Association of high-risk stigmata and worrisome features with advanced neoplasia in intraductal papillary mucinous neoplasms (IPMN): A systematic review.

BACKGROUND: This systematic review aimed to assess the diagnostic accuracy of the International Consensus Fukuoka Guidelines (ICG2017) in identifying high-risk lesions of Intraductal Papillary Mucinous Neoplasms (IPMNs). METHODS: The ICG2017 revision committee conducted a comprehensive literature review to establish evidence-based statements on IPMNs. The review focused on articles examining the diagnostic value of imaging features (e.g., cyst or main pancreatic duct diameter), clinical symptoms associated with IPMN, and serum biomarkers. Five clinical questions regarding high-risk stigmata (HRS) and worrisome features (WF) in the ICG2017 guidelines were addressed. RESULTS: A total of 210 articles were reviewed. The findings revealed a significant association between the presence of mural nodules ≥5 mm in diameter or solid components with contrast enhancement and the diagnosis of high-grade dysplasia or invasive carcinoma. Contrast-enhanced diagnostic tools, such as CT, MRI, or EUS, demonstrated the highest prediction rate and were recommended. Positive cytology was identified as an HRS, while symptoms like acute pancreatitis and cyst diameter growth ≥2.5 mm per year were considered WFs. The use of nomograms and multiple diagnostic factors was recommended for optimal IPMN management. CONCLUSIONS: This systematic review provides evidence supporting the improved diagnostic accuracy of ICG2017 in identifying high-risk lesions of IPMN. The multidisciplinary incorporation of HRS and WF based on imaging findings and clinical symptoms is crucial. These findings should inform the revision of ICG2017, enhancing the evaluation and management of IPMN patients. By implementing these recommendations, clinicians can make more informed decisions, leading to better diagnosis and treatment outcomes for high-risk IPMN cases.

International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas.

This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new "evidence-based guidelines" is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, "stop surveillance" or "continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma", for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed.

Artificial intelligence in a prediction model for postendoscopic retrograde cholangiopancreatography pancreatitis.

OBJECTIVES: In this study we aimed to develop an artificial intelligence-based model for predicting postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: We retrospectively reviewed ERCP patients at Nagoya University Hospital (NUH) and Toyota Memorial Hospital (TMH). We constructed two prediction models, a random forest (RF), one of the machine-learning algorithms, and a logistic regression (LR) model. First, we selected features of each model from 40 possible features. Then the models were trained and validated using three fold cross-validation in the NUH cohort and tested in the TMH cohort. The area under the receiver operating characteristic curve (AUROC) was used to assess model performance. Finally, using the output parameters of the RF model, we classified the patients into low-, medium-, and high-risk groups. RESULTS: A total of 615 patients at NUH and 544 patients at TMH were enrolled. Ten features were selected for the RF model, including albumin, creatinine, biliary tract cancer, pancreatic cancer, bile duct stone, total procedure time, pancreatic duct injection, pancreatic guidewire-assisted technique without a pancreatic stent, intraductal ultrasonography, and bile duct biopsy. In the three fold cross-validation, the RF model showed better predictive ability than the LR model (AUROC 0.821 vs. 0.660). In the test, the RF model also showed better performance (AUROC 0.770 vs. 0.663, P = 0.002). Based on the RF model, we classified the patients according to the incidence of PEP (2.9%, 10.0%, and 23.9%). CONCLUSION: We developed an RF model. Machine-learning algorithms could be powerful tools to develop accurate prediction models.

Factors Related to Delayed Adverse Events of Endoscopic Submucosal Dissection in the Duodenum.

INTRODUCTION: Endoscopic submucosal dissection for duodenal neoplasms (D-ESD) is considered a technically demanding procedure regarding the high risk of delayed adverse events. Data regarding optimal managements of ulcers after D-ESD are lacking. METHODS: A retrospective analysis was performed on consecutive 145 cases of D-ESD for superficial nonampullary duodenal epithelial tumors at a single referral center. Factors related to delayed adverse events and the healing process of ulcers after D-ESD were analyzed. RESULTS: Complete ulcer suture after D-ESD was performed in 128 cases (88%). Two delayed perforation occurred among cases with incomplete suture. Delayed bleeding occurred in 8 cases (6%) within 3 weeks. The ulcer closure rate at second-look endoscopy (SLE) was significantly low among cases with delayed bleeding (12.5% vs. 75%, p = 0.001). The bleeding rate before SLE was significantly high among patients who did not have complete ulcer closure after D-ESD (0.8% vs. 12%, p = 0.036). The ratio of lesions located in the second oral-Vater was significantly low among ulcers re-opened at SLE (38% vs. 14%, p = 0.044). Proton-pump inhibitors (PPIs) were administered for a median of 7 weeks (range 1-8 weeks). At 3 weeks, active ulcer stages were observed in a few cases, and healing or scarring was observed in most cases. CONCLUSIONS: Complete ulcer suture was related to decreased risk of delayed adverse events after D-ESD. From the bleeding period and healing process of D-ESD ulcers, the minimum required length of PPI may be 3 weeks after D-ESD.

Randomized trial comparing 15 vs 5 actuations per pass during endoscopic ultrasound-guided fine-needle biopsy for specimen acquisition of solid pancreatic lesions.

BACKGROUND AND AIM: There is currently no established number of actuations (to-and-fro movements) per pass during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). This study aimed to compare 15 vs 5 actuations in terms of adequate specimen acquisition of solid pancreatic lesions. METHODS: In this prospective, randomized, crossover, noninferiority, single-center study, eligible patients underwent EUS-FNB using a 22-G Franseen needle with both 15 and 5 actuations per pass, performed in a randomized order, from October 2020 to December 2021. The acquired specimens from each pass were separately evaluated. The primary outcome was the accuracy of the histological diagnosis per pass. The noninferiority margin was set as 15%. RESULTS: Data from 85 patients were analyzed, revealing pancreatic cancer in 73 patients. The accuracy of the histological diagnosis in the 15 and 5 actuations groups was 83.5% (71/85) and 77.7% (66/85), respectively. The difference was -5.8% (95% confidence interval -15.6-3.4), which does not indicate noninferiority of the five actuations group. Among the secondary outcomes, the 15 actuations group was significantly superior to the five actuations group in terms of the obtained core tissues (1.88 [interquartile range 0.89-3.64] mm2 vs 1.66 [0.83-2.71] mm2 [P = 0.031]) and subjective evaluation of cytology specimens for pancreatic cancer (69.0% vs. 31.0%, P = 0.005). CONCLUSIONS: The noninferiority of five actuations in the accuracy of the histological diagnosis was not confirmed, and 15 actuations are preferred during EUS-FNB for solid pancreatic lesions.

CO2 enterography in endoscopic retrograde cholangiography using double-balloon endoscopy: A randomized clinical trial.

BACKGROUND AND AIM: Double-balloon endoscopic retrograde cholangiography (DBERC) is a valuable procedure for patients with altered gastrointestinal anatomy. Nonetheless, it is time-consuming and burdensome for both patients and endoscopists, partly because route selection in the reconstructed bowel with complicating loop is challenging. Carbon dioxide insufflation enterography is reportedly useful for route selection in the blind loop. This prospective randomized clinical trial investigated the usefulness of carbon dioxide insufflation enterography for route selection by comparing it with conventional observation. METHODS: Patients scheduled to undergo DBERC were consecutively registered. They were divided into carbon dioxide insufflation enterography and conventional groups via randomization according to stratification factors, type of reconstruction methods, and experience with DBERC. The primary endpoint was the correct rate of initial route selection. The secondary endpoints were the insertion time, examination time, amount of anesthesia drugs, and complications. RESULTS: The correct rate of route selection was significantly higher in the carbon dioxide insufflation enterography group (23/25, 92%) than in the visual method (15/25, 60%) (P = 0.018). The insertion time was significantly shorter in the carbon dioxide insufflation enterography group than in the visual group (10.8 ± 11.1 min vs 29.8 ± 15.7 min; P < 0.001). No significant differences in complications were noted between the two groups. The amounts of sedatives and analgesics used were significantly lower in the carbon dioxide insufflation enterography group (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: Carbon dioxide insufflation enterography can reduce the burden of DBERC on patients and endoscopists by shortening the examination time and reducing the amount of medication.

Diagnostic Performance of Endocytoscopy for Esophageal Eosinophilia.

INTRODUCTION: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. METHODS: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. RESULTS: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94-5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). DISCUSSION/CONCLUSION: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients.

Scoring system for predicting the prognosis of elderly gastric cancer patients after endoscopic submucosal dissection.

OBJECTIVES: Comprehensive assessments of the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the elderly are unavailable. We aimed to create a scoring system to predict the long-term prognosis after ESD for EGC among patients aged ≥75 years. METHODS: We conducted retrospective studies of two cohorts: a single-center cohort (2006-2011) for developing the scoring system, and a multicenter cohort for validating the developed system (2012-2016). In the development cohort, factors related to death after ESD were identified using multivariable Cox regression analysis, and a predictive scoring system was developed. In the validation cohort, the scoring system was validated in 295 patients. RESULTS: In the development cohort, Charlson comorbidity index (CCI) ≥3 (hazard ratio [HR] 3.017), high psoas muscle index (PMI) (HR 2.206), and age ≥80 years (HR 1.978) were significantly related to overall survival after ESD. Therefore, high CCI, low PMI, and age ≥80 years were assigned 1 point each. The patients were categorized into low (≤1 point) and high (≥2 points) score groups based on their total scores. In the validation cohort, 184 and 111 patients were assigned to the low- and high-score groups, respectively. In comparisons based on Kaplan-Meier curves, the 5-year survival rate was 91.5% in the low-score group and 57.8% in the high-score group (log-rank test; P < 0.001). CONCLUSION: Our scoring system including high CCI, low PMI, and age ≥80 years could stratify the long-term prognosis of elderly patients aged ≥75 years after ESD for EGC.

Novel endoscopic approaches using the endocytoscopy for the target biopsy in esophageal eosinophilia.

BACKGROUND AND AIMS: Multiple biopsies are recommended for the diagnosis of eosinophilic esophagitis (EoE) because inflammatory changes are frequently patchy. Reports on EoE using endocytoscopy (ECS) are limited. This present study aimed to assess if diagnostic yield improves by adding ECS on conventional white light imaging (WLI) in patients with esophageal eosinophilia (EE). METHODS: A total of 284 biopsy specimens from 71 patients with a known diagnosis of EE were enrolled and divided into the WLI group (156 specimens) or the ECS group (128 specimens). Four biopsies from 5 and 10 cm proximal to the esophagogastric junction were taken from each patient. In the ECS group, the biopsy was performed where bilobed nuclei were observed. The biopsy sensitivity for EE, eosinophil count of a single specimen and the biopsy sensitivity of each endoscopic finding were evaluated between both groups. RESULTS: The sensitivity of a single biopsy specimen was higher in the ECS group than that of the WLI group (62.5 vs. 41.7%, P < 0.001). In addition, the median eosinophil count in the ECS group was significantly higher [19 vs. 6.5/high-power field (HPF), P < 0.001]. For each endoscopic finding, ECS-based biopsy had higher sensitivity than that of WLI in the diagnosis of edema (33.1 vs. 11.3%, P = 0.007) and linear furrows (75.8 vs. 52%, P = 0.005). CONCLUSION: This study showed that adding ECS to WLI improved the biopsy sensitivity and eosinophil detection in patients with EE.

Results of a Phase II Study on the Use of Neoadjuvant Chemotherapy (FOLFIRINOX or GEM/nab-PTX) for Borderline-resectable Pancreatic Cancer (NUPAT-01).

OBJECTIVE: Given the frequent adverse events with multidrug chemotherapy, not only the survival benefit but also the feasibility of using neoadjuvant chemotherapy to treat pancreatic cancer need to be clarified. SUMMARY OF BACKGROUND DATA: Although the development of multidrug chemotherapy regimens has improved the survival outcomes of patients with unresectable pancreatic cancer, the benefits of these treatments in the neo-adjuvant setting remain controversial. METHODS: Patients with borderline-resectable pancreatic cancer were enrolled and randomly assigned to receive neoadjuvant chemotherapy with either FOLFIRINOX or gemcitabine with nab-paclitaxel (GEM/nab-PTX). After the completion of chemotherapy, patients underwent surgical resection when feasible. This study (NUPAT-01) was a randomized phase II trial, and the primary endpoint was the R0 resection rate. RESULTS: Fifty-one patients were enrolled in this study [FOLFIRINOX (n = 26) and GEM/nab-PTX (n = 25)]. A total of 84.3% (n = 43/51) of the patients eventually underwent surgery, and R0 resection was achieved in 67.4% (n = 33/ 51) of the patients. Adverse events (grade >3) due to neoadjuvant treatment were observed in 45.1% of the patients (n = 23/51), and major surgical complications occurred in 30.0% (n = 13/43), with no mortality noted. The intention-to-treat analysis showed that the 3-year overall survival rate was 54.7%, with a median survival time of 39.4 months, and a significant difference in overall survival was not observed between the FOLFIRINOX and GEM/nab-PTX groups. CONCLUSIONS: These results indicate that neoadjuvant chemotherapy with FOLFIRINOX or GEM/nab-PTX is feasible and well tolerated, achieving an R0 resection rate of 67.4%. The survival of patients was even found to be favorable in the intention-to-treat analysis.

Safety and efficacy of MIKE-1 in patients with advanced pancreatic cancer: a study protocol for an open-label phase I/II investigator-initiated clinical trial based on a drug repositioning approach that reprograms the tumour stroma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are an important component of the tumour microenvironment. Recent studies revealed CAFs are heterogeneous and CAF subset(s) that suppress cancer progression (cancer-restraining CAFs [rCAFs]) must exist in addition to well-characterised cancer-promoting CAFs (pCAFs). However, the identity and specific markers of rCAFs are not yet reported. We recently identified Meflin as a specific marker of rCAFs in pancreatic and colon cancers. Our studies revealed that rCAFs may represent proliferating resident fibroblasts. Interestingly, a lineage tracing experiment showed Meflin-positive rCAFs differentiate into α-smooth muscle actin-positive and Meflin-negative CAFs, which are generally hypothesised as pCAFs, during cancer progression. Using a pharmacological approach, we identified AM80, a synthetic unnatural retinoid, as a reagent that effectively converts Meflin-negative pCAFs to Meflin-positive rCAFs. We aimed to investigate the efficacy of a combination of AM80 and gemcitabine (GEM) and nab-paclitaxel (nab-PTX) in patients with advanced pancreatic cancer. METHODS: The phase I part is a 3 + 3 design, open-label, and dose-finding study. The dose-limiting toxicity (DLT) of these combination therapies would be evaluated for 4 weeks. After the DLT evaluation period, if no disease progression is noted based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or if the patient has no intolerable toxicity, administration of AM80 with GEM and nab-PTX would be continued for up to 24 weeks. The phase II part is an open-label, single-arm study. The maximum tolerated dose (MTD) of AM80 with GEM and nab-PTX, determined in phase I, would be administered until intolerable toxicity or disease progression occurs, up to a maximum of 24 weeks, to confirm efficacy and safety. The primary endpoints are frequency of DLT and MTD of AM80 with GEM and nab-PTX in the phase I part and response rate based on the RECIST in the phase II part. Given the historical control data, we hope that the response rate will be over 23% in phase II. DISCUSSION: Strategies to convert pCAFs into rCAFs have been developed in recent years. We hypothesised that AM80 would be a promising enhancer of chemosensitivity and drug distribution through CAF conversion in the stroma. TRIAL REGISTRATION: Clinicaltrial.gov: NCT05064618 , registered on 1 October 2021. jRCT: jRCT2041210056 , registered on 27 August 2021.

Changes in the gut microbiome in relation to the degree of gastric mucosal atrophy before and after Helicobacter pylori eradication.

OBJECTIVES: Helicobacter pylori infection causes atrophic gastritis, which affects the gut microbiome; the gastric acid concentration depends on the degree of atrophic gastritis. Helicobacter pylori eradication also affects gastric acidity. Here, we determined the differences in the post-eradication changes in the gut microbiome in relation to the progression of gastric atrophy. MATERIALS AND METHODS: Ten patients were included in the closed group and five in the open group, consisting of patients with non-progressive and progressive atrophy, respectively, diagnosed by endoscopy. The faecal microbiome was analysed and compared among three time-points: before eradication, 8 weeks after eradication, and 6 months after eradication. The microbiome was analysed by targeting 16S rRNA using Illumina Miseq. RESULTS: The relative abundance of 14 genera significantly differed between the closed and open groups before eradication, but only 12 and 6 genera presented a significant difference in the relative abundance at 8 weeks and 6 months after eradication, respectively. Of the 12 genera that differed between the closed and open groups before eradication, 8 genera, namely, Actinomyces, Aggregatibacter, Campylobacter, Granulicatella, Pyramidobacter, Streptococcus, Cardiobacterium, and Haemophilus, were oral-origin bacteria. Longitudinal changes showed that Haemophilus and Catenibacterium were consistently significantly more abundant in the open group than in the closed group during the follow-up period. CONCLUSION: The gut microbiome substantially differed depending on the progression of gastric atrophy, but this difference was decreased by eradication, especially the differences in the number of oral bacteria in the gut. Eradication therapy may improve dysbiosis that result from gastric atrophy.

Endoscopic sphincterotomy and endoscopic biliary stenting do not affect the sensitivity of transpapillary forceps biopsy for the diagnosis of bile duct adenocarcinoma.

BACKGROUND: The pathological evaluation of tissues with cholangitis is considered difficult, which can often occur after endoscopic sphincterotomy (EST) and endoscopic biliary stenting (EBS). This study aimed to evaluate the influence of a history of EST and EBS on the sensitivity of transpapillary forceps bile duct biopsy (TB) for bile duct adenocarcinoma. METHODS: This retrospective study included consecutive cases of bile duct adenocarcinoma in which TB was performed before July 2020 until the number exceeded that required to support statistical and noninferiority analyses of the sensitivity of TB between patients with and without each variable. The incidence of postprocedural adverse events related to each factor was also investigated. RESULTS: Overall, 280 samples were required in each group, and 437 subjects (792 samples) were included. The sensitivity of TB was 63.6% for the subjects and 59.6% for the biopsy samples. For the biopsy samples, the sensitivity did not differ significantly between samples from patients with and without a history of EST (59.1% vs. 58.9%, P = 0.952) and EBS (62.1% vs. 55.4%, P = 0.065). The sensitivity was significantly higher for samples from patients with jaundice (67.9% vs. 57.0%, P = 0.008). There were significantly fewer procedure-related adverse events in patients with a history of EST (10.8% vs. 19.0%, P = 0.017) and EBS (12.0% vs. 21.7%, P = 0.005). CONCLUSIONS: A history of EST or EBS did not influence sensitivity of TB but significantly decreased the incidence of adverse events. To safely and reliably perform TB to diagnose bile duct adenocarcinoma, planning, including for EST and EBS, is necessary.

Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan.

BACKGROUND: Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients. METHODS: Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12 weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12 weeks after FMT. For the microbiome, we analyzed the V3-V4 region of the 16S rRNA gene. RESULTS: IBS-SI decreased an average of 115.58 points after 12 weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. α-diversity was increased only in the responder group (p = 0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT. CONCLUSIONS: Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased α-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363 . The study was registered prospectively.

Artificial intelligence-based diagnosis of upper gastrointestinal subepithelial lesions on endoscopic ultrasonography images.

BACKGROUND: Endoscopic ultrasonography (EUS) is useful for the differential diagnosis of subepithelial lesions (SELs); however, not all of them are easy to distinguish. Gastrointestinal stromal tumors (GISTs) are the commonest SELs, are considered potentially malignant, and differentiating them from benign SELs is important. Artificial intelligence (AI) using deep learning has developed remarkably in the medical field. This study aimed to investigate the efficacy of an AI system for classifying SELs on EUS images. METHODS: EUS images of pathologically confirmed upper gastrointestinal SELs (GIST, leiomyoma, schwannoma, neuroendocrine tumor [NET], and ectopic pancreas) were collected from 12 hospitals. These images were divided into development and test datasets in the ratio of 4:1 using random sampling; the development dataset was divided into training and validation datasets. The same test dataset was diagnosed by two experts and two non-experts. RESULTS: A total of 16,110 images were collected from 631 cases for the development and test datasets. The accuracy of the AI system for the five-category classification (GIST, leiomyoma, schwannoma, NET, and ectopic pancreas) was 86.1%, which was significantly higher than that of all endoscopists. The sensitivity, specificity, and accuracy of the AI system for differentiating GISTs from non-GISTs were 98.8%, 67.6%, and 89.3%, respectively. Its sensitivity and accuracy were significantly higher than those of all the endoscopists. CONCLUSION: The AI system, classifying SELs, showed higher diagnostic performance than that of the experts and may assist in improving the diagnosis of SELs in clinical practice.

Comparison of Endoscopic Ultrasonography and Conventional Endoscopy for Prediction of Tumor Depth in Superficial Nonampullary Duodenal Epithelial Tumors.

BACKGROUND: The utility of endoscopic ultrasonography (EUS) in predicting tumor depth among superficial nonampullary duodenal epithelial tumors (SNADETs) is unclear. The aim was to compare EUS with conventional endoscopy (CE) for the evaluation of tumor invasion of SNADETs. METHODS: A retrospective analysis was performed on consecutive 174 lesions/169 patients with duodenal dysplasia or adenocarcinoma with invasion up to submucosa who underwent both CE and EUS before endoscopic (n = 133) or surgical (n = 41) treatment. Endoscopic staging by CE was performed based on the characteristic endoscopic criteria of submucosal invasion (irregular surface, submucosal tumor [SMT]-like marginal elevation, and fusion of converging folds). The diagnostic performance of each test was compared with the final histology. RESULTS: The sensitivity and accuracy of estimating the depth were higher for CE compared to that of EUS (99.4% vs. 89.4%, p < 0.01 and 97.7% vs. 87.9%, p < 0.01, respectively). Univariate analysis of endoscopic factors revealed that tumor diameter, red color, SMT-like appearance, and hypoechogenicity were factors related to advanced histology. Multivariate analysis revealed that the presence of SMT-like appearance based on CE was an independent factor to predict submucosal invasion (p = 0.025). Gross morphology of the combined type was associated to incorrect diagnosis of EUS (p = 0.007). Among 3 cases in which EUS overestimated the tumor depth, carcinoma extension in submucosal Brunner's gland or nontumorous submucosal cystic dilation was observed. CONCLUSION: EUS may not be necessary, and CE may be sufficient for determining the optimal therapeutic strategy for SNADETs.

Preliminary Comparison of Endoscopic Brush and Net Catheters as the Sampling Tool to Analyze the Intestinal Mucus in the Rectum with Ulcerative Colitis Patients.

BACKGROUND: The pathophysiology of ulcerative colitis (UC) remains unclear, but early lesions on the colorectal mucosal surface may play an important role in its etiology. Intestinal mucus samples, including inner and outer layers, are collected by net or brush catheters, but the quality of the samples obtained by each method has not been fully investigated. OBJECTIVE: The purpose of this study was to compare the microbiome and protein content of intestinal mucus collected by net and brush catheters during colonoscopy. METHODS: Intestinal mucus samples from the lower rectum of 4 patients with UC were collected using a net catheter, a brush catheter, and intestinal fluid suction. Microbiome and protein content were analyzed using 16S rRNA gene sequencing and mass spectrometry. RESULTS: The patients demonstrated significant differences in microbiome alpha diversity (p < 0.05), but this difference was not observed between the sampling methods. Net catheter samples demonstrated higher total protein concentrations than brush catheter samples. The brush catheter group had more Lachnospira, a butyrate-producing bacterium, when compared to the net group. The brush catheter group also had more oral bacteria of Staphylococcus and Dialister in those with active phase when compared to the net group. CONCLUSIONS: Brush catheters are more likely to collect the intestinal mucus inner layer, whereas net catheters are more likely to collect larger samples that include the outer mucus layer, as well as the intestinal fluid. Two sampling methods with different types of collection of the mucosa may lead to different results among patients with mucosal vulnerabilities.

Network Analysis of Gut Microbiota Including Fusobacterium and Oral Origin Bacteria and Their Distribution on Tumor Surface, Normal Mucosa, and in Feces in Patients with Colorectal Cancer.

INTRODUCTION: Fusobacterium and several bacteria are reported to be associated with colorectal cancer (CRC). However, their relationship and whether they cause CRC or are just adapted to the cancerous environment is not known. We approached this subject by investigating the correlation and distribution of the bacteria throughout the colon in patients with CRC and elucidated the relationship between microbiota and CRC. METHODS: Twenty-five patients with CRC who underwent colonoscopy for endoscopic submucosal dissection or surgery were prospectively enrolled. Fecal samples were taken before bowel preparation, and mucosal samples were collected from three sites (tumor surface, tumor-adjacent mucosa, and cecum) during colonoscopy using a cytology brush. The microbiota was identified and analyzed by sequencing of the 16S rRNA gene of the V3-V4 region. We evaluated the correlation between the bacteria based on network analysis and the distribution of Fusobacterium in the colon. RESULTS: A network consisting of many bacteria was found in all sites; especially, oral origin bacteria including Fusobacterium formed a positively correlated network on tumor surface. Streptococcus showed a significantly higher relative abundance on tumor surface than in feces. The relative abundance of Fusobacterium had significant positive correlations between tumor surface and feces, tumor-adjacent mucosa, and cecum. CONCLUSION: In patients with CRC, many bacteria were correlated with each other, and Fusobacterium and oral origin bacteria formed a positively correlated network on tumor surface. Fusobacterium was equally distributed on tumor surface and throughout the lumen and mucus in the colon. In the colon where Fusobacterium is widely distributed, Fusobacterium would adhere to the tumor surface and be correlated with oral origin bacteria to make a microenvironment that is favorable for CRC.

Comparison of outcomes between secondary fully covered and uncovered self-expandable metal stents in the treatment of recurrent biliary obstruction of pancreatic cancer.

BACKGROUND: The overall survival (OS) of pancreatic cancer (PC) has been prolonged by advances in chemotherapy, and the number of cases of recurrent biliary obstruction (RBO) after self-expandable metal stent (SEMS) placement is expected to increase. We herein compared outcomes between secondary fully covered SEMS (FC) and uncovered SEMS (UC) for RBO of PC with FC placed as the 1st SEMS. METHODS: Between May 2010 and March 2021, 62 PC patients who underwent SEMS exchange to FC (n = 34) or UC (n = 28) for RBO were retrospectively analyzed. Patient characteristics, OS, time to RBO (TRBO), and stent-related adverse events were compared between the FC and UC groups. Cox's proportional hazard model was used to identify risk factors for RBO with the 2nd SEMS. RESULTS: There was a significant difference between the FC and UC groups only in the 2nd SEMS diameter. Median OS and TRBO were 195 and 238 days in FC patients and 306 and 455 days in UC patients, respectively, with no significant differences between the two groups. No significant differences were observed in the stent-related adverse event rate. In multivariate analyses, only the 2nd SEMS diameter was significant (P = 0.009). Median TRBO were 455, 238, and 103 days in 10-mm UC, 10-mm FC, and 8-mm UC patients, with 10-mm UC patients having significantly longer TRBO than 10-mm FC and 8-mm UC patients (P = 0.020 and 0.001). CONCLUSION: SEMS exchange to 10-mm UC may be appropriate for RBO of PC with FC as the 1st SEMS.

Relationship between psoas muscle index and long-term survival in older patients aged ≥ 80 years after endoscopic submucosal dissection for gastric cancer.

BACKGROUND: In Japan, endoscopic submucosal dissection (ESD) has been widely performed for ESD-adapted gastric cancer, but little is known about the prognostic factors after ESD for gastric cancer in older patients. The psoas muscle index (PMI) is an indicator of sarcopenia calculated from computed tomography images and reportedly related to the prognosis of some diseases. This study aimed to explore factors related to long-term survival after ESD for gastric cancer in patients aged ≥ 80 years. METHODS: We retrospectively reviewed 88 patients (63 men, 25 women) with early gastric cancer who underwent ESD at ≥ 80 years. Possible factors related to death after gastric ESD were analyzed by univariate and multivariate analyses using a Cox proportional hazards model. The estimated overall survival (OS) was compared between the groups stratified by significant factors. RESULTS: The 5-year OS rate was 73.9% (median follow-up period, 5.4 years). In the multivariate analysis, a low PMI (< 6.36 in men, < 3.92 in women) (hazard ratio [HR] 2.89, 95% confidence interval [CI] 1.11-7.54) and high Charlson comorbidity index (CCI) (≥ 3) (HR 1.87, 95% CI 1.14-3.09) were independently related to death after ESD. The 5-year OS rates were significantly higher in the high PMI group (82.3% vs. 70.7%, P = 0.026) and the low CCI group (76.0% vs. 37.9%, P = 0.002). CONCLUSION: In addition to low CCI, high PMI is a predictor of long-term survival after ESD for gastric cancer in patients aged ≥ 80 years.