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Abstract The incidence of duodenal tumors (DTs) is increasing. However, the mechanisms underlying its development remain unclear. Environmental factors, including the microbiome and bile acids (BAs), are believed to influence tumor development. Therefore, we conducted a single-center, prospective, observational study to investigate the potential differences between patients with DTs and healthy controls (HCs) based on these factors. In addition, the BAs in the duodenal fluid were measured using liquid chromatography-tandem mass spectrometry. We recruited 41 patients and performed 16S rRNA-seq. There was no difference in the observed ASVs or PCoA plot of Bray–Curtis dissimilarity between the DTs and HCs. The lithocholic acid concentration was significantly lower in the DT group than in the control group. The ratio of CDCA to LCA was significantly higher in patients with DTs. No significant differences in microbiota were observed between DTs and HCs. In patients with DTs, the lithocholic acid concentration in duodenal was significantly lower than in HCs.

BackgroundRespiratory syncytial virus (RSV) affects children, causing serious infections, particularly in high-risk groups. Given the seasonality of RSV and the importance of rapid isolation of infected individuals, there is an urgent need for more efficient diagnostic methods to expedite this process. ObjectiveThis study aimed to investigate the performance of a machine learning model that leverages the temporal diversity of symptom onset for detecting RSV infections and elucidate its discriminatory ability. MethodsThe study was conducted in pediatric and emergency outpatient settings in Japan. We developed a detection model that remotely confirms RSV infection based on patient-reported symptom information obtained using a structured electronic template incorporating the differential points of skilled pediatricians. An extreme gradient boosting–based machine learning model was developed using the data of 4174 patients aged ≤24 months who underwent RSV rapid antigen testing. These patients visited either the pediatric or emergency department of Yokohama City Municipal Hospital between January 1, 2009, and December 31, 2015. The primary outcome was the diagnostic accuracy of the machine learning model for RSV infection, as determined by rapid antigen testing, measured using the area under the receiver operating characteristic curve. The clinical efficacy was evaluated by calculating the discriminative performance based on the number of days elapsed since the onset of the first symptom and exclusion rates based on thresholds of reasonable sensitivity and specificity. ResultsOur model demonstrated an area under the receiver operating characteristic curve of 0.811 (95% CI 0.784-0.833) with good calibration and 0.746 (95% CI 0.694-0.794) for patients within 3 days of onset. It accurately captured the temporal evolution of symptoms; based on adjusted thresholds equivalent to those of a rapid antigen test, our model predicted that 6.9% (95% CI 5.4%-8.5%) of patients in the entire cohort would be positive and 68.7% (95% CI 65.4%-71.9%) would be negative. Our model could eliminate the need for additional testing in approximately three-quarters of all patients. ConclusionsOur model may facilitate the immediate detection of RSV infection in outpatient settings and, potentially, in home environments. This approach could streamline the diagnostic process, reduce discomfort caused by invasive tests in children, and allow rapid implementation of appropriate treatments and isolation at home. The findings underscore the potential of machine learning in augmenting clinical decision-making in the early detection of RSV infection.

Abstract Pyloric gland adenoma (PGA) is a duodenal neoplasm expressing MUC6 and is often associated with high-grade dysplasia and adenocarcinoma. MUC6 secreted from the pyloric gland cells carries unique O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). The small peptide trefoil factor 2 (TFF2) is also secreted from pyloric gland cells and binds to αGlcNAc. We recently demonstrated that αGlcNAc serves as a tumor suppressor for gastric neoplasm including PGA, but the significance of TFF2 expression remains unknown. We examined 20 lesions representing low- and high-grade PGA in 22 cases by immunohistochemistry for αGlcNAc, TFF2, MUC6, MUC5AC, MUC2 and p53. αGlcNAc, TFF2 and MUC6 were co-expressed on the cell surface and a dot-like pattern in the cytosol in low-grade PGA lesions. High-grade PGA also expressed MUC6, but reduced αGlcNAc and TFF2 expression. The ratios of αGlcNAc or TFF2 to MUC6 score in high-grade PGA were significantly lower than low-grade PGA (P

Background and study aims Colorectal endoscopic submucosal dissection (ESD) of diverticulum-associated lesions is challenging because these lesions require precise excision in narrow spaces. The water pressure method (WPM) uses active water pressure by the waterjet function under saline solution-filled conditions. This study aimed to determine the feasibility of WPM for resection of diverticulum-associated lesions. Patients and methods This was a retrospective, observational case series study. We reviewed diverticulum-associated lesions treated by ESD with WPM at our institution between June 2017 and July 2021. Diverticulum-associated lesions were classified as follows: type 1, lesions in contact with or within 3 mm of the edge of a diverticulum; type 2, lesions that partially infiltrated the interior of a diverticulum; and type 3, lesions that infiltrated the interior of and completely covered the diverticulum. We collected data on the clinical characteristics and outcomes of the lesions. Results Seven diverticulum-associated lesions were treated with ESD using WPM. The median lesion size was 37 mm (interquartile range: 25–54 mm). There were three cases of type 1, three cases of type 2, and one case of type 3. Three lesions were resected circumventing the diverticulum, and four lesions involved resection of the diverticulum. The en bloc resection and R0 resection rates were 86 %. One patient had severe fibrosis, which caused perforation, and in another patient, the diverticulum was too deep and narrow to be completely isolated. Conclusions WPM allowed for precise procedures in the diverticulum. The feasibility of WPM has been suggested for diverticulum-associated lesions, although cases have been complex.

Summary: Background: The impact of stroma-targeting therapy on tumor immune suppression is largely unexplored. An RNA oligonucleotide, STNM01, has been shown to repress carbohydrate sulfotransferase 15 (CHST15) responsible for tumor proteoglycan synthesis and matrix remodeling. This phase I/IIa study aimed to evaluate the safety and efficacy of STNM01 in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). Methods: This was an open-label, dose-escalation study of STNM01 as second-line therapy in gemcitabine plus nab-paclitaxel-refractory PDAC. A cycle comprised three 2-weekly endoscopic ultrasound-guided locoregional injections of STNM01 at doses of 250, 1,000, 2,500, or 10,000 nM in combination with S-1 (80–120 mg twice a day for 14 days every 3 weeks). The primary outcome was the incidence of dose-liming toxicity (DLT). The secondary outcomes included overall survival (OS), tumor response, changes in tumor microenvironment on immunohistopathology, and safety (jRCT2031190055). Findings: A total of 22 patients were enrolled, and 3 cycles were repeated at maximum; no DLT was observed. The median OS was 7.8 months. The disease control rate was 77.3%; 1 patient showed complete disappearance of visible lesions in the pancreas and tumor-draining lymph nodes. Higher tumoral CHST15 expression was associated with poor CD3+ and CD8+ T cell infiltration at baseline. STNM01 led to a significant reduction in CHST15, and increased tumor-infiltrating CD3+ and CD8+ T cells in combination with S-1 at the end of cycle 1. Higher fold increase in CD3+ T cells correlated with longer OS. There were 8 grade 3 adverse events. Interpretation: Locoregional injection of STNM01 was well tolerated in patients with unresectable PDAC as combined second-line therapy. It prolonged survival by enhancing T cell infiltration in tumor microenvironment. Funding: The present study was supported by the Japan Agency for Medical Research and Development (AMED).

Abstract Gastrointestinal fibrosis is a state of accumulated biological entropy caused by a dysregulated tissue repair response. Acute or chronic inflammation in the gastrointestinal tract, including inflammatory bowel disease, particularly Crohn’s disease, induces fibrosis and strictures, which often require surgical or endoscopic intervention. Recent technical advances in endoscopic surgical techniques raise the possibility of gastrointestinal stricture after an extended resection. Compared to recent progress in controlling inflammation, our understanding of the pathogenesis of gastrointestinal fibrosis is limited, which requires the development of prevention and treatment strategies. Here, we focus on gastrointestinal fibrosis in Crohn’s disease and post-endoscopic submucosal dissection (ESD) stricture, and we review the relevant literature.

Abstract Although superficial non‐ampullary duodenal epithelial tumor (SNADET) was previously considered a rare disease, in recent years, the opportunities to detect and treat SNADET are increasing. Considering the high morbidity of pancreatoduodenectomy, endoscopic resection can be a treatment option that preserves the organs and contributes maintain patients’ quality of life. Endoscopic mucosal resection (EMR) is a standard treatment for relatively small lesions in gastrointestinal tracts, however, it is difficult because submucosal fibrosis frequently occurs due to the previous biopsy. Recently, some modified EMR techniques including underwater EMR (UEMR) and cold polypectomy (CP) have been proposed. In UEMR, the duodenal lumen is filled with water or saline and resected the targe lesion with a snare without injection into the submucosa. It would be a treatment option that could reduce candidates for ESD especially SNADET less than 20 mm. CP was reported as a safe and convenient means for SNADET. It would also be one of the standard treatments for diminutive lesions, though there remain some concerns on its resectability. ESD for SNADET is technically challenging, especially with an extremely high risk of adverse event (AE) with a reported bleeding rate of more than 20% and perforation rate up to about 40%. However, modified treatment techniques including the water pressure method and pocket creation method have been reported to potentially contribute to improving outcomes of ESD. Moreover, accumulated evidence shows closing the mucosal defect significantly reduces delayed adverse events after duodenal endoscopic treatments. Further studies are warranted to elucidate curative criteria, long‐term outcomes, and appropriate surveillance strategy.

Abstract A 70‐year‐old female diagnosed with duodenal cancer was referred to our hospital. Esophagogastroduodenoscopy revealed an 80 mm flat elevated lesion was located in the inner wall of the second part of the duodenum and the lesion completely involved major papilla. Endoscopic submucosal dissection (ESD) was performed and the lesion was resected in a single piece including the part of the major papilla. The pathological examination of the resected specimen showed moderately differentiated adenocarcinoma limited in the mucosa in most parts of the lesion, however, cancer cells invaded into the submucosal layer with an invasion depth of 100 μm in only a small area. Lymph ductal involvement was confirmed in that area. Two months after ESD, pylorus‐preserving pancreatoduodenectomy combined with extended lymph node dissection was additionally performed. The postoperative pathological examination revealed lymph ductal involvement was observed in the regional lymph node. While the postoperative clinical course was uneventful, systematic metastasis was pointed out 5 months after surgery. The patient was died 9 months after surgery. Due to its rarity, the natural history of duodenal cancer has been still unclear. In this case, even a lesion with only a localized small area of submucosal invasion developed systemic metastasis, indicating the high malignant potential of duodenal cancer.

Background/Aims: The evaluation of small bowel lesions of Crohn’s disease (CD) using balloon-assisted enteroscopy (BAE) is crucial because mucosal healing is associated with a good prognosis. However, BAE procedures are invasive, requiring sedation or analgesia to reduce the patient’s pain. This study evaluated the clinical usefulness of a novel ultrathin single-balloon enteroscopy (SBE) procedure for CD. Methods: This single-center retrospective study included 102 CD patients who underwent trans-anal SBE between January 2012 and May 2018. Of these patients, 82 underwent enteroscopy using conventional SBE, while 20 underwent ultrathin SBE. Patients were analyzed using propensity score matching, with 20 patients per group. The median duration of the examination, terminal ileum intubation rate, median cecum intubation time, median insertion depth, adverse events, and sedated dose in each group were compared. Results: Before propensity score matching, the conventional SBE group had a larger number of surgical history patients than the ultrathin SBE group (p=0.05). After matching, the two groups did not significantly differ clinically. There were no significant differences in the mean duration of the examination, cecum intubation time, or terminal ileal intubation rate between ultrathin SBE and conventional SBE. The mean insertion depth of ultrathin SBE tended to be deeper than that of conventional SBE (p=0.09). The use of ultrathin SBE also reduced the sedative dose during needed for enteroscopy compared with conventional SBE (p=0.005). Conclusions: Novel ultrathin SBE may be less painful for CD patients than conventional SBE.

Background and Aim Although colorectal laterally spreading tumors (LSTs) can be classified into four subtypes, the histopathological characteristics are known to differ among these subtypes. We therefore performed a logistic regression analysis to determine whether the risk of pathological T1 cancer of large colorectal LSTs can be predicted based on factors such as endoscopic findings in a large group of patients enrolled in a multicenter study in Japan. Methods In the main study, we assessed 1236 colorectal adenomas or early cancers that were classified as LSTs measuring 20 mm or more in diameter and treated endoscopically. Logistic regression analysis was performed to determine whether factors such as the subtype of LST could be used to predict the risk of pathological T1 cancer. A validation study of 356 large colorectal LSTs was conducted to confirm the validity of the results obtained in the main study. Results The locations and tumor diameter of the LSTs in the main study were found to differ significantly according to the LST subclassification (P

Background and study aims Recent advances in endoscopic equipment and diagnostic techniques have improved the detection of dysplasia in the inflamed mucosa of patients with ulcerative colitis (UC). However, it remains difficult to endoscopically identify flat-type dysplasia which has been formerly recognized as invisible dysplasia. Patients and methods In this retrospective, single-center study, we endoscopically identified 10 cases of flat-type-predominant dysplasia by targeted biopsy among 38 intramucosal dysplasia lesions from patients with UC who underwent surgical or endoscopic resection from 2007 to 2017. Their endoscopic and histological features were examined, including color changes, intramucosal vascular density/size, and vascular endothelial growth factor (VEGF) expression. Results All flat-type-predominant dysplasias were endoscopically recognized as demarcated red-colored areas and histologically diagnosed as low- (LGDs) or high-grade dysplasias (HGDs). Immunohistochemical examination using resected specimens revealed that flat-type dysplasia was characterized by significantly increased CD34-positive vascular density (LGDs, 1.7-fold, P

Background and study aims We previously reported a case series of our first 182 colorectal endoscopic submucosal dissections (ESDs). In the initial series, 155 ESDs had been technically feasible, with 137 en bloc resections and 97 en bloc resections with free margins (R0). Here, we present long-term follow-up data, with particular emphasis on cases where either en bloc resection was not achieved or en bloc resection resulted in positive margins (R1). Patients and methods Between September 2012 and October 2015, we performed 182 consecutive ESD procedures in 178 patients (median size 41.0 ± 17.4 mm; localization rectum vs. proximal rectum 63 vs. 119). Data on follow-up were obtained from our endoscopy database and from referring physicians. Results Of the initial cohort, 11 patients underwent surgery; follow-up data were available for 141 of the remaining 171 cases (82,5 %) with a median follow-up of 2.43 years (range 0.15–6.53). Recurrent adenoma was observed in 8 patients (n = 2 after margin positive en bloc ESD; n = 6 after fragmented resection). Recurrence rates were lower after en bloc resection, irrespective of involved margins (1.8 vs. 18,2 %; P

Background and study aims Given that positive lateral margins indicate possible residual carcinoma, salvage endoscopic submucosal dissection (ESD) should be considered for curative therapy. Presence of submucosal fibrosis, however, makes the procedure difficult to perform. We present our case series to discuss the feasibility of salvage ESD and the timing of the procedure.

Background and study aims Duodenal endoscopic submucosal dissection (ESD) is still considered technically challenging; however, few studies have objectively analyzed predictors of the technical difficulty. Therefore, the aim of the current study was to elucidate predictors of the technical difficulty of duodenal ESD. Patients and methods This was a retrospective observational study. From June 2010 to June 2017, a total of 174 consecutive patients with superficial duodenal epithelial neoplasia who underwent ESD were included in this study. We tried to identify predictors for technical difficulty of ESD by defining technical difficulty as either procedure time > 100 minutes or intraprocedural perforation. Moreover, we constructed a scoring system consisting of factors that were significant in the multivariate analysis. Results The proportion of patients with technical difficulty was 34.5 %. In the multivariate analysis, lesion location in flexural part [odds ratio (OR), 2.61; 95 % confidence interval (CI), 1.02 – 6.68], larger lesion size (> 40 mm) (OR, 5.26; 95% CI, 2.15 – 12.9), and occupied circumference > 50 % of the duodenum (OR, 5.80; 95 % CI, 1.83 – 18.4) were associated with technical difficulty. Conclusion A lesion location in flexural part, lesion size >40 mm and occupied circumference > 50 % were risk factors for technical difficulty of duodenal ESD.

Background Dual red imaging (DRI), a novel image-enhanced endoscopy (IEE) technology, has the potential to improve the visibility of blood vessels in deeper tissue using 600 nm and 630 nm wavelength lights in the red band. Aim To confirm the feasibility of DRI in visualization of vessels in deeper tissue and identify pathologically the features of blood vessels visualized by DRI. Methods Study 1: visibility of blood vessels was assessed by five observers in 137 pairs of DRI and white light imaging (WLI) images. The scores for the visibility of thick blood vessels were measured for randomized images and compared with the scoring template as a reference. The difference in visibility score between DRI and WLI was compared in each pair of images. Study 2: blood vessels detected only by DRI were examined pathologically using two pig stomachs. Results Study 1: The mean visibility scores of DRI and WLI for each observer were 1.69 – 2.26 and 1.31 – 1.67, respectively. The mean difference in visibility score and 95 % confidence interval for the five observers was 0.59 [0.46 – 0.72], 0.54 [0.40 – 0.68], 0.34 [0.18 – 0.49], 0.51 [0.36 – 0.66], and 0.71 [0.54 – 0.88]. The visibility was statistically significantly better in DRI than in WLI for all observers (P

Endoscopic submucosal dissection (ESD) is becoming the main procedure for the resection of early gastric cancer (EGC). The absolute indications for treating EGC with endoscopic resection were established by the Japanese Gastric Cancer Association and have been generally accepted. However, the absolute indications for treating EGC are rather strict, and expanded indications have been developed. Many studies have reported favorable long-term outcomes for patients who received curative resection for the expanded indication. ESD preserves the stomach, thereby improving patients’ quality of life compared to surgery; however, a generally higher incidence of metachronous gastric cancer has been reported after ESD for EGC. Therefore, clinicians must pay careful attention during surveillance endoscopy, even after a curative ESD.

IntroductionPatients scheduled to undergo oesophageal, gastric and colorectal endoscopic submucosal dissection (ESD) are to be investigated to verify the efficacy of dual red imaging (DRI) for establishing haemostasis during ESD.Methods and analysisThe trial is designed as a multicentre, open-label randomised, parallel-group, controlled intervention study. Registered patients will be randomly assigned to DRI and white light imaging (WLI) groups. In the DRI group, the mucosal incision and submucosal dissection will be performed by WLI, and haemostasis will be managed by DRI when bleeding occurs. In the WLI group, the mucosal incision and submucosal dissection are to be performed by WLI and the haemostasis management is to be performed by WLI. The primary endpoint is the time from the recognition of bleeding up to the achievement of complete haemostasis (haemostasis time). The secondary endpoints are the operation time, the proportion of cases in which perforation occurs, and the psychological stress experienced by the endoscopist during haemostasis treatment.Ethics and disseminationThis trial was approved by the Keio University Review Board for Clinical Trials (5 December 2016).DiscussionThis will be the first multicentre collaborative research using DRI for haemostasis treatment during ESD. When the safety and simplicity of DRI as a treatment for haemostasis during ESD can be proven, the ESD procedure can be simplified and disseminated more widely in clinical practice.Trial registration numberUMIN000025134

Background and study aims We developed a novel submucosal (SM) injection material that contained pepsin-solubilized collagen (PSC), genipin (Ge) and phosphate buffer (PB). The aim of this study was to validate safety and usability of it for endoscopic resection (ER). Materials and methods In preliminary studies, 1) appropriate warming time and concentration of Ge, and concentration of NaCl in PB, 2) storage modulus of PSC, Ge, and PB mixture (PSC/Ge), and PSC as a mechanical property, 3) histological finding after injection, and histological toxicity of PSC/Ge was evaluated. We injected PSC/Ge, PSC, sodium hyaluronate (SH), dextrose (DW), and normal saline (NS) into SM of resected porcine stomach. We compared mean height of mucosal elevation after immediate injection (MH) and mean retaining rate at 60 minutes (MR) as ex vivo study. Results Optimal condition of PSC/Ge was Ge 5.5 mMol with 24 hours worming time and NaCl 280 mMol. PSC/Ge had better mechanical property than PSC. It was efficiently integrated and confined to the SM with acceptable toxicity. MH of PSC/Ge (5.1 ± 0.74 mm) and PSC (4.8 ± 0.84 mm) were significantly higher than NS (3.2 ± 0.84 mm). MR of PSC/Ge (100 ± 0.0%) was significantly higher than NS (61.7 ± 11.2%), DW (58.3 ± 11.8%) and SH (61.8 ± 8.6%). Conclusion PSC/Ge and PSC has potential to be safe and usable for ER. PSC/Ge was better than PSC because of better mechanical property than PSC.

Background Current guidelines recommend endoscopic submucosal dissection (ESD) as a treatment option for early cancers of the upper gastrointestinal tract with absent or minimal risk of lymph node metastasis. However, due to the low prevalence of these entities, it is difficult to achieve a competence level for ESD of upper gastrointestinal tract cancers in the Western World. Here, we present single-center data on the implementation of upper gastrointestinal ESD after previous experience with 89 colorectal ESD cases. Methods Retrospective case series of 39 consecutive patients with early cancers of the esophagus (n = 13) or cardia and stomach (n = 26) treated with ESD over a 4-year period. Results ESD was technically feasible in all cases with en bloc, R0, and curative resection rates of 100 %, 76.9 %, and 71.8 %, respectively, and a mean procedure time of 100 minutes (30 – 360 minutes). After an initial 20 procedures, the R0 and curative resection rates increased from 65.0 % to 89.5 %, and from 60.0 % to 84.2 %, respectively. Complications were observed in four patients (10.3 %): three perforations, one case of delayed bleeding, and one esophageal stricture. No case required emergency surgery; the 30-day mortality rate was 0 %. Conclusion In this modest case series from Europe, we observed an effectiveness and complication rate for ESD for early esophageal and gastric cancer that are comparable to other series from Europe but also to more abundant data from Asia. The results indicate that even small numbers of upper gastrointestinal cancers can be managed adequately in centers with expertise in colorectal ESD.

Background and study aims Endoscopic full-thickness resection (EFTR) involves several technical issues that need to be addressed. We devised a novel technique termed third-space EFTR and investigated its feasibility and safety in animal models. Methods Third-space EFTR was performed in three isolated porcine stomachs (ex vivo) and four live pigs (in vivo, 1-week survival). The technique involved a circumferential mucosal incision, submucosal tunnelling on the proximal side, endoscopic suturing of the surrounding mucosa, a circumferential seromuscular incision in the submucosal tunnel, transoral retrieval and entry site closure of the tunnel. The technical outcomes were investigated. Results In the ex vivo study, the procedure was successfully completed with R0 resection. In the in vivo study, the procedure was completed in all pigs; however, R0 resection failed in one pig owing to snaring resection. All pigs survived without severe adverse events. Conclusions Our findings indicate that third-space EFTR is feasible and safe. This technique may be useful as a minimally invasive endoscopic option for reliable treatment of small gastric submucosal tumours.

Background and study aims Locoregional triamcinolone acetonide (TAC) injection is increasingly used for prevention of stricture after extensive endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia. However, the safety of intramural TAC injection has not been elucidated. The aim of this study was to assess the clinical courses and histopathological changes after TAC injection into the muscle layer in a porcine model. Methods Three pigs were subjected to ESD under general anesthesia. Two artificial 30-mm lesions were created at the oral and anal ends of the esophagus in each pig. TAC was injected into the muscle layer of the artificial oral ulcers (TAC group) and saline was injected into the muscle layer of the artificial anal ulcers (control group). Endoscopic, macroscopic, and histopathological evaluations were performed. Results The artificial ulcers remained open at sacrifice on day 28 post-ESD in the three ulcers injected with TAC. Esophageal wall perforation and abscess spreading to the mediastinum were observed in two of the three ulcers in the TAC group. The abscesses involved the lungs, bronchi, and aortic adventitia. Severe inflammatory cell infiltration in the muscularis propria layer and significant muscularis propria degradation were observed in all three ulcers in the TAC group. Conclusions This study suggests that TAC may cause deep mural damage when it is injected into the muscularis propria. Care should be taken not to inject TAC into the muscle layer when it is used to prevent post-ESD stricture formation.

Background and study aims In Japan, the elderly population has been increasing annually. The number of elderly patients for whom esophagogastroduodenoscopy (EGD) and colonoscopy (CS) is indicated also has been rising. The aim of this study was to evaluate the safety and efficacy of routine endoscopy in a cohort of octogenarians aged 85 years and older – defined by the World Health Organization as the very elderly. Patients and methods A total of 5,586 patients underwent EGDs, and 2,484 patients underwent CSs performed at the Keio University Hospital from January to September 2014. One hundred eighty-five EGDs and 70 of the CS were performed in the very elderly. Six hundred nine EGDs and 262 CS were performed on younger patients (aged forties). Statistical analysis was performed by univariate and multivariate analyses. Results On univariate analysis, the rate of adverse events (AEs) in the very elderly was significantly higher compared to the younger group (6.3 % vs. 1.1 %; P

Background and study aims Positive horizontal margins in resected specimens are sometimes encountered after endoscopic submucosal dissection (ESD) for early gastric cancers, and appropriate treatment strategies for these cases are not established. The aim of this study was to evaluate current empirical treatments for patients with positive horizontal or indeterminable margins after ESD. Patients and methods We performed a multicenter survey and data from 14 hospitals were collected. The pooled proportions of positive horizontal or indeterminable margins and those of patients followed up without early intervention were calculated using a logistic-normal random-effects model. For calculating pooled estimates, subgroup analyses of high- and non-high-volume centers were conducted. Results A total of 11,796 ESD cases were enrolled and 229 patients (2 %) had positive horizontal or indeterminable margins. Ninety-eight cases were treated within 30 days of ESD and 131 cases were followed up without early treatments. Pooled estimates of positive margins in high- and non-high-volume centers were 1 % (95 % CI: 1 % – 2 %) and 2 % (95 % CI: 1 % – 4 %), respectively, and were not heterogeneous (P = 0.191). The proportion of patients followed up without early intervention ranged from 30 % to 100 %. The pooled estimate was 68 % (95 % CI: 50 % – 83 %). The pooled estimates of high- and non-high-volume centers were 65 % (95 % CI: 38 % – 85 %) and 72 % (95 % CI: 44 % – 89 %), respectively, and were not heterogeneous (P = 0.692). Conclusion There was insufficient consensus regarding treatment strategies used for early gastric cancer with positive horizontal or indeterminable margins after ESD. Further studies are required to establish a consensus.

Background and study aims We sometimes perform gastric endoscopic submucosal dissection (ESD) for total pathologic diagnosis when preoperative diagnosis is difficult. In the present study we analyzed the treatment outcomes and adverse events of diagnostic ESD for early gastric cancer (EGC). Patients and methods We conducted a retrospective analysis of 18 consecutive cases of EGC in 18 patients with a suspected out-of-indication diagnosis who underwent diagnostic ESD, between June 2010 and November 2014. The following parameters were examined: the average length of the longer axis of the lesion; the procedure time; the rates of en bloc resection (ER), complete en bloc resection (CER), and curative resection (CR) as treatment outcomes; and the rates of perforation, delayed bleeding, aspiration pneumonia, disease-related death, and emergency surgery as adverse events. Results The treatment outcomes were as follows: average length of the longer axis of the lesion, 27.4 ± 10.0 mm; procedure time, 87.0 ± 43.1 minutes; ER rate, 18/18 (100.0 %); CER rate, 13/18 (72.2 %); CR rate, 4/18 (22.2 %). CR rate was achieved 37.5 % for the lesions which preoperative diagnosis was more than 30 mm (> 30 mm) in diameter differentiated type with mucosal layer/submucosal layer 1 invasion and ulceration positive. The adverse events (AEs) were perforation in 1 of 18 (5.5 %) patients and delayed bleeding in 1 of 18 (5.5 %). There were no other AEs. Conclusions Diagnostic ESD may be acceptable for future therapeutic strategy when we unconfirmed the pre ESD diagnosis because of lower rate of adverse events and high rate of ER.

Background and study aims Colonoscopies can predict long-term prognoses in patients with ulcerative colitis (UC). Recently, a new imaging technology has been developed that uses 3 types of illumination with center wavelengths of 540 nm, 600 nm, and 630 nm. The use of both the 600-nm and 630-nm lights (Dual red imaging; DRI) is critical for identifying blood vessels in deeper tissue. The aim of this study was to evaluate the usefulness of DRI for assessing the severity of inflammation in patients with UC. Patients and methods A total of 43 UC patients were retrospectively enrolled to evaluate the endoscopic severity of 112 colon segments, and Mayo endoscopic scores, DRI scores and the severity of inflammation on a visual analogue scale (VAS) were compared. The Mayo endoscopic scores, DRI scores, and histologic scores were evaluated, and the interobserver agreement on DRI scores among 5 investigators was also assessed. The usefulness of DRI scores for predicting prognoses was also assessed in patients with clinical remission. Results The DRI scores were closely correlated with the VAS for the severity of colonic inflammation (r = 0.96) and the histologic scores (r = 0.72 – 0.8). The DRI scores had a higher rate of interobserver agreement (κ values = 0.63 – 0.88) than the Mayo endoscopic scores (κ values = 0.44 – 0.59). Inter-observer agreement between 4 non-experts was also excellent (mean κ value = 0.76, range 0.63 – 0.82). The expected time until recurrence was significantly longer in patients with lower DRI scores (P

Although many diagnostic and therapeutic modalities for pancreatic cancer have been proposed, an urgent need for improved therapeutic strategies remains. Oligonucleotide therapeutics, such as those based on antisense RNAs, small interfering RNA (siRNA), microRNA (miRNA), aptamers, and decoys, are promising agents against pancreatic cancer, because they can identify a specific mRNA fragment of a given sequence or protein, and interfere with gene expression as molecular-targeted agents. Within the past 25 years, the diversity and feasibility of these drugs as diagnostic or therapeutic tools have dramatically increased. Several clinical and preclinical studies of oligonucleotides have been conducted for patients with pancreatic cancer. To support the discovery of effective diagnostic or therapeutic options using oligonucleotide-based strategies, in the absence of satisfactory therapies for long-term survival and the increasing trend of diseases, we summarize the current clinical trials of oligonucleotide therapeutics for pancreatic cancer patients, with underlying preclinical and scientific data, and focus on the possibility of oligonucleotides for targeting pancreatic cancer in clinical implications.

Background and study aims: The clinical benefit of endoscopic submucosal dissection (ESD) for superficial duodenal neoplasias has not yet been verified. The aims of this study were to validate the feasibility and long-term outcomes of ESD for nonampullary superficial duodenal neoplasias, larger than 20 mm. Patients and methods: 41 patients, with 41 nonampullary large superficial duodenal neoplasias, who underwent ESD between April 2005 to March 2013 were included in the study. The short- and long-term outcomes were retrospectively evaluated, related to tumor size, resection size, histological type, invasion depth, complete resection rate, operation time, perforation rate, delayed bleeding rate, local recurrence rate, distant metastasis, and survival rate. Results: ESD was successfully completed in 38 of 41 patients (92.7 %). The median sizes of tumors and resected specimens were, respectively, 26 mm (range 20 – 70 mm) and 36.5 mm (range 23 – 80 mm). Histopathological findings showed 13 adenocarcinomas (12 mucosal, 1 submucosal) and 28 adenomas (26 high grade dysplasia, 2 low grade dysplasia). The complete resection rate was 89.5 % (34 /38 tumors). The mean operation time was 128.3minutes. Perforation during ESD occurred in 39 % and delayed bleeding occurred in 18.4 %. The median observation period was 48 months (range 3.2 – 94.1 months), and no local recurrence or distant metastasis was seen during this time, representing a disease-free survival rate of 100 %. Conclusions: ESD for nonampullary large superficial duodenal adenocarcinoma/adenoma is feasible with favorable long-term outcomes. However, because of the high complication rate due to its technical difficulty, experience and skill of the operator, along with adequate perioperative management, are essential.

Endoscopic submucosal dissection is a minimally invasive endoscopic technique for the removal of gastrointestinal tumours that is increasingly being used for colonic neoplasms to spare resection of colon in selected patients. Colonic endoscopic submucosal dissection is technically challenging and was initially pioneered in Japan but increasingly used in selected western centres. Its use in Canada is currently limited, and the authors review the challenges and opportunities, in addition to the unique training infrastructure required to practice the procedure under supervision. Specific tools are required to perform endoscopic submucosal dissection and meticulous attention to detail is essential. The authors provide a combined Japanese and Canadian perspective to this technique, and discuss training and performance of endoscopic submucosal dissection as well as potential indications.

Background and study Aims: To prevent complications after colonic endoscopic submucosal dissection (ESD), we developed a new closure technique using repositionable clips. Patients and methods: The closure of post-ESD mucosal defects was attempted in 19 cases. Mucosal defects were linearly closed by holding and dragging the anal mucosal edge towards the oral mucosal edge using repositionable clips. Standard hemoclips were additionally placed to complete the closure. We retrospectively assessed the feasibility of this technique. Results: Defect closure was successfully completed in 18 cases (94.7 %). The mean defect size and the procedural time were 40.2 ± 12.0 mm (range, 24 – 71 mm) and 10.7 ± 7.2 min (range, 4.0 – 29.9 min), respectively. The mean number of repositionable clips and standard clips required for closure was 1.6 ± 0.8 (range, 1 – 3) and 7.3 ± 3.7 (range, 3 – 16), respectively. No adverse events occurred during procedures and thereafter (95 % confidence interval, 0 – 17.6 %). Conclusions: The new closure technique for large mucosal defects after colonic ESD using repositionable clips was feasible and appeared effective for preventing subsequent adverse events.

Background and study aims: Colorectal endoscopic submucosal dissection (ESD) is an attractive method for en bloc resection of larger flat neoplastic lesions. Experience with this method is limited in the Western World. Patients and methods: A total of 182 consecutive flat or sessile colorectal lesions (cecum n = 43; right-sided colon n = 65; left-sided colon n = 11, rectum: n = 63) with a size > 20 mm (mean 41.0 ± 17.4 mm) were resected in 178 patients. The data were recorded prospectively. Results: ESD was technically feasible in 85.2 % of patients with a mean procedure time of 127.5 min (± 99.8) min and a complication rate of 11.5 % (microperforation 9.3 %, delayed bleeding 2.7 %, no case of emergency surgery, 30-day mortality rate 0 %). For 155 successfully completed procedures the en bloc and R0 resection rates were 88.4 and 62.6 %. Efficacy was better for smaller lesions (20 mm to 49 mm; n = 131) than for larger lesions (50 mm to 140 mm; n = 51) with R0 rates of 70.8 vs. 40.5 % (P 20 mm. Results are satisfactory for lesions up to 50 mm. ESD for larger lesions was associated with low R0 resection rates and very long procedure times. The clinical consequences of microperforations were minor and do not argue against the spread of ESD in the West. Meeting presentations: The data were presented in part at DDW 2014, Chicago IL, USA (Gastrointest Endosc 2014; 79: AB536)

Background and study aims: More secure endoscopic closure techniques for iatrogenic gastric defects are required for safe endoscopic surgery. We developed a novel endoscopic suturing method, endoscopic hand suturing (EHS), of gastric mucosal defects and determined its feasibility and efficacy ex vivo. Materials and methods: We created 24 mucosal defects (each 2 cm in diameter) by endoscopic submucosal dissection. The following three techniques were tested: EHS with a 3 – 0 barbed suture that was grasped with biopsy forceps (n = 6) or a prototype through-the-scope needle holder (n = 6) by endoscopy, looping with endoloops (n = 6) by endoscopy, and clipping with hemoclips (n = 6) by hand. The mucosal edges were attached to each other at three points. The closure strength was compared among the three groups, and the procedural duration was compared between the EHS and looping groups. Results: All 12 lesions were completely closed by EHS. The median strength of the closure, measured with a spring scale, was significantly greater in the EHS group (0.74 kg) than in the looping group (0.33 kg, P = 0.0012) or clipping group (0.07 kg, P = 0.0009). The median procedural duration did not significantly differ between the EHS and looping groups (19.7 vs. 19.8 minutes, P = 1.0000). The use of the needle holder significantly reduced the procedural duration compared with the biopsy forceps. Conclusion: Mucosal defects can be firmly closed with EHS, which may be helpful for establishing a safer and more secure endoscopic surgery.

BACKGROUND AND STUDY AIMS: The duodenum and colorectum are target organs for familial colorectal adenomatous polyposis, however, the association of duodenal epithelial tumors (DETs) and colorectal tumors is still controversial. The aim of our study was to elucidate the association between DET and colorectal tumor. PATIENTS AND METHODS: This was an exploratory cross-sectional study of patients with DETs treated by endoscopic resection at our hospital, between November 2018 and October 2022. Individuals who underwent colonoscopy as part of the health screening comprised the reference control group for comparison. In both groups, lesions suspected of being tumors were resected. The main outcome was the adenoma detection rate (ADR). Other outcomes were the detection rate of advanced neoplasia (AN) and risk factors for colorectal adenoma and AN, evaluated using univariate and multivariable analyses. RESULTS: Analyses were based on the data of 163 individuals in the DET group and 177 in the control group. ADR was higher in the DET (63.2%) than in the control (23.6%) group (p