SAGES Technology and Value Assessment Committee (TAVAC) Safety and Effectiveness Analysis
LINXÂ® Reflux Management System (Torax Medical, Inc.)
SAGES LINXÂ® Safety and Effectiveness Analysis Committee
- Dana Telem, MD, MPH
- Andrew Wright, MD
- Paresh Shah, MD
- TAVAC Committee Chair: Matthew Hutter, MD, MPH
About this update
The original SAGES LINX Safety and Efficacy Analysis (SEA) was completed and published online in 2013.Â The literature presented in this first document was based on the pre-market and the initial post-market experience that had been published in the peer reviewed literature at the time. In the 3 years that have passed since the original SAGES Technology and Value Assessment Committee (TAVAC) LINX SEA was published, sufficient new data has become available to necessitate an update and a fresh look at the SAGES recommendations with regards to this technology.
The LINXÂ® Reflux Management System (Torax Medical, Inc., Shoreview, MN, USA) is comprised of a small expandable ring of linked magnetic beads.Â The device is laparoscopically implanted around the esophagus at the esophagogastric junction to mechanically augment the function of the lower esophageal sphincter (LES) for the treatment of gastroesophageal reflux disease (GERD).
Each bead in the LINX device contains a neodymium iron boron magnetic core coated with biocompatible titanium.Â Sliding titanium wires connect each bead so that they can move independently, but they canât completely separate.Â At rest, each bead is in contact with adjacent beads, minimizing compressive forces upon the esophagus.Â The magnetic attractive forces between each bead augment the pressure of the LES. Â At higher pressures, the magnetic forces are overcome and the ring expands to allow esophageal distention and the passage of a swallowed bolus or other physiologic functions, such as belching or vomiting.
The LINX Reflux Management System is based on the premise that a device placed around the LES can assist, or augment, an incompetent LES to maintain a closed position when challenged by gastric reflux.Â Â The LINX System is indicated for patients diagnosed with GERD as defined by abnormal pH testing, and who continue to have chronic GERD symptoms despite medical therapy for the treatment of reflux.
The LINX device implantation is performed laparoscopically under general anesthesia.Â The procedure uses standard laparoscopic ports, instruments and techniques.Â The device is placed at the end of the esophagus.Â Minimal dissection is required.Â A specialized sizing tool is used to measure the external esophageal circumference in the target area â allowing the surgeon to select the appropriately sized LINX device.Â An uncomplicated procedure can generally be performed in well under 1 hour.Â In contrast to fundoplication, patients are started on a solid diet soon after the procedure.
The LINX System is not intended for use in patients with suspected or known allergies to metals such as iron, nickel, titanium, or stainless steel. The immediate post-approval version of the LINX device was only compatible with a magnetic resonance imaging device (MRI) up to 0.7T (Tesla).Â In June of 2015, the FDA approved the next generation of the device compatible and safe with an MRI up to 1.5 Tesla.Â The LINX System is contraindicated in patients receiving electrical implants such as defibrillators or pacemakers or undergoing insertion of metallic implants in the abdomen.
Development of the LINX device began in 2002.Â Animal testing of the current device began in 2005 .Â An FDA approved Investigational Device Exemption (IDE) feasibility trial (#G060172) enrolled 44 patients at 4 sites in the US and Europe in 2007-2008.Â A 100 patient pivotal trial was subsequently performed at 14 US and European sites. Enrollment occurred throughout 2008-2009.Â Through 2011, 2-year follow-up on the pivotal trial was available.Â An FDA expert panel considered the clinical data from these 2 trials in January 2012, and pre-market approval (PMA #P100049) was granted in March 2012 .
FDA Instructions for Use (2012)
The LINX system is labeled for use in GERD patients with abnormal pH testing who continue to have chronic symptoms despite anti-reflux therapy.
- The LINX device has not been evaluated in patients with a hiatal hernia larger than 3-cm.Â Use of LINX device in patients with a hiatal hernia larger than 3-cm should be considered on the basis of each patient’s medical history and severity of symptoms.
- The safety and effectiveness of the LINX device has not been evaluated in patients with Barrett’s esophagus or Grade C or D (LA classification) esophagitis.
- The safety and effectiveness of the LINX device has not been evaluated in patients with major motility disorders.
- The safety and effectiveness of the LINX Reflux Management System has not been established for the following conditions:
- Suspected or confirmed esophageal or gastric cancer
- Prior esophageal or gastric surgery or endoscopic intervention
- Distal esophageal motility less than 35-mmHg peristaltic amplitude on wet swallows or <70% (propulsive) peristaltic sequences or a known motility disorder (such as Achalasia, Nutcracker Esophagus, and Diffuse Esophageal Spasm or Hypertensive LES).
- Symptoms of dysphagia more than once per week within the last 3 months.
- Esophageal stricture or gross esophageal anatomic abnormalities (Schatzki’s ring, obstructive lesions, etc.).
- Esophageal or gastric varices.
- Morbid obesity (BMI >35).
- Age <21
1. Technology Significance
Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disease in the United States.Â It is also one of the most important in terms of its chronicity, overall cost, adverse impact on quality of life, and potential for complications, such as Barrettâs esophagus and esophageal adenocarcinoma .
Current estimates suggest that GERD affects around 10â20% of adults in Western countries on a daily or weekly basis .Â Up to 50% of patients with GERD may require chronic pharmacologic therapy . Long term GERD pharmacotherapy is exceedingly expensive with an estimated annual cost in the US of $11 billion . The most powerful and commonly prescribed acid suppression medications are proton pump inhibitors (PPIs). PPIs have been linked via retrospective studies to increased risk of enteric infections including Clostridium difficile-associated diarrhea, community-acquired pneumonia, bone fracture, nutritional deficiencies, and interference with metabolism of antiplatelet agents .Â It is estimated that as many as 40% of patients with GERD fail to respond symptomatically to aggressive acid suppression therapy [8,9,10].Â Â As a result, 20-40% of patients are dissatisfied with medical GERD treatment and see no viable alternative to more medications and persistent symptoms .
Some patients with severe GERD and associated complications undergo antireflux surgery.Â Despite the fact that the prevalence of GERD has increased in recent years, utilization of laparoscopic Nissen fundoplication for medically refractory GERD has declined.Â With literally millions of American adults continuing to suffer from GERD symptoms despite aggressive medical therapy, an estimated 24,000 Americans underwent laparoscopic Nissen fundoplication in 2003 . This accounts for less than 1% of patients estimated to be dissatisfied or who suffer from persistent symptoms on acid suppression medical therapy.Â This discrepancy is thought to be at least partly due to concerns over side effects associated with Nissen fundoplication (dysphagia, bloating) as well as the possibility of fundoplication failure with recurrent GERD and need for acid suppression medical therapy or repeat surgery.
Patients with GERD who have persistent symptoms on medical therapy who arenât willing to consider traditional antireflux surgery (or are not referred to a surgeon to be considered) fall into what is known as the GERD treatment gap.Â The LINX system may be an attractive alternative to chronic medical therapy for GERD patients who are hesitant to undergo Nissen fundoplication. Following fundoplication, some patients describe difficulty belching and symptoms of bloating [13,14].Â Data from the premarket trial suggests that following the LINX procedure; most patients maintain their ability to belch and frequent/continuous bloating was reported at a low rate (5% of patients 12 months following LINX implantation described frequent or continuous bloating compared to 40% at baseline) .
Augmentation of the esophageal sphincter with a magnetic device may provide an alternative treatment for patients with incomplete symptom relief on acid suppression medical therapy or who are reluctant to undergo surgical fundoplication.
2. Current Clinical Practice and Alternatives
Mild to moderate cases of GERD are typically treated with lifestyle modifications, over-the-counter medications, and prescription drugs.Â Lifestyle changes include weight loss, avoiding certain foods, managing meal size and timing, and elevating the head of the bed.Â Continuous pharmacotherapy is a mainstay of GERD treatment.Â PPIs work by suppressing stomach acid production and subsequent reflux acidity.Â PPIs do not address the mechanism of regurgitation in patients with pathologic GERD. Â Central to the pathogenesis of GERD is a weak or incompetent LES that opens abnormally and allows the reflux of gastric contents into the esophagus.
In normal subjects, omeprazole treatment does not affect the number of reflux episodes or their duration; rather it converts acid reflux to less acid reflux, thus exposing esophagus to altered gastric juice. These observations may explain the persistence of symptoms and emergence of mucosal injury while on proton pump inhibitor therapy . Â Limitations of PPIs include the need for daily use, high cumulative costs, and decreased efficacy over time.
Surgical procedures are typically considered in patients with symptoms despite optimal PPI therapy and in patients with severe GERD.Â Surgery is used, however in less than 1% of eligible GERD patients, and its usage has been decreasing over the last decade .Â Laparoscopic fundoplication is the most commonly performed antireflux operation.Â The laparoscopic approach to fundoplication was introduced and popularized in the 1990âs.Â The surgical technique involves a complete hiatal dissection with mobilization of the esophagus and fundus, re-approximation of the diaphragmatic crura, and creation of a 360-degree wrap of fundus around the distal esophagus.Â Laparoscopic Nissen fundoplication can be accomplished in 2 hours or less for uncomplicated cases.Â Most patients stay in the hospital for 1-2 days.Â Many surgeons have their patients gradually transition from a soft or pureed diet to a more solid diet over the course of 2-8 weeks .Â Relief of symptoms, especially esophageal symptoms such as heartburn and regurgitation occurs in > 90% of patients and has been demonstrated to be durable beyond 10 years for the majority of patients [18,19].Â Potential surgical side effects following Nissen fundoplication include difficulty swallowing, increased flatus, bloating, early satiety, and inability to vomit or belch [20,21].Â Anatomic failure of the fundoplication with recurrent GERD can occur in 2-17% of cases .Â The published outcomes of antireflux surgery are not always replicated in the community, especially for surgeons who perform laparoscopic antireflux surgery infrequently [23,24].Â SAGES has published a Guidelines for Surgical Treatment of Gastroesophageal Reflux Disease.Â According to this document âThe standardization of antireflux surgery technique is highly desirable, as it has been shown to lead to good postoperative patient outcomes (Grade A). Like any other surgical procedure, laparoscopic antireflux surgery is subject to a learning curve, which may impact patient outcomes. Therefore, surgeons with little experience in advanced laparoscopic techniques and fundoplication in particular should have expert supervision during their early experience with the procedure to minimize morbidity and improve patient outcomes (Grade B).â Â Concerns related to potential side effects, recurrent GERD, and repeat surgery following laparoscopic Nissen fundoplication likely play a role in the fact that most patients who meet indications for antireflux surgery never undergo this procedure.
As an alternative to laparoscopic antireflux surgery, there are other commercially available, FDA approved endoscopic incisionless procedures designed to treat GERD.Â An exhaustive review of these technologies is outside of the scope of this document. A 2013 SAGES Statement on Endoluminal Treatments for GERD focused on 2 endoluminal devices available at the time of the review â EsophyX (Trans Oral Fundoplication or TIF, Endogastric Solutions, Redmond, WA) and Stretta (Mederi Therapeutics, Norwalk, CT) and is available for review.Â . Direct comparisons between LINX and other commercially available products are unavailable. Experience with endoluminal GERD treatments continues to evolve.
3. Clinical Evidence Summary
Clinical studies involving the LINX system were identified via a search of the PubMed/Medline database (www.ncbi.nlm.nih.gov/pubmed) conducted in July 2016.Â The literature search used combinations of the keywords LINX, reflux, magnetic, magnetic sphincter augmentation, and/or GERD. Â Review articles without unique clinical data were excluded.Â Articles pertaining to the use of LINX in patients who have previously undergone bariatric surgery were considered outside the scope of this review and excluded.Â The bibliographies of key references were searched for relevant studies not uncovered in the PubMed search.Â The manufacturerâs website was also used to identify key references.Â Finally, summary reports for unpublished clinical data used in the approval process were identified on the FDA Web site. Patients from the feasibility and the pivotal trial are included in many other case series and case-control series.Â Patients from the post-market experience at numerous centers are represented several times in more recent publications included in this updated review. All references are described in detail in Appendix A.
4. Safety and Efficacy Data
Review of published studies suggests that magnetic sphincter augmentation is safe with no reported deaths and a 0.1% rate of intra/perioperative complications . Long-term efficacy of LINX appears good for typical GERD symptoms with reduced acid exposure, improved GERD symptoms, and freedom from PPI in 85-88% at 3-5 years [28,29,30]. The most common side effect is dysphagia, the rate of which likely differs based on definition and patient population. Early dysphagia within the first few weeks is common at about 70% [31,32]. Dysphagia resolves in most patients and the incidence is roughly 10% at 1 year and 4% at 3 years . The need for endoscopic dilation ranges from 6-12% [27, 33] and the primary reason for explantation appears to be persistent dysphagia with a rate in larger series from 3-6% [27,28,31]. Erosion appear to be rare, with one case reported in the 1st 1,000 patients , one additional published case report , a large series reporting 2 erosions , and several additional reports in the FDA MAUDE dataset (true number unknown, as multiple entries in this dataset may be made for each patient). Based on very limited literature, erosion can be successfully treated with explantation. Initially there were concerns about safety of LINX in patients who might later need an MRI. Patients who underwent LINX implantation prior to May 2015 are limited to MRI under 0.7T, while patients who have LINX subsequent to that date may have MRIs up to 1.5T (Torax website).
The literature search found reports on 2 FDA-approved IDE clinical studies.Â The initial feasibility study was a prospective, multi-center, non-randomized case series that enrolled 44 patients between February 2007 and October 2008 at 4 sites in the US and Europe (11 LINX procedures performed in the US andÂ 33 in Europe).Â Four separate publications report results at 3-months ,1 to 2 years , Â 4 years , and 5 years . Â The pivotal study was a prospective, non-randomized, multi-center clinical trial enrolling 100 patients (96 US and 4 European) at 14 sites (13 US and 1 European).Â Data from 2-year follow-up were presented in FDA documents as part of the pre-market approval process . Â Three-year follow-up on the pivotal trial was published at the time of the first version of this document . Â More recently, 5-year follow-up on the pivotal study cohort was published as well .
Bonavina et al.  conducted a multicenter feasibility trial to evaluate safety and efficacy of the âmagnetic sphincter augmentation device.â Patients with typical heartburn (at least partially responding to proton-pump inhibitors), abnormal esophageal acid exposure, and normal esophageal peristalsis were enrolled. Patients with hiatal hernia >3 cm were excluded from the study. Over a 1-year period, 38 out of 41 enrolled patients underwent this procedure in 3 hospitals. No operative complications were recorded. A free diet was allowed since post-operative day one, and 97%of patients were discharged within 48 h. The mean follow-up was 209 days (range 12â434 days). The GERD-HRQL score decreased from 26.0 to 1.0 (p<0.005). At 3 months postoperatively, 89% of patients were off anti-reflux medications, and 79% of patients had a normal 24-h pH test. All patients preserved the ability to belch. Mild dysphagia occurred in 45% of patients. No migrations or erosions of the device occurred. From this study, the authors suggest that in their experience laparoscopic implantation of the magnetic sphincter augmentation device is safe and well tolerated. They also propose that the short learning curve and minimal dissection required may be advantageous.
Bonavina et al.  later conducted a 1 and 2-year evaluation of the above feasibility trial.Â At baseline, all 44 patients had abnormal esophageal acid exposure on 24-hour pH monitoring and improved, but persistent, typical GERD symptoms while on acid suppression therapy with PPIs. Patients were evaluated after surgery by GERD Health-Related Quality of Life symptom score, PPI usage, endoscopy, esophageal manometry, and 24-hour esophageal pH monitoring. The total mean GERD Health-Related Quality of Life symptom scores improved from a mean baseline value of 25.7 to 3.8 and 2.4 at 1 and 2-year follow-up, representing an 85% and 90% reduction, respectively (P < 0.0001). Complete cessation of PPI use was reported by 90% of patients at 1 year and by 86% of patients at 2 years. Early dysphagia occurred in 43% of the patients and self-resolved by 90 days. One device was laparoscopically explanted for persistent dysphagia without disruption of the anatomy or function of the cardia. There were no device migrations, erosions, or induced mucosal injuries. At 1 and 2 years, 77% and 90% of patients had a normal esophageal acid exposure. The mean percentage time pH was less than 4 decreased from a baseline of 11.9% to 3.1% (P < 0.0001) at 1 year and to 2.4% (P < 0.0001) at 2 years. Patient satisfaction was 87% at 1 year and 86% at 2 years. The authors conclude, âThe new laparoscopically implanted sphincter augmentation device eliminates GERD symptoms without creating undue side effects and is effective at 1 and 2 years of follow-up.â
Lipham et al.  followed this same patient cohort and evaluated these 44 patients at 3 and 4 years.Â Each patient’s baseline GERD status served as the control for evaluations post implant. For esophageal acid exposure, the mean total % time pH < 4 was reduced from 11.9 % at baseline to 3.8 % at 3 years, with 80 % of patients achieving pH normalization. At â¥4 years, 100 % of the patients had improved quality-of-life measures for GERD, and 80 % had complete cessation of the use of proton pump inhibitors (PPIs). There have been no reports of long-term device-related complications such as migration or erosion. The authors concluded that, âSphincter augmentation with the LINX Reflux Management System provided long-term clinical benefits with no safety issues as demonstrated by reduced esophageal acid exposure, improved GERD-related quality of life, and cessation of dependence on PPIs, with minimal side effects and no safety issues. Patients with inadequate symptom control with acid suppression therapy may benefit from treatment with sphincter augmentation.â
Saino et al recently reported the 5-year outcomes of the feasibility trial cohort .Â Of the original 44 patients, 33 were available for follow-up at 5-years. Mean total percentage of time with pH <4 was 11.9% at baseline and 4.6% at
5 years (P < .001), with 85% of patients achieving pH normalization or at least a 50% reduction. Mean total GERD-HRQL score improved significantly from 25.7 to 2.9 (P < .001) when comparing baseline and 5 years, and 93.9% of patients had at least a 50% reduction in total score compared with baseline. Complete discontinuation of PPIs was achieved by 87.8% of patients. No complications occurred in the longer term, including no device erosions or migrations.Â The authors conclude that based on long-term reduction in esophageal acid, symptom improvement, and no late complications, that they have demonstrated the relative safety and efficacy of magnetic sphincter augmentation for GERD.
In the FDA Summary of Safety and Effectiveness Data (SSED) document, with regards to safety, the FDA concludes: âThe safety of the LINX Reflux Management System in the treatment of subjects with GERD was based on adverse event data from 100 subjects followed for up to 24 months. The 12-month data demonstrated 162 total adverse events reported in 76% of the subjects. Most adverse events resolved without sequelae. Dysphagia was the most common adverse event with 76 events being reported in 68% of the subjects, with 11% of the subjects reporting ongoing dysphagia. Eighteen (18) subjects underwent esophageal dilatation and 10 continued to have dysphagia at 24 months. Furthermore, there were several subjects who experienced symptoms of odynophagia/dysphagia that started after 180 days (182-605) and several subjects who had odynophagia and/or dysphagia that took over 180 days to resolve (maximum time noted 447 days). Overall, the incidence of dysphagia was found to be comparable to the incidence of dysphagia that is reported in patients undergoing anti-reflux surgery, such as Nissen fundoplication. Overall, the safety data from the pivotal trial supports a reasonable assurance that the LINX device is safe.â
With regards to effectiveness, based on the pivotal trial data the FDA concludes: âWhile the success criterion for the pre-specified primary objective of the study (pH normalization or a â¥ 50% reduction in distal esophageal acid exposure) was not met, there was improvement in esophageal pH. Sixty four of 100 subjects met the primary endpoint; there were 56 subjects who had normalization of pH and another 8 subjects who had a least a 50% reduction in total time that the pH < 4, however the lower limit of the 97.5% confidence interval was only 53.8% instead of the pre-specified 60%. Even more subjects had success in meeting the secondary objectives of improvement in GERD symptoms and reduction in PPI usage. The success rate for reduction in GERD symptoms was 92% at 12 months and 84% at 24 months. Similarly, reduction of at least 50% in PPI use was seen in 93% of subjects at 12 months and 86% at 24 months. The majority of these subjects, 88 at 12 months and 83 at 24 months, eliminated their use of PPIs. Although the primary objective of the study was not met, FDA considered the improvement in esophageal pH that was seen in 64% of subjects in addition to the improvement in GERD symptoms and reduction in PPI medication use demonstrated a reasonable assurance as to the effectiveness of the LINX Reflux Management System.â
Ganz et al.  published 3-year follow-up data on the 100 patients enrolled in the pivotal trial.Â With regards to safety, âserious adverse events occurred in six patients and required removal of the device in four of the six. In three of the patients, the device was removed at 21, 31, and 93 days after implantation because of persistent dysphagia, with resolution in all three patients after removal, and in one patient, the device was removed at 357 days owing to intermittent vomiting of unknown cause starting 3 months after implantation, without relief after removal.âÂ The most frequent adverse event was dysphagia, which occurred in 68% of patients postoperatively. Ongoing dysphagia was noted in 11% of patients at 1 year, in 5% at 2 years, and in 4% at 3 years. Esophageal dilation for dysphagia was allowed at the discretion of the investigator. A total of 19 patients underwent dilation, with 16 reporting improvement after the procedure.Â Chest radiography and endoscopy performed at 1 year and at 2 years after implantation showed no evidence of device migration or erosion. At 3 years, 2 patients reported an inability to belch or vomit.Â With regards to safety, the authors concluded, âStudies with larger samples and longer term follow-up are needed to confirm these early results and assess longer-term safety.â With regards to effectiveness, these investigators determined that normalization of or at least a 50% reduction in esophageal acid exposure was achieved in 64% of patients (64 of 100; 95% confidence interval [CI], 54 to 73). The secondary efficacy end point, a 50% reduction in the quality of life score, as compared with the score without proton-pump inhibitors at baseline, was achieved in 92% of patients (92 of 100; 95% CI, 85 to 97). A reduction of 50% or more in the average daily dose of proton-pump inhibitors occurred in 93% of patients (93 of 100 patients; 95% CI, 86 to 97). With regards to effectiveness, the authors concluded that the magnetic device decreased exposure to esophageal acid, improved reflux symptoms, and allowed cessation of proton-pump inhibitors in the majority of patients.
Ganz and colleagues later reported the 5-year outcomes for 85 of the 100 patients enrolled in the pivotal trial . Over the follow-up period, no device erosions, migrations, or malfunctions occurred. At baseline, the median GERD-HRQL scores were 27 in patients not taking proton pump inhibitors, and 11 in patients on these medications. Five years after device placement this score decreased to 4. All patients used proton pump inhibitor medications at baseline and at 5 years these medications were only used in 15%.Â Moderate or severe regurgitation occurred in 57% of subjects at baseline, but only 1.2% at 5 years. All patients reported the ability to belch and vomit if needed. Bothersome dysphagia was present in 5% at baseline and in 6% at 5 years. Bothersome gas-bloat was present in 52% at baseline and decreased to 8.3% at 5 years.Â The authors conclude that augmentation of the lower esophageal sphincter with a magnetic device provides significant and sustained control of reflux, with minimal side effects or complications. No new safety risks emerged over a 5-year follow-up period.
Additional notable recent additions to the literature include a safety analysis of the first 1,000 patients implanted with a device .Â Event rates were 0.1% intra/perioperative complications, 1.3% hospital readmissions, 5.6% endoscopic dilations, and 3.4% reoperations. All reoperations were performed non-emergently for device removal, with no complications or conversion to laparotomy. The primary reason for device removal was dysphagia. No device migrations or malfunctions were reported. Erosion of the device occurred in one patient (0.1%). The authors of this study concluded that with regards to safety, the overall event rates were low based on data from 82 institutions, and that the LINX device is a safe therapeutic option.
Asti et al.  reported the results of a retrospective review of prospectively collected data examining the outcomes of 164 patients undergoing LINX implantation with median follow-up of 48 months.Â In eleven patients (6.7%), the device was ultimately removed for heartburn or regurgitation (n=5), dysphagia (n=4), or chest pain (n=2).Â In 2 patients, full-thickness erosion of the esophageal wall with partial endoluminal penetration of the device occurred. The estimated removal-free probability at 80 months was 0.91 [confidence interval
(CI) 0.86â0.96]. The median implant duration was 20 months, with 82% of the patients being explanted between 12 and 24 months after the implant. Device removal was most commonly combined with partial fundoplication. There were no conversions to laparotomy and the postoperative course was uneventful in all patients.Â These authors conclude that laparoscopic removal of the LINX device âcan be safely performed as a 1-stage procedure and in conjunction with fundoplication even in patients presenting with device erosion.â
There are several publications comparing clinical outcomes of the LINX device when compared to laparoscopic Nissen fundoplication.Â Louie et al.  compared perioperative outcomes, symptom control, side effects, adverse events, and pH studies in 34 consecutive patients who underwent LINX to 32 consecutive patients who had laparoscopic Nissen fundoplication.Â All patients with a hiatal hernia > 3-cm were excluded from this analysis.Â Operative time was longer for fundoplication. At 6 months, scores on the Gastroesophageal Reflux Disease Health Related Quality of Life scale improved from 20.6 to 5.0 for LINX vs. 22.8 to 5.1 for fundoplication. Postoperative DeMeester scores (14.2 vs. 5.1, p=0.0001) and the percentage of time pH was less than 4 (4.6 vs. 1.1; p=0.0001) were normalized in both groups. , but lower in the LINX group. LINX resulted in improved gas and bloat sensations (1.32 vs. 2.36; p=0.59) and enabled belching in 67% compared with none of the fundoplication patients.Â The investigators determined that LINX results in similar GERD symptom control with an improved quality of life compared to fundoplication.
Sheu et. al.  compared the outcomes of 12 patients to undergo LINX to 12 patients who had undergone laparoscopic Nissen fundoplication who were matched based on age, gender, and hiatal hernia size. LINX and Nissen fundoplication were both effective treatments for GERD.Â Severe dysphagia requiring endoscopic dilation was more common in LINX (50% vs. 0%; p=0.01).Â There was a non-statistically significant trend towards decreased gastrointestinal symptoms of bloating, flatulence, and diarrhea for LINX.Â These authors concluded that LINX and fundoplication are both effective and safe treatments for GERD. âConsideration to the distinct post-operative symptom profiles should be paid when selecting a surgical therapy for reflux disease.â
Riegler et al.  analyzed a prospective, multicenter registry of patients to undergo LINX and laparoscopic fundoplication for GERD.Â There were 202 LINX and 47 fundoplication patients with 1-year follow-up data at the time of their analysis.Â The fundoplication group was older with a greater frequency of large hiatal hernia and Barrettâs esophagus.Â GERD-health related quality of life score improved following surgery for both procedures. Moderate or severe regurgitation improved from 58.2 to 3.1% after LINX and 60.0 to 13.0% after fundoplication (p = 0.014).
Proton pump inhibitor medications were discontinued by 82% of LINX and 63.% of fundoplication patients (p = 0.009). Symptoms of excessive gas and abdominal bloating were reported by 10% of LINX and 32% of fundoplication patients (p â¤ 0.001). The authors of this study concluded that antireflux surgery should be individualized to the characteristics of each patient, taking into consideration anatomy and side effects. They felt that both LINX and fundoplication showed significant improvements in reflux control, with similar safety and reoperation rates. âIn the treatment continuum of antireflux surgery, MSAD (Magnetic Sphincter Augmentation Device) should be considered as a first-line surgical option in appropriately selected patients without Barrett’s esophagus or a large hiatal hernia in order to avoid unnecessary dissection and preserve the patient’s native gastric anatomy.â
Reynolds was the lead author on 2 additional comparative studies evaluating LINX and fundoplication [42,43]. In the first comparative study to be published, from a series of 62 LINX and 117 laparoscopic Nissen fundoplications, 50 patients in both groups were matched using the “best-fit” model incorporating numerous preoperative variables.Â At 1 year after surgery, both groups had similar GERD Health Related Quality of Life scores and proton-pump inhibitor use.Â There were no patients with severe gas and bloating in the LINX group compared with 10.6% in the LNF group (p = 0.022). More fundoplication patients were unable to belch (8.5% of LINX and 25.5% of fundoplication; p = 0.028) or vomit (4.3% of LINX and 21.3% of fundoplication; p = 0.004). The incidence of postoperative dysphagia was similar between the groups.Â The authors concluded that analogous GERD patients had similar control of reflux symptoms with a lower incidence of gas bloat in LINX.Â In the second comparative trial by Reynolds et al, essentially the same cohort of patients was used to compare charges, complications, and outcome of LINX versus laparoscopic Nissen fundoplication at 1-year.Â There were 52 LINX and 67 fundoplication patients included.Â There was no significant difference between the mean charges.Â The fundoplication procedure was associated with a longer operative time and length of stay.Â Symptomatic outcomes and the ability to discontinue proton pump inhibitor medications were similar between procedures.Â As reported in the previously referenced publication, gas bloat as well as the ability to belch or vomit if needed was better following LINX.Â The authors concluded that fundoplication and LINX are comparable in symptom control, safety, and overall hospital charges.
Warren et. al.  published a multi-institutional retrospective cohort study of patients with GERD undergoing either LINX or laparoscopic Nissen fundoplication.Â Â Comparisons were made at 1 year for the overall group and for a propensity-matched group.Â There were 201 LINX and 214 fundoplication patients that were similar preoperatively with regards to age, gender, and GERD-HRQL scores.Â Obesity, dysphagia, higher DeMeester scores, Barrettâs esophagitis, and hiatal hernias were more prevalent in the fundoplication patients. Propensity-matched cases showed similar GERD-HRQL scores and the differences in ability to belch or vomit, and gas bloat persisted in favor of LINX. Mild dysphagia was higher for LINX (44 vs. 32 %, p=0.03). Resumption of daily PPIs was higher for LINX (24 vs. 12, p=0.02) with similar patient-reported satisfaction rates.
Asti et al published another comparative study evaluating outcomes following LINX and laparoscopic Toupet fundoplication .Â Using the propensity score full matching method and generalized estimating equation, consecutive patients undergoing laparoscopic Toupet or LINX over the same time period were compared. Over a 7-year period, 103 patients underwent a laparoscopic Toupet and 135 a LINX procedure. All patients had a minimum 1-year follow-up. Over time, patients in both groups had similar GERD-HRQL scores, gas-related symptoms, dysphagia, and reoperation-free probability.Â In 2 concurrent cohorts of patients with early stage GERD undergoing laparoscopic Toupet or LINX and matched by propensity score analysis, health-related quality of life significantly improved and GERD-HRQL scores had a similar decreasing trend over time up to 7 years of follow-up. The authors conclude that laparoscopic Toupet and LINX provide similar disease-specific quality of life over time in patients with early stage GERD.
A search of the ClinicalTrials.gov website identified 8 clinical trials sponsored by Torax Medical. Â Five of these studies (all observational) have been completed.Â A post-approval study of the LINX reflux management system (NCT01940185) is active but not recruiting.Â The primary outcome measure of this study is a successful reduction of GERD-HRQL scores and adverse events to 60 months.Â The estimated study completion date is September 2019.Â The CALIBER Study Randomized Controlled Trial of LINX Versus Double-Dose Proton Pump Inhibitor Therapy for Reflux Disease (NCT02505945) is open for enrollment with an estimated study completion date of April 2017.Â This study compares mechanical sphincter augmentation (LINX Reflux Management System) to double-dose proton pump inhibitors (PPIs) for the management of reflux symptoms related to gastroesophageal reflux disease (GERD).Â The percentage of subjects with resolution of the GERD symptom of interest in each arm will be compared for significance. The final study is not yet recruiting. https://clinicaltrials.gov/ct2/results?term=torax+medical&cond=%22Gastroesophageal+Reflux%22 (accessed March 24, 2016)
A review of the FDA MAUDE database (3/1/12-2/29/16) revealed 141 reported adverse events (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/results.cfm).Â All 141 reports describe device explants.Â Over the entire post-FDA approval interval to date, there were 72 reports of devices removed for dysphagia primarily.Â There were 33 reports of devices removed for recurrent or persistent GERD.Â A total of 14 erosions are reported in the MAUDE database at the time of this search.Â It is not possible to determine the incidence of device removal or erosion from the MAUDE database as the denominator is not known, some events may be reported more than 1 time, and some are likely not reported at all.
There are 3 published case reports describing device removal at the time of this review.Â Dysphagia [46,47] and erosion  were the primary indications for device removal in these reports. Lipham  reported 1 erosion in 1,000 patients and Asti  reported 2 in 164 patients.
In November of 2015, the American Medical Association awarded the LINX device a new Category 1 CPT (Current Procedural Terminology) code that will be effective January 1, 2017.Â The criteria for a category 1 CPT code are as follows (https://www.ama-assn.org/ama/pub/physician-resources/solutions-managing-your-practice/coding-billing-insurance/cpt/cpt-process-faq/code-becomes-cpt.page):
- All devices and drugs necessary for performance of the procedure of service have received FDA clearance or approval when such is required for performance of the procedure or service
- The procedure or service is performed by many physicians or other qualified health care professionals across the United States
- The procedure or service is performed with frequency consistent with the intended clinical use (i.e. a service for a common condition should have high volume)
- The procedure or service is consistent with current medical practice
- The clinical efficacy of the procedure or service is documented in literature that meets the requirements set forth in the CPT code change application.
5. Limitations of currently published data
- Patients used repeatedly in some publications
- There may be a publication bias in favor of LINX, as several studies were either funded by the manufacturer or were performed by investigators affiliated with the manufacturer.
- Most studies were performed in high volume centers in highly selected patients and may not reflect broader clinical practice, which may lead to underreporting of complications
- Current studies lack randomization and blinding
6. Expert Panel Recommendation
This expert panel convened by the SAGES Technology and Value Assessment Committee finds that:
With regards to safety:
- Safety analyses suggest the LINX procedure was associated with few serious adverse events and no reported mortality.
- The most common anticipated side effect was acute dysphagia.
- The reported rate of erosion is in the range of 0.1% to 0.2%. Â The published literature on erosions suggests that the device can be safely removed endoscopically or laparoscopically without serious adverse outcomes.
- Some devices require removal, most often for recurrent GERD or persistent and/or severe dysphagia
- No new patterns of failure or complications have been reported in long-term follow-up.
- Longer-term follow-up supports the FDA conclusion that the device is safe.
With regards to efficacy, the panel concludes:
- LINX implant results in pH normalization, improved quality of life, and complete cessation of regular PPI use on a consistent basis.Â The ability to belch and vomit is maintained following implantation of LINX, and de novo moderate-severe gas-bloat is uncommon.
- When compared to laparoscopic fundoplication, rates of success in alleviating GERD symptoms and dysphagia are similar following LINX.Â Bloating side effects may be lower.
- Longer-term follow-up data demonstrates that the LINX Reflux Management System is effective in the management of GERD.
- Longer-term (3-5 years) experience with the LINX Reflux Management System confirms the initial safety profile that led to FDA approval of the device.
- The LINX device has been demonstrated to result in long-term GERD control based on symptomatic outcomes, PPI utilization, and pH studies.
- LINX is a reasonable treatment option for appropriately selected patients with GERD who meet indications for antireflux surgery.Â The LINX procedure is part of the armamentarium in the treatment of GERD. As such, it should be performed by surgeons familiar with the workup and different management alternatives of GERD and not offered in isolation.
- Implantation of the LINX device should be covered and reimbursed by insurance for appropriate patients who meet the selection criteria as described above.
Author Financial Disclosure/Conflict of Interest Statement
Dana Telem, MD:Â Research funding at Cook, Consulting Fees at Ethicon and Medtronic, Honoraria at Gore
Andrew Wright, MD:Â Honoraria at Medtronic.
Paresh Shah, MD:Â Consultant at Stryker, Zmicro, Olympus, Endoevolution
Matthew Hutter, MD: Reimbursed to attend Masters in MIS Forum by Olympus.
This document underwent prescreening review prior to submission to SAGES Board of Governors for approvalÂ by SD Schwaitzberg, MD andÂ Patricia Sylla, MD
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|FDA Summary of Safety and Effectiveness Data ||Multi-institutional, non-randomized, prospective case series (FDA Pivotal Trial, n=100)||LINX reflux management system||Primary endpoint:|
Either normalization of pH, or a reduction of at least 50% in total time that pH <4, relative to baseline. Sixty-four (64) of the 100 implanted subjects achieved success. The lower limit of the 97.5% confidence interval fell below success threshold and, therefore, primary endpoint not met.
First secondary endpoint:
Reduction in GERD symptoms defined by the GERD-HRQL questionnaire. Success was defined as a reduction of 50% in the total GERD-HRQL score at 12 months post implantation as compared to baseline score off PPI therapy. The majority of subjects had at least 50% improvement in their scores.
Second secondary endpoint:
Reduction in PPI use. Success was defined as a reduction in PPI daily use by >_ 50% at 12 months post implantation as compared to a subject’s baseline PPI use. At 24 months, 96% of subjects met the endpoint.
|âAlthough the primary objective of the study was not met, FDA considered the improvement in esophageal pH that was seen in 64% of subjects in addition to the improvement in GERD symptoms and reduction in PPI medication use demonstrated a reasonable assurance as to the effectiveness of the L1NX Reflux Management System.â|
|Ganz, 2013 ||Multi-institutional, non-randomized, prospective case series (FDA Pivotal Trial, n=100)||LINX reflux management system||The primary outcome was achieved in 64% of patients (95% confidence interval|
[CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed.
|In this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety.|
|Bonavina,Â 2008 ||Case series (FDA Feasibility Trial Cohort, n = 41)||Magnetic Sphincter Augmentation (MSA) device||The GERD HRQoL score decreased from 26 to 1 [average follow-up 209 days (range 12-434)]. 89% of patients discontinued use of antireflux medications, and normal 24-hour pH was reported in 79% of patients. All patients were able to belch, and 49% experienced mild dysphagia. No device migrations or erosions occurred.||âLaparoscopic implant of the MSA device is safe and well tolerated.Â It requires minimal surgical dissection and a short learning curve compared to the conventional Nissen fundoplication.â|
|Bonavina,Â 2010 ||Case series (FDA Feasibility Trial Cohort, n = 44)||LINX reflux management system||At 1-year follow-up:|
Gastroesophageal reflux disease (GERD) Health-Related Quality of life (HRQoL) scores improved from 25.7 to 3.8. Patient satisfaction was 87%. Average pH was reduced from 11.9% to 3.1%. 90% of patients discontinued use of proton pump inhibitors (PPIs). 77% of patients experienced normal esophageal exposure.
GERD HRQoL scores improved from 25.7 to 2.4. Patient satisfaction was 86%. Average pH was reduced from 11.9% to 2.4%. 86% of patients discontinued use of PPIs. 90% of patients experienced normal esophageal exposure.
|âThe new laparoscopically implanted sphincter augmentation device eliminates GERD symptoms without creating undue side effects and is effective at 1 and 2 years of follow-up.â|
|Lipham, 2012 ||Case series (FDA Feasibility Trial Cohort, n=44)||LINX reflux management system||At 3-year follow-up:|
Average pH was reduced from 11.9 % to 3.8%.
Normalization of the pH was reported in 18 patients.
At 4-year follow-up:
Quality of life scores for GERD were improved in 23 patients. 20 patients discontinued use of PPIs. There were no reports of death or long-term device-related complications such as migration or erosion.
|âSphincter augmentation with the LINX Reflux Management System provided long-term clinical benefits with no safety issues, as demonstrated by reduced esophageal acid exposure, improved GERD-related quality of life, and cessation of dependence on PPIs, with minimal side effects and no safety issues. Patients with inadequate symptom control with acid suppression therapy may benefit from treatment with sphincter augmentation.â|
New Studies for 2016 Update
|Citation||Study Type||Treatment(s)||Results||Authorâs Conclusions|
|Lipham, 2015 ||Multi-institutional case series (n=1000)||LINX reflux management system||Over 1000 patients worldwide implanted with the MSA device at 82 institutions with median implant duration of 274 days. Event rates were 0.1% intra/perioperative complications, 1.3% hospital readmissions, 5.6% endoscopic dilations, and 3.4% reoperations.|
The primary reason for device removal was dysphagia. No device migrations or malfunctions were reported. Erosion of the device occurred in one patient (0.1%).
|The MSAD is a safe therapeutic option for patients with chronic, uncomplicated gastroesophageal reflux disease.|
|Bonavina, 2013 ||Single institution case series (n=100)||LINX reflux management system||Median implant duration was 3 years. Median total acid exposure time was reduced from 8.0% before implant to 3.2% post implant (p < 0.001). The median GERD Health Related Quality of Life score at baseline was 16 on PPIs and 24 off PPIs and improved to a score of 2 (p < 0.001).|
Freedom from daily dependence on PPIs was achieved in 85%. There have been no long-term complications. Three patients had the device laparoscopically removed with subsequent resolution of symptoms.
|Magnetic sphincter augmentation for GERD in clinical practice provides safe and long-term reduction of esophageal acid exposure, substantial symptom improvement, and elimination of daily PPI use.|
|Ganz, 2015 ||Multi-institutional, non-randomized, prospective case series (FDA Pivotal Trial, n=85)||LINX Reflux Management System||100 adults with GERD underwent surgery to implant MSA. 85 subjects were followed up for 5 years. Over the follow-up period, no device erosions, migrations, or malfunctions occurred. At baseline, the median GERD-HRQL scores were 27 in patients not taking PPIs and 11 in patients on PPIs; 5 years after device placement this score decreased to 4. All patients used PPIs at baseline; this value decreased to 15.3% at 5 years. Moderate or severe regurgitation occurred in 57% of subjects at baseline, but only 1.2% at 5 years. All patients reported the ability to belch and vomit if needed. Bothersome dysphagia was present in 5% at baseline and in 6% at 5 years. Bothersome gas-bloat was present in 52% at baseline and decreased to 8.3% at 5 years.||Augmentation of the lower esophageal sphincter with a magnetic device provides significant and sustained control of reflux, with minimal side effects or complications. No new safety risks emerged over a 5-year follow-up period. These findings validate the long-term safety and efficacy of the magnetic sphincter augmentation device for patients with GERD.|
|Saino, 2015 ||Case Series (FDA Feasibility Trial Cohort, n=33)||LINX Reflux Management System||At 5 years, outcomes were assessed in 33 of 44 patients to undergo MSA implantation surgery. Mean total percentage of time with pH <4 was 11.9% at baseline and 4.6% at|
5 years (P<0.001), with 85% of patients achieving pH normalization or at least a 50% reduction. Mean total GERD-HRQL score improved significantly from 25.7 to 2.9 (P<0.001) when comparing baseline and 5 years, and 93.9% of patients had at least a 50% reduction in total score compared with baseline. Complete discontinuation of PPIs was achieved by 87.8% of patients. No complications occurred in the long term, including no device erosions or migrations at any point.
|Based on long-term reduction in esophageal acid, symptom improvement, and no late complications, this study shows the relative safety and efficacy of magnetic sphincter augmentation for GERD.|
|Schwameis, 2014 ||Single institution case series (n=23)||LINX reflux management system||23 patients with GERD underwent implantation of MSA device. A significant decrease in all major GERD complaints were found: heartburn: 96%-22% (p<0.001); bloating: 70%-30% (p=0.006); respiratory complaints:|
57%-17% (p=0.039); sleep disturbance: 65%-4% (p<0.001). A four-week follow-up reduction of â¥50% of proton pump inhibitor (PPI) dose was achieved in over 80% of patients.Self-limiting difficulty in swallowing was found in 70% within four weeks. One patient required for endoscopic dilation. GERD-related quality of life improved significantly.
|LINX implantation is a standardized, technically simple, safe and well-tolerated expeditious procedure.|
|Reynolds, 2014 ||Prospective, observational, multi-institutional study (n=67)||LINX reflux management system||The mean operative time was 60 minutes and mean length of stay was 11 hours. A total of 77% of patients were no longer taking proton pump inhibitors. The most common postoperative complaint was dysphagia, which resolved in 79% of patients with a median time to resolution of eight weeks. There were eight patients with persistent dysphagia that required balloon dilation with improvement in symptoms.||MSA is a safe and effective alternative to fundoplication for treatment of GERD. The most common postoperative complaint is mild to moderate dysphagia, which usually resolves within 12 weeks.|
|Asti, 2016 ||Single institutional case series (n=164)||LINX reflux management system||Over the study period, 164 patients underwent a laparoscopic LINX implant and had a median follow-up of 48 months. Eleven (6.7%) were explanted at a later date. The estimated removal-free probability at 80 months was 0.91.|
The main presenting symptom requiring device removal was recurrence of heartburn or regurgitation, dysphagia, and chest pain. In 2 patients, full-thickness erosion of the esophageal wall with partial endoluminal penetration of the device occurred.
The median implant duration was 20 months, with 82% of the patients being explanted between 12 and 24 months after the implant. Device removal was most commonly combined with partial fundoplication. There were no conversions to laparotomy and the postoperative course was uneventful in all patients.
|Laparoscopic removal of the LINX device can be safely performed as a 1-stage procedure and in conjunction with fundoplication even in patients presenting with device erosion.|
|Louie, 2014 ||Single institution case-control study (34 MSA, 32 LNF)||LINX reflux management system and laparoscopic Nissen fundoplication||66 patients underwent operations (34 MSA and 32 LNF).|
Operative time was longer for LNF (118 vs. 73 min) and resulted in 1 return to the operating room and 1 readmission. Preoperative symptoms were abolished in both groups. At 6 months, scores on the Gastroesophageal Reflux Disease Health
Related Quality of Life scale improved from 20.6 to 5.0 for MSA vs.
|MSA results in similar objective control of GERD, symptom resolution, and improved quality of life compared with LNF. MSA seems to restore a more physiologic sphincter that allows physiologic reflux, facilitates belching, and creates less bloating and flatulence.|
|Sheu, 2015 ||Single institution case-control study (12 MSA, 12 LNF)||LINX reflux management system and laparoscopic Nissen fundoplication||75% (MSA) and 83% (LNF) reported resolution of GERD at short-term follow-up. Dysphagia was common following both MSA and LNF, but severe dysphagia requiring endoscopic dilation was more frequent after MSA (50 vs. 0 %, p = 0.01). A trend toward decreased adverse GI symptoms of bloating, flatulence, and diarrhea was seen after MSA compared to LNF (0 vs. 33 %). MSA had a shorter operative time (64 vs. 90 min, p < 0.01) but other perioperative outcomes were equivalent to LNF.||MSA and LNF are both effective and safe treatments for GERD; however, severe dysphagia requiring endoscopic intervention is more common with|
MSA. Other adverse GI side effects may be less frequent after MSA.
|Riegler, 2015 ||Prospective, observational, multi-institutional study (202 MSA, 47 LNF)||LINX reflux management system and laparoscopic Nissen fundoplication||The median GERD-health related quality of life score improved from 20.0 to 3.0 after MSA and 23.0 to 3.5 after LNF. Moderate or severe regurgitation improved from 58.2 to 3.1% after MSA and 60.0 to 13.0% after LNF (P = 0.014).|
Discontinuation of PPIs was achieved by 82% of patients after MSA and 63% after LF (P = 0.009). Excessive gas and abdominal bloating were reported by 10.0% of patients after MSA and 31.9% following LNF (Pâ¤0.001). Following
|Antireflux surgery should be individualized to the characteristics of each patient.Â Both MSA and LNF showed significant improvements in reflux control, with similar safety and reoperation rates.|
|Reynolds, 2015 ||Single institution case-control study (50 MSA, 50 LNF, propensity matched)||LINX reflux management system and laparoscopic Nissen fundoplication||MSA and LNF patients were matched using propensity scores incorporating multiple preoperative variables. From a series of 62 MSA and 117 LNF, 50 patients in both groups were matched using the “best-fit” model with a caliper of 0.5 SD. At 1 year after surgery, both groups had similar GERD Health Related Quality of Life scores (4.2 MSA and 4.3 LNF; p = 0.897) and proton-pump inhibitor use (17% of MSA and 8.5% of LNF; p = 0.355). Although there was no difference in the number of patients reporting mild gas and bloating (27.6% MSA and 27.6% LNF; p = 1.000), there were no patients with severe gas and bloating in the MSA group compared with 10.6% in the LNF group (p = 0.022). More LNF patients were unable to belch (8.5% of MSA and 25.5% of LNF; p = 0.028) or vomit (4.3% of MSA and 21.3% of LNF; p = 0.004). The incidence of postoperative dysphagia was similar between the groups (46.8% MSA and 44.7% LNF; p = 0.766).||Analogous GERD patients had similar control of reflux symptoms after both MSA and LNF. The inabilities to belch and vomit were significantly fewer with MSA, along with a significantly lower incidence of severe gasbloat symptoms. These results support the use of MSA as first-line therapy in patients with mild to moderate GERD.|
|Reynolds, 2016 ||Single institution case-control study (52 MSA, 67 LNF)||LINX Reflux Management System and laparoscopic Nissen fundoplication||Retrospective analysis of all patients who underwent MSA or LNF between January 2010 and June 2013. There were 52 MSA and 67 LNF. There was no significant difference between the mean charges for MSA and LNF ($48,491 vs. $50,111, p = 0.506). There were significant differences in OR time (66 min MSA vs. 82 min LNF, p < 0.01) and LOS (17 h MSA vs. 38 h LNF, p < 0.01). At 1-year follow-up, mean GERD-HRQL was 4.3 for MSA versus 5.1 for LNF (p = 0.47) and 85 % of MSA patients versus 92 % of LNF patients were free from PPIs (p = 0.37). MSA patients reported less gas bloat symptoms (23 vs. 53 %, p â¤ 0.01) and inability to belch (10 vs. 36 %, p â¤ 0.01) and vomit (4 vs. 19 %, p â¤ 0.01).||The side effect profile of MSA is better than LNF as evidenced by less gas bloat and increase ability to belch and vomit. LNF and MSA are comparable in symptom control, safety, and overall hospital charges. The charge for the MSA device is offset by less charges in other categories as a result of the shorter operative time and LOS.|
|Warren, 2016 ||A multi-institutional retrospective cohort study (201 MSA, 214 LNF)||LINX Reflux Management System and laparoscopic Nissen fundoplication||A total of 415 patients (201 MSA and 214 NF) underwent surgery. The groups were similar in age, gender, and GERD-HRQL scores but significantly different in preoperative obesity (32 vs. 40 %), dysphagia (27 vs. 39 %), DeMeester scores (34 vs. 39), presence of Barrett’s (18 vs. 31 %) and hiatal hernia (55 vs. 69 %). At a minimum of 1-year follow-up, 354 patients (169 MSA and 185 NF) had significant improvement in GERD-HRQL scores (pre to post: 21-3 and 19-4). MSA patients had greater ability to belch (96 vs. 69%) and vomit (95 vs. 43%) with less gas bloat (47 vs. 59%). Propensity-matched cases showed similar GERD-HRQL scores and the differences in ability to belch or vomit, and gas bloat persisted in favor of MSA. Mild dysphagia was higher for MSA (44 vs. 32 %). Resumption of daily PPIs was higher for MSA (24 vs. 12, p = 0.02) with similar patient-reported satisfaction rates.||MSA for uncomplicated GERD achieves similar improvements in quality of life and symptomatic relief, with fewer side effects, but lower PPI elimination rates when compared to propensity-matched NF cases. In appropriate candidates, MSA is a valid alternative surgical treatment for GERD management.|
|Asti, 2016 ||Single institutional observational cohort study (135 MSA, 103 laparoscopic Toupet fundoplication||LINX Reflux Management System and laparoscopic Toupet fundoplication||Over a 7-year period, 103 patients underwent an LTF (laparoscopic Toupet) and 135 a LINX procedure. All patients had a minimum 1-year follow-up. Over time, patients in both groups had similar GERD-HRQL scores (odds ratio [OR] 1.04, confidence interval [CI] 0.89â1.27; Pâ=â0.578), PPI use (OR 1.18, CI 0.81â1.70; Pâ=â0.388), gas-related symptoms (OR 0.69, CI 0.21â2.28; Pâ=â0.542), dysphagia (OR 0.62, CI 0.26â1.30; Pâ=â0.241), and reoperation-free probability (stratified log-rank testâ=â0.556).|
In 2 concurrent cohorts of patients with early stage GERD undergoing LTF or LINX and matched by propensity score analysis, health-related quality of life significantly improved and GERD-HRQL scores had a similar decreasing trend over time up to 7 years of follow-up.
|LTF and LINX provide similar disease-specific quality of life over time in patients with early stage GERD.|