Testoni S, Barchi A, et al.Transoral Incisionless Fundoplication Leads to Esophageal Mucosa Healing in Responder Patients Followed up to 2 Years, as Documented by Esophageal Mean Nocturnal Baseline Impedance. J Neurogastroenterol Motil. 2024;30:(4):437-46

Авторы: Testoni S.G.G. / Barchi A. / Passaretti S. / Notaristefano Ch. / Ribichini E. / Mandarino F.V. / Biamonte P. / Azzolini F. / Fanti L. / Testoni P.A. / Danese S.

Transoral Incisionless Fundoplication Leads to Esophageal Mucosa Healing in Responder Patients Followed up to 2 Years, as Documented by Esophageal Mean Nocturnal Baseline Impedance

¹ Division of Gastroenterology and Gastrointestinal Endoscopy, Department of Experimental Oncology, IRCCS Ospedale San Raffaele, Milan, Italy; and ² Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milan, Italy


Background/Aims
Decrease of esophageal mean nocturnal baseline impedance reflects loss of mucosal integrity. It can predict response to anti-reflux therapy. Mean nocturnal baseline impedance after transoral incisionless fundoplication for gastroesophageal reflux disease has never been assessed. The aim of the study is to investigate mean nocturnal baseline impedance and conventional pathophysiological parameters following transoral incisionless fundoplication.

Methods
Patients prospectively treated by transoral incisionless fundoplication in a single center were retrospectively reviewed regarding 1- and 2-year 24-hour pH-metry and multichannel intraluminal impedance with calculation of mean nocturnal baseline impedance, gastroesophageal reflux disease-health related quality of life and reflux symptom index scores.

Results
Thirty-eight and 17/38 patients with 1- and 2-year 24-hour pH-multichannel intraluminal impedance assessment and mean nocturnal baseline impedance’s calculation after transoral incisionless fundoplication, respectively, were identified. Mean nocturnal baseline impedance significantly increased up to 2-year follow-up (P = 0.033), along with significant decrease in % of acid exposure time (P = 0.003), gastroesophageal reflux disease-health related quality of life score (P < 0.001), and reflux symptom index (P = 0.008), compared with baseline. The longest orthostatic reflux decreased too, approaching statistical significance (P = 0.054). These significant changes occurred in patients experiencing ≥ 50% reduction of symptom questionnaires’ scores (“responders”). Conversely, mean nocturnal baseline impedance worsened and no significant changes of 24-hour pH-multichannel intraluminal impedance metrics were observed in “non-responder” patients (symptom questionnaires’ scores decrease < 50%).

Conclusion
In patients who responded a significant improvement of mean nocturnal baseline impedance and % acid exposure time was observed up to 2-year follow-up, suggesting that transoral incisionless fundoplication achieves an effective esophageal mucosa healing besides symptom improvement.
(J Neurogastroenterol Motil 2024;30:437-446)

Key Words
Endoscopy, gastrointestinal; Esophageal pH monitoring; Fundoplication; Gastroesophageal reflux; Impedance

Introduction

Gastroesophageal reflux disease (GERD) represents a major concern encountered in clinical practice.^1,2 Besides erosive esophagitis, GERD is associated in most cases with non-erosive reflux disease (NERD), esophageal ineffective motility and changes of the esophageal wall’s internal components due to long acid exposure.³ The intramucosal damage can be documented by the esophageal 24-hour pH-metry and multichannel intraluminal impedance recording (24-hr pH-MII).^4,5 The decrease in esophageal baseline impedance can be a surrogate marker for loss of esophageal mucosa integrity and permeability induced due to reflux.^6-8 The mean nocturnal baseline impedance (MNBI) can predict the esophageal injury and longitudinal reflux burden.⁹ MNBI showed an inverse correlation with dilation of esophageal epithelium’s intercellular spaces and was a significant independent predictor of satisfactory response to anti-reflux therapy.^10,11

Transoral incisionless fundoplication (TIF) is increasingly proposed as a therapy bridging the gap between medical therapy and anti-reflux surgery.^12-16 In fact, proton pump inhibitors (PPIs) are less effective for weakly acidic or alkaline refluxes, may have side effects, or require high-dose maintenance therapy to control symptoms. Anti-reflux surgery, although effective, can lead to persistent troublesome side effects (≤ 20% of cases),^17,18 that limit its use in GERD with mild-to-moderate severity. TIF has been performed using the EsophyX2.0/Z (EndoGastric Solutions, Redmond, WA, USA), currently the most widely used, or MUSE (Medigus Ultrasonic Surgical Endostapler, Medigus, Omer, Israel) devices.¹⁹

Most studies aimed primarily at assessing the clinical efficacy and safety of TIF. Few studies examined the post-TIF pathophysiological parameters with less convincing results. Thus, doubts remain about the true clinical efficacy of TIF in GERD. The esophageal mucosal healing following TIF has never been assessed using MNBI as an indicator.

Therefore, aims of the present study were to assess the MNBI and conventional pathophysiological parameters up to 2-year followup after TIF in GERD patients, and to correlate these metrics with the post-TIF symptomatic outcomes.

Materials and Methods

Study Patients and Design

All patients treated by TIF in a 9-year period, enrolled in 2 prospective observational protocols at San Raffaele Scientific Institute of Milan (Italy), with a 2-year post-TIF symptomatic and functional follow-up were considered for this study.^20,21 Both the protocols (No. EsophyX/2007 and No. MUSE/2015) were approved by the institutional medical Ethics Committee and conducted according to the Declaration of Helsinki. All patients gave written informed consent for the procedures and data management for scientific purposes. The MUSE protocol was registered at ClinicalTrials.Gov (ID: NCT03669874), while for the EsophyX2.0 protocol (started in 2007) the registration was not requested.

Patients were treated with TIF according to the guidelines issued by the Society of American Gastrointestinal and Endoscopic Surgeons.²² Inclusion criteria were chronic (at least 6 months) GERD-related esophageal and/or extra-esophageal symptoms and response to PPIs, endoscopic findings of GERD or Barrett’s esophagus < 3 cm, and evidence of NERD or hypersensitive esophagus at functional tests.^20,21 Exclusion criteria were hiatal hernia > 2.5 cm (non-reducible for TIF with MUSE), functional heartburn, primary motility disorders or ineffective motility at esophageal manometry,^23-25 and local and systemic pathologies affecting the upper gastrointestinal (GI) tract.^20,21

As per protocols, prior to TIF all patients underwent: (1) assessment of symptoms through administration of GERD-Health Related Quality of Life (HRQL) questionnaire in EsophyX2.0 protocol or GERD-HRQL and Reflux Symptom Index (RSI) questionnaires in MUSE protocol (14 days after stopping PPIs);^26-28 (2) assessment of PPIs consumption; (3) upper GI endoscopy to evaluate the presence of hiatal hernia, esophagitis (Los Angeles classification) and Barrett’s esophagus (Prague classification), and the gastroesophageal flap valve’ morphology (Hill’s grade and Jobe’s length;²⁹ (4) esophageal high-resolution manometry (HRM) to exclude major esophageal motility disorders (Chicago classification), and to measure the basal pressure and length of the lower esophageal sphincter; and (5) 24-hr pH-MII recording to exclude functional heartburn. TIF techniques with EsophyX2.0 and MUSE devices have already been described elsewhere.^20,21 EsophyX2.0 reproduces the concept of surgical partial fundoplication, creating a 270° esophago-gastric plication in an intra-abdominal position by deploying multiple polypropylene fasteners under endoscopic control. MUSE reproduces a partial anterior 180° fundoplication under ultrasonographic and software guidance, creating a new 3-cm long valve just below the cardia.

After TIF, patients were followed-up by physicians who were not involved in TIF procedures and aware of post-procedure outcomes as follows: (1) GERD-HRQL and RSI questionnaires at 6 months, and then yearly; (2) esophageal HRM at 6 months; (3) 24-hr pH-MII recording at 1 and 2 years; (4) upper GI endoscopy at 6 and 12 months.

For this study, we retrospectively reviewed the 24-hr pH-MII tracings, with assessment of MNBI as a new impedance metric, and GERD-HRQL and RSI questionnaires at baseline and 1- and 2-year follow-up after TIF.

Twenty-four-hour pH-impedance Recording

The esophageal 24-hr pH-MII catheter, calibrated in pH 4 and pH 7 buffer solutions, consisted of 8 impedance rings and 1 distal pH sensor (VersaFlex Z pH-Impedance catheters; Given Imaging Ltd, Mansfield, MA, USA). A liquid reflux episode detected by MII was defined as a retrograde drop in impedance of more than 50% from baseline in the 2 distal channels. Each reflux episode was defined as acid if there was an associated drop in distal esophageal pH to < 4, and non-acid if there was no such drop; a pH-only episode was defined as a fall in distal pH to < 4 lasting at least 5 seconds, detected only by the pH sensor, without a retrograde drop in impedance.^30,31

The 24-hr pH-MII tracings were reanalyzed to calculate MNBI as described by Martinucci et al,⁸ by extracting the baseline impedance values at the most distal impedance channel (3-cm above the lower esophageal sphincter) across 3 stable nocturnal 10-minute periods (at around 1:00 AM, 2:00 AM, and 3:00 AM), in order to avoid reflux events, swallows, artifacts or pH drops, and averaging the values from the 3 time periods.

Study Endpoints

Primary endpoint was to assess the changes of MNBI, as a marker of esophageal mucosa integrity, in addition to the conventional 24-hr pH-MII metrics at 1- and 2-year follow-up after TIF versus pre-TIF values.

Secondary endpoints were: (1) to assess the one- and 2-year post-TIF symptomatic outcomes based on GERD-HRQL and RSI questionnaires, defining clinical response to TIF as at least a 50% reduction of their scores compared with pre-TIF; (2) and to correlate MNBI and conventional 24-hr pH-MII metrics with the symptomatic outcomes.

Statistical Methods

Data from continuous variables were tested for normal distribution using the Kolmogorov-Smirnov test and are reported as mean (with standard deviation or 95% confidence interval [CI]), unless otherwise indicated. The differences of continuous variables between before and after TIF for each patient, and between clinical responder and non-responder patients’ groups, were analyzed using the paired 2-tailed Student’s t test or the Wilcoxon test, and the unpaired Student’s t test or the Mann-Whitney test, respectively, as appropriate based on data distribution. Categorical data are presented as proportions and compared using the χ-squared test or Fisher’s exact test. Differences were considered statistically significant if P-value ≤ 0.05.

Results

This study included 38 patients with pre- and 2-year post-TIF esophageal 24-hr pH-MII measurements, including MNBI, and symptom questionnaires scores. Baseline patients’ characteristics are reported in Table 1.

Twenty-five out of 38 patients (65.8%) underwent TIF with EsophyX2.0, and 13 out of 38 patients (34.2%) were treated with the MUSE device, with technical success in all cases.

All patients underwent the scheduled symptomatic and functional evaluations at 1-year. Of these, 17/38 (44.7%) patients (9 and 8 treated with EsophyX2.0 and MUSE devices, respectively) attended the functional 2-year follow-up, while the others refused it and were only followed-up clinically.

Two out of 38 patients (5.3%) did not respond to TIF with EsophyX2.0 and subsequently underwent surgical fundoplication after 2 years.

Twenty-four-hour Impedance Recording and Mean Nocturnal Basal Impedance

All 24-hr MII parameters improved after TIF. At 1 year, there were significant reductions in the mean number of total and weakly acid refluxes (P = 0.017 and P = 0.012 vs pre-TIF). These changes were no longer significant 2 years after TIF. The mean number of acid refluxes also decreased from baseline up to 2 years, though not significantly.

The median MNBI increased from 1200 Ω (95% CI, 1000- 1800) at baseline to 1450 Ω (95% CI, 1200-1600) at 1 year but this was not significant. At 2 years, the median MNBI was significantly higher than before TIF (P = 0.033), further increasing up to 1800 Ω (95% CI, 1119.2-2560.3) (Table 2).

Twenty-four-hour pH-metry

The mean percent total acid exposure time (AET%) was lower than baseline 1 year and 2 years after TIF, with a significant difference at 2 years (P = 0.003). The median longest orthostatic reflux (LOR, minutes) followed a similar trend, approaching statistical significance at 2 years (P = 0.054). The mean orthostatic AET% also decreased at 1 year and 2 years, though not significantly. The mean clinostatic AET% and median longest clinostatic reflux (LCR, minutes) were not affected by TIF, remaining substantially unchanged from baseline up to 1 year and 2 years (Table 3).

Symptomatic Scores

Compared with the pre-TIF scores, the median GERD-HRQL score significantly decreased (P < 0.001 at 1 and 2 years) (Table 4). Overall, GERD-HRQL score decreased by a median of 57.5% (95% CI, 79.1-49.6) at 1 year and 65.7% (95% CI, 84.6-50.1) at 2 years, with 65.8% (25/38) and 76.5% (13/17) of patients, respectively, presenting a GERD-HRQL score reduction ≥ 50%.

In MUSE protocol, the median RSI score significantly decreased at 1 (P = 0.002) and 1 years (P = 0.008) (Table 4). Overall, RSI score showed a median decrease of 67.0% (95% CI, 88.0-21.5) at 1 year and 64.5% (95% CI, 81.5-43.6) at 2 years. At least 50% reduction in RSI score was recorded in 61.5% (8/13) and 75.0% (6/8) of patients at 1 and 2 years, respectively. In MUSE protocol, all patients with RSI decrease ≥ 50% presented a decrease ≥ 50% of GERD-HRQL scores up to 2 years, too.

Correlation Between Functional Metrics and Clinical Response

The median MNBI improved in clinical responder patients, changing from 1200 Ω (95% CI, 1000-1800) at baseline to 1500 Ω (95% CI, 1200-1970.6) at 1 year, and, significantly, to 1800 Ω (95% CI, 1353.2-2840.6) at 2 years (P = 0.005). Conversely, nonresponder patients experienced decrease in the median MNBI from 1600 Ω (95% CI, 800-2240.5) at baseline to 1400 Ω (95% CI, 800-1834.2) 1 year and 950 Ω (95% CI, 900-2050) 2 years after TIF, with no significant difference from baseline (Figure).

Responder patients also showed decreases of the mean number of total, acid, and weakly acid refluxes from pre-TIF up to 2 years, although significantly only at 1 year (P = 0.024, P = 0.049, and P = 0.041, respectively) (Tables 5 and 6), along with significant improvement in the mean AET% and median LOR up to 2 years (P = 0.002 and P = 0.001, respectively). In these patients, the post-TIF mean orthostatic AET% also decreased, although this change was not statistically significant; TIF had no effect on the mean clinostatic AET% or median LCR. In contrast, the mean AET% and median LOR remained substantially unchanged from pre-TIF up to 2 years in non-responder patients, who, in addition, did not present any significant changes in the other 24-hr pH-MII conventional metrics (Tables 5 and 6).

Discussion

A still open issue is whether TIF effectively cures GERD, beside improving symptoms, even in the long-term.

TIF, using either the EsophyX2.0 or MUSE device, is effective and safe as surgical fundoplication, with shorter operating time and length of stay (P < 0.001).³² TIF with EsophyX2.0 led to control of GERD symptoms in 75-93% of patients in the shortand medium-term.^12-15 In series of selected patients followed up to 10 years PPIs were discontinued, with 62% completely off-PPIs, and esophagitis was objectively healed in 82% and 84% of patients at 3-year and 10-year follow-up, respectively.³³ Normalization of the numbers of total and acid refluxes and the De Meester score after TIF has been reported in 37% to 89% of patients, respectively.^20,34,35

Only a minority of studies have investigated functional outcomes after TIF, with results not reflecting the clinical investigations. Systematic reviews and network meta-analyses reported TIF had a greater likelihood of improving the GERD-HRQL score compared to anti-reflux surgery, which in turn had a greater likelihood of increasing the % time with esophageal pH > 4 and reducing persistent esophagitis compared with TIF.³⁶ Similarly, TIF was significantly superior to PPIs in improving GERD-HRQL and heartburn scores, but PPIs were superior to TIF in reducing the % time with esophageal pH < 4.^12,37

The diagnostic sensitivity of 24-hr pH-MII metrics is considered suboptimal.^38-40 The diagnostic sensitivity for GERD of symptom index, symptom association probability, and ratio of symptom association probability to symptom index was only of 51%, 47%, and 36%, respectively.⁴¹ TIF seemed to improve the esophageal mucosa impedance and permeability because of reduced AET%.⁴² However, AET%, the most useful functional parameter for GERD diagnosis and predictor of acid reflux burden, is influenced by the day-to-day variability of reflux exposure, and was reported to be normal in 19% of patients with erosive esophagitis and in nearly 50% of NERD patients.^9,38,43 Recently, the 24-hr MII metric MNBI has been proposed for GERD diagnosis, reflecting the longitudinal reflux burden and degree of esophageal mucosa damage more accurately and objectively than other conventional metrics, and identifying responder patients to anti-reflux medical or surgical treatment.^7,43-46 Baseline impedance is not affected by circadian variation and is less influenced by reflux episodes and swallowing if measured during the night.^9,11,41

In this study, we aimed at assessing the changes, up to 2-year follow-up, of MNBI as marker of esophageal mucosa integrity, along with conventional 24-hr pH-MII metrics and GERD-HRQL and RSI scores, in GERD patients treated with TIF. For further information on TIF efficacy in esophageal mucosa healing, we also investigated the relationships between these 24-hr pH-MII metrics and the clinical response, defined as at least 50% decrease of GERD-HRQL and RSI scores.

In our series, in agreement with previous reports, TIF significantly reduced GERD-HRQL and RSI scores at 1 and 2 years. In parallel, MNBI improved 1 and 2 years after TIF, with a significant increase from baseline up to 2 years. MNBI showed a continuously increasing trend in patients who had a clinical response, significant at 2 years, suggesting that repair of esophageal mucosa integrity takes time in patients with long-standing GERD. Conversely, MNBI persistently decreased in non-responder patients, though not significantly compared with pre-TIF.

Low MNBI values reflected impairment of esophageal mucosa integrity even in the absence of macroscopic damage and were inversely related to AET%: the lower the MNBI, the worse the integrity of the esophageal mucosa and the greater its permeability and, thus, the greater the severity of the esophageal mucosa damage.^6,11 MNBI was independently associated with responses to PPIs and more strongly associated with favorable responses to PPIs than AET%.⁴⁴

In support of the adequacy of the newly created valve to limit the reflux, we found a significant reduction of the number of total and weakly acid refluxes 1 year after TIF. The mean number of acid refluxes decreased too, though not significantly. Two years after TIF these metrics were still lower than baseline. At 24-hr pHmetry, the AET%, both total and in orthostatic and clinostatic positions, and the duration of LOR improved up to 2 years after TIF, with significant reduction from baseline for AET% and LOR. Again, these results suggest that TIF may be capable of reducing the esophageal exposure to refluxes and the maximum duration of individual reflux episodes. Patients with clinical response showed improvements of the 24-hr pH-MII parameters up to 2 years after TIF, with significant reduction of the number of total, acid, and weakly acid refluxes at 1 year and of AET% and LOR at 2 years in contrast with the lack of improvement in non-responder patients.

To the best of our knowledge, this is the first study investigating the long-term changes of conventional 24-hr pH-MII metrics and MNBI after TIF for GERD and correlating these metrics with the clinical outcomes. The small number of patients who completed the 2-year follow-up could potentially result in functional results not as striking as the clinical ones. Larger study populations and longer follow-up may probably confirm this. The single-center and the retrospective nature of this study could be limitations, leading to potential selection bias. However, GERD patients in this study were strictly selected for TIF in prospective clinical protocols, with prospective 24-hr pH-MII recordings, taken after standardized positioning of the pH-MII probe, checked by esophageal HRM. In addition, the 24-hr pH-MII tracings were re-analyzed using the same software, and checked by experts in digestive pathophysiology who were unaware of the patients’ clinical response to TIF, thus constituting strengths of the study.

In conclusion, TIF may be a valid and durable procedure for treating GERD in selected patients, regardless of the device used, capable not only to improve subjective symptoms but also the reflux burden. TIF led to significant improvement of symptoms as well as of AET% and MNBI 24-hr pH-MII metrics, considered the best predictors of reflux-related symptom relief,^42,47 and to effective healing of esophageal mucosa over time up to 2 years. It would be useful to increase the population sample and the follow-up time to confirm the efficacy of TIF and include MNBI as part of the functional investigation to appropriately assess the esophageal mucosa healing after TIF.

Financial support: None.

Conflicts of interest: The authors declare they have no competing interests relevant to the content of the study, and that may in any way gain or lose financially from the results of the study or the conclusions of the article. Silvio Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma, and Vifor.

Author contributions: Sabrina G G Testoni, Sandro Passaretti, and Pier A Testoni: conception and design of the study; Sabrina G G Testoni, Alberto Barchi, Chiara Notaristefano, Emanuela Ribichini, Francesco V Mandarino, Paolo Biamonte, Francesco Azzolini, and Lorella Fanti: acquisition of data for the study; Sabrina G G Testoni, Alberto Barchi, and Sandro Passaretti: analysis and interpretation of data for the study; Sabrina G G Testoni and Barchi A: writing of the original draft; and Sandro Passaretti and Silvio Danese: revising critically the draft for important intellectual content. All authors provided the final approval of the version to be published.

Sabrina G G Testoni and Alberto Barchi equally contributed to this study.

*Correspondence: Sandro Passaretti, MD Division of Gastroenterology and Gastrointestinal Endoscopy, Department of Experimental Oncology, Vita-Salute San Raffaele University, IRCCS Ospedale San RaffaeleVia Olgettina 60, Milan, 20132 Italy Tel: +39-02-26436303, E-mail: passaretti.sandro@hsr.it

References

1. Katz PO, Gerson LB, Vela MF. guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013;108:308-328.
2. El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2014;63:871-880.
3. Moayyedi P, Talley NJ. Gastro-oesophageal reflux disease. Lancet 2006;367:20862100.
4. Frazzoni M, de Bortoli N, Frazzoni L, Tolone S, Savarino V, Savarino E. Impedance-pH monitoring for diagnosis of reflux disease: new perspectives. Dig Dis Sci 2017;62:1881-1889.
5. Clarke JO, Ahuja NK, Chan WW, et al. Mucosal impedance for esophageal disease: evaluating the evidence. Ann N Y Acad Sci 2020;1481:247- 257.
6. Kessing BF, Bredenoord AJ, Weijenborg PW, Hemmink GJ, Loots CM, Smout AJ. Esophageal acid exposure decreases intraluminal baseline impedance levels. Am J Gastroenterol 2011;106:2093-2097.
7. de Bortoli N, Martinucci I, Savarino E, et al. Association between baseline impedance values and response proton pump inhibitors in patients with heartburn. Clin Gastroenterol Hepatol 2015;13:1082-1088, e1.
8. Martinucci I, de Bortoli N, Savarino E, et al. Esophageal baseline impedance levels in patients with pathophysiological characteristics of functional heartburn. Neurogastroenterol Motil 2014;26:546-555
9. Frazzoni M, Savarino E, de Bortoli N, et al. Analyses of the post-reflux swallow-induced peristaltic wave index and nocturnal baseline impedance parameters increase the diagnostic yield of impedance-pH monitoring of patients with reflux disease. Clin Gastroenterol Hepatol 2016;14:40-46.
10. Ribolsi M, Guarino MPL, Tullio A, Cicala M. Post-reflux swallowinduced peristaltic wave index and mean nocturnal baseline impedance predict PPI response in GERD patients with extra esophageal symptoms. Dig Liver Dis 2020;52:173-177.
11. Farré R, Blondeau K, Clement D, et al. Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique. Gut 2011;60:885- 892.
12. Xie P, Yan J, Ye L, et al. Efficacy of different endoscopic treatments in patients with gastroesophageal reflux disease: a systematic review and network meta-analysis. Surg Endosc 2021;35:1500-1510.
13. Huang X, Chen S, Zhao H, et al. Efficacy of transoral incisionless fundoplication (TIF) for the treatment of GERD: a systematic review with meta-analysis. Surg Endosc 2017;31:1032-1044.
14. McCarty TR, Itidiare M, Njei B, Rustagi T. Efficacy of transoral incisionless fundoplication for refractory gastroesophageal reflux disease: a systematic review and meta-analysis. Endoscopy 2018;50:708-725.
15. Chandan S, Mohan BP, Khan SR, et al. Clinical efficacy and safety of magnetic sphincter augmentation (MSA) and transoral incisionless fundoplication (TIF2) in refractory gastroesophageal reflux disease (GERD): a systematic review and meta-analysis. Endosc Int Open 2021;9:E583-E598.
16. Rouphael C, Padival R, Sanaka MR, Thota PN. Endoscopic treatments of GERD. Curr Treat Options Gastroenterol 2018;16:58-71.
17. Seeras K, Bittar K, Siccardi MA. Nissen fundoplication. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2022.
18. Garg SK, Gurusamy KS. Laparoscopic fundoplication surgery versus medical management for gastro-oesophageal reflux disease (GORD) in adults. Cochrane Database Syst Rev 2015;2015:CD003243.
19. Gerson L, Stouch B, Lobonţiu A. Transoral incisionless fundoplication (TIF 2.0): a meta-analysis of three randomized, controlled clinical trials. Chirurgia (Bucur) 2018;113:173-184.
20. Testoni SGG, Cilona MB, Mazzoleni G, et al. Transoral incisionless fundoplication with Medigus ultrasonic surgical endostapler (MUSE) for the treatment of gastro-esophageal reflux disease: outcomes up to 3 years. Surg Endosc 2022;36:5023-5031.
21. Testoni PA, Testoni S, Mazzoleni G, Vailati C, Passaretti S. Long-term efficacy of transoral incisionless fundoplication with Esophyx (Tif 2.0) and factors affecting outcomes in GERD patients followed for up to 6 years: a prospective single-center study. Surg Endosc 2015;29:2770-2780.
22. Pearl J, Pauli E, Dunkin B, Stefanidis D. SAGES endoluminal treatments for GERD. Surg Endosc 2017;31:3783-3790.
23. Bredenoord AJ, Fox M, Kahrilas PJ, Pandolfino JE, Schwizer W, Smout AJ; International High Resolution Manometry Working Group. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography. Neurogastroenterol Motil 2012;24(suppl 1):57-65.
24. Kahrilas PJ, Bredenoord AJ, Fox M, et al. The Chicago classification of esophageal motility disorders, v3.0. Neurogastroenterol Motil 2015;27:160-174.
25. Fox MR, Sweis R, Yadlapati R, et al. Chicago classification version 4.0© technical review: update on standard high-resolution manometry protocol for the assessment of esophageal motility. Neurogastroenterol Motil 2021;33:e14120.
26. Velanovich V, Vallance SR, Gusz JR, Tapia FV, Harkabus MA. Quality of life scale for gastroesophageal reflux disease. J Am Coll Surg 1996;183:217-224.
27. Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice 2002;16:274-277.
28. Schindler A, Mozzanica F, Ginocchio D, Peri A, Bottero A, Ottaviani F. Reliability and clinical validity of the Italian reflux symptom index. J Voice 2010;24:354-358.
29. Jobe BA, O’Rourke RW, McMahon BP, et al. Transoral endoscopic fundoplication in the treatment of gastroesophageal reflux disease: the anatomic and physiologic basis for reconstruction of the esophagogastric junction using a novel device. Ann Surg 2008;248:69-76.
30. Johnson LF, Demeester TR. Twenty-four-hour pH monitoring of the distal esophagus. A quantitative measure of gastroesophageal reflux. Am J Gastroenterol 1974;62:325-332.
31. Shay S, Tutuian R, Sifrim D, et al. Twenty-four hour ambulatory simultaneous impedance and pH monitoring: a multicenter report of normal values from 60 healthy volunteers. Am J Gastroenterol 2004;99:1037- 1043.
32. Toomey P, Teta A, Patel K, Ross S, Sukharamwala P, Rosemurgy A. Transoral incisionless fundoplication: is it as safe and efficacious as a Nissen or Toupet fundoplication? Am Surg 2014;80:860-867.
33. Testoni S, Hassan C, Mazzoleni G, et al. Long-term outcomes of transoral incisionless fundoplication for gastro-esophageal reflux disease: systematic-review and meta-analysis. Endosc Int Open 2021;9:E239- E246.
34. Cadière GB, Van Sante N, Graves JE, Gawlicka AK, Rajan A. Two-year results of a feasibility study on antireflux transoral incisionless fundoplication using EsophyX. Surg Endosc 2009;23:957-964.
35. Thosani N, Goodman A, Manfredi M, et al. Endoscopic anti-reflux devices (with videos). Gastrointest Endosc 2017;86:931-948.
36. Richter Je, Kumar A, Lipka S, Miladinovic B, Velanovich V. Efficacy of laparoscopic nissen fundoplication vs transoral incisionless fundoplication or proton pump inhibitors in patients with gastroesophageal reflux disease: a systematic review and network meta-analysis. Gastroenterology 2018;154:1298-1308, e7.
37. Witteman BP, Conchillo JM, Rinsma NF, et al. Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease. Am J Gastroenterol 2015;110:531-542.
38. Savarino E, Tutuian R, Zentilin P, et al. Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease: study using combined impedance-pH off therapy. Am J Gastroenterol 2010;105:1053-1061.
39. Jiang Y, Jiang L, Ye B, Lim L. Value of adjunctive evidence from MII-pH monitoring and high resolution manometry in inconclusive GERD patients with AET 4-6. Therap Adv Gastroenterol 2021;14:17562848211013484.
40. Penagini R, Sweis R, Mauro A, Domingues G, Vales A, Sifrim D. Inconsistency in the diagnosis of functional heartburn: usefulness of prolonged wireless pH monitoring in patients with proton pump inhibitor refractory gastroesophageal reflux disease. J Neurogastroenterol Motil 2015;21:265-272.
41. Frazzoni M, de Bortoli N, Frazzoni L, et al. The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance pH-monitoring. Neurogastroenterol Motil 2017;29:e12947.
42. Vaezi MF, Choksi Y. Mucosal impedance: a new way to diagnose reflux disease and how it could change your practice. Am J Gastroenterol 2017;112:4-7.
43. Patel A, Sayuk GS, Gyawali CP. Parameters on esophageal pH-impedance monitoring that predict outcomes of patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2015;13:884-891.
44. Ribolsi M, Emerenziani S, Borrelli O, et al. Impedance baseline and reflux perception in responder and non-responder non-erosive reflux disease patients. Scand J Gastroenterol 2012;47:1266-1273.
45. Frazzoni L, Frazzoni M, de Bortoli N, et al. Postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance can link PPIresponsive heartburn to reflux better than acid exposure time. Neurogastroenterol Motil 2017;29:e13116.
46. Ribolsi M, Frazzoni M, Marabotto E, et al. Novel impedance-pH parameters are associated with proton pump inhibitor response in patients in inconclusive diagnosis of gastro-oesophageal reflux disease according to Lyon consensus. Aliment Pharmacol Ther 2021;54:412-418.
47. Patel A, Wang D, Sainani N, Sayuk GS, Gyawali CP. Distal mean nocturnal baseline impedance on pH-impedance monitoring predicts reflux burden and symptomatic outcome in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2016;44:890-898.

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