This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page page e76. Learning Objective-Upon completion of this activity, successful learners will be able to list the high resolution manometric criteria for diagnosis of achalasia types I, II, and III; list patient risk factors that could influence selection of myotomy procedure in patients with achalasia; recognize relative risks associated with the various treatment options for achalasia; and identify at least one predictive factor of successful outcome of pneumatic dilatation for treatment of achalasia. BACKGROUND & AIMS: Identification of factors associated with achalasia treatment outcome might help physicians select therapies based on patient characteristics. We performed a systematic review and metaanalysis to identify factors associated with treatment response. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library through February 21, 2019, for randomized controlled trials and cohort, case-control, and cross-sectional studies that reported patient-specific outcomes of treatment (botulinum toxin injection, pneumatic dilation, peroral endoscopic myotomy, or laparoscopic Heller myotomy). We assessed the methodologic quality of the included studies using the quality in prognosis studies tool. We planned qualitative and quantitative analyses. RESULTS: We analyzed data from 75 studies (8 randomized controlled trials, 27 prospective cohort studies, and 40 retrospective studies) on a total of 34 different factors associated with outcomes (3 demographic, 17 clinical, and 14 diagnostic factors). Qualitative assessment showed age, manometric subtype, and presence of a sigmoid-shaped esophagus as factors associated with outcomes of treatment for achalasia with a strong level of evidence. The cumulative evidence for the association with chest pain, symptom severity, and lower esophageal sphincter pressure was inconclusive. A meta-analysis confirmed that older age (mean difference, 7.9 y; 95% CI, 1.5-14.3 y) and manometric subtype 3 (odds ratio, 7.1; 95% CI, 4.1-12.4) were associated with clinical response. CONCLUSIONS: In a systematic review and meta-analysis, we found age and manometric subtype to be associated with outcomes of treatment for achalasia. This information should be used to guide treatment decisions.

Minimally-invasive tools to assess tumour presence and burden may improve clinical management. FDG-PET (metabolic) imaging is the current gold standard for interim response assessment in patients with classical Hodgkin Lymphoma (cHL), but this technique cannot be repeated frequently. Here we show that microRNAs (miRNA) associated with tumour-secreted extracellular vesicles (EVs) in the circulation of cHL patients may improve response assessment. Small RNA sequencing and qRT-PCR reveal that the relative abundance of cHL-expressed miRNAs, miR-127-3p, miR-155-5p, miR-21-5p, miR-24-3p and let-7a-5p is up to hundred-fold increased in plasma EVs of cHL patients pre-treatment when compared to complete metabolic responders (CMR). Notably, in partial responders (PR) or treatment-refractory cases (n = 10) the EV-miRNA levels remain elevated. In comparison, tumour specific copy number variations (CNV) were detected in cell-free DNA of 8 out of 10 newly diagnosed cHL patients but not in patients with PR. Combining EV-miR-127-3p and/or EV-let-7a-5p levels, with serum TARC (a validated protein cHL biomarker), increases the accuracy for predicting PET-status (n = 129) to an area under the curve of 0.93 (CI: 0.87-0.99), 93.5% sensitivity, 83.8/85.0% specificity and a negative predictive value of 96%. Thus the level of tumour-associated miRNAs in plasma EVs is predictive of metabolic tumour activity in cHL patients. Our findings suggest that plasmaThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Background and AimsOne of the most used treatments for achalasia is pneumatic dilation of the lower esophageal sphincter to improve esophageal emptying. Multiple treatment protocols have been described with a varying balloon size, number of dilations, inflation pressure, and duration. We aimed to identify the most efficient and safe treatment protocol.MethodsWe performed a systematic review and meta‐analysis of studies on pneumatic dilation in patients with primary achalasia. Clinical remission was defined as an Eckardt score ≤3 or adequate symptom reduction measured with a similar validated questionnaire. We compared the clinical remission rates and occurrence of complications between different treatment protocols.ResultsWe included 10 studies with 643 patients. After 6 months, dilation with a 30‐mm or 35‐mm balloon gave comparable mean success rates (81% and 79%, respectively), whereas a series of dilations up to 40 mm had a higher success rate of 90%. Elective additional dilation in patients with insufficient symptom resolution was somewhat more effective than performing a predefined series of dilations: 86% versus 75% after 12 months. Perforations occurred most often during initial dilations, and significantly more often using a 35‐mm balloon than a 30‐mm balloon (3.2 vs 1.0%); P = 0.027. A subsequent 35‐mm dilation was safer than an initial dilation with 35 mm (0.97% vs 9.3% perforations), P = 0.0017.ConclusionsThe most efficient and safe method of dilating achalasia patients is a graded approach starting with a 30‐mm dilation, followed by an elective 35‐mm dilation and 40 mm when there is insufficient symptom relief.