Laparoscopic fundoplication for gastro‐oesophageal reflux disease (GORD) in adults
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To compare the effectiveness of total versus partial laparoscopic fundoplication surgery on the outcomes of GORD‐related symptoms, postoperative side effects, quality of life and clinical indicators of gastric functioning in adults with GORD.
Background
Description of the condition
Gastro‐oesophageal reflux disease (GORD) is a term referring to the spectrum of symptoms associated with gastro‐oesophageal reflux. GORD is a chronic, relapsing condition and the main symptoms include intermittent heartburn (a burning sensation that radiates upwards from the sternum), acid regurgitation (reflux), vomiting, chest pain and difficulty swallowing (dysphagia) (Wileman 2010). The majority of patients with GORD have mild symptoms and require little, if any, therapy but significant health service costs arise from patients with more severe disease. Up to 20% of adults in 'westernised' countries experience heartburn, reflux or both at least weekly and GORD is one of the commonest reasons for attending primary care services (Dent 2005; Liker 2005).
Management of GORD should aim to alleviate symptoms, allow healing of damaged oesophageal mucosa and prevent secondary complications (Freston 2004). There is a clinical spectrum of disease severity, from mild symptoms that require medication (e.g. proton pump inhibitors (PPIs)), to those with severe symptoms that often require surgical management. The impact of chronic symptoms on quality of life is considerable; patients with severe GORD often experience sleep disturbance, reduced concentration and interference with physical activity (Hungin 2005). Whilst PPIs are generally assumed to be safe, there are potential side effects and also concerns regarding the impact of long‐term medication use from prolonged acid suppression (Leufkens 1997). Given the considerable cost and potential risks associated with lifetime medical therapy, surgical treatment of chronic GORD can prove an attractive option.
Description of the intervention
Gastro‐oesophageal surgery is an alternative to long‐term medical therapy for GORD. The most common surgical technique is 'fundoplication' which involves the formation of a stomach wrap, where a section of the stomach fundus is wrapped around the lower oesophagus and stitched into place. This stomach wrap helps prevent the reflux of gastric acid when the stomach contracts.
Fundoplication can be performed as open or laparoscopic surgery, although most procedures are now performed laparoscopically. There are two broad categories of fundoplication: either a total (360 degree) wrap or partial wrap. The original 'Nissen' fundoplication uses a full 360 degree wrap. The Nissen procedure involves mobilisation of the oesophagus and the posterior fundus of the stomach is wrapped around the lower oesophagus before a portion of the fundus is translocated anterior to the oesophagus. Sutures are then used to secure the wrap (Khan 2009). Debate exists as to whether division of the short gastric vessels during the Nissen procedure reduces postoperative dysphagia (DeMeester 1986; Watson 1997).
In contrast to a total 360 degree wrap, partial fundoplication involves wrapping the lower oesophagus to a lesser extent. Many different partial fundoplication techniques exist and 90, 120, 180 and 270 degree wraps have been described (Laws 1997; Watson 2000). These partial techniques can be categorised as anterior or posterior fundoplications, according to the anatomical relationship of the stomach fundus to the lower oesophagus (Watson 2007). The commonest partial fundoplication is the posterior 'Toupet' procedure, where the fundus is wrapped posteriorly, encircling 270 degrees of the oesophagus. Anterior fundoplication techniques, such as Watson and Lind, follow the same principles but the fundal wrap is formed to the lower oesophagus.
How the intervention might work
The laparoscopic approach to fundoplication has become the gold standard for the surgical management of GORD (Watson 2000). Wrapping the fundus of the stomach around the lower oesophagus, either completely or partially, creates a high‐pressure zone, reducing gastro‐oesophageal reflux. The proposed benefits of partial fundoplication include fewer postoperative side effects, such as reduced belching and dysphagia, compared to total (Nissen) fundoplication. However, others report that total fundoplication is more effective than partial fundoplication at reducing reflux (Hagedorn 2002; Krysztopik 2002; Munro 2000; Watson 2004). In contrast, other trials have shown broad equivalence between different laparoscopic approaches (Coster 1997; Lundell 1996).
Why it is important to do this review
Whilst the evidence suggests that laparoscopic fundoplication may produce resolution of reflux symptoms in approximately 90% of patients, there are concerns regarding the risks and side effects of surgical treatment. There are few data on long‐term clinical and functional outcome after laparoscopic surgery. There is a lack of consensus over which fundoplication technique provides the best outcome for patients, hence there is a need for a systematic review to compare alternative laparoscopic fundoplication techniques. The purpose of this review is to assess the effectiveness of alternative laparoscopic fundoplication techniques for the treatment of GORD.
Objectives
To compare the effectiveness of total versus partial laparoscopic fundoplication surgery on the outcomes of GORD‐related symptoms, postoperative side effects, quality of life and clinical indicators of gastric functioning in adults with GORD.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials and quasi‐randomised controlled trials (e.g. allocation by date of birth or day of week) comparing total laparoscopic fundoplication with partial laparoscopic fundoplication as the exclusive operative procedure will be eligible for inclusion. If the method of randomisation has not been described, the trial will still be included but the author will be contacted for further clarification. Trials will be included irrespective of the language in which they are reported.
Types of participants
All adults with a diagnosis of GORD, whether subjectively or objectively defined, judged appropriate for surgical management. These are likely to be people who have had symptoms for longer than 12 months.
Types of interventions
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Total laparoscopic fundoplication surgery, which will be defined as any fundoplication technique using a 360 degree wrap.
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Partial laparoscopic fundoplication surgery, which will be defined as any fundoplication technique using a less than 360 degree wrap.
Types of outcome measures
Primary outcomes
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Gastro‐oesophageal reflux symptoms (heartburn, acid reflux, dysphagia)
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Postoperative symptoms (bloating, inability to belch)
Secondary outcomes
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Quality of life
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Conversion to open surgery
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Other postoperative complications
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Surgical mortality
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Length of hospital stay
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Reoperation rate (other than conversion to open)
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Changes in clinical results (pH monitoring, endoscopy, barium meal)
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Cost, cost consequences or formal economic evaluations (such as cost‐effectiveness or cost utility studies)
We will consider and report definitions and timing of assessment for each outcome.
Search methods for identification of studies
Electronic searches
Searches have been developed and refined in conjunction with the Trials Search Co‐ordinator of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group. We will identify trials by searching the following electronic databases:
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the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register (July 2009);
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the Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library) (Appendix 1);
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MEDLINE 1966 to current (Appendix 2); and
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EMBASE 1980 to current (Appendix 3).
We will constrict search strategies using a combination of subject headings and text words relating to surgical interventions used for the treatment of GORD. We will apply no language restrictions. We will conduct full translations of all non‐English language papers at the University of Aberdeen. We will apply the standard Cochrane search strategy filter for identifying randomised controlled trials to all searches.
Searching other resources
We will search the bibliographies and reference lists of all included studies and review papers in order to identify other potentially suitable studies. We will also handsearch published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology).
We will contact experts in the field and ask them to provide details of outstanding clinical trials and any relevant unpublished materials. We will send letters or email requests to authors of included studies requesting information on unpublished data or ongoing studies.
Data collection and analysis
Selection of studies
Two review authors (CM and JB) will review and screen the titles and abstracts of all trials identified from the electronic searches independently and retrieve all potentially eligible studies in hard copy. We will independently review all potentially eligible studies against the pre‐defined inclusion criteria. We will remove duplicate citations although we will obtain duplicate publications reporting data in more than one paper for full consideration. We will include the most recently published data or data on relevant outcomes in the review.
Data extraction and management
Two authors (CM/JB) will conduct full data extraction, with disagreements resolved by a third author (SW). We will store references using RevMan 5.0 (RevMan 2008). We will include the following information from individual studies on data extraction forms:
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publication details;
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study design, study setting, inclusion/exclusion criteria, method of allocation, risk of bias (described below);
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patient population, e.g. age, type of surgical procedure;
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details of intervention, e.g. total or partial;
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outcome measures;
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adverse effects, side effects; and
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withdrawals, length and method of follow up, proportion followed up.
Assessment of risk of bias in included studies
Two review authors will independently assess the methodological quality of each study using the structure recommended in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). Assessors will not be blinded to the authors of individual trials. We will assess the risk of bias (selection, performance, attrition and detection bias) by appraising the following domains in individual trials.
Sequence generation
Was the allocation sequence adequately generated (e.g. coin toss, random number tables, computer‐generated, other). This will be recorded as yes, no or unclear.
Allocation concealment
Was allocation adequately concealed in a way that would not allow both the investigators and the participants to know or influence the intervention group before an eligible participants is entered into the study (e.g. central randomisation or sequentially numbered, opaque, sealed envelopes)? This will be recorded as yes, no or unclear.
Blinding
We will assess details of blinding participants, personnel (surgeons) and outcome assessors. It is not possible to blind surgeons to the surgical intervention, however we will assess whether participants or outcome assessors were blinded to the intervention. This will be considered for separate outcomes. Blinding will be recorded as yes, no or not possible.
Incomplete outcome data
Were incomplete outcome data adequately addressed? Incomplete outcome data essentially include attrition, exclusions and missing data. If any withdrawals occurred, were they described and reported by treatment group with reasons given? Were clear explanations for withdrawals and dropouts in treatment groups recorded? An example of an adequate method to address incomplete outcome data is the use of intention‐to‐treat analysis (ITT). This will be recorded as yes, no, or unclear.
Selective outcome reporting
Are reports of the study free from suggestion of selective outcome reporting? This will be interpreted as no evidence that statistically non‐significant results might have been selectively withheld from publication (e.g. selective under‐reporting of data or selective reporting of a subset of data). This will be recorded as yes, no or unclear.
Other sources of bias
Was the study apparently free of other problems that could put it at a high risk of bias (e.g. baseline imbalance or the use of an insensitive instrument to measure outcomes)? This will be recorded as yes, no or unclear.
Quality assessment/internal validity
Where a difference in opinion exists, the two review authors will consult an arbiter. We will contact authors for clarification where necessary. We will present quality assessment criteria using the 'Risk of bias' summary table for each included study. This will be generated using the Cochrane RevMan 5.0 program (RevMan 2008). In addition to the individual tables for each study, we will generate a 'Risk of bias' summary figure. This figure will provide a summary of all judgements, using colour format, to display whether there is low, unclear or high risk of bias (Higgins 2008).
Measures of treatment effect
For each outcome, we will calculate summary estimates of treatment effect (with 95% confidence intervals (CI)) for each comparison. For continuous outcomes, we will present the mean differences (MD) when appropriate. For dichotomous outcomes, we will present the risk ratio (RR) when appropriate. We will use an intention‐to‐treat analysis.
Unit of analysis issues
We anticipate that the appropriate unit of analysis will be individual patient, rather than surgical unit, hospital or centre. From our initial pilot screen of the published literature, we expect that included studies will be quasi‐experimental or standard randomised controlled trials (RCTs) where individuals are randomised to an intervention or control group.
Dealing with missing data
Where data are missing or unsuitable for analysis (for example, intention‐to‐treat not used) we will contact study authors to request further information. Where data are missing to the extent that the study cannot be included in the meta‐analysis and attempts to retrieve data have been exhausted, we will present the results in the review and discuss them in the context of the findings.
Assessment of heterogeneity
We will investigate the following factors as potential causes of heterogeneity in the included studies using the framework below.
Clinical diversity
This includes study location and setting, full characteristics of participants (for example, age), co‐morbidity and treatments that participants may be receiving on trial entry. We will consider how outcomes were measured, the definition of outcomes and how they were recorded. Depending upon the extent of the clinical diversity, we will either analyse the studies separately or present them using a narrative approach.
Methodological diversity
This includes assessment of the randomisation process, study quality and analytical method.
Statistical diversity
We will consider and test heterogeneity between trials where appropriate. To test for gross statistical heterogeneity between all trials, we will use the Chi2 test for heterogeneity and will quantify heterogeneity using the I2 statistic (Higgins 2008). If heterogeneity exists, we will explore the data and test whether our planned subgroup analyses explain the heterogeneity.
Assessment of reporting biases
We anticipate that all trials will report the primary and secondary outcomes. We will undertake searches for protocol versions of included trials in PubMed (National Library of Medicine) and through UK and other trial registries, where possible. We will contact study authors to attempt to establish a full data set or reasons for the non‐reporting of certain outcomes.
Data synthesis
We will enter and analyse quantitative data in the Cochrane RevMan program (RevMan 2008). For each outcome, we will calculate summary estimates of treatment effect (with 95% confidence interval (CI)) for each comparison. For continuous outcomes, we will calculate mean differences (MD) when appropriate. For dichotomous outcomes, we will calculate the relative risk (RR). Some outcomes are likely to be rare events (e.g. mortality) and we will consider using the Peto odds ratio (OR) which is the appropriate statistic for rare events. We will use a fixed‐effect model when combining study data. However, if there is significant clinical, methodological or statistical heterogeneity we will use a random‐effects model.
Where possible, we will analyse any time to event data as survival (time to event) outcomes, using the appropriate analytical method (as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008)). Where it is not appropriate to pool data, we will present results using a narrative approach and in table format. There may be a risk of multiple testing given the potential number of data comparisons and we will consider using a stricter threshold for statistical significance (P < 0.01).
Subgroup analysis and investigation of heterogeneity
We will analyse studies according to total or partial laparoscopic fundoplication. If possible, we will conduct subgroup analyses on type of partial fundoplication, e.g. total 360 degree fundoplication versus (a) 180 degree or (b) 270 degree fundoplication wraps. Where possible, we also intend to conduct subgroup analysis to investigate whether division of the short gastric vessels impacts upon outcome.
Sensitivity analysis
We will conduct sensitivity analysis by excluding trials of low methodological quality and consider and discuss the results of this analysis in comparison to overall findings.
