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Lee YM, Barazanchi A, Robertson J, Murphy R, Booth MWC. Long-term effect of Roux-en-Y gastric bypass versus sleeve gastrectomy on reflux and Barrett's oesophagus: a randomized controlled trial. ANZ J Surg 2025; 95:911-918. [PMID: 39829211 DOI: 10.1111/ans.19369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 09/09/2024] [Accepted: 11/29/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is a potentially refluxogenic operation while Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is regarded as an anti-reflux procedure. The aim of this study is to compare long-term incidence of Barrett's Oesophagus (BO) and gastroesophageal reflux disease (GORD) following LSG and LRYGB. METHODS Participants of a double-blinded randomized controlled trial comparing banded LRYGB and LSG for remission of type 2 diabetes were contacted to take part. A gastroscopy was performed. Primary outcome was endoscopic and histologic evidence of BO. Secondary outcomes included reflux and regurgitation scores, presence of oesophagitis, proton-pump inhibitor (PPI) usage, Body Mass Index (BMI), and percentage excess weight loss (%EWL). RESULTS Forty-eight of 109 patients were enrolled into the study (LSG 26 vs. LRYGB 22). Mean follow-up was 7.5 years for the LSG group, and 7.4 years for the RYGB group (P = 0.22). 8 LSG patients had BO while 3 LRYGB patients had BO (30.8%vs13.6%, P = 0.19). There was no significant difference in the mean reflux (8.1 ± 9.4(0-36) vs. 9.3 ± 8.8(0-34), P = 0.47) and regurgitation scores (7.7 ± 6.9(0-22) vs. 11.5 ± 10.5(0-44), P = 0.23) for LSG versus LRYGB patients or between those with and without BO. PPI usage before and after surgery was 6/26 (23.1%) versus 13/26 (50.0%) and 8/22 (36.4%) versus 12/22 (54.5%) for LSG and LRYGB patients respectively. PPI usage in patients with and without BO was 7/11 versus 18/37. EWL was significantly greater (P = 0.0013) in the LRYGB group (74.8 ± 28.1%) compared to LSG group (49.7 ± 18.7%). CONCLUSIONS Long-term incidence of BO trended towards but was not significantly higher for LSG compared to LRYGB group. We support routine endoscopic surveillance for bariatric patients.
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Affiliation(s)
- Young Min Lee
- Department of Surgery, North Shore Hospital, Waitemata District Health Board, Auckland, New Zealand
| | - Ahmed Barazanchi
- Department of Surgery, North Shore Hospital, Waitemata District Health Board, Auckland, New Zealand
| | - Jason Robertson
- Department of Surgery, North Shore Hospital, Waitemata District Health Board, Auckland, New Zealand
| | - Rinki Murphy
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Michael W C Booth
- Department of Surgery, North Shore Hospital, Waitemata District Health Board, Auckland, New Zealand
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Kao SS, Wu DC, Chuah SK, Kao JY, Tai WC, Shie CB, Wu IT, Chen WC, Tsay FW, Chen YH, Hsu PI. Comparison of continuous versus on-demand proton pump inhibitor therapy in symptom control of patients with Barrett's esophagus. J Formos Med Assoc 2025. [DOI: 10.1016/j.jfma.2025.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2025] Open
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Valdovinos-García LR, Villar-Chávez AS, Huerta-Iga FM, Amieva-Balmori M, Arenas-Martínez JS, Bernal-Reyes R, Coss-Adame E, Gómez-Escudero O, Gómez-Castaños PC, González-Martínez M, Morel-Cerda EC, Remes-Troche JM, Rodríguez-Leal MC, Ruiz-Romero D, Valdovinos-Diaz MA, Vázquez-Elizondo G, Velarde-Ruiz Velasco JA, Zavala-Solares MR. Good clinical practice recommendations for proton pump inhibitor prescription and deprescription. A review by experts from the AMG. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2025; 90:111-130. [PMID: 40307154 DOI: 10.1016/j.rgmxen.2024.11.002] [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: 05/26/2024] [Accepted: 11/13/2024] [Indexed: 05/02/2025]
Abstract
INTRODUCTION AND AIM Proton pump inhibitors (PPIs) are widely known drugs that are used quite frequently and indicated in both the short and long terms, in numerous acid-related diseases. Our aim was to produce an expert review that establishes recommendations for the adequate prescription and deprescription of PPIs. METHODS A group of experts in PPI use that are members of the Asociación Mexicana de Gastroenterología (AMG), after extensively reviewing the published literature and discussing each recommendation at a face-to-face meeting, prepared the present document of good clinical practice recommendations. This document is not intended to be a clinical practice guideline or utilize the methodology said format requires. RESULTS Eighteen experts on PPI use developed 22 good clinical practice recommendations for prescribing short-term, long-term, and on-demand PPIs, recognizing adverse events, and lastly, deprescribing PPIs, in acid-related diseases. CONCLUSIONS At present, there is scientific evidence on PPI use in numerous diseases, some in the short term (4-8 weeks), others on-demand (for short periods until symptoms improve), or in the long term (without suspending). Numerous adverse effects have been attributed to PPIs, but the majority have no well-established causal association. Nevertheless, PPIs should be suspended when there is no clear indication for their use. These recommendations aim to aid general physicians and specialists, with respect to PPI prescription and deprescription.
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Affiliation(s)
- L R Valdovinos-García
- Departamento de Cirugía Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Instituto Politécnico Nacional, Escuela Superior de Medicina, Mexico City, Mexico.
| | - A S Villar-Chávez
- Servicio de Gastroenterología, Hospital Ángeles Acoxpa, Mexico City, Mexico
| | - F M Huerta-Iga
- Servicio de Gastroenterología, Hospital Ángeles Torreón, Torreón, Mexico
| | - M Amieva-Balmori
- Laboratorio de Fisiología Digestiva y Motilidad Intestinal, Instituto de Investigaciones Médico-Biológicas de la Universidad Veracruzana, Veracruz, Mexico
| | - J S Arenas-Martínez
- Laboratorio de Motilidad Gastrointestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - R Bernal-Reyes
- Consultor de Gastroenterología, Sociedad Española de Beneficencia, Pachuca, Mexico
| | - E Coss-Adame
- Laboratorio de Motilidad Gastrointestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - O Gómez-Escudero
- Clínica de Gastroenterología, Endoscopia y Motilidad Gastrointestinal, Endoneurogastro, Hospital Ángeles Puebla, Puebla, Mexico
| | - P C Gómez-Castaños
- Servicio de Gastroenterología y Endoscopia Gastrointestinal, Centro de Investigación y Docencia en Ciencias de la Salud, Universidad Autónoma de Sinaloa, Culiacán, Mexico
| | - M González-Martínez
- Laboratorio de Motilidad Gastrointestinal, Departamento de Endoscopia, Hospital de Especialidades del CMN Siglo XXI IMSS, Mexico City, Mexico
| | - E C Morel-Cerda
- Departamento de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico
| | - J M Remes-Troche
- Laboratorio de Fisiología Digestiva y Motilidad Intestinal, Instituto de Investigaciones Médico-Biológicas de la Universidad Veracruzana, Veracruz, Mexico
| | - M C Rodríguez-Leal
- Servicio de Gastroenterología, Hospital Ángeles Valle Oriente, Monterrey, Mexico
| | - D Ruiz-Romero
- Servicio de Gastroenterología, Hospital Ángeles Acoxpa, Mexico City, Mexico
| | | | - G Vázquez-Elizondo
- Servicio de Gastroenterología, Centro de Enfermedades Digestivas ONCARE, Monterrey, Mexico
| | - J A Velarde-Ruiz Velasco
- Departamento de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico
| | - M R Zavala-Solares
- Servicio de Gastroenterología, Hospital Ángeles Centro Sur, Querétaro, Mexico
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Shah SL, Dunbar K. Revisiting Proton Pump Inhibitors as Chemoprophylaxis Against the Progression of Barrett's Esophagus. Curr Gastroenterol Rep 2023; 25:374-379. [PMID: 37940812 DOI: 10.1007/s11894-023-00905-5] [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] [Accepted: 10/24/2023] [Indexed: 11/10/2023]
Abstract
PURPOSE OF REVIEW Barrett's esophagus (BE) is associated with chronic gastroesophageal reflux disease and is a known precursor to esophageal adenocarcinoma. While endoscopic surveillance strategies and the role for endoscopic eradication therapy have been well established, there has been much interest in identifying chemopreventive agents to disrupt or halt the metaplasia-dysplasia-carcinoma sequence in patients with BE. RECENT FINDINGS No pharmacological agent has held more hope in reducing the risk of neoplastic progression in BE than proton pump inhibitors (PPIs). However, data supporting PPIs for chemoprevention have largely been from observational cohort and case-control studies with mixed results. In this review, we revisit the literature and highlight the role of PPIs in patients with BE as it pertains to chemoprophylaxis against the progression of BE to dysplasia and esophageal adenocarcinoma.
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Affiliation(s)
- Shawn L Shah
- Division of Gastroenterology and Hepatology, Department of Medicine, Dallas VA Medical Center and University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - Kerry Dunbar
- Division of Gastroenterology and Hepatology, Department of Medicine, Dallas VA Medical Center and University of Texas Southwestern Medical Center, Dallas, TX, USA
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Kim SE, Schlottmann F, Masrur MA. Management of Long-Segment Barrett's Esophagus. J Laparoendosc Adv Surg Tech A 2023; 33:1201-1210. [PMID: 37796531 DOI: 10.1089/lap.2023.0321] [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] [Indexed: 10/06/2023] Open
Abstract
Background: Gastroesophageal reflux disease is a common gastrointestinal disorder with one of its most feared complications being Barrett's esophagus (BE). Currently, most of the recommendations of BE management are driven by the level of dysplasia. However, the length of BE might also be related to the risk of dysplasia/malignant transformation. We aimed to determine the appropriate management of BE based on its length. Materials and Methods: A systematic literature review was conducted with searches made on PubMed, Embase, and Cochrane databases. Long-segment BE (LSBE) was defined as 3 cm or longer and short-segment BE (SSBE) as under 3 cm. Studies evaluating the behavior and management of SSBE and/or LSBE were included for analysis. Results: LSBE have greater risk of dysplasia or progression to esophageal adenocarcinoma compared to SSBE. Despite this greater risk, LSBE and SSBE are currently managed similarly based on the presence and degree of dysplasia. Endoscopic and ablative techniques may have higher level of success and less complications in SSBE, compared to LSBE. Decreasing time interval between surveillance may be a viable option for managing LSBE. Conclusions: Although many algorithms of monitoring and treatment of BE remain the same regardless of segment length, current evidence suggests that more aggressive management for LSBE might be needed due to its higher risk of malignant progression.
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Affiliation(s)
- Sarah E Kim
- Department of Surgery, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Francisco Schlottmann
- Department of Surgery, University of Illinois at Chicago, Chicago, Illinois, USA
- Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires, Argentina
| | - Mario A Masrur
- Department of Surgery, University of Illinois at Chicago, Chicago, Illinois, USA
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Li S, Hoefnagel SJM, Krishnadath KK. Molecular Biology and Clinical Management of Esophageal Adenocarcinoma. Cancers (Basel) 2023; 15:5410. [PMID: 38001670 PMCID: PMC10670638 DOI: 10.3390/cancers15225410] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/10/2023] [Accepted: 11/12/2023] [Indexed: 11/26/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) is a highly lethal malignancy. Due to its rising incidence, EAC has become a severe health challenge in Western countries. Current treatment strategies are mainly chosen based on disease stage and clinical features, whereas the biological background is hardly considered. In this study, we performed a comprehensive review of existing studies and discussed how etiology, genetics and epigenetic characteristics, together with the tumor microenvironment, contribute to the malignant behavior and dismal prognosis of EAC. During the development of EAC, several intestinal-type proteins and signaling cascades are induced. The anti-inflammatory and immunosuppressive microenvironment is associated with poor survival. The accumulation of somatic mutations at the early phase and chromosomal structural rearrangements at relatively later time points contribute to the dynamic and heterogeneous genetic landscape of EAC. EAC is also characterized by frequent DNA methylation and dysregulation of microRNAs. We summarize the findings of dysregulations of specific cytokines, chemokines and immune cells in the tumor microenvironment and conclude that DNA methylation and microRNAs vary with each different phase of BE, LGD, HGD, early EAC and invasive EAC. Furthermore, we discuss the suitability of the currently employed therapies in the clinic and possible new therapies in the future. The development of targeted and immune therapies has been hampered by the heterogeneous genetic characteristics of EAC. In view of this, the up-to-date knowledge revealed by this work is absolutely important for future EAC studies and the discovery of new therapeutics.
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Affiliation(s)
- Shulin Li
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
- Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands
| | | | - Kausilia Krishnawatie Krishnadath
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2650 Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, 2000 Antwerpen, Belgium
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Mari A, Marabotto E, Ribolsi M, Zingone F, Barberio B, Savarino V, Savarino EV. Encouraging appropriate use of proton pump inhibitors: existing initiatives and proposals for the future. Expert Rev Clin Pharmacol 2023; 16:913-923. [PMID: 37632213 DOI: 10.1080/17512433.2023.2252327] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/14/2023] [Accepted: 08/23/2023] [Indexed: 08/27/2023]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) have revolutionized the management of acid-related disorders, representing today the mainstay treatment of these conditions. However, despite their large range of indications and usefulness, the remarkable expansion of their use in the last two decades cannot be explained by the increasing prevalence of acid-related diseases only. An inappropriate prescription for clinical conditions in which the pathogenetic role of acid has not been documented has been described, with the natural consequence of increasing the costs and the potential risk of iatrogenic harm due to adverse events and complications recently emerged. AREAS COVERED In this review, we summarize current indications of PPIs administration, potential adverse events associated with their chronic utilization, and misuse of PPIs. Moreover, we describe existing and possible initiatives for improving the use of PPIs, and some proposals for the future. EXPERT OPINION PPI deprescribing is the preferred and most effective approach to reduce the use of PPIs, rather than adopting sharp discontinuation, probably due to fewer withdrawal symptoms. Nonetheless, large knowledge gaps still exist in clinical practice regarding the optimal approach of PPI deprescribing in various clinical scenarios. Further prospective well-designed international studies are eagerly warranted to improve our perspectives on controlling global PPI inappropriate use.
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Affiliation(s)
- Amir Mari
- Gastroenterology Unit, Nazareth EMMS Hospital, Nazareth, Israel
- The Azrieli Faculty of Medicine, Bar Ilan University, Nazareth, Israel
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Mentore Ribolsi
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Fabiana Zingone
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, ItalyI
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, ItalyI
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | | | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, ItalyI
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Kasiri K, Sherwin CM, Rostamian S, Heidari-Soureshjani S. Assessment of the Relationship Between Gastric-Acid Suppressants and the Risk of Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis. CURRENT THERAPEUTIC RESEARCH 2023; 98:100692. [PMID: 36798525 PMCID: PMC9925855 DOI: 10.1016/j.curtheres.2023.100692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 01/15/2023] [Indexed: 01/26/2023]
Abstract
Background Esophageal cancer is a cancerous tumor that develops in the esophagus. It is the 10th most common cancer and has a low survival rate. Esophageal adenocarcinoma (EAC) is increasing in incidence globally. Those with EAC are affected by Barrett's esophagus metaplasia, which is attributed to genetic predisposition and is more common in men. Studies suggest that gastric acid suppressants, like proton pump inhibitors and histamine-2 receptor antagonists, have anticancer properties and reduce EAC. However, other research has suggested that they are not cancer-protective, and the use of antisecretory drugs is a risk factor for developing EAC. Objective This systematic review and meta-analysis investigated the properties and risk factors associated with using gastric acid suppressants in patients with EAC. Methods This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Information from selected articles, including the lead author's name, year of publication, study setting, sample size, and gender, was extracted and recorded into an Excel (Microsoft, Redmond, Washington) form. Statistical data included odds ratio, hazard ratio, and/or risk ratio, with a 95% CI associated with patients with EAC and receiving gastric acid suppressants. Data were compared with individuals not receiving treatment. Publication bias was assessed using Begg's and Egger's tests. Statistical analyzes used Stata 14.0 (Stata LLC, College Station, Texas). Results The initial electronic literature search retrieved 3761 titles/abstracts. Extensive screening selected 20 articles for analysis. Odds ratios associated with EAC in the individuals using gastric acid suppressants were 0.77 (95% CI, 0.49-1.22; P = 0.274) and 0.67 (95% CI, 0.39-1.29; P = 0.240) for proton pump inhibitors and 1.02 (95% CI, 0.44-2.36; P = 0.967) for histamine-2 receptor antagonists. Conclusions The results found that gastric acid suppressants do not have a protective role in EAC and are not risk factors. Future studies of confounding variables and risk factors are needed to understand what affects EAC development.
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Affiliation(s)
- Karamali Kasiri
- Department of Pediatrics, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Catherine M.T. Sherwin
- Pediatric Clinical Pharmacology and Toxicology, Department of Pediatrics, Wright State University Boonshoft School of Medicine, Dayton Children's Hospital, Dayton, Ohio
| | - Sahar Rostamian
- Shahrekord University of Medical Science, Student Research Committee, Shahrekord, Iran
| | - Saeid Heidari-Soureshjani
- Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran,Address correspondence to: Saeid Heidari-Soureshjani, Kashani street, Shahrekord University of Medical Sciences, Shahrekord, Iran.
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Lin Y, Wang HL, Fang K, Zheng Y, Wu J. International trends in esophageal cancer incidence rates by histological subtype (1990-2012) and prediction of the rates to 2030. Esophagus 2022; 19:560-568. [PMID: 35689719 DOI: 10.1007/s10388-022-00927-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Accepted: 05/24/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND We provide an up-to-date overview of recent international trends (1990-2012) and predicted trends (2013-2030) in the incidence rates of esophageal cancer. METHODS We used data from the Cancer Incidence in Five Continents (CI5plus) database that contains annual incidence data by cancer site, age, and sex as well as corresponding populations. The age-standardized esophageal cancer incidence rates of each country were calculated and plotted from 1990 through 2012 and were predicted to 2030 using a Bayesian age-period-cohort model. RESULTS Globally, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) showed opposing trends between 1990 and 2012; ESCC showed a decreasing trend, with an AAPC of - 1.5 (95% CI - 2.4, - 0.7), yet EAC showed an increasing trend, with an AAPC of 5.2 (95% CI 4.2, 6.2). The increasing trend in EAC was commonly observed in high-income countries. The predicted trend to 2030 indicated that most countries will continue to experience a decreasing trend or a stable trend in esophageal cancer incidence, except Denmark, the Netherlands, and the UK, where the overall esophageal cancer incidence rates, mainly driven by EAC, are predicted to increase. CONCLUSIONS Decreasing trends in ESCC have been observed worldwide in both low- and middle-income countries and high-income countries, which may have been offset by increasing trends in EAC in high-income countries. The changing patterns of these two main subtypes of esophageal cancer may call for interventions, especially innovative interventions, to address obesity, GERD, and Barrett's esophagus.
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Affiliation(s)
- Yushi Lin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Hong-Liang Wang
- Division of Hepatobiliary and Pancreatic Surgery, Hepatobiliary and Pancreatic Interventional Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Kailu Fang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yang Zheng
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Jie Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
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Proton Pump Inhibitor Use and Risk of Gastric Cancer: Current Evidence from Epidemiological Studies and Critical Appraisal. Cancers (Basel) 2022; 14:cancers14133052. [PMID: 35804824 PMCID: PMC9264794 DOI: 10.3390/cancers14133052] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/16/2022] [Accepted: 06/19/2022] [Indexed: 12/12/2022] Open
Abstract
Proton pump inhibitors (PPIs) are used for maintaining or improving gastric problems. Evidence from observational studies indicates that PPI therapy is associated with an increased risk of gastric cancer. However, the evidence for PPIs increasing the risk of gastric cancer is still being debated. Therefore, we aimed to investigate whether long-term PPI use is associated with an increased risk of gastric cancer. We systematically searched the relevant literature in electronic databases, including PubMed, EMBASE, Scopus, and Web of Science. The search and collection of eligible studies was between 1 January 2000 and 1 July 2021. Two independent authors were responsible for the study selection process, and they considered only observational studies that compared the risk of gastric cancer with PPI treatment. We extracted relevant information from selected studies, and assessed the quality using the Newcastle−Ottawa scale (NOS). Finally, we calculated overall risk ratios (RRs) with 95% confidence intervals (CIs) of gastric cancer in the group receiving PPI therapy and the control group. Thirteen observational studies, comprising 10,557 gastric cancer participants, were included. Compared with patients who did not take PPIs, the pooled RR for developing gastric cancer in patients receiving PPIs was 1.80 (95% CI, 1.46−2.22, p < 0.001). The overall risk of gastric cancer also increased in patients with gastroesophageal reflux disease (GERD), H. pylori treatment, and various adjusted factors. The findings were also consistent across several sensitivity analyses. PPI use is associated with an increased risk of gastric cancer in patients compared with those with no PPI treatment. The findings of this updated study could be used in making clinical decisions between physicians and patients about the initiation and continuation of PPI therapy, especially in patients at high risk of gastric cancer. Additionally, large randomized controlled trials are needed to determine whether PPIs are associated with a higher risk of gastric cancer.
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Savarino V, Antonioli L, Fornai M, Marabotto E, Demarzo MG, Zingone F, Ghisa M, Barberio B, Zentilin P, Ribolsi M, Savarino E. An update of pharmacology, efficacy, and safety of vonoprazan in acid-related disorders. Expert Rev Gastroenterol Hepatol 2022; 16:401-410. [PMID: 34550866 DOI: 10.1080/17474124.2021.1984878] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Patients with acid-related disorders (ARDs) of the upper digestive tract remain highly prevalent and need to be continuously investigated to improve their management. AREAS COVERED This review provides a summary of the most recent advancements in the treatment of ARDs with particular focus on the new drugs available to overcome the unmet needs of traditional therapies. EXPERT OPINION Proton pump inhibitors remain the best therapy in treating ARDs, but a consistent proportion of these patients continues to present mucosal lesions or to experience symptoms despite treatment. These cases pertain mainly to the most severe forms of erosive esophagitis or to non-erosive reflux disease. Also, the increasing rate of patients with H. pylori infection not responding to eradication therapy represents a difficult clinical condition. The recent advent of a new class of antisecretory drugs, such as the potassium competitive acid blockers and, among them the most studied vonoprazan, which are characterized by a better pharmacological profile than PPIs (rapid onset of action, longer lasting acid suppression, control of nocturnal acidity), has the potential to overcome the above-mentioned unmet needs. More research should be done to assess their efficacy in Western populations and their safety in patients treated in the long term.
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Affiliation(s)
- Vincenzo Savarino
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Luca Antonioli
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Matteo Fornai
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Maria Giulia Demarzo
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Fabiana Zingone
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Patrizia Zentilin
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Mentore Ribolsi
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico Di Roma, Rome, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Possible Association between the Use of Proton Pump Inhibitors and H 2 Receptor Antagonists, and Esophageal Cancer: A Nested Case-Control Study Using a Korean National Health Screening Cohort. Pharmaceuticals (Basel) 2022; 15:ph15050517. [PMID: 35631344 PMCID: PMC9146181 DOI: 10.3390/ph15050517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/19/2022] [Accepted: 04/21/2022] [Indexed: 12/22/2022] Open
Abstract
Although safety concerns regarding proton pump inhibitor (PPI)/H2-receptor antagonists (H2RA) in the incident esophageal cancer have been raised, the Asian-based report is unclear. We investigated the estimated likelihood of incident esophageal cancer—its mortality depending on prior history of PPI/H2RA use—and gastroesophageal reflux disease (GERD) in Koreans. Using the Korean National Health Insurance Service-Health Screening Cohort data (2002−2015), a case−control study was retrospectively conducted, including 811 patients with incident esophageal cancer and 3244 controls matched with sex, age, income, and residence. Propensity score overlap weighting was adjusted to balance the baseline covariates. Overlap propensity score-weighted logistic regression analyses were assessed to determine associations of the prior exposure of PPI/H2RA (current vs. past) and the medication duration (<30-, 30−90-, vs. ≥90-days) with incident esophageal cancer and its mortality among the total participants or those with/without the GERD episodes, after adjusting for multiple covariates including PPI/H2RA. The current exposure to either PPI or H2RA showed higher odds for incident esophageal cancer than the nonuser group ([13.23; 95%CI 10.25−17.06] and [4.34; 95%CI 3.67−5.14], respectively), especially in all adults over the age of 40 years without GERD. Both current and past exposures to PPI showed a decreased probability of mortality compared with those of the nonuser group ([0.62; 95%CI 0.45−0.86] and [0.41; 95%CI 0.25−0.67], respectively). However, current or past exposure to H2RA harbored the mutually different likelihoods for mortality depending on the presence of GERD and old age. This study carefully speculates on the possible link between PPI/H2RA and incident esophageal cancer in the Korean population. Mortality appears to be affected by certain risk factors depending on drug types, exposure history, old age, and the presence of GERD.
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Syeda S, Rawat K, Shrivastava A. Pharmacological Inhibition of Exosome Machinery: An Emerging Prospect in Cancer Therapeutics. Curr Cancer Drug Targets 2022; 22:560-576. [DOI: 10.2174/1568009622666220401093316] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 12/31/2021] [Accepted: 01/21/2022] [Indexed: 11/22/2022]
Abstract
Abstract:
Exosomes are nanocarriers that mediate intercellular communication, crucial for normal physiological functions. However, exponentially emerging reports have correlated their dysregulated release with various pathologies, including cancer. In cancer, from stromal remodeling to metastasis, where tumor cells bypass the immune surveillance and show drug resistivity, it has been established to be mediated via tumor-derived exosomes. Owing to their role in cancer pathogenicity, exosome-based strategies offer enormous potential in treatment regimens. These strategies include the use of exosomes as a drug carrier or as an immunotherapeutic agent, which requires advanced nanotechnologies for exosome isolation and characterization. In contrast, pharmacological inhibition of exosome machinery surpasses the requisites of nanotechnology and thus emerges as an essential prospect in cancer therapeutics. In this line, researchers are currently trying to dissect the molecular pathways to reveal the involvement of key regulatory proteins that facilitate the release of tumor-derived exosomes. Subsequently, screening of various molecules in targeting these proteins, with eventual abatement of exosome-induced cancer pathogenicity, is being done. However, their clinical translation requires more extensive studies. Here we comprehensively review the molecular mechanisms regulating exosome release in cancer. Moreover, we give insight into the key findings that highlight the effect of various drugs as exosome blockers, which will add to the route of drug development in cancer management.
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Affiliation(s)
- Saima Syeda
- Department of Zoology, University of Delhi, Delhi-110007, India
| | - Kavita Rawat
- Department of Zoology, University of Delhi, Delhi-110007, India
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14
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Yao H, Wang L, Li H, Xu S, Bai Z, Wu Y, Chen H, Goyal H, Qi X. Proton pump inhibitors may reduce the risk of high-grade dysplasia and/or esophageal adenocarcinoma in Barrett's esophagus: a systematic review and meta-analysis. Expert Rev Clin Pharmacol 2022; 15:79-88. [PMID: 34806503 DOI: 10.1080/17512433.2022.2008909] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 10/27/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Barrett's esophagus (BE) is an important risk factor for high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). The effect of proton pump inhibitors (PPIs) on the chemoprevention of HGD and/or EAC arising from BE remains controversial. RESEARCH DESIGN AND METHODS PubMed, EMBASE, and Cochrane Library databases were systematically searched. Risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by a random-effect model. Heterogeneity and its potential source were assessed. RESULTS Fifteen studies with 26,291 BE patients were included. Meta-analysis of eight cohort studies showed that PPIs can significantly reduce the risk of HGD and/or EAC in BE patients (RR = 0.46; P < 0.001), but meta-analysis of six case-control studies showed no significant benefit of PPIs (OR = 0.64; P = 0.334). Heterogeneity was significant among both cohort and case-control studies, which might be attributed to the information sources of PPIs. There was no significant protective effect of high-dose PPIs on HGD and/or EAC in one RCT (RR = 0.84; P = 0.21), meta-analysis of two cohort studies (RR = 0.61; P = 0.28), or meta-analysis of two case-control studies (OR = 0.32; P = 0.08). CONCLUSIONS Chemoprevention of HGD and/or EAC by PPIs may be considered in BE patients. However, there might not be further preventive effect of high-dose PPIs.
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Affiliation(s)
- Haijuan Yao
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China
- Postgraduate College, Liaoning University of Traditional Chinese Medicine, Shenyang, P.R. China
| | - Le Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China
- Postgraduate College, Dalian Medical University, Dalian, China
- Postgraduate College, China Medical University, Shenyang, China
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China
| | - Shixue Xu
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China
- Postgraduate College, China Medical University, Shenyang, China
| | - Zhaohui Bai
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China
| | - Yanyan Wu
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China
- Postgraduate College, Jinzhou Medical University, Jinzhou, China
| | - Hongxin Chen
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China
- Postgraduate College, Liaoning University of Traditional Chinese Medicine, Shenyang, P.R. China
| | - Hemant Goyal
- Department of Medicine, The Wright Center for Graduate Medical Education, Scranton, PA, USA
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China
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15
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Jung HK, Tae CH, Song KH, Kang SJ, Park JK, Gong EJ, Shin JE, Lim HC, Lee SK, Jung DH, Choi YJ, Seo SI, Kim JS, Lee JM, Kim BJ, Kang SH, Park CH, Choi SC, Kwon JG, Park KS, Park MI, Lee TH, Kim SY, Cho YS, Lee HH, Jung KW, Kim DH, Moon HS, Miwa H, Chen CL, Gonlachanvit S, Ghoshal UC, Wu JCY, Siah KTH, Hou X, Oshima T, Choi MY, Lee KJ, The Korean Society of Neurogastroenterology Motility. 2020 Seoul Consensus on the Diagnosis and Management of Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2021; 27:453-481. [PMID: 34642267 PMCID: PMC8521465 DOI: 10.5056/jnm21077] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the "proven GERD" with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Chung Hyun Tae
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Kyung Ho Song
- Division of Gastroenterology, Department of Internal Medicine, CHA Ilsan Medical Center, CHA University School of Medicine, Ilsan, Jeollabuk-do, Korea
| | - Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Gangnam Center, Seoul, Korea
| | - Jong Kyu Park
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do, Korea
| | - Jeong Eun Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Chungcheongnam-do, Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, Korea
| | - Sang Kil Lee
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Da Hyun Jung
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Jin Choi
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seung In Seo
- Division of Gastroenterology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Joon Sung Kim
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Jung Min Lee
- Digestive Disease Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Sun Hyung Kang
- Department of Gastroenterology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Korea
| | - Suck Chei Choi
- Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea
| | - Joong Goo Kwon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Tae Hee Lee
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Seung Young Kim
- Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Young Sin Cho
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Cheonan, Hospital, Cheonan, Chungcheongnam-do, Korea
| | - Han Hong Lee
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Hirota Miwa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Chien-Lin Chen
- Institute of Medical Sciences, Tzu Chi University, and Department of Public Health, College of Medicine, Tzu Chi University, Hualien City, Taiwan
| | - Sutep Gonlachanvit
- Center of Excellence on Neurogastroenterology and Motility, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Uday C Ghoshal
- Departments of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India
| | - Justin C Y Wu
- Institute of Digestive Disease, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, China
| | - Kewin T H Siah
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Hospital, Singapore
| | - Xiaohua Hou
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Tadayuki Oshima
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Mi-Young Choi
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
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Salimian KJ, Birkness-Gartman J, Waters KM. The path(ology) from reflux oesophagitis to Barrett oesophagus to oesophageal adenocarcinoma. Pathology 2021; 54:147-156. [PMID: 34711413 DOI: 10.1016/j.pathol.2021.08.006] [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: 08/09/2021] [Revised: 08/23/2021] [Accepted: 08/23/2021] [Indexed: 02/07/2023]
Abstract
This review seeks to summarise the steps in the path from reflux oesophagitis to Barrett oesophagus to oesophageal adenocarcinoma. The epidemiology, clinical presentation, definitions, pathological features, diagnostic pitfalls, and emerging concepts are reviewed for each entity. The histological features of reflux oesophagitis can be variable and are not specific. Cases of reflux oesophagitis with numerous eosinophils are difficult to distinguish from eosinophilic oesophagitis and other oesophagitides with eosinophils (Crohn's disease, medication effect, and connective tissue disorders). In reflux oesophagitis, the findings are often most pronounced in the distal oesophagus, the eosinophils are randomly distributed throughout the epithelium, and eosinophilic abscesses and degranulated eosinophils are rare. For reflux oesophagitis with prominent lymphocytes, clinical history and ancillary clinical studies are paramount to distinguish reflux oesophagitis from other causes of lymphocytic oesophagitis pattern. For Barrett oesophagus, the definition remains a hotly debated topic for which the requirement for intestinal metaplasia to make the diagnosis is not applied unanimously across the globe. Assessing for dysplasia is a challenging aspect of the histological interpretation that guides clinical management. We describe the histological features that we find useful in making this evaluation. Oesophageal adenocarcinoma has been steadily increasing in incidence and has a poor prognosis. The extent of invasion can be overdiagnosed due to a duplicated muscularis mucosae. We also describe the technical factors that can lead to challenges in distinguishing the mucosal and deep margins of endoscopic resections. Lastly, we give an overview of targeted therapies with emerging importance and the ancillary tests that can identify the cases best suited for each therapy.
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Affiliation(s)
- Kevan J Salimian
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Kevin M Waters
- Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA.
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17
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Wang L, Han H, Wang Z, Shi L, Yang M, Qin Y. Targeting the Microenvironment in Esophageal Cancer. Front Cell Dev Biol 2021; 9:684966. [PMID: 34513829 PMCID: PMC8427432 DOI: 10.3389/fcell.2021.684966] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 07/27/2021] [Indexed: 12/12/2022] Open
Abstract
Esophageal cancer (EC) is the eighth most common type of cancer and the sixth leading cause of cancer-related deaths worldwide. At present, the clinical treatment for EC is based mainly on radical surgery, chemotherapy, and radiotherapy. However, due to the limited efficacy of conventional treatments and the serious adverse reactions, the outcome is still unsatisfactory (the 5-year survival rate for patients is less than 25%). Thus, it is extremely important and urgent to identify new therapeutic targets. The concept of tumor microenvironment (TME) has attracted increased attention since it was proposed. Recent studies have shown that TME is an important therapeutic target for EC. Microenvironment-targeting therapies such as immunotherapy and antiangiogenic therapy have played an indispensable role in prolonging survival and improving the prognosis of patients with EC. In addition, many new drugs and therapies that have been developed to target microenvironment may become treatment options in the future. We summarize the microenvironment of EC and the latest advances in microenvironment-targeting therapies in this review.
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Affiliation(s)
- Lei Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China
| | - Huiqiong Han
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China
| | - Zehua Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China
| | - Litong Shi
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China
| | - Mei Yang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China
| | - Yanru Qin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China
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18
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Medina AL, Troendle DM, Park JY, Thaker A, Dunbar KB, Cheng E. Eosinophilic esophagitis, Barrett's esophagus and esophageal neoplasms in the pediatric patient: a narrative review. Transl Gastroenterol Hepatol 2021; 6:32. [PMID: 34423153 DOI: 10.21037/tgh-20-223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 07/31/2020] [Indexed: 01/07/2023] Open
Abstract
There are several esophageal disorders that can occur in the pediatric population. Eosinophilic esophagitis (EoE) is an eosinophil predominant inflammatory disease of the esophagus that was first characterized in the early 1900's. EoE is the most common pediatric esophageal inflammatory condition after gastroesophageal reflux disease (GERD). Longstanding GERD is a known risk factor for the development of Barrett's esophagus (BE) in both children and adults. BE is associated with the development of dysplasia and, if left undiagnosed, may progress to the development of esophageal adenocarcinoma (EAC). EAC and esophageal squamous cell carcinoma (ESCC) comprise the majority of childhood esophageal malignant neoplasms. The prevalence of EoE continues to rise within the pediatric population. On the other hand, both BE and esophageal neoplasms remain extremely rare in children. The relationship between a chronic inflammatory condition like EoE to BE and/or esophageal neoplasms remains unclear. The current research of these disease entities is prioritized to further understanding the disease pathogenesis and disease progression, exploring new diagnostic modalities, and developing novel treatments or less invasive therapeutic options. The focus of the following narrative review is to provide a summary of the current clinical practices, future research and their implications on these various esophageal disorders.
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Affiliation(s)
- Annette L Medina
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - David M Troendle
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jason Y Park
- Department of Pathology, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ameet Thaker
- Department of Pathology, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Kerry B Dunbar
- Division of Gastroenterology and Hepatology, Department of Medicine, Esophageal Diseases Center, Dallas VA Medical Center, VA North Texas Healthcare System, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Edaire Cheng
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Health Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
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19
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Klaver E, Bureo Gonzalez A, Mostafavi N, Mallant-Hent R, Duits LC, Baak B, Böhmer CJM, van Oijen AHAM, Naber T, Scholten P, Meijer SL, Bergman JJGHM, Pouw RE. Barrett's esophagus surveillance in a prospective Dutch multi-center community-based cohort of 985 patients demonstrates low risk of neoplastic progression. United European Gastroenterol J 2021; 9:929-937. [PMID: 34228885 PMCID: PMC8498404 DOI: 10.1002/ueg2.12114] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 04/18/2021] [Indexed: 12/20/2022] Open
Abstract
Background and Aims Barrett's esophagus (BE) is accompanied by an increased risk of developing esophageal cancer. Accurate risk‐stratification is warranted to improve endoscopic surveillance. Most data available on risk factors is derived from tertiary care centers or from cohorts with limited surveillance time or surveillance quality. The aim of this study was to assess endoscopic and clinical risk factors for progression to high‐grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in a large prospective cohort of BE patients from community hospitals supported by an overarching infrastructure to ensure optimal surveillance quality. Methods A well‐defined prospective multicenter cohort study was initiated in six community hospitals in the Amsterdam region in 2003. BE patients were identified by PALGA search and included in a prospective surveillance program with a single endoscopist performing all endoscopies at each hospital. Planning and data collection was performed by experienced research nurses who attended all endoscopies. Endpoint was progression to HGD/EAC. Results Nine hundred eighty‐five patients were included for analysis. During median follow‐up of 7.9 years (IQR 4.1–12.5) 67 patients were diagnosed with HGD (n = 28) or EAC (n = 39), progression rate 0.78% per patient‐year. As a clinical risk factor age at time of endoscopy was associated with neoplastic progression (HR 1.05; 95% CI 1.03–1.08). Maximum Barrett length and low‐grade dysplasia (LGD) at baseline were endoscopic predictors of progression (HR 1.15; 95% CI 1.09–1.21 and HR 2.36; 95% CI 1.29–4.33). Conclusion Risk of progression to HGD/EAC in a large, prospective, community‐based Barrett's cohort was low. Barrett's length, LGD and age were important risk factors for progression. (www.trialregister.nl NTR1789)
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Affiliation(s)
- Esther Klaver
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Angela Bureo Gonzalez
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Nahid Mostafavi
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Rosalie Mallant-Hent
- Department of Gastroenterology and Hepatology, Flevohospital, Almere, The Netherlands
| | - Lucas C Duits
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Bert Baak
- Department of Gastroenterology and Hepatology, OLVG Oost, Amsterdam, The Netherlands
| | - Clarisse J M Böhmer
- Department of Gastroenterology and Hepatology, Spaarne Hospital, Hoofddorp, The Netherlands
| | - Arnoud H A M van Oijen
- Department of Gastroenterology and Hepatology, Nothwest Clinics, Alkmaar, The Netherlands
| | - Ton Naber
- Department of Internal Medicine, Tergooi Hospitals, Hilversum, The Netherlands
| | - Pieter Scholten
- Department of Gastroenterology and Hepatology, OLVG West, Amsterdam, The Netherlands
| | - Sybren L Meijer
- Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jacques J G H M Bergman
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Roos E Pouw
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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20
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Fedorova E, Watson TJ. Antireflux and Endoscopic Therapies for Barrett Esophagus and Superficial Esophageal Neoplasia. Surg Clin North Am 2021; 101:391-403. [PMID: 34048760 DOI: 10.1016/j.suc.2021.03.002] [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: 11/25/2022]
Abstract
Barrett esophagus (BE), defined as intestinal metaplasia of the distal esophageal mucosa, typically results from chronic gastroesophageal reflux disease and is the only known precursor of esophageal adenocarcinoma. The standard of care for the management of early esophageal neoplasia in the setting of BE has changed drastically over the past 15 years. Further investigation into diagnostic and therapeutic adjuncts will continue to improve our ability to control or cure BE before its advancement to a life-threatening malignancy.
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Affiliation(s)
- Ekaterina Fedorova
- MedStar Franklin Square Medical Center, 9000 Franklin Square Drive, Department of Surgery, Baltimore, MD 21237, USA
| | - Thomas J Watson
- MedStar Georgetown University Hospital, 3800 Reservoir Rd, NW, 4PHC Department of Surgery, Washington, DC 20007, USA.
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Nrf2/Keap1-Pathway Activation and Reduced Susceptibility to Chemotherapy Treatment by Acidification in Esophageal Adenocarcinoma Cells. Cancers (Basel) 2021; 13:cancers13112806. [PMID: 34199909 PMCID: PMC8200109 DOI: 10.3390/cancers13112806] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/02/2021] [Accepted: 06/03/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Inflammation caused by acidic reflux contributes to disease progression in Barrett’s esophagus. Little is known, whether esophageal cancer cells are influenced by acidic reflux and whether reflux influences cancer cell physiology, targeting the Nrf2/Kepa1- and the NFκB-pathway. The understanding mechanisms of the acidic susceptibility in cells from advanced stages of Barrett’s esophagus will provide further evidence, whether it should be prevented during chemotherapy for EAC treatment. Abstract Chronic acid reflux causes cellular damage and inflammation in the lower esophagus. Due to these irritating insults, the squamous epithelium is replaced by metaplastic epithelium, which is a risk factor for the development of esophageal adenocarcinoma (EAC). In this study, we investigated the acid susceptibility in a Barrett’s cell culture in vitro model, using six cell lines, derived from squamous epithelium (EPC1 and EPC2), metaplasia (CP-A), dysplasia (CP-B), and EAC (OE33 and OE19) cells. Cells exposed to acidic pH showed a decreased viability dependent on time, pH, and progression status in the Barrett’s sequence, with the highest acid susceptibility in the squamous epithelium (EPC1 and EPC2), and the lowest in EAC cells. Acid pulsing was accompanied with an activation of the Nrf2/Keap1- and the NFκB-pathway, resulting in an increased expression of HO1—independent of the cellular context. OE33 showed a decreased responsiveness towards 5-FU, when the cells were grown in acidic conditions (pH 6 and pH 5.5). Our findings suggest a strong damage of squamous epithelium by gastroesophageal reflux, while Barrett’s dysplasia and EAC cells apparently exert acid-protective features, which lead to a cellular resistance against acid reflux.
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Andreev DN, Zaborovsky AV, Lobanova EG. Gastroesophageal reflux disease: new approaches to optimizing pharmacotherapy. MEDITSINSKIY SOVET = MEDICAL COUNCIL 2021:30-37. [DOI: 10.21518/2079-701x-2021-5-30-37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Proton pump inhibitors (PPIs) are baseline drugs for induction and maintenance of remission in gastroesophageal reflux disease (GERD). PPIs have proven to be highly effective in healing esophageal mucosal lesions and relieving the symptoms of the disease in most cases. However, according to the literature data, the incidence rate of clinical ineffectiveness of PPIs in the form of partial or complete persistence of current symptoms during administration of standard doses of PPIs ranges from 10 to 40%. Optimization of GERD therapy in PPI refractory patients is a significant challenge. In most cases, experts advise to increase a dose / dosage frequency of PPIs, switch to CYP2C19-independent PPIs (rabeprazole, esomeprazole, dexlansoprazole), add an esophagoprotective or promotility agents to therapy. At the same time, these recommendations have a limited effect in some patients, which opens up opportunities for looking for new solutions related to the optimization of GERD therapy. Today there is growing evidence of the relevance of the role of disruption of the cytoprotective and barrier properties of the esophageal mucosa in the genesis of GERD and the formation of refractoriness. Intercellular contacts ensure the integrity of the barrier function of the esophageal mucosa to protect it from various exogenous intraluminal substances with detergent properties. Acid-peptic attack in patients with GERD leads to alteration of the expression of some tight junction proteins in epithelial cells of the esophageal mucosa. The latter leads to increased mucosal permeability, which facilitates the penetration of hydrogen ions and other substances into the submucosal layer, where they stimulate the terminals of nerve fibers playing a role in the induction and persistence of the symptoms of the disease. The above evidence brought up to date the effectiveness study of the cytoprotective drugs with tropism to the gastrointestinal tract, as part of the combination therapy of GERD.
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Affiliation(s)
- D. N. Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | | | - E. G. Lobanova
- Yevdokimov Moscow State University of Medicine and Dentistry
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Marabotto E, Pellegatta G, Sheijani AD, Ziola S, Zentilin P, De Marzo MG, Giannini EG, Ghisa M, Barberio B, Scarpa M, Angriman I, Fassan M, Savarino V, Savarino E. Prevention Strategies for Esophageal Cancer-An Expert Review. Cancers (Basel) 2021; 13:2183. [PMID: 34062788 PMCID: PMC8125297 DOI: 10.3390/cancers13092183] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/27/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023] Open
Abstract
In the last 30 years, we have witnessed a rapid increase in the incidence and prevalence of esophageal cancer in many countries around the word. However, despite advancements in diagnostic technologies, the early detection of this cancer is rare, and its prognosis remains poor, with only about 20% of these patients surviving for 5 years. The two major forms are the esophageal squamous cell carcinoma (ESCC), which is particularly frequent in the so-called Asian belt, and the esophageal adenocarcinoma (EAC), which prevails in Western populations. This review provides a summary of the epidemiological features and risk factors associated with these tumors. Moreover, a major focus is posed on reporting and highlighting the various preventing strategies proposed by the most important international scientific societies, particularly in high-risk populations, with the final aim of detecting these lesions as early as possible and therefore favoring their definite cure. Indeed, we have conducted analysis with attention to the current primary, secondary and tertiary prevention guidelines in both ESCC and EAC, attempting to emphasize unresolved research and clinical problems related to these topics in order to improve our diagnostic strategies and management.
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Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Gaia Pellegatta
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Milan, Italy;
| | - Afscin Djahandideh Sheijani
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Sebastiano Ziola
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Patrizia Zentilin
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Maria Giulia De Marzo
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Matteo Ghisa
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.G.); (B.B.)
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.G.); (B.B.)
| | - Marco Scarpa
- Clinica Chirurgica 1, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.S.); (I.A.)
| | - Imerio Angriman
- Clinica Chirurgica 1, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.S.); (I.A.)
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, 35121 Padua, Italy;
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.G.); (B.B.)
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Xie Y, Shi L, He X, Luo Y. Gastrointestinal cancers in China, the USA, and Europe. Gastroenterol Rep (Oxf) 2021; 9:91-104. [PMID: 34026216 PMCID: PMC8128023 DOI: 10.1093/gastro/goab010] [Citation(s) in RCA: 119] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 02/26/2021] [Indexed: 12/17/2022] Open
Abstract
Gastrointestinal (GI) cancers, including colorectal cancer, gastric cancer, and esophageal cancer, are a major medical and economic burden worldwide and have the largest number of new cancer cases and cancer deaths each year. Esophageal and gastric cancers are most common in developing countries, while colorectal cancer forms the major GI malignancy in Western countries. However, a great shift in the predominant GI-cancer type is happening in countries under economically transitioning and, at the same time, esophageal and gastric cancers are reigniting in Western countries due to the higher exposure to certain risk factors. The development of all GI cancers is highly associated with lifestyle habits and all can be detected by identified precancerous diseases. Thus, they are all suitable for cancer screening. Here, we review the epidemiological status of GI cancers in China, the USA, and Europe; the major risk factors and their distribution in these regions; and the current screening strategies.
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Affiliation(s)
- Yumo Xie
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Lishuo Shi
- Center for Clinical Research, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiaosheng He
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yanxin Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
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25
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Elliott JA, Reynolds JV. Visceral Obesity, Metabolic Syndrome, and Esophageal Adenocarcinoma. Front Oncol 2021; 11:627270. [PMID: 33777773 PMCID: PMC7994523 DOI: 10.3389/fonc.2021.627270] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 02/19/2021] [Indexed: 12/16/2022] Open
Abstract
Esophageal adenocarcinoma (EAC) represents an exemplar of obesity-associated carcinogenesis, with a progressive increase in EAC risk with increased body mass index. In this context, there is increased focus on visceral adipose tissue and associated metabolic dysfunction, including hypertension, diabetes mellitus and hyperlipidemia, or combinations of these in the metabolic syndrome. Visceral obesity (VO) may promote EAC via both directly impacting on gastro-esophageal reflux disease and Barrett's esophagus, as well as via reflux-independent effects, involving adipokines, growth factors, insulin resistance, and the microbiome. In this review these pathways are explored, including the impact of VO on the tumor microenvironment, and on cancer outcomes. The current evidence-based literature regarding the role of dietary, lifestyle, pharmacologic and surgical interventions to modulate the risk of EAC is explored.
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Affiliation(s)
- Jessie A Elliott
- Trinity St. James's Cancer Institute, Trinity College Dublin and St. James's Hospital, Dublin, Ireland
| | - John V Reynolds
- Trinity St. James's Cancer Institute, Trinity College Dublin and St. James's Hospital, Dublin, Ireland
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26
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Do proton pump inhibitors prevent Barrett's esophagus progression to high-grade dysplasia and esophageal adenocarcinoma? An updated meta-analysis. J Cancer Res Clin Oncol 2021; 147:2681-2691. [PMID: 33575855 DOI: 10.1007/s00432-021-03544-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 01/21/2021] [Indexed: 12/13/2022]
Abstract
PURPOSE Previous research on the association between proton pump inhibitor (PPI) use and the risk of progression to high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) in Barrett's Esophagus (BE) patients has generated inconsistent findings. This meta-analysis was performed to clarify the association. METHODS We performed a comprehensive search strategy to select relevant studies up to September 2020. Heterogeneity was assessed using the I-squared statistic. Odds ratios (OR) and 95% confidence intervals (CI) were calculated through either fixed-effects or random-effects model. Duration-response was also performed to assess the gain effects of different PPI intake duration. Sensitivity analysis, subgroup analyses, and tests for publication bias or other small-study effects were conducted. RESULTS Twelve studies with 155,769 subjects were included. The PPI use was associated with the reduced risk of BE progression to HGD/EAC (OR = 0.47, 95% CI = 0.32-0.71). In the duration-response analysis, the estimated OR for decreased risk of HGD/EAC with PPI intake duration of 12 months was 0.81 (95% CI = 0.71-0.91). Sensitivity analysis suggested the results of this meta-analysis were stable. No publication bias was detected. CONCLUSIONS PPI use is associated with a decreased risk of HGD/EAC in patients with BE. For further investigation, that more well-designed studies are still needed to elucidate the protective effect of PPI usage on BE patients to prevent HGD/EAC.
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27
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Ivashkin VT, Maev IV, Trukhmanov AS, Sheptulin AA, Simanenkov VI, Lapina TL, Khlynov IB, Dekhnich NN, Lopina OD, Alekseeva OP, Korochanskaya NV, Osipenko MF, Pavlov PV, Pirogov SS, Tarasova GN, Uspenskiy YP, Andreev DN, Rumyantseva DE. Deprescribing and Optimal Selection of Proton Pump Inhibitors (Contributions of the 26th United Russian Gastroenterology Week). RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2020; 30:7-18. [DOI: 10.22416/1382-4376-2020-30-6-7-18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Aim. Presentation of the Forum “Deprescribing and optimal selection of proton pump inhibitors” held in Moscow on 29 September 2020 during the 26th United Russian Gastroenterology Week.Key points. The Forum was aimed at discussing issues associated with improving the proton pump inhibitor (PPIs) therapy in treatment and prevention of acid-related diseases and upper gastrointestinal tract (GIT) disorders induced by non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet medications. Deprescribing is considered to be an effective strategy of a motivated reduction of the PPI dosage, duration of therapy and the patient’s transfer from a regular to on-demand intake regimen. The choice of PPI may condition an optimal therapy for acid-related diseases.Conclusion. PPIs prevail in therapies for acid-related diseases and NSAID-induced upper GIT lesions. PPI deprescribing should be a strategy of choice if medically indicated. A non-enzymatic metabolism, high acid suppression, stable antisecretory effect from day 1 of therapy and cytoprotective action justify the application of rabeprazole (Pariet®) for optimising therapies for acid-related diseases and implementing the deprescribing strategy.
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Affiliation(s)
- V. T. Ivashkin
- Sechenov First Moscow State University (Sechenov University)
| | - I. V. Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | | | - A. A. Sheptulin
- Sechenov First Moscow State University (Sechenov University)
| | | | - T. L. Lapina
- Sechenov First Moscow State University (Sechenov University)
| | | | | | | | | | | | | | - P. V. Pavlov
- Sechenov First Moscow State University (Sechenov University)
| | - S. S. Pirogov
- Herzen Moscow Oncology Research Center — Branch of the National Medical Research Radiology Center
| | | | - Yu. P. Uspenskiy
- Saint-Petersburg State Pediatric Medical University; Pavlov First Saint-Petersburg State Medical University
| | - D. N. Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
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28
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Kaul V, Gross S, Corbett FS, Malik Z, Smith MS, Tofani C, Infantolino A. Clinical utility of wide-area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) in identifying Barrett's esophagus and associated neoplasia. Dis Esophagus 2020; 33:5865411. [PMID: 32607543 DOI: 10.1093/dote/doaa069] [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] [Received: 02/02/2020] [Revised: 05/30/2020] [Accepted: 06/05/2020] [Indexed: 12/11/2022]
Abstract
Sampling error during screening and surveillance endoscopy is a well-recognized problem. Wide-area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D), used adjunctively to forceps biopsy (FB), has been shown to increase the detection of Barrett's esophagus (BE) and BE-associated neoplasia. We evaluated the clinical utility of WATS3D and its impact on the management of patients with BE and dysplasia. Between 2013 and 2018, 432 consecutive patients who had a WATS3D positive and an accompanying FB negative result were identified. Physicians were contacted to determine if the WATS3D result impacted their decision to enroll patients in surveillance or increase the frequency of surveillance, recommend ablation, and/or initiate or increase the dose of proton pump inhibitors (PPIs). WATS3D directly impacted the management of 97.8% of 317 BE patients; 96.2% were enrolled in surveillance and 60.2% were started on PPIs or their dose was increased. WATS3D impacted the management of 94.9% and 94.1% of the 98 low-grade dysplasia and 17 high-grade dysplasia patients, respectively. As a result of WATS3D, 33.7% of low-grade dysplasia and 70.6% of high-grade dysplasia patients underwent endoscopic therapy. More than 37% of all dysplasia patients were enrolled in a surveillance program, and nearly 30% were scheduled to be surveilled more frequently. PPIs were either initiated, or the dose was increased in more than 54% of all dysplasia patients. We demonstrate that WATS3D has high clinical utility. By prompting physicians to change their clinical management in patients with negative FB results, WATS3D, used adjunctively to FB, directly impacts patient management, and improves patient outcomes.
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Affiliation(s)
- Vivek Kaul
- Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, New York
| | - Seth Gross
- Division of Gastroenterology, NYU Langone Medical Center, New York, New York
| | - F Scott Corbett
- Suncoast Endoscopy of Sarasota, Gastroenterology Associates of Sarasota, Sarasota, Florida
| | - Zubair Malik
- Division of Gastroenterology, Temple University, Philadelphia, Pennsylvania
| | - Michael S Smith
- Division of Gastroenterology, Temple University, Philadelphia, Pennsylvania
| | - Christina Tofani
- Department of Gastroenterology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
| | - Anthony Infantolino
- Department of Gastroenterology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
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Incidence trends of esophageal cancer in the Czech Republic by histological subtype and stage and prescription rate of acid suppressing drugs. Cancer Epidemiol 2020; 69:101853. [PMID: 33161372 DOI: 10.1016/j.canep.2020.101853] [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: 07/09/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 11/21/2022]
Abstract
BACKGROUND Incidence of esophageal adenocarcinoma (EAC) associated with gastroesophageal reflux disease has increased substantially in developed countries during the past decades. We aimed to analyze trends in incidence of esophageal cancer (EC) by histological subtypes and trends in acid suppressing drugs prescription in the Czech Republic. METHODS The incidence of EC by histological subtypes, sex, and stage from 1984-2017 was examined using data from the Czech National Cancer Registry. Defined daily doses of acid inhibiting drugs were analyzed from annual reports by the State Institute for Drug Control. RESULTS Age standardized incidence of EAC in men increased annually by 4.88 % with 95 % confidence interval (CI) (4.32, 5.45) from 1984 to 2017, and by 5.11 % (95 % CI, 4.02, 6.20) in women. Squamous cell carcinoma increased annually by 5.52 % (95 % CI, 2.49, 8.64) from 1984 to 1994 with subsequent slower increase by 0.87 % (95 % CI, 0.25, 1.50) from 1994 to 2017. It still represents 50 % of all EC in 2017. The comparable early stages of EAC showed similar annual percentage change of 5.77 %. From 2001 to 2018 the use of proton pump inhibitors increased dramatically from 6.8 to 72.9 defined daily doses per 1000 inhabitants. CONCLUSION The incidence of EAC is still increasing in the Czech Republic, however it represents less than half of ECs. The incidence of squamous cell carcinoma is relatively stable. Broad use of acid suppressing drugs did not seem to impact the incidence of EAC even in early stages.
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30
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Amano Y, Ishimura N, Ishihara S. Is Malignant Potential of Barrett's Esophagus Predictable by Endoscopy Findings? Life (Basel) 2020; 10:E244. [PMID: 33081277 PMCID: PMC7602941 DOI: 10.3390/life10100244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/01/2020] [Accepted: 10/14/2020] [Indexed: 12/17/2022] Open
Abstract
Given that endoscopic findings can be used to predict the potential of neoplastic progression in Barrett's esophagus (BE) cases, the detection rate of dysplastic Barrett's lesions may become higher even in laborious endoscopic surveillance because a special attention is consequently paid. However, endoscopic findings for effective detection of the risk of neoplastic progression to esophageal adenocarcinoma (EAC) have not been confirmed, though some typical appearances are suggestive. In the present review, endoscopic findings that can be used predict malignant potential to EAC in BE cases are discussed. Conventional results obtained with white light endoscopy, such as length of BE, presence of esophagitis, ulceration, hiatal hernia, and nodularity, are used as indicators of a higher risk of neoplastic progression. However, there are controversies in some of those findings. Absence of palisade vessels may be also a new candidate predictor, as that reveals degree of intense inflammation and of cyclooxygenase-2 protein expression with accelerated cellular proliferation. Furthermore, an open type of mucosal pattern and enriched stromal blood vessels, which can be observed by image-enhanced endoscopy, including narrow band imaging, have been confirmed as factors useful for prediction of neoplastic progression of BE because they indicate more frequent cyclooxygenase-2 protein expression along with accelerated cellular proliferation. Should the malignant potential of BE be shown predictable by these endoscopic findings, that would simplify methods used for an effective surveillance, because patients requiring careful monitoring would be more easily identified. Development in the near future of a comprehensive scoring system for BE based on clinical factors, biomarkers and endoscopic predictors is required.
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Affiliation(s)
- Yuji Amano
- Department of Endoscopy, New Tokyo Hospital, 1271 Wanagaya, Matsudo, Chiba 270-2232, Japan
| | - Norihisa Ishimura
- Department of Internal Medicine II, Faculty of Medicine, Shimane University, Shimane 693-8501, Japan; (N.I.); (S.I.)
| | - Shunji Ishihara
- Department of Internal Medicine II, Faculty of Medicine, Shimane University, Shimane 693-8501, Japan; (N.I.); (S.I.)
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31
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Scarpignato C, Sloan JA, Wang DH, Hunt RH. Gastrointestinal pharmacology: practical tips for the esophagologist. Ann N Y Acad Sci 2020; 1481:90-107. [PMID: 32822080 DOI: 10.1111/nyas.14447] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 06/19/2020] [Accepted: 07/05/2020] [Indexed: 12/22/2022]
Abstract
Gastroesophageal reflux disease (GERD) is primarily a motor disorder, and its pathogenesis is multifactorial. As a consequence, treatment should be able to address the underlying pathophysiology. Proton pump inhibitors (PPIs) are the mainstay of medical therapy for GERD, but these drugs only provide the control of symptoms and lesions without curing the disease. However, continuous acid suppression with PPIs is recommended for patients with Barrett's esophagus because of their potential chemopreventive effects. In addition to the antisecretory activity, these compounds display several pharmacological properties, often overlooked in clinical practice. PPIs can indeed affect gastric motility, exert a mucosal protective effect, and an antioxidant, anti-inflammatory, and antineoplastic activity, also protecting cancer cells from developing chemo- or radiotherapeutic resistance. Even in the third millennium, current pharmacologic approaches to address GERD are limited. Reflux inhibitors represent a promise unfulfilled, effective and safe prokinetics are lacking, and antidepressants, despite being effective in selected patients, give rise to adverse events in a large proportion of them. While waiting for new drug classes (like potassium-competitive acid blockers), reassessing old drugs (namely alginate-containing formulations), and paving the new avenue of esophageal mucosal protection are, at the present time, the only reliable alternatives to acid suppression.
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Affiliation(s)
- Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta.,Faculty of Medicine, Chinese University of Hong Kong, ShaTin, Hong Kong
| | - Joshua A Sloan
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - David H Wang
- Division of Hematology and Oncology, UT Southwestern Medical Center and VA North Texas Health Care System, Dallas, Texas
| | - Richard H Hunt
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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32
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Brosnan C, Hannan E, Duggan W, Harding T, Maguire D, Stafford AT. Diagnostic Inaccuracies of Barrett's Oesophagus on Gastroscopy: Are We Performing Unnecessary Surveillance? Cureus 2020; 12:e9850. [PMID: 32953357 PMCID: PMC7497227 DOI: 10.7759/cureus.9850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background It is common for patients to enter Barrett's oesophagus (BO) surveillance based on endoscopic appearances before the diagnosis is histologically confirmed. We set out to review this practice by establishing the accuracy of endoscopic diagnoses of BO. Methods All gastroscopy reports in which a diagnosis of BO was recorded were reviewed over one year. These were compared to the histopathological reports to assess diagnostic accuracy. Results BO was diagnosed in 84 procedures. This diagnosis was incorrect according to histology in 42.9% (n=36) of cases. Diagnostic accuracy was higher with gastroenterologists (38.8% incorrect, n=21) compared to surgeons (50% incorrect, n=15). Diagnostic accuracy was higher with consultants (34.9% incorrect, n=22) compared to registrars (66.7% incorrect, n=14). The dose of sedation used had no impact on accuracy. Unnecessary surveillance was booked in 36.1% (n=13) of cases. Conclusion It is insufficient to rely on endoscopic appearances alone to diagnose BO, irrespective of speciality or experience. The diagnosis should only be made after reviewing the histopathology report. This can eliminate unnecessary repeat endoscopy procedures, sparing patients from unjustifiable risk and helping to cut down on long waiting lists in endoscopy departments. The implementation of the Prague classification and Seattle protocol can improve diagnostic accuracy.
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Affiliation(s)
- Conor Brosnan
- General Surgery, St. Michael's Hospital, Dublin, IRL
| | - Enda Hannan
- Colorectal Surgery, Royal College of Surgeons in Ireland, Dublin, IRL
| | | | - Tim Harding
- General Surgery, St. Michael's Hospital, Dublin, IRL
| | - Donal Maguire
- General Surgery, St. Michael's Hospital, Dublin, IRL
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Snider EJ, Kaz AM, Inadomi JM, Grady WM. Chemoprevention of esophageal adenocarcinoma. Gastroenterol Rep (Oxf) 2020; 8:253-260. [PMID: 32843972 PMCID: PMC7434588 DOI: 10.1093/gastro/goaa040] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 05/29/2020] [Accepted: 06/01/2020] [Indexed: 12/12/2022] Open
Abstract
Esophageal adenocarcinoma (EAC) is a major cause of cancer-related death, particularly in Western populations, and is rapidly rising in Asian populations at this time. Virtually all EACs develop from the precursor lesion Barrett's esophagus (BE), which is the most significant risk factor for EAC. However, the rates of progression from BE to EAC are low and patients with BE are asymptomatic. Thus, any strategy for EAC prevention must carry a low risk of harm in order to be clinically useful. Since current EAC-screening and BE-surveillance methods carry some procedural risk and are burdensome, there is an opportunity for chemoprevention, i.e. medications or dietary factors that may prevent BE from progressing to EAC. A variety of candidate chemoprevention therapies have been assessed to date. Proton-pump inhibitors (PPIs) are the best studied and have modest EAC-chemoprevention efficacy in BE patients, with a recent randomized trial showing that high-dose PPI may be more effective than low-dose PPI. Aspirin and other non-steroidal anti-inflammatory drugs have moderate quality observational and randomized-trial evidence for preventing progression of BE to EAC, but their risks for harm have precluded their routine clinical use. Other therapies (statins, metformin, female sex hormones) generally do not have strong evidence to support their use in EAC chemoprevention. Although progress has been made in this field, there is still a need for more effective and safe chemoprevention therapies for EAC.
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Affiliation(s)
- Erik J Snider
- Division of Gastroenterology, Department of Internal Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Andrew M Kaz
- Division of Gastroenterology, Department of Internal Medicine, University of Washington School of Medicine, Seattle, WA, USA
- Gastroenterology Section, VA Puget Sound Health Care System, Seattle, WA, USA
| | - John M Inadomi
- Division of Gastroenterology, Department of Internal Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - William M Grady
- Division of Gastroenterology, Department of Internal Medicine, University of Washington School of Medicine, Seattle, WA, USA
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Savarino V, Marabotto E, Zentilin P, Furnari M, Bodini G, De Maria C, Tolone S, De Bortoli N, Frazzoni M, Savarino E. Pathophysiology, diagnosis, and pharmacological treatment of gastro-esophageal reflux disease. Expert Rev Clin Pharmacol 2020; 13:437-449. [PMID: 32253948 DOI: 10.1080/17512433.2020.1752664] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic, relapsing disorder, whose knowledge has increased in last years thanks to the advent of new sophisticated techniques, such as 24-h impedance-pH monitoring and high-resolution manometry, for the study of esophageal functions. AREAS COVERED This review provides an overview of our advancements in understanding the complex pathophysiology, improving the diagnosis and defining the modern pharmacological therapeutic approach to GERD. EXPERT OPINION The growing clinical application of impedance-pH testing has allowed us to know the diversity of patients with non-erosive reflux disease (NERD), who nowadays represent about 70% of the whole population with reflux symptoms. We have realized that NERD has to be considered as an umbrella term covering various subgroups with different pathophysiologies. The development of new impedance metrics, in particular mean nocturnal baseline impedance, seems to be promising in the improvement of the diagnostic process of this disease. There are no particularly innovative features in the pharmacological therapy of GERD, unless the interest toward drugs is able to increase the defense properties of esophageal mucosa and/or its protection. These compounds can be of help in combination with proton pump inhibitors in NERD patients with partial response to antisecretory drugs alone.
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Affiliation(s)
| | - Elisa Marabotto
- Department of Internal Medicine, University of Genoa , Genoa, Italy
| | | | - Manuele Furnari
- Department of Internal Medicine, University of Genoa , Genoa, Italy
| | - Giorgia Bodini
- Department of Internal Medicine, University of Genoa , Genoa, Italy
| | | | - Salvatore Tolone
- Department of Surgery, University of Campania "Luigi Vanvitelli" , Naples, Italy
| | - Nicola De Bortoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa , Pisa, Italy
| | - Marzio Frazzoni
- Department of Gastroenterology, Gastroenterology Digestive Pathophysiology Unit, Baggiovara Hospital , Modena, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua, Italy
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Ward C, Meehan J, Gray ME, Murray AF, Argyle DJ, Kunkler IH, Langdon SP. The impact of tumour pH on cancer progression: strategies for clinical intervention. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2020; 1:71-100. [PMID: 36046070 PMCID: PMC9400736 DOI: 10.37349/etat.2020.00005] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2019] [Accepted: 02/05/2020] [Indexed: 02/06/2023] Open
Abstract
Dysregulation of cellular pH is frequent in solid tumours and provides potential opportunities for therapeutic intervention. The acidic microenvironment within a tumour can promote migration, invasion and metastasis of cancer cells through a variety of mechanisms. Pathways associated with the control of intracellular pH that are under consideration for intervention include carbonic anhydrase IX, the monocarboxylate transporters (MCT, MCT1 and MCT4), the vacuolar-type H+-ATPase proton pump, and the sodium-hydrogen exchanger 1. This review will describe progress in the development of inhibitors to these targets.
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Affiliation(s)
- Carol Ward
- Cancer Research UK Edinburgh Centre and Edinburgh Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, EH4 2XU Edinburgh, UK
| | - James Meehan
- Cancer Research UK Edinburgh Centre and Edinburgh Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, EH4 2XU Edinburgh, UK
| | - Mark E Gray
- Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, EH25 9RG Midlothian, UK
| | - Alan F Murray
- School of Engineering, Institute for Integrated Micro and Nano Systems, EH9 3JL Edinburgh, UK
| | - David J Argyle
- Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, EH25 9RG Midlothian, UK
| | - Ian H Kunkler
- Cancer Research UK Edinburgh Centre and Edinburgh Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, EH4 2XU Edinburgh, UK
| | - Simon P Langdon
- Cancer Research UK Edinburgh Centre and Edinburgh Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, EH4 2XU Edinburgh, UK
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Dugalic P, Djuranovic S, Pavlovic-Markovic A, Dugalic V, Tomasevic R, Gluvic Z, Obradovic M, Bajic V, Isenovic ER. Proton Pump Inhibitors and Radiofrequency Ablation for Treatment of Barrett's Esophagus. Mini Rev Med Chem 2020; 20:975-987. [PMID: 31644405 DOI: 10.2174/1389557519666191015203636] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 06/04/2019] [Accepted: 06/25/2019] [Indexed: 02/07/2023]
Abstract
Gastroesophageal Reflux Disease (GERD) is characterized by acid and bile reflux in the distal oesophagus, and this may cause the development of reflux esophagitis and Barrett's oesophagus (BE). The natural histological course of untreated BE is non-dysplastic or benign BE (ND), then lowgrade (LGD) and High-Grade Dysplastic (HGD) BE, with the expected increase in malignancy transfer to oesophagal adenocarcinoma (EAC). The gold standard for BE diagnostics involves high-resolution white-light endoscopy, followed by uniform endoscopy findings description (Prague classification) with biopsy performance according to Seattle protocol. The medical treatment of GERD and BE includes the use of proton pump inhibitors (PPIs) regarding symptoms control. It is noteworthy that long-term use of PPIs increases gastrin level, which can contribute to transfer from BE to EAC, as a result of its effects on the proliferation of BE epithelium. Endoscopy treatment includes a wide range of resection and ablative techniques, such as radio-frequency ablation (RFA), often concomitantly used in everyday endoscopy practice (multimodal therapy). RFA promotes mucosal necrosis of treated oesophagal region via high-frequency energy. Laparoscopic surgery, partial or total fundoplication, is reserved for PPIs and endoscopy indolent patients or in those with progressive disease. This review aims to explain distinct effects of PPIs and RFA modalities, illuminate certain aspects of molecular mechanisms involved, as well as the effects of their concomitant use regarding the treatment of BE and prevention of its transfer to EAC.
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Affiliation(s)
- Predrag Dugalic
- Department of Gastroenterology and Hepatology, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Srdjan Djuranovic
- Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Pavlovic-Markovic
- Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Vladimir Dugalic
- Clinical Centre of Serbia, Clinic for Surgery, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ratko Tomasevic
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Zoran Gluvic
- Department of Endocrinology and Diabetes, Faculty of Medicine, University of Belgrade, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
| | - Vladan Bajic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
| | - Esma R Isenovic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
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Amano Y, Nakahara R, Yuki T, Murakami D, Ujihara T, Tomoyuki I, Sagami R, Suehiro S, Katsuyama Y, Hayasaka K, Harada H, Tada Y, Miyaoka Y, Fujishiro H. Relationship between Barrett's esophagus and colonic diseases: a role for colonoscopy in Barrett's surveillance. J Gastroenterol 2019; 54:984-993. [PMID: 31240437 DOI: 10.1007/s00535-019-01600-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 06/18/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Given that risk factors for Barrett's carcinogenesis are predictive, appropriate management and surveillance of Barrett's esophagus (BE) may be provided. The presence of colorectal neoplasms (CRNs) is a possible predictor of the development of BE and the progression to esophageal adenocarcinoma (EAC). We evaluated the relationship between BE or EAC and colonic diseases, including neoplasms and diverticulosis. METHODS Patients (N = 5606) who underwent both colonoscopy and esophagogastroduodenoscopy between January 2016 and December 2017 at three institutions were enrolled. The relationships between the presence of colonic diseases and BE or EAC and other clinical or endoscopic predictors of the presence of BE were investigated retrospectively. RESULTS The prevalence of BE ≥ 1 cm and ≥ 3 cm in length was 13.0% and 0.52%, respectively. BE was closely related with the presence of colorectal adenoma (48.4% vs. 37.2% in non-BE; P < 0.001), adenocarcinoma (16.6% vs. 8.4%, P < 0.001) and colonic diverticulosis (CD) (34.1% vs. 29.3%, P < 0.001). In patients with long-segment BE, CRNs (79.3%, P < 0.001) and CD (48.2%, P = 0.038) were more common. EAC patients also had a statistically significantly higher incidence of CRNs than non-BE patients (87.5% vs. 45.6%, P = 0.027). Diverticulosis at the distal colon correlated significantly with EAC and BE (50.0%, P = 0.010 and 15.4%, P = 0.024, vs. 12.0% in non-BE). Multivariate analysis showed that CRNs (t = 8.55, P < 0.001), reflux esophagitis (t = 5.26, P < 0.001) and hiatal hernia (t = 11.68, P < 0.001) were predictors of BE. CONCLUSIONS The presence of CRNs was strongly associated with BE and EAC. Therefore, colonoscopy may be useful for establishing a strategy for the surveillance of BE.
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Affiliation(s)
- Yuji Amano
- Department of Endoscopy, New Tokyo Hospital, 1271 Wanagaya, Matsudo, 270-2232, Chiba, Japan.
| | - Ryotaro Nakahara
- Department of Gastroenterology, New Tokyo Hospital, Matsudo, Chiba, Japan
| | - Takafumi Yuki
- Department of Gastroenterology, Matsue Red Cross Hospital, Matsue, Japan
| | - Daisuke Murakami
- Department of Gastroenterology, New Tokyo Hospital, Matsudo, Chiba, Japan
| | - Tetsuro Ujihara
- Department of Gastroenterology, New Tokyo Hospital, Matsudo, Chiba, Japan
| | - Iwaki Tomoyuki
- Department of Gastroenterology, New Tokyo Hospital, Matsudo, Chiba, Japan
| | - Ryota Sagami
- Department of Gastroenterology, New Tokyo Hospital, Matsudo, Chiba, Japan
| | - Satoshi Suehiro
- Department of Gastroenterology, New Tokyo Hospital, Matsudo, Chiba, Japan
| | - Yasushi Katsuyama
- Department of Gastroenterology, New Tokyo Hospital, Matsudo, Chiba, Japan
| | - Kenji Hayasaka
- Department of Gastroenterology, New Tokyo Hospital, Matsudo, Chiba, Japan
| | - Hideaki Harada
- Department of Gastroenterology, New Tokyo Hospital, Matsudo, Chiba, Japan
| | - Yasumasa Tada
- Department of Gastroenterology, Matsue Red Cross Hospital, Matsue, Japan
| | - Youichi Miyaoka
- Department of Endoscopy, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Hirofumi Fujishiro
- Department of Gastroenterology, Shimane Prefectural Central Hospital, Izumo, Japan
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Lee L, Ramos-Alvarez I, Ito T, Jensen RT. Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome. Int J Mol Sci 2019; 20:5128. [PMID: 31623145 PMCID: PMC6829234 DOI: 10.3390/ijms20205128] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/08/2019] [Accepted: 10/13/2019] [Indexed: 02/07/2023] Open
Abstract
The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA.
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
| | | | - Tetsuhide Ito
- Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan.
| | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA.
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Evaluation and Management of Premalignant Conditions of the Esophagus: A Systematic Survey of International Guidelines. J Clin Gastroenterol 2019; 53:627-634. [PMID: 31403982 DOI: 10.1097/mcg.0000000000001247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Esophageal cancer represents one of the most lethal forms of malignancy. The growing incidence of esophageal adenocarcinoma represents an emerging public health concern. This review article summarizes current diagnostic, management, and therapeutic practices of premalignant conditions of the esophagus including Barrett's esophagus, tylosis, granular cell tumors, achalasia, and the ingestion of caustic substances. Our report provides clinicians and academics with a global clinical perspective regarding presentation, surveillance guidelines, and therapeutic management of these esophageal conditions.
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Maev IV, Andreev DN, Kucheryavyy YA, Shaburov RI. [Current advances in the treatment of gastroesophageal reflux disease: a focus on esophageal protection]. TERAPEVT ARKH 2019; 91:4-11. [PMID: 32598747 DOI: 10.26442/00403660.2019.08.000387] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 02/07/2023]
Abstract
Gastroesophageal reflux disease (GERD) is characterized by high morbidity and a significant decrease in the quality of life of patients, and is a major risk factor for esophageal adenocarcinoma. Nowadays, antisecretory therapy with proton pump inhibitors (PPI) is the "gold standard" of conservative treatment of GERD, but in some cases this therapy is unsuccessful. According to various studies, the prevalence of refractory GERD can reach 30-40%. The latest scientific data in the field of genetics and pathophysiology of GERD demonstrate that a disruption of the barrier function of the esophageal mucosa and an increase of its permeability can be the leading causes of refractoriness. Thus, the optimal therapy for patients with GERD should not only suppress the secretion of hydrochloric acid, but also restore the barrier function of the mucous membrane, providing an esophagoprotective effect. To achieve these goals, Alfasoxx was developed, which consists of a mixture of low molecular weight hyaluronic acid and low molecular weight chondroitin sulfate dissolved in a bioadhesive carrier (poloxamer 407). The clinical efficacy of this product has been confirmed by three prospective, randomized, placebo - controlled trials. Alfasoxx has a healing and restorative effect towards the esophageal epithelium and due to high ability for bioadhesion provides long - term protection of the mucous membrane of the esophagus. Combination therapy for GERD with the use of PPI and an esophagoprotector offers new perspectives for the treatment of patients with GERD.
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Affiliation(s)
- I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - D N Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - Y A Kucheryavyy
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - R I Shaburov
- Yevdokimov Moscow State University of Medicine and Dentistry
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42
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Fitzgerald RC, Corley DA. Will a Proton Pump Inhibitor and an Aspirin Keep the Doctor Away for Patients With Barrett's Esophagus? Gastroenterology 2019; 156:1228-1231. [PMID: 30849313 DOI: 10.1053/j.gastro.2019.03.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
| | - Douglas A Corley
- Division of Research, Kaiser Permanente Northern California, Oakland, California
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Omeprazole prevents CDX2 and SOX9 expression by inhibiting hedgehog signaling in Barrett's esophagus cells. Clin Sci (Lond) 2019; 133:483-495. [PMID: 30705106 DOI: 10.1042/cs20180828] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 01/19/2019] [Accepted: 01/30/2019] [Indexed: 01/26/2023]
Abstract
Activation of hedgehog (Hh) signaling contributes to the progression of Barrett's esophagus (BE), which increases the risk of esophageal adenocarcinoma. Recent clinical studies revealed that proton-pump inhibitors (PPIs) but not H2 receptor antagonists (H2RAs) were associated with a decreased risk of esophageal adenocarcinoma. We would like to know whether PPIs interfere with BE progression during BE treatment. Here, we explored the role of omeprazole on Hh signaling and expression of two crucial biomarkers of BE, SOX9 and CDX2. We demonstrated that bile acids elevated expression of Hh pathway target genes, such as GLI1 and PTCH1, and induced SOX9 and CDX2 up-regulation in both CP-A and CP-B cells. Omeprazole, but not famotidine, down-regulated these genes induced by bile acids. In addition, omeprazole-induced down-regulation of SOX9 and CDX2 was mediated by Hh signaling. To explore the mechanisms by which omeprazole inhibits Hh signaling, we performed luciferase assay but did not find any effects of omeprazole on the activity of GLI1 promoter, the critical transcription factor of Hh signaling. Therefore, we used miRNA sequencing and a bioinformatics tool in our study to identify the differently expressed miRNAs in BE organoids treated with or without omeprazole, and we identified miR-2116-3p was involved in omeprazole-mediated inhibition of Hh signaling and subsequent down-regulation of SOX9 and CDX2. Collectively, our data indicate omeprazole inhibits Hh signaling and subsequent SOX9 and CDX2 expression via up-regulating miR-2116-3p. We have demonstrated a novel acid-independent mechanism of omeprazole that might yield valuable insight into clinical management of BE progression, irrespective of acid reflux symptoms.
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44
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Chen CH, Lee CZ, Lin YC, Kao LT, Lin HC. Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population-Based Study. J Clin Pharmacol 2018; 59:350-355. [PMID: 30329162 DOI: 10.1002/jcph.1329] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 09/25/2018] [Indexed: 12/17/2022]
Abstract
Although current evidence suggests potential antitumor activity of proton pump inhibitors (PPIs), there is no population-based evidence of an association between PPI use and subsequent breast cancer risks. We used an observational case-control study to examine the association between prior PPI use and breast cancer occurrence. Additional analysis examined dose-response and age-stratified associations of PPIs with breast cancer. This study used data from the Taiwan National Health Insurance Research Dataset. A total of 64,234 women diagnosed with breast cancer between 2004 and in 2013 were selected as cases. Controls were 64,234 women without cancer who were selected by matching them with cases on the basis of sociodemographic characteristics and widely prevalent comorbidities. Each study subject's claims data were tracked back for 5 years to determine precancer prescriptions of PPIs. Logistic regression modeling was used for the analysis. A total of 11,871 (9.24%) women had used PPIs within the prior 5 years, 8.06% and 10.42% among cases and controls, respectively. Breast cancer patients were 25% less likely to have had prior PPI exposure after adjustment for comorbidities that predispose to PPI exposure (95%CI 0.72-0.78) in the risk of breast cancer occurrence. A dose-response effect was also detected, with the highest effect, 35% lower PPI odds (95%CI 0.61-0.70) among patients in the highest exposure category. Our findings may suggest that women at a higher-than-average risk of breast cancer may benefit from PPI prescriptions if they have medical conditions that could benefit from PPIs.
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Affiliation(s)
- Chao-Hung Chen
- Department of Thoracic Surgery, Mackay Memorial Hospital, Taipei, Taiwan.,Department of Cosmetic Applications and Management, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.,Research Center of Sleep Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Cha-Ze Lee
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Yi-Chun Lin
- Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Li-Ting Kao
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.,Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan
| | - Herng-Ching Lin
- School of Health Care Administration, Taipei Medical University, Taipei, Taiwan.,Sleep Research Center, Taipei Medical University Hospital, Taipei, Taiwan
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Savarino V, Marabotto E, Zentilin P, Furnari M, Bodini G, De Maria C, Pellegatta G, Coppo C, Savarino E. Proton pump inhibitors: use and misuse in the clinical setting. Expert Rev Clin Pharmacol 2018; 11:1123-1134. [PMID: 30295105 DOI: 10.1080/17512433.2018.1531703] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered: The following evidence-based indications for PPI use are acknowledged by many scientific societies: treatment of the various forms and complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome. Expert Commentary: Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and the endless expansion of the PPI market has created important problems for many regulatory authorities for two relevant features: the progressive increase of the costs of therapy and the greater potential harms for the patients. The major reasons for the misuse of PPIs are the prevention of gastro-duodenal ulcers in patients without risk factors and the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anti-platelet or anti-coagulant treatment in patients without risk of gastric injury and the overtreatment of functional dyspepsia.
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Affiliation(s)
- Vincenzo Savarino
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Elisa Marabotto
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Patrizia Zentilin
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Manuele Furnari
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Giorgia Bodini
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Costanza De Maria
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Gaia Pellegatta
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Claudia Coppo
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Edoardo Savarino
- b Gastrointestinal Unit, Department of Surgery , Oncology and Gastroenterology, University of Padua , Padua , Italy
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Savarino V, Marabotto E, Zentilin P, Furnari M, Bodini G, De Maria C, Pellegatta G, Coppo C, Savarino E. The appropriate use of proton-pump inhibitors. Minerva Med 2018; 109. [PMID: 29856192 DOI: 10.23736/s0026-4806.18.05705-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Savarino V, Tosetti C, Benedetto E, Compare D, Nardone G. Appropriateness in prescribing PPIs: A position paper of the Italian Society of Gastroenterology (SIGE) - Study section "Digestive Diseases in Primary Care". Dig Liver Dis 2018; 50:894-902. [PMID: 30093304 DOI: 10.1016/j.dld.2018.07.004] [Citation(s) in RCA: 28] [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: 06/03/2018] [Revised: 07/04/2018] [Accepted: 07/09/2018] [Indexed: 02/06/2023]
Abstract
The introduction of proton pump inhibitors (PPIs) into clinical practice about thirty years ago has greatly improved our therapeutic approach to acid-related diseases for their well-recognized efficacy and safety. Despite the well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and this phenomenon poses serious queries that include the onset of potential adverse effects and the increase in health care costs. The major reason explaining this worrying market expansion is the inappropriate use of PPIs. In order to re-establish a correct use of these effective drugs in daily clinical practice, the Italian Society of Gastroenterology (SIGE), nominated a panel of experts who reviewed the available clinical literature and produced a series of updated position statements on the use of PPIs in clinical practice.
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Affiliation(s)
| | | | | | - Debora Compare
- Department of Clinical Medicine and Surgery, University Federico II of Naples, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, University Federico II of Naples, Italy.
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Tan MC, El-Serag HB, Yu X, Thrift AP. Acid suppression medications reduce risk of oesophageal adenocarcinoma in Barrett's oesophagus: a nested case-control study in US male veterans. Aliment Pharmacol Ther 2018; 48:469-477. [PMID: 29956826 DOI: 10.1111/apt.14895] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 04/23/2018] [Accepted: 06/13/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may reduce the risk of oesophageal adenocarcinoma (OAC) in Barrett's oesophagus; however, current epidemiologic studies are inconclusive. AIM To evaluate the independent effects of PPIs and H2RAs on risk of OAC in patients with Barrett's oesophagus. METHODS We conducted a nested case-control study of male veterans diagnosed with Barrett's oesophagus. Cases with incident OAC were matched by incidence density sampling on birth year and Barrett's diagnosis date to controls with Barrett's oesophagus who did not develop OAC. We identified prescription medication usage 1 year prior to Barrett's oesophagus diagnosis to 3 months prior to the OAC diagnosis. Odds ratios (OR) and 95% CI were estimated using conditional logistic regression. RESULTS Compared with 798 controls, the 300 cases were less likely to use PPIs (90.0% vs 94.5%, P = 0.01) and H2RAs (19.7% vs 25.7%, P = 0.04). In the multivariable model including the use of statins, H2RAs, aspirin and nonsteroidal anti-inflammatory drugs, PPI use was associated with 41% lower risk of OAC (OR 0.59, 95% CI 0.35-0.99). While risk reduction of OAC was stronger for high-dose PPIs (omeprazole daily dose >40 mg, adjusted OR 0.11, 95% 0.04-0.36), we did not find a dose-response relationship with PPI duration (P trend = 0.45). Likewise, H2RA use was independently associated with 30% lower risk of OAC (OR 0.70, 95% CI 0.50-0.99). CONCLUSION Use of PPIs and H2RAs among patients with Barrett's oesophagus are associated with lower risk of OAC. Further clinical trials are needed to confirm this possible chemopreventive effect.
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Affiliation(s)
- M C Tan
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.,Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - H B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.,Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - X Yu
- Department of Preventive Medicine and Community Health, Office of Biostatistics, University of Texas Medical Branch, Galveston, TX, USA
| | - A P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.,Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
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Abstract
Barrett's esophagus is common in Western countries, but progression to esophageal adenocarcinoma is uncommon. Chemoprevention therefore needs to consider whether benefits outweigh risks given an otherwise healthy population. This will depend on the particular population at risk and the relative safety of a potential preventive agent. Most evidence regarding the potential benefit of chemoprevention of Barrett's esophagus and prevention of progression to esophageal adenocarcinoma is based on observational studies such as case-control and cohort studies. Given the potential benefits and relatively low risks, patients with BE should receive once-daily PPI therapy, but routine use of twice-daily PPI is not recommended unless necessitated by poor control of reflux symptoms or esophagitis. Recent data suggest that the inverse associations between aspirin/NSAID use and esophageal adenocarcinoma may be the result of reducing neoplastic progression (from metaplasia to dysplasia and carcinoma) rather than initiation of Barrett's esophagus. While substantial associative data suggest a potential benefit of aspirin and nonaspirin NSAIDs in reducing the risk of progression of Barrett's esophagus, the low risk of progression and the potential risks (gastrointestinal bleeding, complicated ulcer disease, hemorrhagic stroke) do not warrant routine use, unless dictated by cardiovascular risk. Chemoprevention after mucosal ablation in those at highest risk of post-ablation recurrence (dysplastic Barrett's) is currently under investigation.
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Affiliation(s)
- Robert S Bresalier
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer, 1515 Holcombe Boulevard Unit 1466, Houston, TX, 77030, USA.
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Abstract
This article reviews esophageal, gastric, and colon cancers for the primary care physician. Risk factors, demographics, and screening are discussed. The rise of Western lifestyle has been a mixed blessing for these cancers. Our modern world has led to the decline of gastric cancer from the leading cause of cancer death before the 1930s to the 13th leading cause of cancer death now. Conversely, esophageal cancer is increasing faster than any other cancer. Screening for esophageal and gastric cancer is not practical in the West, but screening for colon cancer is gratifying for the patient and physician.
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Affiliation(s)
- William R Sonnenberg
- Titusville Area Hospital, 406 West Spruce Street, Titusville, PA 16354, USA; Department of Family & Community Medicine, Penn State Milton S. Hershey Medical Center, 500 University Dr., H154/C1626, Hershey, PA 17033, USA.
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