Repair of Paraesophageal Hiatal HerniaseIs a Fundoplication Needed? A Randomized Controlled Pilot Trial Beat P Mu¨ller-Stich, MD, Verena Achtsta¨tter, MD, Markus K Diener, MD, Matthias Gondan, Rene´ Warschkow, MD, Francesco Marra, MD, Andreas Zerz, MD, Carsten N Gutt, MD, Markus W Bu¨chler, MD, FACS, Georg R Linke, MD
PhD,
The need for a fundoplication during repair of paraesophageal hiatal hernias (PEH) remains unclear. Prevention of gastroesophageal reflux represents a trade-off against the risk of fundoplication-related side effects. The aim of this trial was to compare laparoscopic mesh-augmented hiatoplasty with simple cardiophrenicopexy (LMAH-C) with laparoscopic mesh-augmented hiatoplasty with fundoplication (LMAH-F) in patients with PEH. STUDY DESIGN: The study was designed as a patient- and assessor-blinded randomized controlled pilot trial, registration number: DRKS00004492 (www.germanctr.de/). Patients with symptomatic PEH were eligible and assigned by central randomization to LMAH-C or LMAH-F. Endpoints were postoperative gastroesophageal reflux, complications, and quality of life 12 months postoperatively. RESULTS: Forty patients (9 male, 31 female) were randomized. Patients were well matched for baseline characteristics. At 3 months, the DeMeester score was higher after LMAH-C compared with LMAHF (40.9 39.9 vs. 9.6 17; p ¼ 0.048). At 12 months, the reflux syndrome score was higher after LMAH-C compared with LMAH-F (1.9 1.2 vs. 1.1 0.4; p ¼ 0.020). In 53% of LMAH-C patients and 17% of LMAH-F patients, postoperative esophagitis was present (p ¼ 0.026). Values of dysphagia (2.1 1.6 vs 1.9 1.4; p ¼ 0.737), gas bloating (2.6 1.4 vs 2.8 1.4; p ¼ 0.782), and quality of life (116.0 16.2 vs 115.9 15.8; p ¼ 0.992) were similar. Relevant postoperative complications occurred in 4 (10%) patients and did not differ between the groups. CONCLUSIONS: Laparoscopic repair of PEH should be combined with a fundoplication to avoid postoperative gastroesophageal reflux and resulting esophagitis. Fundoplication-related side effects do not appear to be clinically relevant. Multicenter randomized trials are required to confirm these findings. (J Am Coll Surg 2015;-:1e9. 2015 by the American College of Surgeons)
BACKGROUND:
CME questions for this article available at http://jacscme.facs.org
Since the minimally invasive approach to the repair of paraesophageal hiatal hernias (PEH) was introduced by Cuschieri and colleagues1 in 1992, laparoscopic PEH repair has gained rapid acceptance as a standard method. With implementation of meshes into hiatal hernia surgery, a significant reduction in recurrences could be achieved.2 The need for fundoplication as a routine adjunct to PEH repair continues to be a controversial issue. Arguments for fundoplication include the prevalence of gastroesophageal reflux disease (GERD) in up to 80% of PEH patients and the risk of increased postoperative gastroesophageal reflux after PEH repair in about 30% of patients with no previous history of GERD.3,4 In addition, fundoplication is thought to support the anchoring of the cardia below the diaphragm, thereby reducing the
Disclosure Information: Authors have nothing to disclose. Timothy J Eberlein, Editor-in-Chief, has nothing to disclose. Dr Mu¨ller-Stich and Ms Achtsta¨tter contributed equally to this work. Presented at the 21st International Congress of European Association for Endoscopic Surgery, Vienna, Austria, June 2013. Received December 19, 2014; Revised February 12, 2015; Accepted March 10, 2015. From the Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany (Mu¨ller-Stich, Achtsta¨tter, Diener, Bu¨chler, Linke); the Department of Psychology, University of Copenhagen, Denmark (Gondan); and the Departments of Surgery, Kantonsspital St Gallen, Switzerland (Warschkow, Marra); Kantonsspital Baselland, Liestal, Switzerland (Zerz); and Klinikum Memmingen, Germany (Gutt). Correspondence address: Beat P Mu¨ller-Stich, MD, Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. email: beat. [email protected]
ª 2015 by the American College of Surgeons Published by Elsevier Inc.
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http://dx.doi.org/10.1016/j.jamcollsurg.2015.03.003 ISSN 1072-7515/15
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Abbreviations and Acronyms
ASA GERD GIQLI GSRS LMAH-C
¼ ¼ ¼ ¼ ¼
American Society of Anesthesiologists gastroesophageal reflux disease Gastrointestinal Quality of Life Index Gastrointestinal Symptom Rating Scale laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy LMAH-F ¼ laparoscopic mesh-augmented hiatoplasty with fundoplication PEH ¼ paraesophageal hiatal hernias PPI ¼ proton pump inhibitor
risk of recurrence. For all these reasons, routine addition of fundoplication is commonly recommended. However, it might be possible that simple mesh-augmented restoration of the anatomy in patients with PEH resolves pre-existing GERD.5,6 Even more important, there is a risk of fundoplication-related complications and side effects. The frequency of gas-bloating symptoms after fundoplication are reported to be up to 58%,7 and in about 20% of patients, new symptoms occur postoperatively.8,9 Therefore, intended improvement of GERD represents a trade-off against the risk of fundoplicationrelated side effects. The question arises as to whether routine addition of a fundoplication is reasonable. To date, randomized data are not yet available. Therefore, the aim of this first randomized controlled pilot trial was a comparison of laparoscopic mesh-augmented hiatoplasty with simple cardiophrenicopexy (LMAH-C) to laparoscopic meshaugmented hiatoplasty with fundoplication (LMAH-F) in patients with PEH regarding gastroesophageal reflux, side effects, complications, and quality of life.
METHODS Trial design and patient selection Because data on the effect of a fundoplication following mesh-augmented PEH repair were not available when this study was initiated, a reasonable power calculation was not possible. Therefore, this study was designed as a patient- and assessor-blinded randomized controlled pilot trial. The trial was conducted in 2 participating centers (University of Heidelberg, Germany and Kantonsspital St Gallen, Switzerland) between March 2007 and November 2011. Patients with symptomatic PEH (paraesophageal involvement was confirmed intraoperatively) were eligible. Exclusion criteria were axial sliding hiatal hernias, missing informed consent, previous hiatal hernia surgery, American Society of Anesthesiologists (ASA) score IV to V, achalasia, Zollinger-Ellison syndrome, malignant
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tumor, and incompetence to answer questionnaires. Forty patients were assigned by intraoperative central randomization to LMAH-C (n ¼ 20) or LMAH-F (n ¼ 20). Endpoints were postoperative gastroesophageal reflux, side effects, complications, and quality of life. The trial was conducted according to the guidelines for good clinical practice (Declaration of Helsinki),10 was approved by the local ethics committee, and is registered at German Clinical Trials Register (DRKS00004492). Preoperative assessment Preoperatively, all patients underwent upper-gastrointestinal endoscopy to detect PEH and reflux lesions. Hiatal hernias were classified into type I (sliding), type II (pure paraesophageal), type III (mixed), and type IV (mixed with others rather than only gastric hernia sac content). Esophagitis was graded according to the Los Angeles (LA) classification.11 All patients were scheduled for esophageal pull-through manometry and 24-hour pH monitoring preoperatively. Esophageal pull-through manometry was available in 9 (45%) LMAH-C patients and 12 (60%) LMAH-F patients, and 24-hour pH monitoring was available in 9 (45%) LMAH-C patients and 10 (50%) LMAH-F patients. Reasons for missing pull-through manometry and 24-hour pH monitoring were patients’ intolerance or unfeasibility of the examination for anatomic reasons. Symptoms were preoperatively assessed by means of the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, with additional questions for gas bloating and dysphagia.12 Each item was rated on a 7-point Likert scaling ranging from no discomfort (1) to very severe discomfort (7). Quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI).13 Preoperatively, both questionnaires were requested for patients on and off proton pump inhibitor (PPI) therapy. Additionally, the patients were screened for preoperative evidence of GERD defined in modified manner according to the criteria used by Lundell and colleagues,14 when at least 1 of the following criteria was fulfilled: esophagitis greater than Los Angeles class A, daily need of PPIs due to reflux symptoms, or moderate to severe heartburn or acid regurgitation (GSRS reflux score > 2). Surgical technique The surgical technique of LMAH-C was performed as previously described in detail.6 The operations were performed by surgeons with an experience of at least 25 laparoscopic repairs of PEH. The hernia sac was reduced after incision in the lesser omentum and the peritoneum at the hiatus. A 56F esophageal bougie was used to identify the esophagus. After mobilization of the hernia sac and the distal esophagus, the hiatus was narrowed with 3 to
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4 nonabsorbable multifilament sutures. Attention was paid to ensuring that an intra-abdominal length of the esophagus of at least 4 cm was maintained; this was measured by a laparoscopic instrument placed alongside the esophagus. A circular 8 8 cm heavyweight (85 g/m2) polypropylene mesh (Surgipro, Tyco Healthcare), with an eccentric hole of 1.8 cm diameter, was fixed around the esophagus from behind with 8 to 12 staples (Endo Universal 65 , Tyco Healthcare) toward the diaphragm.6 According to intraoperative randomization done at this point, a cardiophrenicopexy with nonabsorbable, multifilament sutures was added in LMAH-C patients. Stitches for the cardiophrenicopexy were placed posteriorly to the crura and anteriorly to the centrum tendineum.6 In LMAH-F patients, a 360-degree floppy Nissen fundoplication was added without cardiophrenicopexy.15 A 56F esophageal bougie was used as calibration for the diameter. Routine division of short gastric vessels was not performed.16,17 Follow-up assessment For assessment of the perioperative course, operative time, intra- and postoperative complications, length of hospital stay, and need for reintervention were recorded. A contrast swallow was routinely performed at postoperative day 4 to rule out early hernia recurrence. Subsequently, successful return to solid food and absence of infection signs served as discharge criteria. Postoperative morbidity was graded according to the Clavien-Dindo classification.18 Objective evaluation included esophageal pull-through manometry and 24-hour pH monitoring at 3 months as well as upper gastrointestinal endoscopy at 12 months postoperatively. The upper gastrointestinal endoscopy was used to identify a recurrent hiatal hernia. Cephalic displacement of the proximal margin of the gastric mucosal folds > 2 cm in relation to the hiatus served as the endoscopic criterion for diagnosis of recurrent hiatal hernia. Symptom assessment was repeated 3 months and 12 months postoperatively using the GSRS questionnaire with additional questions for gas bloating, vomiting, dysphagia, and pain and the GIQLI questionnaire. Patients were asked whether they were able to belch and to vomit (“I am not able”, “I am able” or “I don’t know”) and if they needed continuous PPI therapy for reflux symptoms. Furthermore, the assessment included questions on the patients’ subjective feeling regarding the surgical success (“poor,” “fair,” “good,” “very good,” and “excellent”) and the patients’ physical state. Finally, the patients were asked whether they would undergo the operation again. Follow-up was assessed by a study nurse blinded for the treatment. Questionnaires were
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consistently filled out by the patients in the waiting room or by postal communication. Patients were screened for postoperative failure of reflux treatment according to the criteria used by Lundell and associates14 when at least 1 of the following criteria was fulfilled: esophagitis greater than Los Angeles class A, daily need of PPI therapy due to reflux symptoms, moderate to severe heartburn or acid regurgitation (GSRS reflux score >2), or need for surgery because of reflux. Statistical analysis Statistical analysis was performed using R software.19 Randomization was computer generated by alternate blocks with RITA software. The surgeons were not involved with the block size. The following tests were used for group comparison at 3 and 12 months postoperatively: t-test, chi-square test, or Mann-Whitney U test. The following tests were used for before-and-after comparison: t-test for depended group comparison, McNemar test, and Wilcoxon paired samples test. For baseline adjusted analysis the following tests were used: 2 2 analysis of variance, logistical regression, and nonparametric repeated measures analysis.20 There was no correction for multiple testing, and missing data were not imputed (available case analysis). A 2-sided p < 0.05 was considered statistically significant. This randomized controlled pilot trial was designed with the aim of generating estimates for the sample size calculation of a future multicenter randomized controlled trial. Symptomatic objective outcomes and quality of life were chosen as endpoints. A post hoc power analysis was performed.
RESULTS Patients Seventy-six patients were assessed for eligibility. Twentyfour patients did not meet inclusion criteria or fulfilled exclusion criteria, and 12 patients refused to participate. Finally, 40 patients with PEH were randomized (Fig. 1). Baseline characteristics were comparable between groups (Table 1). According to the criteria by Lundell and colleagues,14 17 of 20 (85%) LMAH-C patients and 20 of 20 (100%) LMAH-F patients (p ¼ 0.072) were classified as GERD patients preoperatively. Intra- and postoperative course Mean operating time was shorter for LMAH-C (124 minutes; range 85 to 210 minutes) compared with LMAH-F (153 minutes; range 90 to 250 minutes) (p ¼ 0.023). Mean postoperative hospital stay was 7.8 days (range 4 to 25 days) after LMAH-C and 8.0 days (range 4 to 21 days) after LMAH-F (p ¼ 0.846). Overall, 1
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times. Compared with preoperative values, the gas bloating scores improved significantly at 12 months after both LMAH-C (p ¼ 0.001) and LMAH-F (p ¼ 0.008); the dysphagia score did not differ in either group (Figs. 3, 4). One of 17 (6%) LMAH-C patients and 3 of 18 (17%) LMAH-F patients (p ¼ 0.349) reported inability to belch. Three (18%) LMAH-C patients and 8 (44%) LMAH-F patients (p ¼ 0.208) were unable to vomit. Quality of life evaluated by the GIQLI did not differ between groups at 12 months (p ¼ 0.992). Compared with preoperative values, the GIQLI improved after LMAH-C (p < 0.001) as well as after LMAH-F (p ¼ 0.003) (Fig. 5). All patients in both groups who were available for 12-month follow-up would undergo the surgical treatment again. Seventeen of 17 (100%) LMAH-C patients and 17 of 18 (94%) LMAH-F patients assessed the surgical result to be “good” at least, if not “very good” or “excellent” and reported an improved physical state after surgery (p ¼ 0.324).
Figure 1. CONSORT flow diagram. LMAH-C, laparoscopic meshaugmented hiatoplasty with cardiophrenicopexy; LMAH-F, laparoscopic mesh-augmented hiatoplasty with fundoplication.
intraoperative complication that had an influence on the postoperative course occurred. During LMAH-C, an esophageal perforation was resutured laparoscopically and due to a persistent leakage, an esophageal stent was placed 5 days postoperatively by upper-gastrointestinal endoscopy. All procedures were completed laparoscopically without conversion to open surgery. In-hospital morbidity (Clavien grades II to III) occurred in 3 (15%) LMAH-C patients (1 pleural effusion, 1 pneumothorax with need for pleural drainage, 1 urinary infection) and in 1 (5%) LMAH-F patient (pleural effusion) (p ¼ 0.292). Symptomatic outcomes At 12 months, the reflux syndrome score was significantly higher after LMAH-C compared with LMAH-F (Fig. 2). In both groups, the reflux syndrome score improved at 12 months compared with preoperative values, with a significant difference after LMAH-F (p < 0.001) but not after LMAH-C (p ¼ 0.781). The gas bloating and dysphagia values were no different in both groups at all
Objective outcomes Three months postoperatively, 11 (55%) LMAH-C patients and 8 (40%) LMAH-F patients were available for 24-hour pH monitoring. The mean distal esophageal acid exposures (percentage of time with esophageal pH < 4) were 13.6% 13% in LMAH-C patients, and 0.6% 0.8% in LMAH-F patients (p ¼ 0.058). The DeMeester score was higher in LMAH-C patients compared with LMAH-F patients (40.9 39.9 vs 9.6 17; p ¼ 0.048). Eleven (55%) LMAH-C and 9 (45%) LMAH-F patients were available for esophageal pull-through manometry. The lower esophageal sphincter pressure was not different in LMAH-C patients (13.4 9.1 mmHg) and LMAH-F patients (14.9 10.3 mmHg) (p ¼ 0.716). Twelve months after surgery 33 (83%) patients were available for upper-gastrointestinal endoscopy. Esophagitis was documented in 8 of 15 (53%) LMAH-C patients and in 3 of 18 (17%) LMAH-F patients (p ¼ 0.026) (Table 2). Compared with preoperative findings, the frequency and severity of esophagitis increased after LMAHC. A recurrent hiatal hernia was revealed in 5 (33%) LMAH-C patients (all type I hernias) and in 3 (17%) LMAH-F patients (2 type I hernia; 1 type II hernia) (p ¼ 0.266). No mesh-related complications were documented in either group. Twelve months postoperatively, 8 of 17 (47%) LMAH-C patients and 6 of 20 (30%) LMAH-F patients were on daily PPI therapy (p ¼ 0.286). Four of 17 (24%) LMAH-C patients and 3 of 20 (15%) LMAH-F patients (p ¼ 0.336) showed a failure of reflux treatment based on the criteria mentioned above.
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Baseline Characteristics
Characteristics
Sex, n Male Female Age, y, mean SD BMI, kg/m2, mean SD ASA, n ASA I ASA II ASA III Esophagitis, n 24-h-pH-monitoring n DeMeester score, mean SD Manometry, n Pressure LES, mmHg, mean SD GSRS subscores, n Off PPI On PPI Reflux, mean SD Off PPI On PPI Dysphagia, mean SD Off PPI On PPI Gas bloating, mean SD Off PPI On PPI Abdominal pain, mean SD Off PPI On PPI GIQLI Score, mean SD Off PPI On PPI Daily PPI-therapy, n
LMAH-C (n ¼ 20)
LMAH-F (n ¼ 20)
4 16 65 10.6 29.4 4.8
5 15 63 12.3 29.3 5.4
0 14 6 6 9 21.5 15.5 9 9.7 8.3
2 16 2 7 10 57.8 53.5 12 6.1 4.2
16 17
15 19
3.6 2.0 2.3 1.1
4.3 1.6 3.0 1.3
0.300y 0.121y
1.9 1.4 2.6 1.7
2.8 1.5 2.4 1.7
0.110y 0.623y
3.8 1.8 3.4 1.5
3.9 1.5 4.0 1.1
0.841y 0.236y
3.1 1.4 3.0 1.3
3.2 1.2 2.7 1.2
0.913y 0.558y
81.1 21.2 91.4 22.5 17
91.6 23.0 97.8 23.2 20
0.196y 0.405y 0.072*
p Value
0.705*
0.622y 0.928y 0.127*
0.736* 0.066y 0.360y
*Chi-square test. y t-test. ASA, American Society of Anesthesiologists; BMI, body mass index; GIQLI, Gastrointestinal Quality of Life; GSRS, Gastrointestinal Symptom Rating Scale; LMAH-C, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy LMAH-F, laparoscopic mesh-augmented hiatoplasty with fundoplication; PPI, proton pump inhibitor.
During the 12-month follow-up period, 1 of 18 (6%) LMAH-C patients and 4 (20%) LMAH-F patients needed rehospitalization (p ¼ 0.189). All rehospitalized patients needed reintervention. The 1 patient in the LMAH-C group needed rehospitalization 28 days postoperatively for removal of an esophageal stent, which had been placed for the coverage of an esophageal perforation during the postoperative course. The 4 rehospitalized LMAH-F patients needed laparoscopic revision (1 for incarceration of small bowel at the hiatus; 1 for recurrent hiatal hernia; 2 for dysphagia). No mortality occurred in either group.
Considering the 1 LMAH-F patient, who underwent reoperation due to recurrent hiatal hernia during the 12-month follow-up period, and the results of uppergastrointestinal endoscopy at 12 months, there were 5 (33%) cases of documented recurrent hiatal hernia in LMAH-C patients and 4 (21%) in LMAH-F patients (p ¼ 0.420). Post-hoc power analysis Post-hoc power analysis of this study population revealed a power of 81% for detection of significant differences
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Figure 2. Reflux syndrome score. Light gray bar, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy; dark gray bar, laparoscopic mesh-augmented hiatoplasty with fundoplication.
(at a 2-sided significance level of 0.05) within the reflux subscore; it was 9% for failure of reflux treatment and 11% for recurrent hiatal hernia. Therefore, a sample size of 870 patients would be needed for failure of reflux treatment and 502 patients for recurrent hiatal hernia as the endpoint (each with a power of 80%).
DISCUSSION This trial evaluated for the first time the effect of routine fundoplication as an adjunct to mesh-reinforced PEH repair in a patient- and assessor-blinded randomized controlled setting. Twelve months postoperatively, patients with routine fundoplication reported significantly fewer reflux symptoms than did patients without fundoplication. Subjective reflux control was confirmed by 24-hour pH monitoring at 3 months and upper-gastrointestinal endoscopy at 12
Figure 3. Gas-bloat syndrome score. Light gray bar, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy; dark gray bar, laparoscopic mesh-augmented hiatoplasty with fundoplication.
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Figure 4. Dysphagia score. Light gray bar, laparoscopic meshaugmented hiatoplasty with cardiophrenicopexy; dark gray bar, laparoscopic mesh-augmented hiatoplasty with fundoplication.
months, which revealed esophagitis in 53% of patients after LMAH-C and in 17% of patients after LMAH-F, respectively. A total of 24% of LMAH-C patients and 15% of LMAH-F patients showed a failure of reflux treatment according to the definition by Lundell and associates.14 So far, only few cohort studies have evaluated GERD after PEH repair. After PEH repair with fundoplication, values of 10% to 20% postoperative GERD were reported.21,22 After PEH repair without fundoplication, Styger and coworkers4 reported 32% new onset of GERD at a mean follow-up of 3 years. Repair of PEH by LMAH-C without fundoplication was evaluated in 2 cohort studies; postoperative GERD was observed in 20% and 34% of patients, respectively.5,6 In this trial, patients were included independently of the preoperative evidence of GERD. The majority of patients in both groups
Figure 5. Gastrointestinal Quality of Life Index (GIQLI). Light gray bar, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy; Dark gray bar, laparoscopic mesh-augmented hiatoplasty with fundoplication.
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Upper Gastrointestinal Endoscopy
Variable
Endoscopy, n Esophagitis, n LA, A LA, B LA, C LA, D Barrett, n Hiatal hernia, n Type I Type II Type III Mesh complications
LMAH-C LMAH-F Preoperatively
20 6 3 3 0 0 0 20 0 0 20
20 7 3 2 1 1 3 20 0 0 20
LMAH-C LMAH-F 12 mo
15 8 5 2 1 0 1 5 5 0 0 0
18 3 1 1 1 0 3 3 2 1 0 0
p Value, course LMAH-F to LMAH-C Preoperatively 12 mo
p Value, course pre- to postoperatively Group comparison
N/A 0.736*
0.212* 0.026*
0.226y 0.032y 0.066z
0.072* N/A
0.381* 0.266*
N/A 0.273y
N/A
*Chi-square test. y Logistical regression, p value is adjusted for baseline (preoperative), with factor “group” and covariate “baseline-value.” z p value is comparison of both groups adjusted for baseline.20 LA, Los Angeles (classification); LMAH-C, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy; LMAH-F, laparoscopic mesh-augmented hiatoplasty with fundoplication; N/A, not available.
fulfilled the GERD criteria preoperatively, reflecting gastroesophageal reflux to be common in PEH as well. However, objectifying GERD in PEH patients might be difficult due to anatomic reasons. The present data suggest that a routine fundoplication should be added in PEH patients irrespective of the preoperative evidence of GERD to reduce the risk of postoperative persisting or new onset gastroesophageal reflux. The risk of side effects does not seem to be increased by adding a fundoplication after mesh-reinforced PEH repair. Dysphagia symptoms did not differ between LMAH-C and LMAH-F patients 12 months postoperatively and were comparable to the preoperative state within both groups. However, 2 patients, after LMAHF, underwent reoperation due to persisting dysphagia symptoms. Gas bloating symptoms did not differ between both groups postoperatively and decreased within both groups compared with the preoperative state. Still, although not significant, more patients reported an inability to belch and were unable to vomit after LMAH-F. These symptomatic data after LMAH-C are in line with those from previous cohort studies.5,23 Prospective data on side effects after PEH repair with fundoplication are scarce.2 After fundoplication in GERD patients, frequent gas bloating symptoms are reported in up to 58%7 of patients and in about 20%, new symptoms occur postoperatively.8,9 Preoperative impaired quality of life assessed by the GIQLI questionnaire improved significantly after both
LMAH-C and LMAH-F and did not differ between groups at 12 months. Therefore, the higher incidence of reflux symptoms in LMAH-C patients did not seem to affect the overall quality of life. This might be explained by the fact, that PEH patients suffer from various symptoms,24 and postoperative reflux control is not the leading criterion for treatment success, as in typical GERD patients. Additionally, PPIs provide an effective drug therapy with few side effects. Recurrent hiatal hernias at 12-month follow-up were documented in 5 (33%) LMAH-C patients and 4 (21%) LMAH-F patients. Therefore, because recurrence rates between groups were comparable, an additional fundoplication does not seem to decrease the risk of hernia recurrence when a consequent mesh reinforcement of the hiatus is performed. The overall recurrence rates of 33% and 21%, respectively, seem to be higher than those reported for mesh-reinforced PEH repair, which range from 0% to 23%.25 However, it has to be noted that a strong definition for the diagnosis of recurrent hiatal hernia was used in this trial. As recently evaluated by our group, endoscopy might be more sensitive compared with barium swallow in the detection of particularly small hiatal hernias.26 Consequently, endoscopically documented cephalic displacement of the proximal margin of the gastric mucosal folds > 2 cm in relation to the hiatus served as a criterion for a recurrent hiatal hernia. All hernia recurrences in LMAH-C patients were small sliding hernias, and only 1 PEH recurrence was documented after
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LMAH-F. Differing between symptomatic and asymptomatic hiatal hernia recurrences, only 1 LMAH-F patient had reoperation because of a symptomatic hernia recurrence during the 12-month follow-up period. Intraoperative complications and in-hospital morbidity were comparable between groups and were comparable to those in other series of laparoscopic PEH repair published so far, ranging from 4% to 28%.21,27-29 The only major complication in our series was an esophageal perforation during LMAH-C, which was resutured laparoscopically and stented endoscopically postoperatively. A certain morbidity rate after PEH repair seems to be inevitable, which might be explained by the fact that PEHs are more common among elderly people and, furthermore, the procedure involves 2 body cavities. The reoperation rate of 4 (20%) patients after LMAH-F seen within this context might be the consequence of the complex patient group and a random effect of the small sample size. This trial has some limitations. Because data on the effect of a fundoplication after mesh-augmented PEH repair were not available when the study was initiated, a reasonable power calculation was not possible. Therefore, the study was designed as a pilot trial. The data from this study enable the planning of a well-designed confirmative, randomized controlled trial. According to our post-hoc power analysis, 502 and 870 patients would be needed to confirm the difference in recurrent hiatal hernias and postoperative failure in gastroesophageal reflux treatment, respectively, at a level of significance of 0.05 with a power of 80%. Therefore, considering the low incidence of symptomatic PEH patients needing surgery, a confirmative randomized controlled trial seems to be difficult to realize. To date, this pilot trial remains the best evidence available. Objective follow-up by endoscopy, pullthrough manometry, and 24-hour pH monitoring was missing for several patients. The most frequent reason for missing tests was patients’ refusal due to resolution of their symptoms. Therefore, a selection bias cannot be excluded. Finally, this trial evaluated a symptomatic and objective outcome at 12-month follow-up. To draw a definite conclusion on recurrence rates, mesh complications, and symptomatic long-term follow-up, and to enable a comparison with outcomes data from other trials evaluating hiatal hernia repair,30 the scheduled 3- and 5-year follow-up are necessary. However, all these limitations concern both groups investigated in this study and do not produce a bias between groups.
CONCLUSIONS To summarize, this first randomized controlled pilot trial suggests that routine addition of fundoplication in
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mesh-augmented repair of PEHs is reasonable to avoid postoperative gastroesophageal reflux and concomitant esophagitis. Fundoplication-related side effects do not seem to be clinically relevant. Multicenter randomized controlled trials are required to confirm these findings. Author Contributions Study conception and design: Mu¨ller, Achtsta¨tter, Diener, Zerz, Gutt, Bu¨chler, Linke Acquisition of data: Mu¨ller, Achtsta¨tter, Diener, Gondan, Warschkow, Marra, Zerz, Gutt, Linke Analysis and interpretation of data: Mu¨ller, Achtsta¨tter, Diener, Gondan, Warschkow, Marra, Zerz, Gutt, Bu¨chler, Linke Drafting of manuscript: Mu¨ller, Achtsta¨tter, Diener, Gondan, Warschkow, Zerz, Gutt, Bu¨chler, Linke Critical revision: Mu¨ller, Achtsta¨tter, Diener, Gondan, Warschkow, Marra, Zerz, Gutt, Bu¨chler, Linke Acknowledgment: The authors wish to thank Beivin Pyne for revising this manuscript as a native English speaker. REFERENCES 1. Cuschieri A, Shimi S, Nathanson LK. Laparoscopic reduction, crural repair, and fundoplication of large hiatal hernia. Am J Surg 1992;163:425e430. 2. Antoniou SA, Antoniou GA, Koch OO, et al. Lower recurrence rates after mesh-reinforced versus simple hiatal hernia repair: a meta-analysis of randomized trials. Surg Laparosc Endosc Percutan Tech 2012;22:498e502. 3. Maziak D, Todd T, Pearson F. Massive hiatus hernia: evaluation and surgical management. J Thorac Cardiovasc Surg 1998;115:53e60. 4. Styger S, Ackermann C, Schuppisser JP, Tondelli P. [Reflux disease following gastropexy for para-esophageal hiatal hernia]. Schweiz Med Wochenschr 1995;125:1213e1215. 5. Linke GR, Gehrig T, Hogg LV, et al. Laparoscopic meshaugmented hiatoplasty without fundoplication as a method to treat large hiatal hernias. Surg Today 2014;44:820e826. 6. Muller-Stich BP, Linke GR, Borovicka J, et al. Laparoscopic mesh-augmented hiatoplasty as a treatment of gastroesophageal reflux disease and hiatal hernias-preliminary clinical and functional results of a prospective case series. Am J Surg 2008;195:749e756. 7. Heikkinen TJ, Haukipuro K, Bringman S, et al. Comparison of laparoscopic and open Nissen fundoplication 2 years after operation. A prospective randomized trial. Surg Endosc 2000;14:1019e1023. 8. Anvari M, Allen C. Postprandial bloating after laparoscopic Nissen fundoplication. Can J Surg 2001;44:440e444. 9. Booth MI, Jones L, Stratford J, Dehn TC. Results of laparoscopic Nissen fundoplication at 2-8 years after surgery. Br J Surg 2002;89:476e481. 10. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2003;310:2191e2194.
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11. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999;45: 172e180. 12. Kulich KR, Malfertheiner P, Madisch A, et al. Psychometric validation of the German translation of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in patients with reflux disease. Health Qual Life Outcomes 2003;1:62. 13. Eypasch E, Williams JI, Wood-Dauphinee S, et al. Gastrointestinal Quality of Life Index: development, validation and application of a new instrument. Br J Surg 1995;82:216e222. 14. Lundell L, Miettinen P, Myrvold HE, et al. Seven-year followup of a randomized clinical trial comparing proton-pump inhibition with surgical therapy for reflux oesophagitis. Br J Surg 2007;94:198e203. 15. Zacharoulis D, O’Boyle CJ, Sedman PC, et al. Laparoscopic fundoplication: a 10-year learning curve. Surg Endosc 2006; 20:1662e1670. 16. Engstrom C, Jamieson GG, Devitt PG, Watson DI. Metaanalysis of two randomized controlled trials to identify longterm symptoms after division of the short gastric vessels during Nissen fundoplication. Br J Surg 2011;98:1063e1067. 17. Markar SR, Karthikesalingam AP, Wagner OJ, et al. Systematic review and meta-analysis of laparoscopic Nissen fundoplication with or without division of the short gastric vessels. Br J Surg 2011;98:1056e1062. 18. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240: 205e213. 19. R Core Team (2012). A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2012. 20. Noguchi K, Gel YR, Brunner E, Konietschke F. nparLD: An R Software Package for the Nonparametric Analysis of Longitudinal Data in Factorial Experiments. J Statist Software 2012; 50:1e23.
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21. Diaz S, Brunt LM, Klingensmith ME, et al. Laparoscopic paraesophageal hernia repair, a challenging operation: medium-term outcome of 116 patients. J Gastrointest Surg 2003;7:59e66. 22. Muller-Stich BP, Holzinger F, Kapp T, Klaiber C. Laparoscopic hiatal hernia repair: long-term outcome with the focus on the influence of mesh reinforcement. Surg Endosc 2006; 20:380e384. 23. Muller-Stich BP, Koninger J, Muller-Stich BH, et al. Laparoscopic mesh-augmented hiatoplasty as a method to treat gastroesophageal reflux without fundoplication: single-center experience with 306 consecutive patients. Am J Surg 2009; 198:17e24. 24. Carrott PW, Hong J, Kuppusamy M, et al. Clinical ramifications of giant paraesophageal hernias are underappreciated: making the case for routine surgical repair. Ann Thorac Surg 2012;94:421e426. 25. Antoniou SA, Koch OO, Antoniou GA, et al. Mesh-reinforced hiatal hernia repair: a review on the effect on postoperative dysphagia and recurrence. Langenbecks Arch Surg 2012;397: 19e27. 26. Linke GR, Borovicka J, Schneider P, et al. Is a barium swallow complementary to endoscopy essential in the preoperative assessment of laparoscopic antireflux and hiatal hernia surgery? Surg Endosc 2008;22:96e100. 27. Furnee E, Hazebroek E. Mesh in laparoscopic large hiatal hernia repair: a systematic review of the literature. Surg Endosc 2013;27:3998e4008. 28. Gebhart A, Vu S, Armstrong C, et al. Initial outcomes of laparoscopic paraesophageal hiatal hernia repair with mesh. Am Surg 2013;79:1017e1021. 29. Pierre AF, Luketich JD, Fernando HC, et al. Results of laparoscopic repair of giant paraesophageal hernias: 200 consecutive patients. Ann Thorac Surg 2002;74:1909e1915. 30. Oelschlager BK, Pellegrini CA, Hunter JG, et al. Biologic prosthesis to prevent recurrence after laparoscopic paraesophageal hernia repair: long-term follow-up from a multicenter, prospective, randomized trial. J Am Coll Surg 2011;213: 461e468.
PhD,
The need for a fundoplication during repair of paraesophageal hiatal hernias (PEH) remains unclear. Prevention of gastroesophageal reflux represents a trade-off against the risk of fundoplication-related side effects. The aim of this trial was to compare laparoscopic mesh-augmented hiatoplasty with simple cardiophrenicopexy (LMAH-C) with laparoscopic mesh-augmented hiatoplasty with fundoplication (LMAH-F) in patients with PEH. STUDY DESIGN: The study was designed as a patient- and assessor-blinded randomized controlled pilot trial, registration number: DRKS00004492 (www.germanctr.de/). Patients with symptomatic PEH were eligible and assigned by central randomization to LMAH-C or LMAH-F. Endpoints were postoperative gastroesophageal reflux, complications, and quality of life 12 months postoperatively. RESULTS: Forty patients (9 male, 31 female) were randomized. Patients were well matched for baseline characteristics. At 3 months, the DeMeester score was higher after LMAH-C compared with LMAHF (40.9 39.9 vs. 9.6 17; p ¼ 0.048). At 12 months, the reflux syndrome score was higher after LMAH-C compared with LMAH-F (1.9 1.2 vs. 1.1 0.4; p ¼ 0.020). In 53% of LMAH-C patients and 17% of LMAH-F patients, postoperative esophagitis was present (p ¼ 0.026). Values of dysphagia (2.1 1.6 vs 1.9 1.4; p ¼ 0.737), gas bloating (2.6 1.4 vs 2.8 1.4; p ¼ 0.782), and quality of life (116.0 16.2 vs 115.9 15.8; p ¼ 0.992) were similar. Relevant postoperative complications occurred in 4 (10%) patients and did not differ between the groups. CONCLUSIONS: Laparoscopic repair of PEH should be combined with a fundoplication to avoid postoperative gastroesophageal reflux and resulting esophagitis. Fundoplication-related side effects do not appear to be clinically relevant. Multicenter randomized trials are required to confirm these findings. (J Am Coll Surg 2015;-:1e9. 2015 by the American College of Surgeons)
BACKGROUND:
CME questions for this article available at http://jacscme.facs.org
Since the minimally invasive approach to the repair of paraesophageal hiatal hernias (PEH) was introduced by Cuschieri and colleagues1 in 1992, laparoscopic PEH repair has gained rapid acceptance as a standard method. With implementation of meshes into hiatal hernia surgery, a significant reduction in recurrences could be achieved.2 The need for fundoplication as a routine adjunct to PEH repair continues to be a controversial issue. Arguments for fundoplication include the prevalence of gastroesophageal reflux disease (GERD) in up to 80% of PEH patients and the risk of increased postoperative gastroesophageal reflux after PEH repair in about 30% of patients with no previous history of GERD.3,4 In addition, fundoplication is thought to support the anchoring of the cardia below the diaphragm, thereby reducing the
Disclosure Information: Authors have nothing to disclose. Timothy J Eberlein, Editor-in-Chief, has nothing to disclose. Dr Mu¨ller-Stich and Ms Achtsta¨tter contributed equally to this work. Presented at the 21st International Congress of European Association for Endoscopic Surgery, Vienna, Austria, June 2013. Received December 19, 2014; Revised February 12, 2015; Accepted March 10, 2015. From the Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany (Mu¨ller-Stich, Achtsta¨tter, Diener, Bu¨chler, Linke); the Department of Psychology, University of Copenhagen, Denmark (Gondan); and the Departments of Surgery, Kantonsspital St Gallen, Switzerland (Warschkow, Marra); Kantonsspital Baselland, Liestal, Switzerland (Zerz); and Klinikum Memmingen, Germany (Gutt). Correspondence address: Beat P Mu¨ller-Stich, MD, Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. email: beat. [email protected]
ª 2015 by the American College of Surgeons Published by Elsevier Inc.
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http://dx.doi.org/10.1016/j.jamcollsurg.2015.03.003 ISSN 1072-7515/15
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Abbreviations and Acronyms
ASA GERD GIQLI GSRS LMAH-C
¼ ¼ ¼ ¼ ¼
American Society of Anesthesiologists gastroesophageal reflux disease Gastrointestinal Quality of Life Index Gastrointestinal Symptom Rating Scale laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy LMAH-F ¼ laparoscopic mesh-augmented hiatoplasty with fundoplication PEH ¼ paraesophageal hiatal hernias PPI ¼ proton pump inhibitor
risk of recurrence. For all these reasons, routine addition of fundoplication is commonly recommended. However, it might be possible that simple mesh-augmented restoration of the anatomy in patients with PEH resolves pre-existing GERD.5,6 Even more important, there is a risk of fundoplication-related complications and side effects. The frequency of gas-bloating symptoms after fundoplication are reported to be up to 58%,7 and in about 20% of patients, new symptoms occur postoperatively.8,9 Therefore, intended improvement of GERD represents a trade-off against the risk of fundoplicationrelated side effects. The question arises as to whether routine addition of a fundoplication is reasonable. To date, randomized data are not yet available. Therefore, the aim of this first randomized controlled pilot trial was a comparison of laparoscopic mesh-augmented hiatoplasty with simple cardiophrenicopexy (LMAH-C) to laparoscopic meshaugmented hiatoplasty with fundoplication (LMAH-F) in patients with PEH regarding gastroesophageal reflux, side effects, complications, and quality of life.
METHODS Trial design and patient selection Because data on the effect of a fundoplication following mesh-augmented PEH repair were not available when this study was initiated, a reasonable power calculation was not possible. Therefore, this study was designed as a patient- and assessor-blinded randomized controlled pilot trial. The trial was conducted in 2 participating centers (University of Heidelberg, Germany and Kantonsspital St Gallen, Switzerland) between March 2007 and November 2011. Patients with symptomatic PEH (paraesophageal involvement was confirmed intraoperatively) were eligible. Exclusion criteria were axial sliding hiatal hernias, missing informed consent, previous hiatal hernia surgery, American Society of Anesthesiologists (ASA) score IV to V, achalasia, Zollinger-Ellison syndrome, malignant
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tumor, and incompetence to answer questionnaires. Forty patients were assigned by intraoperative central randomization to LMAH-C (n ¼ 20) or LMAH-F (n ¼ 20). Endpoints were postoperative gastroesophageal reflux, side effects, complications, and quality of life. The trial was conducted according to the guidelines for good clinical practice (Declaration of Helsinki),10 was approved by the local ethics committee, and is registered at German Clinical Trials Register (DRKS00004492). Preoperative assessment Preoperatively, all patients underwent upper-gastrointestinal endoscopy to detect PEH and reflux lesions. Hiatal hernias were classified into type I (sliding), type II (pure paraesophageal), type III (mixed), and type IV (mixed with others rather than only gastric hernia sac content). Esophagitis was graded according to the Los Angeles (LA) classification.11 All patients were scheduled for esophageal pull-through manometry and 24-hour pH monitoring preoperatively. Esophageal pull-through manometry was available in 9 (45%) LMAH-C patients and 12 (60%) LMAH-F patients, and 24-hour pH monitoring was available in 9 (45%) LMAH-C patients and 10 (50%) LMAH-F patients. Reasons for missing pull-through manometry and 24-hour pH monitoring were patients’ intolerance or unfeasibility of the examination for anatomic reasons. Symptoms were preoperatively assessed by means of the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, with additional questions for gas bloating and dysphagia.12 Each item was rated on a 7-point Likert scaling ranging from no discomfort (1) to very severe discomfort (7). Quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI).13 Preoperatively, both questionnaires were requested for patients on and off proton pump inhibitor (PPI) therapy. Additionally, the patients were screened for preoperative evidence of GERD defined in modified manner according to the criteria used by Lundell and colleagues,14 when at least 1 of the following criteria was fulfilled: esophagitis greater than Los Angeles class A, daily need of PPIs due to reflux symptoms, or moderate to severe heartburn or acid regurgitation (GSRS reflux score > 2). Surgical technique The surgical technique of LMAH-C was performed as previously described in detail.6 The operations were performed by surgeons with an experience of at least 25 laparoscopic repairs of PEH. The hernia sac was reduced after incision in the lesser omentum and the peritoneum at the hiatus. A 56F esophageal bougie was used to identify the esophagus. After mobilization of the hernia sac and the distal esophagus, the hiatus was narrowed with 3 to
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4 nonabsorbable multifilament sutures. Attention was paid to ensuring that an intra-abdominal length of the esophagus of at least 4 cm was maintained; this was measured by a laparoscopic instrument placed alongside the esophagus. A circular 8 8 cm heavyweight (85 g/m2) polypropylene mesh (Surgipro, Tyco Healthcare), with an eccentric hole of 1.8 cm diameter, was fixed around the esophagus from behind with 8 to 12 staples (Endo Universal 65 , Tyco Healthcare) toward the diaphragm.6 According to intraoperative randomization done at this point, a cardiophrenicopexy with nonabsorbable, multifilament sutures was added in LMAH-C patients. Stitches for the cardiophrenicopexy were placed posteriorly to the crura and anteriorly to the centrum tendineum.6 In LMAH-F patients, a 360-degree floppy Nissen fundoplication was added without cardiophrenicopexy.15 A 56F esophageal bougie was used as calibration for the diameter. Routine division of short gastric vessels was not performed.16,17 Follow-up assessment For assessment of the perioperative course, operative time, intra- and postoperative complications, length of hospital stay, and need for reintervention were recorded. A contrast swallow was routinely performed at postoperative day 4 to rule out early hernia recurrence. Subsequently, successful return to solid food and absence of infection signs served as discharge criteria. Postoperative morbidity was graded according to the Clavien-Dindo classification.18 Objective evaluation included esophageal pull-through manometry and 24-hour pH monitoring at 3 months as well as upper gastrointestinal endoscopy at 12 months postoperatively. The upper gastrointestinal endoscopy was used to identify a recurrent hiatal hernia. Cephalic displacement of the proximal margin of the gastric mucosal folds > 2 cm in relation to the hiatus served as the endoscopic criterion for diagnosis of recurrent hiatal hernia. Symptom assessment was repeated 3 months and 12 months postoperatively using the GSRS questionnaire with additional questions for gas bloating, vomiting, dysphagia, and pain and the GIQLI questionnaire. Patients were asked whether they were able to belch and to vomit (“I am not able”, “I am able” or “I don’t know”) and if they needed continuous PPI therapy for reflux symptoms. Furthermore, the assessment included questions on the patients’ subjective feeling regarding the surgical success (“poor,” “fair,” “good,” “very good,” and “excellent”) and the patients’ physical state. Finally, the patients were asked whether they would undergo the operation again. Follow-up was assessed by a study nurse blinded for the treatment. Questionnaires were
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consistently filled out by the patients in the waiting room or by postal communication. Patients were screened for postoperative failure of reflux treatment according to the criteria used by Lundell and associates14 when at least 1 of the following criteria was fulfilled: esophagitis greater than Los Angeles class A, daily need of PPI therapy due to reflux symptoms, moderate to severe heartburn or acid regurgitation (GSRS reflux score >2), or need for surgery because of reflux. Statistical analysis Statistical analysis was performed using R software.19 Randomization was computer generated by alternate blocks with RITA software. The surgeons were not involved with the block size. The following tests were used for group comparison at 3 and 12 months postoperatively: t-test, chi-square test, or Mann-Whitney U test. The following tests were used for before-and-after comparison: t-test for depended group comparison, McNemar test, and Wilcoxon paired samples test. For baseline adjusted analysis the following tests were used: 2 2 analysis of variance, logistical regression, and nonparametric repeated measures analysis.20 There was no correction for multiple testing, and missing data were not imputed (available case analysis). A 2-sided p < 0.05 was considered statistically significant. This randomized controlled pilot trial was designed with the aim of generating estimates for the sample size calculation of a future multicenter randomized controlled trial. Symptomatic objective outcomes and quality of life were chosen as endpoints. A post hoc power analysis was performed.
RESULTS Patients Seventy-six patients were assessed for eligibility. Twentyfour patients did not meet inclusion criteria or fulfilled exclusion criteria, and 12 patients refused to participate. Finally, 40 patients with PEH were randomized (Fig. 1). Baseline characteristics were comparable between groups (Table 1). According to the criteria by Lundell and colleagues,14 17 of 20 (85%) LMAH-C patients and 20 of 20 (100%) LMAH-F patients (p ¼ 0.072) were classified as GERD patients preoperatively. Intra- and postoperative course Mean operating time was shorter for LMAH-C (124 minutes; range 85 to 210 minutes) compared with LMAH-F (153 minutes; range 90 to 250 minutes) (p ¼ 0.023). Mean postoperative hospital stay was 7.8 days (range 4 to 25 days) after LMAH-C and 8.0 days (range 4 to 21 days) after LMAH-F (p ¼ 0.846). Overall, 1
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times. Compared with preoperative values, the gas bloating scores improved significantly at 12 months after both LMAH-C (p ¼ 0.001) and LMAH-F (p ¼ 0.008); the dysphagia score did not differ in either group (Figs. 3, 4). One of 17 (6%) LMAH-C patients and 3 of 18 (17%) LMAH-F patients (p ¼ 0.349) reported inability to belch. Three (18%) LMAH-C patients and 8 (44%) LMAH-F patients (p ¼ 0.208) were unable to vomit. Quality of life evaluated by the GIQLI did not differ between groups at 12 months (p ¼ 0.992). Compared with preoperative values, the GIQLI improved after LMAH-C (p < 0.001) as well as after LMAH-F (p ¼ 0.003) (Fig. 5). All patients in both groups who were available for 12-month follow-up would undergo the surgical treatment again. Seventeen of 17 (100%) LMAH-C patients and 17 of 18 (94%) LMAH-F patients assessed the surgical result to be “good” at least, if not “very good” or “excellent” and reported an improved physical state after surgery (p ¼ 0.324).
Figure 1. CONSORT flow diagram. LMAH-C, laparoscopic meshaugmented hiatoplasty with cardiophrenicopexy; LMAH-F, laparoscopic mesh-augmented hiatoplasty with fundoplication.
intraoperative complication that had an influence on the postoperative course occurred. During LMAH-C, an esophageal perforation was resutured laparoscopically and due to a persistent leakage, an esophageal stent was placed 5 days postoperatively by upper-gastrointestinal endoscopy. All procedures were completed laparoscopically without conversion to open surgery. In-hospital morbidity (Clavien grades II to III) occurred in 3 (15%) LMAH-C patients (1 pleural effusion, 1 pneumothorax with need for pleural drainage, 1 urinary infection) and in 1 (5%) LMAH-F patient (pleural effusion) (p ¼ 0.292). Symptomatic outcomes At 12 months, the reflux syndrome score was significantly higher after LMAH-C compared with LMAH-F (Fig. 2). In both groups, the reflux syndrome score improved at 12 months compared with preoperative values, with a significant difference after LMAH-F (p < 0.001) but not after LMAH-C (p ¼ 0.781). The gas bloating and dysphagia values were no different in both groups at all
Objective outcomes Three months postoperatively, 11 (55%) LMAH-C patients and 8 (40%) LMAH-F patients were available for 24-hour pH monitoring. The mean distal esophageal acid exposures (percentage of time with esophageal pH < 4) were 13.6% 13% in LMAH-C patients, and 0.6% 0.8% in LMAH-F patients (p ¼ 0.058). The DeMeester score was higher in LMAH-C patients compared with LMAH-F patients (40.9 39.9 vs 9.6 17; p ¼ 0.048). Eleven (55%) LMAH-C and 9 (45%) LMAH-F patients were available for esophageal pull-through manometry. The lower esophageal sphincter pressure was not different in LMAH-C patients (13.4 9.1 mmHg) and LMAH-F patients (14.9 10.3 mmHg) (p ¼ 0.716). Twelve months after surgery 33 (83%) patients were available for upper-gastrointestinal endoscopy. Esophagitis was documented in 8 of 15 (53%) LMAH-C patients and in 3 of 18 (17%) LMAH-F patients (p ¼ 0.026) (Table 2). Compared with preoperative findings, the frequency and severity of esophagitis increased after LMAHC. A recurrent hiatal hernia was revealed in 5 (33%) LMAH-C patients (all type I hernias) and in 3 (17%) LMAH-F patients (2 type I hernia; 1 type II hernia) (p ¼ 0.266). No mesh-related complications were documented in either group. Twelve months postoperatively, 8 of 17 (47%) LMAH-C patients and 6 of 20 (30%) LMAH-F patients were on daily PPI therapy (p ¼ 0.286). Four of 17 (24%) LMAH-C patients and 3 of 20 (15%) LMAH-F patients (p ¼ 0.336) showed a failure of reflux treatment based on the criteria mentioned above.
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Baseline Characteristics
Characteristics
Sex, n Male Female Age, y, mean SD BMI, kg/m2, mean SD ASA, n ASA I ASA II ASA III Esophagitis, n 24-h-pH-monitoring n DeMeester score, mean SD Manometry, n Pressure LES, mmHg, mean SD GSRS subscores, n Off PPI On PPI Reflux, mean SD Off PPI On PPI Dysphagia, mean SD Off PPI On PPI Gas bloating, mean SD Off PPI On PPI Abdominal pain, mean SD Off PPI On PPI GIQLI Score, mean SD Off PPI On PPI Daily PPI-therapy, n
LMAH-C (n ¼ 20)
LMAH-F (n ¼ 20)
4 16 65 10.6 29.4 4.8
5 15 63 12.3 29.3 5.4
0 14 6 6 9 21.5 15.5 9 9.7 8.3
2 16 2 7 10 57.8 53.5 12 6.1 4.2
16 17
15 19
3.6 2.0 2.3 1.1
4.3 1.6 3.0 1.3
0.300y 0.121y
1.9 1.4 2.6 1.7
2.8 1.5 2.4 1.7
0.110y 0.623y
3.8 1.8 3.4 1.5
3.9 1.5 4.0 1.1
0.841y 0.236y
3.1 1.4 3.0 1.3
3.2 1.2 2.7 1.2
0.913y 0.558y
81.1 21.2 91.4 22.5 17
91.6 23.0 97.8 23.2 20
0.196y 0.405y 0.072*
p Value
0.705*
0.622y 0.928y 0.127*
0.736* 0.066y 0.360y
*Chi-square test. y t-test. ASA, American Society of Anesthesiologists; BMI, body mass index; GIQLI, Gastrointestinal Quality of Life; GSRS, Gastrointestinal Symptom Rating Scale; LMAH-C, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy LMAH-F, laparoscopic mesh-augmented hiatoplasty with fundoplication; PPI, proton pump inhibitor.
During the 12-month follow-up period, 1 of 18 (6%) LMAH-C patients and 4 (20%) LMAH-F patients needed rehospitalization (p ¼ 0.189). All rehospitalized patients needed reintervention. The 1 patient in the LMAH-C group needed rehospitalization 28 days postoperatively for removal of an esophageal stent, which had been placed for the coverage of an esophageal perforation during the postoperative course. The 4 rehospitalized LMAH-F patients needed laparoscopic revision (1 for incarceration of small bowel at the hiatus; 1 for recurrent hiatal hernia; 2 for dysphagia). No mortality occurred in either group.
Considering the 1 LMAH-F patient, who underwent reoperation due to recurrent hiatal hernia during the 12-month follow-up period, and the results of uppergastrointestinal endoscopy at 12 months, there were 5 (33%) cases of documented recurrent hiatal hernia in LMAH-C patients and 4 (21%) in LMAH-F patients (p ¼ 0.420). Post-hoc power analysis Post-hoc power analysis of this study population revealed a power of 81% for detection of significant differences
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Figure 2. Reflux syndrome score. Light gray bar, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy; dark gray bar, laparoscopic mesh-augmented hiatoplasty with fundoplication.
(at a 2-sided significance level of 0.05) within the reflux subscore; it was 9% for failure of reflux treatment and 11% for recurrent hiatal hernia. Therefore, a sample size of 870 patients would be needed for failure of reflux treatment and 502 patients for recurrent hiatal hernia as the endpoint (each with a power of 80%).
DISCUSSION This trial evaluated for the first time the effect of routine fundoplication as an adjunct to mesh-reinforced PEH repair in a patient- and assessor-blinded randomized controlled setting. Twelve months postoperatively, patients with routine fundoplication reported significantly fewer reflux symptoms than did patients without fundoplication. Subjective reflux control was confirmed by 24-hour pH monitoring at 3 months and upper-gastrointestinal endoscopy at 12
Figure 3. Gas-bloat syndrome score. Light gray bar, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy; dark gray bar, laparoscopic mesh-augmented hiatoplasty with fundoplication.
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Figure 4. Dysphagia score. Light gray bar, laparoscopic meshaugmented hiatoplasty with cardiophrenicopexy; dark gray bar, laparoscopic mesh-augmented hiatoplasty with fundoplication.
months, which revealed esophagitis in 53% of patients after LMAH-C and in 17% of patients after LMAH-F, respectively. A total of 24% of LMAH-C patients and 15% of LMAH-F patients showed a failure of reflux treatment according to the definition by Lundell and associates.14 So far, only few cohort studies have evaluated GERD after PEH repair. After PEH repair with fundoplication, values of 10% to 20% postoperative GERD were reported.21,22 After PEH repair without fundoplication, Styger and coworkers4 reported 32% new onset of GERD at a mean follow-up of 3 years. Repair of PEH by LMAH-C without fundoplication was evaluated in 2 cohort studies; postoperative GERD was observed in 20% and 34% of patients, respectively.5,6 In this trial, patients were included independently of the preoperative evidence of GERD. The majority of patients in both groups
Figure 5. Gastrointestinal Quality of Life Index (GIQLI). Light gray bar, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy; Dark gray bar, laparoscopic mesh-augmented hiatoplasty with fundoplication.
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Upper Gastrointestinal Endoscopy
Variable
Endoscopy, n Esophagitis, n LA, A LA, B LA, C LA, D Barrett, n Hiatal hernia, n Type I Type II Type III Mesh complications
LMAH-C LMAH-F Preoperatively
20 6 3 3 0 0 0 20 0 0 20
20 7 3 2 1 1 3 20 0 0 20
LMAH-C LMAH-F 12 mo
15 8 5 2 1 0 1 5 5 0 0 0
18 3 1 1 1 0 3 3 2 1 0 0
p Value, course LMAH-F to LMAH-C Preoperatively 12 mo
p Value, course pre- to postoperatively Group comparison
N/A 0.736*
0.212* 0.026*
0.226y 0.032y 0.066z
0.072* N/A
0.381* 0.266*
N/A 0.273y
N/A
*Chi-square test. y Logistical regression, p value is adjusted for baseline (preoperative), with factor “group” and covariate “baseline-value.” z p value is comparison of both groups adjusted for baseline.20 LA, Los Angeles (classification); LMAH-C, laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy; LMAH-F, laparoscopic mesh-augmented hiatoplasty with fundoplication; N/A, not available.
fulfilled the GERD criteria preoperatively, reflecting gastroesophageal reflux to be common in PEH as well. However, objectifying GERD in PEH patients might be difficult due to anatomic reasons. The present data suggest that a routine fundoplication should be added in PEH patients irrespective of the preoperative evidence of GERD to reduce the risk of postoperative persisting or new onset gastroesophageal reflux. The risk of side effects does not seem to be increased by adding a fundoplication after mesh-reinforced PEH repair. Dysphagia symptoms did not differ between LMAH-C and LMAH-F patients 12 months postoperatively and were comparable to the preoperative state within both groups. However, 2 patients, after LMAHF, underwent reoperation due to persisting dysphagia symptoms. Gas bloating symptoms did not differ between both groups postoperatively and decreased within both groups compared with the preoperative state. Still, although not significant, more patients reported an inability to belch and were unable to vomit after LMAH-F. These symptomatic data after LMAH-C are in line with those from previous cohort studies.5,23 Prospective data on side effects after PEH repair with fundoplication are scarce.2 After fundoplication in GERD patients, frequent gas bloating symptoms are reported in up to 58%7 of patients and in about 20%, new symptoms occur postoperatively.8,9 Preoperative impaired quality of life assessed by the GIQLI questionnaire improved significantly after both
LMAH-C and LMAH-F and did not differ between groups at 12 months. Therefore, the higher incidence of reflux symptoms in LMAH-C patients did not seem to affect the overall quality of life. This might be explained by the fact, that PEH patients suffer from various symptoms,24 and postoperative reflux control is not the leading criterion for treatment success, as in typical GERD patients. Additionally, PPIs provide an effective drug therapy with few side effects. Recurrent hiatal hernias at 12-month follow-up were documented in 5 (33%) LMAH-C patients and 4 (21%) LMAH-F patients. Therefore, because recurrence rates between groups were comparable, an additional fundoplication does not seem to decrease the risk of hernia recurrence when a consequent mesh reinforcement of the hiatus is performed. The overall recurrence rates of 33% and 21%, respectively, seem to be higher than those reported for mesh-reinforced PEH repair, which range from 0% to 23%.25 However, it has to be noted that a strong definition for the diagnosis of recurrent hiatal hernia was used in this trial. As recently evaluated by our group, endoscopy might be more sensitive compared with barium swallow in the detection of particularly small hiatal hernias.26 Consequently, endoscopically documented cephalic displacement of the proximal margin of the gastric mucosal folds > 2 cm in relation to the hiatus served as a criterion for a recurrent hiatal hernia. All hernia recurrences in LMAH-C patients were small sliding hernias, and only 1 PEH recurrence was documented after
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LMAH-F. Differing between symptomatic and asymptomatic hiatal hernia recurrences, only 1 LMAH-F patient had reoperation because of a symptomatic hernia recurrence during the 12-month follow-up period. Intraoperative complications and in-hospital morbidity were comparable between groups and were comparable to those in other series of laparoscopic PEH repair published so far, ranging from 4% to 28%.21,27-29 The only major complication in our series was an esophageal perforation during LMAH-C, which was resutured laparoscopically and stented endoscopically postoperatively. A certain morbidity rate after PEH repair seems to be inevitable, which might be explained by the fact that PEHs are more common among elderly people and, furthermore, the procedure involves 2 body cavities. The reoperation rate of 4 (20%) patients after LMAH-F seen within this context might be the consequence of the complex patient group and a random effect of the small sample size. This trial has some limitations. Because data on the effect of a fundoplication after mesh-augmented PEH repair were not available when the study was initiated, a reasonable power calculation was not possible. Therefore, the study was designed as a pilot trial. The data from this study enable the planning of a well-designed confirmative, randomized controlled trial. According to our post-hoc power analysis, 502 and 870 patients would be needed to confirm the difference in recurrent hiatal hernias and postoperative failure in gastroesophageal reflux treatment, respectively, at a level of significance of 0.05 with a power of 80%. Therefore, considering the low incidence of symptomatic PEH patients needing surgery, a confirmative randomized controlled trial seems to be difficult to realize. To date, this pilot trial remains the best evidence available. Objective follow-up by endoscopy, pullthrough manometry, and 24-hour pH monitoring was missing for several patients. The most frequent reason for missing tests was patients’ refusal due to resolution of their symptoms. Therefore, a selection bias cannot be excluded. Finally, this trial evaluated a symptomatic and objective outcome at 12-month follow-up. To draw a definite conclusion on recurrence rates, mesh complications, and symptomatic long-term follow-up, and to enable a comparison with outcomes data from other trials evaluating hiatal hernia repair,30 the scheduled 3- and 5-year follow-up are necessary. However, all these limitations concern both groups investigated in this study and do not produce a bias between groups.
CONCLUSIONS To summarize, this first randomized controlled pilot trial suggests that routine addition of fundoplication in
J Am Coll Surg
mesh-augmented repair of PEHs is reasonable to avoid postoperative gastroesophageal reflux and concomitant esophagitis. Fundoplication-related side effects do not seem to be clinically relevant. Multicenter randomized controlled trials are required to confirm these findings. Author Contributions Study conception and design: Mu¨ller, Achtsta¨tter, Diener, Zerz, Gutt, Bu¨chler, Linke Acquisition of data: Mu¨ller, Achtsta¨tter, Diener, Gondan, Warschkow, Marra, Zerz, Gutt, Linke Analysis and interpretation of data: Mu¨ller, Achtsta¨tter, Diener, Gondan, Warschkow, Marra, Zerz, Gutt, Bu¨chler, Linke Drafting of manuscript: Mu¨ller, Achtsta¨tter, Diener, Gondan, Warschkow, Zerz, Gutt, Bu¨chler, Linke Critical revision: Mu¨ller, Achtsta¨tter, Diener, Gondan, Warschkow, Marra, Zerz, Gutt, Bu¨chler, Linke Acknowledgment: The authors wish to thank Beivin Pyne for revising this manuscript as a native English speaker. REFERENCES 1. Cuschieri A, Shimi S, Nathanson LK. Laparoscopic reduction, crural repair, and fundoplication of large hiatal hernia. Am J Surg 1992;163:425e430. 2. Antoniou SA, Antoniou GA, Koch OO, et al. Lower recurrence rates after mesh-reinforced versus simple hiatal hernia repair: a meta-analysis of randomized trials. Surg Laparosc Endosc Percutan Tech 2012;22:498e502. 3. Maziak D, Todd T, Pearson F. Massive hiatus hernia: evaluation and surgical management. J Thorac Cardiovasc Surg 1998;115:53e60. 4. Styger S, Ackermann C, Schuppisser JP, Tondelli P. [Reflux disease following gastropexy for para-esophageal hiatal hernia]. Schweiz Med Wochenschr 1995;125:1213e1215. 5. Linke GR, Gehrig T, Hogg LV, et al. Laparoscopic meshaugmented hiatoplasty without fundoplication as a method to treat large hiatal hernias. Surg Today 2014;44:820e826. 6. Muller-Stich BP, Linke GR, Borovicka J, et al. Laparoscopic mesh-augmented hiatoplasty as a treatment of gastroesophageal reflux disease and hiatal hernias-preliminary clinical and functional results of a prospective case series. Am J Surg 2008;195:749e756. 7. Heikkinen TJ, Haukipuro K, Bringman S, et al. Comparison of laparoscopic and open Nissen fundoplication 2 years after operation. A prospective randomized trial. Surg Endosc 2000;14:1019e1023. 8. Anvari M, Allen C. Postprandial bloating after laparoscopic Nissen fundoplication. Can J Surg 2001;44:440e444. 9. Booth MI, Jones L, Stratford J, Dehn TC. Results of laparoscopic Nissen fundoplication at 2-8 years after surgery. Br J Surg 2002;89:476e481. 10. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2003;310:2191e2194.
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