PF indicates posterior partial fundoplication; TF, total fundoplication; and QoL, quality of life.
A, Physical component score (PCS). B, Mental component score (MCS). Patients were randomized to either a posterior partial fundoplication (PF, n = 159) or a total fundoplication (TF, n = 151). Box and whisker plots indicate the median value (horizontal line), IQR (box), and 10th and 90th percentile range (whiskers). The circles represent outliers.
eTable. SF-36 Outcomes (Physical (PCS) and Mental Component Score, MCS) at Different Follow-up Time Points
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Analatos A, Håkanson BS, Ansorge C, Lindblad M, Lundell L, Thorell A. Clinical Outcomes of a Laparoscopic Total vs a 270° Posterior Partial Fundoplication in Chronic Gastroesophageal Reflux Disease: A Randomized Clinical Trial. JAMA Surg. 2022;157(6):473–480. doi:10.1001/jamasurg.2022.0805
Does the previously reported advantage of a partial 270° fundoplication, in terms of fewer mechanical adverse effects at 2 years after operation, remain after more than 15 years of follow-up?
Long-term follow-up data were obtained from 310 of 456 patients with chronic gastroesophageal reflux disease originally enrolled and randomized in this double-blind randomized clinical trial. Partial fundoplication and total fundoplication controlled long-term gastroesophageal reflux disease symptoms and quality of life equally well; however, the superiority of a partial fundoplication, as reflected by less dysphagia previously recorded during the first years after surgery, seemed to have disappeared when assessed a decade later.
There seem to be no important long-term differences in the functional outcomes of the 2 studied antireflux surgical procedures.
The efficacy of fundoplication operations in the management of gastroesophageal reflux disease (GERD) has been documented. However, few prospective, controlled series report long-term (>10 years) efficacy and postfundoplication concerns, particularly when comparing various types of fundoplication.
To compare long-term (>15 years) results regarding mechanical complications, reflux control, and quality of life between patients undergoing posterior partial fundoplication (PF) or total fundoplication (TF) (270° vs 360°) in surgical treatment for GERD.
Design, Setting, and Participants
A double-blind randomized clinical trial was performed at a single center (Ersta Hospital, Stockholm, Sweden) from November 19, 2001, to January 24, 2006. A total of 456 patients were recruited and randomized. Data for this analysis were collected from August 1, 2019, to January 31, 2021.
Laparoscopic 270° posterior PF vs 360° TF.
Main Outcomes and Measures
The main outcome was dysphagia scores for solid and liquid food items after more than 15 years. Generic (36-Item Short-Form Health Survey) and disease-specific (Gastrointestinal Symptom Rating Scale) quality of life and proton pump inhibitor consumption were also assessed.
Among 407 available patients, relevant data were obtained from 310 (response rate, 76%; mean [SD] age, 66 [11.2] years; 184 [59%] men). A total of 159 were allocated to a PF and 151 to a TF. The mean (SD) follow-up time was 16 (1.3) years. At 15 years after surgery, mean (SD) dysphagia scores were low for both liquids (PF, 1.2 [0.5]; TF, 1.2 [0.5]; P = .58) and solids (PF, 1.3 [0.6]; TF, 1.3 [0.5]; P = .97), without statistically significant differences between the groups. Reflux symptoms were equally well controlled by the 2 types of fundoplications as were the improvements of quality-of-life scores.
Conclusions and Relevance
The long-term findings of this randomized clinical trial indicate that PF and TF are equally effective for controlling GERD and quality of life in the long term. Although PF was superior in the first years after surgery in terms of less dysphagia recorded, this difference did not prevail when assessed a decade later.
ClinicalTrials.gov Identifier: NCT04182178
Worldwide, surgical practice has long advocated total fundoplication, as originally designed by Nissen,1 to be the criterion standard surgical procedure in the management of chronic gastroesophageal reflux disease (GERD).2-4 Adverse effects of the procedure, predominantly of a mechanical nature,5-7 have not only raised some concern about the procedure but also stimulated further research to control those adverse effects by, for example, technical modifications.8
One of these modifications was to perform a partial wrap, either anterior or posterior.9,10 A series of randomized clinical trials11-14 have reported that partial fundoplication (PF) is followed by fewer postoperative adverse effects and complications of a mechanical nature and associated with fewer problems with flatulence and bloating compared with a total fundoplication (TF). A critical observation was that the advantages of a partial posterior wrap were not gained at the expense of an inferior control of reflux, assessed by symptoms or objective means.15,16 However, on the basis of data from single-institution experiences as well as retrospective analyses, TF has been claimed to be superior to PF in terms of gastroesophageal reflux control, durability of wrap function, number of subsequent herniations, and recurrence rates of GERD.17-21 This claim prompted attempts to further modify PF to encircle 270° of the esophageal circumference. The objective was to maintain the mechanical advantages of the partial wrap without compromising the efficacy to control gastroesophageal reflux.22
Five-year outcomes from a large, double-blind randomized clinical trial22 of 456 patients with chronic GERD found no difference between a 270° posterior PF and a Nissen TF in terms of acid reflux control, GERD symptom control, or improvement of quality of life (QoL). However, the finding of a statistically significant difference in dysphagia scorings in favor of PF after 1 and 2 years suggested that PF can be recommended before the more commonly performed TF for surgical treatment of GERD. The issue of durability of these effects is, however, always of highest concern. In this article, we report on the outcome from this trial cohort after more than 15 years of follow-up.
Originally, 456 patients with chronic GERD were recruited into this randomized clinical trial, of whom 229 were randomized to receive a PF and 227 to receive a TF. The trial was performed at a single center (Ersta Hospital, Stockholm, Sweden) from November 19, 2001, to January 24, 2006. Relevant clinical characteristics, surgical details, and clinical outcomes have been described in detail previously.22 The Regional Ethics Committee in Stockholm approved the study protocol. The study was performed in accordance with the Declaration of Helsinki.23 Patients were invited by mail to participate in the study, and after receiving written information, patients who were willing to participate returned their signed informed consent form together with the completed study questionnaires. The study protocol and an English-translated version can be found in Supplement 1. The study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.
Available patients were invited to participate in the long-term follow-up study. Patients who were deceased, who had been unregistered from the study, or who had emigrated were excluded from the follow-up. Data for this study were collected from August 1, 2019, to January 31, 2021. All included patients completed the same QoL questionnaires as in the original study.22 These questionnaires included the Swedish version of the generic 36-Item Short-Form Health Survey (SF-36),24 the disease-specific Gastrointestinal Symptom Rating Scale (GSRS),25 and a specific dysphagia score questionnaire.26 In the SF-36, data are presented as physical component score (PCS) and mental component score (MCS), respectively. Each subscale score reaches a maximum value of 100, where higher values reflect better health status.24 The GSRS is a validated questionnaire containing 5 dimensions of abdominal symptoms (gastroesophageal reflux, abdominal pain, indigestion, obstipation, and diarrhea).25 The subscales are presented by use of a 7-point Likert scale, and the mean item scores of the respective domains were used throughout the study. A higher value represents more severe symptoms.
For the dysphagia scoring, a standardized specific questionnaire was used, which includes a 4-graded scale to describe dysphagia for solid and liquid food components, respectively, as follows: 1 indicates no episodes of dysphagia; 2, less than 1 episode of dysphagia per day; 3, 1 to 3 episodes of dysphagia per day; and 4, more than 3 episodes of dysphagia per day.26
Based on the predominant finding during the first 2 years after surgery,22 the primary outcome for this specific long-term follow-up was dysphagia scoring for solid food and liquid items 15 years after the surgery. Secondary outcomes were QoL, reflux symptoms, proton pump inhibitor (PPI) consumption, and additional operation rates.
Values are presented as means and standard deviations unless otherwise stated. An intention-to-treat analysis was applied. Comparisons of parametric data were performed by use of a 2-sided t test, whereas for nonparametric data, the Mann-Whitney test and χ2 or Fisher exact test were used when appropriate. For intragroup comparisons vs the baseline at the various follow-up time points (repeated measures), the Friedman test was used, and post hoc analysis was performed by using the Wilcoxon matched pair test. A 2-tailed P < .05 was considered statistically significant. Patients with missing values were not included in the analysis for the time point(s) during which data were missing. Statistical analysis was performed using the SPSS software, version 26.0 (SPSS Inc).
The sample size calculation was based on the findings of a difference of 30% (1.3 [0.9] vs 1.7 [1.2]) in dysphagia scores for solids at 2 years postoperation in the original study.22 To detect this difference at the time of the long-term follow-up with a 95% probability and power of 80%, 141 patients were needed in each group.
Of the 456 originally enrolled patients, 43 patients were deceased, and 6 patients were not available for inclusion at the time of the follow-up for other reasons. Thus, 407 patients were available and invited to participate in the long-term follow-up (Figure 1). Specifically, during the time elapsed since the operation, 70 patients were lost to follow-up in the PF group (17 patients died, 2 patients developed dementia, 2 emigrated, and 49 patients did not respond to the invitation to participate), and 76 patients were lost in the TF group (26 died, 1 emigrated, 1 unregistered from the study, and 48 did not respond). The causes of death in both groups were cardiopulmonary (n = 11), nongastrointestinal malignant neoplasms (n = 7), gastrointestinal malignant neoplasms except esophageal cancer (n = 6), and unidentified causes (n = 18). One patient in the PF group died of esophageal adenocarcinoma. The final response rate was 76% (310 of 407 patients). Of these 310 patients (mean [SD] age, 66 [11.2] years; 184 [59%] male), 159 were originally allocated to a PF and 151 to a TF.
The demographic characteristics are presented in Table 1, showing well-matched groups from which follow-up information was retrieved. The mean (SD) follow-up time was 16 (1.3) years in both groups (P = .64), and the mean (SD) age at follow-up was 65 (11.0) years in the PF group and 67 (11.3) years in the TF group (P = .11). During the follow-up, 4 patients (3%) underwent additional operations in the PF group and 10 (7%) in the TF group, all because of recurrent GERD (P = .08).
The mean dysphagia scores for solid and liquid food items during the entire follow-up period are presented in Table 2. Compared with before surgery, marked improvements were found in dysphagia scores in both groups at 1 year after surgery, which were maintained during the entire follow-up period. Over time, there were only minor changes in the dysphagia scores. Some small differences between the groups were noted, including a statistically significant difference in favor of PF for liquid dysphagia at 1 year postoperation (mean [SD] score for PF, 1.0 [0.3]; for TF, 1.1 [0.4]; P = .04) and for solids at 1 year (mean [SD] score for PF, 1.1 [0.4]; for TF, 1.3 [0.6]; P = .01) and 2 years (mean [SD] score for PF, 1.1 [0.4]; for TF, 1.3 [0.6]; P = .01) postoperation. At 15 years after the surgery, mean (SD) dysphagia scores for solid and liquid remained low but now without statistically significant differences between the groups (liquids: mean [SD] score for PF, 1.2 [0.5]; for TF, 1.2 [0.5]; P = .58; solids: mean [SD] score for PF, 1.3 [0.6]; for TF, 1.3 [0.5]; P = .97).
The SF-36 scores recorded during the 15 years after surgery are presented in Figure 2 and in the eTable in Supplement 2. Both the mean (SD) PCS and MCS were significantly improved compared with baseline at all follow-up points and without statistically significant differences between the groups (mean [SD] baseline PCS scores of 42.0 [10.3] in the PF group and 41.3 [9.8] in the TF group and mean [SD] baseline MCS scores of 41.6 [12.9] in the PF group and 41.5 [12.8] in the TF group vs mean [SD] PCS scores 15 years postoperatively of 44.4 [11.4] in the PF group and 44.1 [13.1] in the TF group and mean [SD] MCS scores 15 years postoperatively of 48.2 [11.1] in the PF group and 48.5 [11.9] in the TF group; P < .001).
At 15 years after surgery, all of the scores in the various domains of the GSRS were low, without any statistically significant differences between the 2 groups (Table 3). The reflux domain was immediately and markedly reduced after surgery and remained so throughout the long-term follow-up. For the remaining domains, only abdominal pain (mean [SD] abdominal pain, 2.1 [1.1] in the PF group vs baseline and 1.9 [1.0] in the TF group vs baseline; P < .001) and indigestion (mean [SD] indigestion, 2.7 [1.2] in the PF group vs baseline and 2.6 [1.1] in the TF group vs baseline; P < .001) were significantly improved compared with baseline values at 15 years postoperatively, again without any intergroup differences.
Fifteen years after surgery, 38 of 159 patients (24%) in the PF group and 42 of 149 patients (28%) in the TF group used PPIs daily. Among these patients, 25 of 38 (66%) in PF group and 28 of 42 (67%) in the TF group reported that they used PPIs to control GERD symptoms. The remaining 13 patients in the PF group and 14 patients in the TF group reported daily PPI intake for a variety of reasons, such as swallowing difficulties and/or abdominal pain.
The main finding in this prospective, double-blind randomized clinical trial with a long follow-up is that irrespective of whether a 270° posterior PF or a 360° TF was used, the effects in terms of reflux control, swallowing function, and self-reported QoL were well sustained after more than 15 years of follow-up. In addition, the previously observed advantage of a posterior partial repair, in the form of fewer mechanical adverse effects, disappeared over time.
In the current long-term follow-up, we observed the same differences in dysphagia for liquid and solid food as were previously reported at 1 and 2 years after surgery for the entire patient cohort during the 5-year follow-up.22 This finding indicates that the current study cohort is representative of the entire group of patients initially included. Moreover, our findings are also in corroboration with previous studies13,27 with smaller groups of patients with GERD presented at 11.5 and 18 years of follow-up.
In this study, we focused on swallowing difficulties and did not capture specific information on other alleged adverse postoperative concerns, such as bloating and flatulence. On the other hand, by the use of the well-validated GSRS instrument, we were able to monitor general abdominal symptoms and complaints and found a similar improvement in both groups for dimensions that could be considered relevant for patients after antireflux surgery, such as reflux, abdominal pain, and indigestion.
An explanatory factor behind the observed convergence toward equality for mechanical adverse effects between the procedures may be related to chronic functional adaptation and coping with the postoperative situation. An additional explanation may be some loosening of the total wrap over time, thereby allowing a more smooth passage of the bolus through the gastroesophageal junction.28 This possibility is supported by the observation in another study29 that an increasing number of patients undergoing TF reported an ability to vomit at a late follow-up.29 However, our data suggest that a slight increase in dysphagia scores in the PF group rather than a reduction of the scores in the TF group might account for the lack of difference between the groups at long-term follow-up.
This study contributes to the growing number of randomized trials with a sufficiently long follow-up period to allow firm conclusions regarding the efficacy over time of reflux control related to the design of the repair. Previous reports30,31 have often focused on the surgical reduction and repair of the hiatal hernia. Thus, it does not seem to be of major relevance whether an anterior or a posterior crural repair is performed.32,33 Our study protocol mandated a crural repair be performed, which may have contributed to the low risk of paraesophageal reherniation, irrespective of which of the 2 types of reconstructions patients were allocated to. Suffice to say that we did not specifically monitor any long-term changes in the hiatal anatomy, but none of our patients had a subsequent operation for a paraesophageal hernia.
Some concern has been raised about the level of reflux control offered by the partial fundoplication compared with the pronounced effect reported after a total wrap.21 From a symptom control perspective, it seems reasonable to conclude that these previously reported differences in esophageal acid exposure do not necessarily translate into a clinically relevant difference in symptom control.11,29 In addition, the 270° wrap has been reported to offer the same degree of pH control as the 360° counterpart.22 The findings in the current study of well-controlled reflux symptoms after a 270° posterior PF at more than 15 years further corroborate this notion. However, there remains a worrying continuous increase over time in the number of patients who are prescribed PPIs, presumably to control recurrent GERD symptoms.34-36 During the first 5 years of follow-up for patients in the current study, this figure was at the 10% level, which increased to 25% at 15 years. Previous observations indicate that few of those who are prescribed PPIs after antireflux surgery are ultimately found to have recurrent GERD,37-39 which was also confirmed in our study cohort. Nevertheless, this trend over time, which has also been observed in population-based studies,35,36 constitutes a concern that needs to be addressed in future studies aiming to identify underlying specific causes of the need for PPI treatment and specifying relevant management strategies.
Strengths of the study include a large cohort of well-matched, randomized patients who were followed for more than 15 years and the use of a well-validated instrument for assessment of multiple aspects of outcome after antireflux surgery.
The study also has some limitations. Adherence to the follow-up protocol is always a problem when covering such a long period as in the current study (>15 years). Among the 456 patients with GERD originally enrolled, 407 were available for long-term follow-up. Of these, we obtained data from 310, resulting in a response rate of 76%. This significant but inevitable loss of patients for long-term follow-up may be 1 factor contributing to the observed convergence toward equity between the procedures regarding mechanical adverse effects over time. Furthermore, it cannot be excluded that those who did not respond may experience more adverse effects and failures, but we have no reason to believe that patients allocated to a particular study group should be overrepresented in this respect. Indeed, higher response rates are always aimed for, but because we obtained long-term follow-up data for approximately 150 patients in both groups, the follow-up rate should be considered acceptable. We were unable to obtain objective measurements regarding reflux control, such as ambulatory 24-hour pH monitoring, but the GSRS reflux domain represents a strong and valid instrument to monitor the level of reflux control.
In this randomized clinical trial of patients with GERD, laparoscopic PF and TF led to similar long-term outcomes for dysphagia control and QoL improvement. Although PF was superior in the first years after surgery in terms of less dysphagia recorded, this difference did not prevail when assessed a decade later.
Accepted for Publication: January 9, 2022.
Published Online: April 20, 2022. doi:10.1001/jamasurg.2022.0805
Corresponding Author: Apostolos Analatos, MD, Department of Surgery, Nyköping Hospital, Olrogsväg 1, 611 39 Nyköping, Sweden (email@example.com).
Author Contributions: Dr Analatos had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Analatos and Håkanson contributed equally to this work.
Concept and design: Analatos, Håkanson, Lundell, Thorell.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Analatos, Håkanson, Ansorge, Lundell.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Analatos, Håkanson, Ansorge, Thorell.
Obtained funding: Analatos, Håkanson, Ansorge, Thorell.
Administrative, technical, or material support: Håkanson, Lindblad.
Supervision: Håkanson, Ansorge, Lindblad, Lundell, Thorell.
Conflict of Interest Disclosures: Dr Thorell has received unrestricted research grants (to institution) from Ethicon Endo-Surgery, is a member of an advisory board for Novo Nordisk and Ethicon Endo-Surgery, and has received speaker honoraria from Kabi Fresenius and Ethicon Endo-Surgery. No other disclosures were reported.
Funding/Support: Dr Thorell received grants from the Stockholm City Council and the Erling-Persson Foundation (grant 140604). Dr Analatos received grants from the Centre for Clinical Research Sörmland, Uppsala University.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 3.