Background Achalasia is a motility disorder of unknown etiology. Previous studies supported the hypothesis that autoimmune‐mediated inflammatory responses produce inhibitory neuronal degeneration. This study was designed to explore the role of mast cells in achalasia. Methods We collected information from 116 patients with achalasia who underwent peroral endoscopic myotomy between December 2016 and May 2017. Lower esophageal sphincter (LES) muscle biopsy was performed in all patients with achalasia, as well as 20 control subjects. The number of mast cells, interstitial cells of Cajal (ICCs), nNOS‐positive cells, and S‐100‐positive cells in the LES were evaluated by immunohistochemistry. Pathological and clinical data were compared between groups. Key Results Compared with controls, the LES of patients with achalasia had significantly fewer ICCs, nNOS‐positive cells, and S‐100‐positive cells and a higher number of mast cells (all P < 0.001). Furthermore, the increased mast cell infiltration was significantly associated with decreased ICCs, nNOS‐positive cells, and S‐100‐positive cells in patients with achalasia (all P < 0.05). Clinically, the number of strongly positive mast cells was highest in patients with type I achalasia and lowest in those with type III achalasia (P < 0.001). In addition, patients with a history of autoimmune disease or viral infection had greater mast cell infiltration in the LES muscle (P = 0.040). Conclusions & Inferences In patients with achalasia, mast cell infiltration in the LES muscle is increased, in association with loss of ICCs and neuronal degeneration. Mast cells may thereby play a crucial role in the development of achalasia.

Background Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune‐mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. Methods We collected information from forty‐seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty‐seven age‐ and sex‐matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. Key Results Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF‐ß1 (P < .001), TGF‐ß2 (P < .001), TGF‐ß3 (P < .001), IL‐1ra (P < .001), IL‐17 (P = .005), IL‐18 (P < .001), IFN‐γ (P < .001), MIG (P < .001), PDGF‐BB (P < .001), IP‐10 (P = .003), and SCGF‐B (P < .001). Gene ontology (GO) and network functional enrichment analysis revealed regulation of signaling receptor activity and receptor‐ligand activity were the most related pathways of these cytokines and chemokines. Levels of twelve cytokines and chemokines were significantly increased in type III compared with I/II achalasia, namely, TGF‐ß2, IL‐1ra, IL‐2Ra, IL‐18, MIG, IFN‐γ, SDF‐1a, Eotaxin, PDGF‐BB, IP‐10, MCP‐1, and TRAIL. Conclusions and Inferences Patients with achalasia exhibited increased levels of serological cytokines and chemokines. Levels of cytokines and chemokines were significantly increased in type III than in type I/II achalasia. Cytokines and chemokines might contribute to the inflammatory development of achalasia.

Background Endoscopic submucosal dissection (ESD) for anastomotic lesions is technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and effectiveness of ESD for anastomotic lesions of the lower gastrointestinal tract. Method We retrospectively investigated 55 patients with anastomotic lesions of the lower gastrointestinal tract who underwent ESD from February 2008 to January 2021. The lesions involving one or both sides of anastomoses were classified into the unilaterally involving anastomosis (UIA) or straddling anastomosis (SA) group, respectively. We collected clinicopathological characteristics, procedure‐related parameters and outcomes, and follow‐up data and analyzed the impact of anastomotic involvement. Results The mean age was 62.5 years, and the median procedure duration was 30 min. The rates of en bloc resection and R0 resection were 90.9% and 85.5%, respectively. Four patients (7.3%) experienced major adverse events (AEs). During a median follow‐up of 66 months (range 14–169), seven patients had local recurrence, and six patients had metastases. The 5‐year disease‐free survival and overall survival rates were 82.4% and 90.7%, respectively. The 5‐year disease ‐specific survival (DSS) rate was 93.3%. Compared with the UIA group, the SA group had significantly longer procedure duration, larger specimen, lower rates of en bloc resection and R0 resection, and shorter disease‐free survival (all P < 0.05). However, rates of AEs did not differ significantly between the two groups. Conclusions The short‐term and long‐term outcomes of ESD for colorectal anastomotic lesions were favorable. Although with technically challenging, ESD could be performed safely and effectively for lesions at the anastomoses.