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Superficial duodenal epithelial tumors are emerging targets for endoscopic submucosal dissection (ESD). However, it is unknown how competence is achieved in duodenal ESD. This study aimed to elucidate the learning curve for duodenal ESD.This retrospective observational study included 100 consecutive patients who underwent duodenal ESD by a single endoscopist between March 2014 and September 2021. The primary outcome was to define the learning curve for duodenal ESD by an endoscopist with sufficient non-duodenal ESD experience. Cumulative sum (CUSUM) curve analysis was used to assess the learning curve in terms of procedural speed. Comparative analyses of phases identified using the CUSUM method were performed.In total, 98 patients were included in the analysis. Evaluation of the cumulative sum curve revealed four distinct phases in the graph: phase I, cases 1-25 (learning phase); phase II, cases 26-47 (proficiency phase); phase III, cases 48-72 (mastery phase); and phase IV, cases 73-98 (after introduction of general anesthesia). The median procedural speed was significantly faster in phase II than in phase I (11.1 mmDuodenal ESD requires 25 cases to gain proficiency and 50 to achieve mastery even for an endoscopist with extensive non-duodenal ESD experience.

Endoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC.We analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes.We examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p 0.99).ME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.

Endoscopic resection (ER) for early gastric cancer (EGC) can preserve the stomach; however, the remaining stomach can develop second gastric cancer. Few reports have prospectively investigated the incidence and treatment outcomes of second gastric cancer.This post-hoc analysis used the dataset of the single-arm confirmatory trial, JCOG0607. The key inclusion criteria for JCOG0607 were solitary differentiated-type EGC and no previous gastrectomy or endoscopic treatment for EGC. Three hundred seventeen patients who underwent curative ER were included in this study. Surveillance endoscopy was performed 1 to 3 months after the initial ER and subsequently annually for at least 5 years. A lesion detected ≤1 year and1 year after the initial ER was defined as overlooked gastric cancer (OGC) and metachronous gastric cancer (MGC), respectively.During a median follow-up period of 6.0 years (interquartile range, 5.1-7.0), 30 OGCs and 61 MGCs were detected in 24 and 48 patients, respectively. The cumulative incidence of OGC at 1 year and MGC at 5 years was 7.6% and 12.7%, respectively. ER and gastrectomy were performed in 85 lesions and 6 lesions, respectively. Pathologic evaluation showed 78 mucosal cancers, 12 submucosal cancers, and 1 advanced cancer. Eventually, 28 OGCs and 52 MGCs fulfilled the pathologic criteria for curative ER.Our study was the first to reveal the actual incidence of second gastric cancer after curative ER for differentiated-type gastric cancer. Most lesions could be treated with ER. Continuous endoscopic surveillance after curative ER is important to detect second gastric cancer.

Endoscopic resection (ER) is feasible for treating well-circumscribed dysplasia in patients with ulcerative colitis (UC). However, long-term prognosis of ER for high-grade dysplasia (HGD) in patients with UC remains unclear. We aimed to evaluate the long-term prognoses of ER for HGD compared with low-grade dysplasia (LGD) and verify the feasibility of ER and follow-up with surveillance colonoscopy for HGD.An observational, single-center retrospective study included 38 and 22 patients with LGD and HGD who were followed-up with surveillance colonoscopy after ER. We evaluated the cumulative incidence rate of metachronous HGD or colorectal cancer (CRC) and identified the characteristics of metachronous dysplasia.The median follow-up period was 56 months, and surveillance colonoscopies were performed 3.6 times (mean). The 5-year cumulative incidence rate of HGD/CRC was relatively high in HGD (24.6%) than in LGD (13.7%), but the difference was not significant (Our results suggest that ER and follow-up with surveillance colonoscopy is feasible in patients with HGD when histological complete resection is achieved.

Summary Our study aimed to compare the treatment outcomes between endoscopic submucosal dissection (ESD) with an insulated-tip knife (ESD-IT) and a needle-type knife (ESD-N) for large superficial esophageal neoplasms, as no study of this kind has been previously reported. We used the dataset of a multicenter, randomized controlled trial that compared conventional ESD (C-ESD) and traction-assisted ESD (TA-ESD) for superficial esophageal neoplasms. We compared the procedural outcomes between ESD-IT and ESD-N in a post hoc analysis and conducted sub-analyses based on traction assistance and electrical knife type. We included 223 (EST-IT, n = 169; ESD-N, n = 54) patients with no significant differences in baseline characteristics. The operator handover rate due to ESD difficulties was significantly higher in ESD-N (ESD-IT = 0.6% vs. ESD-N = 13.0%, P = 0.001), while the injection volume was significantly higher in ESD-IT than in ESD-N (40.0 vs. 20.5 mL, P 0.99; and complication rate: 1.8% vs. 3.7%, P = 0.60 for ESD-IT and ESD-N, respectively). In the sub-analyses, the handover rate was significantly lower with TA-ESD than with C-ESD for ESD-N (3.2% vs. 26.1%, P = 0.034), and a significantly smaller injection volume was used in TA-ESD than in C-ESD for ESD-IT (31.5 vs. 47.0 mL, P

Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups—the very low-risk (VLR)-group and risk (R)-group—based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features—frequently observed in the posterior wall of the middle thoracic esophagus—with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.

Background The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. Methods In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. Results The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P Conclusion The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.

Backgrounds : Endoscopic full-thickness resection (EFTR) without laparoscopic assistance—pure EFTR—is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been applied outside of China due to concerns about pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing regarding its procedure. This study aimed to evaluate the efficacy and safety of endoscopic resection with one port placement (EROPP) for gastric GISTs. Methods This retrospective study included 14 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2021. One camera port was inserted in the umbilicus before starting the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layer around the lesion by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect with an over-the-scope-clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety. Results All procedures were completed successfully without conversion to laparoscopic surgery. The median size of resected tumors was 23 mm (range, 10–35 mm) and the median procedure time was 37 min (range, 22–95 min). The rates of en bloc and curative resection were 100% and 86%, respectively. In two cases, another port was added to aspirate leaking fluid or to check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful and no adverse events were reported Conclusions EROPP is a safe and minimally invasive treatment for gastric GISTs and seems to be suitable as a pure EFTR procedure.

The multi-institutional, single-arm, confirmatory trial (JCOG0607) showed excellent efficacy of endoscopic submucosal dissection (ESD) for the expanded indication of intramucosal intestinal-type early gastric cancer (EGC), which consists of two groups; the lesions 2 cm if clinical finding of ulcer (cUL)-negative or those ≤ 3 cm if cUL-positive because of the expected low risk of lymph node metastasis. However, the proportion of non-curative resections (NCR) requiring additional surgery was high (32.4%). This post hoc analysis aimed to explore the clinical factors associated with NCR.As the expanded indication includes two different groups, we explored the clinical factors associated with NCR separately in cUL-negative ( 2 cm) and cUL-positive (≤ 3 cm) groups using the log-linear model.Two hundred sixty cUL-negative and 206 cUL-positive EGCs were analyzed. The proportions of NCR were 33.8% in the cUL-negative group and 29.6% in the cUL-positive group. A multivariable analysis demonstrated that moderately differentiated predominant histology diagnosed in pre-treatment biopsy (risk ratio (RR), 1.93, 95%CI 1.34-2.77, P0.001) and lesion in the upper stomach (RR, 1.75, 95%CI 1.03-2.96, P=0.038) in the cUL-negative EGCs, and tumor size 2 cm (RR, 1.78, 95%CI 1.22-2.58, P=0.003) and female sex (RR, 1.62, 95%CI 1.07-2.44, P=0.021) in the cUL-positive EGCs were independent factors associated with NCR.Clinical risk factors associated with NCR were different between cUL-negative and cUL-positive EGCs. To avoid NCR, we need to take these factors into account when deciding expanded indication for ESD.

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.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.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%).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.

We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study.We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative,2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C).Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS.ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Superficial nonampullary duodenal epithelial tumors (SNADETs) have become frequently detected and referred for endoscopic resection (ER). However, optimal treatment methods and long-term outcomes after ER of SNADETs have not been fully elucidated. We aimed to clarify them by analyzing our large cohort of patients with SNADETs.We enrolled 190 consecutive tumors from 189 patients undergoing ER between January 2004 and September 2019. Cases were stratified into endoscopic submucosal dissection (ESD), conventional endoscopic mucosal resection, (CEMR) and underwater endoscopic mucosal resection (UEMR). Baseline characteristics and short-term outcomes were compared between the groups. Long-term outcomes were also investigated with a median follow-up of 36 months.ESD significantly exceeded CEMR (96.4% vs. 52.9%;While tumors ≤10 mm seem to be good indications for endoscopic mucosal resection, ESD should be considered for larger tumors to better achieve complete resection. Patients with submucosal invasive carcinomas have a great risk of cancer death. Therefore, a close follow-up and an additional treatment are desirable.

BACKGROUND Postoperative delayed bleeding (PDB) after gastric endoscopic submucosal dissection (ESD) is the most common adverse event in patients receiving antithrombotics even with second-look endoscopy. Moreover, with the increasing prevalence of cardiovascular and cerebrovascular diseases in an aging population with associated lifestyle-related diseases, an increasing number of patients receive antithrombotics. Several attempts have been made to prevent PDB in aging population; however, a consensus has yet to be reached. AIM To examine the efficacy of third-look endoscopy (TLE) for PDB prevention. METHODS One hundred patients with early gastric neoplasms receiving antithrombotics were prospectively enrolled and subjected to ESD with TLE between February 2017 and July 2019. The primary endpoint was PDB rate, which was compared with our preset threshold. Furthermore, we divided the bleeding period into early-and late-onset PDB (E-PDB and L-PDB, respectively) and analyzed its rate. As a secondary analysis, we compared PDB rates with those of a historical control group, using propensity score matching, and calculated the PDB rates per antithrombotic agent use in each group. RESULTS In total, 96 patients and 114 specimens were finally evaluated. The overall PDB rate was 7.9% (9/114) [90%CI: 4.7-13.1, P = 0.005], while the late-and early-onset PDB rates (L-PDB and E-PDB) were 5.3% [90%CI: 2.7-9.9, P < 0.0001] and 2.6% [90%CI: 1.1-6.4, P = 0.51], respectively. Propensity score matching generated 58 matched pairs for TLE and control groups. No differences were found in overall PDB incidence (10.3% vs 20.7%, P = 0.12), whereas L-PDB occurrence significantly differed (5.2% vs 17.2%, P = 0.04) between groups. Considering antithrombotics’ use, the overall PDB rate was higher for direct oral anticoagulants and multiple antithrombotics in the control group, while L-PDB incidence was lower in the TLE group for these agents (8.7% vs 23.1% and 5.0% vs 29.4%, respectively). CONCLUSION TLE for gastric ESD reduces overall PDB, and especially L-PDB incidence, among patients receiving antithrombotics.

The European Society of Gastrointestinal Endoscopy (ESGE) and the Japan Gastroenterological Endoscopy Society (JGES) give no specific recommendations on the best treatment for colorectal neoplasia involving the dental line (DLCN).Aim of this study was to analyse efficacy and safety of Endoscopic Submucosal Dissection in the treatment of colorectal neoplasia involving the dentate line (DLCN) compared to non-DLCN.Retrospective study.We retrospectively evaluated all consecutive patients undergoing ESD for rectal neoplasia at two endoscopical tertiary referral centers (Italy and Japan) from January 2008 to December 2019.Anthropometric, clinical, procedural, and follow-up data was collected, analysed, and compared between patients with DLCN and patients with non-DLCN.Overall, 314 patients were enrolled (163 female, 51.9%). Mean age was 68 years (range, 32-92 years). En-bloc resection was achieved in 311/314 (99%) patients. Lesion size was higher in DLCN group than in the non-DLCN group (46.1 vs 38.9 mm;Retrospective study design.ESD seems to be safe and effective in the treatment of colorectal neoplasia involving the dentate line and can be considered the best therapeutic strategy.

Aim Although rectal neuroendocrine tumors (NETs) are considered to be rare low‐grade malignancies when lymph node metastasis (LNM) is present, their degree of malignancy is comparable to that of colorectal cancer (CRC). However, it remains unclear as to which patients require radical lymph node dissection. The aim of this study was to elucidate the risk factors for LNM and develop a risk‐scoring system for LNM to help determine appropriate therapeutic approaches. Methods In this study, we examined 103 patients with rectal NETs who underwent local resection (n = 55) or radical resection with LN dissection (n = 48). We evaluated each pathological feature, including the depth of submucosal invasion (SM depth) and tumor budding grade. Results According to our univariate analyses and previous reports, the significant five risk factors for LNM were weighted with point values: 2 points for tumor size ≥ 15 mm and muscularis invasion, and 1 point each for SM depth ≥ 2000 µm, positive lymphovascular invasion, budding grade 3, and vertical margin. The area under the receiver operating curve for the scoring system was 0.899 (95% CI: 0.843‐0.955). When a score of 2 was used as the cut‐off value, the sensitivity and specificity for the prediction of LNM were 100% and 72.1%, respectively. Conclusions The risk‐scoring system for LNM of rectal NETs showed high diagnostic performance. Using this risk‐scoring system, it is possible to predict the risk of LNM and thereby potentially avoid unnecessary surgery. Further prospective external validation studies should be performed. The study was registered in the Japanese Clinical Trials Registry as UMIN000036658., The risk‐scoring system for LNM of rectal NETs could predict the risk of LNM and thereby potentially avoid unnecessary surgery.

OBJECTIVES Clinicopathologic characteristics and treatment outcomes of mixed-histological-type (MT) early gastric cancers (EGCs) treated with endoscopic submucosal dissection (ESD) have not been sufficiently elucidated. We aimed to clarify them in comparison with pure-histological-type EGCs. METHODS We used 3022 consecutive EGCs in 2281 patients treated with ESD from our prospectively maintained database. Cases were stratified into four groups according to the final diagnosis of the resected specimen are as follows: 2780 pure differentiated-type (DT), 127 DT-predominant MT (D-MT), 87 pure undifferentiated-type (UDT), and 28 UDT-predominant MT (U-MT). Clinicopathologic characteristics and treatment outcome were compared between pure DT and D-MT, and between pure UDT and U-MT separately. Risk factors for deep submucosal invasion, lymphovascular invasion, and a final diagnosis of MT were identified using multivariate analysis. RESULTS Both D-MT (41.7 vs. 92.0%; P

Objective This study compared the clinicopathological features and treatment outcomes of patients with primary early gastric cancers (EGCs) who had undergone Helicobacter pylori eradication and endoscopic submucosal dissection (ESD) with those of patients who were H. pylori-positive and had undergone ESD. Additionally, we investigated the incidence of metachronous cancer in these patients. Methods We retrospectively analyzed 1849 EGCs in 1407 patients who underwent ESD whom 201 primary EGCs were detected after H. pylori eradication (eradication group) and 1648 primary EGCs were detected in patients infected with H. pylori (infection group). We evaluated the clinicopathological features and treatment outcomes of the first ESD. We next divided 938 patients whose follow-up periods were >1 year into three groups, an eradication group (n = 61), an infection group (n = 562), and an eradication after ESD group (n = 315). The groups' cumulative metachronous occurrence rates were determined. Results The eradication group's median tumor size was significantly smaller, and the tumors were significantly more likely to be flat/depressed than those in the infection group. The groups did not differ regarding the treatment outcomes. The cumulative incidence of metachronous cancer was significantly higher in the eradication group than in the eradication after ESD group (P = 0.0454) and in the infection group than in the eradication after ESD group (P = 0.0233). Conclusion The treatment outcomes for EGC in the eradication group were favorable. The higher incidence of metachronous cancer in the eradication group suggests that careful endoscopic follow-up examinations are required.

Clinicopathological features of early gastric cancers arising in Helicobacter pylori uninfected patients

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.

Thrombotic microangiopathy (TMA) is a serious complication following kidney transplantation. Although intestinal TMA is a major organ injury and causes abdominal pain, diarrhea and bloody stools, the clinical and endoscopic characteristics of small intestinal TMA remain unclear. Here, we report a drug-induced small intestinal TMA, which did not meet the laboratory-defined TMA criteria but was diagnosed by balloon-assisted enteroscopy (BAE). A 32-year-old woman who underwent kidney transplantation at the age of 10 years complained of abdominal pain, diarrhea and bloody stools one month after starting everolimus (EVE) as an immunosuppressant. Although she did not meet the diagnostic criteria for TMA serologically, BAE revealed a circumferential ulcer in the jejunum, and the pathological findings of a biopsy specimen showed microvascular thrombi, compatible with intestinal TMA. Her symptoms improved upon the discontinuation of EVE, demonstrating that EVE can cause drug-induced intestinal TMA. The present case suggests that BAE should be performed when abdominal pain, diarrhea, and bloody stools occur in patients receiving immunosuppressive medication following kidney transplantation, even if there is no evidence of TMA according to the laboratory definition.

Background and Aims This study aimed to evaluate the efficacy of perioperative antibiotics against post–endoscopic submucosal dissection (ESD) coagulation syndrome (PECS) in patients undergoing colorectal ESD. Methods A prospective, multicenter, randomized controlled, parallel, superiority trial was conducted at 21 Japanese tertiary institutions. Patients with superficial colorectal lesions ≥20 mm and those undergoing ESD management for a single lesion were eligible. Patients with perforation during and after ESD were withdrawn. Before the ESD procedure, participants were randomly assigned (1:1) to either undergo conventional treatment (nonantibiotic group) or investigational treatment (antibiotic group). In the antibiotic group, 3 g of ampicillin-sulbactam was administered just before, 8 hours after, and the morning after ESD. The primary endpoint was the incidence of PECS. The onset of PECS was defined as localized abdominal pain (both spontaneous pain and tenderness) and fever (≥37.6°C) or inflammatory response (leukocytosis [≥10,000 cells/μL] or elevated C-reactive protein level [≥.5 mg/dL]). Results From February 5, 2019 to September 7, 2020, 432 patients were enrolled and assigned to the antibiotic group (n = 216) or nonantibiotic group (n = 216). After withdrawal of 52 patients, 192 in the antibiotic group and 188 in the nonantibiotic group were analyzed. PECS occurred in 9 of 192 patients (4.7%) in the antibiotic group and 14 of 188 patients (7.5%) in the nonantibiotic group, with an odds ratio of .61 (95% confidence interval, .23-1.56; P = .29). Conclusions Perioperative use of antibiotics was not effective in reducing the incidence of PECS in patients undergoing colorectal ESD. (Clinical trial registration number: UMIN000035178.)

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

Background Bleeding after endoscopic submucosal dissection (ESD) is a severe adverse event. Recent reports have described the efficacy of the endoscopic shielding method with polyglycolic acid (PGA) sheets and fibrin glue for the prevention of adverse events after ESD. The aim of the present study was to investigate whether the PGA shielding method provides additional benefit in preventing post-ESD bleeding compared with standard care. Methods This was a prospective, multicenter, randomized controlled trial. Patients at high risk of post-ESD bleeding were enrolled in the study. Before ESD, patients were randomized to either the PGA group or the control group. After completing ESD in the PGA group, PGA sheets were placed onto the ulcer floor and adhered with fibrin glue. The primary end point was the post-ESD bleeding rate. Results 140 eligible patients were enrolled from September 2014 to September 2016, and 137 were included in the intention-to-treat analysis (67 in the PGA group and 70 in the control group). Post-ESD bleeding occurred in three patients (4.5 %) in the PGA group and in four patients (5.7 %) in the control group; there was no significant difference between the two groups (P > 0.99). Post-ESD bleeding tended to occur later in the control group than in the PGA group (median 12.5 days [range 8 – 14] vs. 2 days [range 0 – 7], respectively). Conclusion The PGA shielding method did not demonstrate a significant effect on the prevention of post-ESD bleeding.

Background Endoscopic submucosal dissection (ESD) is the treatment of choice for colorectal superficial neoplasia, but certain anatomical locations are challenging even for skilled endoscopists. Ileocecal valve (ICV) is considered a technically challenging site for ESD. Objective Aim of this study was to analyze efficacy and safety of Endoscopic Submucosal Dissection in the treatment of colorectal neoplasia involving the ileocecal valve (ICV) Design Retrospective study. Patients We retrospectively evaluated 1507 consecutive patients undergoing ESD at two tertiary referral centres for ESD (Italy and Japan) from January 2008 to March 2020. Main Outcome Measures Demographic, clinical, procedural, and follow-up data was collected, analysed, and compared between patients with ileocecal valve lesions (ICVL) and patients with non-ICVL. Results Overall, 1507 patients were enrolled (872 M, 57.8%), of these 53 patients had lesions involving the ICV. Mean age was 70.2 years (range, 53–83 years). En-bloc resection was achieved in 52 (98%) patients. The median specimen size of ICVL was 36.4 mm (range, 8–80 mm), significantly smaller than non-ICVL (p = 0.005). Procedure time was significantly longer in the ICVL group, (71.3 vs. 58.9 min; p = 0.03). Non Granular Type Laterally Spreading Tumors (LST-NG) were significantly more frequent in the ICVL group compared to rectum (52.8% vs. 25.7; p = 0.0001). En-bloc resection rate in the ileocecal region did not differ significantly between groups (p = 0.20). Complications such as perforation and postoperative occurred respectively in 3/53 (5.7%) and 1/53 (2%) patient, and were treated conservatively. At first surveillance colonoscopy performed at 6 months, recurrent adenoma was detected in 2/53 patients (3.9%). Conclusions ESD is safe and effective for the treatment of colorectal neoplasia involving the ileocecal valve if performed by expert endoscopist in referral centres.

While endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC. The key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC. Three hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1–99.8). ESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.

BACKGROUND AND AIM Endoscopic resection is feasible for superficial tumors in patients with ulcerative colitis; however, endoscopic resection options have not been evaluated comprehensively. We evaluated the efficacy and safety of endoscopic submucosal dissection and endoscopic mucosal resection, and decision making regarding endoscopic resection options for patients with ulcerative colitis. METHODS Endoscopically treated tumors from patients with ulcerative colitis were analyzed retrospectively. We evaluated en bloc and R0 resection, adverse events, local tumor recurrence, and metachronous lesion occurrence rates. RESULTS We examined 102 tumors (mean size, 12 mm; non-polypoid, 55 tumors) from 74 patients with ulcerative colitis, of whom, 39 and 63 underwent endoscopic submucosal dissection and endoscopic mucosal resection, respectively. The R0 resection rate was significantly higher for endoscopic submucosal dissection (97%) than for endoscopic mucosal resection (80%) (P = 0.0015). For 11-20-mm tumors, the R0 resection rate was significantly higher for endoscopic submucosal dissection (94%) than for endoscopic mucosal resection (55%) (P = 0.0027); the endoscopic submucosal dissection and endoscopic mucosal resection R0 rates did not differ for ≤ 10-mm tumors. The non-polypoid tumor R0 resection rates were significantly higher for endoscopic submucosal dissection (100%) than for endoscopic mucosal resection (65%) (P

BACKGROUND The undifferentiated-type (UDT) component profoundly affects the clinical course of early gastric cancers (EGCs). However, an accurate preoperative diagnosis of the histological types is unsatisfactory. To date, few studies have investigated whether the UDT component within mixed-histological-type (MT) EGCs can be recognized preoperatively. AIM To clarify the histopathological characteristics of the endoscopically-resected MT EGCs for investigating whether the UDT component could be recognized preoperatively. METHODS This was a single-center retrospective study. First, we attempted to clarify the histopathological characteristics of the endoscopically-resected MT EGCs with emphasis on the UDT component. Histopathological examination investigated each lesion’s UDT component: (1) Whole mucosal layer occupation of the UDT component; (2) UDT component exposure to the surface of the mucosa; and (3) existence of a clear border between the differentiated-type and UDT components. Then, preoperative endoscopic images with magnifying endoscopy with narrow-band imaging (ME-NBI) were examined to identify whether the endoscopic UDT component finding was recognizable within the area where it was present in the histopathological examination. The preoperative biopsy results and comparative relationships between endoscopic and histopathological findings were also examined. RESULTS In the histopathological examination, the whole mucosal layer occupation of the UDT component and exposure of the UDT component to the mucosal surface were observed in 67.3% (33/49) and 79.6% (39/49) of samples, respectively. A clear distinction of the border between the differentiated-type and UDT components could not be drawn in 65.3% (32/49) of MT lesions. In the endoscopic examination, the preoperative endoscopic images showed that only 24.5% (12/49) of MT EGCs revealed the UDT component within the area where it was present histopathologically. Histopathological UDT predominance was the single significant factor associated with the presence of the endoscopic UDT component finding (61.5% vs 11.1%, P = 0.0009). Only 26.5% (13/49) of the lesions were diagnosed from the pretreatment biopsy as having a UDT component. Combined results of the pretreatment biopsy and ME-NBI showed the preoperative presence of the UDT component in 40.8% (20/49) of MT EGCs. CONCLUSION Recognition of a UDT component within MT EGCs is difficult even when pretreatment biopsy and ME-NBI are combined. Endoscopic resection plays a significant role in both treatment and diagnosis.

BACKGROUND Persistent Helicobacter pylori (H. pylori) infection causes chronic inflammation, atrophy of the gastric mucosa, and a high risk of developing gastric cancer. In recent years, awareness of eradication therapy has increased in Japan. As H. pylori infections decrease, the proportion of gastric cancers arising from H. pylori uninfected gastric mucosa will increase. The emergence of gastric cancer arising in H. pylori uninfected patients though rarely reported, is a concern to be addressed and needs elucidation of its clinicopathological features. AIM To evaluate the clinicopathological features of early gastric cancer in H. pylori-uninfected patients. METHODS A total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019. Of these, 30 lesions in 30 patients were diagnosed as H. pylori-uninfected gastric cancer (HpUIGC). We defined a patient as H. pylori-uninfected using the following three criteria: (1) The patient did not receive treatment for H. pylori, which was determined by investigating medical records and conducting patient interviews; (2) Lack of endoscopic atrophy; and (3) The patient was negative for H. pylori after being tested at least twice using various diagnostic methods, including serum anti-H. pylori-IgG antibody, urease breath test, rapid urease test, and microscopic examination. RESULTS The frequency of HpUIGC was 1.2% (30/2462) for the patients in our study. The study included 19 males and 11 females with a mean age of 59 years. The location of the stomach lesions was divided into three sections; upper third (U), middle third (M), lower third (L). Of the 30 lesions, 15 were U, 1 was M, and 14 were L. Morphologically, 17 lesions were protruded and flat elevated type (0-I, 0-IIa, 0-IIa + IIc), and 13 lesions were flat and depressed type (0-IIb, 0-IIc). The median tumor diameter was 8 mm (range 2-98 mm). Histological analysis revealed that 22 lesions (73.3%) were differentiated type.The HpUIGC lesions were classified into fundic gland type adenocarcinoma (7 cases), foveolar type well-differentiated adenocarcinoma (8 cases), intestinal phenotype adenocarcinoma (7 cases), and pure signet-ring cell carcinoma (8 cases). Among 30 HpUIGCs, 24 lesions (80%) were limited to the mucosa; wherein, the remaining 6 lesions showed submucosal invasion. One of the submucosal invasive lesions showed more than 500 μm invasion. The mucin phenotype analysis identified 7 HpUIGC with intestinal phenotype and 23 with gastric phenotype. CONCLUSION We elucidated the clinicopathological characteristics of HpUIGC, revealing recognition not only undifferentiated-type but also differentiated-type. In addition, intestinal phenotype tumors were also observed and could be an important tip.

Objectives A Japanese multicenter prospective cohort study examining endoscopic resection (ER) for early gastric cancer (EGC) has been conducted using a Web registry developed to determine the short-term and long-term outcomes based on absolute and expanded indications. We hereby present the short-term outcomes of this study. Methods All consecutive patients with EGC or suspected EGC undergoing ER at 41 participating institutions between July 2010 and June 2012 were enrolled and prospectively registered into the Web registry. The baseline characteristics were entered before ER, and the short-term outcomes were collected at 6 months following ER. Results Nine thousand six hundred and sixteen patients with 10 821 lesions underwent ER (endoscopic submucosal dissection [ESD]: 99.4%). The median procedure time was 76 min, and R0 resections were achieved for 91.6% of the lesions. Postoperative bleeding and intraoperative perforation occurred in 4.4% and 2.3% of the patients, respectively. Significant independent factors correlated with a longer procedure time (120 min or longer) were as follows: tumor size >20 mm, upper-third location, middle-third location, local recurrent lesion, ulcer findings, gastric tube, male gender, and submucosa. Histopathologically, 10 031 lesions were identified as common-type gastric cancers. The median tumor size was 15 mm. Noncurative resections were diagnosed for 18.3% of the lesions. Additional surgery was performed for 48.6% (824 lesions) of the 1695 noncurative ER lesions with a possible risk of lymph node (LN) metastasis. Among them, 64 (7.8%) exhibited LN metastasis. Conclusions This multicenter prospective study showed favorable short-term outcomes for gastric ESD.

Background Endoscopic resection is recommended for non-ampullary duodenal neuroendocrine tumors (NAD-NETs) ≤10 mm in diameter and confined to the submucosal layer, without lymph node or distant metastasis. However, the efficacy and safety of endoscopic submucosal dissection (ESD) for NAD-NET remains unclear. The aim of this study was to assess the short-term efficacy and safety and the long-term outcomes of ESD for NAD-NET. Methods Eight patients with 8 NAD-NETs who underwent ESD between 2015 and 2018 were included. The indications for ESD were: i) tumor ≤10 mm in diameter; ii) NET G1; iii) confined to the submucosal layer; and iv) without lymph node or distant metastasis. We retrospectively assessed the short- and long-term outcomes and safety. Results The median patient age was 69 (48-76) years. All tumors were located in the duodenal bulb and showed 0-Is morphology. The median size was 6.4 (3-9.3) mm. The rates of en bloc resection, histologically free horizontal and vertical margins, and curative resection were 100%, 88%, and 88%, respectively. Intraoperative and postoperative perforation each occurred in 13% of patients, all of whom were treated conservatively and avoided emergent surgery. Delayed bleeding was not observed. No local, lymph node or distant recurrence was observed during a median follow-up period of 34 (18.5-62.5) months. Conclusions The rates of en bloc and curative resection, and histologically free margins were sufficiently high. Although intraoperative and postoperative perforations occurred, emergency surgery was not needed. The results show that ESD is an efficacious and safe treatment for NAD-NET.

Aim To evaluate whether patients with T1 esophageal squamous cell carcinoma receiving definitive radiotherapy can be managed without concurrent chemotherapy, and the role of 18F-fluorodeoxyglucose positron-emission tomography with computed tomography (FDG-PET/CT) in demonstrating local control (LC). Patients and methods Twenty-four out of 37 patients with newly-diagnosed T1 EC treated with definitive radiotherapy between July 2009 and July 2016 were retrospectively analyzed. FDG-PET/CT was performed before treatment. Eleven patients were assigned to a concurrent chemoradiotherapy (CRT) group. Thirteen were placed in a no-CRT group. The two groups were compared and univariate analysis of clinical factors influencing the prognosis in each group was conducted. Results Mean radiotherapy doses were 59.2 Gy in the no-CRT group and 55.5 Gy in the CRT group (p=0.025). Overall survival, disease-free survival, and LC rates at 2 years were lower in the no-CRT group compared to the CRT group. Disease-free survival and LC rates at 2 years were significantly lower in the patients with FDG-avid primary tumor in the no-CRT group (p=0.002 and p=0.002, respectively). All patients with FDG-avid primary tumors in the no-CRT group developed local recurrence. Conclusion It is important to note that all patients with FDG-avid primary tumor in the no-CRT group developed local recurrence. This would suggest that concurrent chemotherapy is an integral part of disease management in patients with T1 esophageal squamous cell carcinoma.

Background and Aims Colorectal neoplasms with submucosal fibrosis are the most challenging targets of endoscopic resection. Water pressure endoscopic submucosal dissection (WP-ESD) is a recently introduced procedure that has several advantages over conventional endoscopic submucosal dissection (C-ESD). This study aimed to assess the efficacy and safety of WP-ESD for fibrotic colorectal neoplasms. Methods This retrospective observational study investigated 133 colorectal neoplasms expected to have submucosal fibrosis that were resected by WP-ESD or C-ESD between April 2012 and April 2020. Eighty-seven lesions after endoscopic or surgical treatment, 18 with biopsy scar with fold convergence and 28 in patients with ulcerative colitis, were included. The differences in treatment outcomes, including procedure time and adverse event proportions, between the WP-ESD and C-ESD groups were analyzed. The clinical course after perforation using WP-ESD was also evaluated, including postprocedural multidetector CT findings obtained immediately after WP-ESD. Results Severe submucosal fibrosis was observed in 96 lesions (72.2%). The median procedure time was significantly shorter in the WP-ESD group than in the C-ESD group (43.5 minutes [interquartile range {IQR}, 32.8-73] vs 72 minutes [IQR, 45-105]; P = .0041). The multivariate analysis revealed WP-ESD as an independent factor for a short procedure time (odds ratio, 2.90; 95% confidence interval, 1.28-6.55). The proportions of post-ESD electrocoagulation syndrome (11.6% vs 13.1%) and perforation (20.4% vs 22.8%) were similar between the groups. Four of 11 patients with perforation who underwent WP-ESD showed fluid collection on postprocedural multidetector CT images. Conclusions WP-ESD can shorten procedure time for treating fibrotic colorectal neoplasms.