Background
Gastro-esophageal reflux disease (GERD) is one of the most common gastrointestinal diseases in which the gastric contents flow into the esophagus through the incompetent lower esophageal sphincter (LES) and can cause troublesome symptoms and complications [
1]. According to epidemiology studies, GERD affects 10–28 % of Europeans [
2] and 3–7 % of Asians [
3] (with an increase in prevalence in some Asian countries), which leads to a considerable healthcare burden and low quality of life.
Currently, the therapy approaches of GERD include lifestyle modifications, proton pump inhibitor-based pharmacologic therapy and surgical intervention [
4]. Fundoplication has achieved an established role in the management of complicated GERD [
5‐
7]. In the last two decades, many studies including randomized controlled trials (RCTs) and meta-analyses have shown that laparoscopic surgery is as effective and safe as open surgery for the treatment of GERD, while reducing the hospital stay and incidence of complications [
8‐
10].
There are two major anti-reflux procedures: 360° total (Nissen) fundoplication and 270° partial (Toupet) fundoplication. Currently laparoscopic Nissen fundoplication (LNF) is the most common surgical procedure for the management of GERD offering promising long-term outcomes [
11] and has been recommended as a choice of surgical therapy by the European Study Group for Antireflux Surgery and the Society of American Gastrointestinal Endoscopic Surgeons [
12]. Nevertheless, LNF can induce functional disorders, such as dysphagia, gas-bloating and an inability to belch. Compared to LNF, several surgeons have stated that laparoscopic Toupet fundoplication (LTF) has a lower prevalence of postoperative complications while obtaining a similar control of reflux [
13], but, several studies have failed to show a significant difference between them [
14,
15]. Also, whether preoperative esophageal motility (EM) should be considered when surgeons select a procedure has not been elucidated. Hence, the controversy regarding the optimal surgical method continues.
Several systematic reviews and meta-analyses have compared outcomes between laparoscopic partial fundoplication and LNF up until 2013. However, generalization of all types of partial fundoplication into one category in a review is not appropriate [
16‐
18]. In the past 3 years, several RCTs [
19‐
21] published comparison between the value of LNF and LTF. Hence, it is necessary to synthesize data from those RCTs with existing RCTs in a meta-analysis to re-evaluate outcomes so that evidence for optimal clinical practice can be provided.
Methods
This meta-analysis was conducted and the results were described according to the PRISMA statement [
22].
Search strategy
Following electronic databases were searched till October 2015: PubMed, Medline, Embase, Cochrane Library (issue 10, 2015) and Springerlink. A manual search was also performed to identify trials in the reference lists of the articles acquired. Only articles written in English were searched. A search strategy using disease-specific terms (e.g., gastro-esophageal reflux disease), management-specific terms (e.g., laparoscopic anti-reflux fundoplication) and terms related to surgical procedures (e.g., Nissen, Toupet, total and partial) were adopted.
Inclusion criteria and exclusion criteria
Inclusion criteria were: (i) RCTs comparing efficacy and adverse outcomes of LNF and 270° LTF; (ii) age ≥16 years; (iii) laparoscopic procedure was carried out in all patients; (iv) duration of follow-up ≥12 months; (v) raw data could be extracted from studies to calculate outcomes; (vi) patients were diagnosed definitively preoperatively.
Exclusion criteria were: (i) non-RCTs; (ii) trials comparing total and non-posterior partial fundoplication (e.g., total vs. anterior fundoplication); (iii) fundoplications were carried out with laparotomy; (iv) trials involving patients aged <16 years; (v) studies published repeatedly in different journals; (vi) studies for which raw data could not be extracted to obtain pooled results and the corresponding author could not provide data requested.
Outcomes of interest and definitions
Outcome parameters were described as below. Subjective evaluation: patient satisfaction with the intervention, postoperative heartburn and regurgitation (defined as subjective persistence of reflux and/or recurrence on a dichotomous scale compared with the preoperative state). Objective evaluation: DeMeester scores on 24-h pH monitoring, LES pressure, and endoscopic esophagitis. Prevalence of perioperative complications, postoperative complications, postoperative dilatation for dysphagia, reoperation, operating time, duration of hospitalization, and mortality were also evaluated. Among the outcomes mentioned above, patient satisfaction, postoperative heartburn and dysphagia were regarded as primary outcome parameters, and the others were regarded as secondary outcome parameters.
Two reviewers extracted details from selected studies independently. Data comprised (i) information provided and the quality of the research: first author, publication year, study population characteristics, study design, sample size, follow-up duration, and inclusion/exclusion criteria; and (ii) outcomes analysis, including beneficial and adverse results. Disagreements between reviewers were resolved by discussion and consensus. If data were missing, the authors of the original studies were contacted to provide the relevant information. Outcomes of interest of repeated RCTs in which the study population arose from the same cohort published in different journals at different phases were extracted based on the article that was published most recently.
Statistical analysis
Data extracted from eligible trials were integrated with Review Manager 5.3 provided by the Cochrane Collaboration. Outcomes reported by two or more studies were pooled in the meta-analysis. Dichotomous and continuous outcomes were presented as risk ratio (RR) and standard mean difference (SMD) respectively. Dichotomous outcomes were pooled using the Mantel-Haenszel method, while continuous outcomes were pooled using the inverse variance method. The fixed-effects model was used if heterogeneity was absent (χ
2 test,
P > 0.1 and
I
2
< 50 %); otherwise the random-effects model was used [
23]. If excessive heterogeneity was present, data were first rechecked. If heterogeneity persisted, sensitivity or subgroup analyses were undertaken to explore its causes. Subgroup analysis was performed to assess the impact of follow-up duration and EM.
Quality assessment
According to Cochrane criteria guidelines, all included studies were evaluated to ascertain if methodological bias was present [
24].
Discussion
Since the first laparoscopic fundoplication was undertaken for GERD in 1991, laparoscopic surgery has been the “gold standard” for patients with medical-refractory GERD [
31]. Although LNF is classic procedure for the treatment of GERD, it is challenged by LTF with less functional disorders.
In the last two decades, several RCTs have been conducted to compare LNF with LTF, but the results have been inconclusive. Between 2010 and 2015, four meta-analyses [
32‐
35] comparing LNF with LTF were published. However, in the included trials, LTF was done with various circumferences (200°–270°), which would induce heterogeneity between trials and reduce the reliability and accuracy of the findings of the meta-analyses above. In addition, these meta-analyses neglected the comparability of baseline information of LNF and LTF. Several trials [
19‐
21] of large-scale and long-term follow-up have been published in recent years, so re-evaluation and syntheses of data in existing trials are important.
According to the findings from the present meta-analysis, the following conclusions can be drawn. First, the prevalence of patient satisfaction was similar between LNF and LTF, and was high (LNF, 89.17 %; LTF, 87.42 %). Second, LTF was as effective as LNF with respect to symptom control. Third, the prevalence of postoperative dysphagia was higher after LNF, but with increasing duration of follow-up, the difference between two arms disappeared. Fourth, LNF was associated with higher LES pressure.
This report demonstrated that the operating time of LTF was longer than that of LNF, which might be due to the fact that the gastric fundus and both sides of the esophagus should be secured, respectively. Prevalence of perioperative complications between the two groups was not significantly different. But it is notable that Strate et al. [
27] and Booth et al. [
28] reported a perforation in the fundal wrap and an episode of perioperative bleeding after LTF. And Guérin et al. [
26] also observed in-hospital bleeding. This phenomenon may be because the esophagus does not have a serosal layer and gastric fundus and both sides of the esophagus wall need to be sutured together, which may increase the risk of perforation and bleeding.
Heartburn and regurgitation are typical symptoms of GERD. Our report showed that LNF and LTF were similar with regard to reflux control. Importantly, objective parameters are not always in accordance with the symptoms or complaints of patients [
27,
36,
37]. The value of laboratory examinations is limited for the diagnosis and evaluation of therapeutic efficacy for GERD, so the definition of “recurrent GERD” based on laboratory measurements alone may not be appropriate. Symptoms combined with objective parameters should be the main indications for surgical therapy, a view that is consistent with that of Tan et al [
34].
With better control of GERD, LNF was previously regarded as the standard treatment for GERD. However, this concept has been challenged owing to postoperative functional disorders. We have shown that LNF is associated with a higher incidence of postoperative dysphagia, gas-bloating and inability to belch. However, subgroup analyses suggested that differences in the prevalence of dysphagia between two techniques disappeared over time. Furthermore, two decades follow-up results of a RCT [
38] comparing open Nissen and Toupet demonstrated no difference in the prevalence of postoperative complications. As a reasonable and accurate index for assessing the efficacy of surgical treatment for GERD [
39,
40], the patient satisfaction was high (≈90 %) and comparable between the two arms.
As for whether preoperative EM was an indication for “tailored therapy”, the subgroup analyses showed that EM was not correlated with postoperative dysphagia, indicating that “tailored therapy” according to EM was not indicated, which was consistent with other reports [
30,
33]. It should be noted that the definition of EM in the included studies was not consistent, which might affect the ability to reach true conclusion.
With regard to reoperation, the most common causes were complications, recurrence of reflux symptoms, and others conditions. Specific data could not be obtained, so subgroup analyses based on causes could not be done.
For baseline information’s comparability was uncertain in two studies [
19,
27], sensitivity analyses were conducted by removing these two studies for three primary outcomes, thought the results were not altered, which was neglected in previous meta-analyses [
32‐
35].
In contrast to previous reviews [
32‐
34], some large-scale studies included in our report were published in the last 3 years, and outcomes were evaluated with long-term follow-up (12–60 months). Hence, the results of our meta-analysis are of credibility and stability. The limitations of our meta-analysis were: (i) methodological quality of some studies included in the meta-analysis was poor (lack of blinding and description of randomization processes); (ii) the number of included studies and sample size was small; and (iii) definitions or evaluation criteria in different studies were not consistent.
Abbreviations
BMI, body mass index; DSGV, division of short gastric vessels; EM, esophageal motility; GERD, gastro-esophageal reflux disease; HR, high risk; LES, lower esophageal sphincter; LNF, laparoscopic Nissen fundoplication; LR, low risk; LTF, laparoscopic Toupet fundoplication; NR, not report; RCTs, randomized controlled trials; RR, risk ratio; SMD, Standard mean difference; UR, Unclear risk
Acknowledgements
We would like to appreciate the reviewers for their helpful suggestions or comments on this paper.