Received: 17 June 2022 DOI: 10.1002/ueg2.12318 ORIGINAL ARTICLE - Accepted: 17 September 2022 UEG and EAES rapid guideline: Update systematic review, network meta‐analysis, CINeMA and GRADE assessment, and evidence‐informed European recommendations on surgical management of GERD Sheraz Markar1,2 | Alexandros Andreou3 | Luigi Bonavina4 | 5,6 7 Ivan D. Florez | Bright Huo | Katerina‐Maria Kontouli | Donald E. Low9 | 8 Dimitris Mavridis8,10 | Nick Maynard1 | Alan Moss11 | Manuel Pera12,13 | Edoardo Savarino14 | Peter Siersema15 | Daniel Sifrim16 | David I. Watson17 | Giovanni Zaninotto18 | Stavros A. Antoniou19 1 Nuffield Department of Surgery, University of Oxford, Oxford, UK 2 Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden 3 Department of Surgery, York Teaching Hospital NHS Foundation Trust, York, UK 4 Department of Biomedical Sciences for Health, Division of General and Foregut Surgery, IRCCS Policlinico San Donato, University of Milan, Milan, Italy 5 Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada 6 Department of Pediatrics, University of Antioquia, Medellin, Colombia 7 Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada 8 Department of Primary Education, School of Education University of Ioannina, Ioannina, Greece 9 Department of Thoracic Surgery and Surgical Oncology, Virginia Mason Medical Center, Seattle, Washington, USA 10 Paris Descartes University, Sorbonne Paris Cité, Faculté de Médecine, Paris, France 11 Action Against Heartburn, London, UK 12 Gastroesophageal Carcinogenesis Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain 13 Section of Gastrointestinal Surgery, Hospital Universitario del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain 14 Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, Padua, Italy 15 Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands 16 Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK 17 Flinders University Discipline of Surgery, Flinders Medical Centre, Bedford Park, South Australia, Australia 18 Department of Surgery and Cancer, Imperial College London, London, UK 19 European University Cyprus, Nicosia, Cyprus Correspondence Sheraz Markar, Nuffield Department of Abstract Surgery, University of Oxford, Oxford, UK. Background: There are several options for the surgical management of GERD in Email: sheraz.markar@nds.ox.ac.uk adults. Previous guidelines and systematic reviews have compared the effects of - This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. © 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology. United European Gastroenterol J. 2022;10:983–998. wileyonlinelibrary.com/journal/ueg2 983 984 - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL Funding information United European Gastroenterology; European total fundoplication versus pooled effects of different techniques of partial Association for Endoscopic Surgery and other fundoplication. Interventional Techniques Objective: To develop evidence‐informed, trustworthy, pertinent recommendations on the use of total, posterior partial and anterior partial fundoplications for the management of GERD in adults. Methods: We performed an update systematic review, network meta‐analysis, and evidence appraisal using the GRADE and the Confidence in Network Meta‐Analysis methodologies. An international, multidisciplinary panel of surgeons, gastroenter- ologists, and a patient representative reached unanimous consensus through an evidence‐to‐decision framework to select among multiple interventions, and a Delphi process to formulate the recommendation. The project was developed in an online authoring and publication platform (MAGICapp), and was overseen by an external auditor. Results: We suggest posterior partial fundoplication over total posterior or anterior 90° fundoplication in adult patients with GERD. We suggest anterior >90° fundo- plication as an alternative, although relevant comparative evidence is limited (weak recommendation). The guideline, with recommendations, evidence summaries and decision aids in user friendly formats can also be accessed in MAGICapp: https:// app.magicapp.org/#/guideline/j20X4n. Conclusion: This rapid guideline was developed in line with highest methodological standards and provides evidence‐informed recommendations on the surgical man- agement of GERD. It provides user‐friendly decision aids to inform healthcare professionals' and patients' decision making. KEYWORDS AGREE‐S, fundoplication, GERD, guideline, Nissen, Toupét INTRODUCTION Key summary Gastroesophageal reflux disease (GERD) affects a substantial pro- � Various surgical options exist for the management of portion of the general population.1,2 Laparoscopic antireflux surgery GERD in adults. has been established as an effective treatment for patients who do � We summarized evidence through network meta‐ not wish to receive medication, and patients with persistent symp- analysis of interventions. toms despite medication.3 � We suggest partial posterior fundoplication over total Laparoscopic Nissen procedure has become the most established posterior or anterior 90° fundoplication. antireflux operation, however it is associated with dysphagia in about � We suggest anterior >90 degrees may be an alternative. 13% of patients beyond 1 year after surgery.4 Partial fundoplications have been proposed as alternatives, however concerns have been raised about their long‐term effectiveness with regard to reflux control.5 Evidence on several partial antireflux procedures has been (EAES),8 we decided to develop a rapid guideline on the surgical 6,7 pooled in previous clinical practice guidelines. Different partial management of GERD. fundoplications, such as Toupét, Dor, and anterior fundoplications The aim of this rapid guideline is to assist surgeons, patients, may have distinct effect on reflux control and postoperative and other healthcare professionals in selecting the most appro- dysphagia. Summarizing the effect of these procedures may not priate surgical option(s) for the management of GERD. The provide the best information for clinical decision making. objective is to reduce the long‐term side effects and improve the In light of this gap in evidence and informed by an annual survey quality of life and experience of patients undergoing antireflux of members of the European Association for Endoscopic Surgery surgery. MARKAR ET AL. - 985 METHODS further relevant conflicts. We invited key opinion leaders as external advisors, who are authors in studies that expressed an opinion on the This rapid guideline follows AGREE‐S, GRADE, Institute of Medicine, effectiveness of an intervention, or are performing research on a Guidelines International Network (GIN) and Cochrane Rapid Reviews topic that could be affected by a recommendation of this guideline. Methods Group development and reporting standards.9–13 An These members were not involved in the decisions on the strength, AGREE‐S reporting checklist is provided in Supplementary file 2. the direction or the wording of the recommendations, but they were GRADE guidance published in a series of articles in the Journal of consulted in the development of the evidence‐to‐decision frame- Clinical Epidemiology was consulted for up‐to‐date information. work, as per GRADE and GIN guidance. The composition of the Importantly, the development of this guideline was informed by the guideline development group and each member's role are available in GRADE methodology to appraise the certainty of the evidence from a the online appendix.19 network meta‐analysis, the Confidence in Network Meta‐Analysis (CINeMA) methodology, and the GRADE evidence‐to‐decision framework to choose from multiple interventions.14–17 This process Health question was facilitated by the use of MAGICapp, an online authoring and publication platform. Which procedure should be used among of 360°, 270°, 300°, anterior 180°, posterior 180°, anterior 120°, anterior 90° fundoplications, Hill and LINX® for adult patients with GERD? This guideline applies to Steering group patients with documented GERD without or with a small hiatal hernia (<2 cm), and no significant esophageal body hypomotility (ineffective The steering group consisted of two general surgeons who perform esophageal motility—more than 70% of weak contractions or 50% laparoscopic antireflux surgery (SAA, SM). A member of the steering failed swallows, and esophageal scleroderma) undergoing laparo- group is a certified guideline methodologist with vast experience in scopic surgery. evidence outreach, synthesis, assessment and guideline development (SAA). The guideline methodologist was the senior author of a network meta‐analysis comparing different antireflux procedures,18 Terminology which may be considered an indirect conflict. The other member of the steering group (SM) was the content coordinator of this project We used the term ‘total posterior’ to denote a 360° wrap, Nissen 19 and disclosed no direct nor indirect conflict. We therefore consider procedure; ‘partial posterior’ to denote a 180°—300° wrap, including that a potential indirect conflict has not affected the content of this Toupét fundoplication; anterior 90° to denote a partial anterior wrap, guideline. An external auditor, lead of the AGREE Collaboration, was approximately 90°; and anterior >90° to denote an anterior wrap of overseeing the project from the outset (IDF), receiving all email >90°, including Dor procedure. The terms used are summarized in communications of the steering group and the guideline development Table 1 and Figure 1. group, and participated in the consensus meeting. Protocol Guideline panel A protocol was developed a priori by the steering group.20 The The guideline panel consisted of 3 general surgeons, 2 gastroenter- protocol draft was made publicly available through the EAES website ologists, and a patient representative. The patient representative and EAES members were invited through email to comment on the (AM) is a lead member of Action Against Heartburn, a not‐for‐profit content. The guideline question and outcomes of interest were organization raising awareness on GERD and upper gastrointestinal refined in collaboration with the panel members. Amendments to the cancer. He was regular member of the guideline panel, with equal protocol with justifications are provided below. contribution and voting rights from the start of the guideline devel- opment process. Panel members watched a short video tutorial outlining the guideline development methodology. The composition of panel members aimed to be representative of different parts of TABLE 1 Terminology used in this report Europe and different age groups. The majority of panel members Term Explanation disclosed no direct nor indirect conflicts.19 A panel member disclosed being author in studies comparing antireflux surgery and LINX®, Total posterior 360° wrap, Nissen however we found no relevant evidence based on randomized Partial posterior 180°—300° wrap, including oupét fundoplication controlled trials comparing LINX® with other antireflux surgical Anterior 90° Partial anterior wrap, approximately 90° procedures with the predefined panel‐set minimum follow‐up for Anterior >90° Anterior wrap of >90°, including Dor critical outcomes (see Study selection and Results). We identified no 986 - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL FIGURE 1 (a) total posterior; (b) partial posterior; (c) anterior 90°; (d) anterior >90° Rating the importance of outcomes The two latter outcomes were prioritized by members of the panel and external advisors. They also nominated a number of out- The importance of outcomes was rated by panel members using the comes, which were not prioritized: irritable bowel syndrome (irritable GRADE scale.21 The classification of outcomes into each of the three bowel syndrome, dumping syndrome, Barrett's esophagus, adeno- categories (not important, important, critical) was made by the steering carcinoma (rare and rarely reported outcomes); ability to perform group under consideration of panel members' ratings available online.19 activities/work without any symptoms, and patient satisfaction We considered the importance of outcomes as follows: (rarely reported outcome and/or quality of life was used as surro- gate). We considered heartburn, regurgitation and gas bloat as sur- 1. 30‐day complications Clavien‐Dindo ≥3: critical rogates for symptom recurrence. 2. 30‐day complications Clavien‐Dindo ≤2: important 3. Dysphagia beyond 6 months: important 4. Symptom recurrence beyond 5 years: important Setting minimal important differences 5. Quality of life: critical 6. Reoperation: critical (set post hoc) The evidence‐to‐decision framework was set within a fully contex- 7. Use of antacids: important (set post hoc) tualized approach.22 An anonymous web‐based survey of panel MARKAR ET AL. - 987 members was performed to define minimal important differences. outcomes with a more than 1 year of follow‐up. Panel members and The results of the survey are available online.19 external advisors were provided with the list of included articles and Under consideration of panel's responses, the following minimal they were asked whether they are aware of any other trials important differences were set: addressing the clinical question. A member of the advisory group pointed out another 2 available randomized controlled trials that 1. 30‐day complications Clavien‐Dindo ≥3: 10 per 1000 were missed from the evidence search.25,26 2. 30‐day complications Clavien‐Dindo ≤2: 50 per 1000 3. Dysphagia: 25 per 1000 Heartburn: 25 per 1000 4. Regurgitation: 25 per 1000 Data extraction 5. Gas bloat: 25 per 1000 6. Quality of life: 0.2/0.5 standard deviations (small/moderate Outcome data were extracted by one reviewer (BO), and cross‐ difference) checked in detail by the senior author. Data from the previous sys- 7. Reoperation: 10 per 1000 (set post hoc) tematic review were cross checked by one of the reviewers (BH). The 8. Use of antacids: 100 per 1000 (set post hoc) data extraction spreadsheet and detailed risk of bias assessments per outcome or group of outcomes with justifications are available online The outcome quality of life was reported with different scales also for third‐party use under the Creative Commons license, after (Gastrointestinal Quality of Life Index, Short Form 36), we therefore approval by the senior author.19 calculated standardized mean differences. Although no universal Particular care was taken to avoid double‐counting of data from 23 cutoff can be applied, we considered the above differences in different reports of the same trial, by cross checking the trial regis- standard deviation units as important based on expert guidance tration number, country and institution, the authors' names, years of (INGUIDE certification program). patient recruitment, sample size, and other information. The senior author of several randomized trials was an external advisor, and was consulted in case it was unclear whether there was an overlap of Search strategy patient populations in different reports (DIW). We used PlotDigitizer (http://plotdigitizer.sourceforge.net) to We updated a previous systematic review on the surgical manage- retrieve data from graphs, when absolute values were not provided in ment of GERD.18 We used the same search syntax with publication the study reports. date limits from date of the previous search up to 9 November 2021. In the context of this rapid guideline, we searched PubMed only. After discussion among the guideline development group, the present Risk of bias assessment guideline considered additionally the Hill procedure and LINX®, therefore two additional separate search strategies were developed We performed de novo risk of bias assessments using RoB‐2.27 Risk and PubMed was searched with no date restrictions. The search of bias assessments were performed by one of the reviewers (BH) strategies were developed by the guideline methodologist. Informa- and cross checked by the senior author in detail (SAA). For the tion on the search of the previous systematic review is provided purposes of outcome‐specific risk of bias assessment, outcomes were 18 elsewhere. The search syntax, date limits, and summary search grouped as follows: 30‐day complications Clavien‐Dindo; dysphagia, results are provided in the online appendix.19 heartburn, regurgitation, gas bloat; quality of life; reoperation; use of antacids. We considered longest‐term follow‐up data, with a mini- mum follow‐up of 12 months (except for perioperative complica- Study selection tions). Risk of bias assessment and visual summarization were performed with the RoB‐2 tool and the respective Excel Study selection was performed by an ad hoc evidence outreach team application.28 24 (BH, AA) using the platform Rayyan. Both reviewers were blinded to each other's judgement and, after unblinding, disagreements were resolved through arbitration by the senior author. We considered Statistical analysis randomized controlled trials only, comparing either laparoscopic antireflux surgery, or a modification, with each other or with antacid Network meta‐analysis is a popular statistical method that synthe- medication. Antacid medication was used as a common comparator in sizes direct and indirect evidence, and as a result, allows estimation the context of network meta‐analysis. Overarching inclusion criteria of the relative effectiveness between any pair of interventions within were adult patients with symptoms of GERD and no hiatal hernia, or a network of treatments with increased precision.29,30 Moreover, a hiatal hernia with size smaller than 2 cm documented in cross network meta‐analysis can rank all the available treatments in the sectional imaging, barium studies, or esophagogastroscopy. We only network. By the term network, we refer to a plot consisting of nodes included studies in the quantitative analysis which reported on and edges. Nodes represent treatments and edges represent direct 988 - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL evidence; studies directly comparing the treatments (nodes) con- between the study populations, settings and interventions (which nected by the edge. The size of the nodes is proportional to the was judged as low risk across outcomes), and the presence of direct number of studies that include the specific treatment, and the evidence; if only indirect evidence was present (which does not allow thickness of the edges is proportional to the inverse of the variance for assessment of inconsistency), we downgraded the evidence cer- of each comparison. tainty by one level. Heterogeneity judgements were based upon We conducted a frequentist fixed and random effects network statistical calculations of heterogeneity and consistency. If substan- 31 meta‐analysis using the graph theory approach for each outcome in tial heterogeneity or inconsistency were found, we downgraded the R (version 4.0.6) with ‘netmeta’ package.32 We estimated the summary certainty in the evidence by one or two levels. Judgements on odds ratio for all dichotomous outcomes with 95% confidence in- imprecision were based upon minimal important differences that tervals. There was only one continuous outcome, quality of life, for were set by majority voting of the guideline panel in advance, ac- which we reported the standardized mean difference, with its 95% cording to principles of a fully contextualized approach (minimal confidence interval. We chose standardized mean difference as an important differences for each outcome were based upon the effect size because there were various different scales used across assumption that each outcome is the only outcome of interest).22 studies. All the relative effects estimates and their corresponding 95% For each outcome, we stratified interventions by certainty confidence intervals are summarized on the lower diagonal of a league (moderate‐to‐high or low‐to‐very low). We then grouped in- table. On the upper diagonal, we reported all direct estimates. We also terventions within each stratum into 3 groups according to their provided the 95% prediction intervals for all outcomes. We ranked all statistical ranking: among the best, inferior to the best/better than the the available treatments in each outcome, from best to worst, using P‐ worst, and among the worst. The classified rankings were considered 33 scores. A value close to 1 means that the intervention is very effi- by panel members as complementary to the GRADE evidence tables. cacious, whereas a value close to 0 means the opposite. Network meta‐ This process facilitates assessment of both the certainty of the evi- analysis makes two significant assumptions, transitivity, and consis- dence on each intervention along with their ranking.39 29 tency. The transitivity assumption suggests that all effect modifiers have a similar distribution across all studies in each outcome and is evaluated clinically by inspecting differences in effect modifiers across Evidence‐to‐decision framework and development of trials and comparisons. The statistical manifestation of transitivity is recommendations the consistency assumption. This assumption refers to the agreement of direct and indirect evidence for those comparisons that have both The guideline panel reviewed the evidence tables and the stratified sources of evidence. We evaluated the consistency assumption glob- rankings. In an in‐person consensus meeting, panel members pro- ally using the design by treatment model34 and locally using the node‐ vided their judgements on: splitting method.35 In addition, we assessed for potential reporting bias using the comparison‐adjusted funnel plot, which is an extension � the magnitude of benefit of each intervention 36 of the funnel plot in pairwise meta‐analysis. � the magnitude of harm of each intervention We performed a sensitivity analysis of studies with a follow‐up � the certainty of the evidence for each intervention over the 3 years. � any variability in patients' values and preferences � costs or savings related to each intervention � effect of each intervention on equity Assessment of the certainty of evidence � acceptability of each intervention � feasibility of each intervention We constructed GRADE evidence profiles of certainty for each pairwise comparison separately and for each outcome using MAGI- Panel members then participated in an online Delphi process to Capp. The certainty of evidence is determined by the risk of bias formulate the recommendation. A draft of the recommendation was across studies, incoherence, indirectness, imprecision, publication developed by the steering group, and panel members were invited to bias and other parameters.37 To inform calculations of absolute ef- anonymously propose modifications. fect differences, we performed proportion meta‐analyses of fre- quencies of baseline risks/effects provided by the source studies; these are available in the online appendix.19 Amendments to the protocol We used the CINeMA software to summarize risk of bias ac- cording to the contribution of each study to the network for the Following panel members' and advisors' input, we considered 14,38 respective outcome. The overall risk of (within study) bias was 12 month follow‐up rather than 6 month follow‐up for important based upon the highest proportion of risk of bias contributed to the outcomes. Furthermore, following panel's and advisors' majority network, as per CINeMA methodology.38 Judgements on publication voting, we decided to group total anterior with partial anterior repair. (reporting) bias were based on comparison‐adjusted funnel plots. However, sensitivity analyses assuming different effects for anterior Judgements on indirectness were based on conceptual differences 90° and anterior >90° repairs suggested substantial differences, and MARKAR ET AL. - 989 therefore we retained the network which considers anterior 90° and total fundoplication with regards to dysphagia, however with similar anterior >90° repairs separately. effects on reflux control in the long term. Total fundoplication may be currently the most frequently performed antireflux surgery in Europe. Centers offering antireflux surgery may need to include RESULTS posterior partial fundoplication in their services, and training cen- ters in the field of antireflux surgery may need to incorporate 40–81 We included 43 reports from the original review, and we iden- partial fundoplications in their future surgical curriculums. tified additionally 8 reports in the update search,25,26,82–87 which Centralization of antireflux surgeries has been suggested by registry included LINX® and Hill procedures. No randomized trials on Hill analyses. were identified, and 2 reports of the same trial on LINX®, that re- ported on 6‐ and 12 month follow‐up; these were excluded from the analysis due to insufficient follow‐up.86,87 Implications for healthcare professionals Overall, we included 49 reports of 31 randomized trials. Several studies reported on multiple randomized trials.25,41,57,82 In a scoping Surgeons performing antireflux surgery are advised to perform search of trial registries (see Validity period), we identified 1 un- partial posterior fundoplication for gastroesophageal reflux dis- published trial and 1 trial published only in abstract form88,89; we did ease, as it is likely associated with lower risk of short‐term not consider that this introduced publication bias. Detailed reasons complications and long‐term dysphagia, and may be associated for exclusion can be found online.19 with a lower risk of major complications and reoperation, Patient inclusion and exclusion criteria, surgical procedures, and compared to the most frequently performed total posterior fun- outcome assessment were similar or similarly distributed within the doplication. Transition to partial fundoplication is unlikely to pose network, therefore we considered that the condition of transitivity is substantial technical difficulties for experienced surgeons per- met. Detailed data are available online.19 forming antireflux surgery. Network plots and risk of bias contribution charts per outcome or group of outcomes are available in the Appendix. Node size is proportional to the number of studies; node color corresponds to the Implications for patients proportion of risk of bias; edge width is proportional to the inverse variance; and edge color corresponds to the average risk of bias. A Patients with gastroesophageal reflux disease wishing to receive classified rankings table is available in the Appendix. antireflux surgery can be informed that total posterior and partial There was unanimous consensus on the direction, the strength, posterior fundoplications are surrounded by low to moderate cer- and the wording of the recommendations.19 tainty evidence for most outcomes, and that partial posterior fun- Table 2 summarizes the evidence on the comparison between doplication appears to confer similar antireflux control compared to partial posterior and total posterior fundoplication. Evidence tables total fundoplication, with a lower risk of short and long‐term adverse for other comparisons are provided in the Appendix. effects and reoperation. Table 3 summarizes the evidence‐to‐decision considerations. Implications for researchers Recommendation Researchers in the field of antireflux surgery are advised to collect We suggest posterior partial fundoplication over total and report a minimum of critical and important outcomes, including posterior or anterior 90° fundoplication in adult patients major and minor complications, ideally graded using the Clavien‐ with gastroesophageal reflux disease. Anterior >90° fun- Dindo classification; heartburn; regurgitation; dysphagia; gas‐bloat; doplication is suggested as an alternative, although relevant ability to belch; reoperation; use of antacids; and, importantly, quality comparative evidence is limited (weak recommendation). of life. Development of a core outcome set for antireflux surgery is recommended. The majority of evidence refers to total posterior and partial posterior fundoplications. Anterior >90° fundoplication, for example, Dor, may be at least as effective and safe as other anti- DISCUSSION reflux procedures, however it is supported by limited evidence. RCTs addressing the comparative effects of partial posterior and Implications for policy makers anterior >90° fundoplication are desired. A minimum of 5 year follow‐up is data is considered informative to guide clinical decision Summary evidence and cost‐related considerations suggest that making. Further research on LINX® with longer‐term follow‐up is posterior partial fundoplication may perform better compared to desired. TABLE 2 Evidence table for the comparison partial posterior versus total posterior fundoplication 990 - Absolute effect estimates Partial Total Outcome Study results and posterior posterior Certainty of the evidence Timeframe measurements fundoplication fundoplication (quality of evidence) Plain language summary Major complications Odds ratio: 1.92 40 per 1000 74 per 1000 Low Total posterior fundoplication (Clavien‐Dindo ≥3) 30 days (CI 95% 0.76–4.76) may increase major Due to serious imprecision, or in‐hospital complications (Clavien‐Dindo ≥3) Based on data due to serious risk of biasa from 890 participants in 11 studies Follow up 30 days Difference: 34 more per 1000 (CI 95% 9 fewer—126 more) Minor complications Odds ratio: 1.22 58 per 1000 70 per 1000 Moderate Total posterior fundoplication (Clavien‐Dindo <3) 30 days (CI 95% 0.35–4.35) b probably increases Due to serious imprecision or in‐hospital minor complications Based on data (Clavien‐Dindo <3) from 690 participants in 9 studies Follow up 30 days Difference: 12 more per 1000 (CI 95% 37 fewer—153 more) Dysphagia Longest Odds ratio: 3.45 80 per 1000 231 per 1000 Moderate Total posterior follow‐up (>1 year) (CI 95% 2.08–5.56) fundoplication probably increases dysphagia Based on data from 2304 participants in 19 studies Follow up 1–12 years Difference: Due to serious risk of biasc (median, 3 years) 151 more per 1000 (CI 95% 73 more—246 more) Gas‐bloat Longest Odds ratio: 1.35 186 per 1000 236 per 1000 Very low We are uncertain whether follow‐up (>1 year) (CI 95% 0.78–2.38) total posterior fundoplication increases \or decreases Based on data from Due to very serious imprecision, gas‐bloat 1403 participants due to serious publication in 12 studies bias, due to serious inconsistency, due to serious risk of biasd UNITED EUROPEAN GASTROENTEROLOGY JOURNAL T A B L E 2 (Continued) MARKAR Absolute effect estimates ET AL. Partial Total Outcome Study results and posterior posterior Certainty of the evidence Timeframe measurements fundoplication fundoplication (quality of evidence) Plain language summary Follow up 1–12 years Difference: (median, 1.3 years) 50 more per 1000 (CI 95% 35 fewer—166 more) Heartburn Longest Odds ratio: 1.18 159 per 1000 182 per 1000 Very low We are uncertain follow‐up (>1 year) (CI 95% 0.69–2.0) whether total posterior fundoplication increases Based on data from or decreases heartburn 1548 participants in 15 studies Follow up 1– Difference: Due to very serious 12 years (median 23 more imprecision, due to 4.3 years) per 1000 (CI 95% serious risk of biase 44 fewer—115 more) Regurgitation Longest Odds ratio: 1.02 133 per 1000 135 per 1000 Very low We are uncertain whether follow‐up (>1 year) (CI 95% 0.48–2.17) total posterior fundoplication increases or decreases Based on data regurgitation from 1047 participants in 10 studies Follow up 1–12 years Difference: Due to very serious imprecision, (median, 1 year) 2 more per 1000 due to serious risk of biasf (CI 95% 64 fewer—117 more) Reoperation Longest Odds ratio: 1.85 42 per 1000 75 per 1000 Low Total posterior fundoplication follow‐up (>1 year) (CI 95% 0.91–3.7) may increase reoperation Based on data from 1886 participants in 15 studies Follow up 1–20 years Difference: 33 Due to serious imprecision, (median, 2 years) more per 1000 due to serious risk of biasg (CI 95% 4 fewer—98 more) (Continues) - 991 992 - T A B L E 2 (Continued) Absolute effect estimates Partial Total Outcome Study results and posterior posterior Certainty of the evidence Timeframe measurements fundoplication fundoplication (quality of evidence) Plain language summary Use of antacids Longest Odds ratio: 0.84 129 per 1000 111 per 1000 Low Total posterior fundoplication follow‐up (>1 year) (CI 95% 0.4–1.75) may have little or no difference on use of antacids Based on data from 1756 participants in 12 studies Follow up 1–20 years Difference: 18 fewer per Due to very (median, 5 years) 1000 (CI 95% 73 serious risk of biash fewer—77 more) Quality of life Longest Measured by: various SD SD Very low We are uncertain whether follow‐up (>1 year) total posterior fundoplication Scale: High better improves or worsens quality of life Based on data from Mean Mean Due to very 442 participants in serious risk of bias, 4 studies due to very serious imprecisioni Follow up 1–10 years (median, 2 years) Abbreviations: CI, confidence interval; SD, standard deviation. a Risk of Bias: serious. Imprecision: serious; wide confidence intervals. b Imprecision: serious; wide confidence intervals. c Risk of Bias: serious. d Risk of Bias: serious. Inconsistency: serious; inconsistency between direct and indirect evidence. Imprecision: very serious; very wide confidence intervals. Publication bias: serious; asymmetrical funnel plot. e Risk of Bias: serious. Imprecision: very serious; very wide confidence intervals. f Risk of Bias: serious. Imprecision: very serious; very wide confidence intervals. g Risk of Bias: serious. Imprecision: serious; wide confidence intervals. h Risk of Bias: very serious. i Risk of Bias: very serious. Imprecision: very serious; wide confidence intervals, low number of patients. UNITED EUROPEAN GASTROENTEROLOGY JOURNAL MARKAR ET AL. - 993 TABLE 3 Evidence to decision considerations Benefits and harms Benefits referred to effective antireflux control, which appeared to be similar Substantial net benefits of the suggested among the competing interventions. Harms were related to major alternative postoperative complications (partly due to intractable early postoperative dysphagia), long‐term postoperative dysphagia, insufficient reflux control, and risk of reoperation, where total posterior fundoplication conferred inferior outcomes compared to posterior partial fundoplication. Anterior >90° had similar outcomes compared to partial posterior fundoplication, however the latter had a better profile of effects in the network of interventions. Summary Partial posterior fundoplication appeared to confer moderate benefits with trivial or no harms. Total posterior and anterior >90° fundoplication was associated with small benefits and trivial (>90° fundoplication) or moderate harms (total posterior fundoplication). Certainty of the Certainty of the evidence for each intervention was very low to low. This was Low evidence due to the lack of evidence on critical outcomes, such as quality of life, and due to low/very low certainty evidence owing to imprecision (wide confidence intervals, because of sparse network comparisons for some interventions—especially anterior 90° and to a lesser extent anterior >90°), or risk of bias, which was, however, fair overall. Summary Overall certainty of evidence was judged to be low for partial posterior and anterior >90°, and very low for anterior 90°. It was considered to be low for total posterior fundoplication, although no unanimus consensus was reached (low vs. very low). Preferences and No relevant research in the form of patient interviews, surveys, or focus Substantial variability is expected values groups was found in a scoping search. In the lack of relevant research, the panel, with particular input from the patient representative, suggested that substantial variability is expected with regards to patients' preferences and values (e.g., use of antacid medication or particular symptoms). Summary In the lack of relevant research, the panel suggested that there may be substantial variability in patients' values and preferences. Resources We found no relevant evidence in a scoping search for cost‐effectiveness No important issues with the recommended studies within the last 10 years. A healthcare utilization analysis focusing alternative on a 3‐month period following surgery for GERD and paraesophageal hernia found that patients who are readmitted accrue costs that almost double the overall cost of care compared to the initial hospitalizationa. Summary The panel considered that readmissions for management of adverse effects, including dilatations and revision surgery may result in substantial healthcare cost and resources utilization. In these terms, total posterior fundoplication and anterior 90° fundoplication may confer moderate relative cost, whereas partial posterior fundoplication may result in moderate savings. Equity The panel did not identify any parameters related to different interventions Important issues that may affect equity in the access of healthcare or in the use of healthcare resources. Acceptability Empirical and published evidence suggests that posterior total fundoplication No important issues with the recommended is the antireflux surgery of choice for most surgeons. alternative Summary The panel considered that, in view of limited evidence and low penetration, anterior 90° fundoplication might not be acceptable by many surgeons. Considering that total posterior fundoplication is the most frequently performed antireflux surgery, it was considered to be most acceptable. (Continues) 994 - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL T A B L E 3 (Continued) Changing practice to posterior partial or anterior >90° fundoplication may be a challenge. Detailed review of the evidence presented herein, auditing the first 10–15 cases and comparing the outcome to local historical controls and visiting centers where posterior partial fundoplication is the procedure of choice might facilitate implementation of the recommendation. Feasibility The panel did not identify any issxxues related to the feasibility of the various No important issues with the recommended alternatives. alternative a Kleppe KL, Xu Y, Funk LM, Wang X, Havlena JA, Greenberg JA, Lidor AO. Healthcare spending and utilization following antireflux surgery: examining costs and reasons for readmission. Surgical Endoscopy 2020; 34 (1):240–248. Monitoring A CK NO W L E D GE M E NT S This project was funded by United European Gastroenterology and Use of the guideline by EAES members will be monitored through an the European Association for Endoscopic Surgery. The funding bodies online survey 2 years after publication. Feedback from target users in had no influence on the development of this rapid guideline or its the form of email communication, letters to the editor, and comments protocol. There is no grant number linked to this research. in social media will be documented to be addressed in future versions of this guideline. CO N F L I C T O F I N T E R E S T The authors declare no direct conflicts of interest related to this work. Indirect conflicts of external advisors were documented and Validity period managed as per Guidelines International Network Standards. Detailed conflict of interest statements of all contributors can be A scoping search of ClinicalTrials.gov, the EU Clinical Trials Register, found in http://osf.io/xwdyj. A patient version of this guideline is the WHO International Clinical Trials Registry Platform, EORTC and available in Supplementary file 1. the ISRCTN registry for clinical trials on patients >18 years of age registered within the last 5 years identified 2 studies; 1 study with DA T A A V A I L A B I L I T Y S T A T E M E N T anticipated completion date in 2011 published in abstract form, and Data derived from public domain resources. another which is not published and with no information about its current status, with anticipated completion date in 2014.88,89 Under U E G D I S C LA I M E R consideration that a median of 2.5 reports of RCTs (range, 2–6) were These guidelines have been developed with reasonable care and with published annually over the past 10 years, substantial new evidence the best of knowledge available to the authors at the time of prep- that could pragmatically change the direction of the recommendation aration. They are intended to assist healthcare professionals and al- or the magnitude of effects is expected after 6 years. The validity of lied healthcare professionals as an educational tool to provide the present version of this rapid guideline is set until 2028. Please information that may support them in providing care to patients. read the Disclosure for further information regarding validity. Patients or other community members using these guidelines shall do so only after consultation with a health professional and shall not mistake these guidelines as professional medical advice. These Update guidelines must not substitute seeking professional medical and health advice from a health professional. An update of this rapid guideline is planned to take place in 2028. It These guidelines may not apply to all situations and should be will address LINX® if additional evidence with longer‐term follow‐up interpreted in the light of specific clinical situations and resource will be available. The EAES Research Committee/Guidelines Sub- availability. It is up to every clinician to adapt these guidelines to local committee will keep monitoring new evidence and update this regulations and to each patient's individual circumstances and needs. document if new data become published. The information in these guidelines shall not be relied upon as being complete, current or accurate, nor shall it be considered as inclusive of all proper treatments or methods of care or as a legal standard of CONCLUSION care. UEG makes no warranty, express or implied, in respect of these This rapid guideline was developed with strict methodological guidelines and cannot be held liable for any damages resulting from criteria, network meta‐analysis of RCTs and a structured evidence‐ the application of these guidelines, in particular for any loss or to‐decision framework, and provides a weak recommendation in damage (whether direct or indirect) resulting from a treatment based favor of partial posterior fundoplication over other alternatives. on the guidance given herein. MARKAR ET AL. - 995 UEG shall not be held liable to the utmost extent permissible R E F E R EN C E S according to the applicable laws for any content available on such 1. El‐Serag HB, Sweet S, Winchester CC, Dent J. Update on the external websites, which can be accessed by using the links included epidemiology of gastro‐oesophageal reflux disease: a systematic review. Gut. 2014;63(6):871–80. https://doi.org/10.1136/gutjnl‐ herein. 2012‐304269. Epub 2013 Jul 13 2. Gisbert JP, Cooper A, Karagiannis D, Hatlebakk J, Agréus L, Jablo- E A E S D I SC L AI M E R nowski H, et al. Impact of gastroesophageal reflux disease on pa- This clinical practice guideline has been developed under the auspice tients' daily lives: a European observational study in the primary care setting. Health Qual Life Outcome. 2009;7(1):60. https://doi. of the European Association for Endoscopic Surgery (EAES). It is org/10.1186/1477‐7525‐7‐60 intended to be used primarily by health professionals (e.g., surgeons, 3. Tristão LS, Tustumi F, Tavares G, Bernardo WM. Fundoplication anaesthetists, physicians) and to assist in making informed clinical versus oral proton pump inhibitors for gastroesophageal reflux dis- decisions on diagnostic measures and therapeutic management. It is ease: a systematic review and meta‐analysis of randomized clinical trials. Esophagus. 2021;18(2):173–80. https://doi.org/10.1007/ also intended to inform individual practice of allied health pro- s10388‐020‐00806‐w. Epub 2021 Feb 2 fessionals (e.g., surgical nurses, dieticians, physical rehabilitation 4. Tian ZC, Wang B, Shan CX, Zhang W, Jiang DZ, Qiu M. A meta‐ therapists, psychologists); to inform strategic planning and resource analysis of randomized controlled trials to compare long‐term out- management by health care authorities (e.g., regional and national comes of nissen and toupet fundoplication for gastroesophageal reflux disease. PLoS One. 2015;10(6):e0127627. https://doi.org/10. authorities, health care institutions, hospital administration author- 1371/journal.pone.0127627 ities); and to inform patients wishing to obtain an overview of the 5. Limpert PA, Naunheim KS. Partial versus complete fundoplication: is condition of interest and its management. there a correct answer? Surg Clin. 2005;85(3):399–410. https://doi. The use of recommendations contained herein must be informed org/10.1016/j.suc.2005.01.008 by supporting evidence accompanying each recommendation and by 6. Fuchs KH, Babic B, Breithaupt W, Dallemagne B, Fingerhut A, Fur- nee E, et al. European Association of Endoscopic Surgery (EAES). research evidence that might not have been published by the time of EAES recommendations for the management of gastroesophageal writing the present document. Users must thus base their actions reflux disease. Surg Endosc. 2014;28(6):1753–73. https://doi.org/10. informed by newly published evidence at any given point in time. 1007/s00464‐014‐3431‐z. Epub 2014 May 2 The information in the guideline should not be relied upon as 7. Slater BJ, Dirks RC, McKinley SK, Ansari MT, Kohn GP, Thosani N, et al. SAGES guidelines for the surgical treatment of gastroesopha- being complete or accurate, nor should it be considered as inclusive geal reflux (GERD). Surg Endosc. 2021;35(9):4903–17. https://doi. of all proper treatments or methods of care or as a statement of org/10.1007/s00464‐021‐08625‐5. Epub 2021 Jul 19 the standard of care. With the rapid development of scientific 8. EAES Guidelines Subcommittee: living review of surgical guidelines. knowledge, new evidence may emerge between the time the Accessed January 1, 2022. https://eaes.eu/about%2Deaes/commit tees/consensus%2Dguideline%2Dsubcommittee%2Dprojects/%23 guideline is developed and when it is published or read. The living%2Dreview guideline is not continually updated and may not reflect the most 9. Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE handbook for recent evidence. The guideline addresses only the topics specifically grading quality of evidence and strength of recommendations. identified therein and is not applicable to other interventions, dis- Accessed 1 January 2022. https://gdt.gradepro.org/app/handbook/ handbook.html. Updated October 2013 eases, or stages of diseases. This guideline does not mandate any 10. AGREE‐S: AGREE II extension for guidelines on surgical in- particular course of medical care. Further, the guideline is not terventions. Accessed January 1, 2022. https://agree‐s.org/ intended to substitute the independent professional judgment of 11. Institute of medicine (US) committee on standards for developing the treating provider, as the guideline does not necessarily account trustworthy clinical practice guidelines: clinical practice guidelines we can trust. 2011. for individual variation among patients. 12. Qaseem A, Forland F, Macbeth F, Ollenschläger G, Phillips S, van der Even if evidence on a topic suggests a specific diagnostic and/or Wees P. Board of trustees of the guidelines international network. treatment action, users and especially health professionals may need Guidelines international network: toward international standards to decide against the suggested or recommended action in view of for clinical practice guidelines. Ann Intern Med. 2012;156(7): circumstances related to patient values, preferences, co‐morbidities 525–31. https://doi.org/10.7326/0003‐4819‐156‐7‐201204030‐ 00009 and disease characteristics; available human, monetary and material 13. Garritty C, Gartlehner G, Nussbaumer‐Streit B, King VJ, Hamel C, resources; and healthcare infrastructures. Kamel C, et al. Cochrane Rapid Reviews Methods Group offers EAES provides this guideline on an ‘as is’ basis, and makes no evidence‐informed guidance to conduct rapid reviews. J Clin Epi- warranty, express or implied, regarding the guideline. demiol. 2021;130:13–22. https://doi.org/10.1016/j.jclinepi.2020.10. 007. Epub 2020 Oct 15 14. Papakonstantinou T, Nikolakopoulou A, Higgins JPT, Egger M, Sal- ORCID anti G. CINeMA: software for semiautomated assessment of the Sheraz Markar https://orcid.org/0000-0002-4040-5681 confidence in the results of network meta‐analysis. Campbell Syst Luigi Bonavina https://orcid.org/0000-0002-4880-1670 Rev. 2020;16(1):1–15. https://doi.org/10.1002/cl2.1080 15. Brignardello‐Petersen R, Bonner A, Alexander PE, Siemieniuk RA, Ivan D. Florez https://orcid.org/0000-0002-0751-8932 Furukawa TA, Rochwerg B, et al, GRADE Working Group. Advances Bright Huo https://orcid.org/0000-0003-4999-4328 in the GRADE approach to rate the certainty in estimates from a Stavros A. Antoniou https://orcid.org/0000-0002-4630-6748 network meta‐analysis. J Clin Epidemiol. 2018;93:36–44. https://doi. 996 - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL org/10.1016/j.jclinepi.2017.10.005. Epub 2017 Oct 17. Erratum in: J 30. Mavridis D, Giannatsi M, Cipriani A, Salanti G. A primer on Clin Epidemiol. 2018 Jun, 98:162 network meta‐analysis with emphasis on mental health. Evid Based 16. Brignardello‐Petersen R, Murad MH, Walter SD, McLeod S, Ment Health. 2015;18(2):40–6. https://doi.org/10.1136/eb‐2015‐ Carrasco‐Labra A, Rochwerg B, et al, GRADE Working Group. 102088 GRADE approach to rate the certainty from a network meta‐anal- 31. Rücker G, Schwarzer G. Reduce dimension or reduce weights? ysis: avoiding spurious judgments of imprecision in sparse networks. Comparing two approaches to multi‐arm studies in network meta‐ J Clin Epidemiol. 2019;105:60–7. https://doi.org/10.1016/j.jclinepi. analysis. Stat Med. 2014;33(25):4353–69. https://doi.org/10.1002/ 2018.08.022. Epub 2018 Sep 22 sim.6236. Epub 2014 Jun 18 17. Yepes‐Nuñez JJ, Li SA, Guyatt G, Jack SM, Brozek JL, Beyene J, et al. 32. Rücker G, Krahn U, Konig J, Efthimiou O, Davies A, Papakon- Development of the summary of findings table for network meta‐ stantinou T, et al. Netmeta: network meta analysis using frequentist analysis. J Clin Epidemiol. 2019;115:1–13. https://doi.org/10.1016/ methods. R package version 2.1‐0. Accessed 1 January 2022. https:// j.jclinepi.2019.04.018. Epub 2019 May 2 cran.r‐project.org/web/packages/netmeta/index.html 18. Andreou A, Watson DI, Mavridis D, Francis NK, Antoniou SA. 33. Rücker G, Schwarzer G. Ranking treatments in frequentist network Assessing the efficacy and safety of laparoscopic antireflux pro- meta‐analysis works without resampling methods. BMC Med Res cedures for the management of gastroesophageal reflux disease: a Methodol. 2015;15(1):58. https://doi.org/10.1186/s12874‐015‐ systematic review with network meta‐analysis. Surg Endosc. 0060‐8 2020;34(2):510–20. https://doi.org/10.1007/s00464‐019‐07208‐9. 34. Higgins JP, Jackson D, Barrett JK, Lu G, Ades AE, White IR. Consis- Epub 2019 Oct 18 tency and inconsistency in network meta‐analysis: concepts and 19. Antoniou SA. Appendix files for UEG and EAES Rapid Guideline: models for multi‐arm studies. Res Synth Methods. 2012;3(2):98–110. update systematic review, network meta‐analysis, CINeMA and https://doi.org/10.1002/jrsm.1044 GRADE assessment, and evidence‐informed European recommen- 35. Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in dations on surgical management of GERD. Accessed 1 June 2022. mixed treatment comparison meta‐analysis. Stat Med. 2010;29(7‐ https://osf.io/xwdyj/ 8):932–44. https://doi.org/10.1002/sim.3767 20. Antoniou SA. Protocol for the EAES rapid guideline on the man- 36. Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. agement of GERD. Accessed 1 June 2022. https://eaes.eu/wp‐ Graphical tools for network meta‐analysis in STATA. PLoS One. content/uploads/2022/01/Protocol‐UEG‐EAES‐Rapid‐Guideline‐Up 2013;8(10):e76654. https://doi.org/10.1371/journal.pone.0076654 date‐systematic‐review‐network‐meta‐analysis‐CINeMA‐and‐GRAD 37. Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE handbook: 5 E‐assessment.pdf quality of evidence. Accessed 1 January 2022. https://gdt.gradepro. 21. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, et al. org/app/handbook/handbook.html%23h.9rdbelsnu4iy GRADE guidelines: 2. Framing the question and deciding on impor- 38. Nikolakopoulou A, Higgins JPT, Papakonstantinou T, Chaimani A, Del tant outcomes. J Clin Epidemiol. 2011;64(4):395–400. https://doi. Giovane C, Egger M, et al. CINeMA: an approach for assessing confi- org/10.1016/j.jclinepi.2010.09.012. Epub 2010 Dec 30 dence in the results of a network meta‐analysis. PLoS Med. 2020; 22. Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, et al. 17(4):e1003082. https://doi.org/10.1371/journal.pmed.1003082 The GRADE Working Group clarifies the construct of certainty of 39. Florez ID, Veroniki AA, Al Khalifah R, Yepes‐Nuñez JJ, Sierra JM, evidence. J Clin Epidemiol. 2017;87:4–13. https://doi.org/10.1016/j. Vernooij RWM, et al. Comparative effectiveness and safety of in- jclinepi.2017.05.006. Epub 2017 May 18 terventions for acute diarrhea and gastroenteritis in children: a sys- 23. Tsujimoto Y, Fujii T, Tsutsumi Y, Kataoka Y, Tajika A, Okada Y, et al. tematic review and network meta‐analysis. PLoS One. 2018;13(12): Minimal important changes in standard deviation units are highly e0207701. https://doi.org/10.1371/journal.pone.0207701 variable and no universally applicable value can be determined. J 40. Roks DJ, Koetje JH, Oor JE, Broeders JA, Nieuwenhuijs VB, Haze- Clin Epidemiol. 2022;145:92–100. https://doi.org/10.1016/j.jclinepi. broek EJ. Randomized clinical trial of 270° posterior versus 180° 2022.01.017. Epub ahead of print anterior partial laparoscopic fundoplication for gastro‐oesophageal 24. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan‐a reflux disease. Br J Surg. 2017;104(7):843–51. https://doi.org/10. web and mobile app for systematic reviews. Syst Rev. 2016;5(1): 1002/bjs.10500. Epub 2017 Mar 13 210. https://doi.org/10.1186/s13643‐016‐0384‐4 41. Roks DJ, Broeders JA, Baigrie RJ. Long‐term symptom control of 25. Hopkins RJ, Irvine T, Jamieson GG, Devitt PG, Watson DI. Long‐term gastro‐oesophageal reflux disease 12 years after laparoscopic Nis- follow‐up of two randomized trials comparing laparoscopic Nissen sen or 180° anterior partial fundoplication in a randomized clinical 360° with anterior 90° partial fundoplication. Br J Surg. trial. Br J Surg. 2017;104(7):852–6. https://doi.org/10.1002/bjs. 2020;107(1):56–63. https://doi.org/10.1002/bjs.11327. Epub 2019 10473. Epub 2017 Feb 3 Sep 10 42. Cai W, Watson DI, Lally CJ, Devitt PG, Game PA, Jamieson GG. Ten‐ 26. Rudolph‐Stringer V, Bright T, Irvine T, Thompson SK, Devitt PG, year clinical outcome of a prospective randomized clinical trial of Game PA, et al. Randomized trial of laparoscopic nissen versus laparoscopic Nissen versus anterior 180(degrees) partial fundopli- anterior 180 degree partial fundoplication ‐ late clinical outcomes at cation. Br J Surg. 2008;95(12):1501–5. https://doi.org/10.1002/bjs. 15 to 20 years. Ann Surg. 2022;275(1):39–44. https://doi.org/10. 6318 1097/SLA.0000000000004643 43. Lundell L, Attwood S, Ell C, Fiocca R, Galmiche JP, Hatlebakk J, et al. 27. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, LOTUS trial collaborators. Comparing laparoscopic antireflux sur- et al. RoB 2: a revised tool for assessing risk of bias in randomised gery with esomeprazole in the management of patients with chronic trials. BMJ. 2019;366:l4898. https://doi.org/10.1136/bmj.l4898 gastro‐oesophageal reflux disease: a 3 year interim analysis of the 28. Current version of RoB 2. Accessed January 1, 2022. https://www. LOTUS trial. Gut. 2008;57(9):1207–13. https://doi.org/10.1136/gut. riskofbias.info/welcome/rob‐2‐0‐tool/current‐version‐of‐rob‐2 2008.148833. Epub 2008 May 9 29. Salanti G. Indirect and mixed‐treatment comparison, network, or 44. Mickevicius A, Endzinas Z, Kiudelis M, Jonaitis L, Kupcinskas L, multiple‐treatments meta‐analysis: many names, many benefits, Maleckas A, et al. Influence of wrap length on the effectiveness of many concerns for the next generation evidence synthesis tool. Res Nissen and Toupet fundoplication: a prospective randomized study. Synth Methods. 2012;3(2):80–97. https://doi.org/10.1002/jrsm. Surg Endosc. 2008;22(10):2269–76. https://doi.org/10.1007/s0046 1037. Epub 2012 Jun 11 4‐008‐9852‐9. Epub 2008 Apr 9 MARKAR ET AL. - 997 45. Booth MI, Stratford J, Jones L, Dehn TC. Randomized clinical trial of gastro‐oesophageal reflux disease. Br J Surg. 2005;92(6):700–6. laparoscopic total (Nissen) versus posterior partial (Toupet) fundo- https://doi.org/10.1002/bjs.4933 plication for gastro‐oesophageal reflux disease based on preopera- 59. Ludemann R, Watson DI, Jamieson GG, Game PA, Devitt PG. Five‐year tive oesophageal manometry. Br J Surg. 2008;95(1):57–63. https:// follow‐up of a randomized clinical trial of laparoscopic total versus doi.org/10.1002/bjs.6047 anterior 180 degrees fundoplication. Br J Surg. 2005;92(2):240–3. 46. Watson DI, Jamieson GG, Pike GK, Davies N, Richardson M, Devitt https://doi.org/10.1002/bjs.4762 PG. Prospective randomized double‐blind trial between laparo- 60. Watson DI, Jamieson GG, Lally C, Archer S, Bessell JR, Booth M, scopic Nissen fundoplication and anterior partial fundoplication. Br et al. International Society for Diseases of the Esophagus‐‐Austral- J Surg. 1999;86(1):123–30. https://doi.org/10.1046/j.1365‐2168. asian Section. Multicenter, prospective, double‐blind, randomized 1999.00969.x trial of laparoscopic nissen vs anterior 90 degrees partial fundopli- 47. Strate U, Emmermann A, Fibbe C, Layer P, Zornig C. Laparoscopic cation. Arch Surg. 2004;139(11):1160–7. https://doi.org/10.1001/ fundoplication: nissen versus Toupet 2 year outcome of a prospec- archsurg.139.11.1160 tive randomized study of 200 patients regarding preoperative 61. Daud WN, Thompson SK, Jamieson GG, Devitt PG, Martin IJ, Wat- esophageal motility. Surg Endosc. 2008;22(1):21–30. https://doi.org/ son DI. Randomized controlled trial of laparoscopic anterior 180° 10.1007/s00464‐007‐9546‐8. Epub 2007 Nov 20 partial versus posterior 270° partial fundoplication. ANZ J Surg. 48. Guérin E, Bétroune K, Closset J, Mehdi A, Lefèbvre JC, Houben JJ, 2015;85(9):668–72. https://doi.org/10.1111/ans.12476. Epub 2013 et al. Nissen versus Toupet fundoplication: results of a randomized Nov 28 and multicenter trial. Surg Endosc. 2007;21(11):1985–90. https:// 62. Chrysos E, Athanasakis E, Pechlivanides G, Tzortzinis A, Mantides A, doi.org/10.1007/s00464‐007‐9474‐7 Xynos E. The effect of total and anterior partial fundoplication on 49. Wang B, Zhang W, Liu S, Du Z, Shan C, Qiu M. A Chinese randomized antireflux mechanisms of the gastroesophageal junction. Am J Surg. prospective trial of floppy Nissen and Toupet fundoplication for 2004;188(1):39–44. https://doi.org/10.1016/j.amjsurg.2003.10.023 gastroesophageal disease. Int J Surg. 2015;23(Pt A):35–40. https:// 63. Qin M, Ding G, Yang H. A clinical comparison of laparoscopic Nissen doi.org/10.1016/j.ijsu.2015.08.074. Epub 2015 Sep 7 and Toupet fundoplication for gastroesophageal reflux disease. J 50. Engström C, Lönroth H, Mardani J, Lundell L. An anterior or posterior Laparoendosc Adv Surg Tech. 2013;23(7):601–4. https://doi.org/10. approach to partial fundoplication? Long‐term results of a randomized 1089/lap.2012.0485. Epub 2013 Apr 24 trial. World J Surg. 2007;31(6):1221–5. https://doi.org/10.1007/ 64. Hagedorn C, Jönson C, Lönroth H, Ruth M, Thune A, Lundell L. Ef- s00268‐007‐9004‐8. Epub 2007 Apr 24; discussion 1226‐7 ficacy of an anterior as compared with a posterior laparoscopic 51. Anvari M, Allen C, Marshall J, Armstrong D, Goeree R, Ungar W, et al. partial fundoplication: results of a randomized, controlled clinical A randomized controlled trial of laparoscopic nissen fundoplication trial. Ann Surg. 2003;238(2):189–96. https://doi.org/10.1097/01.sla. versus proton pump inhibitors for treatment of patients with chronic 0000080821.08262.53 gastroesophageal reflux disease: one‐year follow‐up. Surg Innovat. 65. Koch OO, Kaindlstorfer A, Antoniou SA, Luketina RR, Emmanuel K, 2006;13(4):238–49. https://doi.org/10.1177/1553350606296389 Pointner R. Comparison of results from a randomized trial 1 year 52. Djerf P, Montgomery A, Hallerbäck B, Håkansson HO, Johnsson F. after laparoscopic Nissen and Toupet fundoplications. Surg Endosc. One‐ and ten‐year outcome of laparoscopic anterior 120° versus 2013;27(7):2383–90. https://doi.org/10.1007/s00464‐013‐2803‐0. total fundoplication: a double‐blind, randomized multicenter study. Epub 2013 Jan 30 Surg Endosc. 2016;30(1):168–77. https://doi.org/10.1007/s00464‐ 66. Chrysos E, Tsiaoussis J, Zoras OJ, Athanasakis E, Mantides A, Kat- 015‐4177‐y. Epub 2015 Apr 1 samouris A, et al. Laparoscopic surgery for gastroesophageal reflux 53. Mehta S, Bennett J, Mahon D, Rhodes M. Prospective trial of lapa- disease patients with impaired esophageal peristalsis: total or partial roscopic nissen fundoplication versus proton pump inhibitor therapy fundoplication? J Am Coll Surg. 2003;197(1):8–15. https://doi.org/ for gastroesophageal reflux disease: seven‐year follow‐up. J Gas- 10.1016/S1072‐7515(03)00151‐0 trointest Surg. 2006;10(9):1312–6. https://doi.org/10.1016/j.gassur. 67. Broeders JA, Broeders EA, Watson DI, Devitt PG, Holloway RH, 2006.07.010. Discussion 1316‐7 Jamieson GG. Objective outcomes 14 years after laparoscopic 54. Woodcock SA, Watson DI, Lally C, Archer S, Bessell JR, Booth M, anterior 180‐degree partial versus nissen fundoplication: results et al. International Society fir Disease of the Esophagus— from a randomized trial. Ann Surg. 2013;258(2):233–9. https://doi. australasian Section. Quality of life following laparoscopic anterior org/10.1097/SLA.0b013e318278960e 90°versus Nissen fundoplication: results from a multicenter ran- 68. Aye RW, Swanstrom LL, Kapur S, Buduhan G, Dunst CM, Knight A, domized trial. World J Surg. 2006;30(10):1856–63. PMID: et al. A randomized multiinstitution comparison of the laparoscopic 16983477. https://doi.org/10.1007/s00268‐005‐0623‐7 Nissen and Hill repairs. Ann Thorac Surg. 2012;94(3):951–7. https:// 55. Spence GM, Watson DI, Jamiesion GG, Lally CJ, Devitt PG. Single doi.org/10.1016/j.athoracsur.2012.04.083. Epub 2012 Jul 20; center prospective randomized trial of laparoscopic Nissen versus discussion 957‐8 anterior 90° fundoplication. J Gastrointest Surg. 2006;10(5):698–705. 69. Watson DI, Devitt PG, Smith L, Jamieson GG. Anterior 90° partial vs PMID: 16713542. https://doi.org/10.1016/j.gassur.2005.10.003 Nissen fundoplication‐‐5 year follow‐up of a single‐centre rando- 56. Mahon D, Rhodes M, Decadt B, Hindmarsh A, Lowndes R, Beck- mised trial. J Gastrointest Surg. 2012;16(9):1653–8. https://doi.org/ ingham I, et al. Randomized clinical trial of laparoscopic Nissen 10.1007/s11605‐012‐1920‐8. Epub 2012 May 26 fundoplication compared with proton‐pump inhibitors for treatment 70. Zornig C, Strate U, Fibbe C, Emmermann A, Layer P. Nissen vs Toupet of chronic gastro‐oesophageal reflux. Br J Surg. 2005;92(6):695–9. laparoscopic fundoplication. Surg Endosc. 2002;16(5):758–66. https://doi.org/10.1002/bjs.4934 https://doi.org/10.1007/s00464‐001‐9092‐8. Epub 2002 Feb 8 57. Baigrie RJ, Cullis SN, Ndhluni AJ, Cariem A. Randomized double‐ 71. Cao Z, Cai W, Qin M, Zhao H, Yue P, Li Y. Randomized clinical trial of blind trial of laparoscopic Nissen fundoplication versus anterior laparoscopic anterior 180° partial versus 360° Nissen fundoplica- partial fundoplication. Br J Surg. 2005;92(7):819–23. https://doi.org/ tion: 5 year results. Dis Esophagus. 2012;25(2):114–20. https://doi. 10.1002/bjs.4803 org/10.1111/j.1442‐2050.2011.01235.x. Epub 2011 Aug 24 58. Cookson R, Flood C, Koo B, Mahon D, Rhodes M. Short‐term cost 72. Fibbe C, Layer P, Keller J, Strate U, Emmermann A, Zornig C. effectiveness and long‐term cost analysis comparing laparoscopic Esophageal motility in reflux disease before and after fundoplica- Nissen fundoplication with proton‐pump inhibitor maintenance for tion: a prospective, randomized, clinical, and manometric study. 998 - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL Gastroenterology. 2001;121(1):5–14. https://doi.org/10.1053/gast. fundoplication: four randomized trials. Ann Surg. 2012;255(4): 2001.25486 637–42. https://doi.org/10.1097/SLA.0b013e31824b31ad 73. Anvari M, Allen C, Marshall J, Armstrong D, Goeree R, Ungar W, 83. Galmiche JP, Hatlebakk J, Attwood S, Ell C, Fiocca R, Eklund S, et al. et al. A randomized controlled trial of laparoscopic Nissen fundo- Laparoscopic antireflux surgery vs esomeprazole treatment for plication versus proton pump inhibitors for the treatment of patients chronic GERD: the LOTUS randomized clinical trial. JAMA. 2011; with chronic gastroesophageal reflux disease (GERD): 3 year out- 305(19):1969–77. https://doi.org/10.1001/jama.2011.626 comes. Surg Endosc. 2011;25(8):2547–54. https://doi.org/10.1007/ 84. Håkanson BS, Lundell L, Bylund A, Thorell A. Comparison of lapa- s00464‐011‐1585‐5. Epub 2011 Apr 22 roscopic 270° posterior partial fundoplication vs total fundoplication 74. Goeree R, Hopkins R, Marshall JK, Armstrong D, Ungar WJ, Goldsmith for the treatment of gastroesophageal reflux disease: a randomized C, et al. Cost‐utility of laparoscopic Nissen fundoplication versus clinical trial. JAMA Surg. 2019;154(6):479–86. https://doi.org/10. proton pump inhibitors for chronic and controlled gastroesophageal 1001/jamasurg.2019.0047 reflux disease: a 3 year prospective randomized controlled trial and 85. Spechler SJ, Hunter JG, Jones KM, Lee R, Smith BR, Mashimo H, economic evaluation. Value Health. 2011;14(2):263–73. https://doi. et al. Randomized trial of medical versus surgical treatment for re- org/10.1016/j.jval.2010.09.004 fractory heartburn. N Engl J Med. 2019;381(16):1513–23. https:// 75. Raue W, Ordemann J, Jacobi CA, Menenakos C, Buchholz A, Hart- doi.org/10.1056/NEJMoa1811424 mann J. Nissen versus Dor fundoplication for treatment of gastro- 86. Bell R, Lipham J, Louie B, Williams V, Luketich J, Hill M, et al. esophageal reflux disease: a blinded randomized clinical trial. Dig Laparoscopic magnetic sphincter augmentation versus double‐dose Surg. 2011;28(1):80–6. https://doi.org/10.1159/000323630. Epub proton pump inhibitors for management of moderate‐to‐severe 2011 Feb 4 regurgitation in GERD: a randomized controlled trial. Gastrointest 76. Khan M, Smythe A, Globe J, Stoddard CJ, Ackroyd R. Randomized Endosc. 2019;89(1):14–22. https://doi.org/10.1016/j.gie.2018.07. controlled trial of laparoscopic anterior versus posterior fundopli- 007. Epub 2018 Jul 18 cation for gastro‐oesophageal reflux disease. ANZ J Surg. 2010; 87. Bell R, Lipham J, Louie BE, Williams V, Luketich J, Hill M, et al. 80(7‐8):500–5. https://doi.org/10.1111/j.1445‐2197.2009.05197.x Magnetic sphincter augmentation superior to proton pump in- 77. Nijjar RS, Watson DI, Jamieson GG, Archer S, Bessell JR, Booth M, hibitors for regurgitation in a 1‐year randomized trial. Clin Gastro- et al. International Society for the Diseases of the Esophagus‐ enterol Hepatol. 2020;18(8):1736–43. https://doi.org/10.1016/j.cgh. Australasian Section. 5 year follow‐up of a multicenter, double‐ 2019.08.056. Epub 2019 Sep 10 blind randomized clinical trial of laparoscopic Nissen vs anterior 88. Djerf P. Laparoscopic nissen versus anterior partial fundoplication. 90 degrees partial fundoplication. Arch Surg. 2010;145(6):552–7. Accessed 1 January 2022. https://clinicaltrials.gov/ct2/show/NCT0 https://doi.org/10.1001/archsurg.2010.81 1669330 78. Shaw JM, Bornman PC, Callanan MD, Beckingham IJ, Metz DC. 89. Chiu PW. A prospective randomized trial comparing laparoscopic Long‐term outcome of laparoscopic Nissen and laparoscopic Toupet nissen against anterior partial fundoplication in treating gastro- fundoplication for gastroesophageal reflux disease: a prospective, esophageal reflux disease among Chinese patients. Accessed 1 randomized trial. Surg Endosc. 2010;24(4):924–32. https://doi.org/ January 2022. https://clinicaltrials.gov/ct2/show/NCT00480285 10.1007/s00464‐009‐0700‐3. Epub 2009 Sep 30 79. Khan MA, Smythe A, Globe J, Stoddard CJ, Ackroyd R. Randomized controlled trial of laparoscopic Nissen versus Lind fundoplication for S U P P O R T I N G I N F O RM A T I O N gastro‐oesophageal reflux disease. Scand J Gastroenterol. 2009; Additional supporting information can be found online in the Sup- 44(3):269–75. https://doi.org/10.1080/00365520802495552 porting Information section at the end of this article. 80. Koch OO, Antoniou SA, Kaindlstorfer A, Asche KU, Granderath FA, Pointner R. Effectiveness of laparoscopic total and partial fundo- plication on extraesophageal manifestations of gastroesophageal reflux disease: a randomized study. Surg Laparosc Endosc Percuta- How to cite this article: Markar S, Andreou A, Bonavina L, neous Tech. 2012;22(5):387–91. https://doi.org/10.1097/SLE.0b013 Florez ID, Huo B, Kontouli K‐M, et al. UEG and EAES rapid e31825efb5b 81. Koch OO, Kaindlstorfer A, Antoniou SA, Asche KU, Granderath FA, guideline: Update systematic review, network meta‐analysis, Pointner R. Laparoscopic Nissen versus Toupet fundoplication: CINeMA and GRADE assessment, and evidence‐informed objective and subjective results of a prospective randomized trial. European recommendations on surgical management of Surg Endosc. 2012;26(2):413–22. https://doi.org/10.1007/s00464‐ GERD. United European Gastroenterol J. 2022;10(9):983–98. 011‐1889‐5. Epub 2011 Sep 5 82. Broeders JA, Roks DJ, Jamieson GG, Devitt PG, Baigrie RJ, Watson DI. https://doi.org/10.1002/ueg2.12318 Five‐year outcome after laparoscopic anterior partial versus Nissen