Interventional procedure overview of laparoscopic insertion of a magnetic ring for gastro-oesophageal reflux disease
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Summary of key evidence on laparoscopic insertion of a magnetic ring for GORD
Study 1 Zhuang QJ (2021)
Study type | Systematic review and meta-analysis |
|---|---|
Country | Not reported for individual studies |
Publication period | 2013 to 2020 |
Study population and number | n=1,138 (15 studies) patients with refractory GORD |
Age and sex | Mean age ranged from 42 to 62 years; 52.6% male |
Patient selection criteria | Inclusion criteria: (1) single-arm studies evaluating the efficacy and safety of magnetic sphincter augmentation (MSA) in treating refractory GORD, or comparative studies comparing MSA with PPI or LNF; (2) patients with typical GORD symptoms whose GORD partially responded to PPI and who had pathological reflux confirmed by oesophageal reflux monitoring; (3) included at least 20 patients in the study; and (4) reported postoperative PPI use or GORD-HRQL explicitly as an outcome measure. Exclusion criteria: (1) studies evaluating patients with specific phenotypes of GORD as predominant study patients, such as those evaluating MSA efficacy among patients with large hiatus hernia, Barrett's oesophagus or erosive esophagitis; (2) poorly described diagnostic criteria, unsuitable interventions or outcomes; (3) duplications (for duplicate publications, the one with the largest number of patients was included); (4) studies for which the full text could not be obtained; and (5) reviews, editorials, commentaries, case report or case series, or studies on animals. |
Technique | Laparoscopic insertion of a magnetic ring, PPI or LNF |
Follow up | 5 years |
Conflict of interest/source of funding | None |
Analysis
Study design issues: This systematic review and meta-analysis evaluated the therapeutic effect and safety of MSA in refractory GORD and compared MSA efficacy with PPI or LNF. Primary outcome was the rate of postoperative PPI use, and secondary outcomes included postoperative GORD-HRQL, normalisation of acid exposure time and incidence of procedure-related adverse events.
The favourable outcome of antireflux surgery included a complete and long-lasting alleviation of symptoms, absence of postoperative adverse events and retaining the ability to belch. Symptom relief was defined as complete cessation of PPI and an at least 50% reduction in the GORD-HRQL score compared with their baseline data.
Two authors screened the literatures and extracted the data independently. Any disagreement was revolved by discussion with a third author. For publications that shared the same patient cohort, only those with the most complete follow-up data were extracted for the meta-analysis. Data extraction was done
Study population issues: Of the 15 included studies, there were 10 single-arm studies, 1 RCT (shared the same patient population with different follow-up duration) and 3 cohort studies. Among 10 single-arm studies, there were 8 studies of fair quality and 2 studies of high quality using the methodological index for non-randomised studies. For the comparative studies between MSA and LNF, 2 studies were at low risk of bias and 1 study at high risk using the Newcastle–Ottawa Scale. The study comparing MSA with PPI was of fair quality using the Jadad scale.
Other issues: The efficacy of MSA might be affected by selection bias, patients with less advanced GORD tend to choose MSA while those with severe GORD would turn to fundoplication. Significant heterogeneity was found in analyses of postoperative dysphagia, dilation and reserved ability to belch, and the heterogeneity was probably because of the use of inconsistent assessment criteria.
Key efficacy findings
Number of patients analysed: 1,138 (15 studies)
Pooled rate of postoperative PPI use:
Within 1 year: 13.0% (95% CI 9.9% to 17.4%; Cochrane Q P = 0.12, I2 = 43%; 6 studies, n=631)
Within 2 years: 13.8% (95% CI 8.3% to 20.6%; Cochrane Q P=0.89, I2=0%; 2 studies, n=125)
Within 5 years: 19.4% (95% CI 9.9% to 35.9%; Cochrane Q P=0.13, I2=55%; 2 studies, n=117)
When combining those who completely ceased PPI and those with a 50% reduction in PPI dosage as the 'treatment-responsive' group, the pooled rate of postoperative PPI use was 9.9% (95% CI 7.4% to 12.3%).
Pooled rate of GORD-HRQL improvement (at least 50% reduction in GORD-HRQL):
The total pooled rate of GORD-HRQL improvement was 88% (95% CI 84% to 92%; Cochrane Q P=0.17, I2=40%; 4 studies, n=395).
Pooled rated of normalisation in acid exposure time: 75% in 1 year after MSA (95% CI 68% to 82%; Cochrane Q P=0.29, I2=19%; 3 studies).
Ability to belch: nearly all patients reported the retention of their belching ability (3 studies).
Comparison between MSA and double-dose PPI: 1 RCT
Complete cessation of PPI: 91% compared with 0%
Symptom alleviation (improvement in GORD-HRQL): 81% compared with 8%
Comparison between MSA and LNF:
Daily PPI use after surgery: 148 patients in the MSA group and 146 patients in the LNF group (RR 1.55, 95% CI 0.49 to 4.94, p=0.46, Cochrane Q P=0.27, I2=19%; 2 studies)
GORD-HRQL score: 180 compared with 152 patients (WMD 0.20, 95%CI -1.60 to 2.00, p=0.83; Cochrane Q P=0.79, I2=0%; 3 studies)
Gas-bloat syndrome: 148 compared with 146 patients (RR 0.69, 95% CI 0.51 to 0.93, p=0.01; Cochrane Q P=0.39, I2=0%; 2 studies)
Ability to belch: 170 compared with 152 patients (RR 1.48, 95% CI 0.76 to 2.86, p=0.25; Cochrane Q P<0.00001, I2=92%; 3 studies).
Key safety findings
Postoperative dysphagia was reported in 7 studies:
Pooled incidence of postoperative dysphagia: 29% in 1 year after MSA (95% CI 13% to 46%; Cochrane Q P<0.00001, I2=96%; 6 studies, n=543).
Only one study reported that 3.6% to 5.6% of patients complained of dysphagia 1 year after MSA.
Pooled rate of dilation in 1 year: 7.4% (95% CI 2.9% to 13.7%; Cochrane Q P=0.0005, I2=80%; 5 studies, n=543).
Implant removal in 5-year follow up: n=15 (5 studies, n=543; 14 patients had their implants removed because of persistent dysphasia, chest pain or unresolved GORD symptoms; and 1 reported implant erosion and the device was removed eventually).
Comparison between MSA and double-dose PPI: 1 RCT
MSA: transient dysphagia, 28%; ongoing dysphagia, 4%
Comparison between MSA and LNF:
Postoperative dysphagia: 146 compared with 120 patients (RR 1.21, 95% CI 0.92 to 1.60, p=0.18; Cochrane Q P=0.89, I2=0%; 2 studies)
LNF: retroesophageal abscesses, n=2 (these 2 patients needed further surgical drainage)
Study 2 Guidozzi N (2019)
Study type | Systematic review and meta-analysis |
|---|---|
Country | Not reported for individual studies |
Publication period | Up to 2019 |
Study population and number | n=12,697 (19 studies; MSA, n=12,230; fundoplication, n=467) Patients with GORD |
Age and sex | Not reported |
Patient selection criteria | Inclusion criteria: publications were included if they were cohort or comparative studies investigating MSA for treating GORD including more than 20 patients. Comparative studies were included in a pooled analysis that compared MSA with fundoplication (partial or total) for treating GORD. Exclusion criteria: studies were excluded if they included less than 20 patients receiving MSA, or for comparative studies if MSA was not compared with fundoplication. |
Technique | Laparoscopic insertion of a LINX device Laparoscopic fundoplication |
Follow up | 6 to 44 months when reported |
Conflict of interest/source of funding | Financial support: one author was supported by the National Institute for Health Research. The views expressed were those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Conflicts of interest: none. |
Analysis
Study design issues: This systematic review and meta-analysis primarily compared clinical outcomes of laparoscopic fundoplication with the insertion of a LINX device in managing GORD associated symptoms and complications. The secondary objective was to evaluate the current literature published on the LINX device in substantial case series, in order to identify the true rate of complications, specifically focusing on erosion caused by the device. Two authors examined the abstracts of the articles to determine their suitability for inclusion in the pooled analysis.
Study population issues: The systematic review identified 6 cohort studies that directly compared MSA with fundoplication, comprising of 1,099 patients, 632 having MSA and 467 having fundoplication. This systematic review also included 13 single-arm cohort studies, comprising of 11,598 patients, evaluating clinical outcomes from MSA.
Other issues: A random-effects model was used to correct for the heterogeneity of the analysed data, however, there remained several other limitations. MSA studies might potentially underreport complications associated with device implantation, leading to publication bias. Many MSA studies and comparative studies had relatively small recruitment populations, leading to numerous underpowered studies. Reporting bias was also a limitation to consider, because insertion of the MSA device is a novel procedure, which some surgeons might be technically invested in, driving promising outcomes. Meta-analysis of data on reoperation rates was based upon comparative studies with limited follow up, and might be expected to change over time with more extended follow up. There was also significant variation in the follow-up protocols and specifically length of follow up between individual studies.
Key efficacy findings
Number of patients analysed: 12,697 (19 studies)
13 single-arm cohort studies (n=11,598)
Postoperative PPI therapy: 13.2% (138/1,043)
6 cohort studies (n=1,099): MSA compared with fundoplication
Pooled OR of postoperative PPI therapy: 1.08 (95% CI 0.40 to 2.95; p=0.877; 5 studies)
Heterogeneity: Cochran Q=14.27; p=0.007, I2=72%
WMD of postoperative GORD-HRQOL score: 0.34 (95% CI −0.70 to 1.37; p=0.525; 3 studies)
Heterogeneity: Cochran Q=6.79; p=0.033, I2=70.6%
Pooled OR of postoperative gas bloating: 0.34 (95% CI 0.16 to 0.71; p=0.004; 5 studies)
Heterogeneity: Cochran Q=10.76; p=0.029, I2=62.8%
Pooled OR of ability to belch: 12.34 (95% CI 6.43 to 23.7; p<0.001; 4 studies)
Heterogeneity: Cochran Q=1.46; p=0.669, I2=0%
Key safety findings
13 single-arm cohort studies (n=11,598)
Postoperative dilation: 7.8% (164/2,112)
Device removal or reoperation: 3.3% (69/2,098)
Overall rate of oesophageal erosion: 0.3% (31/11,530)
6 cohort studies (n=1,099): MSA compared with fundoplication
Pooled OR of postoperative dysphagia: 0.94 (95% CI 0.57 to 1.55; p=0.822; 4 studies)
Heterogeneity: Cochran Q=3.77; p=0.288, I2=20.4%
Pooled OR of needing for reoperation: 1.23 (95% CI 0.26 to 5.8; p=0.797; 4 studies)
Heterogeneity: Cochran Q=5.83; p=0.12, I2=48.5%
Study 3 Aiolfi A (2018)
Study type | Systematic review and meta-analysis |
|---|---|
Country | US (n=5) and Europe (n=2) |
Publication period | 2014 to 2017 |
Study population and number | n=1,211 (7 studies; 686 MSA and 525 fundoplication) patients with GORD |
Age and sex | Mean age ranged from 39.3 to 54 years; 51.1% male |
Patient selection criteria | Inclusion criteria: studies comparing laparoscopic MSA with laparoscopic partial or total fundoplication. |
Technique | Laparoscopic insertion of a magnetic ring: LINX® (Thorax Medical) MSA device Fundoplication: total (Nissen) or partial (Toupet) fundoplication |
Follow up | Follow up: 6 to 12 months |
Conflict of interest/source of funding | None |
Analysis
Study design issues: This systematic review and meta-analysis compared early outcomes of MSA and fundoplication. This study was done according to the PRISMA statement. Three authors independently extracted data from eligible studies. Disagreements between authors were resolved by consensus; if no agreement could be reached, a fourth senior author, made the decision. Three investigators independently assessed the methodological quality of the papers using the Newcastle–Ottawa Scale.
Study population issues: Across the 7 studies, the sample size ranged from 24 to 415. There were no randomised controlled studies. All reports were observational, cohort studies. There was one prospective and one propensity score matched study. Each study reached a Newcastle–Ottawa Scale score of 6 or 7 (median 6.8), suggesting a good quality level.
Of the 1,211 patients, the mean BMI ranged from 23.9 to 30; the mean hernia size ranged from 1 to 2 cm; esophagitis grade B or above was present in 15.4% of patients and Barrett oesophagus in 16.2%. The operative time ranged from 42 to 73 minutes in the MSA group and from 76 to 118 minutes in the fundoplication group.
Other issues: The heterogeneity of PPI suspension rate, postoperative gas/bloat symptoms and ability to vomit was moderate in the meta-analysis. Possible sources of heterogeneity might be related to different types of fundoplication, definition and perception of postoperative symptoms, the lack of validated guidelines on PPI dose and timing of PPI suspension.
Key efficacy findings
Number of patients analysed: 1,211 (7 studies)
Regurgitation (2 studies): Comparing with preoperative baseline, a statistically significant improvement was noted for both procedures.
Hospital length of stay: MSA, 13 to 48 hours; fundoplication, 26 to 48 hours.
Estimated pooled mean difference for postoperative GORD-HRQL: −0.48 (95% CI -1.05 to 0.09; p=0.101; 6 studies, n=1,083)
Heterogeneity: I2=0.0%; 95% CI 0.0 to 42.3%; p=0.82
Estimated pooled OR of PPI suspension: 0.81 (95% CI 0.42 to 1.58; p=0.548; 6 studies, n=1,098).
Heterogeneity: I2=63.9%; 95% CI 12.7 to 85.1%; p=0.016
Estimated pooled OR of gas/bloat symptoms: 0.39 (95% CI 0.25 to 0.61; p<0.001; 5 studies, n=1,042)
Heterogeneity: I2=49.6%; 95% CI 0.0 to 81.5%; p=0.09
Estimated pooled OR for the ability to vomit: 10.10 (95% CI 5.33 to 19.15; p<0.001; 6 studies, n=1,048)
Heterogeneity: I2=44%; 95% CI 0.0 to 78.0%; p=0.112
Estimated pooled OR for the ability to belch: 5.53 (95% CI 3.73 to 8.19; p<0.001; 7 studies, n=1,107)
Heterogeneity: I2=8.2%; 95% CI 0.0 to 73.2%; p=0.365
Key safety findings
Overall postoperative morbidity: MSA, 0 to 3%; fundoplication, 0 to 7%. There was no mortality.
Endoscopic dilation needed: MSA, 9.3%; fundoplication, 6.6%
Estimated pooled OR of endoscopic dilation: 1.56 (95% CI 0.61 to 3.95; p=0.119; 5 studies, n=535).
Heterogeneity: I2=35%; 95% CI 0.0 to 75.6%; p=0.19
Reoperation:
MSA, n=13 (12 device removals [1 for erosion] and 1 crural release)
Fundoplication, n=11 (5 herniation of the fundic wrap, 3 persistent GORD, 2 retroesophageal abscess and 1 crural release)
Estimated pooled OR of reoperation: 0.54 (95% CI 0.22 to 1.34; p=0.183; 3 studies, n=1,187)
Heterogeneity: I2=0.0%; 95% CI 0.0 to 4.1%; p=0.814
Study 4 Bell R (2019, 2020)
Study type | Randomised controlled trial (CALIBER; NCT02505945) |
|---|---|
Country | US (21 sites) |
Recruitment period | 2015 to 2017 |
Study population and number | n=134 (laparoscopic insertion of a magnetic ring, n=47; twice-daily PPIs, n=87) Patients with GORD |
Age and sex | Median 46 (range 21 to 76) years; 58% MALE |
Patient selection criteria | Inclusion criteria: patients aged at least 21 years, with moderate-to-severe regurgitation symptoms while having once-daily PPIs for at least 8 weeks and actively seeking alternative, surgical treatment, and with objective confirmation of GORD. Patients also had body mass index <35 kg/m2, abnormal pH testing results, normal oesophageal motility, hiatal hernia of <3 cm by endoscopy, and absence of Barrett's oesophagus or Los Angeles Classification Grade C or D esophagitis. |
Technique | Laparoscopic insertion of a magnetic ring BID PPIs: twice-daily omeprazole, 20 mg, 30 minutes before breakfast and 30 minutes before dinner. |
Follow up | 12 months |
Conflict of interest/source of funding | Conflicts of interest: Reginald Bell, F. Paul Buckley III, Jon Gould, Leena Khaitan, Shanu Kothari, and John Lipham receive honoraria from Ethicon for teaching services. The remaining authors disclose no conflicts. Funding: editorial support for this study was provided by Ethicon, Inc. |
Analysis
Follow-up issues: Of the 152 enrolled patients, 3 patients withdrew before having the MSA procedure, and 1 patient failed to start twice-daily PPI therapy. During the follow-up period, in the twice-daily PPI therapy group, 4 patients lost to follow up and 9 patients discontinued the intervention (8 patients voluntarily withdrew and 1 patient discontinued because of adverse event). One patient who had twice-daily PPI therapy was excluded from analysis because the patient completed 6-month testing off of allocated intervention. In total, 134 patients were included in the 6-month analysis. Between 6 and 12 months, 9 patients were lost to follow up (2 patients in the MSA arm and 7 patients in the MSA crossover arm and step-down PPI arm).
Study design issues: This randomised, controlled, prospective, double-arm, crossover study compared the effects of MSA with twice-daily PPI therapy in patients with GORD (moderate-to-severe regurgitation despite once-daily PPI therapy). The primary end point was the percent of patients in both treatment arms who had elimination of moderate-to-severe regurgitation. Secondary endpoints included: (1) change from baseline scores (while on PPIs) in the GORD-HRQL questionnaire and RDQ, and percentage of patients achieving ≥50% decrease in GORD-HRQL score from baseline; (2) differences between treatment arms in oesophageal reflux parameters (number of reflux episodes and percentage of time with pH <4); and (3) PPI use.
The sample size needed for statistical significance was calculated a priori, with the assumptions that the success rate in the MSA group would be at least 70%, and the difference in success rates between the MSA and twice-daily PPI groups would be at least 30%, with a power calculation of 85%. Given these assumptions, a minimum of 108 patients randomised and followed to 6 months was needed for statistical significance. Additional participants were randomised (n=152) to ensure that a minimum of 50 participants was randomised to MSA and to ensure the sample size requirement of 108 participants, with final end-point data, was met.
Enrolled patients were randomly assigned 2:1 to either twice-daily PPI therapy (n=102) or laparoscopic MSA (primary MSA cohort) (n=50). Patients assigned to the MSA group had laparoscopic MSA by a study investigator trained and experienced in MSA. Postoperatively, patients were instructed to have a soft mechanical diet, including small bites of food regularly, to minimise capsular contracture around the MSA device, and patients were monitored by routine postoperative methods.
At 6 months, eligible patients in the twice-daily PPI arm could cross over to receive a laparoscopic MSA (MSA crossover cohort) if both moderate-severe regurgitation persisted, and impedance-pH testing showed persistent excess reflux burden. Those that did not qualify for crossover were placed on a reduced 20-mg daily dose of omeprazole (step-down cohort).
As a result, 79 patients in the twice-daily PPI arm completed 6-month impedance or pH testing per protocol (85 were completed, but 6 tests were deemed invalid, or the patient was not taking medication as assigned). Of the 79 patients, 31 patients met all crossover requirements and 48 were placed on a reduced dose of 20-mg omeprazole daily as the step-down arm. All patients then had additional evaluation at 12 months, including standardised quality of life surveys, RDQ and GORD-HRQL, as well as specific questions about bloating, diarrhoea, flatulence, and medication use.
Study population issues: At baseline, demographic variables and baseline disease characteristics between both treatment arms were similar, with the exception of the DeMeester scores (MSA, 40.3 [IQR 28.1 to 53.0]; twice-daily PPI, 30.9 [IQR 24.3 to 39.5]), which were significantly higher in the patients assigned to the MSA. The population was 88% white, 5% Hispanic, 3% African American, 3% Asian, and 1% reported other. The average length of PPI use for all patients was 8.4 years. The RCT was included in Zhuang (2021).
Key efficacy findings
Number of patients analysed: 134
Outcomes at 6 months (laparoscopic MSA, n=47; twice-daily PPI, n=87):
Foregut symptom questionnaire – MSA compared with twice-daily PPI:
Relief from moderate-to-severe regurgitation: 89% (42/47, including 79% reported no regurgitation and 10.6% mild regurgitation) compared with 10% (10/101, including 3% reported no regurgitation and 7% mild regurgitation), p<0.001
ITT: 84% (42/50) compared with 10% (10/102), p<0.001
RDQ regurgitation score:
MSA: mean score improved from 4.2 at baseline to 1.6 at 6 months (1=no symptoms, 6=severe)
Twice-daily PPI: mean score was 4.4 at baseline and 4.3 at 6 months
GORD-HRQL:
≥50% improvement in GORD-HRQL score: 81% (38/47) in the MSA group compared with 8% (7/87) in the BID PPI group, p<0.001
MSA: mean GORD-HRQL score decreased from 24 at baseline while having treatment with PPIs to 6 at 6 months while not having treatment with PPIs
Twice-daily PPI: mean GORD-HRQL score was 25 at baseline taking once-daily PPI to 24 at 6 months
Difference between groups: p<0.002
Satisfaction with current condition: 81% (38/47) compared with 2% (2/87)
Discontinued PPI use: 91% (43/47) in the MSA arm at 6 months
Oesophageal reflux parameters: MSA compared with twice-daily PPI
Normal number of reflux episodes (<57): 91% (40/44) compared with 58% (46/79), p<0.001
Normal DeMeester score (<14.7): 89% (39/44) compared with 71% (56/79), p=0.059
Mean DeMeester score: 8 compared with 18, p=0.059
Normal acid exposures by percentage of time with pH<4: 89% (39/44) compared with 75% (59/79), p=0.065
Mean oesophageal acid exposure (percentage of time with pH <4): 2% compared with 5%, p=0.065
Outcomes at 12 months: (MSA, n=44; laparoscopic MSA crossover, n=31; step-down PPI, n=49)
MSA crossover cohort at study completion (6 months postimplantation)
Relief of moderate-severe regurgitation: 94% (29/31) with 68% (21/31) reporting elimination of all regurgitation.
Median RDQ regurgitation scores: improved from 4 (IQR 3.25 to 4.75) off PPI and 3.5 (IQR 2.5 to 4) on PPI at baseline to 0 (IQR 0 to 1.125; p<0.001) at 6 months postimplantation.
Median GORD-HRQL: improved from 26 (IQR, 21 to 30) off PPI and 21 (IQR 18 to 27) on PPI at baseline to 4 (IQR 1 to 7) after MSA implantation (p<0.001).
>50% improvement in baseline GORD-HRQL on PPIs: 80.6% (25/31).
Median RDQ heartburn scores: improved from 3.5 (IQR 2.25 to 4.5) off PPI, 2.38 (IQR 1.5 to 3.6) on PPI to 0 (IQR 0 to 0.5; p<0.001).
Median DeMeester pH score: improved to 6 (IQR 2.2 to 17.6) postoperatively from 31.7 (IQR 25.2 to 36.8) preoperatively (p<0.001).
Normal DeMeester score: 70% (21/30) at 6 months postimplantation.
Step-down PPI cohort at study completion
Relief of moderate-severe regurgitation: 17% (8/48) with 1 of 48 reporting complete regurgitation resolution.
Median RDQ regurgitation, heartburn and GORD-HRQL scores: no statistically significant change from baseline (exact data not reported).
Median DeMeester score tested on daily PPIs remained elevated at 16.7 (IQR 1.9 to 164) and was normal in 54%.
Treatment results based on final treatment arm (MSA or PPI)
Resolution of moderate-severe regurgitation:
MSA patients: 96% (72/75)
Total MSA patients: 93% (71/78)
Primary MSA patients: 98% (43/44)
Twice-daily PPIs patients: 11%
Step-down PPI patients: 19% (8/43) p<0.001 compared with MSA
Complete elimination of regurgitation: MSA, 73% (51/75); step-down PPI, 2%; p<0.001
Median RDQ score:
MSA: 0 (IQR 0 to 0.5) at 12 months post-MSA implantation
PPI: no significant improvement happened (exact data not reported)
GORD-HRQL: baseline, 30±10 off PPIs and 24±10 on daily PPIs; 6 months, 6; 12 months, 5; p<0.001
Successful change of ≥50% from baseline score on PPIs: 6 months, 81% (61/75); 12 months 93% (41/44); p<0.001
Dysphagia scores ≥3 (bothersome every day or worse): baseline, 27% of patients off PPIs, 15% of patients on PPIs; 6 months, 11% (8/75); 12 months (3/44); p=0.0184
Frequent or continuous bloating: baseline, 58% of patients off PPIs, 55% of patients on PPIs; 6 months, 15% (11/75); 12 months, 27% (12/44); p=0.0416.
No change was seen in the patient who had medical treatment.
PPIs discontinuation: MSA, 91% (68/75) at study completion
Median total oesophageal acid exposure at study completion:
all MSA patients: baseline, 10.7% (IQR 7.7% to 13.9%); study completion, 1.3% (IQR, 0.4% to 5.3%), p<0.001
primary MSA patients: baseline, 11.5% (IQR 7.9% to 14.8%) to 1.3% (IQR 0.2% to 5.3%); p<0.001
DeMeester scores in all MSA patients: baseline, 40.5 (IQR 25.7 to 49.5); study completion, 5.3 (IQR 1.2 to 18.5); normalisation, 70% (48/69)
Endoscopic evaluation: esophagitis in patients with confirmed abnormal oesophageal acid exposure was present at baseline in 35% (42/119) of the patients who completed 12-month evaluation (off PPI x 7 days), in 5 of 72 (7%) MSA patients at follow up, and persisted in 8 of 47 (17%) patients maintained on single-dose PPI.
Key safety findings
Laparoscopic MSA group – adverse events at 6 months:
Dysphagia: 32% (n=15), rated mild in 19% (n=9), moderate in 9% (n=4) and severe in 4% (n=2)
Transient dysphagia (minimal or resolved by 6 months): n=13
Ongoing dysphagia: n=2
Intervention needed for postoperative dysphagia:
medication (oral corticosteroids): n=3
endoscopic dilation: n=3
surgical intervention (laparoscopic hiatal hernia repair): n=1
Other adverse events in both groups were minor and did not fit any particular pattern; details were not reported.
Laparoscopic MSA group – adverse events at 12 months:
Dysphagia: 39.6% (n=19) in MSA patients and 33.3% (n=10) in MSA crossover patients
No serious perioperative adverse events happened in any arm of the study.
Study 5 Bonavina L (2020)
Study type | Non-randomised comparative study (registry; NCT01624506) |
|---|---|
Country | Austria, Germany, Italy and UK (22 centres) |
Recruitment period | 2009 to 2014 |
Study population and number | n=631 (MSA, n=465; fundoplication, n=166) patients with GORD |
Age and sex | MSA: mean 46.6 years; 63.7% male Fundoplication: mean 56.3 years; 49.4% male |
Patient selection criteria | Inclusion criteria: patients had a diagnosis of GORD confirmed by abnormal oesophageal acid exposure on a prolonged pH or pH impedance study and chronic reflux symptoms despite the daily use of medical therapy with PPIs. Patients with severe GORD were also included: large hiatal hernia (>3 cm diameter of the oesophageal hiatus), Barrett's oesophagus, motility disorder, and/or Grade C or D esophagitis by Los Angeles classification. Patients without advanced GORD characteristics were considered to have moderate GORD (abnormal oesophageal pH, reflux symptoms despite medication). Exclusion criteria: Patients had known conditions that would make it unlikely for them to complete the 3-year follow up (for example, life expectancy less than 3 years). |
Technique | Laparoscopic insertion of a magnetic ring: The MSA device (LINX system) was placed using the minimal dissection technique. Fundoplication: Nissen fundoplication, 62%; Toupet fundoplication, 31%; other/unspecified fundoplication procedure, 7% |
Follow up | 3 years |
Conflict of interest/source of funding | LB and TH received consulting fees from Torax Medical Inc. In the past. SS received a research grant from Torax Medical Inc. Ms. DeMarchi was an employee of Ethicon. LB, SS and TH declared no current conflict of interest. This work was sponsored and partially funded by Torax Medical, Inc. |
Analysis
Study design issues: This prospective, multicentre, observational registry evaluated the long-term safety and effectiveness outcomes of MSA and fundoplication in clinical practice
Study population issues: At baseline, statistically significant differences in patient's characteristics were detailed in the table below. The proportion of patients with moderate or severe GORD was 90.8% and 9.2%, respectively, in the MSA group and was 18.1% and 81.9% in the fundoplication group. The median GORD-HRQL score was 22.0 in the MSA group and 23.0 in the fundoplication group (p=0.0620).
Measure | MSA (n=465) | Fundoplication (n=166) | P value |
|---|---|---|---|
Age, years (mean±SD) | 46.6±13.6 | 56.3±12.6 | <0.0001 |
BMI (kg/m2) (mean±SD) | 25.7±3.7 | 27.81±4.0 | <0.0001 |
Oesophagitis, % of patients | 0.0130 | ||
None | 53.0% | 40.9% | |
Grade A | 31.7% | 29.6% | |
Grade B | 13.5% | 16.4% | |
Grade C | 1.1% | 8.2% | |
Grade D | 0.7% | 5.0% | |
Barrett's oesophagus, % of patients | 1.7% | 12.7% | <0.0001 |
Hiatal hernia size, % of patients | <0.0001 | ||
None | 19.7% | 7.5% | |
1 to 3 cm | 78.9% | 44.4% | |
>3 cm | 1.4% | 48.1% |
Other issues: Two groups were not comparable in some baseline characteristics, suggesting the results were confounded. Also, the procedure to implant MSA has evolved to include full crural and gastroesophageal junction dissection as opposed to the minimal dissection used in this study. The timeframe for this study would determine if the procedural modifications were relevant to the outcomes in this study population. The current procedure theoretically might provide better outcomes for patients as compared with those done under the "minimal dissection" protocol as the hiatal hernia was often addressed.
Key efficacy findings
Number of patients analysed: 631
Procedure time and hospital stay: MSA, n=459; fundoplication, n=163
Mean procedure time, minutes: MSA, 43.2±19.7 minutes; fundoplication, 79.7±47.7 minutes
Length of stay <24 hours: MSA, 36.1%; fundoplication, 11.4%
Length of stay >48 hours: MSA, 50.8%; fundoplication, 72.3%
238 of 465 patients were German patients, have longer stay built into reimbursement.
Measure | MSA | Fundoplication |
|---|---|---|
Satisfaction with current condition (from GORD-HRQL) | ||
Baseline | 4.6% (21/460; 95% CI 2.7% to 6.5%) | 3.7% (6/164; 95% CI 0.8% to 6.5%) |
12 months | 75.3% (326/433; 95% CI 71.2% to 79.4%) | 77.2% (122/158; 95% CI 70.7% to 83.8%) |
24 months | 78.9% (254/322; 95% CI 74.4% to 83.3%) | 83.3% (90/108; 95% CI 76.3% to 90.4%) |
36 months | 78.2% (230/294; 95% CI 73.5% to 82.9%) | 76.5% (65/85; 95% CI 67.5% to 85.5%) |
GORD interfering with sleep | ||
Baseline | 73.3% (333/454; 95% CI 69.3% to 77.4%) | 78.0% (128/164; 95% CI 71.7% to 84.4%) |
12 months | 11.9% (50/419; 95% CI 8.8% to 15.0%) | 9.6% (15/157; 95% CI 5.0% to 14.2%) |
24 months | 11.7% (37/315; 95% CI 8.2% to 15.3%) | 5.5% (6/109; 95% CI 1.2% to 9.8%) |
36 months | 9.0% (26/290; 95% CI 5.7% to 12.3%) | 10.7% (9/84; 95% CI 4.1% to 17.3%) |
Ability to belch | ||
Baseline | 96.7% (441/456; 95% CI 95.1% to 98.3%) | 93.9% (154/164; 95% CI 90.2% to 97.6%) |
12 months | 96.7% (406/420; 95% CI 94.9% to 98.4%) | 88.5% (138/156; 95% CI 83.4% to 93.5%) |
24 months | 97.2% (308/317; 95% CI 95.3% to 99.0%) | 92.5% (99/107; 95% CI 87.5% to 97.5%) |
36 months | 97.6% (284/291; 95% CI 95.8% to 99.4%) | 91.7% (77/84; 95% CI 85.8% to 97.6%) |
Ability to vomit | ||
Baseline | 96.6% (343/355; 95% CI 94.8% to 98.4%) | 92.0% (115/125; 95% CI 87.2% to 96.8%) |
12 months | 89.7% (191/213; 95% CI 85.6% to 93.8%) | 55.8% (29/52; 95% CI 42.3% to 69.3%) |
24 months | 85.8% (133/155; 95% CI 80.3% to 91.3%) | 52.6% (20/38; 95% CI 36.7% to 68.5%) |
36 months | 91.2% (134/147; 95% CI 86.6% to 95.8%) | 68.0% (17/25; 95% CI 49.8% to 86.2%) |
Use of PPIs | ||
Baseline | 97.8% (453/463; 95% CI 95.6% to100%) | 95.8% (158/165; 95% CI 91.6% to 100%) |
12 months | 18.9% (81/428; 95% CI 15.2% to 22.6%) | 19.7% (31/157; 95% CI 13.5% to 26.0%) |
24 months | 21.4% (74/346; 95% CI 17.1% to 25.7%) | 18.1% (21/116; 95% CI 11.1% to 25.1%) |
36 months | 24.2% (76/314; 95% CI 19.5% to 28.9%) | 19.5% (17/87; 95% CI 11.2% to 27.9%) |
Willingness to have surgery again | ||
12 months | 89.5% (366/409; 95% CI 86.5% to 92.5%) | 91.1% (143/157; 95% CI 86.6% to 95.5%) |
24 months | 90.6% (281/310; 95% CI 87.4% to 93.9%) | 94.4% (102/108; 95% CI 90.1% to 98.8%) |
36 months | 93.1% (270/290; 95% CI 90.2% to 96.0%) | 94.0% (79/84; 95% CI 89.0% to 99.1%) |
Measure | MSA | Fundoplication | ||
|---|---|---|---|---|
Mean GORD-HRQL±SD Median (min, max) | Mean GORD-HRQL±SD Median (min, max; 95% CL) p value | Mean GORD-HRQL±SD Median (min, max) | Mean GORD-HRQL±SD Median (min, max; 95% CL) p value | |
Baseline | n=457 22.0±9.1 22.0 (0.0, 47.0) | n=163 23.6±9.8 23.0 (3.0, 47.0) | ||
Paired baseline/month 12 | n=414 21.9±9.0 22.5 (0.0, 46.0) | n=152 23.4±9.9 23.0 (3.0, 47.0) | ||
Month 12 | n=418 5.2±6.4 3.0 (0.0, 42.0) | n=414 -16.7±10.0 -17.0 (-41.0, 21.0; 95% CL -17.6 to -15.7) p<0.001 | n=154 4.9±7.2 3.0 (0.0, 48.0) | n=152 -18.5±11.5 -19.5 (-45.0, 20.0; 95% CL -20.3 to -16.6) p<0.001 |
Pared baseline/month 24 | n=296 21.6±9.2 22.0 (0.0, 41.0) | n=103 23.9±10.1 24.0 (3.0, 47.0) | ||
Month 24 | n=300 4.9±6.1 2.0 (0.0, 35.0) | n=296 -16.7±10.6 -17.0 (-39.0, 28.0; 95% CL -17.9 to -15.5) p<0.001 | n=105 3.9±4.4 3.0 (0.0, 19.0) | n=103 -20.0±10.0 -20.0 (-45.0, 0.0; 95% CL -22.0 to -18.1) p<0.001 |
Paired baseline/month 36 | n=278 21.3±9.3 22.0 (0.0, 41.0) | n=80 22.5±9.7 22.5 (3.0, 47.0) | ||
Month 36 | n=283 4.6±6.0 3.0 (0.0, 39.0) | n=278 -16.6±10.2 -18.0 (-41.0 to 12.0; 95% CL -17.8 to -15.4) p<0.001 | n=82 4.9±7.1 3.0 (0.0 to 45.0) | n=80 -17.8±10.6 -18.0 (-39.0, 17.0; 95% CL -20.1 to -15.4) p<0.001 |
Timepoint | MSA | Fundoplication | Q7 p value |
|---|---|---|---|
Baseline | |||
Score | 1.0±1.3 | 1.3±1.5 | 0.0227 |
% Q7>3.0 | 15.7% | 24.4% | 0.0174 |
12 months | |||
Score | 0.8±1.1 | 0.6±1.1 | - |
% Q7>3.0 | 8.8% | 7.6% | |
24 months | |||
Score | 0.6±0.9 | 0.4±0.9 | - |
% Q7>3.0 | 4.4% | 4.6% | |
36 months | |||
Score | 0.5±0.9 | 0.4±1.1 | - |
% Q7>3.0 | 3.8% | 4.8% |
Key safety findings
Intraoperative complication rate: MSA (n=459), 1.8%; fundoplication (n=163), 1.2%
Procedure-related complication rate: MSA (n=459), 2.0%; fundoplication (n=163), 1.8%
Measure | MSA (n=459) | Fundoplication (n=163) |
|---|---|---|
Outpatient clinic visits | ||
12 months | 18.9% | 15.3% |
24 months | 14.7% | 12.9% |
36 months | 10.5% | 8.0% |
Return to clinic for GORD symptoms | ||
12 months | 58.5% | 54.2% |
24 months | 80.4% | 86.7% |
36 months | 87.9% | 100% |
Return to clinic because of procedural complaint/complication | ||
12 months | 39.3% | 41.7% |
24 months | 19.2% | 20.0% |
36 months | 15.2% | 0.0% |
Surgical intervention | ||
12 months | 1.6% | 1.9% |
24 months | 1.2% | 0.0% |
36 months | 0.6% | 0.0% |
Device removal | ||
12 months | 1.5% (n=7) | NA |
24 months | 2.0% (n=9) | NA |
36 months | 2.4% (n=11) | NA |
Surgical intervention: The intervention for the MSA group was the removal of the device for dysphagia (45%), ongoing GORD (18%), vomiting/regurgitation (18%), gastric pain (9.5%) and need for MRI (9.5%). There were no complications noted during the removal procedures. Two patients had fundoplication at the time of the device removal. The interventions for the fundoplication group were revision of a Nissen wrap because of ongoing GORD, reherniation and a sigmoid resection secondary to diverticulitis. No complications or ongoing sequelae were reported.
Study 6 Ayazi S (2020a)
Analysis
Follow-up issues: Patients were assessed at 2 weeks, 6 weeks, 6 months, and 12 months after the procedure.
Study design issues: This study evaluated the outcomes of MSA in patients with GORD and determined the factors predicting favourable outcomes. Disease-related quality of life measures included GORD-HRQL and RSI.
Patients were assessed for resolution of their reflux symptoms, use of antisecretory medications, and procedure-related complications. Length of hospital stay, need for readmission within 90 days after operation, and need for postoperative dilation and device removal were also recorded.
A 50% improvement in the GORD-HRQL total score compared with baseline on antisecretory therapy was considered clinically significant. Favourable outcomes were defined as freedom from PPIs and ≥50% improvement in GORD-HRQL total score. Persistent dysphagia was defined as a postoperative dysphagia score >3 on GORD-HRQL "difficulty swallowing" item at 3 months or later after MSA.
Study population issues: At baseline, 46.1% of patients had oesophagitis and 88.1% had hernia (≤3 cm, 67.5%; ≥3 cm, 14.8%; paraesophageal hernia, 5.8%); and the mean DeMeester score was 33.9±29.4.
Key efficacy findings
Number of patients analysed: 553
Patient satisfaction with the procedure: 86.7%
Free of PPI use: 92.7%
≥50% improvement in GORD-HRQL total score: 84%
Measurement | Before operation | After operation | P value |
|---|---|---|---|
GORD-HRQL scoring, mean±SD | |||
Heartburn score | 14.7±8.7 | 3.1±5.8 | <0.001 |
Regurgitation score | 12.7±9.0 | 2.6±5.0 | <0.001 |
Total score | 33.8±18.7 | 7.2±9.0 | <0.001 |
RSI scoring | |||
Difficulty swallowing score, mean±SD | 1.7±1.6 | 1.0±1.3 | <0.001 |
Difficulty swallowing score ≥3 | 33.7% | 15.8% | <0.001 |
22.2±10.9 | 8.7±8.7 | <0.001 | |
LOS resting characteristic (n=109) | |||
Resting pressure, mmHg | 23.1±14.3 | 27.7±14.1 | 0.009 |
Overall length, cm | 2.9±0.8 | 3.2±0.9 | 0.003 |
Intra-abdominal length, cm | 1.0±1.0 | 1.7±1.2 | 0.001 |
Composite pH score | 32.9±31.9 | 12.3±25.9 | <0.001 |
Post measure | Small (sizes 13 and 14; n=327) | Medium (size 15; n=138) | Large (sizes 16 and 17; n=85) | P value |
|---|---|---|---|---|
GORD-HRQL total score, mean±SD | 9.0±11.1 | 6.0±7.7 | 5.7±8.3 | 0.0034 |
Favourable surgical outcome | 77.4% | 85.3% | 80.0% | 0.3521 |
Persistent dysphagia | 20.2% | 12.3% | 11.9% | 0.0991 |
DeMeester score, mean±SD | 7.2±10.2 | 18.8±33.2 | 21.0±42.8 | <0.0001 |
Normalisation of DeMeester score | 82.4% | 69.1% | 65.7% | 0.0349 |
Proportion of patients having a favourable outcome: 80%
Proportion of patients having normalisation of their oesophageal acid exposure: 76.1%
Variable | Parameter (SE) | OR (95% CI) | P value |
|---|---|---|---|
Age (<45 years) | 1.43 (0.66) | 4.17 (1.14 to 15.23) | 0.0305 |
Sex (male) | 0.91 (0.42) | 2.49 (1.09 to 5.66) | 0.0301 |
GORD-HRQL total score (>15) | 2.01 (0.41) | 7.47 (3.32 to 16.81) | <0.0001 |
Abnormal DeMeester score (>14.7) | 0.93 (0.41) | 2.55 (1.14 to 5.68) | 0.0225 |
Discharged home on the day of operation: 93% (n=514)
At least 1 overnight stay: 7% (n=39), with a mean of 1.5±1.0 nights
Key safety findings
Major complications: n=2 (0.4%)
CO2 retention needing reintubation: n=1
mediastinal abscess needing drainage and intravenous antibiotic: n=1
Minor complications: n=49 (8.9%)
poor postoperative pain control: n=4
significant nausea during immediate postoperative period: n=5
hypoxia needing supplemental oxygenation: n=7
lethargy: n=3
abdominal pain needing additional evaluation: n=5
bothersome nausea or vomiting needing emergency department visit: n=11
dysphagia needing hospital admission: n=7
abdominal wall hematoma at gastric pacer insertion site: n=1
deep vein thrombosis: n=1
urinary retention: n=1
cardiac arrhythmia: n=1
dyspnoea needing additional workup: n=2
aspiration pneumonia: n=1
There was 1 death from causes unrelated to placement of the LINX device.
Postoperative endoscopic dilation: n=169 (99 patients needed 1, and 70 needed more than 1)
Indications for dilation:
dysphagia: n=129 (23.3%)
chest pain: n=14 (2.5%)
both dysphagia and chest pain: n=26 (4.7%)
Device removal: n=37 (6.7%)
Reasons for device removal:
troublesome dysphagia or chest pain not responding to dilation: n=20 (3.6%) Of these patients, 1 patient had pseudoachalsia not responding to dilation and 1 patient needed explanation 2 days after device implantation because of acute dysphagia
recurrence of hernia and migration of the device: n=3
recurrence of hernia and mediastinal abscess: n=1
worsening typical reflux symptoms, n=4
worsening atypical reflux symptoms, n=3
possible titanium allergy, n=1
unexplained leukocytosis: n=1
need for subsequent operation: n=2
esophagectomy for oesophageal adenocarcinoma: n=1
gastrectomy for severe gastroparesis: n=1
removal indicated by device malfunction: n=2
disconnected device: n=2
Readmission:
Readmission within 30 days from operation: 4.2% (n=23)
Readmission between 30 and 90 days from operation: 1.4% (n=8)
One patient was readmitted 3 times, 2 patients needed 2 readmissions, and the remaining patients were readmitted only once after the procedure.
Study 7 Ferrari D (2020)
Study type | Case series (retrospective) |
|---|---|
Country | Italy (single centre) |
Recruitment period | 2007 to 2014 |
Study population and number | n=124 patients with GORD |
Age and sex | Mean 44 years; 66.9% (88/124) male |
Patient selection criteria | Initial inclusion criteria: persistent reflux symptoms despite optimal PPI therapy, abnormal oesophageal acid exposure confirmed by ambulatory oesophageal pH monitoring, hiatus hernia <3 cm, esophagitis < grade B, body mass index <35 kg/m2, and absence of specific motility disorders. With further clinical experience and research, the criteria have been expanded to include patients with larger hiatus hernia, short Barrett's oesophagus, and mild oesophageal dysmotility. Exclusion criteria: patients with recurrent GORD after failed fundoplication or other surgical/endoscopic procedures at the esophagogastric junction, and to those with known history of nickel allergy or eating disorders. |
Technique | Laparoscopic insertion of a magnetic ring: the MSA device was implanted via laparoscopy. Under general anaesthesia, the esophago-gastric junction was exposed after incision of the peritoneal reflection. The posterior vagus nerve was identified and separated from the oesophagus for a length of about 1 cm. No short gastric vessels were divided. The oesophageal circumference was measured with an appropriate magnetic sizer inserted through the retroesophageal tunnel. A minimal or formal posterior crural repair was done depending on the size of the hiatal defect and the degree of hiatus hernia. |
Follow up | Median 9 years (IQR 2) |
Conflict of interest/source of funding | None |
Analysis
Follow-up issues: Two patients died during the follow up for unrelated reasons (exact year not reported).
Study design issues: This study reported the long-term outcomes of patients followed for a minimum of 6 years. GORD-HRQL, use of PPI, and oesophageal pH monitoring parameters were compared with patients' own preoperative data. Favourable outcome of the MSA procedure was defined as ≥50% improvement in GORD-HRQL total score and PPI discontinuation. GORD-HRQL, use of PPI, and oesophageal acid exposure were compared with baseline.
In terms of surgical approach, over the study period and starting from 2014, modifications of the surgical technique occurred. First, formal mediastinal dissection became routine practice; second, a new generation MSA device was introduced for use in magnetic resonance up to 1.5 T; third, a new generation sizer device for measuring the oesophageal circumference was introduced.
Study population issues: Although 211 patients with GORD having laparoscopic MSA were followed up for less than 6 years, this study reported the long-term (6 to 12 years) safety and efficacy outcomes in 124 patients. Of the 124 patients, 21 patients had esophagitis (grade A, n=11; grade B, n=9; grade C, n=1), 4 patients had Barrett's oesophagus, and 106 patients had hiatal hernia (1 cm in length, n=37; 2 cm in length, n=44, 3 cm in length, n=20; ≥4 cm in length, n=5).
Key efficacy findings
Number of patients analysed: 124
Average percent reduction (±SD) of total GORD-HRQL score:
year 6: 77%±32%
year 7: 80%±29%
year 8: 82%±25%
year 9: 86%±22%
year 10: 92%±10%
year 11: 97%±4%
year 12: 95%±8%
No oesophageal symptom (grade 0 to 1): 74.2% (n=92)
Mean total GORD-HRQL score: baseline, 19.9; final follow up, 4.01; p<0.001
Proportion of patients who met the criteria of favourable long-term outcome: 89%
Clinically significant improvement in GORD-HRQL is also reflected by the reported patient satisfaction, which occurred in 92.7% of patients.
Grade 2 to 4 regurgitation: baseline, 59.6%; final follow up, 9.6%; p<0.01
Daily use of PPIs: complete reduction, 79%; at least 50% reduction, 89.5%
Upper gastrointestinal endoscopy after 6 years of follow up:
Hiatus hernia: 6.5% (n=7)
Grade A oesophagitis, 4.7% (n=5)
Incomplete intestinal metaplasia, 2.8% (n=3)
Hill grade (n=45): at the latest endoscopic follow up, 41 patients (91%) retained their preoperative Hill grade I or improved, 3 (7%) remained stable, and in 1 (2%) patient the Hill grade worsened (p<0.01)
Measure | Baseline (n=124) | 6 to 12 years (n=91) | P value |
|---|---|---|---|
Total time (%) | |||
pH<4 | 9.7±6.4 | 4.2±4.9 | <0.001 |
Upright | 9.7±7.8 | 4.6±4.9 | <0.001 |
Supine | 8.3±9.6 | 3.3±7.4 | <0.001 |
Reflux episodes | |||
Total number | 92.2±92.2 | 71.5±67.7 | 0.125 |
Number lasting >5 minutes | 6.1±6.0 | 4.3±5.8 | 0.036 |
Longest (minutes) | 32.9±34.2 | 19.6±31.5 | 0.005 |
DeMeester score | 40.7±26.5 | 16.3±18.8 | <0.001 |
Oesophageal pH testing off PPI therapy showed that the mean percentage of time that pH was <4 decreased from 9.7% at baseline to 4.2% at latest follow up (p<0.001).
Eighty-nine percent of patients who completed oesophageal pH monitoring at 6- to 12 years follow up had either normal oesophageal acid exposure or had at least a 50% reduction compared with baseline.
Proportion of patients with a successful clinical outcome: 81%
Long-term results in 32 patients with follow up more than 10 years:
GORD-HRQL score: median 2
Dysphagia: 0
Ability to belch: n=32 (100%)
Ability to vomit: n=29 (90.6%)
Occasional PPI use: n=7 (21.8%)
Daily PPI use: n=3 (9.4%)
Overall patient satisfaction: n=30 (93.8%)
Predictors of long-term clinical success:
Univariate analysis: age at intervention <40 years, preoperative GORD-HRQL total score >15, duration of symptoms, regurgitation, atypical symptoms and absence of generalised anxiety disorder were statistically significant as independent predictors of clinical success.
Multivariate analysis: independent predictive variables of successful outcome were confirmed to be age <40 years (OR 4.17) and GORD-HRQL score >15 (OR 4.09).
Key safety findings
Laparoscopic device removal: 9.2% (n=31) the most common one-stage remedial procedure was a laparoscopic Toupet fundoplication (n=18).
<6 years (n=28) | 6 to 12 years (n=3) | |
|---|---|---|
Erosion | 6 | 0 |
Regurgitation | 6 | 0 |
Heartburn | 5 | 1 |
Dysphagia | 5 | 1 |
"Foreign body" sensation | 2 | 0 |
Odynophagia | 1 | 0 |
Pharyngodinia | 1 | 0 |
Chronic cough | 1 | 0 |
Need of magnetic resonance study | 1 | 1 |
Study 8 Ferrari D (2021)
Study type | Non-randomised comparative study (retrospective) |
|---|---|
Country | Italy (single centre) |
Recruitment period | Not reported |
Study population and number | n=336 (non-severe GORD, n=234; severe GORD, n=102) patients with GORD |
Age and sex | Non-severe GORD: mean 45.2 years, 69.3% male Severe GORD: mean 46.2 years, 62.8% male |
Patient selection criteria | Inclusion criteria: age between 18 and 65 years and a minimum postoperative follow up of 6 months. Inclusion criteria for the severe GORD group: LOS basal pressure <5 mmHg or distal oesophageal amplitude <30 mmHg on oesophageal manometry, biopsy-proven Barrett's metaplasia, presence of stricture or grade C to D esophagitis on upper gastrointestinal endoscopy, and/or DeMeester score >50 on ambulatory oesophageal pH monitoring. Exclusion criteria: previous esophagogastric surgery and documented allergy to titanium or nickel. |
Technique | Laparoscopic insertion of a magnetic ring: under general anaesthesia, the gastroesophageal junction was dissected, the posterior vagus nerve was identified and separated from the oesophageal wall, and the oesophagus was encircled with a Penrose drain. No short gastric vessels were divided. In patients with hiatal hernia >3 cm, mediastinal dissection and posterior crural repair were routinely done. The oesophageal circumference is measured with a magnetic sizer device. The correct size of MSA was decided by increasing 2 or 3 beads from the point of sizer release. Finally, the LINX device was inserted through the retroesophageal tunnel and locked anteriorly. |
Follow up | Severe GORD: median 24 months (IQR 75), mean 49.6 months Non-severe GORD: median 32 months (IQR 84), mean 50.8 months |
Conflict of interest/source of funding | Conflict of Interest: the research was done in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding: this study was supported by A.I.R.ES. (Associazione Italiana Ricerca ESofago). |
Analysis
Follow-up issues: Patients were followed up at 2 weeks, 6 months and then each year after the operation.
Study design issues: This study evaluates the short- and long-term effectiveness of MSA in patients with severe GORD compared with patients with mild-to-moderate disease. Postoperative assessments included GORD-HRQL, FOSS, upper gastrointestinal endoscopy, barium swallow study, oesophageal manometry and oesophageal pH monitoring. A FOSS score >1 identified severe postoperative dysphagia.
Study population issues: At baseline, demographic characteristics were similar between the 2 groups. However, patients with severe GORD had a statistically significantly higher rate of preoperative dysphagia (severe GORD, 12%; non-severe GORD, 6%; p=0.0460), higher scores of GORD-HRQL questionnaire (severe GORD, 21.0±7.5; non-severe GORD, 19.2±7.7; p=0.0479), higher PPI use (severe GORD, 86%; non-severe GORD, 71%; p=0.0034), and higher DeMeester score (severe GORD, 58.3±33.5; non-severe GORD, 26.2±12; p<0.0001). The main preoperative reasons accounting for disease severity were DeMeester score >50 (49% of patients), biopsy-proven Barrett's metaplasia (33.3%), and LOS basal pressure <5 mmHg (27.5%).
Key efficacy findings
Number of patients analysed: 336
Non-severe GORD (n=234) | Severe GORD (n=102) | P value | |
|---|---|---|---|
Duration of intervention, minutes | 61.4±30 | 61.1±24.5 | 0.9292 |
Number of beads | 13.9±1.3 | 14.1±1.4 | 0.2062 |
Crural repair | 40.2% (n=94) | 49% (n=50) | 0.1345 |
Length hospital stay, days | 1.4±0.7 | 1.2±0.6 | 0.0125 |
Non-severe GORD (n=234) | Severe GORD (n=102) | P value | |
|---|---|---|---|
Follow up, months | 50.8±44.2 | 49.6±43.7 | 0.8185 |
GORD-HRQL score | 3.8±5.7 | 3.9±4.8 | 0.8870 |
Use of PPI | 13.2% (n=31) | 15.6% (n=16) | 0.5597 |
LOS resting pressure, mmHg | 24.3±10.4 | 21.4±12.3 | 0.0271 |
LOS overall length, cm | 3.2±1.3 | 3.1±1.4 | 0.5270 |
LOS abdominal length, cm | 1.4±1.4 | 1.4±1.5 | 1.000 |
DEA, mmHg | 82.4±44.4 | 66.8±28.9 | 0.0011 |
Acid exposure time | 3.6±4.4% | 4.5±4.4% | 0.0856 |
DeMeester score | 13.4±15.9 | 17±16.3 | 0.0591 |
DeMeester >14.7 | 27.8% (n=20) | 41.7% (n=15) | 0.1476 |
Overall, 122 patients had oesophageal manometry at a median of 12 months (IQR = 30) after surgery, and 108 patients had postoperative oesophageal pH monitoring at a median of 28 months (IQR 51) after surgery.
Key safety findings
Non-severe GORD (n=234) | Severe GORD (n=102) | P value | |
|---|---|---|---|
Follow up, months | 50.8±44.2 | 49.6±43.7 | 0.8185 |
Occasional postoperative dysphagia | 14.1 (n=33) | 25.4% (n=26) | 0.0124 |
Recurrent hiatal hernia | 2.6% (n=6) | 3.9% (n=4) | 0.5209 |
Endoscopic dilation | 2.1% (n=5) | 2.9% (n=3) | 0.6562 |
Device removal | 10.2% (n=24) | 7.8% (n=8) | 0.4903 |
Study 9 Ayazi S (2020b)
Study type | Non-randomised comparative study (retrospective) |
|---|---|
Country | US (single centre) |
Recruitment period | 2013 to 2017 |
Study population and number | n=350 (no hiatal hernia, n=65; small hiatal hernia, n=205, large hiatal hernia, n=58; paraesophageal hernia, n=22) patients with GORD |
Age and sex | Mean 53.5 years; 40.3% (141/350) male |
Patient selection criteria | Inclusion criteria: symptomatic GORD patients 18 years or older with persistent GORD or laryngopharyngeal reflux symptoms despite maximal antisecretory therapy and objective evidence of reflux disease based on increased oesophageal acid exposure on pH monitoring or a positive impedance-pH. Exclusion criteria: patients with a previous history of oesophageal or gastric surgery, gross anatomic abnormalities such as oesophageal stricture, significant oesophageal dysmotility or a known allergy to titanium. |
Technique | Laparoscopic insertion of a magnetic ring: this procedure was done laparoscopically and consisted of complete posterior mediastinal oesophageal mobilisation with restoration of intra-abdominal oesophageal length (≥ 3 cm), interrupted posterior crural closure (without pledgets or mesh) and device placement at the level of the gastro-oesophageal junction with the posterior vagus nerve trunk located on the outside of the magnetic ring (LINX device). |
Follow up | Mean 13.6 months (SD 10.4) |
Conflict of interest/source of funding | None |
Analysis
Follow-up issues: Patients were followed up at 2 weeks, 6 weeks, 3 months and then yearly after surgery.
Study design issues: This study compared the outcome of MSA across the spectrum of hiatal hernias commonly encountered in patients with GORD and reviewed the pattern of hiatal hernia recurrence. Patients were divided into 4 groups based on hiatal hernia status: no hiatal hernia, small hiatal hernia (< 3 cm), large hiatal hernia (≥ 3 cm), and paraesophageal hernia. Patient satisfaction, GORD-HRQL and RSI data, freedom from PPI, need for postoperative dilation, length of hospitalisation, 90-day readmission rate, need for device removal, and hiatal hernia recurrence were compared between groups.
Study population issues: At baseline, 285 of the 350 patients were found to have a hiatal hernia. Patients with a large or paraesophageal hernia were statistically significantly older compared with those with a small or no hernia (60.4 [SD 10.7] compared with 51.5 [SD 14], p<0.0001). There was also a higher percentage of women among those with large or paraesophageal hernia (70% compared with 56.7%, p=0.037). The total sample of 350 patients was likely to be covered in Ayazi (2020a).
Key efficacy findings
Number of patients analysed: 350
Measurement | % (n) | No hiatal hernia, % (n) | Small hiatal hernia, % (n) | Large hiatal hernia, % (n) | Paraesophageal hernia, % (n) | p value |
Total | 100% (n=350) | 18.6% (n=65) | 58.6% (n=205) | 16.6% (n=58) | 6.2% (n=22) | N/A |
Satisfaction from surgery | n=277 | |||||
No | 11.2% (n=31) | 13.3% (n=6) | 12.1% (n=20) | 7.8% (n=4) | 6.2% (n=10 | 0.73 |
88.8% (n=246) | 86.7% (n=39) | 87.9% (n=145) | 92.2% (n=47) | 93.8% (n=15) | ||
GORD-HRQL total score clinical improvement | n=280 | |||||
No | 20.7% (n=58) | 20.9% (n=9) | 22.2% (n=38) | 18.0% (n=9) | 12.5% (n=2) | 0.77 |
Yes | 79.3% (n=222) | 79.1% (n=34) | 77.8% (n=133) | 82.0% (n=41) | 87.5% (n=14) | |
Normalisation of acid exposure | n=193 | |||||
DeMeester score <14.7 | 74.1% (n=143) | 71.1% (n=27) | 79.3% (n=88) | 65.6% (n=21) | 58.3% (n=7) | 0.21 |
Freedom from PPI use | n=282 | |||||
Yes | 91.8% (n=259) | 93.2% (n=41) | 91.8% (n=156) | 90.4% (n=47) | 93.8% (n=15) | 0.96 |
No | 8.2% (n=23) | 6.8% (n=3) | 8.2% (n=14) | 9.6% (n=5) | 6.2% (n=1) |
There was an improvement in the overall prevalence of dysphagia when compared with baseline (11.7 compared with 35%, p<0.001).
Of the patients that returned for high-resolution manometry (n=95) at 1-year after MSA, there was no difference in oesophageal function (peristalsis or pressure) when compared with preoperative values.
Key safety findings
Measurement | % (n) | No hiatal hernia, % (n) | Small hiatal hernia, % (n) | Large hiatal hernia, % (n) | Paraesophageal hernia, % (n) | p value |
Total | 100% (n=350) | 18.6% (n=65) | 58.6% (n=205) | 16.6% (n=58) | 6.2% (n=22) | |
Hospitalisation | ||||||
Same day discharge | 92.3% (n=323) | 93.9% (n=61) | 95.6% (n=196) | 84.5% (n=49) | 77.3% (n=17) | 0.002 |
≥1 day hospital stay | 7.7% (n=27) | 6.1% (n=4) | 4.4% (n=9) | 15.5% (n=9) | 22.7% (n=5) | |
Readmission within 90 days | 5.4% (n=19) | 0.0% (n=0) | 6.8% (n=14) | 3.5% (n=2) | 13.7% (n=3) | 0.049 |
Major complications | 0.6% (n=2) | 0.0% (n=0) | 0.0% (n=0) | 3.4% (n=2) | 0.0% (n=0) | |
Minor complications | 10.6% (n=37) | 3.1% (n=2) | 11.2% (n=23) | 10.4% (n=6) | 27.3% (n=6) | |
Overall complications | 11.1% (n=39) | 3.1% (n=2) | 11.2% (n=23) | 13.8% (n=8) | 27.3% (n=6) | 0.015 |
Hiatal hernia recurrence on upper endoscopy | n=24 | n/a | n=20 | n=1 | n=3 |
Major complications included CO2 retention requiring reintubation (n=1) and mediastinal abscess requiring drainage and intravenous antibiotic (n=1).
Minor complications included poor postoperative pain control (n=2), significant nausea during immediate postoperative period (n=3), hypoxia requiring supplemental oxygenation (n=6), lethargy (n=2), abdominal pain needing further evaluation (n=5), persistent nausea and vomiting (n=8), abdominal wall hematoma at gastric pacer insertion site (n=1), DVT (n=1), urinary retention (n=1), and dyspnoea needing further workup (n=2).
Hiatal hernia recurrence: recurrence rate increased in a stepwise fashion with an increase in preoperative hiatal hernia size (0%, 10.1%, 16.6% and 20%, p=0.032). Patients with a minimal dissection had a higher hiatal hernia recurrence rate compared with those with a full dissection (21% compared with 7.9%, p=0.033). Of 24 patients found to have hiatal hernia recurrence on endoscopy, 7 needed reoperation. Patient with minimal dissection was more likely to need reoperation compared with those with a full dissection (10.5% compared with 1.5%, p=0.0133).
Measurement | % (n) | No hiatal hernia, % (n) | Small hiatal hernia, % (n) | Large hiatal hernia, % (n) | Paraesophageal hernia, % (n) | p value |
Dysphagia | 15.3% (n=41) | 15.8% (n=6) | 15.7% (n=31) | 5.8% (n=3) | 5.9% (n=1) | 0.08 |
Need for endoscopic dilation | 23.4% (n=82) | 20.0% (n=13) | 26.3% (n=54) | 24.1% (n=14) | 4.5% (n=1) | 0.12 |
Device removal | 5.1% (n=18) | 6.1% (n=4) | 6.4% (n=13) | 1.7% (n=1) | 0.0% (n=0) | 0.28 |
All the removals were for persistent dysphagia or oesophageal spasm unresponsive to endoscopic dilation. There were no device erosions in this study.
Study 10 DeMarchi J (2021)
Study type | Review of the MAUDE database and the Ethicon's complaint database |
|---|---|
Country | US (350 centres), outside the US (90 centres) |
Recruitment period | 2013 to 2020 |
Study population and number | n=27,779 patients implanted with LINX devices |
Age and sex | Not reported |
Patient selection criteria | Not reported |
Technique | Laparoscopic insertion of a magnetic ring: LINX device implantation |
Follow up | >5 years |
Conflict of interest/source of funding | All the authors were employed by Ethicon Inc. |
Analysis
Study design issues: This study described the safety profile of the LINX® device. The MAUDE database and Ethicon's complaint database were queried for all device removals. The end point was based on the time from implant to explant in months. Incomplete data were apparent in both databases.
This analysis included patients from the geographies in which the clasp-closure MSA device was commercially available, beginning in 2013. It did not include the original device design that was secured by sutures nor the size 12-bead device. Neither of those device options are commercially available today.
Study population issues: Based on implant duration, 31.8% (n=8,836) of patients had less than 1 year after implantation, 46.7% (n=12,961) had 1 to 3 years, 14.6% (n=4,060) had 3 to 5 years, and 6.9% (n=1,922) had more than 5 years.
Key efficacy findings
Number of patients analysed: 27,779
Key safety findings
Reasons for removal | Number of removals | Percentage of total removals | Mean time to removal, months (±SD) |
|---|---|---|---|
Dysphagia | 292 | 47.9% | 10.9±11.9 |
Persistent GORD | 125 | 20.5% | 20.5±13.0 |
Erosion | 27 | 4.4% | 25.0±12.9 |
Abdominal pain/pain | 46 | 7.6% | 15.8±14.3 |
Discontinuous device* | 17 | 2.8% | 33.7±6.0 |
Need for MRI | 11 | 1.8% | 28.6±13.2 |
Vomiting | 16 | 2.6% | 7.4±8.2 |
Gastroparesis | 4 | 0.7% | 20.7±18.5 |
Device migration | 3 | 0.5% | 12.6±17.7 |
Other/unknown | 68 | 11.2% | 6.8±6.4 |
Total removals | 609 | 100.0% | 14.6±13.4 |
*Discontinuous devices were the result of a manufacturing issue that resulted in a voluntary recall in 2018.
The overall 7-year cumulative risk of explant was 4.81% (95% CI 4.31% to 5.36%).
The cumulative risk of erosion at 7 years was 0.28% (95% CI: 0.17% to 0.46%).
Device size and removal rate:
13 beads: 3.5%
14 beads: 2.4%
15 beads: 1.7%
16 beads: 1.5%
17 beads: 1.3%
Device size was significantly related (Chi-square p value < 0.0001) to the likelihood of an explant, with the smallest size having the highest explant rate.
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