Table of Contents  

Kristo and Schoppmann: Surgical therapies for gastro-oesophageal reflux disease

Introduction

Gastro-oesophageal reflux disease (GORD) and its tremendous growth due to rising obesity represents a huge socioeconomic problem today.1 Prevalence rates > 30% are currently reported, and longitudinal studies demonstrate a worrisome 50% rise in patients reporting symptoms of GORD.2 Malignant transformation and oesophageal cancer are observed more frequently in advanced stages of GORD, and are associated with poor overall survival rates, even in young patients.3

A weak lower oesophageal sphincter (LOS) was established decades ago as a cause of abnormal gastro-oesophageal reflux. Strengthening the LOS as a prophylactic measure against GORD therefore seems reasonable. Recently, Kwiatek et al.4 tested a novel functional luminal imaging probe in a prospective case–control series and reported that distensibility of the LOS was greater in patients with GORD.

Implantation of external devices to support the LOS dates back to 1979, when Angelchik5 successfully implanted a silicone device around the LOS in 46 patients. Subsequently, the mechanism of action was investigated in animal studies, in which rubber bands were placed around the LOS in canines.6 Samelson et al.6 noticed that circumferential silk ligatures placed 3 cm distal to the LOS resulted in increased LOS opening pressures. Moreover, after placing the silicone prosthesis around the LOS, acid exposure times were reduced from 35.4% to 1.8% in myomectomized dogs. Although short-term results were quite promising, serious adverse events such as perforations occurred in the long term, necessitating major surgical resections.7 It was realized that inflexible silicone migrates and erodes over time, which is incompatible with long-term control of symptoms of GORD.

All newly established devices try to avoid this deficiency. Magnetic sphincter augmentation, electrical sphincter stimulation and endoscopic fundoplication incorporate novel methods that expand the therapeutic armamentarium. This article focuses on these newly established interventions and compares them with the current standard surgical approach of laparoscopic fundoplication.

Magnetic sphincter augmentation

Magnetic sphincter augmentation utilizes magnetism, a force not known to decrease over time, to stabilize the LOS in a minimally invasive fashion. The LINX® Reflux Management System (Torax Medical, St. Paul, MN, USA) contains a variable number of titanium beads, each with a magnetic core, connected by a distensible titanium ring (Figure 1). LINX is intended to open when swallowing and prevent reflux that can damage the oesophagus (Figure 2).

FIGURE 1

The LINX device consists of titanium beads with magnetic cores connected by a distensible titanium ring.

HMJ-745-fig1.jpg
FIGURE 2

Postoperative barium swallow showing the subdiaphragmatic position of the LINX device.

HMJ-745-fig2.jpg

Ganz et al.8 demonstrated feasibility in animal studies in which magnetic force was shown to increase LOS pressures while preserving swallowing and belching functions. The authors reported that the device was safely implanted in all animals, with no impact on eating behaviour or visible endoscopic inflammation. Furthermore, gastric yield pressures correlated significantly with magnetic forces. Importantly, Bonavina et al.9 presented the first data regarding humans, enrolling patients with typical heartburn who responded at least partially to proton pump inhibitors (PPIs). GORD health-related quality-of-life (GORD-HRQL) scores dropped significantly, from 26 to 1, with no operative complications observed after a mean follow-up of 209 days. Postoperatively, 89% of patients were no longer taking antireflux medication and 79% had normal 24-hour pH levels. Mild dysphagia was registered frequently in 45% of study participants but was predominantly self-limiting. One device was removed owing to persisting dysphagia. Thus, a minimally invasive surgical option for treatment of GORD was born. Subsequently, these patients were tracked for up to 2 years, with striking results. Mean GORD-HRQL scores improved, from a baseline of 26 to 2.4 at 2 years, with 90% of patients presenting with a normal distal oesophagus acid exposure time.10 Almost 90% of study participants were satisfied with surgical outcomes as no migration or erosion occurred, and dysphagia resolved within 90 days. Furthermore, at 4 years, Lipham et al.11 reported the absence of major adverse events and a reduction of acid exposure time from 11.9% to 3.8% postoperatively. Interestingly, all patients showed an improved quality of life, with 80% undergoing no medical antireflux treatment. The authors stated that patients with inadequate medical symptom control are potential candidates for this novel therapeutic intervention. Even if it is necessary to remove the device, as with the patient mentioned previously with persisting symptoms of GORD, other surgical interventions remain feasible.

Similarly, Ganz et al.12 prospectively evaluated the implantation of the LINX device in 100 patients with GORD who responded at least partially to PPIs. Although the trial was criticized for its defensive design, the results confirmed prior data. The primary outcome was defined as normalization of oesophageal acid exposure or a reduction of ≥ 50% at 1 year. This primary parameter was achieved in 64% of patients, whereas 93% experienced a reduction in their PPI intake of ≥ 50%. Additionally, an overwhelming majority (92%) reported an improvement of ≥ 50% in quality of life. Nevertheless, only patients with limited GORD were included in the trial; exclusion criteria included large hiatal hernia, Los Angeles grade C and D oesophagitis, Barrett’s oesophagus, a body mass index of > 35 kg/m2 and abnormal oesophageal motility.

The outcomes of our own patient-adapted surgical antireflux strategy support the data of Ganz et al.:8 patients have experienced a significant decrease in typical and atypical symptoms of GORD after the implantation of the LINX device.13 Within the first 4 weeks following surgery, 70% of patients had difficulty swallowing, which was self-limiting. One patient required endoscopic dilatation, which did not result in any major adverse events.

Our institution also participated in a trial to compare magnetic sphincter augmentation with laparoscopic fundoplication.14 We published 1-year results of 202 patients with LINX implantation and 47 patients who underwent laparoscopic fundoplication. Laparoscopic fundoplication was associated with advanced GORD and was less effective than LINX in reducing rates of excessive gas and abdominal bloating. This can be explained by the fact that LINX preserves belching (98.4%) and vomiting (91.3%) in the majority of cases. Although both strategies were effective in controlling symptoms and improving GORD-HRQL, LINX had higher PPI cessation rates (81.8% vs. 63%). Similar comparative studies have been published and have revealed that patients receiving LINX are often self-referred.15,16

Currently, LINX implantation inclusion criteria extend relatively far owing to the notable results in patients with limited disease. Recently, Rona et al.17 reported outcomes of LINX use in patients with large hiatal hernia. Interestingly, LINX decreased the postoperative intake of PPI in comparison with small hiatal hernia, which was also reflected in improved GORD-HRQL. Symptom improvement and resolution, as well as interventions owing to dysphagia, were similar between groups. Therefore, LINX can also be implanted after prior hiatal repair.

To conclude, LINX seems to represent a more physiological antireflux mechanism than laparoscopic fundoplication. The ability to belch and vomit is maintained and rates of gas bloating syndrome are lower. LINX enriches the interventional armamentarium and has proven long-term efficacy; it is a major part of our individualized concept for GORD at our centre.

Electrical sphincter stimulation

Electrical sphincter stimulation is a novel LOS supportive device that can address changing lifestyle behaviours. Interestingly, prevention of experimentally induced reflux by electrical stimulation was first tested decades ago.18 Subsequently, Clarke et al.19 evaluated on-demand LOS stimulation using an endoscopically implanted system in dogs. Stimulation amplitudes of 3–10 mA with a frequency of 20 Hz and a pulse width of 200 μs were able to significantly increase LOS pressure, indicating its potential for preventing GORD in humans. Subsequently, Sanmiguel et al.20 investigated effects of low- and high-frequency stimulation on LOS function in animals. The authors reported that low- but not high-frequency stimulation was able to increase LOS pressure. Additionally, they discovered that a rise in LOS pressure was mediated by cholinergic pathways and that nitric oxide was responsible for relaxation.

EndoStim® (EndoStim BV, the Hague, Netherlands) was developed as an electrical stimulator for GORD in humans. The device is implanted in a minimally invasive fashion by a laparoscopic procedure. Two needle electrodes are placed at the LOS level and secured (Figure 3). After fixation, endoscopy is performed to check that perforation has not occurred. The needle electrodes are connected to a generator that delivers energy for the stimulation process, which is placed in a subcutaneous pocket (Figure 4).

FIGURE 3

Intraoperative situs during an EndoStim implantation. Needle electrodes are positioned at the level of the lower oesophageal sphincter and secured by clips.

HMJ-745-fig3.jpg
FIGURE 4

Postoperative radiograph showing electrodes positioned at the lower oesophageal sphincter level and connected to a subcutaneous generator.

HMJ-745-fig4.jpg

Rodriguez et al.22 first reported implantation in humans during elective cholecystectomy. Ten patients received high-frequency, low-energy or low-frequency, high-energy stimulation. Both methods increased LOS pressure while sparing oesophageal peristalsis and relaxation. Importantly, no adverse events such as cardiac arrhythmia were noted. Similar outcomes were reported in a trial in which five patients with symptoms of GORD received electrical sphincter stimulation.21 As a result, short-term stimulation of the LOS was ready to be tested on patients with GORD.

Rodriguez et al.22 treated 24 patients with long-term intermittent electrical stimulation therapy, delivering energy with a frequency of 20 Hz and amplitudes of 3–8 mA during 30-minute sessions. Patients were at least partially responsive to PPI, had a hiatal hernia size of ≤ 3 cm and oesophagitis of Los Angeles grade C or below. At 1 year, median GORD-HRQL scores dropped from 9 to 2, with a reduction in oesophageal acid exposure time from 10.1% to 3.3%. Moreover, 69% experienced normal 24-hour pH levels or an improvement of ≥ 50%. Strikingly, 96% of participants were no longer taking PPI medication. Again, no serious adverse events were noted.

Currently, an international multicentre trial is being performed, and interim results are promising.23 Data for 44 patients with an incomplete response to PPIs have been reported, with 16 patients receiving hiatal repair. A significant improvement in GORD-HRQL has been reported, which accompanies a decrease in oesophageal acid exposure time. Patients have responded well to therapy, particularly concerning regurgitation, without any patients experiencing dysphagia. EndoStim has also demonstrated sustained antireflux effects. Recently, the results of 2 years’ intermittent EndoStim treatment were revealed.24 Median distal oesophageal acid exposure time dropped from 10% at baseline to 4% at 2 years, with 76.2% of patients no longer undergoing medical antireflux therapy. The authors emphasized a significant improvement of typical and atypical symptoms of GORD, with no serious device-related adverse events at 2 years. No patients were unsatisfied with electrical stimulation therapy.

In summary, long-term intermittent electrical stimulation of the LOS is effective as a treatment of GORD. Typical and atypical symptoms respond excellently to EndoStim therapy, with a significant reduction in oesophageal acid exposure time. Stimulation is associated with high PPI cessation rates and high patient satisfaction levels, and avoids the risk of post-interventional dysphagia. Nevertheless, extended long-term results are awaited.

Laparoscopic fundoplication

Laparoscopic fundoplication remains the standard and most commonly used surgical antireflux treatment, and has proven long-term efficacy (Figure 5). Both open and laparoscopic approaches offer adequate control of GORD symptoms, but the open procedure is associated with a higher risk of reoperation.25 As a result of its long history, patients should be informed that successful fundoplication could provide lifelong relief from symptomatic disease and improved quality of life.26 However, two potential complications of fundoplication should be acknowledged: dysphagia and gas bloating syndrome. A meta-analysis of outcomes of Nissen fundoplication and Toupet fundoplication revealed that the prevalence of dysphagia and gas bloating syndrome was higher following Nissen fundoplication.27 Nevertheless, subgroup analysis revealed no differences in dysphagia rates. Disappointing results were reported by Vakil et al.,28 who observed that only 61% of their patients were satisfied; 32% were still taking PPIs on a regular basis, 11% required oesophageal dilatation for dysphagia and 7% underwent repeat surgical procedures. Complications after antireflux surgery were also evaluated by Dominitz et al.,29 who reviewed 3145 patients after surgical antireflux treatment. The authors reported that dysphagia was observed in 19.4% of patients, with repeat surgery being performed in 2.3%. Postoperatively, nearly 50% of patients received at least three prescriptions for H2 receptor antagonists, PPIs or motility-stimulating agents despite surgical therapy. Therefore, these issues require treatment in a highly specialized centre where patients are informed that fundoplication is a highly effective surgical antireflux procedure with proven long-term efficacy when performed by specialized teams.

FIGURE 5

Intraoperative situs of a laparoscopic Nissen fundoplication.

HMJ-745-fig5.jpg

Endoscopic fundoplication

Endoscopic fundoplication is a surgical antireflux procedure that tries to mimic the outcome of laparoscopic fundoplication while taking an endoscopic approach. The endoscopic recreation of a barrier against reflux is intended to decrease GORD symptoms.

Initial long-term results were disappointing. Suturing with the EndoCinch™ device (Bard Endoscopic Technologies, Billerica, MA, USA) was tolerated, with no major complication in the short or long term, but associated with an 80% treatment failure rate.30 Eighteen months after endoscopic gastroplication, symptoms remained unchanged in most patients. This was mainly attributed to a loss of placed sutures in the majority of patients. In only 17% of patients were all sutures still in situ, whereas no sutures at all were observed in 26% of patients. These results clearly demonstrated the need for technological improvement.

Alternatively, the EsophyX® device (EndoGastric solutions, Redmond, WA, USA) allows the creation of a full-thickness gastro-oesophageal fundoplication ≤ 3.5 cm above the gastro-oesophageal junction.31 Jobe et al.32 tested transoral incisionless fundoplication (TIF) with this new device in 21 canines. The authors developed two different procedures: TIF 1.0 and TIF 2.0. TIF 2.0 was characterized by additional circumferential tightening and, in comparison with TIF 1.0, produced outcomes closer to the outcomes of laparoscopic fundoplication. Later, Cadière et al.33 demonstrated technical feasibility in humans, enrolling 19 patients with chronic GORD, PPI dependence and good oesophageal motility. Newly created endoscopic antireflux valves had a median length of 4 cm and a circumference of 210°. Additionally, all hiatal hernias could be reduced. At 1 year, median length was 3 cm with a circumference of 200°. Importantly, 81% of valves retained their tightness, leading to an 82% satisfaction rate. The majority of patients (82%) were no longer taking PPIs, with 63% experiencing regular oesophageal acid exposure. However, at 3 years clinical practice was disappointing. Witteman et al.34 reported that 36% had undergone laparoscopic fundoplication owing to ineffectiveness of TIF. However, endoscopic fundoplication improved quality of life and reduced PPI intake in only a subgroup of patients. Interestingly, valves classified as Hill grade I or grade II, good oesophageal motility, number of fasteners and hiatal hernias of ≤ 2 cm predict good results.35 Therefore, appropriate patient selection is crucial for good treatment response.

Recently, randomized data on endoscopic fundoplication were published. Trad et al.36 randomized 63 patients to either endoscopic fundoplication or PPI therapy. Strikingly, in these carefully selected patients, TIF was more effective at eliminating regurgitation and atypical GORD symptoms than medical antireflux therapy at 6 months. Hunter et al.37 observed similar results: TIF was particularly effective in patients with troublesome regurgitation despite PPI therapy.

Currently, MUSE™ (Medigus, Omer, Israel), a video- and ultrasound-guided endoscopic stapler that mimics an anterior fundoplication, is also being evaluated for endoscopic treatment of GORD. Initial results are promising and long-term data are awaited.38

Conclusion

Endoscopic fundoplication is a procedure that tries to mimic the outcome of laparoscopic fundoplication and is currently being tested in patients with limited GORD. Patients with troublesome regurgitation despite PPI therapy, small hiatal hernias, Hill grade I or grade II valves and good oesophageal motility are potential candidates for this treatment. Nevertheless, long-term observations are needed to confirm technical stability.

References

1. 

Kristo I, Asari R, Rieder E, Riegler V, Schoppmann SF. Treatment of Barrett’s esophagus: update on new endoscopic surgical modalities. Minerva Chir 2015; 70:107–18.

2. 

Hallan A, Bomme M, Hveem K, Moller-Hansen J, Ness-Jensen E. Risk factors on the development of new-onset gastroesophageal reflux symptoms. A population-based prospective cohort study: the HUNT study. Am J Gastroenterol 2015; 110:393–400; quiz 401. https://doi.org/10.1038/ajg.2015.18

3. 

Boys JA, Oh DS, Lewis JS, DeMeester SR, Hagen JA. Esophageal adenocarcinoma in patients younger than 40 years: a two-decade experience at a public and private hospital. Am Surg 2015; 81:974–8.

4. 

Kwiatek MA, Pandolfino JE, Hirano I, Kahrilas PJ. Esophagogastric junction distensibility assessed with an endoscopic functional luminal imaging probe (EndoFLIP). Gastrointest Endosc 2010; 72:272–8. https://doi.org/10.1016/j.gie.2010.01.069

5. 

Angelchik JP, Cohen R. A new surgical procedure for the treatment of gastroesophageal reflux and hiatal hernia. Surg Gynecol Obstet 1979; 148:246–8.

6. 

Samelson SL, Weiser HF, Bombeck CT, et al. A new concept in the surgical treatment of gastroesophageal reflux. Ann Surg 1983; 197:254–9. https://doi.org/10.1097/00000658-198303000-00002

7. 

Kauten JR, Mansour KA. Complications of the Angelchik prosthesis in the management of gastroesophageal reflux. Am Surg 1986; 52:208–13.

8. 

Ganz RA, Gostout CJ, Grudem J, Swanson W, Berg T, DeMeester TR. Use of a magnetic sphincter for the treatment of GERD: a feasibility study. Gastrointest Endosc 2008; 67:287–94. https://doi.org/10.1016/j.gie.2007.07.027

9. 

Bonavina L, Saino GI, Bona D, et al. Magnetic augmentation of the lower esophageal sphincter: results of a feasibility clinical trial. J Gastrointest Surg 2008; 12:2133–40. https://doi.org/10.1007/s11605-008-0698-1

10. 

Bonavina L, DeMeester T, Fockens P, et al. Laparoscopic sphincter augmentation device eliminates reflux symptoms and normalizes esophageal acid exposure: one- and 2-year results of a feasibility trial. Ann Surg 2010; 252:857–62. https://doi.org/10.1097/SLA.0b013e3181fd879b

11. 

Lipham JC, DeMeester TR, Ganz RA, et al. The LINX® reflux management system: confirmed safety and efficacy now at 4 years. Surg Endosc 2012; 26:2944–9. https://doi.org/10.1007/s00464-012-2289-1

12. 

Ganz RA, Peters JH, Horgan S, et al. Esophageal sphincter device for gastroesophageal reflux disease. N Engl J Med 2013; 368:719–27. https://doi.org/10.1056/NEJMoa1205544

13. 

Schwameis K, Schwameis M, Zorner B, et al. Modern GERD treatment: feasibility of minimally invasive esophageal sphincter augmentation. Anticancer Res 2014; 34:2341–8.

14. 

Riegler M, Schoppman SF, Bonavina L, Ashton D, Horbach T, Kemen M. Magnetic sphincter augmentation and fundoplication for GERD in clinical practice: one-year results of a multicenter, prospective observational study. Surg Endosc 2015; 29:1123–9. https://doi.org/10.1007/s00464-014-3772-7

15. 

Reynolds JL, Zehetner J, Wu P, Shah S, Bildzukewicz N, Lipham JC. Laparoscopic magnetic sphincter augmentation vs laparoscopic Nissen fundoplication: a matched-pair analysis of 100 patients. J Am Coll Surg 2015; 221:123–8. https://doi.org/10.1016/j.jamcollsurg.2015.02.025

16. 

Sheu EG, Nau P, Nath B, Kuo B, Rattner DW. A comparative trial of laparoscopic magnetic sphincter augmentation and Nissen fundoplication. Surg Endosc 2015; 29:505–9. https://doi.org/10.1007/s00464-014-3704-6

17. 

Rona KA, Reynolds J, Schwameis K, et al. Efficacy of magnetic sphincter augmentation in patients with large hiatal hernias. Surg Endosc 2017; 31:2096–102. https://doi.org/10.1007/s00464-016-5204-3

18. 

Ellis F, Berne TV, Settevig K. The prevention of experimentally induced reflux by electrical stimulation of the distal esophagus. Am J Surg 1968; 115:482–7. https://doi.org/10.1016/0002-9610(68)90191-8

19. 

Clarke JO, Jagannath SB, Kalloo AN, Long VR, Beitler DM, Kantsevoy SV. An endoscopically implantable device stimulates the lower esophageal sphincter on demand by remote control: a study using a canine model. Endoscopy 2007; 39:72–6. https://doi.org/10.1055/s-2006-945102

20. 

Sanmiguel CP, Hagiike M, Mintchev MP, et al. Effect of electrical stimulation of the LES on LES pressure in a canine model. Am J Physiol Gastrointest Liver Physiol 2008; 295:G389–94. https://doi.org/10.1152/ajpgi.90201.2008

21. 

Banerjee R, Pratap N, Kalpala R, Reddy DN. Effect of electrical stimulation of the lower esophageal sphincter using endoscopically implanted temporary stimulation leads in patients with reflux disease. Surg Endosc 2014; 28:1003–9. https://doi.org/10.1007/s00464-013-3271-2

22. 

Rodriguez L, Rodriguez P, Gomez B, et al. Long-term results of electrical stimulation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease. Endoscopy 2013; 45:595–604. https://doi.org/10.1055/s-0033-1344213

23. 

Kappelle WF, Bredenoord AJ, Conchillo JM, et al. Electrical stimulation therapy of the lower oesophageal sphincter for refractory gastro-oesophageal reflux disease – interim results of an international multicentre trial. Aliment Pharmacol Ther 2015; 42:614–25. https://doi.org/10.1111/apt.13306

24. 

Rodriguez L, Rodriguez P, Gomez B, et al. Two-year results of intermittent electrical stimulation of the lower esophageal sphincter treatment of gastroesophageal reflux disease. Surgery 2015; 157:556–7. https://doi.org/10.1016/j.surg.2014.10.012

25. 

Oor JE, Roks DJ, Broeders JA, Hazebroek EJ, Gooszen HG. Seventeen-year outcome of a randomized clinical trial comparing laparoscopic and conventional Nissen fundoplication: a plea for patient counseling and clarification. Ann Surg 2016; 266:23–8. https://doi.org/10.1097/SLA.0000000000002106

26. 

Neuvonen P, Sand J, Matikainen M, Rantanen T. Does Nissen fundoplication provide lifelong reflux control? Symptomatic outcome after 31–33 years. World J Surg 2017; 41:2046–52. https://doi.org/10.1007/s00268-017-3924-8

27. 

Du X, Hu Z, Yan C, Zhang C, Wang Z, Wu J. A meta-analysis of long follow-up outcomes of laparoscopic Nissen (total) versus Toupet (270 degrees) fundoplication for gastro-esophageal reflux disease based on randomized controlled trials in adults. BMC Gastroenterol 2016; 16:88. https://doi.org/10.1186/s12876-016-0502-8

28. 

Vakil N, Shaw M, Kirby R. Clinical effectiveness of laparoscopic fundoplication in a U.S. community. Am J Med 2003; 114:1–5. https://doi.org/10.1016/S0002-9343(02)01390-6

29. 

Dominitz JA, Dire CA, Billingsley KG, Todd-Stenberg JA. Complications and antireflux medication use after antireflux surgery. Clin Gastroenterol Hepatol 2006; 4:299–305. https://doi.org/10.1016/j.cgh.2005.12.019

30. 

Schiefke I, Zabel-Langhennig A, Neumann S, Feisthammel J, Moessner J, Caca K. Long term failure of endoscopic gastroplication (EndoCinch). Gut 2005; 54:752–8. https://doi.org/10.1136/gut.2004.058354

31. 

Bell RC, Cadiere GB. Transoral rotational esophagogastric fundoplication: technical, anatomical, and safety considerations. Surg Endosc 2011; 25:2387–99. https://doi.org/10.1007/s00464-010-1528-6

32. 

Jobe BA, O’Rourke RW, McMahon BP, et al. Transoral endoscopic fundoplication in the treatment of gastroesophageal reflux disease: the anatomic and physiologic basis for reconstruction of the esophagogastric junction using a novel device. Ann Surg 2008; 248:69–76. https://doi.org/10.1097/SLA.0b013e31817c9630

33. 

Cadière GB, Rajan A, Germay O, Himpens J. Endoluminal fundoplication by a transoral device for the treatment of GERD: a feasibility study. Surg Endosc 2008; 22:333–42. https://doi.org/10.1007/s00464-007-9618-9

34. 

Witteman BP, Strijkers R, de Vries E, et al. Transoral incisionless fundoplication for treatment of gastroesophageal reflux disease in clinical practice. Surg Endosc 2012; 26:3307–15. https://doi.org/10.1007/s00464-012-2324-2

35. 

Testoni PA, Testoni S, Mazzoleni G, Vailati C, Passaretti S. Long-term efficacy of transoral incisionless fundoplication with Esophyx (Tif 2.0) and factors affecting outcomes in GERD patients followed for up to 6 years: a prospective single-center study. Surg Endosc 2015; 29:2770–80. https://doi.org/10.1007/s00464-014-4008-6

36. 

Trad KS, Barnes WE, Simoni G, et al. Transoral incisionless fundoplication effective in eliminating GERD symptoms in partial responders to proton pump inhibitor therapy at 6 months: the TEMPO Randomized Clinical Trial. Surg Innov 2015; 22:26–40. https://doi.org/10.1177/1553350614526788

37. 

Hunter JG, Kahrilas PJ, Bell RC, et al. Efficacy of transoral fundoplication vs omeprazole for treatment of regurgitation in a randomized controlled trial. Gastroenterol 2015; 148:324–33.e325. https://doi.org/10.1053/j.gastro.2014.10.009

38. 

Zacherl J, Roy-Shapira A, Bonavina L, et al. Endoscopic anterior fundoplication with the Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease: 6-month results from a multi-center prospective trial. Surg Endosc 2015; 29:220–9. https://doi.org/10.1007/s00464-014-3731-3


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