Endoscopic retrograde appendicitis therapy (ERAT) vs appendectomy for acute uncomplicated appendicitis: A prospective multicenter randomized clinical trial.

OBJECTIVE: To compare the efficacy and feasibility of endoscopic retrograde appendicitis therapy (ERAT) with appendectomy for treating acute uncomplicated appendicitis. METHODS: This was a prospective multicenter randomized trial in which consecutive patients were randomized at a ratio of 1:1 to receive either ERAT or appendectomy. The outcomes included technical success rate, procedure time, postoperative pain relief, postoperative analgesic use, time to soft diet intake, length of postoperative hospital stay, postoperative complications, and recurrence rate. RESULTS: From August 2013 to December 2015, 110 patients with acute uncomplicated appendicitis were randomized to ERAT or appendectomy. The technical success rate was 94.55% for ERAT compared with 100% for appendectomy. Recurrence of appendicitis within 3-year follow-up occurred in 8 patients following ERAT. Postoperative abdominal pain was less frequent with ERAT than with appendectomy (21.15% [11/52] vs 87.27% [48/55], P < 0.001). Soft diet intake begun earlier after ERAT than appendectomy (6 h vs 48 h, P < 0.001), and post-procedure hospital stay was shorter (3 days vs 5 days, P < 0.001), as was the use of analgesics postoperatively (9.09% vs 49.09%, P < 0.001). CONCLUSIONS: ERAT is a feasible, safe, and effective alternative approach for the management of acute uncomplicated appendicitis. Compared with appendectomy, advantages of ERAT include no skin wound, organ preservation, reduced postoperative pain, early food intake, quick recovery, fewer postoperative complications, and shorter post-procedure hospitalization. The unsolved problem related to ERAT is the recurrence of appendicitis.

Laparoscopic resection is not superior to endoscopic resection for relative small gastric gastrointestinal stromal tumors: A propensity score-matched study.

Background and Aim: Endoscopic resection (ER) and laparoscopic resection (LAP) have been recommended for the treatment of gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. However, the therapeutic approach for gastric GISTs between 2 and 5 cm in diameter is still under debate. In this retrospective study, we aimed to evaluate the feasibility, efficacy, and safety of ER for gastric GISTs (2-5 cm) compared with LAP. Methods: From January, 2011 to January, 2018, 197 patients with GISTs at our institution with tumor diameter between 2 and 5 cm were included in our study. Clinical baseline characteristics, histopathological results, and perioperative outcomes were collected and compared in all the patients. Propensity score matching (PSM) methods were used to balance baseline characteristics. Results: There was no significant difference in age (p = 0.246), gender (p = 0.572), tumor location (p = 0.333), pathological risk classification (p = 0.543), Ki-67 index (p = 0.212), and follow-up time (p = 0.831) in the ER and LAP groups. However, significance difference was found in times to liquid diet intake (4.45 ± 1.2 vs. 5.40 ± 1.5 days, p = 0.013) and hospital stays (7.72 ± 1.1 vs. 10.01 ± 1.3 days, p < 0.001). During the follow-up period, there was one recurrence in the ER group vs. two recurrences in the LAP group. After PSM, the tumor size was balanced between the two groups with 49 patients in each group. The times to liquid diet intake (4.18 ± 1.3 vs. 5.16 ± 1.6 days, p = 0.042) and hospital stay days (7.12 ± 1.1 vs. 9.94 ± 1.3, p < 0.0001) were still short in the ER group. Conclusions: ER is more associated with a quick postoperative recovery than LAP. ER could be an alternative approach for gastric GISTs (2-5 cm). However, the long-term follow-up outcomes are still unclear and random control trials are needed.

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.

A reliable detachable balloon that prevents abdominal cavity contamination during transrectal natural orifice transluminal endoscopic surgery.

OBJECTIVE: To evaluate the efficacy and safety of a detachable endoluminal balloon in the prevention of abdominal cavity contamination during transrectal natural orifice transluminal endoscopic surgery (NOTES). METHODS: The efficacy and safety of a detachable endoluminal balloon to maintain disinfection in the distal colon of the pigs were evaluated. The bacterial loads and colonic cleanliness were monitored. Additionally, the device was applied to another nine pigs that underwent a cholecystotomy by transrectal NOTES. Necropsy and pathological examination were performed after 28-day follow-up. RESULTS: All animals exposed to the device and one of the seven pigs not exposed to the device scored three points on the bowel cleanliness scale (P < 0.001). After 30 min bacterial loads of the test (with balloon occlusion) and control (without balloon occlusion) groups showed a significant difference (0.8 × 103 CFU/mL vs 186.8 × 103 CFU/mL, P < 0.01). Cholecystotomy by transrectal NOTES with the device was successfully performed. The mean intraperitoneal procedure time was 102.9 ± 37.7 min. There were no procedure-related adverse events. During the follow-up, all animals presented normal behavior and appetite. No peritoneal infection or adhesion was detected at autopsy. Cholecystotomy and rectal incision were histologically healed and no histological abnormalities were detected in the colon related to balloon placement. CONCLUSIONS: The detachable balloon provides a reliable solution for preventing peritoneal contamination during transluminal operations. The technique may assist in future transrectal NOTES.

Reductions in myeloid-derived suppressor cells and lung metastases using AZD4547 treatment of a metastatic murine breast tumor model.

BACKGROUND: AZD4547, a small-molecule inhibitor targeting the tyrosine kinase of Fibroblast Growth Factor Receptors (FGFRs), is currently under phase II clinical study for human subjects having breast cancer, while the underlying mechanism remains elusive. The aim of this study is to explore the potential mechanism by which AZD4547 inhibits breast tumor lung metastases at the level of the tumor microenvironment. METHODS: First, through in vitro experiments, we investigated the efficacy of the FGFRs inhibitor AZD4547 on 4T1 tumor cells for their proliferation, apoptosis, migration, and invasion. Second, by in vivo animal experiments, we evaluated the effects of AZD4547 on tumor growth and lung metastases in 4T1 tumor-bearing mice. Finally, we examined the impact of AZD4547 on the infiltration of myeloid-derived suppressor cells (MDSCs) in lung, spleens, peripheral blood and tumor. RESULTS: Through this study we found that AZD4547 could efficiently suppress tumor 4T1 cells through restraining their proliferation, blocking migration and invasion, and inducing apoptosis in vitro. In animal model we also demonstrated that AZD4547 was able to inhibit tumor growth and lung metastases, consistent with the decreased MDSCs accumulation in the tumor and lung tissues, respectively. Moreover, the reduced number of MDSCs in peripheral blood and spleens were also observed in the AZD4547-treated mice. Importantly, through the AZD4547 treatment, the CD4(+) and CD8(+) T-cells were significantly increased in tumor and spleens. CONCLUSION: Our studies showed that AZD4547 can inhibit breast cancer cell proliferation, induce its apoptosis and block migration and invasion in vitro and suppress tumor growth and lung metastases by modulating the tumor immunologic microenvironment in vivo.

[Construction of a eukaryotic expression plasmid containing gp120 gene of HIV-1 subtype B and its expression in HepG2 cells].

OBJECTIVE: To construct an eukaryotic expression plasmid containing gp120 gene of HIV-1 subtype B and obtain gp120 gene expression in HepG2 cells. METHODS: According to the published gp120 gene sequence in Genbank, a pair of primers was designed and synthesized. The PCR amplification product of gp120 gene was cloned into pMD-18T vector using TA cloning followed by BamHI and XhoI digestion and sequence analysis. The target gene was then subcloned into a highly efficient eukaryotic expression vector pcDNA3.1 (+). The recombinant plasmid was sequenced and identified by restrictive endonuclease digestion, and transfected into HepG2 cells via liposome. The expression of gp120 gene was analyzed by RT-PCR and Western blotting, respectively. RESULTS: Restriction endonuclease digestion and sequence analysis verified successful construction of the recombinant vector pcDNA3.1(+)/gp120. The target fragment gp120 was identical with U26942 in Genbank, and the expression of gp120 gene was detected in the lysate of the transfected HepG2 cells by RT-PCR and Western blotting. CONCLUSION: The eukaryotic expression plasmid for gp120 has been constructed successfully, which is capable of stable expression in HepG2 cells.