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Kuipers T, Nijhuis RABO, Masclee GMC, Bredenoord AJ. Effects of Benesco™ on Esophageal Sensitivity, Mucosal Barrier Function, and Reflux Symptoms: A Mechanistic Study. Dig Dis Sci 2025; 70:285-291. [PMID: 39630400 DOI: 10.1007/s10620-024-08765-3] [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: 08/20/2024] [Accepted: 11/18/2024] [Indexed: 01/25/2025]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases in the western world. Proton pump inhibitors (PPIs) are the cornerstone of GERD management however a subset of patients seeks for (natural) alternative therapies. Benesco™ is an over-the-counter supplement, of which the active ingredient is quercetin and has a presumed positive effect on esophageal barrier function. The aim of this study was therefore to evaluate the effect of benesco™ on esophageal sensitivity, mucosal barrier function, and reflux symptoms. METHODS Patients with GERD were evaluated using acid perfusion tests, an upper endoscopy with electrical tissue impedance spectroscopy, and esophageal biopsies. RESULTS 8 patients (3 men, median age 45 (34-64)) were included. The perfusion sensitivity score (PSS) did not change significantly after treatment with benesco™ (90.5 (21.4-129.7) to 62.5 (16.4-96.9) p = 0.123). Esophageal sensitivity based on the maximum reported VAS score during the esophageal acid perfusion test did not change significantly after treatment with benesco™ (7.4 (5.3-9.8) to 7.7 (5.3-8.7) p = 0.482). Furthermore, no effects were seen on measures of mucosal barrier function such as extracellular in vivo impedance (ETIS) (6807 (5153-8883) Ω·m vs 6702 (5106-7847) Ω·m, p = 0.575), in vitro transepithelial electrical resistance (TEER) (183 (153-204) Ω.cm2 vs 201 (128-250) Ω.cm2, p = 1.000), or fluorescein flux (896 (73-1922) nmol/cm2/h vs 811 (187-2693) nmol/cm2/h, p = 0.237). CONCLUSION We did not observe an improvement of acid perception, mucosal barrier function, or reflux symptoms by benesco™ in this study. TRIAL REGISTRATION Dutch Trial Register number: NL9324.
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Affiliation(s)
- Thijs Kuipers
- Dept. of Gastroenterology and Hepatology, Amsterdam University Medical Center Location University of Amsterdam, Boelelaan, 1117, Amsterdam, the Netherlands.
- Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, the Netherlands.
| | - Renske A B Oude Nijhuis
- Dept. of Gastroenterology and Hepatology, Amsterdam University Medical Center Location University of Amsterdam, Boelelaan, 1117, Amsterdam, the Netherlands
- Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, the Netherlands
| | - Gwen M C Masclee
- Dept. of Gastroenterology and Hepatology, Amsterdam University Medical Center Location University of Amsterdam, Boelelaan, 1117, Amsterdam, the Netherlands
- Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, the Netherlands
| | - Albert J Bredenoord
- Dept. of Gastroenterology and Hepatology, Amsterdam University Medical Center Location University of Amsterdam, Boelelaan, 1117, Amsterdam, the Netherlands
- Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, the Netherlands
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Angeramo CA, Lendoire M, Herbella FAM, Schlottmann F. Efficacy and safety of antireflux mucosectomy versus radiofrequency ablation of the lower esophageal sphincter for the treatment of GERD: a systematic review and meta-analysis. Gastrointest Endosc 2024:S0016-5107(24)03830-6. [PMID: 39716536 DOI: 10.1016/j.gie.2024.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 11/19/2024] [Accepted: 12/11/2024] [Indexed: 12/25/2024]
Abstract
BACKGROUND AND AIMS GERD affects 10% to 30% of the population. Endoscopic antireflux therapies have been proposed for carefully selected patients. In this study, we compared outcomes between endoscopic antireflux mucosectomy (ARMS) and endoscopic radiofrequency ablation of the lower esophageal sphincter (Stretta procedure) for the treatment of GERD. METHODS A systematic review using the MEDLINE database was performed to identify original articles analyzing outcomes after ARMS and Stretta procedures. The main outcomes were patient satisfaction, GERD Health-Related Quality of Life (GERD-HRQL) scores, proton pump inhibitor (PPI) use, and DeMeester scores. Secondary outcomes were postprocedural adverse events. A meta-analysis of proportions and linear regression models was used to assess the effect of each endoscopic procedure on the different outcomes. RESULTS Sixty-six studies comprising 3767 patients were included, with 3074 patients (81.60%) undergoing Stretta and 693 (18.40%) ARMS. The weighted pooled patient satisfaction rates were 65% (95% confidence interval [CI], 52-76) for ARMS and 77% (95% CI, 64-87) for Stretta. Both treatments significantly reduced PPI use (from 100% to 40.18% for ARMS vs from 99.42% to 48.51% for Stretta, P = .20) and improved GERD-HRQL scores (pre 19.75 to post 8.24 for ARMS vs pre 21.02 to post 10.45 for Stretta, P = .70). DeMeester scores improved similarly after both procedures (pre 44.99 to post 15.02 for ARMS vs pre 52.29 to post 28.99 for Stretta, P = .48). ARMS was associated with higher overall morbidity (25% vs 17%, P = .001) and greater risks of stricture (odds ratio [OR], 13.03; 95% CI, 7.83-21.71), bleeding (OR, 13.16; 95% CI, 8.60-20.15), and perforation (OR, 13.03; 95% CI, 7.82-21.71) compared with Stretta. CONCLUSIONS Both Stretta and ARMS are effective endoscopic treatment modalities for GERD. Although their clinical efficacy appears to be similar, the increased risk of dysphagia, bleeding, and perforation after ARMS should not be underestimated.
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Affiliation(s)
- Cristian A Angeramo
- Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires, Argentina
| | - Mateo Lendoire
- Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires, Argentina
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Schlottmann F, Bertona S, Herbella FAM, Patti MG. Gastroesophageal reflux disease: indications for antireflux surgery, outcomes, and side effects. Expert Rev Gastroenterol Hepatol 2024; 18:693-703. [PMID: 39632344 DOI: 10.1080/17474124.2024.2438719] [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: 02/26/2024] [Revised: 10/21/2024] [Accepted: 12/03/2024] [Indexed: 12/07/2024]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a frequent digestive disorder that presents with a broad spectrum of symptoms. Global consensus on which patients should be selected for anti-reflux surgery is lacking. AREAS COVERED This evidence-based review will analyze current indications for anti-reflux surgery, outcomes of the operation, and potential side effects. EXPERT COMMENTARY Treatment of GERD has three main purposes: control symptoms, improve quality of life, and prevent potential serious complications such as bleeding, esophageal stenosis, Barrett's esophagus, and esophageal adenocarcinoma. Although medical therapy is effective in the majority of patients, some might require anti-reflux surgery in order to achieve these goals. Adequate patient selection for anti-reflux surgery is critical to obtain optimal outcomes. Most patients undergoing a fundoplication have adequate long-term symptomatic relief. However, potential side effects of anti-reflux surgery should also be discussed with patients to help manage expectations from the operation.
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Affiliation(s)
- Francisco Schlottmann
- Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires, Argentina
- Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Sofia Bertona
- Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires, Argentina
| | | | - Marco G Patti
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
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Bortolotti M. Problems with repairing gut sphincters malfunctions. World J Gastrointest Surg 2024; 16:2396-2408. [PMID: 39220086 PMCID: PMC11362937 DOI: 10.4240/wjgs.v16.i8.2396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 06/24/2024] [Accepted: 07/15/2024] [Indexed: 08/16/2024] Open
Abstract
Correcting a gut sphincter malfunction is a difficult problem. Because each sphincter has two opposite functions, that of closure and opening, repairing one there is a risk of damaging the other. Indeed, widening a narrow sphincter, such as lower esophageal sphincter (LES) and anal sphincter, may cause gastroesophageal reflux and fecal incontinence, respectively, whereas narrowing a wide sphincter, may cause a difficult transit. All the corrective treatments for difficult or retrograde transit concerning LES and anal sphincter with their unwanted consequences have been analyzed and discussed. To overcome the drawbacks of sphincter surgical repairs, researchers have devised devices capable of closing and opening the gut lumen, named artificial sphincters (ASs). Their function is based on various mechanisms, e.g., hydraulic, magnetic, mechanical etc, operating through many complicated components, such as plastic cuffs, balloons, micropumps, micromotors, connecting tubes and wires, electromechanical clamps, rechargeable batteries, magnetic devices, elastic bands, etc. Unfortunately, these structures may facilitate the onset of infections and induce a local fibrotic reaction, which may cause device malfunctioning, whereas the compression of the gut wall to occlude the lumen may give rise to ischemia with erosions and other lesions. Some ASs are already being used in clinical practice, despite their considerable limits, while others are still at the research stage. In view of the adverse events of the ASs mentioned above, we considered applying bioengineering methods to analyze and resolve biomechanical and biological interaction problems with the aim to conceive and build efficient and safe biomimetic ASs.
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Affiliation(s)
- Mauro Bortolotti
- Department of Internal Medicine and Gastroenterology, S Orsola-Malpighi Polyclinic, University of Bologna, Bologna 40138, Italy
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Kuipers T, Oude Nijhuis RAB, van den Wijngaard RM, Oors JM, Smout AJPM, Bredenoord AJ. Ziverel for PPI-refractory reflux symptoms: efficacy and mechanisms of action in humans. Scand J Gastroenterol 2024; 59:384-389. [PMID: 38088584 DOI: 10.1080/00365521.2023.2290457] [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: 10/03/2023] [Accepted: 11/28/2023] [Indexed: 04/04/2024]
Abstract
OBJECTIVES It is thought that esophageal hypersensitivity in combination with an impaired mucosal barrier function contributes to PPI-resistant reflux symptoms. Ziverel, a bioadhesive agent that coats the esophageal wall, was shown to have a positive effect on reflux symptoms. However, the mechanisms of action are unclear. We aimed to assess the effect of Ziverel on esophageal sensitivity to acid and mucosal barrier function. METHODS We performed a double-blind randomized placebo-controlled crossover trial in PPI-refractory patients with reflux symptoms. Patients were assigned (1:1) to 14 days of Ziverel followed by 14 days of placebo or opposite treatment order. The effect was evaluated using acid perfusion tests, an upper endoscopy with electrical tissue impedance spectroscopy (ETIS) and esophageal biopsies. The primary outcome was the esophageal sensitivity based on perfusion sensitivity score. Secondary outcomes included mucosal barrier function and reflux symptoms and correlations between the different outcomes. RESULTS Perfusion sensitivity score was not significantly different during treatment with Ziverel (106 (73-115)) and placebo (102 (67-110)) (p = 0.508) along with total RDQ score (2.6 (1.9-3.3) vs 2.8 (1.6-3.5) p = 0.456). ETIS showed comparable values during treatment with Ziverel (13514 (8846-19734)Ω·m) and placebo (13217 (9127-24942)Ω·m (p = 0.650)). Comparing Ziverel and placebo no difference was seen in transepithelial electrical resistance (TEER) 203 (163-267) Ω.cm2 vs 205 (176-240) Ω.cm2 (p = 0.445) and fluorescein flux 775 (17-6964) nmol/cm2/h vs 187 (4-12209) nmol/cm2/h (p = 0.638). CONCLUSION Ziverel did not show a benefit on acid sensitivity, reflux symptoms or esophageal mucosal integrity compared to placebo in PPI-refractory patients with reflux symptoms.Trial registration: Netherlands Trial Register number: NL7670.
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Affiliation(s)
- Thijs Kuipers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
| | - Renske A B Oude Nijhuis
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
| | | | - Jac M Oors
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
| | - André J P M Smout
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
| | - Albert J Bredenoord
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
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Davis TA, Gyawali CP. Refractory Gastroesophageal Reflux Disease: Diagnosis and Management. J Neurogastroenterol Motil 2024; 30:17-28. [PMID: 38173155 PMCID: PMC10774805 DOI: 10.5056/jnm23145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 10/16/2023] [Indexed: 01/05/2024] Open
Abstract
Gastroesophageal reflux disease (GERD) is common, with increasing worldwide disease prevalence and high economic burden. A significant number of patients will remain symptomatic following an empiric proton pump inhibitor (PPI) trial. Persistent symptoms despite PPI therapy are often mislabeled as refractory GERD. For patients with no prior GERD evidence (unproven GERD), testing is performed off antisecretory therapy to identify objective evidence of pathologic reflux using criteria outlined by the Lyon consensus. In proven GERD, differentiation between refractory symptoms (persisting symptoms despite optimized antisecretory therapy) and refractory GERD (abnormal reflux metrics on ambulatory pH impedance monitoring and/or persistent erosive esophagitis on endoscopy while on optimized PPI therapy) can direct subsequent management. While refractory symptoms may arise from esophageal hypersensitivity or functional heartburn, proven refractory GERD requires personalization of the management approach, tapping from an array of non-pharmacologic, pharmacologic, endoscopic, and surgical interventions. Proper diagnosis and management of refractory GERD is critical to mitigate undesirable long-term complications such as strictures, Barrett's esophagus, and esophageal adenocarcinoma. This review outlines the diagnostic workup of patients presenting with refractory GERD symptoms, describes the distinction between unproven and proven GERD, and provides a comprehensive review of the current treatment strategies available for the management of refractory GERD.
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Affiliation(s)
- Trevor A Davis
- Division of Pediatric Gastroenterology, Washington University School of Medicine, Saint Louis Children’s Hospital, St. Louis, MO, USA
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
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Bortolotti M. Is patient satisfaction sufficient to validate endoscopic anti-reflux treatments? World J Gastroenterol 2022; 28:3743-3746. [PMID: 36161053 PMCID: PMC9372810 DOI: 10.3748/wjg.v28.i28.3743] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 06/08/2022] [Accepted: 07/08/2022] [Indexed: 02/06/2023] Open
Abstract
Endoscopic anti-reflux treatment is emerging as a new option for gastro-esophageal reflux disease (GERD) treatment in patients with the same indications as for laparoscopic fundoplication. There are many techniques, the first of which are transoral incisionless fundoplication (TIF) and nonablative radio-frequency (STRETTA) that have been tested with comparative studies and randomized controlled trials, whereas the other more recent ones still require a deeper evaluation. The purpose of the latter is to verify whether reflux is abolished or significantly reduced after intervention, whether there is a valid high pressure zone at the gastroesophageal junction, and whether esophagitis, when present, has disappeared. Unfortunately in a certain number of cases, and especially in the more recently introduced ones, the evaluation has been based almost exclusively on subjective criteria, such as improvement in the quality of life, remission of heartburn and regurgitation, and reduction or suspension of antacid and antisecretory drug consumption. However, with the most studied techniques such as TIF and STRETTA, an improvement in symptoms better than that of laparoscopic fundoplication can often be observed, whereas the number of acid episodes and acid exposure time are similar or higher, as if the acid refluxes are better tolerated by these patients. The suspicion of a local hyposensitivity taking place after anti-reflux endoscopic intervention seems confirmed by a Bernstein test at least for STRETTA. This examination should be done for all the other techniques, both old and new, to identify the ones that reassure rather than cure. In conclusion, the evaluation of the effectiveness of the endoscopic anti-reflux techniques should not be based exclusively on subjective criteria, but should also be confirmed by objective examinations, because there might be a gap between the improvement in symptoms declared by the patient and the underlying pathophysiologic alterations of GERD.
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Affiliation(s)
- Mauro Bortolotti
- Department of Internal Medicine and Gastroenterology, S. Orsola-Malpighi Polyclinic, University of Bologna, Bologna 40138, Italy
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Efficacy of Endoscopic Radiofrequency Ablation for Treatment of Reflux Hypersensitivity: A Study Based on Rome IV Criteria. Gastroenterol Res Pract 2022; 2022:4145810. [PMID: 35386530 PMCID: PMC8977342 DOI: 10.1155/2022/4145810] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 02/14/2022] [Accepted: 03/10/2022] [Indexed: 11/17/2022] Open
Abstract
Objective. Effective therapies for reflux hypersensitivity are lacking. Endoscopic radiofrequency ablation may reduce the sensitivity of the distal esophagus through direct interference with nociceptors or vagal afferent fibers and thus may be useful in reflux hypersensitivity. The aim of this study is to assess the effectiveness and possible mechanisms of endoscopic radiofrequency ablation in reflux hypersensitivity patients. Methods. Patients with reflux hypersensitivity who fulfilled the Rome IV criteria and who wished to receive further treatment were recruited. Endoscopic radiofrequency ablation was delivered to the gastroesophageal junction. Data were collected by questionnaire using a 6-point Likert scale. The primary outcome measure was effect on symptoms including heartburn, regurgitation, and chest pain. The secondary outcomes were degree of satisfaction, medication use, acid exposure time (AET), low esophageal sphincter (LES) pressure, and total reflux episodes. We also assessed positive cell density of transient receptor potential vanilloid type 1 receptor (TRPV1) and calcitonin gene-related peptide (CGRP), both of which are biomarkers of afferent fibers, in biopsies obtained from esophageal mucosa 0.5 cm-1 cm above the Z line. These scales will be administered at baseline, 3-month follow-up, 6-month follow-up, and 12-month follow-up. Results. A total of 22 reflux hypersensitivity patients were enrolled (14 males, median age 50.0 years). A significant improvement in symptom scores (heartburn, regurgitation, and chest pain) was noted at 3 months, 6 months, and 12 months (
). Satisfaction with life increased to 72.7% (16/22), 72.7% (16/22), and 68.2% (15/22) at 3, 6, and 12 mo, respectively, compared with baseline (
). Nineteen patients reduced their medication use after treatment. Of these, 22.7% (5/22), 31.8% (7/22), and 40.9% (9/22) subjects stopped medication use at 3 mo, 6 mo, and 12 mo, respectively. No statistical differences were noted in AET, LES pressure, or total reflux episodes from preoperation to 12 mo postoperation. After treatment, the positive cell density of both TRPV1 and CGRP decreased significantly; however, only TRPV1 had a positive correlation with heartburn (
,
) and chest pain (
,
). Conclusion. Endoscopic radiofrequency ablation was an effective and safe therapeutic option in reflux hypersensitivity patients. Further studies with large sample size are required to validate the role of radiofrequency in reflux hypersensitivity.
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Xie P, Yan J, Ye L, Wang C, Li Y, Chen Y, Li G. Efficacy of different endoscopic treatments in patients with gastroesophageal reflux disease: a systematic review and network meta-analysis. Surg Endosc 2021; 35:1500-1510. [PMID: 33650003 DOI: 10.1007/s00464-021-08386-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 02/09/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Both transoral incisionless fundoplication (TIF) and radiofrequency ablation (Stretta) are representative endoscopic treatments for gastroesophageal reflux disease (GERD), but they have not been directly compared. This systematic review and network meta-analysis (NMA) evaluated the comparative effects of Stretta, TIF, and proton pump inhibitors (PPIs). METHODS PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Embase were searched for randomized controlled trials (RCTs) that compared the efficacy of either the Stretta, TIF, or PPIs/sham procedure for GERD treatment. The NMA was conducted using frequentist methods. RESULTS A total of 516 participants from 10 RCTs were included in this NMA. Both Stretta (mean difference, MD - 9.77, 95% confidence interval, CI - 12.85 to - 6.70) and TIF (MD - 12.22, 95% CI - 15.93 to - 8.52) were significantly superior to PPIs at improving health-related quality of life (HRQL) scores and heartburn scores (Stretta: MD - 1.53, 95% CI - 2.98 to - 0.08; TIF: MD - 9.60, 95% CI - 17.79 to - 1.41). Stretta (MD - 3.77, 95% CI - 6.88 to - 0.65) was less effective at increasing lower esophageal sphincter (LES) pressure than TIF. Stretta was significantly superior to TIF (MD - 3.25, 95% CI - 5.95 to - 0.56) at improving esophageal acid exposure. Regarding the decrease in PPIs utility and esophagitis incidence, no significant differences were found between TIF and Stretta. CONCLUSION In terms of short-term reduction of the HRQL score and heartburn score in patients with GERD, TIF and Stretta may be comparable to each other, and both may be more effective than PPIs. TIF may increase the LES pressure in comparison with Stretta and PPIs. PPIs may reduce the percentage of time pH < 4.0 when compared with TIF. This evidence should be interpreted with caution given the small number of included studies and inherent heterogeneity. Registration No. CRD42020188345.
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Affiliation(s)
- Peiwei Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Jing Yan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Ling Ye
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Chong Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Yuanyuan Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Youxiang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Guohua Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China.
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Huynh P, Konda V, Sanguansataya S, Ward MA, Leeds SG. Mind the Gap: Current Treatment Alternatives for GERD Patients Failing Medical Treatment and Not Ready for a Fundoplication. Surg Laparosc Endosc Percutan Tech 2020; 31:264-276. [PMID: 33347088 PMCID: PMC8154178 DOI: 10.1097/sle.0000000000000888] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 10/05/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND Gastroesophageal reflux disease is associated with Barrett esophagus, esophageal adenocarcinoma, and significantly impacts quality of life. Medical management is the first line therapy with surgical fundoplication as an alternative therapy. However, a small portion of patients who fail medical therapy are referred for surgical consultation. This creates a "gap" in therapy for those patients dissatisfied with medical therapy but are not getting referred for surgical consultation. Three procedures have been designed to address these patients. These include radiofrequency ablation (RFA) of the lower esophageal sphincter, transoral incisionless fundoplication (TIF), and magnetic sphincter augmentation. MATERIALS AND METHODS A Pubmed literature review was conducted of all publications for RFA, TIF, and MSA. Four most common endpoints for the 3 procedures were compared at different intervals of follow-up. These include percent of patients off proton pump inhibitors (PPIs), GERD-HRQL score, DeMeester score, and percent of time with pH <4. A second query was performed for patients treated with PPI and fundoplications to match the same 4 endpoints as a control. RESULTS Variable freedom from PPI was reported at 1 year for RFA with a weighted mean of 62%, TIF with a weighted mean of 61%, MSA with a weighted mean of 85%, and fundoplications with a weighted mean of 84%. All procedures including PPIs improved quality-of-life scores but were not equal. Fundoplication had the best improvement followed by MSA, TIF, RFA, and PPI, respectively. DeMeester scores are variable after all procedures and PPIs. All MSA studies showed normalization of pH, whereas only 4 of 17 RFA studies and 3 of 11 TIF studies reported normalization of pH. CONCLUSIONS Our literature review compares 3 rival procedures to treat "gap" patients for gastroesophageal reflux disease with 4 common endpoints. Magnetic sphincter augmentation appears to have the most reproducible and linear outcomes but is the most invasive of the 3 procedures. MSA outcomes most closely mirrors that of fundoplication.
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Affiliation(s)
- Phuong Huynh
- Division of Minimally Invasive Surgery, Baylor University Medical Center
- Center for Advanced Surgery, Baylor Scott & White Health
| | - Vani Konda
- Center for Esophageal Diseases, Baylor University Medical Center, Dallas
| | | | - Marc A. Ward
- Division of Minimally Invasive Surgery, Baylor University Medical Center
- Center for Advanced Surgery, Baylor Scott & White Health
- Texas A&M College of Medicine, Bryan, TX
| | - Steven G. Leeds
- Division of Minimally Invasive Surgery, Baylor University Medical Center
- Center for Advanced Surgery, Baylor Scott & White Health
- Texas A&M College of Medicine, Bryan, TX
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Zerbib F, Sacher-Huvelin S, Coron E, Coffin B, Melchior C, Ponchon T, Cholet F, Chabrun E, Vavasseur F, Gorbatchef C, Zalar A, Mion F, Robaszkiewicz M, Le Rhun M, Leroy M, Paul Galmiche J, Bruley des Varannes S. Randomised clinical trial: oesophageal radiofrequency energy delivery versus sham for PPI-refractory heartburn. Aliment Pharmacol Ther 2020; 52:637-645. [PMID: 32656869 DOI: 10.1111/apt.15936] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 06/04/2020] [Accepted: 06/11/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Oesophageal radiofrequency reduces use of proton pump inhibitors (PPIs) in patients with gastro-oesophageal reflux disease responding to PPIs. AIM To determine the efficacy of oesophageal radiofrequency in patients with PPI-refractory heartburn. METHODS A randomised, double-blind, sham-controlled multicentre study was designed to assess the efficacy of oesophageal radiofrequency in PPI non-responding patients with heartburn. Patients had moderate-to-severe heartburn defined by at least 3 occurrences a week, and not improved by continuous PPI treatment. The primary endpoint was clinical success at week 24, defined by intake of less than 7 PPI doses over the 2 preceding weeks and adequate symptom control determined by the patient. RESULTS Sixty two patients were randomised, 29 to the oesophageal radiofrequency group and 33 to the sham group. Intention-to-treat analysis showed that 1/29 (3.4%) and 5/33 (15.1%) achieved the primary endpoint in the oesophageal radiofrequency and sham groups, respectively (NS). There was no significant difference between oesophageal radiofrequency and sham regarding the number of days without heartburn, days with PPI consumption in the last 2 weeks, and patients not taking PPIs. No pH-impedance parameter was associated with clinical response. The occurrence of adverse events was similar in both groups. CONCLUSION This sham-controlled, randomised study did not demonstrate any efficacy of oesophageal radiofrequency for the treatment of PPI-refractory heartburn regarding symptom relief or consumption of PPIs. ClinicalTrials.gov NCT01682265.
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Affiliation(s)
- Frank Zerbib
- Gastroenterology Department, CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Sylvie Sacher-Huvelin
- Gastroenterology Department, CHU de Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), CIC1413, Université de Nantes, Nantes, France
| | - Emmanuel Coron
- Gastroenterology Department, CHU de Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), CIC1413, Université de Nantes, Nantes, France
| | - Benoit Coffin
- Gastroenterology Department, AP-HP, Hôpital Louis Mourier, Colombes, Université de Paris, Paris, France
| | - Chloé Melchior
- Gastroenterology Department, Rouen University Hospital and INSERM CIC-CRB 1404 and INSERM U1073, Institute for Research and Innovation in Biomedicine, Normandy University, Rouen, France
| | - Thierry Ponchon
- Gastroenterology Department, CHU de Lyon, Hôpital Edouard Herriot, Université de Lyon, Lyon, France
| | - Franck Cholet
- Gastroenterology Department, CHRU de Brest, Hôpital de la Cavale Blanche, Université de Brest, Brest, France
| | - Edouard Chabrun
- Gastroenterology Department, CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Fabienne Vavasseur
- Gastroenterology Department, CHU de Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), CIC1413, Université de Nantes, Nantes, France
| | - Caroline Gorbatchef
- Gastroenterology Department, AP-HP, Hôpital Louis Mourier, Colombes, Université de Paris, Paris, France
| | - Alberto Zalar
- Gastroenterology Department, Rouen University Hospital and INSERM CIC-CRB 1404 and INSERM U1073, Institute for Research and Innovation in Biomedicine, Normandy University, Rouen, France
| | - François Mion
- Digestive Physiology Department, Hospices Civils de Lyon, Université de Lyon, Inserm U1082 LabTau, Lyon, France
| | - Michel Robaszkiewicz
- Gastroenterology Department, CHRU de Brest, Hôpital de la Cavale Blanche, Université de Brest, Brest, France
| | - Marc Le Rhun
- Gastroenterology Department, CHU de Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), CIC1413, Université de Nantes, Nantes, France
| | - Maxime Leroy
- Methodology and Biostatistics Department, CHU de Nantes, Université de Nantes, Nantes, France
| | - Jean Paul Galmiche
- Gastroenterology Department, CHU de Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), CIC1413, Université de Nantes, Nantes, France
| | - Stanislas Bruley des Varannes
- Gastroenterology Department, CHU de Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), CIC1413, Université de Nantes, Nantes, France
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12
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Ihde GM. The evolution of TIF: transoral incisionless fundoplication. Therap Adv Gastroenterol 2020; 13:1756284820924206. [PMID: 32499834 PMCID: PMC7243382 DOI: 10.1177/1756284820924206] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 04/15/2020] [Indexed: 02/04/2023] Open
Abstract
Transoral incisionless fundoplication (TIF) was introduced in 2006 as a concerted effort to produce a natural orifice procedure for reflux. Since that time, the device, as well as the procedure technique, has evolved. Significant research has been published during each stage of the evolution, and this has led to considerable confusion and a co-mingling of outcomes, which obscures the results of the current device and procedure. This report is intended to review the identified stages and literature associated with each stage to date and to review the current state of treatment outcomes.
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13
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Liu PP, Meng QQ, Lin H, Han Y, Qian W, Li ZS, Wang LW. Radiofrequency ablation is safe and effective in the treatment of Chinese patients with gastroesophageal reflux disease: A single-center prospective study. J Dig Dis 2019; 20:229-234. [PMID: 30873743 DOI: 10.1111/1751-2980.12722] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Revised: 03/09/2019] [Accepted: 03/13/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVE This study aimed to evaluate the safety and efficiency of radiofrequency ablation (RFA) in Chinese patients with gastroesophageal reflux disease (GERD). METHODS This was a single-center, prospective study including 27 Chinese patients with GERD. The outcomes in all patients were evaluated before and at 3, 6, and 12 months after RFA, including their GERD health-related quality of life (GERD-HRQL) score, esophageal acid exposure, DeMeester score, lower esophageal sphincter (LES) resting pressure, and patient's satisfaction with symptom control. Furthermore, rabeprazole sodium (RS) administration, reflux esophagitis (RE), and intraoperative and postoperative complications were also evaluated. RESULTS RFA treatment significantly reduced the GERD-HRQL score, the percentage of time that esophageal pH < 4, and the DeMeester score, and significantly increased the LES resting pressure in GERD patients. A need for RS administration was reduced and RE symptoms were relieved. Satisfaction rate of 92.6% and 96.3% was reported by these patients at 6 and 12 months post-treatment, respectively. Mild bleeding (<20 mL) occurred in one patient during RFA, and no serious intraoperative and postoperative complications were observed. CONCLUSION RFA is safe and effective in the treatment of GERD in Chinese patients.
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Affiliation(s)
- Pei Pei Liu
- Digestive Endoscopy Center, Department of Gastroenterology, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Qian Qian Meng
- Digestive Endoscopy Center, Department of Gastroenterology, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Han Lin
- Digestive Endoscopy Center, Department of Gastroenterology, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Yan Han
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wei Qian
- Digestive Endoscopy Center, Department of Gastroenterology, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Zhao Shen Li
- Digestive Endoscopy Center, Department of Gastroenterology, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Luo Wei Wang
- Digestive Endoscopy Center, Department of Gastroenterology, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
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Chang KJ. Endoscopic foregut surgery and interventions: The future is now. The state-of-the-art and my personal journey. World J Gastroenterol 2019; 25:1-41. [PMID: 30643356 PMCID: PMC6328959 DOI: 10.3748/wjg.v25.i1.1] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 12/13/2018] [Accepted: 12/14/2018] [Indexed: 02/06/2023] Open
Abstract
In this paper, I reviewed the emerging field of endoscopic surgery and present data supporting the contention that endoscopy can now be used to treat many foregut diseases that have been traditionally treated surgically. Within each topic, the content will progress as follows: "lessons learned", "technical considerations" and "future opportunities". Lessons learned will provide a brief background and update on the most current literature. Technical considerations will include my personal experience, including tips and tricks that I have learned over the years. Finally, future opportunities will address current unmet needs and potential new areas of development. The foregut is defined as "the upper part of the embryonic alimentary canal from which the pharynx, esophagus, lung, stomach, liver, pancreas, and part of the duodenum develop". Foregut surgery is well established in treating conditions such as gastroesophageal reflux disease (GERD), achalasia, esophageal diverticula, Barrett's esophagus (BE) and esophageal cancer, stomach cancer, gastric-outlet obstruction, and obesity. Over the past decade, remarkable progress in interventional endoscopy has culminated in the conceptualization and practice of endoscopic foregut surgery for various clinical conditions summarized in this paper. Regarding GERD, there are now several technologies available to effectively treat it and potentially eliminate symptoms, and the need for long-term treatment with proton pump inhibitors. For the first time, fundoplication can be performed without the need for open or laparoscopic surgery. Long-term data going out 5-10 years are now emerging showing extended durability. In respect to achalasia, per-oral endoscopic myotomy (POEM) which was developed in Japan, has become an alternative to the traditional Heller's myotomy. Recent meta-analysis show that POEM may have better results than Heller, but the issue of post-POEM GERD still needs to be addressed. There is now a resurgence of endoscopic treatment of Zenker's diverticula with improved technique (Z-POEM) and equipment; thus, patients are choosing flexible endoscopic treatment as opposed to open or rigid endoscopy options. In regard to BE, endoscopic submucosal dissection (ESD) which is well established in Asia, is now becoming more mainstream in the West for the treatment of BE with high grade dysplasia, as well as early esophageal cancer. In combination with all the ablation technologies (radiofrequency ablation, cryotherapy, hybrid argon plasma coagulation), the entire spectrum of Barrett's and related dysplasia and early cancer can be managed predominantly by endoscopy. Importantly, in regard to early gastric cancer and submucosal tumors (SMTs) of the stomach, ESD and full thickness resection (FTR) can excise these lesions en-bloc and endoscopic suturing is now used to close large defects and perforations. For treatment of patients with malignant gastric outlet obstruction (GOO), endoscopic gastro-jejunostomy is now showing better results than enteral stenting. G-POEM is also emerging as a treatment option for patients with gastroparesis. Obesity has become an epidemic in many western countries and is becoming also prevalent in Asia. Endoscopic sleeve gastroplasty (ESG) is now becoming an established treatment option, especially for obese patients with body mass index between 30 and 35. Data show an average weight loss of 16 kg after ESG with long-term data confirming sustainability. Finally, in respect to endo-hepatology, there are many new endoscopic interventions that have been developed for patients with liver disease. Endoscopic ultrasound (EUS)-guided liver biopsy and EUS-guided portal pressure measurement are exciting new frontiers for the endo-hepatologists.
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Affiliation(s)
- Kenneth J Chang
- H.H. Chao Comprehensive Digestive Disease Center, University of California, Irvine Medical Center, Orange, CA 92868, United States
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15
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Abstract
Proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) is defined by the presence of troublesome GERD symptoms despite PPI optimization for at least 8 weeks in the setting of ongoing documented pathologic gastroesophageal reflux. It arises from a dysfunction in protective systems to prevent reflux and as propagation of physiologic reflux events. Treatment possibilities include pharmacologic options, invasive management strategies, and endoluminal therapies. Management strategy should be personalized to the patient's needs and mechanistic dysfunction. This article reviews the definition, mechanisms, and management options for PPI-refractory GERD.
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Affiliation(s)
- Rena Yadlapati
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, 12631 East 17th Avenue B158, Aurora, CO 80045, USA.
| | - Kelli DeLay
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, 12631 East 17th Avenue B158, Aurora, CO 80045, USA
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Hillman L, Yadlapati R, Whitsett M, Thuluvath AJ, Berendsen MA, Pandolfino JE. Review of antireflux procedures for proton pump inhibitor nonresponsive gastroesophageal reflux disease. Dis Esophagus 2017; 30:1-14. [PMID: 28859357 PMCID: PMC5789775 DOI: 10.1093/dote/dox054] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 04/20/2017] [Indexed: 12/11/2022]
Abstract
Up to 40% of patients with gastroesophageal reflux disease (GERD) report persistent symptoms despite proton pump inhibitor (PPI) therapy. This review outlines the evidence for surgical and endoscopic therapies for the treatment of PPI nonresponsive GERD. A literature search for GERD therapies from 2005 to 2015 in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified 2928 unique citations. Of those, 45 unique articles specific to surgical and endoscopic therapies for PPI nonresponsive GERD were reviewed. Laparoscopic fundoplication (n = 19) provides symptomatic and physiologic relief out to 10 years, though efficacy wanes with time. Magnetic sphincter augmentation (n = 6) and transoral incisionless fundoplication (n = 9) improve symptoms in PPI nonresponders and may offer fewer side effects than fundoplication, though long-term follow-up is lacking. Radiofrequency energy delivery (n = 8) has insufficient evidence for routine use in treating PPI nonresponsive GERD. Electrical stimulator implantation (n = 1) and endoscopic mucosal surgery (n = 2) are newer therapies under evaluation for the treatment of GERD. Laparoscopic fundoplication remains the most proven therapeutic approach. Newer antireflux procedures such as magnetic sphincter augmentation and transoral incisionless fundoplication offer alternatives with varying degrees of success, durability, and side effect profiles that may better suit individual patients. Larger head-to-head comparison trials are needed to better characterize the difference in symptom response and side effect profiles.
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Affiliation(s)
- L. Hillman
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - R. Yadlapati
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - M. Whitsett
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - A. J. Thuluvath
- Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA
| | - M. A. Berendsen
- Galter Health Sciences Library, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - J. E. Pandolfino
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
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17
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Systematic review and meta-analysis of controlled and prospective cohort efficacy studies of endoscopic radiofrequency for treatment of gastroesophageal reflux disease. Surg Endosc 2017; 31:4865-4882. [PMID: 28233093 DOI: 10.1007/s00464-017-5431-2] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Accepted: 01/20/2017] [Indexed: 01/08/2023]
Abstract
BACKGROUND The endoscopic radiofrequency procedure (Stretta) has been used for more than a decade to treat patients with gastroesophageal reflux disease (GERD). However, the efficacy of the procedure in improving objective and subjective clinical endpoints needs to be further established. AIM To determine the efficacy of the Stretta procedure in treating patients with GERD, using a systematic review and meta-analysis of controlled and cohort studies. METHODS We conducted a systematic search of the PubMed and Cochrane databases for English language clinical studies of the Stretta procedure, published from inception until May 2016. Randomized controlled trials (RCTs) and cohort studies that included the use of the Stretta procedure in GERD patients were included. A generalized inverse weighting was used for all outcomes. Results were calculated by both fixed effects and random effects model. RESULTS Twenty-eight studies (4 RCTs, 23 cohort studies, and 1 registry) representing 2468 unique Stretta patients were included in the meta-analysis. The (unweighted) mean follow-up time for the 28 studies was 25.4 [14.0, 36.7] months. The pooled results showed that the Stretta reduced (improved) the health-related quality of life score by -14.6 [-16.48, -12.73] (P < 0.001). Stretta also reduced (improved) the pooled heartburn standardized score by -1.53 [-1.97, -1.09] (P < 0.001). After Stretta treatment, only 49% of the patients using proton pump inhibitors (PPIs) at baseline required PPIs at follow-up (P < 0.001). The Stretta treatment reduced the incidence of erosive esophagitis by 24% (P < 0.001) and reduced esophageal acid exposure by a mean of -3.01 [-3.72, -2.30] (P < 0.001). Lower esophageal sphincter (LES) basal pressure was increased post Stretta therapy by a mean of 1.73 [-0.29, 3.74] mmHg (P = NS). CONCLUSIONS The Stretta procedure significantly improves subjective and objective clinical endpoints, except LES basal pressure, and therefore should be considered as a viable alternative in managing GERD.
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Affiliation(s)
- Prateek Sharma
- Veterans Affairs Medical Center, University of Kansas School of Medicine, Kansas City, Missouri.
| | - Philip Katz
- Albert Einstein Medical Center, Philadelphia, Pennsylvania
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19
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Liang WT, Wang ZG, Wang F, Yang Y, Hu ZW, Liu JJ, Zhu GC, Zhang C, Wu JM. Long-term outcomes of patients with refractory gastroesophageal reflux disease following a minimally invasive endoscopic procedure: a prospective observational study. BMC Gastroenterol 2014. [PMID: 25304252 DOI: 10.1186/1471-230x-14-1781471-230x-14-178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is the most common digestive disease, affecting one third of the world's population. The minimally invasive endoscopic Stretta procedure is being increasingly used as an alternative strategy to manage refractory GERD. However, long-term benefits of this procedure have to be further evaluated in clinical settings. This prospective observational study was therefore conducted to evaluate the outcome of patients with refractory GERD 5 years after the Stretta procedure. METHODS A total of 152 patients with refractory GERD underwent the Stretta procedure in our department between April 2007 and September 2008. They were followed up for 5 years, during which the primary outcome measures including symptom scores of heartburn, regurgitation, chest pain, cough and asthma and the secondary outcome measures including proton pump inhibitor (PPI) use and patients' satisfaction were analysed at 6, 12, 24, 36, 48 and 60 months respectively. RESULTS Of the 152 patients, 138 completed the designated 5-year follow-up and were included in the final analysis. At the end of the 5-year follow-up, the symptom scores of heartburn (2.47 ± 1.22 vs. 5.86 ± 1.52), regurgitation (2.23 ± 1.30 vs. 5.56 ± 1.65), chest pain (2.31 ± 0.76 vs. 4.79 ± 1.59), cough (3.14 ± 1.43 vs. 6.62 ± 1.73) and asthma (3.26 ± 1.53 vs. 6.83 ± 1.46) were all significantly decreased as compared with the corresponding values before the procedure (P < 0.001). After the Stretta procedure, 59 (42.8%) patients achieved complete PPI therapy independence and 104 (75.4%) patients were completely or partially satisfied with the GERD symptom control. Moreover, no severe complications were observed except for complaint of abdominal distention in 12 (8.7%) patients after the Stretta procedure. CONCLUSION The Stretta procedure may achieve an effective and satisfactory long-term symptom control and considerably reduce the reliance on medication without significant adverse effects in adult patients with refractory GERD, thereby having profound clinical implications.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Ji-Min Wu
- Department of Gastroesophageal Reflux Disease, Second Artillery General Hospital of the Chinese People's Liberation Army, 16 Xinwai Street, Xicheng District, Beijing 100088, China.
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20
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Liang WT, Wang ZG, Wang F, Yang Y, Hu ZW, Liu JJ, Zhu GC, Zhang C, Wu JM. Long-term outcomes of patients with refractory gastroesophageal reflux disease following a minimally invasive endoscopic procedure: a prospective observational study. BMC Gastroenterol 2014; 14:178. [PMID: 25304252 PMCID: PMC4287567 DOI: 10.1186/1471-230x-14-178] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Accepted: 09/29/2014] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is the most common digestive disease, affecting one third of the world's population. The minimally invasive endoscopic Stretta procedure is being increasingly used as an alternative strategy to manage refractory GERD. However, long-term benefits of this procedure have to be further evaluated in clinical settings. This prospective observational study was therefore conducted to evaluate the outcome of patients with refractory GERD 5 years after the Stretta procedure. METHODS A total of 152 patients with refractory GERD underwent the Stretta procedure in our department between April 2007 and September 2008. They were followed up for 5 years, during which the primary outcome measures including symptom scores of heartburn, regurgitation, chest pain, cough and asthma and the secondary outcome measures including proton pump inhibitor (PPI) use and patients' satisfaction were analysed at 6, 12, 24, 36, 48 and 60 months respectively. RESULTS Of the 152 patients, 138 completed the designated 5-year follow-up and were included in the final analysis. At the end of the 5-year follow-up, the symptom scores of heartburn (2.47 ± 1.22 vs. 5.86 ± 1.52), regurgitation (2.23 ± 1.30 vs. 5.56 ± 1.65), chest pain (2.31 ± 0.76 vs. 4.79 ± 1.59), cough (3.14 ± 1.43 vs. 6.62 ± 1.73) and asthma (3.26 ± 1.53 vs. 6.83 ± 1.46) were all significantly decreased as compared with the corresponding values before the procedure (P < 0.001). After the Stretta procedure, 59 (42.8%) patients achieved complete PPI therapy independence and 104 (75.4%) patients were completely or partially satisfied with the GERD symptom control. Moreover, no severe complications were observed except for complaint of abdominal distention in 12 (8.7%) patients after the Stretta procedure. CONCLUSION The Stretta procedure may achieve an effective and satisfactory long-term symptom control and considerably reduce the reliance on medication without significant adverse effects in adult patients with refractory GERD, thereby having profound clinical implications.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Ji-Min Wu
- Department of Gastroesophageal Reflux Disease, Second Artillery General Hospital of the Chinese People's Liberation Army, 16 Xinwai Street, Xicheng District, Beijing 100088, China.
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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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Ates F, Francis DO, Vaezi MF. Refractory gastroesophageal reflux disease: advances and treatment. Expert Rev Gastroenterol Hepatol 2014; 8:657-67. [PMID: 24745809 DOI: 10.1586/17474124.2014.910454] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
'Refractory gastroesophageal reflux disease' is one of the most common misnomers in the area of gastroesophageal reflux disease. The term implies reflux as the underlying etiology despite unresponsiveness to aggressive proton pump inhibitor therapy. The term should be replaced with 'refractory symptoms.' We must acknowledge that in many patients symptoms of reflux often overlap with non-GERD causes such as gastroparesis, dyspepsia, hypersensitive esophagus and functional disorders. Lack of response to aggressive acid suppressive therapy often leads to diagnostic testing. In majority of patients these tests are normal. The role of non-acid reflux in this group is uncertain and patients should not undergo surgical fundoplication based on this parameter. In patients unresponsive to acid suppressive therapy GERD is most commonly not causal and a search for non-GERD causes must ensue.
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Affiliation(s)
- Fehmi Ates
- Division of Gastroenterology, Hepatology, and Nutrition, Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, C2104-MCN, Nashville, TN, USA
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Galmiche JP, Zerbib F, des Varannes SB. Treatment of GORD: Three decades of progress and disappointments. United European Gastroenterol J 2014; 1:140-50. [PMID: 24917952 DOI: 10.1177/2050640613484021] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2013] [Accepted: 03/01/2013] [Indexed: 12/16/2022] Open
Abstract
The treatment of GORD has been revolutionized by the introduction, in the 1980s, of proton-pump inhibitors as the mainstay of medical therapy and by the development of laparoscopic antireflux surgery which has definitively replaced open surgery. However, despite these major advances, many unmet therapeutic needs still persist and justify novel therapeutic approaches. The aim of this historical review is to recall the main discoveries in the treatment of GORD that have occurred during the last three decades and to discuss why some initially promising drugs or techniques have not translated into clinical applications. A careful analysis of these previous disappointing experiences should help to identify high priorities and better research programmes on the management of GORD.
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Affiliation(s)
| | - Frank Zerbib
- CHU Bordeaux, Bordeaux, France ; Bordeaux Segalen University, Bordeaux, France
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Durability of Stretta Radiofrequency Treatment for GERD: Results of an 8-Year Follow-Up. Gastroenterol Res Pract 2014; 2014:531907. [PMID: 24959175 PMCID: PMC4052191 DOI: 10.1155/2014/531907] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2013] [Revised: 04/15/2014] [Accepted: 04/29/2014] [Indexed: 02/07/2023] Open
Abstract
From June 2002 to March 2013 26 patients that underwent Stretta procedure (16 females, 10 males) reached to date an eight-year follow-up. Primary end point of the study was to verify the durability of the procedure at this time. All patients underwent clinical evaluation by upper endoscopy, oesophageal pressure, and pH studies. For each patient 8-year data were compared to those recorded at baseline and at 4 years. There was a significant decrease in both heartburn and GERD HRQL scores at 4 years (P = 0.001) and at 8 years (P = 0.003) as well as a significant increase of QoL scores at each control time (mental SF-36 and physical SF-36, P = 0.001). After 4 and 8 years, 21 patients (80.7%, P = 0.0001) and 20 patients (76.9%, P = 0.0001) were completely off PPIs. Median LES pressure did not show significant amelioration at 4 and 8 years and mean oesophageal acid exposure significantly improved at 4 years (P = 0.001) but returned to baseline values after 8 years. This further follow-up study of ours from four to eight years confirms that RF energy delivery for GERD provides durable improvement in symptoms and in quality of life and reduces antireflux drugs consumption.
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Martinucci I, Bortoli ND, Giacchino M, Bodini G, Marabotto E, Marchi S, Savarino V, Savarino E. Esophageal motility abnormalities in gastroesophageal reflux disease. World J Gastrointest Pharmacol Ther 2014; 5:86-96. [PMID: 24868489 PMCID: PMC4023328 DOI: 10.4292/wjgpt.v5.i2.86] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2013] [Revised: 01/02/2014] [Accepted: 01/16/2014] [Indexed: 02/06/2023] Open
Abstract
Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett’s esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.
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Noar M, Squires P, Noar E, Lee M. Long-term maintenance effect of radiofrequency energy delivery for refractory GERD: a decade later. Surg Endosc 2014; 28:2323-33. [PMID: 24562599 DOI: 10.1007/s00464-014-3461-6] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Accepted: 01/21/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND Patients with gastroesophageal reflux disease (GERD) often seek alternative therapy for inadequate symptom control, with over 40% not responding to medical treatment. We evaluated the long-term safety, efficacy, and durability of response to radiofrequency treatment of the lower esophageal sphincter (Stretta). METHODS Using an intent-to-treat analysis, we prospectively assessed 217 patients with medically refractory GERD before and after Stretta. There was no concurrent control group in the study. Primary outcome measure was normalization of GERD-health-related quality of life (GERD-HRQL) in 70% or greater of patients at 10 years. Secondary outcomes were 50% reduction or elimination of proton pump inhibitors (PPIs) and 60% or greater improvement in satisfaction at 10 years. Successful treatment was defined as achievement of secondary outcomes in a minimum of 50% of patients. Complications and effect on existing comorbidities were evaluated. The results of a 10-year study are reported. RESULTS The primary outcome was achieved in 72% of patients (95% confidence interval 65-79). For secondary outcomes, a 50% or greater reduction in PPI use occurred in 64% of patients, (41% eliminating PPIs entirely), and a 60% or greater increase in satisfaction occurred in 54% of patients. Both secondary endpoints were achieved. The most common side effect was short-term chest pain (50%). Pre-existing Barrett's metaplasia regressed in 85% of biopsied patients. No cases of esophageal cancer occurred. CONCLUSIONS In this single-group evaluation of 217 patients before and after Stretta, GERD-HRQL scores, satisfaction, and PPI use significantly improved and results were immediate and durable at 10 years.
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Affiliation(s)
- Mark Noar
- Heartburn & Reflux Study Center, Endoscopic Microsurgery Associates PA, 7402 York Road 100, Towson, MD, 21204, USA,
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Abstract
OPINION STATEMENT "Refractory GERD" is one the most common misnomers in the area of gastroesophageal reflux disease. The term implies reflux as the underlying etiology despite unresponsiveness to aggressive, often twice-daily proton pump inhibitor therapy. The term should be replaced with "refractory symptoms." We must acknowledge that in many patients, symptoms of reflux often overlap with non-GERD causes such as gastroparesis, dyspepsia, hypersensitive esophagus, and functional disorders. Lack of response to aggressive acid suppressive therapy often leads to esophagogastroduodenoscopy followed by pH or impedance monitoring. In the majority of patients these tests are normal. The role of non-acid reflux measured by impedance pH testing in this group is uncertain at best and the results from this test alone should not be used to refer patients to surgical fundoplication. In patients unresponsive to acid suppressive therapy, reflux is most commonly not causal and a search for non-GERD causes must ensue.
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Locke GR, Horwhat J, Mashimo H, Savarino E, Zentilin P, Savarino V, Zerbib F, Armbruster SP, Wong RK, Moawad F. Endotherapy for and tailored approaches to treating GERD, and refractory GERD. Ann N Y Acad Sci 2013; 1300:166-186. [PMID: 24117641 DOI: 10.1111/nyas.12240] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This paper presents commentaries on how endoluminal antireflux procedures compare to laparoscopic fundoplication; new endoscopic procedures being studied to treat refractory gastroesophageal reflux disease (GERD); the new Stretta; the relationship between obesity and proton pump inhibitor (PPI) resistance; data concerning acid hypersensitivity and sensory receptors (vallinoid, TRPV1) causing refractory GERD; whether microscopic esophagitis is relevant in determining symptoms of non-erosive reflux disease (NERD); how concomitant functional gastrointestinal disorders affect the PPI response in NERD; the evidence that a functional esophagus is associated with inflammatory bowel syndrome (IBS); the role of GABA agonists in the treatment of refractory GERD; the role of biofeedback and antidepressants in refractory GERD; and endoluminal fundoplication using the EsophyX device.
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Affiliation(s)
- G Richard Locke
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John Horwhat
- Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Hiroshi Mashimo
- VA Boston Healthcare System/Harvard Medical School, Boston, Massachusetts
| | - Edoardo Savarino
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | | | | | - Frank Zerbib
- Department of Gastroenterology, CHU Bordeaux, Saint Andre Hospital, Bordeaux, France
| | - Steven P Armbruster
- Department of Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Roy K Wong
- Department of Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Fouad Moawad
- Department of Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
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29
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30
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Triadafilopoulos G. Stretta for refractory GERD: now more than ever. Am J Gastroenterol 2013; 108:1655-6. [PMID: 24091509 DOI: 10.1038/ajg.2013.277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- George Triadafilopoulos
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
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31
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Franciosa M, Triadafilopoulos G, Mashimo H. Stretta Radiofrequency Treatment for GERD: A Safe and Effective Modality. Gastroenterol Res Pract 2013; 2013:783815. [PMID: 24078808 PMCID: PMC3775401 DOI: 10.1155/2013/783815] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2013] [Revised: 06/17/2013] [Accepted: 07/03/2013] [Indexed: 12/28/2022] Open
Abstract
Gastroesophageal reflux disease is one of the leading gastrointestinal disorders. Current treatments include lifestyle modifications, pharmacological therapies, surgical fundoplications, and, more recently, endoscopic procedures. The rising concern of long-term side effects of the popular proton-pump inhibitors and the more recent evidence raising doubts about the durability of fundoplication have spurred reinterest in endoscopic procedures to treat reflux disorders. In the aftermath of several innovative antireflux procedures that were introduced and failed clinically or financially over the past decade, there is lingering confusion regarding the merits of the presently available interventions. This paper focuses on one endoscopic procedure, Stretta, which now enjoys the longest experience, a recent meta-analysis, and robust data supporting its safety, efficacy, and durability. Stretta reduces esophageal acid exposure, decreases the frequency of transient lower esophageal relaxation, increases patient satisfaction, decreases medication use, and improves quality of life. As such, this procedure remains a valuable nonsurgical treatment option in the management of gastroesophageal reflux disease.
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Affiliation(s)
- Mark Franciosa
- Center for Swallowing and Motility Disorders, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02132, USA
| | - George Triadafilopoulos
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94040, USA
| | - Hiroshi Mashimo
- Center for Swallowing and Motility Disorders, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02132, USA
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32
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Zerbib F, Simon M. Novel therapeutics for gastro-esophageal reflux symptoms. Expert Rev Clin Pharmacol 2013; 5:533-41. [PMID: 23121276 DOI: 10.1586/ecp.12.38] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Approximately 20-30% of patients with gastro-esophageal reflux symptoms report inadequate symptom relief while on proton-pump inhibitor therapy. The mechanisms involved are failure of the antireflux barrier (transient lower esophageal sphincter relaxations), high proximal extent of the refluxate, esophageal hypersensitivity and impaired mucosal integrity. Persisting acid or nonacid reflux can be demonstrated in 40-50% of cases, suggesting that there is room for antireflux therapy in these patients. New antireflux compounds have been shown to decrease the occurrence of transient lower esophageal sphincter relaxations. The most promising classes of compounds are GABA type B agonists and metabotropic glutamate receptor 5 antagonists, which can reduce both reflux episodes and symptoms, but the development of these compounds has been abandoned for either safety issues or lack of efficacy. Esophageal hypersensitivity and impaired mucosal integrity may prove to be relevant therapeutic targets in the future.
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Affiliation(s)
- Frank Zerbib
- CHU Bordeaux, Saint André Hospital, Gastroenterology Department, Bordeaux, F-33075, France.
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Abstract
Up to a third of the patients who receive proton pump inhibitor (PPI) once daily will demonstrate lack or partial response to treatment. There are various mechanisms that contribute to PPI failure and they include residual acid reflux, weakly acidic and weakly alkaline reflux, esophageal hypersensitivity, and psychological comorbidity, among others. Some of these underlying mechanisms may coincide in the same patient. Evaluation for proper compliance and adequate dosing time of PPIs should be the first management step before ordering invasive diagnostic tests. Doubling the PPI dose or switching to another PPI is the second step of management. Upper endoscopy and pH testing appear to have limited diagnostic value in patients who failed PPI treatment. In contrast, esophageal impedance with pH testing (multichannel intraluminal impedance MII-pH) on therapy appears to provide the most insightful information about the subsequent management of these patients (step 3). In step 4, treatment should be tailored to the specific underlying mechanism of patient's PPI failure. For those who demonstrate weakly acidic or weakly alkaline reflux as the underlying cause of their residual symptoms, transient lower esophageal sphincter relaxation reducers, endoscopic treatment, antireflux surgery and pain modulators should be considered. In those with functional heartburn, pain modulators are the cornerstone of therapy.
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Affiliation(s)
- T Hershcovici
- The Neuroenteric Clinical Research Group, Southern Arizona VA Health Care System, Tucson, AZ 87523, USA
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Radiofrequency energy delivery to the lower esophageal sphincter reduces esophageal acid exposure and improves GERD symptoms: a systematic review and meta-analysis. Surg Laparosc Endosc Percutan Tech 2012; 22:283-8. [PMID: 22874675 DOI: 10.1097/sle.0b013e3182582e92] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE Studies of endoscopic application of radiofrequency energy to the lower esophageal sphincter for gastroesophageal reflux control have produced conflicting reports of its effectiveness. This study aimed to conduct a meta-analysis of randomized controlled trials and cohort studies to assess the impact of this treatment. METHODS Twenty studies were included. Outcomes analyzed included gastroesophageal reflux disease (GERD) symptom assessment, quality of life, esophageal pH, and esophageal manometry. RESULTS A total of 1441 patients from 18 studies were included. Radiofrequency treatment improved heartburn scores (P=0.001), and produced improvements in quality of life as measured by GERD-health-related quality-of-life scale (P=0.001) and quality of life in reflux and dyspepsia score (P=0.001). Esophageal acid exposure decreased from a preprocedure Johnson-DeMeester score of 44.4 to 28.5 (P=0.007). CONCLUSIONS Radiofrequency ablation of the lower esophageal sphincter produces significant improvement in reflux symptoms and may represent an alternative to medical treatment and surgical fundoplication in select patients.
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Zerbib F, Bruley des Varannes S, Simon M, Galmiche JP. Functional heartburn: definition and management strategies. Curr Gastroenterol Rep 2012; 14:181-8. [PMID: 22451252 DOI: 10.1007/s11894-012-0255-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Functional heartburn (FH) is a functional gastro-intestinal disorder characterized by symptoms of heartburn not related to gastro-esophageal reflux. The absence of evidence of reflux-related symptoms relies on absence of esophagitis at endoscopy (including biopsies to exclude eosinophilic esophagitis), a normal esophageal acid exposure during esophageal pH-monitoring together with a negative symptom-reflux association analysis and an unsatisfactory response to proton pump inhibitor therapy. Addition of impedance measurement to pH-monitoring is likely to increase the number of patients with recognized reflux-related symptoms. The pathophysiology of functional heartburn remains largely unknown but involves disturbed esophageal perception and psychological factors such as depression, anxiety and somatization. The treatment of FH remains largely empirical and an individual approach is therefore recommended. The clinician should provide reassurance and refrain from performing too many invasive tests or therapeutic procedures. The use of pain modulators is recommended by most experts despite the lack of appropriate clinical trials to support it.
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Affiliation(s)
- Frank Zerbib
- Gastroenterology and Hepatology Department, Saint André Hospital, Centre Hospitalier Universitaire de Bordeaux.
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36
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Gill RS, Collins JS, Talley NJ. Management of noncardiac chest pain in women. ACTA ACUST UNITED AC 2012; 8:131-43; quiz 144-5. [PMID: 22375717 DOI: 10.2217/whe.12.3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Noncardiac chest pain (NCCP) is very prevalent in the community. Although mortality remains low, morbidity and the financial implications are high. Women, especially those of middle age, should be thoroughly investigated as per current guidelines for coronary artery disease before labeling their chest pain as NCCP. Gastroesophageal reflux disease is the most common cause of NCCP; however other esophageal pathology including esophageal hypersensitivity, neuromuscular disease and eosinophilic esophagitis may also cause NCCP. Proton pump inhibitors are commonly used initially to manage NCCP, although patients who do not respond to this therapy require further investigation and differing treatment regimes. This article will focus on current knowledge regarding GI tract-related NCCP management strategies.
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Affiliation(s)
- Raghubinder S Gill
- Gosford Hospital, Division of Gastroenterology, New South Wales, Australia
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37
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Fass R. Alternative therapeutic approaches to chronic proton pump inhibitor treatment. Clin Gastroenterol Hepatol 2012; 10:338-45; quiz e39-40. [PMID: 22178462 DOI: 10.1016/j.cgh.2011.12.020] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2011] [Revised: 12/05/2011] [Accepted: 12/06/2011] [Indexed: 02/07/2023]
Abstract
Chronic consumption of proton pump inhibitors (PPIs) by patients with gastroesophageal reflux disease is very common, primarily because of their potent and profound effect on acid secretion that results in an unsurpassed rate of symptom resolution and esophageal healing. However, there have been a growing number of reports over the past few years about various side effects caused by chronic PPI treatment. Concerns have been raised by patients and physicians alike about the common practice of prescribing PPIs, often more than once daily, on a long-term basis. As a result, there has been a resurgence of interest in alternative therapeutic modalities for chronic PPI treatment. These include novel endoscopic and surgical techniques, as well as other available therapeutic strategies that are likely to be revisited, such as histamine-2-receptor antagonists, intermittent and on-demand PPI treatment, and antireflux surgery, among others.
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Affiliation(s)
- Ronnie Fass
- The Neuroenteric Clinical Research Group, Southern Arizona VA Health Care System and University of Arizona Health Sciences Center, Tucson, Arizona 85723-0001, USA.
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38
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Abstract
Gastro-oesophageal reflux disease (GORD or GERD) is a very common disorder, and advancement in drug development over the years has markedly improved disease management. Proton pump inhibitors (PPIs) remain the mainstay of treatment for GERD due to their profound and consistent inhibitory effect on acid secretion. However, PPIs do not reduce the number of reflux events and do not provide long-term cure for GERD. In addition, although the safety profile of PPIs is excellent, recent population-based studies have suggested that long-term PPI use may be associated with a variety of adverse events. They include osteoporosis-related hip and spine fractures, community-acquired and nosocomial pneumonia, various enteric and non-enteric infections, fundic gland polyps and many others. Consequently, there is growing interest by patients and physicians alike in current, as well as future, non-PPI-related therapeutic strategies for GERD. This includes repositioning histamine H(2) receptor antagonists and prokinetics in our current GERD therapeutic algorithms and a resurgence of non-medical therapeutic modalities for GERD, such as anti-reflux surgery, endoscopic treatment, alternative and complementary medicine and psychological interventions. Furthermore, there will be renewed efforts in further developing new medical and non-medical therapeutic modalities for GERD.
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Affiliation(s)
- Tiberiu Hershcovici
- The Neuroenteric Clinical Research Group, Southern Arizona VA Health Care System, Tucson, AZ 85723-0001, USA
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39
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Arts J, Bisschops R, Blondeau K, Farré R, Vos R, Holvoet L, Caenepeel P, Lerut A, Tack J. A double-blind sham-controlled study of the effect of radiofrequency energy on symptoms and distensibility of the gastro-esophageal junction in GERD. Am J Gastroenterol 2012; 107:222-30. [PMID: 22108449 DOI: 10.1038/ajg.2011.395] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Several studies have reported symptom relief in gastro-esophageal reflux disease (GERD) patients treated with radiofrequency delivery (Stretta procedure) at the gastro-esophageal junction (GEJ), but the mechanism underlying this improvement is unclear. The objective of this study was to test the hypothesis that Stretta alters GEJ resistance. METHODS We conducted a double-blind randomized cross-over study of Stretta and sham treatment. Consecutive GERD patients were included in the study. The study was conducted in a tertiary care center. Patients underwent two upper gastrointestinal endoscopies with 3 months interval, during which active or sham Stretta treatment was performed in a randomized double-blind manner. Symptom assessment, endoscopy, manometry, 24-h esophageal pH monitoring, and a distensibility test of the GEJ were done before the start of the study and after 3 months. RESULTS Barostat distensibility test of the GEJ before and after administration of sildenafil was the main outcome measure. In all, 22 GERD patients (17 females, mean age 47±12 years) participated in the study; 11 in each group. Initial sham treatment did not affect any of the parameters studied. Three months after initial Stretta procedure, no changes were observed in esophageal acid exposure and lower esophageal sphincter (LES) pressure. In contrast, symptom score was significantly improved and GEJ compliance was significantly decreased. Administration of sildenafil, an esophageal smooth muscle relaxant, normalized GEJ compliance again to pre-Stretta level, arguing against GEJ fibrosis as the underlying mechanism. CONCLUSIONS The limitation of this study was reflux evaluation did not include impedance monitoring. In this sham-controlled study, Stretta improved GERD symptoms and decreased GEJ compliance. Decreased GEJ compliance, which reflects altered LES neuromuscular function, may contribute to symptomatic benefit by decreasing refluxate volume.
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Affiliation(s)
- J Arts
- Department of Gastroenterology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium
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40
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Abstract
The lower esophageal sphincters (LES) together with the crural diaphragm are the major antireflux barriers protecting the esophagus from reflux of gastric content. However, reflux of gastric contents into the esophagus is a normal phenomenon in healthy individuals occurring primarily during episodes of transient lower esophageal sphincter relaxation (TLESR), defined as LES relaxation in the absence of a swallow. Transient lower esophageal sphincter relaxation is also the dominant mechanism of pathologic reflux in gastroesophageal reflux disorder (GERD) patients. Frequency of TLESR does not differ significantly between healthy individuals and those with GERD, but TLESRs are more likely to be associated with acid reflux in GERD patients. Understanding the mechanisms responsible for elicitation of a TLESR, using recently introduced novel technology is an area of intense interest. Pharmacologic and non-pharmacologic manipulation of receptors involved in the control of TLESR has recently emerged as a potential target for GERD therapy.
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Affiliation(s)
- T Hershcovici
- The Neuroenteric Clinical Research Group, Southern Arizona VA Health Care System, University of Arizona Health Sciences Center, Tucson, AZ 85723-0001 USA
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Medical treatment of GORD. Emerging therapeutic targets and concepts. Best Pract Res Clin Gastroenterol 2010; 24:937-46. [PMID: 21126705 DOI: 10.1016/j.bpg.2010.08.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2010] [Revised: 08/25/2010] [Accepted: 08/27/2010] [Indexed: 01/31/2023]
Abstract
Approximately 20-30% of patients with gastro-oesophageal reflux symptoms report inadequate symptom relief while on PPI therapy. Persisting acid or non-acid reflux can be demonstrated in 40-50% of them suggesting that there is room for anti-reflux therapy in these patients. New anti-reflux compounds aim at decreasing the occurrence of transient lower oesophageal sphincter relaxations (TLOSRs) which represent the main mechanism of all types of reflux. The most promising classes of compounds are GABA(B) agonists and mGluR5 antagonists which have been shown to reduce both reflux episodes and symptoms and are currently under evaluation in phase II and III clinical trials. Compounds that target TLOSR activity represent a promising new therapeutic option for patients who suffer from GORD symptoms. These drugs will probably be developed as add-on therapy in combination with PPIs provided the tolerability and safety issues are resolved.
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42
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Louis H, Devière J. Ensocopic-endoluminal therapies. A critical appraisal. Best Pract Res Clin Gastroenterol 2010; 24:969-79. [PMID: 21126708 DOI: 10.1016/j.bpg.2010.10.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2010] [Accepted: 10/07/2010] [Indexed: 02/06/2023]
Abstract
Due to its large prevalence, gastro-oesophageal reflux disease is an ideal target for companies developing medical devices designed to cure reflux. Indeed, because medications leave part of the patients unsatisfied, there is a potential place for alternative therapies, capable of restoring an efficacious anti-reflux barrier, but without the drawbacks of surgery. For more than a decade, several novel endoluminal therapies were developed, clinically evaluated, put on the market and, for many of them, withdrawn due to economic considerations, lack of efficacy or complications. These therapies were designed to act on the gastro-oesophageal junction and reinforce mechanically the anti-reflux barrier by three different ways: suturing, radiofrequency energy application, or implantation of foreign materials. Most of the published data come from open uncontrolled studies with short-term enthusiastic results. There are a few randomized control trials assessing the true efficacy of these modalities, showing often less impressive results than the open studies did, due to a high placebo effect in mild gastro-oesophageal reflux disease. Although endoscopic treatment of gastro-oesophageal disease is still an interesting topic of investigation, one can draw some lessons from the recent experiences and foresee which place these techniques could find in the management of patients suffering from reflux.
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Affiliation(s)
- Hubert Louis
- Department of Gastroenterology and Hepatopancreatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
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Abstract
PURPOSE OF REVIEW We critically analyze existing endoscopy-based interventions for gastroesophageal reflux disease (GERD). The focus is on the effectiveness of available procedures and to delineate goals for future research. RECENT FINDINGS Recent evaluations of the EndoCinch system reveal poor long-term results and no significant improvement over sham therapy due to poor apposition of mucosa with stitches. Recent studies with transoral incisionless fundoplication demonstrate improvement in GERD symptoms, quality of life, esophageal acid exposure, esophagitis, resting lower esophageal sphincter pressure and medication use. The SRS endoscopic stapling system creates a partial fundoplication wrap, and a preliminary study demonstrated improved symptoms and acid exposure. The Stretta system delivers radiofrequency energy to the gastroesophageal junction. A large prospective series demonstrates sustained improvement in GERD symptoms, quality of life and proton pump inhibitor therapy elimination after radiofrequency ablation at the gastroesophageal junction. A sham-controlled study showed improvement in symptoms at 6 months. SUMMARY EndoCinch plication requires further study and modification of technique before it can be recommended for general clinical use. Transoral incisionless fundoplication is a very promising procedure in its early stages of development. Further evaluation of procedure safety and durability is needed. Radiofrequency ablation therapy has been reintroduced and may have potential in patients with refractory GERD.
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Coron E, Sebille V, Cadiot G, Zerbib F, Ducrotte P, Ducrot F, Pouderoux P, Arts J, Le Rhun M, Piche T, Bruley des Varannes S, Galmiche JP. Clinical trial: Radiofrequency energy delivery in proton pump inhibitor-dependent gastro-oesophageal reflux disease patients. Aliment Pharmacol Ther 2008; 28:1147-58. [PMID: 18616516 DOI: 10.1111/j.1365-2036.2008.03790.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Radiofrequency (RF) energy delivery is an endoscopic procedure developed for the treatment of gastro-oesophageal reflux disease. AIM To compare RF and a proton pump inhibitor strategy (PPI) in PPI-dependent patients by carrying out a prospective, randomized trial. METHODS Patients with PPI-dependent typical reflux symptoms were randomly allocated to either RF or PPI regimen alone. The primary endpoint, evaluated at 6-month, was defined as the possibility for the patient to stop or to decrease PPI use to <50% of the effective dose required at baseline. RESULTS In the RF group, 18/20 patients stopped (n = 3) or decreased (n = 15) PPI use as compared to eight of 16 in the PPI group (P = 0.01). None of the control patients could stop PPI. Health-related quality of life scores were not different between groups. No significant change in oesophageal acid exposure (OAE) was noted between baseline and 6-months after RF. No severe complication was reported. CONCLUSIONS Radiofrequency energy delivery is a safe and effective therapeutic option, allowing reduction in or discontinuation of PPI therapy in patients with PPI-dependent symptoms, without loss of quality of life. However, in a majority of patients, PPI therapy cannot be completely stopped. The efficacy of RF does not seem to be related to a decrease in OAE.
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Affiliation(s)
- E Coron
- Institut des Maladies de l'Appareil Digestif, CHU Hôtel-Dieu, Nantes
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Sidhu AS, Triadafilopoulos G. Neuro-regulation of lower esophageal sphincter function as treatment for gastroesophageal reflux disease. World J Gastroenterol 2008; 14:985-90. [PMID: 18286675 PMCID: PMC2689423 DOI: 10.3748/wjg.14.985] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The junction between the esophagus and the stomach is a specialized region, composed of lower esophageal sphincter (LES) and its adjacent anatomical structures, the gastric sling and crural diaphragm. Together these structures work in a coordinated manner to allow ingested food into the stomach while preventing reflux of gastric contents across the esophago-gastric junction (EGJ) into the esophagus. The same zone also permits retrograde passage of air and gastric contents into esophagus during belching and vomiting. The precise coordination required to execute such a complicated task is achieved by a finely-regulated high-pressure zone. This zone keeps the junction between esophagus and stomach continuously closed, but is still able to relax briefly via input from inhibitory neurons that are responsible for its innervation. Alterations of the structure and function of the EGJ and the LES may predispose to gastroesophageal reflux disease (GERD).
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Systematic review: endoluminal therapy for gastro-oesophageal reflux disease: evidence from clinical trials. Eur J Gastroenterol Hepatol 2007; 19:1125-39. [PMID: 17998840 DOI: 10.1097/meg.0b013e3282f16a21] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
During the last few decades many endoscopic interventions have been developed as an alternative for the treatment of gastro-oesophageal reflux disease (GORD). In many countries, these interventions are thus being performed in the general clinical setting. The aim of this study is to systematically review the evidence on the effect of endoscopic therapies for GORD. A systematic search of the literature on this subject in English, indexed in MEDLINE (1966 to May 2007) and in the Cochrane Library, was carried out. For the study selection, retrospective and prospective open-label and randomized, sham-controlled trials were taken into account. The exclusion criteria included the following: case series that included fewer than 10 patients, abstracts, studies involving children or those with a follow-up shorter than 3 months. For data extraction, two reviewers, using standardized forms, independently abstracted data on study design and methods, population, sample size, function studies (e.g. pH-metry), type of endoscopic treatment, follow-up, health-related and quality of life scores, outcomes and complications. Data synthesis involved the following: 43 studies, including four randomized, sham-controlled trials that met the inclusion criteria, out of 4182 citations. The primary end point in most studies was the reduction of the use of proton pump inhibitors (PPIs) by more than 50%. In view of these findings, the majority of studies suggested the efficacy of endoluminal therapies for the control of symptoms in GORD. In the sham-controlled studies, the effect of placebo was, nevertheless, as high as 50%. Most studies were small feasibility studies, with follow-ups of less than 1 year. No study comparing endoscopic techniques with other established treatment options such as PPIs existed. All endoscopic therapies were associated with a small but important percentage of mild to severe complications, which included perforation, abscess and death. In conclusion, the data from most of the short-term follow-up and the few sham-controlled studies demonstrate that subgroups of patients experienced improvement or resolution of typical GORD symptoms and decreased PPI usage. Currently, however, there are not enough scientific and clinical data on safety, efficacy and durability to support the use of endoluminal therapies for GORD in routine clinical practice.
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Is the Stretta procedure safe and effective for the long-term control of symptoms in patients with refractory GERD? ACTA ACUST UNITED AC 2007; 4:654-5. [PMID: 17971797 DOI: 10.1038/ncpgasthep0978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2007] [Accepted: 08/21/2007] [Indexed: 12/18/2022]
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