10-year follow-up results of the European Achalasia Trial: a multicentre randomised controlled trial comparing pneumatic dilation with laparoscopic Heller myotomy.

OBJECTIVE: As achalasia is a chronic disorder, long-term follow-up data comparing different treatments are essential to select optimal clinical management. Here, we report on the 10-year follow-up of the European Achalasia Trial comparing endoscopic pneumodilation (PD) with laparoscopic Heller myotomy (LHM). DESIGN: A total of 201 newly diagnosed patients with achalasia were randomised to either a series of PDs (n=96) or LHM (n=105). Patients completed symptom (Eckardt score) and quality-of-life questionnaires, underwent functional tests and upper endoscopy. Primary outcome was therapeutic success defined as Eckardt score <3 at yearly follow-up. Secondary outcomes were the need for retreatment, lower oesophageal sphincter pressure, oesophageal emptying, gastro-oesophageal reflux and the rate of complications. RESULTS: After 10 years of follow-up, LHM (n=40) and PD (n=36) were equally effective in both the full analysis set (74% vs 74%, p=0.84) and the per protocol set (74% vs 86%, respectively, p=0.07). Subgroup analysis revealed that PD was superior to LHM for type 2 achalasia (p=0.03) while there was a trend, although not significant (p=0.05), that LHM performed better for type 3 achalasia. Barium column height after 5 min at timed barium oesophagram was significantly higher for patients treated with PD compared with LHM, while other parameters, including gastro-oesophageal reflux, were not different. CONCLUSIONS: PD and LHM are equally effective even after 10 years of follow-up with limited risk to develop gastro-oesophageal reflux. Based on these data, we conclude that PD and LHM can both be proposed as initial treatment of achalasia.

Ziverel for PPI-refractory reflux symptoms: efficacy and mechanisms of action in humans.

OBJECTIVES: It is thought that esophageal hypersensitivity in combination with an impaired mucosal barrier function contributes to PPI-resistant reflux symptoms. Ziverel, a bioadhesive agent that coats the esophageal wall, was shown to have a positive effect on reflux symptoms. However, the mechanisms of action are unclear. We aimed to assess the effect of Ziverel on esophageal sensitivity to acid and mucosal barrier function. METHODS: We performed a double-blind randomized placebo-controlled crossover trial in PPI-refractory patients with reflux symptoms. Patients were assigned (1:1) to 14 days of Ziverel followed by 14 days of placebo or opposite treatment order. The effect was evaluated using acid perfusion tests, an upper endoscopy with electrical tissue impedance spectroscopy (ETIS) and esophageal biopsies. The primary outcome was the esophageal sensitivity based on perfusion sensitivity score. Secondary outcomes included mucosal barrier function and reflux symptoms and correlations between the different outcomes. RESULTS: Perfusion sensitivity score was not significantly different during treatment with Ziverel (106 (73-115)) and placebo (102 (67-110)) (p = 0.508) along with total RDQ score (2.6 (1.9-3.3) vs 2.8 (1.6-3.5) p = 0.456). ETIS showed comparable values during treatment with Ziverel (13514 (8846-19734)Ω·m) and placebo (13217 (9127-24942)Ω·m (p = 0.650)). Comparing Ziverel and placebo no difference was seen in transepithelial electrical resistance (TEER) 203 (163-267) Ω.cm2 vs 205 (176-240) Ω.cm2 (p = 0.445) and fluorescein flux 775 (17-6964) nmol/cm2/h vs 187 (4-12209) nmol/cm2/h (p = 0.638). CONCLUSION: Ziverel did not show a benefit on acid sensitivity, reflux symptoms or esophageal mucosal integrity compared to placebo in PPI-refractory patients with reflux symptoms.Trial registration: Netherlands Trial Register number: NL7670.

Development of a Preliminary Question Prompt List as a Communication Tool for Adults With Achalasia: A Modified Delphi Study.

BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions that enhance patient-physician communication by encouraging patients to ask questions during consultations. AIM: The aim of this study was to develop a preliminary achalasia-specific QPL created by esophageal experts. METHODS: The QPL content was derived through a modified Delphi method consisting of 2 rounds. In round 1, experts provided 5 answers to the prompts "What general questions should patients ask when given a new diagnosis of achalasia" and "What questions do I not hear patients asking, but given my expertise, I believe they should be asking?" In round 2, experts rated questions on a 5-point Likert scale. Questions considered "essential" or "important" were accepted into the QPL. Feedback regarding the QPL was obtained in a pilot study wherein patients received the QPL before their consultation and completed surveys afterwards. RESULTS: Nineteen esophageal experts participated in both rounds. Of 148 questions from round 1, 124 (83.8%) were accepted into the QPL. These were further reduced to 56 questions to minimize redundancy. Questions were categorized into 6 themes: "What is achalasia," "Risks with achalasia," "Symptom management in achalasia," "Treatment of achalasia," "Risk of reflux after treatment," and "Follow-up after treatment." Nineteen patients participated in the pilot, most of whom agreed that the QPL was helpful (84.2%) and recommended its wider use (84.2%). CONCLUSIONS: This is the first QPL developed specifically for adults with achalasia. Although well-received in a small pilot, follow-up studies will incorporate additional patient feedback to further refine the QPL content and assess its usability, acceptability, and feasibility.

Pneumatic dilation for persistent dysphagia after antireflux surgery, a multicentre single-blind randomised sham-controlled clinical trial.

OBJECTIVE: There is no evidence-based treatment for persistent dysphagia after laparoscopic fundoplication. The aim of this study was to evaluate the effect of pneumatic dilation on persistent dysphagia after laparoscopic fundoplication. DESIGN: We performed a multicentre, single-blind, randomised sham-controlled trial of patients with persistent dysphagia (>3 months) after laparoscopic fundoplication. Patients with an Eckardt symptom score ≥4 were randomly assigned to pneumatic dilation (PD) using a 35 mm balloon or sham dilation. Primary outcome was treatment success, defined as an Eckardt score <4 and a minimal reduction of 2 points in the Eckardt score after 30 days. Secondary outcomes included change in stasis on timed barium oesophagogram, change in high-resolution manometry parameters and questionnaires on quality of life, reflux and dysphagia symptoms. RESULTS: Forty-two patients were randomised. In the intention-to-treat analysis, the success rates of PD (7/21 patients (33%)) and sham dilation (8/21 patients (38%)) were similar after 30 days (risk difference -4.7% (95% CI (-33.7% to 24.2%) p=0.747). There was no significant difference in change of stasis on the timed barium oesophagogram after 2 min (PD vs sham: median 0.0 cm, p25-p75 range 0.0-4.3 cm vs median 0.0 cm, p25-p75 range 0.0-0.0; p=0.122) or change in lower oesophageal sphincter relaxation pressure (PD vs sham: 10.54±6.25 vs 14.60±6.17 mm Hg; p=0.052). Quality of life, reflux and dysphagia symptoms were not significantly different between the two groups. CONCLUSION: Pneumatic dilation with a 35 mm balloon is not superior to sham dilation for the treatment of persistent dysphagia after fundoplication.

Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial.

BACKGROUND & AIMS: Experimental studies have suggested that sleep position plays a role in the occurrence of nocturnal gastroesophageal reflux and the left lateral decubitus position is most favorable. The aim of this study was to evaluate the effect of a novel electronic sleep positional therapy wearable device on sleep position and nocturnal reflux symptoms. METHODS: We performed a double-blind, randomized, sham-controlled trial in patients with nocturnal symptoms of gastroesophageal reflux. Patients were advised to sleep in the left lateral decubitus position and were assigned randomly (1:1) to an electronic sleep positional therapy wearable device, programmed to either produce a vibration when in the right lateral position (intervention) or only during the first 20 minutes (sham). The primary outcome was treatment success, defined as a 50% or more reduction in the nocturnal reflux score. Secondary outcomes included change in sleep position and reflux symptoms. RESULTS: One hundred patients were randomized. In the intention-to-treat analysis, the rate of treatment success was 44% in the intervention group (22 of 50) vs 24% in the sham group (12 of 50) (risk difference, 20%; 95% CI, 1.8%-38.2%; P = .03). Treatment led to a significant avoidance of sleeping in the right lateral decubitus position (intervention 2.2% vs sham 23.5%; P = .000) and increased time sleeping in the left lateral decubitus position (intervention 60.9% vs sham 38.5%; P = .000). More reflux-free nights were observed in the intervention group (intervention 9 nights [interquartile range, 6-11 nights] vs sham 6 nights [interquartile range, 3-9 nights]; P = .01). CONCLUSIONS: Sleep positional therapy using an electronic wearable device promotes sleeping in the left lateral decubitus position and effectively alleviates nocturnal reflux symptoms compared with sham treatment (https://www.trialregister.nl, NL8655).

Associations Between Sleep Position and Nocturnal Gastroesophageal Reflux: A Study Using Concurrent Monitoring of Sleep Position and Esophageal pH and Impedance.

INTRODUCTION: The aim of this study was to investigate the effect of spontaneous sleep positions on the occurrence of nocturnal gastroesophageal reflux. METHODS: In patients referred for ambulatory pH-impedance reflux monitoring, the concurrent sleep position was measured using a sleep position measurement device (measuring left, right, supine, and prone positions). RESULTS: Fifty-seven patients were included. We observed a significantly shorter acid exposure time in the left (median 0.0%, P25-P75, 0.0%-3.0%), compared with the right lateral position (median 1.2%, 0.0%-7.5%, P = 0.022) and the supine position (median 0.6%, 0.00%-8.3%, P = 0.022). The esophageal acid clearance time was significantly shorter in the left lateral decubitus position (median 35 seconds, 16-115 seconds), compared with the supine (median 76 seconds, 22-257 seconds, P = 0.030) and right lateral positions (median 90 seconds, 26-250 seconds, P = 0.002). DISCUSSION: The left lateral decubitus position is associated with significantly shorter nocturnal esophageal acid exposure time and faster esophageal acid clearance compared with the supine and right lateral decubitus positions (see visual abstract).

Reflux symptoms and oesophageal acidification in treated achalasia patients are often not reflux related.

OBJECTIVE: After treatment, achalasia patients often develop reflux symptoms. Aim of this case-control study was to investigate mechanisms underlying reflux symptoms in treated achalasia patients by analysing oesophageal function, acidification patterns and symptom perception. DESIGN: Forty treated achalasia patients (mean age 52.9 years; 27 (68%) men) were included, 20 patients with reflux symptoms (RS+; Gastro-Oesophageal Reflux Disease Questionnaire (GORDQ) ≥8) and 20 without reflux symptoms (RS-: GORDQ <8). Patients underwent measurements of oesophagogastric junction distensibility, high-resolution manometry, timed barium oesophagogram, 24 hours pH-impedance monitoring off acid-suppression and oesophageal perception for acid perfusion and distension. Presence of oesophagitis was assessed endoscopically. RESULTS: Total acid exposure time during 24 hours pH-impedance was not significantly different between patients with (RS+) and without (RS-) reflux symptoms. In RS+ patients, acid fermentation was higher than in RS- patients (RS+: mean 6.6% (95% CI 2.96% to 10.2%) vs RS-: 1.8% (95% CI -0.45% to 4.1%, p=0.03) as well as acid reflux with delayed clearance (RS+: 6% (95% CI 0.94% to 11%) vs RS-: 3.4% (95% CI -0.34% to 7.18%), p=0.051). Reflux symptoms were not related to acid in both groups, reflected by a low Symptom Index. RS+ patients were highly hypersensitive to acid, with a much shorter time to heartburn perception (RS+: 4 (2-6) vs RS-:30 (14-30) min, p<0.001) and a much higher symptom intensity (RS+: 7 (4.8-9) vs RS-: 0.5 (0-4.5) Visual Analogue Scale, p<0.001) during acid perfusion. They also had a lower threshold for mechanical stimulation. CONCLUSION: Reflux symptoms in treated achalasia are rarely caused by gastro-oesophageal reflux and most instances of oesophageal acidification are not reflux related. Instead, achalasia patients with post-treatment reflux symptoms demonstrate oesophageal hypersensitivity to chemical and mechanical stimuli, which may determine symptom generation.

The Role of Symptom Association Analysis in Gastroesophageal Reflux Testing.

Gastroesophageal reflux disease is characterized by the reflux of gastric contents into the esophagus with an estimated worldwide prevalence of 8%-33%. The current paradigm in gastroesophageal reflux disease diagnosis relies on recognition of symptoms and/or the presence of mucosal disease at the time of esophagogastroduodenoscopy. Recognition of symptoms, however, can arise with challenges, particularly when patients complain of less typical symptoms. Since first reported in 1969 by Spencer et al., the application of prolonged intraesophageal pH monitoring to identify pathologic reflux has evolved considerably. Utility of pH monitoring aims to investigate the degree of acid burden and frequency of reflux episode, and the relationship between symptoms and acid reflux events. This relationship is represented by either the Symptom Index, Symptom Sensitivity Index, Symptom Association Probability, or Ghillebert Probability Estimate. This article reviews symptom-association analysis during esophageal reflux testing, covering the literature on current methods of reflux testing, interpretation of symptom association, and practical issues that can arise during symptom analysis.

Effect of Peroral Endoscopic Myotomy vs Pneumatic Dilation on Symptom Severity and Treatment Outcomes Among Treatment-Naive Patients With Achalasia: A Randomized Clinical Trial.

Importance: Case series suggest favorable results of peroral endoscopic myotomy (POEM) for treatment of patients with achalasia. Data comparing POEM with pneumatic dilation, the standard treatment for patients with achalasia, are lacking. Objective: To compare the effects of POEM vs pneumatic dilation as initial treatment of treatment-naive patients with achalasia. Design, Setting, and Participants: This randomized multicenter clinical trial was conducted at 6 hospitals in the Netherlands, Germany, Italy, Hong Kong, and the United States. Adult patients with newly diagnosed achalasia and an Eckardt score greater than 3 who had not undergone previous treatment were included. The study was conducted between September 2012 and July 2015, the duration of follow-up was 2 years after the initial treatment, and the final date of follow-up was November 22, 2017. Interventions: Randomization to receive POEM (n = 67) or pneumatic dilation with a 30-mm and a 35-mm balloon (n = 66), with stratification according to hospital. Main Outcomes and Measures: The primary outcome was treatment success (defined as an Eckardt score ≤3 and the absence of severe complications or re-treatment) at the 2-year follow-up. A total of 14 secondary end points were examined among patients without treatment failure, including integrated relaxation pressure of the lower esophageal sphincter via high-resolution manometry, barium column height on timed barium esophagogram, and presence of reflux esophagitis. Results: Of the 133 randomized patients, 130 (mean age, 48.6 years; 73 [56%] men) underwent treatment (64 in the POEM group and 66 in the pneumatic dilation group) and 126 (95%) completed the study. The primary outcome of treatment success occurred in 58 of 63 patients (92%) in the POEM group vs 34 of 63 (54%) in the pneumatic dilation group, a difference of 38% ([95% CI, 22%-52%]; P < .001). Of the 14 prespecified secondary end points, no significant difference between groups was demonstrated in 10 end points. There was no significant between-group difference in median integrated relaxation pressure (9.9 mm Hg in the POEM group vs 12.6 mm Hg in the pneumatic dilation group; difference, 2.7 mm Hg [95% CI, -2.1 to 7.5]; P = .07) or median barium column height (2.3 cm in the POEM group vs 0 cm in the pneumatic dilation group; difference, 2.3 cm [95% CI, 1.0-3.6]; P = .05). Reflux esophagitis occurred more often in the POEM group than in the pneumatic dilation group (22 of 54 [41%] vs 2 of 29 [7%]; difference, 34% [95% CI, 12%-49%]; P = .002). Two serious adverse events, including 1 perforation, occurred after pneumatic dilation, while no serious adverse events occurred after POEM. Conclusions and Relevance: Among treatment-naive patients with achalasia, treatment with POEM compared with pneumatic dilation resulted in a significantly higher treatment success rate at 2 years. These findings support consideration of POEM as an initial treatment option for patients with achalasia. Trial Registration: Netherlands Trial Register number: NTR3593.

Modern diagnosis of GERD: the Lyon Consensus.

Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are of value in determining need for further investigation. Conclusive evidence for reflux on oesophageal testing include advanced grade erosive oesophagitis (LA grades C and D), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal oesophageal acid exposure time (AET) >6% on ambulatory pH or pH-impedance monitoring. A normal endoscopy does not exclude GERD, but provides supportive evidence refuting GERD in conjunction with distal AET <4% and <40 reflux episodes on pH-impedance monitoring off proton pump inhibitors. Reflux-symptom association on ambulatory reflux monitoring provides supportive evidence for reflux triggered symptoms, and may predict a better treatment outcome when present. When endoscopy and pH or pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (histopathology scores, dilated intercellular spaces), motor evaluation (hypotensive lower oesophageal sphincter, hiatus hernia and oesophageal body hypomotility on high-resolution manometry) and novel impedance metrics (baseline impedance, postreflux swallow-induced peristaltic wave index) can add confidence for a GERD diagnosis; however, diagnosis cannot be based on these findings alone. An assessment of anatomy, motor function, reflux burden and symptomatic phenotype will therefore help direct management. Future GERD management strategies should focus on defining individual patient phenotypes based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the oesophagogastric junction and psychometrics defining symptomatic presentations.

Screening for dysplasia with Lugol chromoendoscopy in longstanding idiopathic achalasia.

BACKGROUND: Achalasia patients with longstanding disease are considered to be at risk for developing esophageal cancer. Endoscopic screening is not standardized and detection of dysplastic lesions is difficult, for which Lugol chromoendoscopy could be helpful. Aim was to evaluate the efficacy of screening for esophageal dysplasia and carcinoma in patients with longstanding achalasia using Lugol chromoendoscopy. METHODS: In this cohort study achalasia patients underwent three-annual screening by Lugol chromoendoscopy between January 2000 and March 2016. Patients with low-grade dysplasia (LGD) underwent yearly screening, patients with high-grade dysplasia (HGD) or carcinoma were treated. RESULTS: In total, 230 achalasia patients (144 male, median age 52 years (IQR 43-63) at first endoscopy) were included. Three patients (1.3%, 2 male, age 68 years (range 50-87)) developed esophageal squamous cell carcinoma (ESCC), without LGD at the preceding screening. Incidence rate for ESCC was 63 (95% CI 13-183) per 100 000 persons-years. LGD was observed in 4 patients (1.7%, 2 male, age 64 years (range 57-73)), without progression to HGD/ESCC during a follow-up of 9 (IQR 7-14) years. ESCC/LGD was diagnosed 30 (IQR 14-36) years after onset of symptoms and 22 (IQR 4-13) years after diagnosis. Lugol chromoendoscopy tripled the detection rate of suspected lesions (111 lesions white light versus 329 lesions Lugol), but only 8% was histopathological confirmed ESCC or LGD. CONCLUSION: Achalasia patients with longstanding disease (>20 years) have an increased risk to develop esophageal dysplasia and carcinoma. Endoscopic screening using white light and Lugol chromoendoscopy does not accurately identify precursor lesions for ESCC and therefore cannot be systematically recommended.

Management of recurrent symptoms after per-oral endoscopic myotomy in achalasia.

BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) has been rapidly gaining ground as a treatment for achalasia. Although POEM is a safe and effective treatment, a subset of patients has persistent or recurrent symptoms after POEM. This study aimed to examine the efficacy of different retreatments after failed POEM. METHODS: POEM was performed on 441 patients with achalasia at 3 tertiary-care hospitals between 2010 and 2015. A review of prospectively collected data was conducted. All patients with achalasia with significant persistent or recurrent symptoms within 3 years after POEM, defined as an Eckardt symptom score >3, were included. RESULTS: Forty-three of 441 patients (9.8%) had persistent or recurrent symptoms after POEM, of which 34 (8%) received 1 or more retreatments. Retreatment with laparoscopic Heller myotomy and retreatment with POEM showed a modest efficacy of 45% and 63%, respectively, whereas pneumatic dilatation showed a poor efficacy of only 0% to 20%, depending on the size of the balloon. Male patients were more likely to have retreatment failure than female patients (P = .038). CONCLUSIONS: In patients with achalasia with persistent or recurrent symptoms after failed POEM, retreatment with laparoscopic Heller myotomy or retreatment with POEM has a higher efficacy than retreatment with pneumatic dilatations. Failure of retreatment occurred more often in male patients.

Challenges of peroral endoscopic myotomy in the treatment of distal esophageal spasm.

OBJECTIVE: Distal esophageal spasm (DES) is a rare motility disorder characterized by premature and rapidly propagated contractions of the distal esophagus. Treatment options are limited and often poorly effective. Peroral endoscopic myotomy (POEM) seems an effective and attractive new treatment option for DES. In this case report we describe some of the difficulties that could arise. MATERIALS AND METHODS: A 84-year old man with therapy-refractory DES and complaints of severe dysphagia and chest pain underwent a POEM procedure under general anesthesia. A longer myotomy was performed to cleave the circular muscle layer from start till end of the spastic contractions. RESULTS: The length of the myotomy was 16 cm. Hyperactive spastic contractions during the procedure complicated the creation of the submucosal tunnel, extended the duration (134 vs. 60-90 min for achalasia), increased postoperative pain and prolonged hospital admission. Intravenously nitroglycerin peroperative diminished spastic contractions. Postoperative a remnant of spastic contractions was present, proximal to the myotomy, causing persistent symptoms. CONCLUSION: Performing POEM for DES is challenging due to reactive hyperactive spastic contractions during the procedure causing technical difficulties and an extended procedure. A long myotomy, several centimeters above the proximal border of the spastic region, is essential to prevent remnants of spasticity.

Speech Therapy as Treatment for Supragastric Belching.

The purpose of this study was to describe a newly developed speech therapy program as an innovating therapeutic approach and to assess the results of this intervention in patients with supragastric belching. This is a retrospective analysis of prospectively gathered data from 73 patients with supragastric belching who were treated with speech therapy between 2007 and 2017. Of these, 48 were included for evaluation of therapy. Thirty patients had supragastric belching proven by 24-h impedance measurements. Eighteen patients were diagnosed by an experienced speech language pathologist as having supragastric belching according to precise criteria. Speech therapy consists of explanation, creating awareness of esophageal air influx and exercises to discontinue the supragastric belching mechanism. Therapy effect was measured by comparing visual analogue scale (VAS) scores on belching and related symptoms. The median symptom duration at the start of therapy was 2 years. Supragastric belching symptoms decreased significantly with a total median VAS score of 406 (291-463) prior to treatment and a median VAS score of 125 (17-197) following treatment. Forty patients (83%) had a sufficient to major result with a median therapy duration of 3 months and ten sessions. Speech therapy was an effective treatment in the majority of patients with supragastric belching.

Determinants of reflux-induced chronic cough.

OBJECTIVE: Gastro-oesophageal reflux is considered to be an important contributing factor in chronic unexplained cough. It remains unclear why some reflux episodes in the same patient causes cough while others do not. To understand more about the mechanism by which reflux induces cough, we aimed to identify factors which are important in triggering cough. DESIGN: In this multicentre study, 49 patients with reflux-associated chronic cough were analysed using 24-hour pH-impedance-pressure monitoring. The characteristics of reflux episodes that were followed by cough were compared with reflux episodes not associated with cough. RESULTS: The majority (72.4%) of the reflux episodes were acidic (pH<4). Compared with reflux episodes that were not followed by cough, reflux episodes that were followed by a cough burst were associated with a higher proximal extent (p=0.0001), a higher volume clearance time (p=0.002) and a higher acid burden in the preceding 15 min window (p=0.019) and higher reflux burden in the preceding 30 min window (p=0.044). No significant difference was found between the two groups when looking at the nadir pH, the pH drop, the acid clearance time or the percentage of reflux episodes which were acidic. CONCLUSIONS: The presence of a larger volume of refluxate and oesophageal exposure to reflux for a longer period of time seems to play an important role in inducing cough, while the acidity of the refluxate seems to be less relevant. This helps explain the observation that most patients with chronic cough tend not to benefit from acid inhibitory treatment.

Determinants of the Association between Non-Cardiac Chest Pain and Reflux.

OBJECTIVES: Gastroesophageal reflux is considered to be the most common gastrointestinal cause of non-cardiac chest pain (NCCP). It remains unclear why some reflux episodes in the same patient cause chest pain while others do not. To understand more about the mechanisms by which reflux elicits chest pain, we aimed to identify factors which are important in triggering chest pain. METHODS: In this multicenter study, 120 patients with NCCP were analyzed using 24-h pH-impedance monitoring. In the patients with a positive association between reflux and chest pain, the characteristics of the reflux episodes which were followed by a chest pain episode were compared with chest pain-free reflux episodes. RESULTS: Using 24-h pH-impedance monitoring, 40% of the NCCP patients were identified as having reflux as a possible cause of their chest pain. Reflux episodes that were associated with chest pain had a higher proximal extent (P=0.007), a higher volume clearance time (P=0.030), a higher 15-minute acid burden (P=0.041), were more often acidic (P=0.011), had a lower nadir pH (P=0.044), and had a longer acid duration time (P=0.027) than reflux episodes which were not followed by chest pain. Patients who experienced typical reflux symptoms were more likely to have reflux as the cause of their chest pain (52 vs. 31.4%, P=0.023). CONCLUSIONS: The presence of a larger volume of acid refluxate for a longer period of time appears to be an important determinant of perceiving a reflux episode as chest pain. 24-h pH-impedance monitoring is an important tool in identifying gastroesophageal reflux as a potential cause of symptoms in patients with NCCP.

Complications of botulinum toxin injections for treatment of esophageal motility disorders†.

In achalasia and spastic esophageal motility disorders, botulinum toxin (botox) injection is considered an effective and low-risk procedure for short-term symptom relief. It is mainly offered to medically high-risk patients. However, no analysis of risks of botox injections has been performed. To determine the incidence and risk factors of procedure-related complications after esophageal botox injections, we analyzed the records of all patients undergoing botox injection therapy for esophageal motility disorders at four university hospitals in Europe and North America between 2008 and 2014. Complications were assigned grades according to the Clavien-Dindo classification. In 386 patients, 661 botox treatments were performed. Main indications were achalasia (51%) and distal esophageal spasm (DES) (30%). In total, 52 (7.9%) mild complications (Clavien-Dindo grade I) were reported by 48 patients, the majority consisting of chest pain or heartburn (29 procedures) or epigastric pain (5 procedures). No ulceration, perforation, pneumothorax, or abscess were reported. One patient died after developing acute mediastinitis (Clavien-Dindo grade V) following injections in the body of the esophagus. In univariate logistic regression, younger age was associated with an increased risk of complications (OR 1.43, 95%CI 1.03-1.96). Treatment for DES, injections into the esophageal body, more injections per procedure, more previous treatments and larger amount of injected botulinum toxin were no risk factors for complications. Esophageal botox injection seems particularly appropriate for high-risk patients due to low complication rate. However, it should not be considered completely safe, as it is associated with rare side effects that cannot be predicted.

Long-term results of the European achalasia trial: a multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy.

OBJECTIVE: Achalasia is a chronic motility disorder of the oesophagus for which laparoscopic Heller myotomy (LHM) and endoscopic pneumodilation (PD) are the most commonly used treatments. However, prospective data comparing their long-term efficacy is lacking. DESIGN: 201 newly diagnosed patients with achalasia were randomly assigned to PD (n=96) or LHM (n=105). Before randomisation, symptoms were assessed using the Eckardt score, functional test were performed and quality of life was assessed. The primary outcome was therapeutic success (presence of Eckardt score ≤3) at the yearly follow-up assessment. The secondary outcomes included the need for re-treatment, lower oesophageal sphincter pressure, oesophageal emptying and the rate of complications. RESULTS: In the full analysis set, there was no significant difference in success rate between the two treatments with 84% and 82% success after 5 years for LHM and PD, respectively (p=0.92, log-rank test). Similar results were obtained in the per-protocol analysis (5-year success rates: 82% for LHM vs. 91% for PD, p=0.08, log-rank test). After 5 years, no differences in secondary outcome parameter were observed. Redilation was performed in 24 (25%) of PD patients. Five oesophageal perforations occurred during PD (5%) while 12 mucosal tears (11%) occurred during LHM. CONCLUSIONS: After at least 5 years of follow-up, PD and LHM have a comparable success rate with no differences in oesophageal function and emptying. However, 25% of PD patients require redilation during follow-up. Based on these data, we conclude that either treatment can be proposed as initial treatment for achalasia. TRIAL REGISTRATION NUMBERS: Netherlands trial register (NTR37) and Current Controlled Trials registry (ISRCTN56304564).

Mucosal integrity and sensitivity to acid in the proximal esophagus in patients with gastroesophageal reflux disease.

Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) (P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Ω·m) compared with the proximal esophagus (8,170 Ω·m) (P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol·cm(-2)·h(-1)) than in the proximal segment (368 nmol·cm(-2)·h(-1)) (P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability.