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The outcomes of peroral endoscopic myotomy for advanced achalasia are not well known. This study aimed to evaluate the outcomes of peroral endoscopic myotomy for achalasia with megaesophagus, which is one of the characteristics of advanced achalasia. Methods:In total, 234 patients with achalasia who underwent peroral endoscopic myotomy in our hospital from April 2015 to March 2019 were included in this retrospective observational study. Megaesophagus was defined as a maximum esophageal diameter of 6 cm or more. Outcomes, including clinical success (Eckardt score ≤3 without retreatment) at the 1-year follow-up, technical success, and perioperative complications, were investigated and compared between patients with and without megaesophagus. Results:Eleven patients (4.7%) were diagnosed with megaesophagus. The clinical success rate achieved was 63.6% in patients with megaesophagus, with a significant decrease in the Eckardt score (6 vs. 2, p=0.003) and integrated relaxation pressure (28 mmHg vs. 9 mmHg, p=0.028). The technical success rate was 100%. However, patients with megaesophagus had a significantly lower clinical success rate than those without megaesophagus (63.6% vs. 96.0%, p=0.002). Furthermore, patients with megaesophagus had significantly higher rates of major adverse events than those without megaesophagus (18.2% vs. 2.7%, p=0.048). Conclusions:Peroral endoscopic myotomy improved achalasia-related symptoms, and this was technically feasible in patients with megaesophagus. However, the clinical success rate was somewhat low, and the rate of major adverse events was high. Therefore, peroral endoscopic myotomy should be carefully performed for advanced achalasia with megaesophagus.

Esophageal cancer has the sixth highest mortality rate worldwide. Cancer-associated fibroblasts (CAFs) are involved in the progression of various cancers. Previously, we demonstrated an association between high expression of the CAF marker, fibroblast activation protein, and poor prognosis of esophageal squamous cell carcinoma (ESCC). We also established CAF-like cells by indirect co-culture of bone marrow-derived mesenchymal stem cells with ESCC cell lines and found metallothionein 2A (MT2A) to be highly expressed in them. Here, to explore the function of MT2A in CAFs, we silenced MT2A in the CAF-like cells and ESCC cell lines using small interfering RNA. MT2A knockdown in the CAF-like cells suppressed expression and secretion of insulin-like growth factor binding protein 2 (IGFBP2); recombinant IGFBP2 promoted migration and invasiveness of ESCC cells via NFκB, Akt, and Erk signaling pathways. Furthermore, MT2A knockdown in the ESCC cell lines inhibited their growth, migration, and invasiveness. Immunohistochemistry demonstrated that high MT2A expression in the cancer stroma and cancer nest of ESCC tissues correlated with poor prognosis of ESCC patients. Hence, we report that MT2A in CAFs and cancer cells contributes to ESCC progression. MT2A and IGFBP2 are potential novel therapeutic targets in ESCC.

TakashiToyonaga has received a portion of the sales of Flush knife-BT and Flush Knife-BTS, which were developed in collaboration with FUJIFILM Medical Co., Ltd., as royalties. He has also received a portion of the sales of Coagrasper G, which were developed in collaboration with Olympus Corporation, as royalties. The other authors have no conflicts of interest or financial ties to disclose.

Video 1 How to prepare a clip with a looped thread, and colorectal endoscopic submucosal dissection using the clip with looped thread method. ▶ Fig. 1 A clip with a looped thread. a A looped thread. b Tying the looped thread to a clip. c The clip with the looped thread. Indo Naohiko et al. Counter-traction using clip and loop for colorectal ESD … Endoscopy 2019; 51: E233-E234 E233 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.