2) Esophageal sphincter device for gastroesophageal reflux disease
Ganz RA, Peters JH, Horgan S, Bemelman WA, Dunst CM, Edmundovicz SA,
Lipham JC, Luketich JD, Melvin WS, Oelschlager BK, Schlack-Haerer SC,
Smith CD, Smith CC, Dunn D, Taiganides PA: N Engl J Med 2013;368:719-27
Aim and study design
A multicenter trial was designed to assess the safety and effectiveness of a
magnetic device (LINX Reflux Management System, Torax Medical,
Minneapolis, USA) that augments the resistance of the lower esophageal
sphincter to reflux. Between January and September 2009, 100 patients with
gastroesophageal reflux disease (GERD) were enrolled in 13 centers in the
United States and one in Netherlands. Eligible individuals were 18 to 75 years
of age. All had at least a 6-month history of GERD, a partial response to daily
proton-pump inhibitors (PPI), and an abnormal esophageal acid exposure
documented by pH monitoring. Patients with large hiatal hernia, grade C or D
esophagitis, body-mass index greater than 35, Barrett’s esophagus,
esophageal motility disorders, dysphagia, and allergy to nickel were excluded
from the study. In addition to endoscopy and pH monitoring, all patients
underwent esophageal manometry and barium esophagogram. Annual
screening was planned for a total 5 years.
The magnetic device was implanted through a standard laparoscopic
approach by academic or community surgeons who had experience with
fundoplication. The primary end-points were the number of patients in whom
acid exposure was normalized or was decreased by 50% or more. The
secondary end-points were the number of patients with a reduction of 50% or
more in the total score for quality of life, and a reduction of 50% or more in the
dose of PPI. End-point analyses were performed according to the intention-totreat principle.
Results
The median duration of therapy with PPI was 5 years. The median percent
time with pH below 4 during a median pH-monitoring period of 45 hours was
10.9% (4.8-25.4), and the median DeMeester score was 36.6 (16.3-83.8). The
median quality of life score was 27 off-PPI and 11 on-PPI.
The median time required for device implantation was 36 minutes. No
reversions to fundoplication nor intraoperative complications occurred. All
patients were discharged home within one day. The primary end-point, i.e.
normalization or a 50% reduction in esophageal acid exposure, was obtained
in 64% of patients (95% confidence interval 54-73). The secondary end-point,
i.e. a 50% reduction in the quality of life score, was obtained in 92% of patients
(95% confidence interval 56-96). Finally, 93% of patients reported a 50% or
more reduction in the average daily dose of PPI. The median quality of life
score was significantly decreased at one year post implantation and remained
stable at 2 and 3 years (p<0.005). All individual components of the pH
monitoring significantly improved after surgery (p<0.001).
Dysphagia was the most frequent adverse event and was reported by 68% of
the patients. Endoscopic dilatation was performed in 19 patients and was
successful in 16. The percentage of patients with esophagitis significantly
decreased after operation (p<0.001). Removal of the device was required in 6
patients because of persistent dysphagia (n=3), persistent reflux symptoms
(n=1), persistent chest pain (n=1), and intermittent vomiting (n=1). The
procedure of removal was uneventful; in 3 of the 6 patients a Nissen
fundoplication was performed. At 1 and 2 years after implantation there was no
evidence of device migration or erosion. At 3 years, only 2 patients reported
the inability to belch or vomit.
Conclusions
This single-group trial confirmed that a magnetic device designed to augment
the lower esophageal sphincter can be safely and effectively implanted using a
standard laparoscopic approach. The device decreased esophageal acid
exposure, improved reflux symptoms, and allowed cessation of proton-pump
inhibitors in the majority of patients.
CRITICAL APPRAISAL
About 40% of patients with typical symptoms of gastroesophageal reflux
disease (GERD) are refractory to pharmacologic therapy with proton-pump
inhibitors (PPI) despite dose optimization (1). Laparoscopic Nissen
fundoplication, the gold standard of surgical therapy, is largely underused and
commonly reserved for patients with severe complications of GERD. This
leaves a significant gap in the treatment continuum for GERD in the current
clinical practice (2).
1) The LINX Reflux Management System was designed to provide a
permanent solution to GERD by augmenting the lower esophageal sphincter
barrier with a simple, reproducible, and reversible laparoscopic procedure that
does not alter gastric anatomy.
2) The short-term, mid-term, and the 4-year results of a prospective feasibility
clinical study evaluating 44 patients in whom the LINX was implanted at four
study centers in the USA and Europe between February 2007 and October
2008 have been published (3-5). Ganz et al have now reproduced the results
of this feasibility study, but in a larger cohort of patients. No significant
differences were found between the studies in terms of safety and efficacy.
The median DeMeester score before and after magnetic sphincter
augmentation improved from 42.3 to 14.7 in the feasibility study and from 36.6
to 13.5 in the study by Ganz et al.; pH normalization rates were 80% and 58%,
respectively. A reduction of at least 50% in the GERD-HRQL score compared
to baseline off PPIs was achieved by 100% of patients in the feasibility study
and 92% in the comparative study. Elimination of daily PPI use was reported in
80% and 87% of the patients, respectively.
3) At the University of Milan Medical School we have been involved both in
the feasibility trial and in a registry of anti-reflux surgery, which is currently
enrolling European patients to include treatment with either the LINX System
or the Nissen fundoplication. The clinical outcomes over a six-year period in
our clinical institution replicate the results from both the feasibility trial and the
current trial by Ganz et al., showing that reduction in acid exposure,
improvement in quality of life and elimination of PPI can be achieved in routine
clinical practice (Bonavina L et al., J Am Coll Surg, in press).
4) The consistency of the results between these independent studies further
supports magnetic sphincter augmentation as an important addition to the
treatment options available for antireflux surgery. Further clinical experience
and close patient follow-up are necessary to establish whether this innovation
represents a true paradigm shift in the treatment of GERD.
References
1. Katz PO, Gerson LB, Vela MF: Guidelines for the diagnosis and treatment
of gastroesophageal reflux disease. Am J Gastroenterol 2013;108:308-328
2. Bonavina L, DeMeester TR, Ganz RA: LINX™ Reflux Management
System: magnetic sphincter augmentation in the treatment of
gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol
2012;6:667-74
3. Bonavina L, Saino GI, Bona D, Lipham J, Ganz RA, Dunn D, DeMeerster
TR: Magnetic augmentation of the lower esophageal sphincter: results of a
feasibility clinical trial. J Gastrointest Surg 2008; 12:2133-40
4. Bonavina L, DeMeester TR, Fockens P, Dunn D, Saino G, Bona D, Lipham
J, Bemelman W, Ganz RA: Laparoscopic Sphincter Augmentation Device
Eliminates Reflux Symptoms and Normalizes Esophageal Acid Exposure.
One- and 2-year results of a feasibility trial. Ann Surg; 2010; 252:857-862
5. Lipham JC, DeMeester TR, Ganz RA, Bonavina L, Saino G, Dunn DH,
Fockens P, Bemelman W: The LINX® reflux management system: confirmed
safety and efficacy now at 4 years. Surg Endosc. 2012;26:2944-9
Critical appraisal by Luigi Bonavina, MD, Professor of Surgery, Chief of the
Division of General Surgery, Department of Biomedical Sciences for Health,
University of Milan Medical School, IRCCS Policlinico San Donato. Via
Morandi 30, 20097 San Donato Milanese (Milano), Italy
Tel. +39 02 52774621 / Fax +39 02 52774395
email luigi.bonavina@unimi.it