Focal Distal Esophageal Dilation (Blown-Out Myotomy) After Achalasia Treatment: Prevalence and Associated Symptoms.

INTRODUCTION: Peroral endoscopic myotomy (POEM) may result in a distended distal esophagus, referred to as a blown-out myotomy (BOM), the relevance of which is uncertain. The aim of this study was to investigate the prevalence, risk factors, and associated symptoms of BOM after achalasia treatment. METHODS: A data set of the locally treated patients in a randomized controlled trial comparing POEM with pneumatic dilation (PD) was analyzed. A BOM is defined as a >50% increase in esophageal diameter at its widest point in the distal esophagus between the lower esophageal sphincter and 5 cm above. RESULTS: Seventy-four patients were treated in our center, and 5-year follow-up data were available in 55 patients (32 patients [58%] randomized to POEM, 23 [42%] PD). In the group initially treated with POEM, the incidence of BOM increased from 11.5% (4/38) at 3 months, to 21.1% (8/38) at 1 year, 27.8% (10/36) at 2 years, and 31.3% (10/32) at 5 years. None of the patients treated with PD alone developed a BOM. Patients who developed a BOM had a higher total Eckardt score and Eckardt regurgitation component compared with patients who underwent POEM without BOM development (3 [2.75-3.25] vs 2 [1.75-3], P = 0.032, and 1 [0.75-1] vs 0 [0-1], P = 0.041). POEM patients with a BOM more often report reflux symptoms (85% [11/13] vs 46% [2/16], P = 0.023) and had a higher acid exposure time (24.5% [8-47] vs 6% [1.2-18.7], P = 0.027). DISCUSSION: Thirty percent of the patients treated with POEM develop a BOM, which is associated with a higher acid exposure, more reflux symptoms, and symptoms of regurgitation.

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.

The Effect of STW5 (Iberogast) on Reflux Symptoms in Patients With Concurrent Dyspeptic Symptoms: A Double-blind Randomized Placebo-controlled Crossover Trial.

Background/Aims: It has been suggested that STW5 (Iberogast) reduces heartburn symptoms in patients with functional dyspepsia, but underlying mechanisms of action are unclear. The aim of this study is to investigate whether STW5 affects esophageal sensitivity or esophageal motility, thereby reducing occurrence and perception of reflux events. Methods: We performed a double-blind, randomized, placebo-controlled, crossover trial in patients with functional dyspepsia (Rome IV) and reflux symptoms. After 4 weeks of treatment with either placebo or STW5, patients were studied with an esophageal acid perfusion test and ambulatory 24-hour pH-impedance monitoring. Results: A total of 18 patients (7 men, median age 54, range [19-76]), were included in the study. Although we found no statistical difference in our primary outcome the total Reflux Disease Questionnaire score 2.33 (0.25-4.33) vs 2.67 (1.17-4.00), P = 0.347, "gastroesophageal reflux disease" and "regurgitation" subscale scores were lower after STW5 treatment compared to placebo (P = 0.049 and P = 0.007). There was no statistical difference in number of reflux events, acid exposure time and acid sensitivity scores between STW5 and placebo. In a subgroup analysis of patients with pH-metry confirmed gastroesophageal reflux disease, treatment with STW5 significantly reduced the total number of acidic reflux events (P = 0.028). Moreover, in patients with reflux esophagitis, the median lag time to acid perception increased after STW5 treatment (P = 0.042). Conclusions: We found some indications pointing towards a beneficial effect of STW5 on reflux symptoms in dyspeptic patients, with reduction of esophageal hypersensitivity as a potential underlying mechanism. Our findings will have to be confirmed in larger studies.

The clinical effect of benesco™ on reflux symptoms: A double-blind randomized placebo-controlled trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases in the western world. Lifestyle modifications and proton pump inhibitors (PPIs) form the basis of the management of GERD. A subset of patients seeks for (natural) alternative therapies besides PPIs. benesco™ is an over-the-counter nutrition based on quercetin which has a presumed positive effect on esophageal barrier function. Therefore we aim to assess the effect of benesco™ on reflux symptoms. METHODS: We performed a double-blind randomized placebo-controlled trial in participants with reflux symptoms. Participants were assigned randomly (1:1) to receive 6 weeks of benesco™ (three times daily one lozenge containing 200 mg of quercetin) or placebo. The primary outcome was treatment success (≥50% reduction in Reflux Disease Questionnaire Score). Secondary outcomes included GERD-related quality of life, reflux-free days and nights, and participant-reported treatment success. KEY RESULTS: One hundred participants were randomized. Treatment success was seen in 18 (39%) of 46 participants in the intervention group versus 21 (47%) of 45 in the placebo group (p = 0.468). In the intervention group 10 (1-21) reflux-free days were reported compared to 10 (2-25) in the placebo group (p = 0.673). In addition, 38 (34-41) versus 39 (35-42) reflux-free nights were reported (p = 0.409). CONCLUSIONS & INFERENCES: In our trial benesco™ showed no significant benefit over placebo at group level.

The effect of sleep positional therapy on nocturnal gastroesophageal reflux measured by esophageal pH-impedance monitoring.

BACKGROUND & AIMS: The aim of the study was to evaluate the effect of an electronic positional therapy wearable device on nocturnal gastroesophageal reflux measured by pH-impedance reflux monitoring. METHODS: We performed a single-center, prospective, interventional study in 30 patients with nocturnal reflux symptoms and a nocturnal esophageal acid exposure time (AET) ≥1.5% measured off acid-suppressive medication by ambulatory pH-impedance reflux monitoring. Patients were treated with an electronic positional therapy wearable device for 2 weeks. The device vibrates in the right lateral decubitus position so it conditions patients to avoid that sleep position. After 2 weeks treatment, the pH-impedance study was repeated. Primary outcome was the change in nocturnal AET. Secondary outcomes include change in number of reflux episodes and reflux symptoms. RESULTS: Complete data were available for 27 patients (13 females, mean age 49.8 years). The median nocturnal AET decreased from 6.0% (IQR, 2.3-15.3) to 3.1% (0.1-10.8) after 2 weeks of treatment (p = 0.079). The number of reflux episodes was significantly reduced after 2 weeks of treatment (baseline: 8.0 (3.0-12.3) vs. end: 3.0 (1.0-8.0); p = 0.041). Treatment led to a statistically significant decrease in time spent in right lateral decubitus position (baseline: mean 36.9% ± 15.2% vs. end: 2.7% ± 8.2%; p = <0.001) and an increase in the left lateral decubitus position (baseline 29.2% ± 14.8% vs. end: 63.3% ± 21.9%; p = <0.001). Symptom improvement was reported by 70.4% of the patients. CONCLUSIONS: Sleep positional therapy using an electronic wearable device promotes sleeping in the left lateral decubitus position and improves reflux parameters measured by pH-impedance reflux monitoring.

Decompensation as initial presentation in patients with liver cirrhosis is associated with an increased risk of future decompensation and mortality.

BACKGROUND AND AIMS: The clinical course of patients with liver cirrhosis and adherence to hepatocellular carcinoma (HCC) screening guidelines are not well studied in the Netherlands. We investigated this and potential risk factors for decompensation and transplant-free survival (TFS) in a large regional cohort. METHODS: We performed a retrospective cohort study of patients with confirmed liver cirrhosis in Amsterdam, the Netherlands. Clinical parameters, decompensation events, development of HCC, and medication use were extracted from medical records. RESULTS: In total, 681 hospitalized and outpatients were included. Mortality risk was increased by: age (aHR 1.07, p < 0.01), smoking (aHR 1.83, p < 0.01), decompensated initial presentation (aHR 1.43, p = 0.04) and increased MELD (aHR 1.07, p < 0.01). PPI use tended to increase mortality risk (aHR 1.35, p = 0.05). The risk of future decompensation was increased with increased age (aHR 1.02, p < 0.01), decompensated initial presentation (aHR 1.37, p = 0.03) and alcohol misuse as etiology (aHR 1.34, p = 0.04). Adequately screened patients for HCC had a longer TFS compared to patients who were not (48 vs 22 months), p < 0.01). CONCLUSIONS: In patients with cirrhosis, decompensation at initial presentation was associated with an increased risk of future decompensation and mortality. Alcoholic cirrhosis was associated with an increased risk of future decompensation. Adequate HCC surveillance was associated with markedly better survival.

Peroral endoscopic myotomy versus pneumatic dilation in treatment-naive patients with achalasia: 5-year follow-up of a randomised controlled trial.

BACKGROUND: 2-year follow-up data from our randomised controlled trial showed that peroral endoscopic myotomy is associated with a significantly higher efficacy than pneumatic dilation as initial treatment of therapy-naive patients with achalasia. Here we report therapeutic success rates in patients treated with peroral endoscopic myotomy compared with pneumatic dilation at the 5-year follow-up. METHODS: We did a multicentre, randomised controlled trial in six hospitals in the Netherlands, Germany, Italy, Hong Kong, and the USA. Adults aged 18-80 years with newly diagnosed symptomatic achalasia (based on an Eckardt score >3) were eligible for inclusion. Patients were randomly assigned (1:1) to peroral endoscopic myotomy or pneumatic dilation using web-based randomisation with a random block size of 8 and stratification according to site. Randomisation concealment for treatment type was double blind until official study enrolment. Treatment was unmasked because of the different technical approach of each procedure. Patients in the pneumatic dilation group were dilated with a single series of 30-35 mm balloons. The need for subsequent dilations in the pneumatic dilation group, and the need for dilation after initial treatment in the peroral endoscopic myotomy group, was considered treatment failure. The primary outcome was therapeutic success (Eckardt score ≤3 in the absence of severe treatment-related complications and no need for retreatment). Analysis of the primary outcome was by modified intention to treat, including all patients randomly assigned to a group, excluding those patients who did not receive treatment or were lost to follow-up. Safety was assessed in all included patients. This study is registered at the Dutch Trial Registry, NTR3593, and is completed. FINDINGS: Between Sept 21, 2012, and July 20, 2015, 182 patients were assessed for eligibility, 133 of whom were included in the study and randomly assigned to peroral endoscopic myotomy (n=67) or pneumatic dilation (n=66). 5-year follow-up data were available for 62 patients in the peroral endoscopic myotomy group and 63 patients in the pneumatic dilation group. 50 (81%) patients in the peroral endoscopic myotomy group had treatment success at 5 years, compared with 25 (40%) in the pneumatic dilation group, an adjusted absolute difference of 41% (95% CI 25-57; p<0·0001). Reasons for failure were no initial effect of treatment (one patient in the peroral endoscopic myotomy group vs 12 patients in the pneumatic dilation group) and recurrent symptoms causing treatment failure (11 patients in the peroral endoscopic myotomy group [seven patients between 2 and 5 years] vs 25 patients in the pneumatic dilation group [nine patients between 2 and 5 years]); one patient in the pneumatic dilation group had treatment failure due to an adverse event. Proton-pump inhibitor use (mostly daily) was significantly higher after peroral endoscopic myotomy than after pneumatic dilation among patients still in clinical remission (23 [46%] of 50 patients vs three [13%] of 24 patients; p=0·008). 5-year follow-up endoscopy of patients still in clinical remission showed reflux oesophagitis in 14 (33%) of 42 patients in the peroral endoscopic myotomy group (12 [29%] grade A or B, two [5%] grade C or D) and two (13%) of 16 patients in the pneumatic dilation group (two [13%] grade A or B, none grade C or D; p=0·19). No intervention-related serious adverse events occurred between 2 and 5 years after treatment. The following non-intervention-related serious adverse events occurred between 2 and 5 years: a stroke (one [2%]) in the peroral endoscopic myotomy group; and death due to a melanoma (one [2%]) and dementia (one [2%]) in the pneumatic dilation group. INTERPRETATION: Based on this study, peroral endoscopic myotomy should be proposed as an initial treatment option for patients with achalasia. Although our study has shown that peroral endoscopic myotomy has greater long-term efficacy with a low risk of major treatment-related complications, this should not lead to abandonment of pneumatic dilation from clinical practice. Ideally, all treatment options should be discussed with treatment-naive patients with achalasia and a shared decision should be made. FUNDING: Fonds NutsOhra and European Society of Gastrointestinal Endoscopy.

Systematic review: Clinical effectiveness of interventions for the treatment of nocturnal gastroesophageal reflux.

BACKGROUND: Nocturnal gastroesophageal reflux symptoms have a major impact on sleep quality and are associated with complicated gastroesophageal reflux disease (GERD). We performed a systematic review to assess the data on the effectiveness of the currently available interventions for the treatment of nocturnal reflux symptoms. METHODS: We searched PubMed, EMBASE, and the Cochrane Library. All prospective, controlled, and uncontrolled clinical trials in adult patients describing interventions (lifestyle modifications, surgical and pharmacological) for nocturnal gastroesophageal reflux symptoms were assessed for eligibility. A narrative descriptive summary of findings is presented together with summary tables for study characteristics and quality assessment. KEY RESULTS: The initial reference search yielded 3067 citations; 66 citations were screened in full text, of which 31 articles were included. Studies on lifestyle modifications include head of bed elevation (n = 5), prolonging dinner-to-bed time (n = 2), and promoting left lateral decubitus position (n = 2). Placebo-controlled clinical trials investigating proton pump inhibitors (PPIs) (n = 11) show success rates ranging from 34.4% to 80.8% in the PPI group versus 10.4%-51.7% in the placebo group. Laparoscopic fundoplication is reserved for severe disease only. There is insufficient evidence for a recommendation on the use of nasal continuous positive airway pressure (nCPAP), hypnotics, baclofen and adding bedtime H2 receptor antagonists for reducing nocturnal reflux. CONCLUSION INFERENCES: A sequential treatment strategy, including head of bed elevation, prolonging dinner-to-bed time, promoting left lateral decubitus position and treatment with acid-suppressive medication is recommended for nocturnal gastroesophageal reflux symptoms. Currently, there is insufficient evidence for the use of nCPAP, hypnotics, baclofen and adding bedtime H2 receptor antagonists.

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).