Loss of E-cadherin (E-cad) triggers invasion, metastasis, and dedifferentiation in various epithelial carcinomas. Recently, it has been reported that two transcription factors, Snail and SIP1 (Smad interacting protein 1), directly repress transcription of the E-cad gene by binding E-box on E-cad promoter. Our aim is to solve the molecular mechanism of Snail and SIP1 in hepatocellular carcinoma (HCC). We first showed an inverse correlation between E-cad and Snail/SIP 1 expression among five HCC lines with different phenotypes. The result indicated that undifferentiated, but not differentiated type expressed Snail/SIP1. Then, we established transfectants stably expressing Snail and SIP1 in two differentiated cells with E-cad expression. Suppressed expression of E-cad, morphologic change into fibroblastoid feature, and remarkable acceleration of invasion activity were observed in the transfectants. In reverse transcriptionpolymerase chain reaction series of genes relating to motility and invasion, we demonstrated striking evidence that matrix metalloproteinase (MMP-1), MMP-2, MMP-7, and MT1-MMP expressions were strongly upregulated by Snail. On the other hand, MMP-1, MMP-2, and MT1-MMP expressions were enhanced by SIP1 transfection, however, the intensity was weaker than that in Snail transfection. In conclusion, Snail or SIP1 expression may be induced during HCC progression, where Snail/SIP1 directly represses E-cad gene transcription and activates cancer invasion via the upregulation of the MMP gene family.

Objectives Some patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) therapy. Anti‐reflux mucosectomy (ARMS) is a minimally invasive endoscopic procedure for treatment of GERD. In this study, we retrospectively evaluated the outcomes of ARMS performed in patients with PPI‐refractory GERD at our institution. Methods A total of 109 patients with PPI‐refractory GERD who underwent ARMS were retrospectively reviewed. Pre‐ and post‐ARMS questionnaire scores, acid exposure time (AET), DeMeester score, proximal extent, and PPI discontinuation rate were compared. Results There was a significant improvement in the symptom score (P < 0.01) and 40–50% of patients were able to discontinue PPI after ARMS. In patients who were followed up for 3 years, sustained improvement in subjective symptoms was observed. AET and DeMeester score significantly improved after ARMS (P < 0.01); however, there was no significant improvement in proximal extent (P = 0.0846). Conclusions Anti‐reflux mucosectomy is an effective minimally invasive therapy for patients with PPI‐refractory GERD. The therapeutic efficacy is attributable to suppression of acid backflow due to contraction of the scar tissue in cardia.

Background Peroral endoscopic myotomy (POEM) has become the minimally invasive endoscopic treatment for achalasia; however, gastroesophageal reflux (GER) post-POEM has been reported. A pilot study was conducted in which an endoscopic fundoplication was added to the standard POEM (POEM + F) procedure to overcome this issue. We report the technical details of POEM + F and short-term safety results. Methods POEM + F was performed in 21 patients. After completing myotomy, the endoscope was advanced from the submucosal tunnel into the peritoneal cavity. A partial mechanical barrier was created by retracting the anterior gastric wall at the esophagogastric junction with the use of endoclips and an endoloop. Results POEM + F was technically feasible in all cases and created a visually recognizable fundoplication. The clinical course after POEM + F was uneventful. No immediate or delayed complications occurred. Conclusion POEM + F may help mitigate the post-POEM incidence of GER and serve as a minimally invasive endoscopic alternative to a laparoscopic Heller-Dor procedure. This is the largest case series of peroral natural orifice transluminal endoscopic surgery without laparoscopic assistance in the human foregut.

Background The incidence of proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) has been increasing. While surgical intervention with Laparoscopic Nissen Fundoplication remains the gold standard, less invasive anti-reflux interventions are desired. We have developed a minimally invasive anti-reflux mucosal ablation (ARMA) treatment. Herein, we report its technical details and describe its feasibility, safety, and efficacy in PPI-refractory GERD. Methods We conducted a prospective single-center single-arm interventional trial evaluating the outcome of ARMA in 12 patients with PPI-refractory GERD. GERD-Health Related Quality of Life Questionnaire (GERD-HRQL) evaluation, Frequency Scale for the Symptoms of GERD (FSSG) assessment, and impedance-pH monitoring were performed at baseline and at 2 months post-ARMA. Results A total of 12 patients underwent ARMA with a median follow-up duration of 9 months (range: 6 – 14 months). Median GERD-HRQL score significantly improved from 30.5 to 12 (P = 0.002); median FSSG score significantly improved from 25 to 10.5 (P = 0.002), and median DeMeester score decreased from 33.5 to 2.8 (P = 0.049) at 2 months follow-up. No immediate complications were observed. Conclusion Our pilot study has shown that ARMA, a new endoscopic treatment for PPI-refractory GERD, is simple, safe, and improves GERD-related symptoms and objective acid reflux parameters.

Significant correlations were found between mean ADC values and differentiation grade. ADC may be useful as an imaging biomarker of tumor aggressiveness, but it cannot serve as an independent biomarker of advanced rectal cancer.