Long-Term Outcomes of Transoral Incisionless Fundoplication in a High-Risk Pediatric Population

Abstract

Introduction:

Laparoscopic Nissen fundoplication (LNF) is the standard for surgical treatment of gastroesophageal reflux disease (GERD), but postoperative complications and pain are common in patients with severe neurological impairment (NI) and those undergoing reoperative procedures. Transoral incisionless fundoplication (TIF) is an endoscopic alternative to treat GERD. Long-term results in pediatric populations are unknown.

Methods:

Eleven patients who underwent TIF between January 2008 and September 2010 were included. A retrospective chart review was performed to evaluate long-term patient outcomes. Median follow-up was 5.6 years (range = 0.42–8.76 years).

Results:

Average patient age was 16.5 ± 5.1 years. Severe NI was present in 81.8% (9/11) of patients, and 63.6% (7/11) had undergone one or more prior fundoplication attempts. Overall, symptomatic reflux recurred or persisted in 54.5% (6/11) of patients. Recurrent symptoms were more common among those who had previous fundoplications than those who did not (71.4% [5/7] vs. 25% [1/4]). Four patients went on to require reoperation, including one laparoscopic Nissen and three disconnects. At last follow-up, 81.8% (9/11) of patients were still on antireflux medications.

Conclusions:

This is the first report of long-term outcomes for treatment of GERD using TIF in a pediatric population. The recurrence rate was high, likely related to the fact that the population treated was extremely high risk. Recurrence was higher in patients with a prior fundoplication, perhaps identifying prior antireflux operations as a relative contraindication to TIF. Nevertheless, complications were low, and a subset of patients did receive a durable benefit from the procedure.

Introduction

Laparoscopic Nissen fundoplication (LNF) is the standard for operative management of gastroesophageal reflux disease (GERD). However, postoperative pain and surgical complications such as gas-bloat syndrome, exacerbations of esophageal and/or gastrointestinal dysmotility, impaired gastric accommodation, bleeding, and recurrent GERD are not uncommon in children.¹ Populations at increased risk for higher morbidity include children undergoing redo fundoplications and those with significant neurological impairment (NI). The incidence of complications increases from 14% for primary procedures to as high as 44% for those undergoing reoperative fundoplications due to development of adhesions.^2–4 Similarly, the rate of postoperative complications, recurrent GERD, and mortality is higher for those with severe NI,^5–8 and management is complicated both by their unusual presentation and by their underlying comorbidities.

Transoral incisionless fundoplication (TIF) was designed to treat GERD by deploying multiple nonabsorbable polypropylene fasteners through the esophagus and stomach in an approximately 270° circumferential pattern meant to construct a new 3–5 cm long valve around the gastroesophageal junction. Long-term data of 3–6 years in highly selected adult populations are available,^9–11 but data in children are limited. We have previously reported our early results using the EsophyX system (EndoGastric Solutions, Inc., Redmond, WA) to perform TIF as a minimally invasive alternative to LNF in high-risk pediatric patients.¹² Although we achieved good early results with resolution of GERD in 10 of 11 children (90.9%) at a follow-up of 8.2 ± 4.2 months, long-term outcomes have never been reported in children. This study updates our previous analysis to determine whether TIF remains a durable solution to treat children with GERD, including those requiring complex reoperation and those with significant NI.

Materials and Methods

Patient population and study design

Eleven pediatric patients underwent TIF at C.S. Mott Children's Hospital between January 2008 and September 2010. Short-term outcomes for these 11 patients were previously published.¹² The initial diagnosis of GERD was established through clinical presentation, upper gastrointestinal contrast studies, and/or pH probe monitoring. Decisions to proceed with TIF were made based on persistent symptoms after failure of medical and, often, prior surgical treatment.

A retrospective chart review was performed with IRB approval (HUM00122142) to determine long-term freedom from symptoms, reoperation, and use of antireflux medications. Follow-up was determined by the last documented outpatient visit that evaluated for symptomatic reflux, which was typically a visit to surgery or gastroenterology clinic. Alternatively, follow-up ended at death or reoperation. Clinical symptoms of interest were gagging or dysphagia, feeding intolerance, retching or emesis, chest or abdominal pain, aspiration, and chronic cough, as reported by the patients or their family and documented in the record. When available, postoperative upper gastrointestinal radiographic studies, pH probe studies, and esophagogastroduodenoscopies (EGDs) were reviewed. Recurrent GERD was defined as either one of the mentioned studies demonstrating GERD or the presence of symptoms clinically adjudicated to be from GERD. In many cases, symptoms were relieved by the initial procedure and later returned. If patients required reoperation for their symptoms, they were considered to have had recurrent GERD.

Procedure details

The TIF-II procedure was performed for all patients using the EsophyX system (EndoGastric Solutions, Inc., Redmond, WA). Initial endoscopic evaluation was performed before the procedure in all patients to ensure favorable anatomy. Detailed steps of this procedure were previously reported.^12,13 In brief, at least two rows of full-thickness esophagogastric fundoplications were created around a 270° wrap for a length of at least 2.5–3 cm. Owing to the size of the device, children had to be at least 25 kg to undergo the procedure. Postoperatively, those on oral feeds were instructed to maintain a soft diet for 2 weeks, and patients were routinely maintained on their antireflux medications until re-evaluation in clinic.

Statistical analysis

Data presented are descriptive in nature. Continuous variables are presented as mean ± standard deviation or median (range), as appropriate. Categorical variables are summarized as frequencies.

Results

Patient characteristics

Description of this population was previously published.¹² In brief, the age of patients at the time of surgery was 16.5 ± 5.1 years. Although 2 patients were older than 18 years, they were both severely neurologically impaired and 1 had had a previous fundoplication as a child. The oldest patient was 28 years old at the time of surgery but only weighed 38 kg. Mean weight at the time of surgery was 45.7 ± 13.3 kg, which was low for age in most cases. Seven patients (63.6%) had prior fundoplications, and 1 patient had failed two prior fundoplications (both a Thal and a Nissen about 6 years before TIF). Severe NI was present in 9 patients (81.8%). The most common etiology was spastic quadriplegic cerebral palsy (77.8% [7/9]), but 1 patient had suffered severe anoxic brain injury during a motor vehicle accident with a near drowning and another suffered from intrauterine cocaine and alcohol exposure. Patients with NI commonly had a history of epilepsy (88.9% [8/9]) and g-tube dependence (88.9% [8/9]). Only 2 patients who were receiving tube feeds were also able to take some degree of an oral diet. Of the 2 patients without NI, 1 had a prior esophageal atresia and tracheoesophageal fistula, and 1 had recurrent aspiration pneumonia since birth with complaints of burning chest pain, particularly when supine, and an EGD that showed a gaping gastroesophageal junction. All 11 patients were on anti-reflux medications at the time of surgery. In addition, 6 of 11 (54.5%) were on two or more medications for GERD.

Long-term follow-up

Average follow-up was 4.78 ± 2.46 years (median = 5.6, range = 0.42–8.76 years). Summaries of the history, pre- and postoperative symptoms, studies, and outcomes for each patient are presented in Table 1. Overall incidence of preoperative presenting symptoms and recurrent/persistent symptoms at last follow-up are documented in Table 2. Recurrence of reflux symptoms occurred in 54.5% (6/11) of patients. Four of the 11 patients required an additional operation. One patient went on to require a Nissen (patient 4, Table 1) and 3 patients (27.3%) subsequently required a disconnect operation (patients 2, 5, and 6, Table 1). The 3 patients who required a disconnect had all failed a previous Nissen, and the patient who subsequently required a Nissen also had recurrence of symptoms after that operation. Two patients (patients 8 and 9, Table 1) were noted to have esophageal dysmotility. Since gagging and dysphagia were the only symptoms remaining at last follow-up for patient 9, that patient was not adjudicated to have had recurrent reflux. Among the patients who had previous operations before the TIF, 71.4% (5/7) had recurrent reflux symptoms. Among patients without a prior fundoplication, long-term success was seen in 75% (3/4) of patients.

Table 1.

Patient Summaries

				Preoperative			Postoperative
PT# (Age in years)	PMH	Prior Fundoplication	Symptoms	pH probe	EGD	UGI	Symptoms	pH probe ^a	UGI ^a	Reop	Recurrent reflux
1 (14)	NI	N	Gagging/dysphagia, aspiration pneumonia, chronic cough	n/a	−HH	+	Chronic cough	n/a	n/a	No	No
2 (8)	NI	Y	Gagging, retching/emesis, aspiration pneumonia, chronic cough	n/a	−HH	−	Gagging, retching/emesis, aspiration pneumonia	−	+	Yes	Yes
3 (13)	NI	Y	Chest/abdominal pain	+	−HH	−	None	n/a	−	No	No
4 (14)	CA	N	Chest/abdominal pain, throat burning, aspiration pneumonia	n/a	−HH, wide EGJ	−	Dysphagia, chest/abdominal pain	−	+	Yes	Yes
5 (14)	NI	Y	Aspiration	n/a	+HH	Slipped prior wrap	Aspiration	n/a	n/a	Yes	Yes
6 (16)	NI	Y	Dysphagia, retching/emesis	n/a	−HH	−	Gagging, retching/emesis	n/a	+	Yes	Yes
7 (16)	NI	Y	Gagging, aspiration pneumonia	+	+HH	−	Gagging, aspiration pneumonia	n/a	−	No	Yes
8 (16)	EA/TEF	Y (x2)	Acid reflux, gagging, recurrent peptic strictures	−	−HH, +S	n/a	Dysphagia, recurrent peptic strictures, chest/abdominal pain	n/a	− +DM	No	Yes
9 (16)	NI	N	Gagging/dysphagia, retching/emesis, throat pain	n/a	−HH	+	Gagging/dysphagia	n/a	− +DM	No	No
10 (23)	NI	Y	Gagging, retching/emesis, aspiration of feeds	−	−HH	−	None	n/a	n/a	No	No
11 (29)	NI	N	Gagging, aspiration pneumonia, chronic cough	n/a	−HH	+	None	n/a	n/a	No	No

Last available study, not necessarily completed at the time of the last clinical follow-up.

PT#, patient number; PMH, past medical history; EA/TEF, esophageal atresia/tracheoesophageal fistula; NI, neurological impairment; CA, chronic aspiration; EGD, esophagogastroduodenoscopy; UGI, upper gastrointestinal contrast study; Reop, reoperation; Y, yes; N, no; HH, hiatal hernia; S, stricture; DM; esophageal dysmotility; n/a, not available; EGJ, esophagogastric junction; +, positive study; −, negative study.

Table 2.

Pre- and Postoperative Reflux Symptoms

Symptoms	Preoperative	Postoperative at last follow-up
Gagging/dysphagia	72.7% (8/11)	54.5% (6/11)
Feeding intolerance	18.2% (2/11)	27.3% (3/11)
Retching/emesis	45.5% (5/11)	18.2% (2/11)
Chest/abdominal pain	18.2% (2/11)	18.2% (2/11)
Aspiration	63.6% (7/11)	27.3% (3/11)
Chronic cough	27.3% (3/11)	18.2% (2/11)

Short-term complications of the surgery in this population have been previously reported.¹² No patients experienced gas-bloat as a side effect of the surgery. One patient without a history of dysphagia developed difficulty swallowing bread, raw vegetables, pills, and large fluid boluses post-TIF. It is unclear from our documentation when in the postoperative course these symptoms first developed.

At last follow-up, 81.8% (9/11) of patients were still on antireflux medications, and 18.2% (2/11) were on two antireflux medications. Two deaths occurred in follow-up. The first patient died of causes unrelated to the operation without recurrent reflux at 5 months postoperatively. The second patient died 1.5 years after TIF as a consequence of respiratory failure and the decision to pursue comfort measures, and he had recurrent symptoms at the time. There were no technical failures of the TIF identified, but when reoperation was needed, the TIFs were noted to be subjectively difficult to takedown. A gastrotomy was created during the course of dissection for 1 patient undergoing reoperative disconnect, but no injuries were made to the esophagus during reoperative dissection.

Discussion

This is the first report of long-term outcomes for TIF in a pediatric population. TIF is a low-risk alternative to Nissen fundoplication, but these 11 patients comprise the only pediatric cohort in which this procedure has been studied. Although the recurrence rate in this study was quite high, it should be noted that this was a very challenging group of patients who underwent TIF. Despite that, the procedure provided a durable, minimally invasive option for a subset of patients.

The population in this study is high risk both because the majority have severe NI and because many have had prior fundoplications. GERD is present in up to 77% of children with severe NI,¹⁴ but it is typically diagnosed in a delayed manner due to communication deficits. Therefore, suspicion for the diagnosis is based more frequently on objective symptoms such as vomiting, regurgitation, gagging, chronic cough or aspiration, feeding intolerance, agitation, or aggressive behavior,¹⁵ rather than subjective symptoms such as heartburn and abdominal pain. Such symptoms may indicate a more advanced stage of the disease, or they could be multifactorial or have etiologies apart from reflux. Swallowing disorders, esophageal dysmotility, and delayed gastric emptying are present in up to 60%–67% of these children,¹⁵ thereby exacerbating reflux symptoms and often mandating placement of a gastrostomy tube at the time of fundoplication. Given the severity of NI in this population, it is possible that many of the gagging episodes identified were due to copious oral secretions with poor oropharyngeal handling of the saliva or behaviors associated with anxiety rather than reflux. Moreover, NI often carries risk factors for recurrent GERD, including postoperative retching, aerophagia, and need for esophageal dilatation.¹⁶ In addition, a history of prior operations, including both fundoplications and gastrostomy tubes, changes the anatomy and significantly increases the adhesions in the operative field. Comorbidities such as extreme scoliosis may also increase the difficultly of the operation.

In a selected adult population, long-term results with TIF have been promising, although somewhat dependent on how success is defined. For patients in the TIF EsophyX versus Medical Proton Pump Inhibitor (PPI) Open Label (TEMPO) randomized trial, elimination of regurgitation and atypical symptoms off of PPIs was 83% at 3 years post-TIF.¹¹ In a separate multicenter prospective study, 59% of patients achieved elimination of daily bothersome heartburn symptoms at 3 years follow-up.⁹ Discontinuation of PPI usage was achieved in 52% of patients, despite the fact that only 39% of those tested had normal pH probes. Finally, a single center study that followed TIF patients as long as 6 years demonstrated that 85.7% of patients had either stopped or halved their PPI therapy, but complete response was achieved in only 30% of patients.¹⁰ The 45.5% freedom from reflux symptoms seen in our study at last follow-up was less than reported in adults but not remarkably so considering that these studies excluded patients with prior fundoplications, esophageal strictures, motility disorders, and reflux esophagitis. Unfortunately, freedom from antireflux medications cannot be used as a marker of success in this cohort because use of antireflux medications tends to remain relatively unchanged after fundoplication in children with NI.¹⁷ Despite this, we did see a reduction in the number of patients requiring more than one antireflux medication. Our long-term results likely speak of the severity of the underlying NI, as well as the fact that many patients have already failed prior attempts at fundoplication.

It is important to note that the results reported here are inferior to those achieved with a Nissen fundoplication in pediatric patients. Recurrence rates after Nissen fundoplication range from 4% to 20% for patients with NI and from 0.4% to 8.7% for patients who are neurologically normal (NN) with follow-up as far as 7 years,^{6–8,18–20} whereas recurrence rate in this study is much higher. Still, comparison of our population with these data should be tempered by the fact that the patients in this study were often both NI and selected because they had previously failed one or more Nissen fundoplications, and it was our judgment that performing a redo operation would either be at higher than normal risk for failure or that it would be very difficult to complete. Neurologically impaired patients are also more prone to operative complications than those without NI.^6–8,19,20 In one combined study of 7467 patients, major complications, such as wrap disruption, respiratory problems, and gas bloat, occurred in 4.2% of NN and 12.8% of NI patients.⁶ Similarly, reoperation was performed in 3.6% of NN and 11.8% of NI patients. There are data to suggest that compared with open fundoplication, LNF is associated with fewer postoperative complications such as retching and airway problems but a higher risk of recurrent GERD (OR = 2.98, 95% CI = 1.29–6.87).^21,22 Regardless, quality of life studies for NI patients after fundoplication do demonstrate improvements in emotional, physical, and social functions, feeding indexes, perception of the children's comfort, caregiver's attitudes toward their child, and parents' overall quality of life.^23,24 As expected, outcomes with traditional fundoplication depend on both the surgical approach and the underlying medical condition of the patient, but the importance of providing a durable operation is clear.

As already noted, many of the patients in this study had previously undergone a prior surgical fundoplication. Adult data reporting the results of revision of a failed fundoplication using TIF were similar to our own short-term results.^12,25 The 11 patients reported by Bell et al.¹ developed a postoperative bleed and 2 patients required laparoscopic revision of the TIF. At a median follow-up of 14 months, 8/10 patients reported resolution of their primary symptoms, but long-term results have not been reported. When redo antireflux surgery is considered in adults, complications increase to as high as 37%–44%^2–4 because increased fibrosis carries risk of gastric, esophageal, and vagal nerve injury that is higher than with a virgin operative field. It is reasonable to extrapolate that a similar trend of increased morbidity with reoperative surgery may be seen in children.³ TIF, therefore, has the potential benefit of a lesser complication rate. However, our data suggest that durability remains an issue in comparison with Nissen fundoplication, and it is conceivable that prior fundoplication should remain a relative contraindication to TIF.

If a higher failure rate is accepted with TIF, the feasibility of reoperation after completion of TIF must be considered. In our hands, there were no major complications during reoperation, but it was noted to be a more challenging operation. After EsophyX fundoplication, the wrap has to be taken down by cutting the polypropylene fasteners, and the fasteners tend to remain fixed to the crura with firm adhesions between the stomach, esophagus, and diaphragm. In one adult study, mobilization and dissection of this wrap were associated with a 27% incidence of gastric perforation, compared with 0%–2% during primary antireflux surgery and 13% during repeat antireflux surgery.²⁶ Incidence of dysphagia may also be increased to 22%–27% when a Nissen is performed after a TIF, and this may prove more difficult to deal with than recurrent reflux in a healthy population.^26,27 We only had 1 patient develop a new diagnosis of dysphagia postoperatively, but exacerbation of dysphagia may be under-reported because most of our patients were exclusively fed through gastrostomy tubes and/or already had the diagnosis preoperatively. Despite these risks, the two small series in the literature show reasonable short-term control of reflux symptoms for re-operation after TIF. In our study, the 1 patient who had a Nissen post-TIF failed that operation, as well. More commonly in our series, severe NI patients had previously failed Nissen before failing TIF, and they went on to receive disconnect operations.

Although this is the only study looking at long-term results in a pediatric population that has undergone TIF, there are several limitations. First, all of our patients were high risk, many with atypical symptoms, and we cannot say how this procedure would hold up in a healthier population. Second, this is a relatively small population that comprises an early experience with the procedure, and our study is a retrospective report. Third, we did not have routine objective testing with either pH probes or UGI at set postoperative intervals, which makes delineation of outcomes more subjective. Fourth, the EsophyX system has undergone several iterations from the device used in this study.

In conclusion, TIF carried a high risk of recurrence in this difficult pediatric population, but it was associated with a brief hospital stay and few perioperative complications. Larger series both in high-risk pediatric NI and low-risk pediatric NN patients are required to better assess efficacy and to determine whether TIF is a reasonable alternative to LNF for select pediatric patients.

Footnotes

Acknowledgment

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Disclosure Statement

No competing financial interests exist.

References

Di Lorenzo

, Orenstein

. Fundoplication: Friend or foe?. J Pediatr Gastroenterol Nutr, 2002; 34:117–124.

Furnee

, Draaisma

, Broeders

, Gooszen

. Surgical reintervention after failed antireflux surgery: A systematic review of the literature. J Gastrointest Surg, 2009; 13:1539–1549.

Peters

, Mukhtar

, Yunus

, et al. Meta-analysis of randomized clinical trials comparing open and laparoscopic anti-reflux surgery. Am J Gastroenterol, 2009; 104:1548–1561; quiz 1547, 1562.

Symons

, Purkayastha

, Dillemans

, et al. Laparoscopic revision of failed antireflux surgery: A systematic review. Am J Surg, 2011; 202:336–343.

Esposito

, Montupet

, van Der Zee

, et al. Long-term outcome of laparoscopic Nissen, Toupet, and Thal antireflux procedures for neurologically normal children with gastroesophageal reflux disease. Surg Endosc, 2006; 20:855–858.

Fonkalsrud

, Ashcraft

, Coran

, et al. Surgical treatment of gastroesophageal reflux in children: A combined hospital study of 7467 patients. Pediatrics, 1998; 101(3 Pt 1):419–422.

Smith

, Othersen

Jr. , Gogan

, Walker

JD.

Nissen fundoplication in children with profound neurologic disability. High risks and unmet goals. Ann Surg, 1992; 215:654–658; discussion 658–659.

Subramaniam

, Dickson

. Long-term outcome of Boix-Ochoa and Nissen fundoplication in normal and neurologically impaired children. J Pediatr Surg, 2000; 35:1214–1216.

Muls

, Eckardt

, Marchese

, et al. Three-year results of a multicenter prospective study of transoral incisionless fundoplication. Surg Innov, 2013; 20:321–330.

10.

Testoni

, Testoni

, Mazzoleni

, Vailati

, Passaretti

. 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; 29:2770–2780.

11.

Trad

, Fox

, Simoni

, et al. Transoral fundoplication offers durable symptom control for chronic GERD: 3-year report from the TEMPO randomized trial with a crossover arm. Surg Endosc, 2017; 6:2498–2508.

12.

Chen

, Jarboe

, Teitelbaum

. Effectiveness of a transluminal endoscopic fundoplication for the treatment of pediatric gastroesophageal reflux disease. Pediatr Surg Int, 2012; 28:229–234.

13.

Bell

, Cadiere

. Transoral rotational esophagogastric fundoplication: Technical, anatomical, and safety considerations. Surg Endosc, 2011; 25:2387–2399.

14.

Del Giudice

, Staiano

, Capano

, et al. Gastrointestinal manifestations in children with cerebral palsy. Brain Dev, 1999; 21:307–311.

15.

Gossler

, Schalamon

, Huber-Zeyringer

, Hollwarth

. Gastroesophageal reflux and behavior in neurologically impaired children. J Pediatr Surg, 2007; 42:1486–1490.

16.

Ngerncham

, Barnhart

, Haricharan

, Roseman

, Georgeson

, Harmon

. Risk factors for recurrent gastroesophageal reflux disease after fundoplication in pediatric patients: A case-control study. J Pediatr Surg, 2007; 42:1478–1485.

17.

Lee

, Sydorak

, Chiu

, Hsu

, Applebaum

, Haigh

. Long-term antireflux medication use following pediatric Nissen fundoplication. Arch Surg, 2008; 143:873–876; discussion 876.

18.

Kawahara

, Nakajima

, Yagi

, Okuyama

, Kubota

, Okada

. Mechanisms responsible for recurrent gastroesophageal reflux in neurologically impaired children who underwent laparoscopic Nissen fundoplication. Surg Endosc, 2002; 16:767–771.

19.

Mathei

, Coosemans

, Nafteux

, et al. Laparoscopic Nissen fundoplication in infants and children: Analysis of 106 consecutive patients with special emphasis in neurologically impaired vs. neurologically normal patients. Surg Endosc, 2008; 22:1054–1059.

20.

Vane

, Harmel

Jr. , King

, Boles

Jr . The effectiveness of Nissen fundoplication in neurologically impaired children with gastroesophageal reflux. Surgery, 1985; 98:662–667.

21.

Lei

, Ren

, Yang

, Bai

. Outcome evaluation of laparoscopic and open nissen fundoplication in children-a systematic review and meta-analysis. Am Surg, 2017; 83:90–97.

22.

, Wu

, Feng

, Lai

, Chen

. Laparoscopic versus open Nissen fundoplication in children: A systematic review and meta-analysis. J Pediatr Surg, 2016; 51:1731–1736.

23.

Engelmann

, Gritsa

, Ure

. Impact of laparoscopic anterior 270 degrees fundoplication on the quality of life and symptoms profile of neurodevelopmentally delayed versus neurologically unimpaired children and their parents. Surg Endosc, 2010; 24:1287–1295.

24.

O'Neill

, O'Neill

, Goth-Owens

, Horn

, Cobb

. Care-giver evaluation of anti-gastroesophageal reflux procedures in neurologically impaired children: What is the real-life outcome?. J Pediatr Surg, 1996; 31:375–380.

25.

Bell

, Hufford

, Fearon

, Freeman

. Revision of failed traditional fundoplication using EsophyX transoral fundoplication. Surg Endosc, 2013; 27:761–767.

26.

Furnee

, Broeders

, Draaisma

, et al. Laparoscopic Nissen fundoplication after failed EsophyX fundoplication. Br J Surg, 2010; 97:1051–1055.

27.

Fumagalli Romario

, Barbera

, Repici

, Porta

, Malesci

, Rosati

. Nissen fundoplication after failure of endoluminal fundoplication: Short-term results. J Gastrointest Surg, 2011; 15:439–443.