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.

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.

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.

Vatalanib, a tyrosine kinase inhibitor, decreases hepatic fibrosis and sinusoidal capillarization in CCl4-induced fibrotic mice.

Among the various consequence arising from lung injury, hepatic fibrosis is the most severe. Decreasing the effects of hepatic fibrosis remains one of the primary therapeutic challenges in hepatology. Dysfunction of hepatic sinusoidal endothelial cells is considered to be one of the initial events that occur in liver injury. Vascular endothelial growth factor signaling is involved in the progression of genotype changes. The aim of the present study was to determine the effect of the tyrosine kinase inhibitor, vatalanib, on hepatic fibrosis and hepatic sinusoidal capillarization in a carbon tetrachloride (CCl4)­induced mouse model of liver fibrosis. Liver fibrosis was induced in BALB/c mice using CCl4 by intraperitoneal injection for 6 weeks. The four experimental groups included a control, and three experimental groups involving administration of CCl4, vatalanib and a combination of the two. Histopathological staining and measuring live hydroxyproline content evaluated the extent of liver fibrosis. The expression of α­smooth muscle actin (SMA) and cluster of differentiation (CD) 34 was detected by immunohistochemistry. Collagen type I, α­SMA, transforming growth factor (TGF)­ß1 and vascular endothelial growth factor receptor (VEGFR) expression levels were measured by reverse transcription-quantitative polymerase chain reaction (RT­qPCR). The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Liver fibrosis scores and hydroxyproline content were decreased in both vatalanib groups. In addition, both doses of vatalanib decreased mRNA expression levels of hepatic α-SMA, TGF-ß1, collagen­1, VEGFR1, and VEGFR2. Levels of α­SMA and CD34 protein were decreased in the vatalanib group compared with the CCl4 group. There were significant differences in the number of fenestrae per sinusoid between the groups. The present study identified that administration of vatalanib was associated with decreased liver fibrosis and hepatic sinusoidal capillarization in CCl4-induced mouse models, and is a potential compound for counteracting liver fibrosis.

Esophago-Cardial-Gastric Tunneling Peritoneoscopy: In Vivo Dog Survival Study.

BACKGROUND: Diagnostic peritoneoscopy is typically performed by using a rigid laparoscope. Inspired by gastric submucosal tunneling for peritoneal natural orifice transluminal endoscopic surgery access and peroral endoscopic myotomy for the treatment of achalasia, we developed a novel esophago-cardial-gastric tunneling (ECGT) peritoneoscopy technique with a flexible endoscope. This study aims to evaluate its feasibility and safety. MATERIALS AND METHODS: The study comprised 10 Beagle dogs. A longitudinal mucosal incision was made on the esophageal wall, and a submucosal tunnel was created through the cardia into the stomach. An incision was made in the muscular layer of the stomach, and then the endoscope was advanced into the peritoneal cavity. Peritoneoscopy with the flexible endoscope was performed. After intraperitoneal exploration, the esophageal mucosal entry was closed with endoclips. All dogs resumed food intake 12 hours after the procedures. Diets, behavior, and body temperature of all of the dogs were observed. Endoscopic examinations were performed 4 weeks after the procedure, and then the animals were sacrificed for necropsy. RESULTS: The ECGT peritoneoscopy was successfully done in all dogs. Diets, behavior, and body temperature were normal in all dogs. The entry of the esophagus was healed well in 9 dogs; the mucosa of the entry was torn in 1 dog, but the submucosal tunnel was healed well at the cardia. Necropsy showed complete closure of the gastric serosal exit, and no intraperitoneal abscess was found. Histopathological examinations showed submucosal tunnels healed well. CONCLUSIONS: The ECGT peritoneoscopy is feasible and safe for peritoneal exploration. It should be a good choice for the clinical application of diagnostic peritoneoscopy.

Human recombinant endostatin Endostar attenuates hepatic sinusoidal endothelial cell capillarization in CCl4­induced fibrosis in mice.

The aim of the present study was to detect the effect of the recombinant human endostatin Endostar on hepatic sinusoidal capillarization in CCl4­induced murine models of liver fibrosis. The liver fibrosis model was induced in BALB/c mice using intraperitoneal injection of CCl4 for 6 weeks. Animals were divided into the following six treatment groups: Group 1, normal animals; group 2, CCl4­induced liver fibrosis; group 3, CCl4+Endostar 20 mg/kg/day for 6 weeks; group 4, CCl4+Endostar 10 mg/kg/day for 6 weeks; group 5, CCl4+Endostar 20 mg/kg/day for 4 weeks; and group 6, CCl4+Endostar 10 mg/kg/day for 4 weeks. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 1 and 2 expression was detected by western blot analysis. There were significant differences in the number of fenestrae per sinusoid between the normal control and untreated model fibrotic mice (P<0.01), and between the untreated model and Endostar­treated mice (P<0.05). Endostar treatment was associated with reduced levels of VEGFR1 and VEGFR2 in liver tissues (P<0.01), as well as with decreased hepatic sinusoidal endothelial cell capillarization in CCl4­induced mouse models of liver fibrosis, and this effect may involve the VEGF pathway. However, further studies are required to confirm its involvement in other causes of liver fibrosis.

Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice.

Decreasing hepatic fibrosis remains one of the major therapeutic challenges in hepatology. The present study aims to evaluate the effect of Endostar on both CCl4-induced liver fibrosis in mice and a hepatic stellate cell (HSC) line. Two main models were studied: (i) a liver fibrosis model was induced in BALB/c mice using CCl4 by intraperitoneal injection for six weeks. Six animal groups were studied: group 1: normal animals; group 2: CCl4-induced liver fibrosis; group 3: CCl4 + Endostar 20 mg/kg/d, six weeks; group 4: CCl4 + Endostar 10 mg/kg/d, six weeks; group 5: CCl4 + Endostar 20 mg/kg/d, four weeks; group 6: CCl4 + Endostar 10 mg/kg/d, four weeks corresponded to different Endostar doses and duration of administration. Liver fibrosis was evaluated by histopathological staining and liver hydroxyproline content. Expressions of collagen type I, α-smooth muscle actin (α-SMA), TGF-ß1 and VEGFR were measured by real-time polymerase chain reaction (PCR). (ii) A liver cell model. HSC-T6 cells were cultured with or without Endostar for 12 h or 24 h. Expressions of collagen type I, α-SMA, and TGF-ß1 were measured by real-time PCR. Collagen I and transforming growth factor ß1 (TGF-ß1) contents in cell supernatant were measured by enzyme-linked immunosorbent assay. As compared to the group without Endostar, liver fibrosis scores and hydroxyproline content were decreased in both Endostar groups (P < 0.05). Moreover, Endostar inhibited the hepatic expression of α-SMA, TGF-ß1, Collagen-1, VEGFR1, and VEGFR2 mRNA (P < 0.05). In the HSC-T6 cell line model, Endostar profoundly inhibited the expression of α-SMA, Collagen-1, and TGF-ß1 mRNA. Expressions of Collagen-1 and TGF-ß1 protein were decreased in the Endostar group as compared to the normal controls in the supernatant of HSC-T6 cells (P < 0.05). Endostar decreased both liver fibrosis in CCl4-induced mice and collagen synthesis in HSCs in vitro. Therefore, this recombinant human endostatin is a promising compound for counteracting liver fibrosis.

Tunneling endoscopic muscularis dissection for subepithelial tumors originating from the muscularis propria of the esophagus and gastric cardia.

BACKGROUND AND AIMS: Endoscopic resection of esophageal or cardial subepithelial tumors (SETs) originating from the muscularis propria (MP) is rarely done due to the high risk of perforation, fistula formation, and secondary infection. The aim of this study was to evaluate the preliminary clinical feasibility and safety of tunneling endoscopic muscularis dissection (tEMD) for resection of SETs located in the esophagus and gastric cardia METHODS: Twelve patients with SETs originating from the MP of the esophagus (n = 7) or cardia (n = 5) were treated by tEMD. The procedure included creation of a submucosal tunnel to reach the tumor, dissection of the tumor from the surrounding submucosal tissue and the unaffected MP layer, full-thickness resection of the tumor and affected MP, and subsequent closure of the tunnel mucosal entry with endoscopic clips. RESULTS: The en bloc resection rate was 100 % (seven lesions affected the deep MP so complete MP resection was performed; five lesions affected the superficial MP for a partial MP resection). The average tumor size was 18.5 ± 6.9 (range 10-30) mm. The mean operating time was 78.3 ± 25.5 (range 50-130) min. The histological diagnoses were two gastrointestinal stromal tumors with very low risk, nine leiomyomas, and one schwannoma. Air leakage and effusion included subcutaneous and mediastinal emphysema in eight patients (66.7 %), pneumothorax in four (33.3 %), pneumoperitoneum in three (25.0 %), and small pleural effusion in two (16.7 %). All air leakage and effusion cases were resolved with conservative management. No patient developed delayed hemorrhage and chronic fistula after tEMD. During the mean follow-up time of 7.1 ± 4.3 (range 2-15) months, no tumor recurrence was found in any patient. CONCLUSIONS: tEMD appears to be a feasible minimally invasive and effective treatment for patients with SETs originating from the MP layer of the esophagus and cardia.

Feasibility and safety of functional cholecystectomy by pure NOTES: a pilot animal study.

BACKGROUND: NOTES cholecystectomy has become one of the hottest areas of research. But most of the cases need the assistance of the laparoscope. This study is conducted to evaluate the feasibility and safety of a newly proposed operative method-functional cholecystectomy by pure NOTES. MATERIALS AND METHODS: The functional cholecystectomy was performed on eight female miniature pigs. An incision was made on the vaginal wall, and an endoscope was inserted into the peritoneal cavity to create a pneumoperitoneum to expose the intra-abdominal viscera, gallbladder, and cystic duct. The cystic duct was isolated and closed with a clip. Then, an injection needle was inserted into the gallbladder to suck up the bile. After the gallbladder was washed with saline, an incision was made on the wall of the gallbladder, and the tip of the endoscope was inserted into the gallbladder cavity. After the endoscope was withdrawn, the gallbladder incision was closed with clips in four pigs and was suspended in the other four pigs. The vaginal incision was closed with clips. All the animals were closely monitored and euthanized 28 days after the procedure. Necropsy was performed. RESULTS: The functional cholecystectomy was successfully completed in all eight pigs. No severe intraoperative complications occurred. The animals recovered well postoperatively. At necropsy, no macroscopic signs of intraperitoneal infection or bile leakage in the peritoneal cavity were observed, and the clips were still present on the cystic duct in a good position in all cases. The gallbladder incision healed, with no sign of bile leakage or injury to the adjacent organs. CONCLUSIONS: We successfully performed the functional cholecystectomy by transvaginal approach on pigs, which appears to be feasible, safe, and convenient. Functional cholecystectomy provides a new fitting path to pure NOTES.