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Nguyen T, Barnhill K, Zhornitskiy A, Yu KS, Fuller G, Makaroff K, Spiegel BMR, Gresham G, Almario CV. Comparing the efficacy of different proton pump inhibitor dosing regimens for the treatment of gastroesophageal reflux disease: a systematic review and meta-analysis. Dis Esophagus 2025; 38:doae109. [PMID: 39673371 DOI: 10.1093/dote/doae109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 11/05/2024] [Accepted: 11/14/2024] [Indexed: 12/16/2024]
Abstract
Several proton pump inhibitor (PPI) dosing regimens that vary by strength and frequency (once [Qday] or twice [BID] daily) are available to treat gastroesophageal reflux disease (GERD). We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the impact of various PPI regimens on esophageal healing and GERD and heartburn symptoms. To identify relevant studies, we searched EMBASE and PubMed in January 2023, which yielded 1381 records. Eligible RCTs included those that enrolled adults diagnosed with GERD and compared different dosing regimens within the same PPI. The outcomes were esophageal healing and resolution of GERD and heartburn symptoms within 12 weeks (i.e. short-term) and > 12 weeks (i.e. long-term). Meta-analysis pooling of the odds ratios with 95% confidence intervals were estimated using the random-effects inverse-variance model. Overall, a total of 38 RCTs across 20 countries (N = 15,540 patients, mean age 50 years, 55% male) were included. Most PPI trials compared half standard dose Qday versus standard dose Qday or standard dose Qday versus double standard dose Qday. In general, when considering daily dosing, higher PPI strength significantly improved esophageal healing and relief of GERD symptoms both in the short- and long-term. Fewer trials compared Qday versus BID dosing; the impact of BID dosing on outcomes was inconsistent across the different PPI strength comparisons. In conclusion, this meta-analysis revealed that increasing PPI Qday dosages led to improved GERD outcomes. However, few studies compared Qday to BID dosing; as twice daily PPI usage is common in clinical practice, further studies are warranted to determine whether such dosing improves clinical outcomes.
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Affiliation(s)
- Tyra Nguyen
- Division of Population Sciences, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Katherine Barnhill
- Division of Population Sciences, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Alex Zhornitskiy
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
| | - Kyung Sang Yu
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
| | - Garth Fuller
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
| | - Katherine Makaroff
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
| | - Brennan M R Spiegel
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Gillian Gresham
- Division of Population Sciences, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Christopher V Almario
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Department of Medicine, Los Angeles, CA, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Laine L, Spechler S, Yadlapati R, Schnoll-Sussman F, Smith N, Leifke E, Harris T, Hunt B, Fass R, Katz P. Vonoprazan is Efficacious for Treatment of Heartburn in Non-erosive Reflux Disease: A Randomized Trial. Clin Gastroenterol Hepatol 2024; 22:2211-2220.e10. [PMID: 38750866 DOI: 10.1016/j.cgh.2024.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 04/29/2024] [Accepted: 05/07/2024] [Indexed: 06/22/2024]
Abstract
BACKGROUND & AIMS Potassium-competitive acid blockers have documented efficacy for erosive esophagitis. We performed a randomized trial in United States subjects diagnosed with non-erosive reflux disease of vonoprazan vs placebo for 4 weeks, followed by a 20-week active-treatment extension. METHODS Adult subjects with heartburn ≥4 days/week during screening without erosive esophagitis on endoscopy were randomized to placebo, vonoprazan 10 mg, or vonoprazan 20 mg. After 4 weeks, subjects on placebo were re-randomized to vonoprazan 10 mg or 20 mg, and those already on vonoprazan continued at the same dose for 20 weeks. Electronic diaries were completed twice daily. The primary endpoint was percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days). RESULTS Among 772 randomized subjects, the percentage of 24-hour heartburn-free days was 27.7% for placebo vs 44.8% for vonoprazan 10 mg (least squares mean difference, 17.1%; P < .0001) and 44.4% for vonoprazan 20 mg (least squares mean difference, 16.7%; P < .0001). Differences in percentage of subjects with a 24-hour heartburn-free day for vonoprazan 10 mg vs placebo and vonoprazan 20 mg vs placebo were 8.3% and 11.6% on day 1 and 18.1% and 23.2% on day 2. The mean/median percentages of 24-hour heartburn-free days over the extension period were similar across the 4 study arms: 61%-63%/76%-79%. CONCLUSIONS Vonoprazan reduced heartburn symptoms in subjects diagnosed with non-erosive reflux disease, with the benefit appearing to begin as early as the first day of therapy. Treatment effect persisted after the initial 4-week placebo-controlled period throughout the 20-week extension period. The 2 vonoprazan doses (10 mg and 20 mg) were similar in efficacy. (ClinicalTrials.gov: NCT05195528).
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Affiliation(s)
- Loren Laine
- Yale School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System, West Haven, Connecticut.
| | - Stuart Spechler
- Baylor University Medical Center, Dallas, Texas; Baylor Scott & White Research Institute, Dallas, Texas
| | - Rena Yadlapati
- University of California San Diego, La Jolla, California
| | | | - Neila Smith
- Phathom Pharmaceuticals, Buffalo Grove, Illinois
| | | | - Tom Harris
- Phathom Pharmaceuticals, Buffalo Grove, Illinois
| | - Barbara Hunt
- Phathom Pharmaceuticals, Buffalo Grove, Illinois
| | - Ronnie Fass
- MetroHealth Medical System, Case Western Reserve University, Cleveland, Ohio
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Liu J, Yin M, Lv C, Wang W, Huang Y, Tian J, Wang B, Song G, Yu Y. Post-reflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance predict proton pump inhibitor response in patients with reflux hypersensitivity. J Gastroenterol Hepatol 2024; 39:2402-2408. [PMID: 39118430 DOI: 10.1111/jgh.16718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 07/14/2024] [Accepted: 07/30/2024] [Indexed: 08/10/2024]
Abstract
BACKGROUND AND AIM Post-reflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) have been shown to influence proton pump inhibitor (PPI) response in GERD patients. However, currently, little data concerning these variables in patients with reflux hypersensitivity (RH) are available. In this study, we aimed to evaluate, in RH patients, the prevalence of PPI responders and nonresponders and investigate the predictive value of impedance-pH variables, including PSPW and MNBI, on responses to PPI. METHODS A total of 108 RH patients who met ROME IV criteria were prospectively recruited from June 2018 to December 2022. The prevalence of PPI responders/nonresponders was calculated, and impedance-pH variables were compared between the response and nonresponse groups. Multiple logistic regression was used to investigate predictors for PPI response. RESULTS Among 108 patients with RH, 60 patients (55.56%) were the PPI responders, and 48 (44.44%) were the nonresponders. Compared with the nonresponders, the PPI responders had a lower PSPW index (47.05 ± 4.43 vs 51.33 ± 3.50, P = 0.004) and a decreased value of MNBI (1866.68 ± 390.62 vs 2181.14 ± 338.42, P = 0.017). Multivariate logistic regression revealed that only the pathologic PSPW index (OR: 2.064) and MNBI (OR: 1.800) significantly influenced PPI response. CONCLUSIONS Nearly half of RH patients were PPI nonresponders. Impedance-pH monitoring was more valuable than pH-only monitoring in associating PPI response to reflux in RH patients owing to the appraisal of the PSPW index and MNBI.
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Affiliation(s)
- Jie Liu
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Mengqing Yin
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Chaolan Lv
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Wei Wang
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Yizhou Huang
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Jiashuang Tian
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Bo Wang
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Gengqing Song
- Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Yue Yu
- Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
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Kim SY, Lee KJ. Potential Risks Associated With Long-term Use of Proton Pump Inhibitors and the Maintenance Treatment Modality for Patients With Mild Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2024; 30:407-420. [PMID: 39397619 PMCID: PMC11474548 DOI: 10.5056/jnm24059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/16/2024] [Accepted: 06/01/2024] [Indexed: 10/15/2024] Open
Abstract
Gastroesophageal reflux disease (GERD) significantly affects the health-related quality of life and healthcare costs. The prevalence of this disease is increasing in Asia, leading to a rapid increase in the demand of proton pump inhibitors (PPIs). Despite effective symptom management during initial treatment, relapse rates after PPI cessation remain high in patients with GERD, warranting longterm maintenance therapy. Concerns regarding potential side effects related to the long-term use of PPIs are escalating with increased usage. Studies have reported diverse side effects of PPIs, such as increased fracture risk, cardiovascular concerns, enteric infections, neurological diseases, and potential associations with gastric cancer. However, definitive causal relationships remain unclear. This review comprehensively summarizes the latest knowledge on the potential risks associated with long-term use of PPIs. Continuous or noncontinuous therapy can be used as a maintenance treatment modality for GERD. For patients with mild GERD, including those with nonerosive and mildly erosive reflux disease, on-demand therapy following a sufficient period of continuous maintenance therapy is recommended as a long-term maintenance treatment option.
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Affiliation(s)
- Seung Young Kim
- Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
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Sachar M, Mautner Wizentier M, Risner E, Asmail H, Omara M, Chablaney S, Khan A, Knotts R. Risk factors associated with functional esophageal disorders (FED) versus gastroesophageal reflux disease (GERD). Surg Endosc 2024; 38:2842-2849. [PMID: 38528263 DOI: 10.1007/s00464-024-10714-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 01/28/2024] [Indexed: 03/27/2024]
Abstract
INTRODUCTION Despite the high prevalence of typical symptoms of gastroesophageal reflux disease (GERD), approximately 30% of patients have functional esophageal disorders (FED) on ambulatory reflux monitoring, which may include reflux hypersensitivity (RH; defined as physiologic acid exposure but temporally correlated symptoms of reflux), or functional heartburn (FH; defined as physiologic acid exposure and negative symptom correlation). There are limited epidemiological data characterizing these conditions. We investigated demographic and socioeconomic factors as well as medical comorbidities which may predispose to FED versus pathologic GERD. METHODS Adult patients with reflux symptoms for at least 3 months were studied with 24-h pH-impedance testing from 11/2019 to 3/2021. Participants were categorized into pathologic GERD, FH, or RH using pH-impedance data and reported symptom correlation. Demographic data, including age, gender, race/ethnicity, zip code, insurance status, and medical comorbidity data were retrospectively retrieved from the electronic medical record on all participants. RESULTS 229 patients were included. Non-Hispanic Asian ethnicity (OR 5.65; p = 0.01), underweight BMI (OR 7.33; p = 0.06), chronic pain (OR 2.33; p < 0.01), insomnia (OR 2.83; p = 0.06), and allergic rhinitis (OR 3.90; p < 0.01) were associated with a greater risk for FED. Overweight BMI (OR 0.48; p = 0.03) and alcohol use (OR 0.57; p = 0.06) were associated with a decreased risk for FED. DISCUSSION This is the first report of a greater risk of FED in patients with underweight BMI, insomnia, chronic pain, allergic rhinitis, or of Asian or Hispanic ethnicities. The weak associations between female gender and anxiety are corroborated in other studies. Our findings enable clinicians to better screen patients with reflux for this disorder.
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Affiliation(s)
- Moniyka Sachar
- Department of Medicine, New York University Langone Health, 247 E 28th Street, New York, NY, 10016, USA.
| | | | - Emma Risner
- Department of Biostatistics, New York University School of Public Health, New York, USA
| | - Hannah Asmail
- Department of Biostatistics, New York University School of Public Health, New York, USA
| | - Mathew Omara
- Division of Gastroenterology & Hepatology, Department of Medicine, Center for Esophageal Health, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
| | - Shreya Chablaney
- Division of Gastroenterology & Hepatology, Department of Medicine, Center for Esophageal Health, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
| | - Abraham Khan
- Division of Gastroenterology & Hepatology, Department of Medicine, Center for Esophageal Health, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
| | - Rita Knotts
- Division of Gastroenterology & Hepatology, Department of Medicine, Center for Esophageal Health, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
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Corazziari ES, Gasbarrini A, D'Alba L, D'Ovidio V, Riggio O, Passaretti S, Annibale B, Cicala M, Repici A, Bassotti G, Ciacci C, Di Sabatino A, Neri M, Bragazzi MC, Ribichini E, Radocchia G, Iovino P, Marazzato M, Schippa S, Badiali D. Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial. Am J Gastroenterol 2023; 118:2014-2024. [PMID: 37307528 PMCID: PMC10617666 DOI: 10.14309/ajg.0000000000002360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 05/09/2023] [Indexed: 06/14/2023]
Abstract
INTRODUCTION In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure. METHODS In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed. RESULTS A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm. DISCUSSION Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).
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Affiliation(s)
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie Dell'Apparato Digerente, Università Cattolica Del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS. Rome, Italy
| | - Lucia D'Alba
- Department of Gastroenterology and Digestive Endoscopy, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy
| | - Valeria D'Ovidio
- Unit of Gastroenterology and Digestive Endoscopy, S. Eugenio Hospital, Rome, Italy
| | - Oliviero Riggio
- Dipartimento di Medicina Traslazionale e di Precisione, Sapienza University of Rome, Rome, Italy
| | - Sandro Passaretti
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Bruno Annibale
- Dipartimento Scienze Medico-Chirurgiche e Medicina Traslazionale, Universita' Sapienza Roma, Ospedale Universitario Sant'Andrea, Rome, Italy
| | - Michele Cicala
- Department of Digestive Diseases, Campus Bio Medico University, Rome, Italy
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Gabrio Bassotti
- Gastroenterology & Hepatology Section, Department of Medicine & Surgery, University of Perugia, Perugia, Italy
| | - Carolina Ciacci
- PO di Malattie Dell'Apparato Digerente, Università di Salerno, AOU San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy
| | | | - Matteo Neri
- Department of Medicine and Ageing Sciences and Center for Advanced Studies and Technology (CAST), “G. D'Annunzio” University of Chieti-Pescara, Chieti-Pescara, Italy
| | | | - Emanuela Ribichini
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giulia Radocchia
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Paola Iovino
- PO di Malattie Dell'Apparato Digerente, Università di Salerno, AOU San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy
| | - Massimiliano Marazzato
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Serena Schippa
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Danilo Badiali
- Dipartimento di Medicina Traslazionale e di Precisione, Sapienza University of Rome, Rome, Italy
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Ribolsi M, Savarino E. Towards a better diagnosis of gastro esophageal reflux disease. Expert Rev Gastroenterol Hepatol 2023; 17:999-1010. [PMID: 37800858 DOI: 10.1080/17474124.2023.2267435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 10/03/2023] [Indexed: 10/07/2023]
Abstract
INTRODUCTION GERD is a common disorder and is characterized by the presence of typical or atypical symptoms. In GERD patients, the presence of mucosal alterations in endoscopy is detected in up to 30% of individuals. The clinical presentation of GERD patients may be complex and their management is challenging, due to the heterogeneous clinical presentation. The present review has been performed searching all relevant articles in this field, over the past years, using PubMed database. AREAS COVERED The diagnosis and management of GERD have been significantly improved in the last years due to the increasing availability of reflux monitoring techniques and the implementation of new procedures in the therapeutic armamentarium. Beside traditional impedance-pH variables, new metrics have been developed, increasing the diagnostic yield of reflux monitoring and better predicting the treatment response. Traditional pharmacological treatments include acid-suppressive-therapy and/or anti-acid. On the other hand, surgical treatment and, more recently, endoscopic procedures represent a promising field in the therapeutic approach. EXPERT OPINION Diagnosis and treatment of GERD still represent a challenging area. However, we believe that an accurate upfront evaluation is, nowadays, necessary in addressing patients with GERD to a more accurate diagnosis as well as to the best treatment options.
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Affiliation(s)
- Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | - Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
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Pennington E, Bell S, Hill JE. Should video laryngoscopy or direct laryngoscopy be used for adults undergoing endotracheal intubation in the pre-hospital setting? A critical appraisal of a systematic review. JOURNAL OF PARAMEDIC PRACTICE : THE CLINICAL MONTHLY FOR EMERGENCY CARE PROFESSIONALS 2023; 15:255-259. [PMID: 38812899 PMCID: PMC7616025 DOI: 10.1002/14651858] [Citation(s) in RCA: 2723] [Impact Index Per Article: 1361.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The safety and utility of endotracheal intubation by paramedics in the United Kingdom is a matter of debate. Considering the controversy surrounding the safety of paramedic-performed endotracheal intubation, any interventions that enhance patient safety should be evaluated for implementation based on solid evidence of their effectiveness. A systematic review performed by Hansel and colleagues (2022) sought to assess compare video laryngoscopes against direct laryngoscopes in clinical practice. This commentary aims to critically appraise the methods used within the review by Hansel et al (2022) and expand upon the findings in the context of clinical practice.
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Affiliation(s)
| | - Steve Bell
- Consultant Paramedic, North West Ambulance Service NHS Trust
| | - James E Hill
- University of Central Lancashire, Colne, Lancashire
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Barberio B, Visaggi P, Savarino E, de Bortoli N, Black CJ, Ford AC. Comparison of acid-lowering drugs for endoscopy negative reflux disease: Systematic review and network Meta-Analysis. Neurogastroenterol Motil 2023; 35:e14469. [PMID: 36153790 PMCID: PMC10078414 DOI: 10.1111/nmo.14469] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/29/2022] [Accepted: 09/12/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network meta-analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine-2-receptor antagonists, potassium-competitive acid blockers (PCABs), and alginates in patients with endoscopy-negative reflux disease. METHODS We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy-negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to P-score. KEY RESULTS We identified 23 RCTs containing 10,735 subjects with endoscopy-negative reflux disease. Based on failure to achieve complete relief of symptoms between ≥2 and <4 weeks, omeprazole 20 mg o.d. (P-score 0.94) ranked first, with esomeprazole 20 mg o.d. or 40 mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10 mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at ≥4 weeks, dexlansoprazole 30 mg o.d. (P-score 0.95) ranked first, with 30 ml alginate q.i.d. combined with omeprazole 20 mg o.d., and 30 ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at ≥4 weeks, dexlansoprazole 60 mg o.d. ranked first (P-score 0.90), with dexlansoprazole 30 mg o.d. and rabeprazole 20 mg o.d. second and third. All drugs were safe and well-tolerated. CONCLUSIONS & INFERENCES Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy-negative reflux disease. Future RCTs should aim to better classify patients with endoscopy-negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short- and long-term.
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Affiliation(s)
- Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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Han X, Zhang Y, Lee A, Li Z, Gao J, Wu X, Zhao J, Wang H, Chen D, Zou D, Owyang C. Upregulation of acid sensing ion channels is associated with esophageal hypersensitivity in GERD. FASEB J 2021; 36:e22083. [PMID: 34918385 PMCID: PMC8715981 DOI: 10.1096/fj.202100606r] [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] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 11/03/2021] [Accepted: 11/22/2021] [Indexed: 12/13/2022]
Abstract
Proton pump inhibitors (PPIs) are the mainstay of therapy for gastroesophageal reflux disease (GERD) but up to 60% of patients have inadequate response to therapy. Acid sensing ion channels (ASICs) play important roles in nociception. This study aimed to investigate whether the increased expression of ASICs results in neuronal hyperexcitability in GERD. Esophageal biopsies were taken from GERD patients and healthy subjects to compare expression of ASIC1 and 3. Next, gene and protein expression of ASIC1 and 3 from esophageal mucosa and dorsal root ganglia (DRG) neurons were measured by qPCR, Western‐blot and immunofluorescence in rodent models of reflux esophagitis (RE), non‐erosive reflux disease (NERD), and sham operated groups. Excitability of DRG neurons in the GERD and sham groups were also tested by whole‐cell patch‐clamp recordings. We demonstrated that ASIC1 and 3 expression were significantly increased in patients with RE compared with healthy controls. This correlated positively with symptom severity of heartburn and regurgitation (p < .001). Next, ASIC1 and 3 gene and protein expression in rodent models of RE and NERD were similarly increased in esophageal mucosa as well as T3–T5 DRG neurons compared with sham operation. DRG neurons from RE animals showed hyperexcitability compared with sham group. However, intrathecal injection of ASIC specific inhibitors, PcTx1 and APTEx‐2, as well as silencing ASIC1 and 3 genes with specific siRNAs prevented visceral hypersensitivity. Overall, upregulation of ASIC1 and 3 may lead to visceral hypersensitivity in RE and NERD and may be a potential therapeutic target for PPI non‐responsive patients.
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Affiliation(s)
- Xu Han
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yawen Zhang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Allen Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Zhaoshen Li
- Division of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Jun Gao
- Division of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Xiaoyin Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Jiulong Zhao
- Division of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Hui Wang
- Division of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Di Chen
- Division of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Duowu Zou
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chung Owyang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
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11
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Patel D, Fass R, Vaezi M. Untangling Nonerosive Reflux Disease From Functional Heartburn. Clin Gastroenterol Hepatol 2021; 19:1314-1326. [PMID: 32246998 DOI: 10.1016/j.cgh.2020.03.057] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 03/23/2020] [Accepted: 03/23/2020] [Indexed: 02/07/2023]
Abstract
Heartburn is a common symptom in clinical practice, but as many as 70% of patients have normal findings from upper endoscopy. Most of these patients have nonerosive reflux disease (NERD) or functional esophageal disorders. NERD is the most common phenotype of gastroesophageal reflux disease, and functional heartburn is the most common cause for refractory heartburn. In patients with NERD, symptoms arise from gastroesophageal reflux and esophageal hypersensitivity, whereas in patients with functional heartburn, symptoms result from esophageal hypersensitivity. A diagnosis of NERD requires endoscopy and reflux testing, whereas a diagnosis of functional heartburn also requires esophageal manometry. NERD is treated most commonly with medical, endoscopic, and surgical antireflux approaches, whereas functional heartburn as well as NERD can be treated with neuromodulators, psychological intervention, and complementary medicine options.
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Affiliation(s)
- Dhyanesh Patel
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee.
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, MetroHealth System, Case Western Reserve University, Cleveland, Ohio
| | - Michael Vaezi
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
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12
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Zerbib F, Bredenoord AJ, Fass R, Kahrilas PJ, Roman S, Savarino E, Sifrim D, Vaezi M, Yadlapati R, Gyawali CP. ESNM/ANMS consensus paper: Diagnosis and management of refractory gastro-esophageal reflux disease. Neurogastroenterol Motil 2021; 33:e14075. [PMID: 33368919 DOI: 10.1111/nmo.14075] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 11/11/2020] [Accepted: 12/13/2020] [Indexed: 02/08/2023]
Abstract
Up to 40% of patients with symptoms suspicious of gastroesophageal reflux disease (GERD) do not respond completely to proton pump inhibitor (PPI) therapy. The term "refractory GERD" has been used loosely in the literature. A distinction should be made between refractory symptoms (ie, symptoms may or may not be GERD-related), refractory GERD symptoms (ie, persisting symptoms in patients with proven GERD, regardless of relationship to ongoing reflux), and refractory GERD (ie, objective evidence of GERD despite adequate medical management). The present ESNM/ANMS consensus paper proposes use the term "refractory GERD symptoms" only in patients with persisting symptoms and previously proven GERD by either endoscopy or esophageal pH monitoring. Even in this context, symptoms may or may not be reflux related. Objective evaluation, including endoscopy and esophageal physiologic testing, is requisite to provide insights into mechanisms of symptom generation and evidence of true refractory GERD. Some patients may have true ongoing refractory acid or weakly acidic reflux despite PPIs, while others have no evidence of ongoing reflux, and yet others have functional esophageal disorders (overlapping with proven GERD confirmed off therapy). In this context, attention should also be paid to supragastric belching and rumination syndrome, which may be important contributors to refractory symptoms.
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Affiliation(s)
- Frank Zerbib
- CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | | | - Ronnie Fass
- Digestive Health Center, MetroHealth System, Cleveland, OH, USA
| | - Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL, USA
| | - Sabine Roman
- Hospices Civils de Lyon, Hôpital E Herriot, Digestive Physiology, Université de Lyon, Inserm U1032, LabTAU, Lyon, France
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy
| | - Daniel Sifrim
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Michael Vaezi
- Division of Gastroenterology, Vanderbilt University, Nashville, TN, USA
| | - Rena Yadlapati
- Division of Gastroenterology, University of California San Diego School of Medicine, La Jolla, CA, USA
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
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13
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Abstract
Interpreting natural course studies have been very difficult due to their retrospective design, lack of standardization, reliability of reported mucosal findings, liberal use of antireflux medications and accuracy of chart documentation. Studies provided a wide range of progression rates of patients from nonerosive reflux disease (NERD) to erosive esophagitis (EE). However, direct progression from NERD to Barrett's esophagus appears to be an uncommon phenomenon. Importantly, progression of NERD patients was commonly reported to low grades of EE, which are currently considered inconclusive of gastroesophageal reflux disease. Reports of progression rates from low grades to high grades EE also vary considerably. Progression of patients with EE, without metaplastic epithelium underneath the inflammation, to Barrett's esophagus is relatively uncommon. Recently, it was also recognized that regression from high grades to low grades EE and from EE to NERD is a common phenomenon affecting up to 25% of the patients from each group.
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14
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Zhou J, Shrestha P, Qiu Z, Harman DG, Teoh WC, Al-Sohaily S, Liem H, Turner I, Ho V. Distinct Microbiota Dysbiosis in Patients with Non-Erosive Reflux Disease and Esophageal Adenocarcinoma. J Clin Med 2020; 9:jcm9072162. [PMID: 32650561 PMCID: PMC7408827 DOI: 10.3390/jcm9072162] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/03/2020] [Accepted: 07/06/2020] [Indexed: 02/06/2023] Open
Abstract
Non-erosive reflux disease (NERD) and esophageal adenocarcinoma (EAC) are often regarded as bookends in the gastroesophageal reflux disease spectrum. However, there is limited clinical evidence to support this disease paradigm while the underlying mechanisms of disease progression remain unclear. In this study, we used 16S rRNA sequencing and mass-spectrometer-based proteomics to characterize the esophageal microbiota and host mucosa proteome, respectively. A total of 70 participants from four patient groups (NERD, reflux esophagitis, Barrett’s esophagus, and EAC) and a control group were analyzed. Our results showed a unique NERD microbiota composition, distinct to control and other groups. We speculate that an increase in sulfate-reducing Proteobacteria and Bacteroidetes along with hydrogen producer Dorea are associated with a mechanistic role in visceral hypersensitivity. We also observed a distinct EAC microbiota consisting of a high abundance of lactic acid-producing bacteria (Staphylococcus, Lactobacillus, Bifidobacterium, and Streptococcus), which may contribute towards carcinogenesis through dysregulated lactate metabolism. This study suggests the close relationship between esophageal mucosal microbiota and the appearance of pathologies of this organ.
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Affiliation(s)
- Jerry Zhou
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
- Correspondence: ; Tel.: +61-2-4620-3865
| | - Prapti Shrestha
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
| | - Zhiguang Qiu
- Hawkesbury Institute for the Environment, Western Sydney University, Penrith, NSW 2750, Australia;
| | - David G. Harman
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
| | - Wun-Chung Teoh
- Department of Gastroenterology, Campbelltown Hospital, Campbelltown, NSW 2560, Australia;
| | - Sam Al-Sohaily
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
- Department of Gastroenterology, Campbelltown Hospital, Campbelltown, NSW 2560, Australia;
| | - Han Liem
- Nepean Hospital, Kingswood, NSW 2747, Australia;
| | - Ian Turner
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
- Department of Gastroenterology, Campbelltown Hospital, Campbelltown, NSW 2560, Australia;
| | - Vincent Ho
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; (P.S.); (D.G.H.); (S.A.-S.); (I.T.); (V.H.)
- Department of Gastroenterology, Campbelltown Hospital, Campbelltown, NSW 2560, Australia;
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15
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Pauwels A, Boecxstaens V, Andrews CN, Attwood SE, Berrisford R, Bisschops R, Boeckxstaens GE, Bor S, Bredenoord AJ, Cicala M, Corsetti M, Fornari F, Gyawali CP, Hatlebakk J, Johnson SB, Lerut T, Lundell L, Mattioli S, Miwa H, Nafteux P, Omari T, Pandolfino J, Penagini R, Rice TW, Roelandt P, Rommel N, Savarino V, Sifrim D, Suzuki H, Tutuian R, Vanuytsel T, Vela MF, Watson DI, Zerbib F, Tack J. How to select patients for antireflux surgery? The ICARUS guidelines (international consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for antireflux surgery). Gut 2019; 68:1928-1941. [PMID: 31375601 DOI: 10.1136/gutjnl-2019-318260] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 05/28/2019] [Accepted: 05/29/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery. DESIGN We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous. RESULTS Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett's oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis. CONCLUSION With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.
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Affiliation(s)
- Ans Pauwels
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Veerle Boecxstaens
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
- Department of Surgical Oncology, Oncological and Vascular Access Surgery, Leuven, Belgium
- Department of Oncology, KU Leuven, Leuven, Belgium
| | | | | | - Richard Berrisford
- Peninsula Oesophago-gastric Surgery Unit, Derriford Hospital, Plymouth, Plymouth, UK
| | - Raf Bisschops
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
- Gastroenterology and Hepatology, University Hospital Gasthuisberg, Leuven, Belgium
| | - Guy E Boeckxstaens
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Serhat Bor
- Gastroenterology, Ege University School of Medicine, İzmir, Turkey
| | - Albert J Bredenoord
- Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, Netherlands
| | - Michele Cicala
- Digestive Diseases, Universita Campus Bio Medico, Roma, Italy
| | - Maura Corsetti
- Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - Fernando Fornari
- Programa de Pós-Graduação: Ciências em Gastroenterologia e Hepatologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Chandra Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri, USA
| | - Jan Hatlebakk
- Gastroenterology, Haukeland Sykehus, University of Bergen, Bergen, Norway
| | - Scott B Johnson
- Department of Cardiothoracic Surgery, University of Texas Health Science Center, San Antonio, USA
| | - Toni Lerut
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Lars Lundell
- Department of Surgery, Karolinska, Stockholm, Sweden
| | - Sandro Mattioli
- Department of Medical and Surgical Sciences, Universita degli Studi di Bologna, Bologna, Emilia-Romagna, Italy
| | - Hiroto Miwa
- Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Philippe Nafteux
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Taher Omari
- Department of Gastroenterology, Flinders University, Adelaide, Australia
| | - John Pandolfino
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, USA
| | - Roberto Penagini
- Department of Pathophysiology and Transplantation, Ospedale Maggiore Policlinico, Milano, Lombardia, Italy
| | - Thomas W Rice
- Thoracic Surgery, Emeritus Staff Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, USA
| | - Philip Roelandt
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
- Gastroenterology and Hepatology, University Hospital Gasthuisberg, Leuven, Belgium
| | - Nathalie Rommel
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
- Neurosciences, KU Leuven, Leuven, Belgium
| | - Vincenzo Savarino
- Internal Medicine and Medical Specialties, Universita di Genoa, Genoa, Italy
| | - Daniel Sifrim
- Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
| | - Hidekazu Suzuki
- Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Radu Tutuian
- Gastroenteroloy, Tiefenauspital Bern, Bern, Switzerland
| | - Tim Vanuytsel
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
- Gastroenterology and Hepatology, University Hospital Gasthuisberg, Leuven, Belgium
| | | | - David I Watson
- Department of Surgery, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia
| | - Frank Zerbib
- Department of Gastroenterology, Bordeaux University Hospital, Université de Bordeaux, Bordeaux, France
| | - Jan Tack
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
- Gastroenterology and Hepatology, University Hospital Gasthuisberg, Leuven, Belgium
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16
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Ribolsi M, Giordano A, Guarino MPL, Tullio A, Cicala M. New classifications of gastroesophageal reflux disease: an improvement for patient management? Expert Rev Gastroenterol Hepatol 2019; 13:761-769. [PMID: 31327288 DOI: 10.1080/17474124.2019.1645596] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 07/12/2019] [Indexed: 12/18/2022]
Abstract
Introduction: Gastroesophageal reflux disease (GERD) is a very common and often debilitating disease. In the broad spectrum of GERD phenotypes, three main groups may be traditionally distinguished: 1) patients only affected by esophageal and/or extra-esophageal symptoms; 2) patients with erosive esophagitis and 3) patients with further complications. Areas covered: This review provides an overview on the current classifications of GERD patients, and their impact on their management. Expert opinion: In 2017, the GERD Consensus Working Group focused the attention on patients unresponsive to PPIs. In this scenario, a diagnosis of GERD might be confirmed by evident signs of erosive esophagitis and the finding of pH or multichannel intraluminal impedance-pH tests, such as more than 6%. The 'Lyon Consensus' panel of experts confirmed that positive indices of reflux-symptom association, without other altered parameters, represent reflux hypersensitivity. GERD requires a customized management; it is crucial to assess frequency and severity of symptoms and their response to an optimal course of therapy as well as to explore the endoscopic alterations and consider other diagnoses responsible for persistent symptoms.
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Affiliation(s)
- Mentore Ribolsi
- a Unit of Gastroenterology and Digestive Endoscopy, University Campus Bio Medico , Rome , Italy
| | - Antonio Giordano
- a Unit of Gastroenterology and Digestive Endoscopy, University Campus Bio Medico , Rome , Italy
| | | | - Alessandro Tullio
- a Unit of Gastroenterology and Digestive Endoscopy, University Campus Bio Medico , Rome , Italy
| | - Michele Cicala
- a Unit of Gastroenterology and Digestive Endoscopy, University Campus Bio Medico , Rome , Italy
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17
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Kim EJ, Lee OY, Lee KN, Lee SJ, Jang JY, Cho JW, Kim TO. Efficacy and Safety of AlbisD Compared With Omeprazole 20 mg in Patients With Non-erosive Reflux Disease: A Randomized, Open-label, Active-controlled, Pilot Study. J Neurogastroenterol Motil 2019; 25:403-412. [PMID: 31327222 PMCID: PMC6657924 DOI: 10.5056/jnm18185] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 05/15/2019] [Accepted: 06/24/2019] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Proton pump inhibitors (PPIs) are frequently used to treat non-erosive reflux disease (NERD), but their effect is limited. It is not known whether a potential alternative, AlbisD, containing ranitidine hydrochloride, sucralfate hydrate, and tripotassium dicitrato bismuthate, is effective and safe in treating NERD. The aim of the study is to evaluate the efficacy and safety of AlbisD compared with omperazole in patients with NERD. Methods This was a multicenter, randomized, open-label, parallel-group, non-inferiority comparative study. A total of 126 patients with NERD were randomly allocated to either AlbisD twice daily or omeprazole 20 mg once daily for 4 weeks from February 2016 to August 2016. The study patients had histories of heartburn or regurgitation of moderate severity (> score 2) and a frequency of at least 2 episodes per week, and had no mucosal breaks of the esophagus on endoscopy. The primary efficacy variable was complete cure of heartburn at week 4. Secondary efficacy variables evaluating symptoms of heartburn and acid reflux as well as safety profiles were compared in the 2 groups at week 2 and 4 after treatment. Results A total of 113 patients completed the study (57 and 56 in AlbisD and omeprazole groups, respectively). The proportion of patients with complete cure of heartburn at week 4 was not significantly different between the AlbisD and omeprazole groups (35.1% vs 32.1% respectively, P = 0.740). There were no significant differences between the 2 groups in the any secondary variables including proportions of days without heartburn or acid reflux over 4 weeks (including daytime and nighttime). Adverse events were similarly reported in the 2 groups (7 [12.3%] vs 6 [10.7%]), and there were no serious adverse events. Conclusions The efficacy and safety of AlibsD in treating NERD patients are not inferior to those of omeprazole. Therefore, AlbisD can be an alternative to PPIs for NERD.
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Affiliation(s)
- Eun Jin Kim
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Oh Young Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Kang Nyeong Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Sung Joon Lee
- Department of Internal Medicine, Kangwon National University College of Medicine, Seoul, Korea
| | - Jae-Young Jang
- Department of Internal Medicine, Kyunghee University College of Medicine, Seoul, Korea
| | - Jin Woong Cho
- Department of Internal Medicine, Presbyterian Medical Center, Chonju, Korea
| | - Tae-Oh Kim
- Department of Internal Medicine, Inje University College of Medicine, Seoul, Korea
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18
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Khoury T, Mari A, Amara H, Jabaren M, Watad A, Nseir W, Sbeit W, Mahamid M. Impact of Chronic Statins Use on the Development of Esophagitis in Patients with Gastroesophageal Reflux Disease. Can J Gastroenterol Hepatol 2019; 2019:6415757. [PMID: 30854351 PMCID: PMC6378002 DOI: 10.1155/2019/6415757] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 12/21/2018] [Accepted: 01/02/2019] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND AND AIMS We aimed to assess whether chronic statins used (> 6 months) were protective of the development of esophagitis in patients with gastroesophageal reflux disease. In the presence of esophagitis, complications such as strictures, Barrett's esophagus, and adenocarcinoma were the most common. Statins, lipid lowering drugs with a pleiotropic effect, are recently implicated in various pathologies. Nevertheless, the possible impact of statins in esophagitis development has never been assessed. METHODS We performed a retrospective, cross-sectional, single center study that included 4148 gastroesophageal reflux disease patients from 2014 and 2018 at EMMS Nazareth Hospital. We divided the patients into 5 groups. The groups were split into positive control group, which was the nonesophagitis group, and the other 4 groups were A-D (as per Los Angeles classification). RESULTS Overall, out of the 4148 patients included, 48% were males and 2840 patients were in the control group. In groups A, B, C, and D there were 818, 402, 72, and 16 patients, respectively. Logistic regression analysis revealed that chronic statins usage is protective by preventing development esophagitis (OR 0.463 [95%CI 0.370-0.579], p < 0.0001). NSAIDS use, Hiatus hernia, and H. pylori were promoting factors (OR, 1.362, 1.779, and 1.811; 95% CI, 1.183-1.569, 1.551-2.040, and 1.428-2.298; P<0.0001, P<0.0001, and P<0.0001, respectively). CONCLUSION Using chronic statins was protective to the development of esophagitis among GERD patients. Our findings of potential clinical application mandate further randomized controlled trials to better assess the impact of statins on esophagitis.
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Affiliation(s)
- Tawfik Khoury
- Gastroenterology and Endoscopy United, The Nazareth Hospital, EMMS, Nazareth, Bar Ilan University, Tel-Aviv, Israel
- Institute of Gastroenterology and Liver Disease, Galilee Medical Center, Bar Ilan Faculty of Medicine, Safed, Israel
| | - Amir Mari
- Gastroenterology and Endoscopy United, The Nazareth Hospital, EMMS, Nazareth, Bar Ilan University, Tel-Aviv, Israel
| | - Hana Amara
- Gastroenterology and Endoscopy United, The Nazareth Hospital, EMMS, Nazareth, Bar Ilan University, Tel-Aviv, Israel
| | - Mohamed Jabaren
- Cardiology Department., Haemek Medical Center, Afula, Israel
| | - Abdulla Watad
- Department of Medicine ‘B' Sheba Medical Center, Tel-Hashomer, Israel
| | - Wiliam Nseir
- Internal Medicine Department A, Badeh Barouch Medical Center, Poria, Israel
| | - Wisam Sbeit
- Institute of Gastroenterology and Liver Disease, Galilee Medical Center, Bar Ilan Faculty of Medicine, Safed, Israel
| | - Mahmud Mahamid
- Gastroenterology and Endoscopy United, The Nazareth Hospital, EMMS, Nazareth, Bar Ilan University, Tel-Aviv, Israel
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Surdea-Blaga T, Negrutiu DE, Palage M, Dumitrascu DL. Food and Gastroesophageal Reflux Disease. Curr Med Chem 2019; 26:3497-3511. [PMID: 28521699 DOI: 10.2174/0929867324666170515123807] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 04/28/2017] [Accepted: 04/28/2017] [Indexed: 02/08/2023]
Abstract
Gastroesophageal reflux disease is a chronic condition with a high prevalence in western countries. Transient lower esophageal sphincter relaxation episodes and a decreased lower esophageal sphincter pressure are the main mechanisms involved. Currently used drugs are efficient on reflux symptoms, but only as long as they are administered, because they do not modify the reflux barrier. Certain nutrients or foods are generally considered to increase the frequency of gastroesophageal reflux symptoms, therefore physicians recommend changes in diet and some patients avoid bothering foods. This review summarizes current knowledge regarding food and gastroesophageal reflux. For example, fat intake increases the perception of reflux symptoms. Regular coffee and chocolate induce gastroesophageal reflux and increase the lower esophageal exposure to acid. Spicy foods might induce heartburn, but the exact mechanism is not known. Beer and wine induce gastroesophageal reflux, mainly in the first hour after intake. For other foods, like fried food or carbonated beverages data on gastroesophageal reflux is scarce. Similarly, there are few data about the type of diet and gastroesophageal reflux. Mediterranean diet and a very low carbohydrate diet protect against reflux. Regarding diet-related practices, consistent data showed that a "short-meal-to-sleep interval" favors reflux episodes, therefore some authors recommend that dinner should be at least four hours before bedtime. All these recommendations should consider patient's weight, because several meta-analyses showed a positive association between increased body mass index and gastroesophageal reflux disease.
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Affiliation(s)
- Teodora Surdea-Blaga
- 2nd Dept. of Internal Medicine, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj-Napoca, Romania
| | - Dana E Negrutiu
- 2nd Dept. of Internal Medicine, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj-Napoca, Romania
| | - Mariana Palage
- Department of Therapeutic Chemistry, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj- Napoca, Romania
| | - Dan L Dumitrascu
- 2nd Dept. of Internal Medicine, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj-Napoca, Romania
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Melendez-Rosado J, Gutierrez-Blanco D, Schneider A, Menzo EL, Szomstein S, Rosenthal RJ. Impact of preoperative wireless pH monitoring in the evaluation of esophageal conditions prior to bariatric surgery in a severely obese patient population. Surg Obes Relat Dis 2018; 15:288-294. [PMID: 30642753 DOI: 10.1016/j.soard.2018.11.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 10/31/2018] [Accepted: 11/20/2018] [Indexed: 01/03/2023]
Abstract
BACKGROUND Sleeve gastrectomy (SG) is currently the most commonly performed bariatric procedure in the United States; however, it can be associated with development of de novo gastroesophageal reflux (GERD) or worsening of existing GERD. Preoperative esophagogastroduodenoscopy (EGD) and findings of esophagitis are commonly used as screening tool, but the alternative use of preoperative objective measurement of acid reflux has not been studied. OBJECTIVE The aim of this study was to evaluate if preoperative objective measurement of acid reflux by using wireless pH monitoring (WPHM) could have an impact on surgical planning and outcomes. SETTING Academic Center of Excellence. METHODS Retrospective review of a prospectively collected database of 43 adult obese patients with reflux symptoms who underwent outpatient EGD and WPHM between September 2011 and September 2017. RESULTS Change in planned surgical management from SG to Roux-en-Y-gastric bypass with the use of WPHM occurred in 21.0% (n = 9) of patients. Only 2.3% (n = 1) developed de novo GERD after SG. Nonerosive reflux disease was the most common esophageal condition on preoperative EGD. EGD, as a single diagnostic tool, appeared insufficient to diagnose acid reflux and help with the decision planning in this patient population. CONCLUSIONS Based on objective data obtained by measurement of GERD, using preoperative WPHM compared with preoperative EGD alone aids in a better patient selection for either SG or Roux-en-Y-gastric bypass. Our cohort with preoperative WPHM required no surgical conversions or revisions.
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Affiliation(s)
- Jose Melendez-Rosado
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, Florida
| | - David Gutierrez-Blanco
- Department of General Surgery and the Bariatric and Metabolic Institute, Cleveland Clinic Florida, Weston, Florida
| | - Alison Schneider
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, Florida
| | - Emanuele Lo Menzo
- Department of General Surgery and the Bariatric and Metabolic Institute, Cleveland Clinic Florida, Weston, Florida
| | - Samuel Szomstein
- Department of General Surgery and the Bariatric and Metabolic Institute, Cleveland Clinic Florida, Weston, Florida
| | - Raul J Rosenthal
- Department of General Surgery and the Bariatric and Metabolic Institute, Cleveland Clinic Florida, Weston, Florida.
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21
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Forootan M, Zojaji H, Ehsani MJ, Darvishi M. Advances in the Diagnosis of GERD Using the Esophageal pH Monitoring, Gastro-Esophageal Impedance-pH Monitoring, And Pitfalls. Open Access Maced J Med Sci 2018; 6:1934-1940. [PMID: 30455777 PMCID: PMC6236049 DOI: 10.3889/oamjms.2018.410] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 09/27/2018] [Accepted: 10/01/2018] [Indexed: 01/28/2023] Open
Abstract
PH monitoring is not capable of detecting all types of reflux, especially when the amount of acid is very low or not at all in the refluxate. Multichannel intraluminal impedance-pH monitoring (MII-pH) is used as a new method to assess bolus transport. The types of reflexes including acid, weak acid and weak alkaline MII-pH is capable of distinguishing more reflux episodes based upon use of physical and chemical parameters of the refluxate, leads to a diagnosis of normal acid reflux from abnormal nonacidic reflux. 24-h oesophagal pH monitoring can be effectively used to assess the potential relationship between symptoms and refluxes. MII-pH is capable of distinguishing more reflux episodes based upon use of physical and chemical parameters of the refluxate, leads to a diagnosis of normal acid reflux from abnormal nonacidic reflux. It can be used to confirm gastro-oesophagal reflux episodes, where has a sensitivity and specificity for diagnosing GERD in comparison with endoscopy or pH-metry.
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Affiliation(s)
- Mojgan Forootan
- Department of Gastroenterology, Gastrointestinal and liver Diseases Research Center (RCGLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Homayoun Zojaji
- Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Javad Ehsani
- Department of Gastroenterology and Hepatology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Darvishi
- Infectious Diseases and Tropical Medicine Research Center (IDTMRC), Department of Aerospace and Subaquatic Medicine, AJA University of Medical Sciences, Tehran, Iran
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22
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Gallusi G, Pontone S. Treatment of PPI-resistant gastro-oesophageal reflux: A systematic review. Arab J Gastroenterol 2018; 19:51-55. [PMID: 29935866 DOI: 10.1016/j.ajg.2018.02.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2016] [Revised: 05/10/2017] [Accepted: 02/20/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND STUDY AIMS Several studies have demonstrated the superiority of proton-pump inhibitors (PPIs) in resolving erosive gastro-oesophageal reflux disease (GORD). However, this first line of treatment can fail to control symptoms in around 30% of cases, especially in the presence of non-erosive GORD. In situations where the first line of treatment fails, there is a lack of concordance regarding the best strategy to apply. This study presents a systematic review of the trials which have tested second-line treatments after PPI failure. METHODS The study was conducted according to the PRISMA statement. The systematic review included medical trials written in English which were published between 2000 and 2016 and were retrieved from PubMed and Scopus using the keywords 'PPI-resistant gastro-oesophageal reflux', 'alginate AND gastro-oesophageal reflux', 'hyaluronic acid AND gastro-oesophageal reflux', 'prokinetics AND gastro-oesophageal reflux', 'sucralfate AND gastro-oesophageal reflux' and 'baclofen AND gastro-oesophageal reflux'. RESULTS Ten randomised and non-randomised studies were included, which included 1515 patients of both sexes (mean age = 49.19 years, age range = 18-85, males = 700; 46.2%). CONCLUSIONS A personalised choice of the best treatment for PPI-resistant GORD should be based on the results of an upper endoscopy and pH/MII monitoring. For patients in situations where the first line of treatment fails, we encourage the execution of trials for testing double doses of PPIs against alternative medicaments.
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Affiliation(s)
- Giulia Gallusi
- Division of Gastroenterology, Department of Clinical Medicine "Sapienza" University of Rome, Italy
| | - Stefano Pontone
- Department of Surgical Sciences, "Sapienza" University of Rome, Italy.
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Ranaldo N, Losurdo G, Iannone A, Principi M, Barone M, De Carne M, Ierardi E, Di Leo A. Tailored therapy guided by multichannel intraluminal impedance pH monitoring for refractory non-erosive reflux disease. Cell Death Dis 2017; 8:e3040. [PMID: 28880273 PMCID: PMC5636981 DOI: 10.1038/cddis.2017.436] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023]
Abstract
A relevant percentage of non-erosive reflux disease (NERD) is refractory to proton pump inhibitors (PPIs) treatment. Multichannel intraluminal impedance pH (MII-pH) monitoring should give useful pathophysiological information about refractoriness. Therefore, our aim was to assess whether this technique could be useful to guide a 'tailored' therapy in refractory NERD. We retrospectively recruited NERD patients undergoing MII-pH monitoring for unsuccessful treatment. All patients had undergone upper endoscopy, and those with erosive esophagitis were excluded. No patient received PPI during MII-pH monitoring. Subjects were subgrouped into three categories: acid reflux, non-acid reflux and functional heartburn. MII-pH-guided therapy was performed for 4 weeks as follows: patients with acid reflux received PPI at double dose, patients with non-acid reflux PPI at full dose plus alginate four times a day and patients with functional heartburn levosulpiride 75 mg per day. A visual analog scale (VAS) ranging from 0 to 100 mm was administered before and after such tailored therapy to evaluate overall symptoms. Responders were defined by VAS improvement of at least 40%. Sixty-nine patients with refractory NERD were selected (female-male ratio 43 : 26, mean age 47.6±15.2 years). Overall effectiveness of tailored therapy was 84% without statistical difference among subgroups (88.5% acid reflux, 92% non-acid reflux, 66.6% functional heartburn; P=0.06). Univariate analysis showed that therapy failure directly correlated with functional heartburn diagnosis (OR=4.60) and suggested a trend toward a negative correlation with smoking and a positive one with nausea. However, at multivariate analysis, these parameters were not significant. Functional heartburn experienced a lower median percent VAS reduction than acid reflux (52.5% versus 66.6%, P<0.01) even if equal to non-acid reflux (66.6%). In conclusion, a tailored approach to refractory NERD, guided by MII-pH monitoring, demonstrated to be effective and should be promising to cure symptom persistence after conventional therapy failure. Nevertheless, standardized guidelines are advisable.
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Affiliation(s)
- Nunzio Ranaldo
- Gastroenterology Section, Department of Emergency and Organ Transplantation, Piazza Giulio Cesare, University of Bari, Bari, Italy
| | - Giuseppe Losurdo
- Gastroenterology Section, Department of Emergency and Organ Transplantation, Piazza Giulio Cesare, University of Bari, Bari, Italy
| | - Andrea Iannone
- Gastroenterology Section, Department of Emergency and Organ Transplantation, Piazza Giulio Cesare, University of Bari, Bari, Italy
| | - Mariabeatrice Principi
- Gastroenterology Section, Department of Emergency and Organ Transplantation, Piazza Giulio Cesare, University of Bari, Bari, Italy
| | - Michele Barone
- Gastroenterology Section, Department of Emergency and Organ Transplantation, Piazza Giulio Cesare, University of Bari, Bari, Italy
| | - Massimo De Carne
- Gastroenterology Section, IRCCS 'De Bellis', Castellana Grotte (BA), Italy
| | - Enzo Ierardi
- Gastroenterology Section, Department of Emergency and Organ Transplantation, Piazza Giulio Cesare, University of Bari, Bari, Italy
| | - Alfredo Di Leo
- Gastroenterology Section, Department of Emergency and Organ Transplantation, Piazza Giulio Cesare, University of Bari, Bari, Italy
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Crespin OM, Liu LWC, Parmar A, Jackson TD, Hamid J, Shlomovitz E, Okrainec A. Safety and efficacy of POEM for treatment of achalasia: a systematic review of the literature. Surg Endosc 2016; 31:2187-2201. [PMID: 27633440 DOI: 10.1007/s00464-016-5217-y] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Accepted: 08/23/2016] [Indexed: 01/30/2023]
Abstract
INTRODUCTION Peroral endoscopic myotomy (POEM) is a novel intervention for the treatment of achalasia, which combines the advantages of endoscopic access and myotomy. The purpose of this study was to perform a systematic review of the literature to evaluate the efficacy and safety of POEM. METHODS The systematic review was conducted following the PRISMA guidelines. Evidence-Based Medicine Reviews, Cochrane Central Register of Controlled Trials, Ovid MEDLINE (R) including in-process and non-indexed citations were searched for POEM studies using the keywords: esophageal achalasia, POEM, endoscopy, natural orifice surgery, laparoscopic Heller myotomy (LHM), and related terms. Eckardt score, lower esophageal sphincter (LES) pressure, and reported complications were the main outcomes. Two authors reviewed the search result independently. A third reviewer resolved all disagreements. Data abstraction was pilot-tested and approved by all authors. Data were examined for clinical, methodological, and statistical heterogeneity with the aim of determining whether evidence synthesis using meta- analysis was possible. RESULTS The search strategy retrieved 2894 citations. After removing duplicates and applying the exclusion criteria, 54 studies were selected for full-text review of which a total of 19 studies were considered eligible for further analysis. There were 10 retrospective and 9 prospective studies, including 1299 POEM procedures. No randomized control trial (RCT) was identified. Overall, the pre- and post-POEM Eckardt scores and LES pressure were significantly different. The most frequently reported complications were mucosal perforation, subcutaneous emphysema, pneumoperitoneum, pneumothorax, pneumomediastinum, pleural effusion, and pneumonia. The median follow-up was 13 months (range 3-24). CONCLUSION POEM is a safe and effective alternative for the treatment of achalasia. However, only short-term follow-up data compared with LHM are available. RCTs and long-term follow-up studies are needed to establish the efficacy and safety of POEM in the management of patients with achalasia.
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Affiliation(s)
- Oscar M Crespin
- Division of General Surgery, University Health Network, Toronto, ON, Canada. .,Department of Surgery, University of Toronto, Toronto, ON, Canada.
| | - Louis W C Liu
- Division of Gastroenterology, University Health Network, Toronto, ON, Canada
| | - Ambica Parmar
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Timothy D Jackson
- Division of General Surgery, University Health Network, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Jemila Hamid
- Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.,Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada
| | - Eran Shlomovitz
- Division of General Surgery, University Health Network, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, ON, Canada.,Division of Interventional Radiology, University Health Network, Toronto, ON, Canada
| | - Allan Okrainec
- Division of General Surgery, University Health Network, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, ON, Canada
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The efficacy and safety of proton-pump inhibitors in treating patients with non-erosive reflux disease: a network meta-analysis. Sci Rep 2016; 6:32126. [PMID: 27581096 PMCID: PMC5007473 DOI: 10.1038/srep32126] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2016] [Accepted: 08/02/2016] [Indexed: 01/10/2023] Open
Abstract
Proton-pump inhibitors (PPIs) have been proved as safe and effective ways to treat patients with non-erosive reflux disease (NERD). However, less is known about the comparisons among different PPIs and their best dosage. We aimed to synthesize the available evidence through network meta-analysis to investigate the efficacy and safety of different PPIs in treating patients with NERD. Fifteen studies with 6309 patients were included in the meta-analyses. For the rate of symptomatic relief, compared with control groups, all interventions except rabeprazole 5 mg significantly increased rate of symptomatic relief. Among the comparisons of different interventions, omeprazole 20 mg group was associated with a higher rate of symptomatic relief in contrast to omeprazole 10 mg group (odds ratio, OR: 1.89, 95% confidence interval, CI: 1.34, 2.67; p-value: 0.0005) or rabeprazole 5 mg group (OR: 2.51, 95%CI: 1.16, 5.42; p-value: 0.019); dexlansoprazole 30 mg therapy significantly improved the rate of symptomatic relief compared with rabeprazole 5 mg group (OR: 2.64, 95%CI: 1.08, 6.43; p-value: 0.03). For the rate of adverse events, there was no significant difference among all interventions.
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26
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Patti MG, Vela MF, Odell DD, Richter JE, Fisichella PM, Vaezi MF. The Intersection of GERD, Aspiration, and Lung Transplantation. J Laparoendosc Adv Surg Tech A 2016; 26:501-5. [PMID: 27218671 DOI: 10.1089/lap.2016.0170] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Lung transplantation is a radical but life-saving treatment option for patients with end-stage lung diseases, such as idiopathic pulmonary fibrosis (IPF) and scleroderma. In light of the proposed association and controversy linking gastroesophageal reflux disease (GERD) to IPF and lung transplant outcome, the American Gastroenterological Association convened during the DDW in Washington in May 2015 a multidisciplinary group of experts in the field of GERD and lung transplantation to make considerations about the care of these patients based on available data and subsequent expert panel discussion at this symposium. The following topics were discussed: (1) pathophysiology of GERD-induced pulmonary symptoms, (2) GERD evaluation before and after lung transplantation, (3) outcome of lung transplantation for IPF and scleroderma, and (4) role of laparoscopic fundoplication before or after lung transplantation.
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Affiliation(s)
- Marco G Patti
- 1 Pritzker School of Medicine, University of Chicago , Chicago, Illinois
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27
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Bayerdörffer E, Bigard MA, Weiss W, Mearin F, Rodrigo L, Dominguez Muñoz JE, Grundling H, Persson T, Svedberg LE, Keeling N, Eklund S. Randomized, multicenter study: on-demand versus continuous maintenance treatment with esomeprazole in patients with non-erosive gastroesophageal reflux disease. BMC Gastroenterol 2016; 16:48. [PMID: 27080034 PMCID: PMC4831110 DOI: 10.1186/s12876-016-0448-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 02/25/2016] [Indexed: 12/16/2022] Open
Abstract
Background Most patients with gastroesophageal reflux disease experience symptomatic relapse after stopping acid-suppressive medication. The aim of this study was to compare willingness to continue treatment with esomeprazole on-demand versus continuous maintenance therapy for symptom control in patients with non-erosive reflux disease (NERD) after 6 months. Methods This multicenter, open-label, randomized, parallel-group study enrolled adults with NERD who were heartburn-free after 4 weeks’ treatment with esomeprazole 20 mg daily. Patients received esomeprazole 20 mg daily continuously or on-demand for 6 months. The primary variable was discontinuation due to unsatisfactory treatment. On-demand treatment was considered non-inferior if the upper limit of the one-sided 95 % confidence interval (CI) for the difference between treatments was <10 %. Results Of 877 patients enrolled, 598 were randomized to maintenance treatment (continuous: n = 297; on-demand: n = 301). Discontinuation due to unsatisfactory treatment was 6.3 % for on-demand and 9.8 % for continuous treatment (difference −3.5 % [90 % CI: −7.1 %, 0.2 %]). In total, 82.1 and 86.2 % of patients taking on-demand and continuous therapy, respectively, were satisfied with the treatment of heartburn and regurgitation symptoms, a secondary variable (P = NS). Mean study drug consumption was 0.41 and 0.91 tablets/day, respectively. Overall, 5 % of the on-demand group developed reflux esophagitis versus none in the continuous group (P < 0.0001). The Gastrointestinal Symptom Rating Scale Reflux dimension was also improved for continuous versus on-demand treatment. Esomeprazole was well tolerated. Conclusions In terms of willingness to continue treatment, on-demand treatment with esomeprazole 20 mg was non-inferior to continuous maintenance treatment and reduced medication usage in patients with NERD who had achieved symptom control with initial esomeprazole treatment. Trial registration ClinicalTrials.gov identifier (NCT number): NCT02670642; Date of registration: December 2015.
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Affiliation(s)
| | - Marc-Andre Bigard
- Gastroenterology Unit, University Hospital, Vandoeuvre les Nancy, France
| | - Werner Weiss
- 4th Medical Department, Hospital Rudolfstiftung, Vienna, Austria
| | - Fermín Mearin
- Gastroenterology Service, Centro Médico Teknon, Barcelona, Spain
| | - Luis Rodrigo
- Gastroenterology Service, Hospital Central de Asturias, Oviedo, Spain
| | | | - Hennie Grundling
- Department of Internal Medicine, Universitas Hospital, Bloemfontein, South Africa
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Nakagawa K, Koike T, Iijima K, Saito M, Kikuchi H, Hatta W, Ara N, Uno K, Asano N, Shimosegawa T. Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients. World J Gastroenterol 2015; 21:13352-13359. [PMID: 26715820 PMCID: PMC4679769 DOI: 10.3748/wjg.v21.i47.13352] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Revised: 04/13/2015] [Accepted: 09/30/2015] [Indexed: 02/07/2023] Open
Abstract
AIM To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients. METHODS Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance - pH on rabeprazole. The symptom index (SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter. RESULTS In 14 (40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes (46.7%) than in distal ones (5.7%) (P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and distal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (29.4%) and distal ones (14.3%) (NS). CONCLUSION The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.
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Refractory chronic cough due to gastroesophageal reflux: Definition, mechanism and management. World J Methodol 2015; 5:149-56. [PMID: 26413488 PMCID: PMC4572028 DOI: 10.5662/wjm.v5.i3.149] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 07/06/2015] [Accepted: 07/11/2015] [Indexed: 02/06/2023] Open
Abstract
Refractory chronic cough due to gastroesophageal reflux is a troublesome condition unresponsive to the standard medical anti-reflux therapy. Its underlying mechanisms may include incomplete acid suppression, non-acid reflux, transient lower esophageal sphincter relaxations and esophageal hypersensitivity. The diagnosis of this disorder depends on both the findings of multi-channel intraluminal impedance-pH monitoring and the subsequent intensified anti-reflux therapy. The strategies of pharmacological treatment for refractory chronic cough due to reflux include the optimization of proton pump inhibitors and add-on therapies with histamine H2 receptor antagonists, baclofen and gabapentin. However, the further study is needed to satisfy its management.
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Dickman R, Maradey-Romero C, Gingold-Belfer R, Fass R. Unmet Needs in the Treatment of Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2015; 21:309-19. [PMID: 26130628 PMCID: PMC4496897 DOI: 10.5056/jnm15105] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 06/17/2015] [Accepted: 06/18/2015] [Indexed: 12/13/2022] Open
Abstract
Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder. Proton pump inhibitors have profoundly revolutionized the treatment of GERD. However, several areas of unmet need persist despite marked improvements in the ther-apeutic management of GERD. These include the advanced grades of erosive esophagitis, nonerosive reflux disease, main-tenance treatment of erosive esophagitis, refractory GERD, postprandial heartburn, atypical and extraesophageal manifestations of GERD, Barrett's esophagus, chronic protein pump inhibitor treatment, and post-bariatric surgery GERD. Consequently, any fu-ture development of novel therapeutic modalities for GERD (medical, endoscopic, or surgical), would likely focus on the afore-mentioned areas of unmet need.
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Affiliation(s)
- Ram Dickman
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio,
USA
| | - Carla Maradey-Romero
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio,
USA
| | - Rachel Gingold-Belfer
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio,
USA
| | - Ronnie Fass
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio,
USA
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Sano H, Iwakiri K, Kawami N, Tanaka Y, Sakamoto C. Mechanisms of acid reflux and how refluxed Acid extends proximally in patients with non-erosive reflux disease. Digestion 2015; 90:108-15. [PMID: 25196607 DOI: 10.1159/000365588] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 06/27/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS The mechanisms that cause acid reflux in patients with non-erosive reflux disease (NERD), including those that determine how acid extends proximally, are not yet clear. METHODS Concurrent esophageal manometry and pH monitoring were performed for 3 h after a meal in 13 patients with NERD, 12 with mild reflux esophagitis (RE), and 13 healthy subjects (HS). RESULTS Transient lower esophageal sphincter (LES) relaxation (TLESR) was the major mechanism of acid reflux in all three groups. LES pressure did not differ between the groups. At 2 cm above the LES, there were no differences between the three groups in the number of TLESR-related acid reflux episodes, rate of TLESRs and rate of acid reflux during TLESR. However, at 7 cm above the LES, the rate of acid reflux during TLESRs was significantly higher in patients with NERD (mean ± SEM 42.3 ± 4.8) than in those with mild RE (28.0 ± 3.8) and HS (10.8 ± 2.5). CONCLUSIONS TLESRs are the sole motor events underlying acid reflux episodes in patients with NERD. Acid extends proximally more readily in patients with NERD than in HS and those with mild RE.
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Affiliation(s)
- Hirohito Sano
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
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Lundell L. The physiological background behind and course of development of the first proton pump inhibitor. Scand J Gastroenterol 2015; 50:680-4. [PMID: 25857639 DOI: 10.3109/00365521.2015.1013981] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
UNLABELLED Gastric acid secretion and its related diseases and their treatments have generated important contributions to gastroenterology and its development as an autonomous medical specialty. The discovery of histamine receptors and the subsequent H2-receptor antagonists (1972) changed the practice of gastroenterology forever. Gastric acid was effectively inhibited and ulcers could be healed to an extent which had not previously been seen. An additional milestone along the same avenue was offered by the identification of hydrogen potassium adenosine triphosphatase (H(+)K(+)-ATPase) as the proton pump of the parietal cell. Nowadays, proton pump inhibitors (PPIs) are widely used. However, we need to reconsider the physiology and pathophysiology of acid secretion and its long-term inhibition to avoid potential negative effects on general health. PPIs are generally considered among the safest class of drugs. In the late 1960s, a research project was initiated to develop an antisecretory drug which could be used in acid hypersecretory disease states such as peptic ulcer disease based on the option to synthesize a local anesthetic drug that could be orally administered and therefore have its main action on the gastrin cells. This concept was soon found to be a blind track and further development of the basic compounds CMN131 by the synthesis of H77/67 were found to be active in the gastric acid secretion, and the benzimidazol analog of H77/67 was then synthesized a year later and was tested and found to exert powerful acid inhibitory effects. Binding studies with the substituted benzimidazoles clarified specific binding to H+/K+/ATPase in the secretory vesicles of the parietal cells. Since weak bases like aminopyrine accumulate in the acid compartment of the parietal cells, the chemists changed the substituents of the heterocyclic ring and obtained a compound with a weak base property with an optimal PkA value, thereby maximizing the accumulation of the compound at the site of action. This compound H168/68 was synthesized in 1979 and was given the generic name omeprazole. Omeprazole was soon shown to be a very potent inhibitor of the proton pump in vitro as well as in preparation from the human stomach tissue. Pharmacological studies showed long-lasting effect on acid secretion and a specific binding to the target site and soon found the compound to exert unique therapeutic effects. CONCLUSION The development of the first PPI omeprazole represents an exceptional example of a unique and fruitful collaboration between people with in-depth knowledge of gastric physiology and pharmacology. Frontline expertise in biochemistry and applied clinical science were added to these components, resulting in one of the greatest therapeutic advances during the last decades of the former century.
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Affiliation(s)
- Lars Lundell
- Surgical Gastroenterology, Centre for Digestive Diseases, Karolinska University Hospital , Stockholm , Sweden
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Penagini R, Sweis R, Mauro A, Domingues G, Vales A, Sifrim D. Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2015; 21:265-72. [PMID: 25843078 PMCID: PMC4398246 DOI: 10.5056/jnm14075] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 12/01/2014] [Accepted: 12/07/2014] [Indexed: 12/13/2022] Open
Abstract
Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients’ outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38–57 years]) with a diagnosis of functional heart-burn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index ≥ 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients (P < 0.003) increased the dose of proton pump inhibitors or underwent fundoplication after the pH test. Outcome was positive in 77% of non-erosive reflux disease vs 43% of functional heartburn patients (P < 0.05). Conclusions One-third of patients classified as functional heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients’ management.
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Affiliation(s)
- Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Milan, Italy
| | - Rami Sweis
- University College London Hospital, London, United Kingdom
| | - Aurelio Mauro
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Milan, Italy
| | | | - Andres Vales
- Esophageal Lab, Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Daniel Sifrim
- Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
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Rey JW, Deris N, Marquardt JU, Thomaidis T, Moehler M, Kittner JM, Nguyen-Tat M, Dümcke S, Tresch A, Biesterfeld S, Goetz M, Mudter J, Neurath MF, Galle PR, Kiesslich R, Hoffman A. High-definition endoscopy with iScan and Lugol's solution for the detection of inflammation in patients with nonerosive reflux disease: histologic evaluation in comparison with a control group. Dis Esophagus 2014; 29:185-91. [PMID: 25515856 DOI: 10.1111/dote.12308] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonerosive reflux disease (NERD) is commonly diagnosed in patients with symptoms of reflux. The aim of the present study was to determine whether high-definition endoscopy (HD) plus equipped with the iScan function or chromoendoscopy with Lugol's solution might permit the differentiation of NERD patients from those without reflux symptoms, proven by targeted biopsies of endoscopic lesions. A total of 100 patients without regular intake of proton pump inhibitors and with a normal conventional upper endoscopy were prospectively divided into NERD patients and controls. A second upper endoscopy was performed using HD+ with additional iScan function and then Lugol's solution was applied. Biopsy specimens were taken from the gastroesophageal junction in all patients. A total of 65 patients with reflux symptoms and 27 controls were included. HD(+) endoscopy with iScan revealed subtle mucosal breaks in 52 patients; the subsequent biopsies confirmed esophagitis in all cases. After Lugol's solution, 58 patients showed mucosal breaks. Sensitivity for the iScan procedure was 82.5%, whereas that for Lugol's solution was 92.06%. Excellent positive predictive values of 100% and 98.3%, respectively, were noted. The present study suggests that the majority of patients with NERD and typical symptoms of reflux disease can be identified by iScan or Lugol's chromoendoscopy as minimal erosive reflux disease (ERD) patients.
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Affiliation(s)
- J W Rey
- First Department of Internal Medicine, University Medical Center, Mainz, Germany.,Department of Internal Medicine II, HSK Hospital, Wiesbaden, Germany
| | - N Deris
- First Department of Internal Medicine, University Medical Center, Mainz, Germany
| | - J U Marquardt
- First Department of Internal Medicine, University Medical Center, Mainz, Germany
| | - T Thomaidis
- First Department of Internal Medicine, University Medical Center, Mainz, Germany
| | - M Moehler
- First Department of Internal Medicine, University Medical Center, Mainz, Germany
| | - J M Kittner
- First Department of Internal Medicine, University Medical Center, Mainz, Germany
| | - M Nguyen-Tat
- First Department of Internal Medicine, University Medical Center, Mainz, Germany
| | - S Dümcke
- Max Planck Institute for Plant Breeding Research Cologne, Cologne, Germany.,Institute for Genetics, University of Cologne, Cologne, Germany
| | - A Tresch
- Max Planck Institute for Plant Breeding Research Cologne, Cologne, Germany.,Institute for Genetics, University of Cologne, Cologne, Germany
| | - S Biesterfeld
- Institute for Pathology, University Hospital, Düsseldorf, Germany
| | - M Goetz
- First Department of Internal Medicine, University Medical Center, Mainz, Germany.,First Department of Internal Medicine, University Hospital, Tübingen, Germany
| | - J Mudter
- First Department of Internal Medicine, University Hospital, Erlangen, Germany
| | - M F Neurath
- First Department of Internal Medicine, University Hospital, Erlangen, Germany
| | - P R Galle
- First Department of Internal Medicine, University Medical Center, Mainz, Germany
| | - R Kiesslich
- First Department of Internal Medicine, University Medical Center, Mainz, Germany.,Department of Internal Medicine II, HSK Hospital, Wiesbaden, Germany
| | - A Hoffman
- First Department of Internal Medicine, University Medical Center, Mainz, Germany.,Department of Internal Medicine II, HSK Hospital, Wiesbaden, Germany
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Abstract
Gastroesophageal reflux disease (GERD) is frequently diagnosed by symptoms and good response to acid suppression with proton pump inhibitors. Further work up is required when the diagnosis of GERD is uncertain, for alarm symptoms, PPI-refractoriness, and often for extraesophageal presentations. Useful tools include endoscopy for mucosal assessment and reflux monitoring (pH or impedance-pH) to quantify reflux burden. Objective documentation of pathological reflux is mandatory prior to anti-reflux surgery. In some patients, symptoms that can be attributed to GERD may have other causes; in these patients, testing that excludes GERD helps direct the diagnostic and treatment efforts to other causes.
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Burgstaller JM, Jenni BF, Steurer J, Held U, Wertli MM. Treatment efficacy for non-cardiovascular chest pain: a systematic review and meta-analysis. PLoS One 2014; 9:e104722. [PMID: 25111147 PMCID: PMC4128723 DOI: 10.1371/journal.pone.0104722] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 07/12/2014] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Non-cardiovascular chest pain (NCCP) leads to impaired quality of life and is associated with a high disease burden. Upon ruling out cardiovascular disease, only vague recommendations exist for further treatment. OBJECTIVES To summarize treatment efficacy for patients presenting with NCCP. METHODS Systematic review and meta-analysis. In July 2013, Medline, Web of Knowledge, Embase, EBSCOhost, Cochrane Reviews and Trials, and Scopus were searched. Hand and bibliography searches were also conducted. Randomized controlled trials (RCTs) evaluating non-surgical treatments in patients with NCCP were included. Exclusion criteria were poor study quality and small sample size (<10 patients per group). RESULTS Thirty eligible RCT's were included. Most studies assessed PPI efficacy for gastroesophageal reflux disorders (GERD, n = 10). Two RCTs included musculoskeletal chest pain, seven psychotropic drugs, and eleven various psychological interventions. Study quality was high in five RCTs and acceptable in 25. PPI treatment in patients with GERD (5 RCTs, 192 patients) was more effective than placebo [pooled OR 11.7 (95% CI 5.5 to 25.0, heterogeneity I2 = 6.1%)]. The pooled OR in GERD negative patients (4 RCTs, 156 patients) was 0.8 (95% CI 0.2 to 2.8, heterogeneity I2 = 50.4%). In musculoskeletal NCCP (2 RCTs, 229 patients) manual therapy was more effective than usual care but not than home exercise [pooled mean difference 0.5 (95% CI -0.3 to 1.3, heterogeneity I2 = 46.2%)]. The findings for cognitive behavioral treatment, serotonin reuptake inhibitors, tricyclic antidepressants were mixed. Most evidence was available for cognitive behavioral treatment interventions. LIMITATIONS Only a small number of studies were available. CONCLUSIONS Timely diagnostic evaluation and treatment of the disease underlying NCCP is important. For patients with suspected GERD, high-dose treatment with PPI is effective. Only limited evidence was available for most prevalent diseases manifesting with chest pain. In patients with idiopathic NCCP, treatments based on cognitive behavioral principles might be considered.
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Affiliation(s)
- Jakob M. Burgstaller
- Horten Center for Patient Oriented Research and Knowledge Transfer, Department of Internal Medicine, University of Zurich, Zurich, Switzerland
| | - Boris F. Jenni
- Horten Center for Patient Oriented Research and Knowledge Transfer, Department of Internal Medicine, University of Zurich, Zurich, Switzerland
| | - Johann Steurer
- Horten Center for Patient Oriented Research and Knowledge Transfer, Department of Internal Medicine, University of Zurich, Zurich, Switzerland
| | - Ulrike Held
- Horten Center for Patient Oriented Research and Knowledge Transfer, Department of Internal Medicine, University of Zurich, Zurich, Switzerland
| | - Maria M. Wertli
- Horten Center for Patient Oriented Research and Knowledge Transfer, Department of Internal Medicine, University of Zurich, Zurich, Switzerland
- Cantonal Hospital Winterthur, Winterthur, Switzerland
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Abstract
There has been a marked decline over the last several years in drug development for gastroesophageal reflux disease and specifically for nonerosive reflux disease (NERD), despite there being many areas of unmet need. In contrast, we have seen a proliferation, during the same period of time, in development of novel, nonmedical therapeutic strategies for NERD using cutting-edge technology. Presently, compliance and lifestyle modifications are readily available noninvasive therapeutic interventions for NERD. Other nonmedical therapies include, the Stretta procedure, transoral incisionless fundoplication, and the magnetic sphincter augmentation device (LINX). Antireflux surgery, in experienced hands, has been repeatedly shown to be efficacious in resolving NERD-related symptoms. Psychological therapeutic interventions and alternative medicine techniques, such as acupuncture, continue to show promise, especially in NERD patients who failed antireflux treatment.
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Park CH, Kim HS, Lee SK. Effects of the New Prokinetic Agent DA-9701 Formulated With Corydalis Tuber and Pharbitis Seed in Patients With Minimal Change Esophagitis: A Bicenter, Randomized, Double Blind, Placebo-controlled Study. J Neurogastroenterol Motil 2014; 20:338-346. [PMID: 24953714 PMCID: PMC4102148 DOI: 10.5056/jnm14019] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Revised: 03/11/2014] [Accepted: 03/18/2014] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIMS DA-9701 (Motilitone) is a new prokinetic agent formulated with Corydalis Tuber and Pharbitis Seed. We assessed the efficacy of DA-9701 in symptomatic patients with minimal change esophagitis. METHODS Patients with minimal change esophagitis presenting with reflux or dyspeptic symptoms were randomly assigned to receive either DA-9701 30 mg or placebo t.i.d. (means 3 times a day). After 4 weeks of treatment, the primary efficacy end point determined by changes of the Nepean dyspepsia index questionnaire-Korean version (NDI-K) symptom scores, was analyzed. RESULTS Forty-two and 39 patients were assigned to the treatment and control groups, respectively. After 4 weeks, NDI-K symptom scores were reduced from 35.4 to 13.5 (P < 0.001) and from 43.0 to 27.7 (P < 0.001) in the treatment and the control groups, respectively. However, changes in the symptom scores did not differ between the 2 groups (P = 0.741). Although the quality of life scores were significantly improved after 4 weeks in both groups, changes in the quality of life score between the baseline value and that at 4 weeks did not differ between the 2 groups. The reflux symptom score was significantly improved in the treatment group compared to the placebo group in patients aged 65 years or older (P = 0.035). CONCLUSIONS Although NDI-K symptom scores and quality of life scores were improved after 4 weeks of treatment compared with baseline values in patients with minimal change esophagitis, DA-9701 did not improve the symptom scores or quality of life scores compared with the placebo.
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Affiliation(s)
- Chan Hyuk Park
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun-Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do, Korea
| | - Sang Kil Lee
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
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Yu YY, Fang DC, Fan LL, Chang H, Wu ZL, Cao Y, Lan CH. Efficacy and safety of esomeprazole with flupentixol/melitracen in treating gastroesophageal reflux disease patients with emotional disorders. J Gastroenterol Hepatol 2014; 29:1200-1206. [PMID: 24955450 DOI: 10.1111/jgh.12552] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/29/2014] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM This study was designed to demonstrate the safety and efficacy of esomeprazole combined with flupentixol/melitracen for the treatment of gastroesophageal reflux disease (GERD) patients with emotional disorders. METHODS Two hundred eighty-nine GERD patients with emotional disorders were divided randomly into two groups: group 1 received esomeprazole only (monotherapy) and group 2 received esomeprazole and flupentixol/melitracen (combination therapy). The patients' GERD questionnaire (GerdQ) and hospital anxiety and depression (HAD) scores were obtained before and after treatment. Changes in the scores, rates of symptom remission, and adverse effects were compared between the two groups. RESULTS After 2 weeks of treatment, the average decrease in GerdQ score in the combination group (4.04 ± 2.34) was significantly greater than that in the monotherapy group (3.34 ± 2.74; P < 0.05). Significant differences between the two groups were also found for changes in HAD anxiety scores (5.45 ± 2.41 vs 3.34 ± 2.43, P < 0.05), depression scores (5.47 ± 2.47 vs 3.00 ± 3.28, P < 0.05), and anxiety-depression scores (5.20 ± 2.71 vs 3.60 ± 2.56, P < 0.05). The remission of symptoms (eructation, abdominal pain, anorexia, and other accompanying symptoms) in the combination group was significantly better than that in the monotherapy group, and no significant difference in the incidence of adverse events was observed between the two groups. CONCLUSIONS The combination therapy has better efficacy than the monotherapy in improving the symptoms of gastroesophageal reflux in patients with emotional disorders. In addition, this combination treatment is safe, with a low incidence of adverse events.
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EAES recommendations for the management of gastroesophageal reflux disease. Surg Endosc 2014; 28:1753-73. [PMID: 24789125 DOI: 10.1007/s00464-014-3431-z] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Accepted: 01/08/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is one of the most frequent benign disorders of the upper gastrointestinal tract. Management of GERD has always been controversial since modern medical therapy is very effective, but laparoscopic fundoplication is one of the few procedures that were quickly adapted to the minimal access technique. The purpose of this project was to analyze the current knowledge on GERD in regard to its pathophysiology, diagnostic assessment, medical therapy, and surgical therapy, and special circumstances such as GERD in children, Barrett's esophagus, and enteroesophageal and duodenogastroesophageal reflux. METHODS The European Association of Endoscopic Surgery (EAES) has tasked a group of experts, based on their clinical and scientific expertise in the field of GERD, to establish current guidelines in a consensus development conference. The expert panel was constituted in May 2012 and met in September 2012 and January 2013, followed by a Delphi process. Critical appraisal of the literature was accomplished. All articles were reviewed and classified according to the hierarchy of level of evidence and summarized in statements and recommendations, which were presented to the scientific community during the EAES yearly conference in a plenary session in Vienna 2013. A second Delphi process followed discussion in the plenary session. RESULTS Recommendations for pathophysiologic and epidemiologic considerations, symptom evaluation, diagnostic workup, medical therapy, and surgical therapy are presented. Diagnostic evaluation and adequate selection of patients are the most important features for success of the current management of GERD. Laparoscopic fundoplication is the most important therapeutic technique for the success of surgical therapy of GERD. CONCLUSIONS Since the background of GERD is multifactorial, the management of this disease requires a complex approach in diagnostic workup as well as for medical and surgical treatment. Laparoscopic fundoplication in well-selected patients is a successful therapeutic option.
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Martín-Pérez J, Arteaga-González I, Martín-Malagón A, Díaz-Luis H, Casanova-Trujillo C, Carrillo-Pallarés A A. Frequency of abnormal esophageal acid exposure in patients eligible for bariatric surgery. Surg Obes Relat Dis 2014; 10:1176-80. [PMID: 25443048 DOI: 10.1016/j.soard.2014.04.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Revised: 03/22/2014] [Accepted: 04/09/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND Obesity and gastroesophageal reflux disease (GERD) are both high-prevalence diseases in developed nations. Obesity has been identified as an important risk factor in the development of GERD. The objective of this study was to determine the frequency of abnormal esophageal acid exposure in patients candidate for bariatric surgery and its relationship with any clinical and endoscopic findings before surgery. METHODS Data collected from a group of 88 patients awaiting bariatric surgery included a series of demographic variables and symptoms typical of GERD. The tests patients underwent included manometry, pH monitoring, and upper gastrointestinal endoscopy. Univariate and multivariate analyses were conducted on the variables related to the onset of reflux. RESULTS Esophageal pH monitoring tests were positive in 65% of the patients. Manometries showed lower esophageal sphincter hypotonia in 46%, while 20% returned abnormal upper endoscopy results. Out of the 45% of patients who were asymptomatic or returned normal endoscopies, half returned positive esophageal pH tests. In turn, among the 55% of patients who had symptoms or an abnormal upper endoscopy, three quarters had pH tests that diagnosed reflux. pH tests were also positive in 80% of symptomatic patients and 100% of patients with esophagitis (P<.042). No statistically significant relationship was found between body mass index, sex, age, manometry, or hiatus hernia and the positive pH monitoring. CONCLUSION Frequency of abnormal esophageal acid exposure among obese patients is high. There is a relationship between the presence of symptoms and reflux. But the absence of symptoms does not rule out the presence of abnormal esophageal function tests.
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Affiliation(s)
- Jesica Martín-Pérez
- Department of Surgery, University Hospital of Canarias (HUC), Santa Cruz de Tenerife, Spain
| | - Ivan Arteaga-González
- Department of Surgery, University Hospital of Canarias (HUC), Santa Cruz de Tenerife, Spain.
| | - Antonio Martín-Malagón
- Department of Surgery, University Hospital of Canarias (HUC), Santa Cruz de Tenerife, Spain
| | - Hermógenes Díaz-Luis
- Department of Surgery, University Hospital of Canarias (HUC), Santa Cruz de Tenerife, Spain
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Puesta al día en el reflujo gastroesofágico. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 37:73-82. [DOI: 10.1016/j.gastrohep.2013.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 11/17/2013] [Accepted: 11/18/2013] [Indexed: 02/08/2023]
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Zhang JX, Ji MY, Song J, Lei HB, Qiu S, Wang J, Ai MH, Wang J, Lv XG, Yang ZR, Dong WG. Proton pump inhibitor for non-erosive reflux disease: A meta-analysis. World J Gastroenterol 2013; 19:8408-8419. [PMID: 24363534 PMCID: PMC3857466 DOI: 10.3748/wjg.v19.i45.8408] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Revised: 09/04/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy, safety and influential factors of proton pump inhibitor (PPI) treatment for non-erosive reflux disease (NERD).
METHODS: PubMed, MEDLINE, EMBASE and the Cochrane Library were searched up to April 2013 to identify eligible randomized controlled trials (RCTs) that probed into the efficacy, safety and influential factors of PPI treatment for NERD. The rates of symptomatic relief and adverse events were measured as the outcomes. After RCT selection, assessment and data collection, the pooled RRs and 95%CI were calculated. This meta-analysis was performed using the Stata 12.0 software (Stata Corporation, College Station, Texas, United States). The level of evidence was estimated by the Grading of Recommendations Assessment, Development and Evaluation system.
RESULTS: Seventeen RCTs including 6072 patients met the inclusion criteria. The results of the meta-analysis showed that PPI treatment was significantly superior to H2 receptor antagonists (H2RA) treatment (RR = 1.629, 95%CI: 1.422-1.867, P = 0.000) and placebo (RR = 1.903, 95%CI: 1.573-2.302, P = 0.000) for the symptomatic relief of NERD. However, there were no obvious differences between PPI and H2RA (RR = 0.928, 95%CI: 0.776-1.110, P = 0.414) or PPI and the placebo (RR = 1.000, 95%CI: 0.896-1.116, P = 0.997) regarding the rate of adverse events. The overall rate of symptomatic relief of PPI against NERD was 51.4% (95%CI: 0.433-0.595, P = 0.000), and relief was influenced by hiatal hernia (P = 0.030). The adverse rate of PPI against NERD was 21.0% (95%CI: 0.152-0.208, P = 0.000), and was affected by hiatal hernia (P = 0.081) and drinking (P = 0.053).
CONCLUSION: PPI overmatched H2RA on symptomatic relief rate but not on adverse rate for NERD. Its relief rate and adverse rate were influenced by hiatal hernia and drinking.
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Cicala M, Emerenziani S, Guarino MPL, Ribolsi M. Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease. World J Gastroenterol 2013; 19:6529-6535. [PMID: 24151377 PMCID: PMC3801364 DOI: 10.3748/wjg.v19.i39.6529] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Revised: 07/31/2013] [Accepted: 08/16/2013] [Indexed: 02/06/2023] Open
Abstract
Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.
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de Bortoli N, Martinucci I, Bellini M, Savarino E, Savarino V, Blandizzi C, Marchi S. Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome. World J Gastroenterol 2013; 19:5787-5797. [PMID: 24124323 PMCID: PMC3793133 DOI: 10.3748/wjg.v19.i35.5787] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Revised: 11/14/2012] [Accepted: 12/27/2012] [Indexed: 02/06/2023] Open
Abstract
Several studies indicate a significant degree of overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). Likewise, both functional heartburn (FH) and IBS are functional digestive disorders that may occur in the same patients. However, data establishing a solid link between FH and IBS are lacking, mainly because the clinical definition of FH has undergone substantial changes over the years. The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS. In particular, several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH (as defined by the Rome III criteria) from GERD via pathophysiological investigations. Independent of these critical issues, there is preliminary evidence supporting a significant degree of FH-IBS overlap. This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications, particularly to distinguish FH from GERD. This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.
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Chen CL, Hsu PI. Current advances in the diagnosis and treatment of nonerosive reflux disease. Gastroenterol Res Pract 2013; 2013:653989. [PMID: 23935610 PMCID: PMC3725792 DOI: 10.1155/2013/653989] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Accepted: 06/13/2013] [Indexed: 02/06/2023] Open
Abstract
Nonerosive reflux disease (NERD) is a distinct pattern of gastroesophageal reflux disease (GERD). It is defined as a subcategory of GERD characterized by troublesome reflux-related symptoms in the absence of esophageal mucosal erosions/breaks at conventional endoscopy. In clinical practice, patients with reflux symptoms and negative endoscopic findings are markedly heterogeneous. The potential explanations for the symptom generation in NERD include microscopic inflammation, visceral hypersensitivity (stress and sleep), and sustained esophageal contractions. The use of 24-hour esophageal impedance and pH monitoring gives further insight into reflux characteristics and symptom association relevant to NERD. The treatment choice of NERD still relies on acid-suppression therapy. Initially, patients can be treated by a proton pump inhibitor (PPI; standard dose, once daily) for 2-4 weeks. If initial treatment fails to elicit adequate symptom control, increasing the PPI dose (standard dose PPI twice daily) is recommended. In patients with poor response to appropriate PPI treatment, 24-hour esophageal impedance and pH monitoring is indicated to differentiate acid-reflux-related NERD, weakly acid-reflux-related NERD (hypersensitive esophagus), nonacid-reflux-related NERD, and functional heartburn. The response is less effective in NERD as compared with erosive esophagitis.
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Affiliation(s)
- Chien-Lin Chen
- Department of Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien 970, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung 813, Taiwan
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Management of gastro-oesophageal reflux disease symptoms that do not respond to proton pump inhibitors. Curr Opin Gastroenterol 2013; 29:431-6. [PMID: 23549342 DOI: 10.1097/mog.0b013e328360433c] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Treatment-refractory gastro-oesophageal reflux disease (GERD) remains a significant problem in the gastroenterology clinic. In recent years, several studies have investigated the assessment and treatment of refractory GERD. RECENT FINDINGS Patients presenting with 'refractory GERD' in fact represent a quite heterogeneous group consisting of those with ongoing reflux-related symptoms and those with reflux-unrelated problems such as functional heartburn, dyspepsia or even eosinophilic oesophagitis. The greatest symptom indicators of persistent true reflux are retrosternal burning and acid taste in the mouth alone. Combined pH-impedance studies allow detection of reflux regardless of pH, and weakly acidic reflux has been suggested as a mechanism of residual symptoms in some patients. The use of reflux-symptom association calculations may help to determine the symptom causation, but refinement and outcome studies are needed. New treatments of refractory GERD have been disappointing. Surgery remains an option in very carefully selected patients, but again better outcome studies are required. SUMMARY Careful history and investigation is required in the assessment of the proton pump inhibitor (PPI)-refractory patient. Care to exclude alternative diagnoses is needed, and to phenotype those with reflux-related symptoms. Optimization of PPI therapy may help, as may surgery in selected patients.
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Acid sensitization of esophageal mucosal afferents: implication for symptom perception in patients across the gastroesophageal reflux disease spectrum. Clin J Pain 2013; 29:70-7. [PMID: 22330131 DOI: 10.1097/ajp.0b013e3182478826] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Sensitization of esophageal chemoreceptors, either directly by intermittent acid exposure or indirectly through esophagitis-associated inflammatory mediators, is likely to be the mechanism underlying the perception of heartburn. AIMS To compare basal esophageal sensitivity with electrical stimulation and acid, and to compare the degree of acid-induced sensitization in controls and in patient groups across the entire spectrum of gastroesophageal reflux disease: erosive oesophagitis (EO), nonerosive reflux disease (NERD), and functional heartburn (FH). METHODS Esophageal sensory and pain thresholds to electrical stimulation were measured before, 30, and 60 minutes after an intraesophageal infusion of saline or HCl. Patients received a 30-minute infusion of 0.15 M HCl and controls were randomized to receive either HCl (n = 11) or saline (n = 10). After electrical sensory threshold testing, participants received another 30-minute infusion of HCl to determine whether sensitivity to acid is increased by prior acid exposure RESULTS All patient groups had higher basal sensory thresholds than healthy controls (controls, 13 ± 1.4 mA; FH, 20 ± 5.1 mA; NERD, 21 ± 5.1 mA; EO, 23 ± 5.4 mA; P < 0.05). Acute esophageal acid exposure reduced sensory thresholds to electrical stimulation in FH and NERD patients (P < 0.05). The level of acid sensitivity during the first HCl infusion was comparable between all patient groups and controls. The secondary infusion caused increased discomfort in all participants (P < 0.01). This acid-induced sensitization to HCl was significantly elevated in the patient groups ( P < 0.05). CONCLUSIONS (1) Esophageal acid infusion sensitizes it to subsequent electrical and chemical stimulation. (2) The acid-related sensitization is greater in gastroesophageal reflux disease than in controls and may influence in part symptom perception in this population. (3) Acid-related sensitization within the gastroesophageal reflux disease population is not dependant on mucosal inflammation.
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Sigterman KE, van Pinxteren B, Bonis PA, Lau J, Numans ME, Cochrane Upper GI and Pancreatic Diseases Group. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev 2013; 2013:CD002095. [PMID: 23728637 PMCID: PMC7066537 DOI: 10.1002/14651858.cd002095.pub5] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Approximately 25% of adults regularly experience heartburn, a symptom of gastro-oesophageal reflux disease (GORD). Most patients are treated empirically (without specific diagnostic evaluation e.g. endoscopy. Among patients who have an upper endoscopy, findings range from a normal appearance, mild erythema to severe oesophagitis with stricture formation. Patients without visible damage to the oesophagus have endoscopy negative reflux disease (ENRD). The pathogenesis of ENRD, and its response to treatment may differ from GORD with oesophagitis. OBJECTIVES Summarise, quantify and compare the efficacy of short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in adults with GORD, treated empirically and in those with endoscopy negative reflux disease (ENRD). SEARCH METHODS We searched MEDLINE (January 1966 to November 2011), EMBASE (January 1988 to November 2011), and EBMR in November 2011. SELECTION CRITERIA Randomised controlled trials reporting symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be either from an empirical treatment group (no endoscopy used in treatment allocation) or from an endoscopy negative reflux disease group (no signs of erosive oesophagitis). DATA COLLECTION AND ANALYSIS Two authors independently assessed trial quality and extracted data. MAIN RESULTS Thirty-four trials (1314 participants) were included: fifteen in the empirical treatment group, fifteen in the ENRD group and four in both. In empirical treatment of GORD the risk ratio (RR) for heartburn remission (the primary efficacy variable) in placebo-controlled trials for PPI was 0.37 (two trials, 95% confidence interval (CI) 0.32 to 0.44), for H2RAs 0.77 (two trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (one trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were more effective than H2RAs (seven trials, RR 0.66, 95% CI 0.60 to 0.73) and prokinetics (two trials, RR 0.53, 95% CI 0.32 to 0.87).In treatment of ENRD, the RR for heartburn remission for PPI versus placebo was 0.71 (ten trials, 95% CI 0.65 to 0.78) and for H2RA versus placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.78 (three trials, 95% CI 0.62 to 0.97) and for PPI versus prokinetic 0.72 (one trial, 95% CI 0.56 to 0.92). AUTHORS' CONCLUSIONS PPIs are more effective than H2RAs in relieving heartburn in patients with GORD who are treated empirically and in those with ENRD, although the magnitude of benefit is greater for those treated empirically.
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Affiliation(s)
- Kirsten E Sigterman
- Technische Universität München Klinikum rechts der IsarInstitut für Allgemeinmedizin / Institute of General PracticeOrleansstrasse 47MunichGermany81667
| | | | - Peter A Bonis
- Tufts Medical Centre/Division of GastroenterologyTufts Medical Centre800 Washington StreetBox 63BostonMAUSA02111
| | - Joseph Lau
- Brown University Public Health ProgramCenter for Evidence‐based Medicine121 S. Main StreetProvidenceRIUSA02912
| | - Mattijs E Numans
- VU University Medical CenterDepartment of General Practice and Elderly Care Medicine, EMGO Institute for Health and Care Research, and Alzheimer CenterVan der Boechorststraat 712AmsterdamNetherlands
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Quigley EMM, Lacy BE. Overlap of functional dyspepsia and GERD--diagnostic and treatment implications. Nat Rev Gastroenterol Hepatol 2013; 10:175-86. [PMID: 23296247 DOI: 10.1038/nrgastro.2012.253] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
GERD and functional dyspepsia are the two most prevalent upper gastrointestinal disorders. Gastro-oesophageal reflux is most commonly diagnosed using the cardinal symptoms of heartburn and regurgitation. Patients might also be diagnosed using a questionnaire, after empiric treatment with an acid suppressant, after upper endoscopy or by pH testing. Functional dyspepsia is best diagnosed using symptoms outlined by the Rome committee in conjunction with a normal upper endoscopy. Theoretically, distinguishing these two populations should be easy for all health-care providers. In reality, however, carefully separating out these two populations can be quite difficult, as substantial overlap exists epidemiologically, symptomatically and even diagnostically. This overlap renders precise diagnosis a challenge; given the limited treatment options, the primary goal is to identify those patients who will respond to acid suppressive therapy. Despite the frequency with which functional dyspepsia and GERD overlap, remarkably few studies have investigated this overlap. Most recommendations are based on data derived from separate studies of functional dyspepsia and GERD. A further limitation of existing studies is their failure to differentiate between the various diagnostic categories into which the individual presenting with heartburn might belong.
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