 934 patients) were analyzed. Patients receiving combination treatment achieved a scarring stage significantly more often than those on a PPIs alone at 4 or 8 weeks after ESD, (risk ratio = 1.36, 95% CI; 1.06-1.75). No study reported amount of blood transfused. There were no significant between treatment-group differences in terms of delayed bleeding (risk ratio = 0.58, 95% CI; 0.17-1.99). Neither location of ulcer nor Helicobacter pylori infection was related to ulcer scarring stage. CONCLUSION The limited evidences suggested combination treatment may be more effective in accelerating the process of ulcer healing in patients undergoing gastric ESD than the use of PPI alone, but does not appear to alter delayed bleeding risk.
Collapse
Affiliation(s)
- Rapat Pittayanon
- Division of Gastroenterology, McGill University and the McGill University Health Centre, Montreal, Canada.,Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital the Thai Red Cross, Bangkok, Thailand
| | - Myriam Martel
- Division of Gastroenterology, McGill University and the McGill University Health Centre, Montreal, Canada
| | - Alan Barkun
- Division of Gastroenterology, McGill University and the McGill University Health Centre, Montreal, Canada
| |
Collapse
|
|
12
|
Abstract
The paper highlights the features of drug use in the legal aspect. It analyzes instructions for medical use of proton pump inhibitors (PPIs) and gastric protective agents. Taking into account the characteristics of indications registered in the instruction, the authors discuss the possibility of using various PPIs. The instruction for medical application is an official document approved by the Ministry of Health, the basis of which is the data of trials carried out by a manufacturer, and it should be a key or fundamental source for a physician in choosing a medication. The use of a drug with no indications given in the manual (the so-called 'off-label' use in foreign practice), is a clinical trial of a sort conducted by a physician individually, by taking upon himself/herself a legal liability. If arguments break out over the correct choice of this or that drug in treating the specific patient, the instruction containing the indications for use of specific medications to treat a specific disease is one of the proofs that the physician has correctly chosen the drug or a criterion for skilled medical care. The inclusion of chronic gastritis as a primary and only diagnosis into the primary documentation substantially limits the possibilities of using PPIs. When a PPI is indicated for therapy of erosive gastritis, a formal rationale is contained only in the instruction for use of Controloc. There are no registered indications for PPI use to treat chronic non-erosive gastritis; the gastric protective agent Rebagit is indicated.
Collapse
Affiliation(s)
- V I Simanenkov
- I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint Petersburg, Russia
| | - S S Vyalov
- Peoples' Friendship University of Russia, Ministry of Education and Science of Russia, Moscow, Russia
| |
Collapse
|
|
13
|
Fujishiro M, Yoshida S, Matsuda R, Narita A, Yamashita H, Seto Y. Updated evidence on endoscopic resection of early gastric cancer from Japan. Gastric Cancer 2017; 20:39-44. [PMID: 27704225 DOI: 10.1007/s10120-016-0647-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 09/23/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Endoscopic resection for early gastric cancer (EGC) plays a central role in the treatment of EGC in Japan. However, there is still room for improvement, and it is necessary to summarize the recently obtained knowledge from Japan for further improvement. METHODS We conducted a PubMed search to select relevant articles in the 5 years until September 18, 2016, using the keywords "gastric cancer" and "endoscopic treatment," "endoscopic submucosal dissection," "endoscopic mucosal resection," or "polypectomy" and filtering article types as "clinical study" or "clinical trial." RESULTS Among the 329 articles selected automatically from the keywords "polypectomy" (1 article), "endoscopic mucosal resection" (29 articles), "endoscopic submucosal dissection" (77 articles), and "endoscopic treatment" (222 articles) in combination with "gastric cancer," 32 relevant articles from Japanese investigators were chosen. Seven articles were categorized into "equipment," 4 into "preparation and sedation," 17 into "complications and their prevention," and 4 into "therapeutic outcomes." Among them, CO2 insufflation, propofol sedation, and how to prevent post-endoscopic submucosal dissection (ESD) ulcer bleeding and achieve post-ESD ulcer healing were intensively investigated. Long-term outcomes of endoscopic mucosal resection and ESD were also reported as favorable outcomes. CONCLUSIONS Endoscopic resection for EGC is still developing toward an ideal form, pursuing a more reliable, safer, and faster minimally invasive treatment.
Collapse
Affiliation(s)
- Mitsuhiro Fujishiro
- Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Shuntaro Yoshida
- Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Rie Matsuda
- Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Akiko Narita
- Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hiroharu Yamashita
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
14
|
Yakovenko EP, Agafonova NA, Ivanov AN, Yakovenko AV, Aldiyarova MA, Volosheinikova TV, Grigoryeva YV, Soluyanova IP. [The cytoprotective drug rebamipide in therapy for inflammatory and erosive-ulcerative lesions of the gastrointestinal tract]. TERAPEVT ARKH 2016; 88:88-92. [PMID: 27070169 DOI: 10.17116/terarkh201688488-92] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Rebamipide is a cytoprotесtive drug that stimulates the generation of endogenous prostaglandins in the gastric and small intestinal mucosa and accelerates the healing of erosions and ulcers caused by Helicobacter pylori infection and NSAID administration. The major properties of rebamipide include stimulation of prostaglandins and synthesis of muсus glycoproteins, inhibition of reactive oxygen species, inflammatory cytokines, and chemokines, and suppression of neutrophil activation. This paper shows the ability of rebamipide to enhance the efficiency of therapy for Helicobacter pylori-induced infection, to reduce inflammation, including that after infection eradication, to accelerate ulcer healing, and to prevent the progression of preneoplastic lesions.
Collapse
Affiliation(s)
- E P Yakovenko
- N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow, Russia
| | - N A Agafonova
- N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow, Russia
| | - A N Ivanov
- N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow, Russia
| | - A V Yakovenko
- N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow, Russia
| | - M A Aldiyarova
- N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow, Russia
| | - T V Volosheinikova
- Clinical Hospital, Department for Presidential Affairs of the Russian Federation, Moscow, Russia
| | - Yu V Grigoryeva
- Clinical Hospital, Department for Presidential Affairs of the Russian Federation, Moscow, Russia
| | - I P Soluyanova
- Amusk State Medical Academy, Ministry of Health of Russia, Blagoveshchensk, Amursk Region
| |
Collapse
|
|
15
|
Kamada T, Sato M, Tokutomi T, Watanabe T, Murao T, Matsumoto H, Manabe N, Ito M, Tanaka S, Inoue K, Shiotani A, Akiyama T, Hata J, Haruma K. Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study. BIOMED RESEARCH INTERNATIONAL 2015; 2015:865146. [PMID: 26060821 PMCID: PMC4427810 DOI: 10.1155/2015/865146] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 04/18/2015] [Accepted: 04/20/2015] [Indexed: 01/04/2023]
Abstract
Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369.
Collapse
Affiliation(s)
- Tomoari Kamada
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan
| | | | | | | | - Takahisa Murao
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan
| | - Hiroshi Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan
| | - Noriaki Manabe
- Division of Endoscopy and Ultrasound, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan
| | - Masanori Ito
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical Sciences, Hiroshima University, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Kazuhiko Inoue
- Department of General Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan
| | - Akiko Shiotani
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan
| | - Takashi Akiyama
- Department of Pathology, Kawasaki Medical School, Kurashiki 701-0192, Japan
| | - Jiro Hata
- Division of Endoscopy and Ultrasound, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan
| | - Ken Haruma
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan
| |
Collapse
|
|
16
|
Li W, Zhao Y, Xu X, Ma W, Gao P, Wang Y, Liang K, Li R. Rebamipide suppresses TNF-α mediated inflammation in vitro and attenuates the severity of dermatitis in mice. FEBS J 2015; 282:2317-26. [PMID: 25817390 DOI: 10.1111/febs.13278] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 03/08/2015] [Accepted: 03/10/2015] [Indexed: 12/13/2022]
Abstract
Rebamipide is a routine drug for the treatment of gastritis in a clinical setting. Recently, it has been shown to protect against various inflammatory diseases, and has provided a potential therapy for these diseases. However, whether rebamipide has a role in dermatitis remains to be elucidated. Here, we found that rebamipide alleviated the inflammatory reaction induced by tumor necrosis factor-α in RAW264.7, a stable macrophage cell line. Furthermore, rebamipide treatment repressed activation of nuclear factor-kappaB signaling, a well-established inflammatory signaling pathway. Moreover, an oxazolone-induced dermatitis mouse model was established to investigate the role of rebamipide in vivo. PBS control group exhibited typical skin inflammation, whereas treatment with rebamipide remarkably attenuated a dermatitis phenotype in this mouse model. The protective role of rebamipide in dermatitis in vivo was probably due to its inhibition of nuclear factor-kappaB signaling. Collectively, rebamipide may represent a promising molecular target for the prevention and treatment of inflammatory skin diseases.
Collapse
Affiliation(s)
- Weiwei Li
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China
| | - Yunpeng Zhao
- Department of Orthopaedics, Qilu Hospital, Shandong University, Jinan, China
| | - Xiangling Xu
- Department of Gynaecology and Obstetrics, Jinan Central Hospital, Shandong University, Jinan, China
| | - Weiyuan Ma
- Department of Dermatology, Qilu Hospital, Shandong University, Jinan, China
| | - Peng Gao
- Department of Orthopaedics, Zhangqiu People Hospital, Jinan, China
| | - Yan Wang
- Department of Pathology and Physiopathology, Shandong University Medical School, Jinan, China
| | - Ke Liang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China
| | - Ruifeng Li
- Department of Pathology and Physiopathology, Shandong University Medical School, Jinan, China
| |
Collapse
|
|
17
|
Nishizawa T, Suzuki H, Kanai T, Yahagi N. Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective agents for endoscopic submucosal dissection-induced ulcer: a systematic review and meta-analysis. J Clin Biochem Nutr 2015. [PMID: 25759512 DOI: 10.3164/jcbn.14.101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Mucosal protective agents may improve healing of patients with endoscopic submucosal dissection-induced ulcers. The present study systematically evaluated published clinical trials to determine whether combined therapeutic use of mucosal protective agents and proton pump inhibitors can improve the outcome of patients with endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitors alone. PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify eligible randomized trials for systematic review. We identified 11 randomized trials for inclusion in our study (1,160 patients). Pooled endoscopic submucosal dissection-induced ulcer healing rates were 45.8% and 34.4% for patients with or without mucosal protective agents, respectively. The odds ratio was 2.28 (95% confidence interval, 1.57-3.31) with no significant study heterogeneity. In conclusion, the systematic review and meta-analysis showed that the combined therapeutic use of proton pump inhibitors and mucosal protective agents improved healing rates of endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitor monotherapy.
Collapse
Affiliation(s)
- Toshihiro Nishizawa
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan ; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Naohisa Yahagi
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| |
Collapse
|
|
18
|
Nishizawa T, Suzuki H, Kanai T, Yahagi N. Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective agents for endoscopic submucosal dissection-induced ulcer: a systematic review and meta-analysis. J Clin Biochem Nutr 2014; 56:85-90. [PMID: 25759512 PMCID: PMC4345174 DOI: 10.3164/jcbn.14-101] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Accepted: 08/26/2014] [Indexed: 01/17/2023] Open
Abstract
Mucosal protective agents may improve healing of patients with endoscopic submucosal dissection-induced ulcers. The present study systematically evaluated published clinical trials to determine whether combined therapeutic use of mucosal protective agents and proton pump inhibitors can improve the outcome of patients with endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitors alone. PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify eligible randomized trials for systematic review. We identified 11 randomized trials for inclusion in our study (1,160 patients). Pooled endoscopic submucosal dissection-induced ulcer healing rates were 45.8% and 34.4% for patients with or without mucosal protective agents, respectively. The odds ratio was 2.28 (95% confidence interval, 1.57–3.31) with no significant study heterogeneity. In conclusion, the systematic review and meta-analysis showed that the combined therapeutic use of proton pump inhibitors and mucosal protective agents improved healing rates of endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitor monotherapy.
Collapse
Affiliation(s)
- Toshihiro Nishizawa
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan ; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Naohisa Yahagi
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| |
Collapse
|
|
19
|
Wang J, Guo X, Ye C, Yu S, Zhang J, Song J, Cao Z, Wang J, Liu M, Dong W. Efficacy and safety of proton pump inhibitors (PPIs) plus rebamipide for endoscopic submucosal dissection-induced ulcers: a meta-analysis. Intern Med 2014; 53:1243-8. [PMID: 24930641 DOI: 10.2169/internalmedicine.53.2160] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE To compare the efficacy of proton pump inhibitors (PPIs) with rebamipide versus PPIs alone for the treatment of ulcers after endoscopic submucosal dissection (ESD). METHODS PubMed, Web of Science, Medline, Embase, the Cochrane Central Register of Controlled Trials and China Naitonal Knowledge Infrastructure were searched up to the end of October 2013 in order to identify all randomized controlled trials reporting the effects of PPIs plus rebamipide on healing ulcers after ESD. The outcome measurement was complete ulcer healing. RESULTS A total of six studies involving 724 patients were included. The pooled data suggested a significantly higher rate of ulcer healing after endoscopic therapy among patients treated with PPIs plus rebamipide than among those treated with PPIs alone [odds ratio (OR)=2.40, 95% confidence interval (CI): 1.68-3.44]. The subgroup analysis showed PPI plus rebamipide therapy to be more effective in healing ESD-induced ulcers than treatment with PPIs alone after both four (OR=2.22, 95%CI: 1.53-3.24) and eight weeks of treatment (OR=3.19, 95%CI: 1.22-8.31). In addition, the combination therapy was found to be significantly more effective than the use of PPIs alone for all ESD ulcers greater than 20 mm in size (OR=4.77, 95%CI: 2.22-10.26). There were no significant differences between the treatment groups with regard to ulcer location (low, middle or upper stomach) or the presence of absence of H. pylori infection. No serious adverse events were observed in either group. CONCLUSION The results of this meta-analysis suggest that treatment with PPIs plus rebamipide is superior to PPI monotherapy for healing ESD-induced ulcers over four weeks, particularly large ulcers. However, more well-designed trials are needed to confirm these findings.
Collapse
Affiliation(s)
- Jun Wang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, China
| | | | | | | | | | | | | | | | | | | |
Collapse
|