Abstract and Introduction
Abstract
Objectives Transoral incisionless fundoplication (TIF) was developed in an attempt to create a minimally invasive endoscopic procedure that mimics antireflux surgery. The objective of this trial was to evaluate effectiveness of TIF compared with proton pump inhibition in a population consisting of gastroesophageal reflux disease (GERD) patients controlled with proton pump inhibitors (PPIs) who opted for an endoscopic intervention over lifelong drug dependence.
Methods Patients with chronic GERD were randomized (2:1) for TIF or continuation of PPI therapy. American Society of Anesthesiologists >2, body mass index >35 kg/m, hiatal hernia >2 cm, and esophageal motility disorders were exclusion criteria. Primary outcome measure was GERD-related quality of life. Secondary outcome measures were esophageal acid exposure, number of reflux episodes, PPI usage, appearance of the gastroesophageal valve, and healing of reflux esophagitis. Crossover for the PPI group was allowed after 6 months.
Results A total of 60 patients (TIF n=40, PPI n=20, mean body mass index 26 kg/m, 37 male) were included. At 6 months, GERD symptoms were more improved in the TIF group compared with the PPI group (P<0.001), with a similar improvement of distal esophageal acid exposure (P=0.228) compared with baseline. The pH normalization for TIF group and PPI group was 50% and 63%, respectively. All patients allocated for PPI treatment opted for crossover. At 12 months, quality of life remained improved after TIF compared with baseline (P<0.05), but no improvement in esophageal acid exposure compared with baseline was found (P=0.171) and normalization of pH was accomplished in only 29% in conjunction with deteriorated valve appearances at endoscopy and resumption of PPIs in 61%.
Conclusion Although TIF resulted in an improved GERD-related quality of life and produced a short-term improvement of the antireflux barrier in a selected group of GERD patients, no long-term objective reflux control was achieved.
Introduction
Gastroesophageal reflux disease (GERD) was defined in the Montreal consensus as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Typical symptoms include heartburn, regurgitation, belching, and dysphagia. Esophageal complications of GERD are associated with mucosal injury of the esophagus and include esophagitis, stricture formation, Barrett's esophagus, and esophageal cancer. The so-called atypical symptoms are related to extraesophageal complications of the disease, such as laryngitis, cough, asthma, and dental erosions. The need for a long-term treatment of GERD has become increasingly apparent in the past two decades as a result of a growing incidence and prevalence of this chronic disease. The likelihood of developing GERD increases with the severity of the anatomical disorder and dysfunction of the gastroesophageal junction (GEJ) that represents the primary defense against reflux of gastric content into the esophagus. Although proton pump inhibitors (PPIs) are effective in controlling symptoms, the disease is not cured and patients will often have a lifelong commitment to drug therapy. Studies have shown that up to 50% of patients treated with PPIs continue to have abnormal acid reflux and up to 35% experience a relapse of symptoms after a 3-year follow-up, requiring titration with increasing doses of PPIs and later referral for surgery.
The merits of early surgery in GERD patients have been demonstrated in several randomized controlled trials. Antireflux surgery was shown to be more effective than pharmacological antisecretory therapies in terms of patient satisfaction, clinical outcome, and healthcare cost reduction in the long-term management of GERD. Hence, operative restoration of GEJ competence at the anatomic, mechanic, and physiologic levels seems critical in GERD treatment, but this has not yet been established without side effects and/or complications. Disadvantages of surgery are the invasiveness and fundoplication-related side effects that frequently compromise the otherwise excellent postsurgical results. Persistent dysphagia, inability to belch and vomit, as well as gas bloating and flatulence are common and difficult to treat. To minimize the risk of chronic complications, a variety of factors need to be taken into account, including technical aspects of the operation. Restoration of the anatomy, mechanics, and physiology of the GEJ, with "tailoring" of the valve to the individual patient needs, seems crucial for an adequate repair that should allow air to be vented from the stomach, without jeopardizing the efficacy of the antireflux barrier.
The field of endoscopic fundoplication has gained popularity over the past few years, and in an attempt to create a less invasive procedure that mimics antireflux surgery with fewer side effects, transoral incisionless fundoplication (TIF) was developed. The technique was designed to construct a partial fundoplication at the GEJ, restoring the angle of His, and reducing small hiatal hernia, by means of natural orifice surgery, using the EsophyX device. The device was cleared by the US Food and Drug Administration for treatment of symptomatic chronic GERD in 2007, after it was demonstrated to be safe and effective in a company-sponsored multicenter study.
Several initial reports on TIF were encouraging and showed effectiveness in reducing typical and atypical GERD symptoms, eliminating daily PPI dependence, as well as in normalizing distal esophageal pH. On the contrary, other early experiences reported substantial failures rates. The available data on the TIF technique are of limited quality and extracted from uncontrolled studies with generally a short follow-up duration.
All previous studies included patients who were referred for surgical management as they were refractory to PPI treatment and would otherwise probably have undergone conventional laparoscopic antireflux surgery. Because important components of antireflux surgery, such as extragastric mobilization of the stomach and esophagus, allowing hernia reduction and crural closure, are not achievable with TIF, the procedure would only be suitable for few selected surgical candidates. We hypothesized that the procedure would be more beneficial to patients who are well controlled with medication, but opt for a more definitive GERD therapy. Particularly patients who have elements of volume reflux and regurgitation in their symptom complex may benefit from endoscopic fundoplication. If proven effective, endoscopic fundoplication would be an alternative to PPI treatment and might also be cost effective if PPI cessation can be maintained.
The primary objective of this trial was to evaluate the effectiveness of TIF procedure in treating GERD patients who were well controlled on daily PPI therapy. The study tested the hypothesis that TIF would be as effective as PPI treatment in controlling GERD symptoms, esophageal acid exposure, and esophagitis, but would be more effective in controlling nonacidic reflux and thereby improve the quality of life. Secondary objectives were the evaluation of effectiveness of the TIF procedure in restoring the anatomy, biomechanics, geometry, and physiology of the antireflux barrier.