Endoscopic resection for gastric submucosal tumors: Japanese multicenter retrospective study.

OBJECTIVES: Limited information is available on the efficacy and safety of endoscopic resection (ER) of gastric submucosal tumors (SMTs) in Japanese endoscopic practice where ER for gastric tumors is extremely popular. METHODS: We conducted this study to elucidate the current scenario of ER for gastric SMTs in Japanese endoscopic practice. Patients (from 12 institutions) with gastric SMTs who underwent ER were enrolled from the first case until August 2020. RESULTS: We enrolled 117 patients with 118 lesions. The number of patients who underwent ER increased over the years. The mean endoscopic tumor size was 20 ± 7.2 (8-40) mm. The growth type was primarily intraluminal (90%). The mean resection and wound closure times were 58 ± 38 (range, 12-254) min and 31 ± 41 (range, 3-330) min, respectively. Complete ER was achieved for 117 (99%) lesions. Full-thickness resection rate was 44%; however, only 12 (10%) patients required abdominal paracentesis for decompression. Endoscopic treatments were completed in 115 (97%) lesions, while three lesions required conversions to laparoscopic surgery due to luminal collapse, uncontrolled bleeding, and difficulty in defect closure. Gastrointestinal stromal tumors were the most common pathology (74%). No recurrence was observed during the mean follow-up period of 4.3 ± 2.9 years. The 5-year overall survival rate was 98.9% (95% confidence interval 97.8-100%). CONCLUSION: Performance of ER for gastric SMTs is increasing in Japan. The technique seems feasible in Japanese endoscopic practice, warranting further validation in a prospective study.

[Establishment of Mono-scaled Benefit/Risk Analysis of HPV Vaccine].

Decisions concerning approval of human papillomavirus (HPV) vaccines and their use are based on expert evaluation of the vaccines. However, the quantitative differences between vaccine benefits and risks are difficult for non-experts to understand. In this study, we developed a new method to calculate the benefits and risks of the HPV vaccines using disability-adjusted life year (DALY) as the mono-scaled weight for various benefits and risks relevant to the vaccines. We evaluated benefits as a gain of DALY values for cervical cancer and risks as the loss of DALY values for various adverse events by the vaccination. To calculate the loss of DALY values, we integrated all adverse events in the International Classification of Diseases chapters. The novel method reflected the men-women ratio of this epidemiological disease to a certain extent. Among the vaccinated women, 111372 and 477190 received a bivalent and quadrivalent vaccine, respectively. The DALY rate of cervical cancer was 148.7. The calculated benefit for the bivalent and quadrivalent vaccines was 149.1 and 638.8, respectively, and set as the theoretical maximum. The risk was calculated as 129.3 and 49.6 in the bivalent and quadrivalent vaccines, respectively. Since HPV vaccines prevent several other cancers, the benefit of the vaccination extends beyond the risk according to this new method.

Long-term outcomes of over-the-scope clip for refractory gastrointestinal diseases.

BACKGROUND: The Over-The-Scope Clip (OTSC) can effectively treat refractory gastrointestinal diseases. However, most reports have focused on short-term effectiveness. We examined clinical outcomes of the deployed clips and long-term characteristics. MATERIAL AND METHODS: Of 47 patients with OTSC treatment, 35 with follow-up periods of ≥3 months were retrospectively examined. The indications were 11 bleedings, 17 perforations, and seven fistulas. The observation period was defined as medium-term (3 to <12 months) or long-term (≥12 months). The primary outcome was the clinical success rate without disease recurrence. The secondary outcomes were the complication rate, survival duration, and clip retention rate. RESULTS: The medium- and long-term clinical success rates were 100% during the observation period (median, 44 months; range, 3-78 months). The complication rate was 2.9% (n = 1). The median survival time was 1,634 days for bleeding, 1,757 days for perforation, and 444 days for fistulas. The overall clip retention rates were 56.4%, 38.1%, 30.9%, and 25.9% after one, six, and 12 months and at the final follow-up, respectively. The average clip retention duration was 244 days in bleeding, 656 days in perforations, and 188 days in fistulas. CONCLUSIONS: Regardless of clip detachment, the OTSC can be effective in long-term.

Wafer paper and ring-mounted polyglycolic acid sheet method for shielding artificial gastric floor.

BACKGROUND: The management of postoperative bleeding, after gastric endoscopic submucosal dissection (ESD), has become particularly important because of the recent increase in antithrombotic use. Endoscopic shielding with polyglycolic acid (PGA) sheets has been shown to be effective. However, shrinkage and early displacement of the sheet remain challenges. This study aimed to determine the efficacy and safety of our developed method, named wafer paper and ring-mounted PGA sheet (WaRP). MATERIAL AND METHODS: Twenty-four patients with antithrombotic uptake who underwent the WaRP method following gastric ESD were retrospectively examined. This involved the delivery of a PGA sheet wrapped in wafer paper with ring-thread, and its fixation on the gastric floor using hemoclips. The primary outcome was the technical success rate of the WaRP, and several secondary outcomes were evaluated. RESULTS: The technical success rate of WaRP was 100%. The procedure lasted a mean of 10.5 min (SD 6.7 min). The prevalence of complete retention at follow-up endoscopy was 83.3% (20/24). There were no WaRP-associated complications, but post-ESD hemorrhage occurred in two patients undergoing hemodialysis (8.3%). CONCLUSIONS: The WaRP method is a simple and reliable means of PGA sheet delivery and placement that reduces the incidence of post-ESD hemorrhage.

Efficacy of polyglycolic acid sheeting with fibrin glue for perforations related to gastrointestinal endoscopic procedures: a multicenter retrospective cohort study.

OBJECTIVES: Gastrointestinal (GI) perforations are one of the major adverse events of endoscopic procedures. Polyglycolic acid (PGA) sheets with fibrin glue have been reported to close GI perforations. However, its clinical outcome has not yet been fully investigated; thus, we conducted a multicenter retrospective observational study to assess the efficacy of PGA sheeting for GI perforation. METHODS: The medical records of patients who underwent PGA sheeting for endoscopic GI perforations between April 2013 and March 2018 in 18 Japanese institutions were retrospectively analyzed. PGA sheeting was applied when the clip closure was challenging or failed to use. Perforations were filled with one or several pieces of PGA sheets followed by fibrin glue application through an endoscopic catheter. Nasal or percutaneous drainage and endoscopic clipping were applied as appropriate. Clinical outcomes after PGA sheeting for intraoperative or delayed perforations were separately evaluated. RESULTS: There were 66 intraoperative and 24 delayed perforation cases. In intraoperative cases, successful closure was attained in 60 cases (91%). The median period from the first sheeting to diet resumption was 6 days (interquartile range [IQR], 4-8.8 days). Large perforation size (≥ 10 mm) and duodenal location showed marginal significant relationship to higher closure failure of intraoperative perforations. In delayed perforation cases, all cases had successful closure. The median period from the first sheeting to diet resumption was 10 days (IQR, 6-37.8 days). No adverse events related to PGA sheeting occurred. CONCLUSION: Endoscopic PGA sheeting could be a therapeutic option for GI perforations related to GI endoscopic procedures.

Traction-assisted endoscopic full-thickness resection followed by O-ring and over-the-scope clip closure in the stomach: an animal experimental study.

Background and study aims Exposed endoscopic full-thickness resection (EFTR) enables the operator to obtain a sufficient surgical margin. However, insufflation leakage and secure endoscopic full-thickness closure (EFTC) remain problematic. This study aimed to evaluate the safety and feasibility of a new exposed EFTR. Patients and methods Exposed EFTR was performed for 2-cm virtual lesions in different locations of the upper stomach in four dogs. EFTR mainly involved half-circumferential EFTR of the endpoint and clip-line traction. Pulley traction was applied with the forward approach for the greater curvature. EFTC involved endoscopic ligation with O-ring closure to diminish insufflation leakage, followed by over-the-scope clip closure. Results Complete resection and technical success were achieved in all four cases. One case of intraoperative bleeding was endoscopically managed. No postoperative complications occurred in any cases. The median maximum resected size was 27.5 mm. The median procedure time of the total operation, EFTR, and EFTC was 76, 37, and 35.5 minutes, respectively. The 1-month survival rate was 100 %. Conclusions This therapeutic strategy may lead to the establishment of exposed EFTR.

Efficacy of crystal violet for identifying the distal end in esophageal submucosal tunnel resection.

BACKGROUND: Endoscopic submucosal tunnel dissection (ESTD) has recently been an effective procedure for resecting large early esophageal neoplasm. However, excessive dissection beyond the distal limit may occur because the prepared distal end often cannot be distinguished through the tunnel. This study aimed to assess the efficacy and safety of a novel crystal violet navigation (CVN) for identifying the distal end. MATERIAL AND METHODS: In the observational case series study, all 22 patients who underwent esophageal ESTD using the CVN were included. When setting the distal end, the distal incision line was dyed purple using a crystal violet solution. The rates of purple color identified via the tunnel, successful tunnel penetration without extra dissection, en bloc and curative resection, procedure time for ESTD and CVN, and procedure-associated complications were evaluated. RESULTS: The rates of purple color and successful tunnel penetration were both 100%. En bloc and curative resection were 100%, and 86%, respectively. The mean total procedure time was 103.9 ± 46.2 (mean ± SD) minutes, while the mean time for the CVN was 14.1 ± 3.44 s. No complications were observed. CONCLUSIONS: The simple CVN method can be a navigation tool for identifying the distal end during the ESTD procedure.

Rebleeding after placing over-the-scope clips: Rare complication of prophylactic closure after gastric endoscopic submucosal dissection.

Monopolar hemostatic forceps may still be able to treat for rebleeding with above mentioned challenging characteristics, and it is earning a lace in the new enodscopic hemostasis repertoire.

Antihypertensive drug telmisartan inhibits cell proliferation of gastrointestinal stromal tumor cells in vitro.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. The angiotensin II type 1 receptor blockers, telmisartan and candesartan, are widely used antihypertensive drugs that inhibits cancer cell proliferation; however, its underlying mechanisms in mesenchymal tumors, including GIST, remains unknown. The present study aimed to investigate the effect of telmisartan on GIST­T1 cells and its underlying mechanism. Telmisartan and candesartan inhibited the proliferation of these cells by blocking the G0 to G1 cell cycle transition, which was accompanied by a decrease in cell cycle­related proteins such as cyclin D1. Furthermore, telmisartan exposure significantly altered microRNA expression in vitro. In conclusion, telmisartan suppressed human GIST cell proliferation by inducing cell cycle arrest in vitro.

Outcomes of Endoscopic Submucosal Dissection for Subepithelial Lesions Localized Within the Submucosa, Including Neuroendocrine Tumors: A Multicenter Prospective Study.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) seems to be a reasonable option for gastrointestinal subepithelial lesions (SELs) localized within the submucosa. Indications for ESD include small neuroendocrine tumors (NETs) and indeterminate SELs. However, the prospective data regarding ESD and surveillance remain unclear. This study was performed to prospectively investigate the outcomes of ESD, including organ-specific outcomes and the mid-term prognosis. METHODS: This prospective multicenter study included 57 patients who underwent ESD for SELs localized within the submucosa [definite NETs (n = 42) and indeterminate SELs (n = 15)]. The efficacy and safety of ESD were evaluated in the whole cohort and in subgroups (NETs and indeterminate SELs). All patients were followed up. RESULTS: The rates of en bloc resection, curative resection, and complications were 98.2%, 66.7%, and 7.7% for the overall population (n=57); 100%, 61.9%, and 2.4% for NETs (n=42); and 93.3%, 80.0%, and 20.0% for indeterminate SELs (n=15), respectively. The rates of curative resection for NETs were poorer in the stomach (20%, n=5) and duodenum (33%, n=3) than in the rectum (71%, n=34). Including 11 of 16 patients with NETs who underwent a conservative approach resulting in non-curative resection, no patients developed tumor recurrence during the follow-up period (median, 24.5 months; range, 1-60 months). ESD followed by surveillance demonstrated acceptable mid-term outcomes for non-curative NETs. CONCLUSIONS: ESD can be an efficient therapy for SELs localized within the submucosa. However, gastric and duodenal ESD for NETs may be limited in terms of its curative and technical aspects. Clinicians should be aware of the potential complications of ESD for indeterminate SELs.

Endoscopic Submucosal Dissection for Neoplasia of the Greater Curvature of the Upper and Middle Stomach: J-shaped Superficial Cutting and Splashed Dissection.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) has become a standard treatment for early gastric neoplasia. However, as the upper and middle body of the greater curvature has a rich vasculature and submucosal fibrosis, ESD of neoplasia in these locations requires a specific strategy. We aimed to investigate the efficacy and safety of the J-shaped superficial cutting and splashed submucosal dissection (JSCS) technique for neoplasia of the greater curvature by comparing ESD using JSCS with conventional ESD. METHODS: Twenty-two patients who underwent ESD for gastric neoplasia affecting the upper and middle body of the greater curvature were divided into two groups for retrospective analysis. Nine patients underwent conventional ESD (c-Group), while 13 underwent ESD with JSCS (j-Group). Primary outcome was the en bloc resection rate. Secondary outcomes included complete resection (R0) rate, procedure time, perforation rate, total bleeding time, and the total number of massive bleeding events and of hemostatic forceps times applied during ESD. RESULTS: There were no significant differences between both groups (c-Group vs j-Group) in en bloc resection rate, or R0 resection rate. Compared with the c-Group, the j-Group tended to have a decreased mean procedure time (mean 133 minutes vs 74 minutes, p=0.11) and perforation rate (11% vs 0%, p=0.41). Compared with the c-Group, the j-Group had significantly fewer bleeding incidents (13.4 times vs 6.6 times, p=0.0095), shorter total bleeding time (17.6 min vs 7.4 min, p=0.036), and fewer usages of hemostatic forceps (6.3 times vs 2.4 times, p=0.026) during ESD. CONCLUSION: Endoscopic submucosal dissection with JSCS is superior to conventional ESD, as it reduces intraprocedural bleeding. This technique has the potential to become the standard strategy for neoplasia affecting the upper and middle body of the greater curvature.

Galectin-9 Induces Mitochondria-Mediated Apoptosis of Esophageal Cancer In Vitro and In Vivo in a Xenograft Mouse Model.

Galectin-9 (Gal-9) enhances tumor immunity mediated by T cells, macrophages, and dendritic cells. Its expression level in various cancers correlates with prognosis. Furthermore, Gal-9 directly induces apoptosis in various cancers; however, its mechanism of action and bioactivity has not been clarified. We evaluated Gal-9 antitumor effect against esophageal squamous cell carcinoma (ESCC) to analyze the dynamics of apoptosis-related molecules, elucidate its mechanism of action, and identify relevant changes in miRNA expressions. KYSE-150 and KYSE-180 cells were treated with Gal-9 and their proliferation was evaluated. Gal-9 inhibited cell proliferation in a concentration-dependent manner. The xenograft mouse model established with KYSE-150 cells was administered with Gal-9 and significant suppression in the tumor growth observed. Gal-9 treatment of KYSE-150 cells increased the number of Annexin V-positive cells, activation of caspase-3, and collapse of mitochondrial potential, indicating apoptosis induction. c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) phosphorylation were activated and could be involved in apoptosis. Therefore, Gal-9 induces mitochondria-mediated apoptosis of ESCC and inhibits cell proliferation in vitro and in vivo with JNK and p38 activation.

Pure laparoscopic pancreas parenchymal dissection using CUSA for distal pancreatectomy.

Although stapler dissection and closure is commonly used for laparoscopic distal pancreatectomy (LDP), it is risky in patients with thick pancreatic parenchyma or titanium allergy. We performed laparoscopic pancreatic parenchymal dissection with cavitron ultrasonic surgical aspirator (CUSA) successfully in a patient with titanium allergy. Slinging the pancreas with nylon tape delineates the surgical plane. Pancreatic parenchyma was transected by CUSA in an almost bloodless field. Pancreatic duct branches and vessels were adequately exposed and dissected with a vessel sealing system. The main pancreatic duct was closed with Hem-O-lock. CUSA is an alternative to stapler dissection during LDP in select patients.

Over-the-scope clip system: A review of 1517 cases over 9 years.

Rescue therapy for gastrointestinal (GI) refractory bleeding, perforation, and fistula has traditionally required surgical interventions owing to the limited performance of conventional endoscopic instruments and techniques. An innovative clipping system, the over-the-scope clip (OTSC), may play an important role in rescue therapy. This innovative device is proposed as the final option in endoscopic treatment. The device presents several advantages including having a powerful sewing force for closure of GI defects using a simple mechanism and also having an innovative feature, whereby a large defect and fistula can be sealed using accessory forceps. Consequently, it is able to provide outstanding clinical effects for rescue therapy. This review clarifies the current status and limitations of OTSC according to different indications of GI refractory disease, including refractory bleeding, perforation, fistula, and anastomotic dehiscence. An extensive literature search identified studies reported 10 or more cases in which the OTSC system was applied. A total of 1517 cases described in 30 articles between 2010 and 2018 were retrieved. The clinical success rates and complications were calculated overall and for each indication. The average clinical success rate was 78% (n = 1517) overall, 85% for bleeding (n = 559), 85% (n = 351) for perforation, 52% (n = 388) for fistula, 66% (n = 97) for anastomotic dehiscence, and 95% (n = 122) for other conditions, respectively. The overall and severe OTSC-associated complications were 1.7% (n = 23) and 0.59% (n = 9), respectively. This review concludes that the OTSC system may serve as a safe and productive device for GI refractory diseases, albeit with limited success for fistula.