24-hour pH-impedance monitoring on therapy to select patients with refractory reflux symptoms for antireflux surgery. A single center retrospective study

Размещено на http://www.allbest.ru/

24-hour pH-impedance monitoring on therapy to select patients with refractory reflux symptoms for antireflux surgery. A single center retrospective study

M. Desjardin,* G. Luc,† D. Collet† & F. Zerbib*

* Gastroenterology and Hepatology Department, Hфpital Saint Andrй, Centre Hospitalier Universitaire de Bordeaux and Universitй de Bordeaux, Bordeaux, France.

† Digestive Surgery Department, Hфpital Haut Lйvкque, Centre Hospitalier Universitaire de Bordeaux and Universitй de Bordeaux, Bordeaux, France.

Key Messages

In patients with refractory reflux symptoms, the role of antireflux surgery is debated. There is no consensus regarding patients' selection for surgery, especially if preoperative ambulatory reflux monitoring should be performed `off' or `on' PPIs.

Data of preoperative pH-impedance monitoring on PPIs are limited and data from available studies show favorable outcome in the vast majority of cases.

We conducted a retrospective study in two groups of patients with favorable (n = 26) and unsatisfactory outcomes (n = 7) who had preoperative esophageal pH-impedance monitoring on double dose PPIs.

On therapy, neither pH-impedance reflux parameters nor positive SI could help to discriminate patients with favorable and unsatisfactory outcomes. Only a positive SAP was significantly associated with successful clinical outcome.

laparoscopic fundoplication refractory gastroesophageal

Abstract

Background Treatment of gastro-esophageal reflux refractory symptoms is challenging. This monocenter retrospective study assessed the value of preoperative pH-impedance monitoring `on' therapy to predict functional outcome after laparoscopic fundoplication in patients with refractory reflux symptoms.

Methods Patients with a preoperative pH-impedance monitoring `on' proton pump inhibitors (PPIs) twice daily were assessed at least 6 months after a laparoscopic fundoplication for refractory reflux symptoms. Failure of fundoplication was defined by a Visick score > 2. Postoperative symptoms were assessed by the reflux disease questionnaire (RDQ). The pH-impedance parameters analyzed were the number of reflux events (total, acid, non-acid), esophageal acid exposure time, esophageal bolus exposure time, and symptom-reflux association defined by symptom index (SI) >50% and symptom association probability (SAP) >95%.

Key Results Thirty-three patients (18 female patients, median age 46 years) were assessed after a mean follow-up of 41.3 (range 7-102.2) months. Seven (21.2%) patients were considered as failures. Compared to patients with favorable outcome, these patients were more often `on' PPI therapy (86% vs 23%, p < 0.05) and had higher RDQ scores in each domain: heartburn (p < 0.05), regurgitation (p < 0.05) and dyspepsia (p < 0.05). A positive SAP was the only pH-impedance parameter statistically associated with successful postoperative outcome (p = 0.004).

Conclusions & Inferences On therapy, a preoperative positive symptom association probability is the only pH-impedance parameter associated with favorable outcome after laparoscopic fundoplication for refractory reflux symptoms. These results should be confirmed by prospective studies.

Keywords fundoplication, gastro-esophageal reflux, pH-impedance monitoring.

Introduction

In gastro-esophageal reflux (GER) disease, most symptoms and esophageal mucosal lesions can be effectively treated by acid suppressive therapies, especially proton pump inhibitors (PPIs).[1] However, although there is no widely admitted definition of refractoriness, it is now considered that 30-40% of patients with reflux symptoms fail to respond adequately to PPIs.[2-5] Nowadays, considering the widespread use of these drugs, reflux symptoms refractory to PPIs has become one the most common presentation of GER in gastrointestinal clinical practice. These refractory patients may suffer from functional heartburn, dyspepsia or have persistent acid or weakly acidic reflux, associated or not with esophageal hypersensitivity and psychological co-morbidities.[6] During the past 10-15 years, new compounds supposed to reinforce the antireflux barrier failed to demonstrate any significant clinical benefit or safety profile and have been abandoned.[7, 8] Antireflux surgery is frequently performed for refractory reflux symptoms, although generally considered by experts as having less favorable clinical outcome compared to that obtained in patients with adequate symptom control with PPIs.[5, 9] If surgery can be a valuable option in refractory patients, there is yet no consensus regarding how patients selection should be obtained, and especially if preoperative ambulatory reflux monitoring should be performed `off' or `on' PPIs.[6] Some data suggest that if no esophagitis is present at baseline, a positive 24-hour pH monitoring `off' PPIs preoperatively (i.e., either abnormal esophageal acid exposure or positive symptom association analysis) is associated with favorable outcome after fundoplication.[10-12] By contrast, some authors favor the use of pH-impedance `on' PPIs to demonstrate either the persistence of abnormal GER or a temporal relationship between the persistent symptoms and reflux episodes.[13, 14] However, data are scarce, and since virtually, all the patients in these series have favorable outcome, it is impossible to determine which relevant reflux parameters should be taken into account for the selection of patients.

The aim of this retrospective study was to determine the value of 24-hour pH-impedance monitoring performed `on' PPIs to select patients with refractory reflux symptoms for fundoplication.

Patients and Methods

Patients

We retrospectively included all patients who had laparoscopic fundoplication for refractory reflux symptoms at the Digestive Surgery Department of the Bordeaux University Hospital (Hфpital du Haut Lйvкque). Only patients with a preoperative pH-impedance monitoring on PPI were analyzed. The indication for surgery could be typical (heartburn, regurgitation) and/or atypical reflux symptoms.

Laparoscopic fundoplication

Surgery was very standardized, and consisted in (i) dissection of the abdominal part of the esophagus with identification of the vagus, (ii) mobilization of the fundus with division of two or three short vessels, (iii) non-calibrated closure of the hiatus thanks to two or three non-absorbable stitches and (iv) creation of a posterior 3 cm wrap anchored by three rows of three non-absorbable stitches to the crura, right and left edge of the esophagus. The procedure was achieved by laparoscopy in all cases even in patients who had had a previous fundoplication.

24-hour pH-impedance monitoring

The 24-hour pH-impedance recordings were performed at the Gastroenterology department of the Bordeaux University Hospital (Hфpital Saint Andrй) according to a technique previously described in details.[15] Briefly, esophageal impedance-pH monitoring was performed using a Sleuth® Multi-channel Intraluminal Impedance ambulatory system (Sandhill Scientific, Inc., Highland Ranch, CO, USA). The system includes a portable data logger with impedance-pH amplifiers and a catheter containing one antimony pH electrode (positioned 5 cm above the Lower esophageal sphincter (LES)) and six pairs of impedance electrodes positioned in the esophageal body to record pH at 5 cm and impedance at 3, 5, 7, 9, 15, and 17 cm proximal to the LES. The six impedance and pH signals were recorded at 50 Hz on a 128 MB CompactFlash card for further analysis. The studies were performed on an outpatient basis after an overnight fast. Patients were taking double dose PPIs for at least 2 weeks (single dose twice daily before meals). Before the start of the recordings, the pH recorder was calibrated using pH 4.0 and pH 7.0 buffer solutions. After LES location by esophageal manometry, the impedance-pH catheter was passed transnasally under topical anesthesia. Subjects were discharged and were encouraged to maintain normal activities, sleep schedule, and eat their usual meals at their normal times. They were asked to remain upright during the day, and lie down only during their usual bedtime. Event markers on the data-logger recorded symptoms, meal times and posture changes. The data stored on the CompactFlash card were downloaded onto a personal computer and visually analyzed using assistance of dedicated software (Bioview Analysis®, version 5.0.9; Sandhill Scientific, Inc.). All tracings were analyzed by one experimented investigator (FZ). Analysis included identification, and characterization of individual reflux events, and measure of clearance times (bolus and pH clearance). Meals were excluded for the analysis.

Liquid reflux was defined as a retrograde 50% drop in impedance starting distally (at the level of the LES) and propagating to at least the next two more proximal impedance measuring segments. Only liquid reflux episodes lasting at least three s were taken into account. Gas reflux was defined as a rapid (3 kЩ/s) increase in impedance >5000 Щ, occurring simultaneously at least in two esophageal measuring segments, in the absence of swallowing. Mixed liquid-gas reflux was defined as gas reflux occurring immediately before or during a liquid reflux. Gas reflux events without liquid (belches) were not considered for this study. Reflux episodes were characterized by pH-metry as acid, weakly acidic, or weakly alkaline according to the Porto consensus report[16]: (i) Acid reflux: reflux with a nadir pH less than 4; (ii) Weakly acidic reflux: reflux events that result in an esophageal pH between 4 and 7; (iii) Weakly alkaline reflux: reflux episodes during which nadir esophageal pH does not drop below 7. Weakly acidic and weakly alkaline reflux events were considered as a whole as `non-acid' reflux events.

Each reflux parameter was considered as normal or abnormal compared to normal values obtained by our group in 40 healthy subjects studied on PPIs in ambulatory conditions with non-standardized meals.[17] The 95th percentile values obtained in this series were considered to be the upper limit of normal (ULN) values. For the present study, the following parameters were taken into account: Total number of reflux events (ULN: 57), acid reflux events (ULN: 7), non-acid reflux events (ULN: 55), 24-h esophageal acid exposure (%) (ULN: 0.4%), and 24-h bolus exposure (reflux percent time) (ULN: 2.1%).

The symptom-reflux association analysis was performed using both symptom index (SI)[18] and symptom association probability (SAP).[19] Separate analysis was performed for each individual symptom if patients recorded different types of symptoms. Symptom index and SAP were calculated for acid and weakly acid reflux using a dedicated software: Symptoms were considered as being related to reflux if they occurred within a 2-min time window after the onset of the reflux episode. A positive SI (SI+) was declared if ?50%; SAP was considered positive if ?95%. Patients were considered to have positive symptom-reflux association if they had positive SI or SAP. As a whole, pH-impedance monitoring was considered as `positive' if one of the reflux parameter was abnormal or if a positive SI or SAP was present.

Assessment of symptomatic outcome

The functional results of the fundoplication were evaluated after a minimal follow-up of 6 months using the Visick score and the reflux disease questionnaire (RDQ). Questionnaires were sent to patients with an explicative notice about the aim of the study and instructions to fill them out. Patients who did not sent back the questionnaires were contacted by telephone by a gastroenterologist and answered during the interview to each items.

Visick score is a simple clinical score which evaluates symptoms and need for treatment after GI surgery[20]: Visick I, no symptoms (complete satisfaction); Visick II, infrequent or minor symptoms (patients with mild symptoms not requiring medical treatment), Visick III, significant symptoms (patients requiring medical treatment for their symptoms); and Visick IV, severe intractable symptoms (patients having severe symptoms despite drug treatment). In our study, failure of fundoplication was defined by a Visick scale >2.

The RDQ is a validated symptomatic questionnaire of 12 items which describe frequency and severity of symptoms of three different domains: heartburn, regurgitation, and upper abdominal pain (dyspepsia). Each item is rated from 1 to 6, for a total score of 72 points. For each domain, four questions are asked and the sub-total score ranged from 4 to 24. The RDQ total score was the mean score of the 12 items and thus ranged from 1 to 6. Rey et al. calculated thresholds differentiating troublesome from non-troublesome GER symptoms based on the Montreal definition. A RDQ above 3.18 and 3.06 were considered as significantly associated with troublesome symptoms in patients off and on PPI, respectively.[21]

Statistical analysis

Statistical analyses took into account size of group inferior than 30 patients. Results were expressed as median. The Fisher's exact test and the Wilcoxon signed rank test were used as appropriate. Differences with a p < 0.05 were considered statistically significant.

Results

Between June 2005 and December 2013, 227 patients underwent a laparoscopic fundoplication in our center, among whom 34 met the inclusion criteria of the present study, i.e., indication was refractory reflux symptoms and a pre-operative pH-impedance monitoring on double dose PPIs was available. One patient had severe postoperative dysphagia and was excluded from the analysis. Among the 33 patients available for the analysis, there were 18 female, with a median age of 46.5 years (range 17-64 years). Preoperatively, 30 patients had typical symptoms, 22 atypical symptoms and 19 both typical and atypical symptoms. Gastro-esophageal reflux disease (GERD) was documented pre-operatively in 26 out of 27 patients with available data: 20 patients had erosive esophagitis and nine had a positive pH monitoring off PPI. One patient had a normal endoscopy and a normal pH monitoring off PPI and data were missing for six patients. Three patients had already undergone a fundoplication for GERD. At the time of outcome assessment, the mean follow-up was 41.3 months (range 7-102.2 months). Twenty-nine patients were evaluated more than 1 year after surgery and 18 patients after 2 years.

Functional outcome and symptoms assessment

According to our definition (Visick score >2), 7/33 (21.2%) patients were considered as failures. The seven patients who failed surgery were younger (median age 31.0 year vs 47.5 years, p = 0.02), and more often on PPI therapy (86% vs 23.1%, p < 0.05). Preoperatively, all failed patients had typical symptoms, while 5/7 also had atypical symptoms. All failed patients had a documented GERD before surgery. There was no difference between the failure and success groups regarding preoperative symptoms, endoscopy results and time elapsed between surgery and assessment (Table 1).

Table 1. Demographic and clinical characteristics of patients in the failure (Visick score >2) and success (Visick score ?2) groups after laparoscopic fundoplication in 33 patients

*RDQ >3.06 without PPI, RDQ >3.18 with PPI. PPI, proton pump inhibitors; RDQ, reflux disease questionnaire.

There was a good correlation between the Visick score and the total RDQ score: 6/7 patients of the failure group had an abnormal RDQ score. All but one patient had persisting typical and atypical symptoms. As compared to the success group, patients with failures had higher RDQ scores for each individual domain of the score: heartburn (p < 0.05), regurgitation (p = 0.05) and dyspepsia (p < 0.05) (Table 1).

Value of preoperative pH-impedance monitoring

According to the normal values on PPIs published by our group, 31/33 patients had an abnormal preoperative pH-impedance monitoring (6/7 in the failure group, 25/26 in the success group, NS). Taken individually, quantitative pH-impedance parameters, i.e., number of reflux events (total, acid, non-acidic), acid exposure time and bolus exposure time, were similar in both groups (Table 2).

Table 2. Parameters of the preoperative pH-impedance monitoring on PPI in 33 patients who had laparoscopic fundoplication

GER, gastro-esophageal reflux; PPI, proton pump inhibitors.

Symptom association analysis was first analyzed as a whole (Fig. 1), whatever the symptom considered. A positive symptom association analysis, i.e., either a positive SI or SAP, was more often associated with a successful postoperative outcome, but the difference was not statistically significant (57.1% in the failure group vs 88.5% in the success group, p = 0.092) (Fig. 1). No patient in the failure group had a positive SAP preoperatively, while 78% (21/27) of patients had a positive SAP in the success group (p = 0.004). By contrast, 57.1% of patients in the failure group had a positive SI, as compared to 81% in the success group (NS).

Figure 1. Results of preoperative pH-impedance monitoring on PPIs. Bars indicate the percentages of patients with positive symptom association analysis (all types of symptoms) in successful (n = 26) and failed (n = 7) laparoscopic fundoplication for refractory reflux symptoms, *p = 0.004. SI, symptom index; SAP, symptom association probability.

Fig. 2 illustrates the results of symptom association analysis for heartburn and regurgitation. The proportion of patients with a positive SI for heartburn was similar in both groups, while 58% of patients had a positive SI for regurgitation in the success group compared to only 29% in the failure group, but the difference was not statistically significant. No patient in the failure group had a positive SAP for regurgitation preoperatively, while in the success group 23% had a positive SAP for heartburn (NS) and 42% for regurgitation (p = 0.067). 66% of patients with a positive SAP for regurgitation had positive SAP for weakly acidic reflux, but as a whole, there was no significant difference between the two groups when symptom association analysis was made according to reflux type (acid vs non acid).

Figure 2. Results of preoperative pH-impedance monitoring on PPIs. Bars indicate the percentages of patients with positive symptom association analysis for heartburn and regurgitation in successful (n = 26) and failed (n = 7) laparoscopic fundoplication for refractory reflux symptoms. There was no significant difference between groups. SI, symptom index; SAP, symptom association probability.

The results of this analysis were similar when the failure and success groups were determined according to the RDQ scores.

In this cohort, three patients had already undergone a fundoplication, one in the success group and two in the failure group. We performed the same analysis in the 30 patients without previous surgery, who were 25 in the success group and five in the failure group (median age 48 and 31 years, respectively, p = 0.08). The results were similar to those obtained in the whole cohort: (i) quantitative pH-impedance parameters, i.e., number of reflux events (total, acid, non acidic), acid exposure time and bolus exposure time, were similar in both groups (data not shown); (ii) regarding symptom association analysis, no patient in the failure group had a positive SAP preoperatively, while 76% (19/25) of patients had a positive SAP in the success group (p = 0.003); by contrast, 84% (21/25) of patients in the failure group had a positive SI, as compared to 80% (4/5) in the success group (NS).

Discussion

The management of patients with refractory reflux symptoms is challenging, especially when laparoscopic fundoplication is considered. In these patients, fundoplication has less favorable clinical outcome compared to patients with adequate PPI symptom control.[5, 9] However, there is yet no consensus regarding the best way to select the subgroup of patients who may benefit from surgery. The present study shows that a positive SAP on preoperative 24-hour pH-impedance monitoring performed on double dose PPIs is associated with successful clinical outcome, even when patients with previous fundoplication were removed from the analysis. By contrast, neither pH-impedance reflux parameters nor positive SI could help to discriminate patients with favorable and unsatisfactory outcomes.

Whether preoperative evaluation of reflux should be performed `off' or `on' PPIs remains debated. Studies with pH monitoring `off' therapy have shown that either abnormal esophageal exposure time[10, 22, 23] or a positive symptom association analysis[11, 12] are good predictors of favorable postoperative outcome. One additional study also reported favorable outcomes in patients with normal acid exposure time but abnormal number of reflux episodes detected by esophageal impedance monitoring.[24] Compared to studies `off' therapy, recording `on' treatment may help to identify patients with persisting symptoms actually related to GER. However, data on preoperative assessment `on' PPIs with pH-impedance monitoring are scarce. Mainie et al. have reported favorable results of fundoplication in 18 of 19 patients with persistent symptoms despite PPI therapy and positive SI for non-acid reflux on esophageal pH-impedance monitoring, but the respective roles of SAP and reflux parameters were not evaluated in this study.[14] Frazzoni et al. reported a successful postsurgical outcome in 34 out of 38 patients (89%) with refractory symptoms.[13] Patients were selected on the basis of a pH-impedance `on' PPIs showing a positive SAP or SI, and/or abnormal esophageal acid exposure time, and/or abnormal number of total reflux events. In both studies from Mainie and Frazzoni, the success rate of surgery was very high, thus suggesting that, whatever the parameter taken into account, a positive pH-impedance study on therapy was useful to select patients for surgery.

By contrast to these two studies, we carefully assessed the relevance of each individual reflux parameter and symptom-association indices separately. This analysis could be performed because we identified two distinct groups of patients with favorable (n = 26) and unfavorable (n = 7) clinical outcome following fundoplication based on the Visick and RDQ scores. Acid exposure time has been shown to be associated with therapeutic response in patients `off' PPIs,[10, 22, 23, 25] but this parameter was not relevant in the present study performed `on' therapy. The same holds true for bolus exposure time and number of reflux events. When symptom association analysis is considered, a positive SAP, but not a positive SI, is associated with a favorable outcome. It is interesting to note that no patient with failed surgery had a positive SAP preoperatively, although the difference failed to reach the statistical significance when heartburn and regurgitation were considered separately. The agreement between SI and SAP is poor[26, 27] and it cannot be stated which test should be used in clinical practice, and which should be taken into account if discrepancy exists between SI and SAP. In the present study, SAP appears to be more useful than SI, which is consistent with a recent study from Patel et al. who reported that SAP for impedance-detected reflux off PPIs was better than SI to predict response to anti-reflux therapy.[25] This needs to be confirmed in larger series. Recently, a new impedance parameter, i.e., the postreflux swallow-induced peristaltic wave (PSPW) index has been shown to provide a clear-cut separation of refractory GERD from functional heartburn at on therapy pH-impedance monitoring.[28] Whether this parameter could prove useful in predicting positive surgical outcome deserves further evaluation.

We have included three patients with previous fundoplication, one in the success group and two in the failure group. The relevance of pH-impedance monitoring in these patients is a matter of debate since previous surgery might affect both reflux parameters and surgery outcome. On the other hand, the value of symptom association analysis is not supposed to be influenced by previous procedures, and the results of the study are not modified by inclusion of these three patients.

This study has several limitations in addition to its retrospective design: (i) we included non-consecutive patients since only a minority of patients operated had a preoperative pH-impedance monitoring `on' PPIs, (ii) there was no clear selection criteria for surgery (most surgeon-based decisions), and (iii) no postoperative pH-impedance monitoring was available and it was therefore not possible to determine if failures were related to a failed surgical procedure.

In conclusion, this study suggests that pH-impedance monitoring `on' PPI therapy may help to select the best candidates for laparoscopic fundoplication in patients with refractory reflux symptoms, especially when a positive SAP is present. The relevance of this index and/or other pH-impedance parameters (such as the number of reflux events or PSPW index) should be further evaluated by prospective studies.

Funding No funding declared.

Conflicts of Interest F.Zerbib is consultant and speaker for Given Imaging/Covidien. The other authors have no competing interests.

Author Contribution

DC and GL operated the patients and collected data, analyzed data and approved final draft; MD collected and analyzed data, approved the final draft; FZ designed the study, wrote the paper and approved final draft.

References

1. Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997; 112: 1798-810.

2. Inadomi JM, McIntyre L, Bernard L, Fendrick AM. Step-down from multiple- to single-dose proton pump inhibitors (PPIs): a prospective study of patients with heartburn or acid regurgitation completely relieved with PPIs. Am J Gastroenterol 2003; 98: 1940-4.

3. Carlsson R, Dent J, Watts R, Riley S, Sheikh R, Hatlebakk J, Haug K, de Groot G et al. Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. International GORD Study Group. Eur J Gastroenterol Hepatol 1998; 10: 119-24.

4. Organization TG. The 2000 Gallup Study of Consumers' Use of Stomach Relief Products: Gallup Organization, 2000.

5. Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut 2009; 58: 295-309.

6. Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut 2012; 61: 1340-54.

7. Vakil NB, Huff FJ, Bian A, Jones DS, Stamler D. Arbaclofen placarbil in GERD: a randomized, double-blind, placebo-controlled study. Am J Gastroenterol 2011; 106: 1427-38.

8. Boeckxstaens GE, Beaumont H, Hatlebakk JG, Silberg DG, Bjцrck K, Karlsson M, Denison H. A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial. Gut 2011; 60: 1182-8.

9. Lundell L. Surgical therapy of gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol 2010; 24: 947-59.

10. Broeders JA, Draaisma WA, Bredenoord AJ, Smout AJ, Broeders IA, Gooszen HG. Impact of symptom-reflux association analysis on long-term outcome after Nissen fundoplication. Br J Surg 2011; 98: 247-54.

11. Bell RC, Hanna P, Brubaker S. Laparoscopic fundoplication for symptomatic but physiologic gastroesophageal reflux. J Gastrointest Surg 2001; 5: 462-7.

12. Broeders JA, Draaisma WA, Bredenoord AJ, de Vries DR, Rijnhart-de Jong HG, Smout AJ, Gooszen HG. Oesophageal acid hypersensitivity is not a contraindication to Nissen fundoplication. Br J Surg 2009; 96: 1023-30.

13. Frazzoni M, Piccoli M, Conigliaro R, Manta R, Frazzoni L, Melotti G. Refractory gastroesophageal reflux disease as diagnosed by impedance-pH monitoring can be cured by laparoscopic fundoplication. Surg Endosc 2013; 27: 2940-6.

14. Mainie I, Tutuian R, Agrawal A, Adams D, Castell DO. Combined multichannel intraluminal impedance-pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication. Br J Surg 2006; 93: 1483-7.

15. Zerbib F, des Varannes SB, Roman S, Pouderoux P, Artigue F, Chaput U, Mion F, Caillol F et al. Normal values and day-to-day variability of 24-h ambulatory oesophageal impedance-pH monitoring in a Belgian-French cohort of healthy subjects. Aliment Pharmacol Ther 2005; 22: 1011-21.

16. Sifrim D, Castell D, Dent J, Kahrilas PJ. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut 2004; 53: 1024-31.

17. Zerbib F, Roman S, Bruley Des Varannes S, Gourcerol G, Coffin B, Ropert A, Lepicard P, Mion F. Normal values of pharyngeal and esophageal 24-hour pH impedance in individuals on and off therapy and interobserver reproducibility. Clin Gastroenterol Hepatol 2013; 11: 366-72.

18. Wiener GJ, Richter JE, Copper JB, Wu WC, Castell DO. The symptom index: a clinically important parameter of ambulatory 24-hour esophageal pH monitoring. Am J Gastroenterol 1988; 83: 358-61.

19. Weusten BL, Roelofs JM, Akkermans LM, Van Berge-Henegouwen GP, Smout AJ. The symptom-association probability: an improved method for symptom analysis of 24-hour esophageal pH data. Gastroenterology 1994; 107: 1741-5.

20. Visick AH. A study of the failures after gastrectomy. Ann R Coll Surg Engl 1948; 3: 266-84.

21. Rey E, Barcelo M, Zapardiel J, Sobreviela E, Munoz M, Diaz-Rubio M. Is the reflux disease questionnaire useful for identifying GERD according to the Montreal definition? BMC Gastroenterol 2014; 14: 17.

22. Campos GM, Peters JH, DeMeester TR, Oberg S, Crookes PF, Tan S, DeMeester SR, Hagen JA et al. Multivariate analysis of factors predicting outcome after laparoscopic Nissen fundoplication. J Gastrointest Surg 1999; 3: 292-300.

23. Khajanchee YS, Hong D, Hansen PD, Swanstrom LL. Outcomes of antireflux surgery in patients with normal preoperative 24-hour pH test results. Am J Surg 2004; 187: 599-603.

24. del Genio G, Tolone S, del Genio F, Aggarwal R, d'Alessandro A, Allaria A, Rossetti G, Brusciano L et al. Prospective assessment of patient selection for antireflux surgery by combined multichannel intraluminal impedance pH monitoring. J Gastrointest Surg 2008; 12: 1491-6.

25. 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: 884-91.

26. Mainie I, Tutuian R, Shay S, Vela M, Zhang X, Sifrim D, Castell DO. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Gut 2006; 55: 1398-402.

27. Zerbib F, Roman S, Ropert A, des Varannes SB, Pouderoux P, Chaput U, Mion F, Vйrin E et al. Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy. Am J Gastroenterol 2006; 101: 1956-63.

28. Frazzoni M, Manta R, Mirante VG, Conigliaro R, Frazzoni L, Melotti G. Esophageal chemical clearance is impaired in gastro-esophageal reflux disease-a 24-h impedance-pH monitoring assessment. Neurogastroenterol Motil 2013; 25: 399-406, e295.

Размещено на Allbest.ru