Digital single-operator cholangioscope for endoscopic retrograde appendicitis therapy.

BACKGROUND: This study aimed to investigate the diagnostic and therapeutic value of a digital single-operator cholangioscope (SOC) system for endoscopic management of acute appendicitis. METHODS: 14 patients with acute uncomplicated simple or supportive appendicitis were evaluated between November 2018 and September 2020. The diagnosis of acute appendicitis was confirmed by direct colonoscopy imaging and cholangioscope. The success rate of digital SOC-assisted endoscopic retrograde appendicitis therapy (ERAT), the procedure time, postoperative length of hospital stay, complications, and recurrence rate were recorded. RESULTS: Technical success rate was 100 %, with high quality imaging of the appendiceal cavity achieved using SOC in all 14 patients. The mean procedure time was 37.8 (standard deviation [SD] 22) minutes. All patients experienced immediate relief from abdominal pain after the procedure. Mean postoperative hospitalization was 1.9 (SD 0.7) days. No recurrence occurred during 2-24 months of follow-up. CONCLUSION: Digital SOC-assisted ERAT provided a feasible, safe, and effective alternative approach for diagnosis and management of acute uncomplicated appendicitis without the need for X-ray or ultrasonic guidance.

ATF2 accelerates the invasion and metastasis of hepatocellular carcinoma through targeting the miR-548p/TUFT1 axis.

AIM: Due to high invasion and metastasis, hepatocellular carcinoma (HCC) is known as one of the most fatal carcinomas. We aim to further investigate regulatory mechanisms of invasion and metastasis to elucidate HCC pathogenesis and develop novel medications. METHODS: Patient specimens were collected for assessing gene expression and correlation between gene expressions. The expression of Ki67 and E-cadherin in subcutaneous xenograft tumor were examined by immunohistochemistry staining. The expression of activating transcription factor 2 (ATF2), miR-548p and TUFT1 were determined using Real-time quantitative reverse transcription polymerase chain reaction. Epithelial-mesenchymal transition and PI3K/AKT signaling-associated markers were examined with western blot. The proliferation, migration and invasion were assessed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide, colony formation and transwell assays, respectively. Cell apoptosis was assessed via Annexin V and propidium iodide staining. Gene interaction was confirmed using chromatin immunoprecipitation and luciferase activity assays. Subcutaneous and intravenous xenograft mouse models were established for analyzing HCC growth and metastasis in vivo. RESULTS: ATF2 was up-regulated in HCC patients and cells. ATF2 promoted HCC cell proliferation, migration and invasion and inhibited cell apoptosis through directly targeting miR-548p and controlling its expression. miR-548p suppressed HCC cell proliferation, migration and invasion and enhanced cell apoptosis. miR-548p directly bound to the 3'UTR of TUFT1 to restrain its expression and subsequently suppress the PI3K/AKT signaling. ATF2 knock-down significantly suppressed the growth and metastasis of HCC. CONCLUSION: ATF2 accelerates HCC progression by promoting cell proliferation, migration, invasion and metastasis, which is dependent on regulating the miR-548p/TUFT1 axis.

Advancing flexible endoscopy to natural orifice transluminal endoscopic surgery.

PURPOSE OF REVIEW: This review is an update on the recent advancements and clinical applications of flexible endoscopy in the context of natural orifice translumenal endoscopic surgery (NOTES). We focus on recent developments in gastrointestinal luminal and transluminal NOTES. RECENT FINDINGS: NOTES has evolved from a hybrid approach utilizing a laparoscopic assistant to pure NOTES without laparoscopic assistance. Current experimental and clinical studies focus on the implementation of new minimally invasive approaches as well as on the training in the use of these procedures. In recent years, flexible endoscopic-NOTES and endoluminal surgery have increasingly reported favorable results in preclinical and experimental settings using flexible endoscopic cholecystectomy, cholecystolithotomy, and appendectomy. Additionally, flexible endoscopic lymphadenectomy and thyroidectomy are among the new interventions that are opening new frontiers for endoscopists to explore. SUMMARY: Flexible endoscopy has paved way to new frontiers for endoscopists and surgeons. As the armamentarium of interventional endoscopy increases and the ability of endoscopists to perform advanced interventions safely fosters an inevitable step forward that will involve the integration of new technology with innovative thinking.

Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses.

BACKGROUND: Herpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic HSV (oHSV) T-Vec. However, transcription regulatory sequence (TRS) and transcription regulatory factor (TRF) of HSV US12 are seldom reported. METHODS: Previously, our laboratory isolated a new HSV strain named HSV-1-LXMW from a male patient with oral herpes in Beijing, China. Firstly, the genetic tree was used to analyze its genetic relationship. The US12 TRS and TRF in HSV-1-LXMW were found by using predictive software. Secondly, the further verification by the multi-sequence comparative analysis shown that the upstream DNA sequence of HSV US12 gene contained the conserved region. Finally, the results of literature search shown that the expression of transcription factors was related to the tissue affinity of HSV-1 and HSV-2, so as to increase the new understanding of the transcriptional regulation of HSV biology and oncolytic virus (OVs) therapy. RESULTS: Here we reported the transcriptional regulation region sequence of our new HSV-1-LXMW, and its close relationship with HSV-1-CR38 and HSV-1-17. Importantly we identified eight different kinds of novel TRSs and TRFs of HSV US12 for the first time, and found they are conserved among HSV-1 (c-Rel, Elk-1, Pax-4), HSV-2 (Oct-1, CF2-II, E74A, StuAp) or both HSVs (HNF-4). The TRFs c-Rel and Oct-1 are biologically functional respectively in immune escape and viral replication during HSV infection. CONCLUSIONS: Our findings have important implication to HSV biology, infection, immunity and oHSVs.

A snare-assisted pure NOTES retrograde cholecystectomy using a single channel flexible endoscope: a pilot experiment in a porcine model.

BACKGROUND AND AIM: Natural orifice transluminal endoscopic surgery (NOTES) cholecystectomy is an emerging technology. Interest is ongoing and developments have been rapid but NOTES cholecystectomy has failed to gain traction. Here, we share our experience of snare-assisted pure NOTES retrograde cholecystectomy using porcine models. MATERIALS AND METHODS: Under general anesthesia, an incision was created on the posterior vagina wall and an endoscope with a snare attached to the transparent cap was introduced into the pelvic cavity and then upward into peritoneal cavity. After locating the liver and gallbladder, the fundic wall of gallbladder was grasped using a biopsy forceps and the snare was released to ligate the fundus. The gallbladder was then carefully dissected from the gallbladder bed using hook/IT knives with the assistance of the snare. The cystic duct and cystic artery were identified, clipped twice and isolated from the gallbladder using the hook knife to cut between the clips. The specimen was then removed through the vagina using the snare. RESULTS: This procedure was successfully performed in 8 consecutive pigs. The average procedure time was 53 min (range 40-60 min). No severe bleeding or other complication was observed either during or after the procedure. Normal diets were given on the same day of the procedure. All animals recovered uneventfully. CONCLUSION: We successfully performed snare-assisted pure NOTES retrograde cholecystectomy in pigs using standard endoscopic instruments. In our experience, pure NOTES cholecystectomy using the retrograde approach performed with a single channel flexible endoscope proved safe and feasible with a short procedure time and quick recovery. The translation of this technique to human subjects seems straight forward and provides a new fitting path to pure NOTES.

Mucosal loss as a critical factor in esophageal stricture formation after mucosal resection: a pilot experiment in a porcine model.

BACKGROUND AND AIM: Esophageal stricture is a major complication of large areas endoscopic submucosal dissection (ESD). Until now, the critical mechanism of esophageal stricture remains unclear. We examined the role of mucosal loss versus submucosal damage in esophageal stricture formation after mucosal resection using a porcine model. MATERIALS AND METHODS: Twelve swine were randomly divided into two groups, each of 6. In each group, two 5-cm-long submucosal tunnels were made to involve 1/3rd of the widths of the anterior and posterior esophageal circumference. The entire mucosal roofs of both tunnels were resected in group A. In group B, the tunnel roof mucosa was incised longitudinally along the length of the tunnel, but without excision of any mucosa. Stricture formation was evaluated by endoscopy after 1, 2, and 4 weeks, respectively. Anatomical and histological examinations were performed after euthanasia. RESULTS: Healing observed on endoscopy in both groups after 1 week. Group A (mucosa resected) developed mild-to-severe esophageal stricture, dysphagia, and weight loss. In contrast, no esophageal stricture was evident in group B (mucosa incisions without resection) after 2 and 4 weeks, respectively. Macroscopic examination showed severe esophageal stricture and shortening of esophagus in only group A. Inflammation and fibrous hyperplasia of the submucosal layer was observed on histological examination in both groups. CONCLUSION: The extent of loss of esophageal mucosa appears to be a critical factor for esophageal stricture. Inflammation followed by fibrosis may contribute to alteration in compliance of the esophagus but is not the main mechanism of postresection stricture.