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Abstract Background Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions. Methods SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112). Results SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components. Conclusion Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.

Abstract Objective Few reports have explored the application of urinary trypsinogen‐2 measurement in the early diagnosis of post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, and none have demonstrated the benefits of noninvasive testing. This study aimed to evaluate the clinical application of the rapid urinary trypsinogen‐2 dipstick test (Nipro, Japan) compared with serum amylase and lipase levels for the early diagnosis of post‐ERCP pancreatitis (PEP). Methods A total of 100 consecutive patients (54 men and 46 women) who were admitted and underwent ERCP at Tokyo Medical University Hospital from August 2021 to December 2021 were recruited. All patients underwent rapid urinary trypsinogen‐2 measurement using the dipstick test before and after ERCP. Measurements were taken 24 h before ERCP for pre‐ERCP and 1–4 h after ERCP for post‐ERCP. Additionally, serum amylase and lipase levels were measured at 8:00 a.m. of the day after ERCP (at least 8 h after ERCP), and their diagnostic abilities for PEP were compared and evaluated. Results PEP occurred in 5/100 patients (5%). The sensitivity, specificity, positive predictive value, and negative predictive value of the dipstick test for diagnosing PEP were 100%, 83.2%, 23.8%, and 100%, respectively. These results were comparable to the diagnostic performance of serum amylase and lipase levels at 8:00 a.m. on the day after ERCP (at least 8 h after ERCP). However, false positives must be considered. Conclusion The dipstick test may be useful in clinical practice as a noninvasive screening test for the early prediction of PEP.

IntroductionPatients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and metabolites. Thus, we compared the microbiome and metabolome changes for each SARS-CoV-2 variant in patients with COVID-19.Materials and methodsWe conducted a multicenter observational study of patients with COVID-19 and performed fecal microbiome, metabolome, and calprotectin analyses and compared the results among the different SARS-CoV-2 variants.ResultsTwenty-one patients with COVID-19 were enrolled and stratified according to the SARS-CoV-2 strain: six with the Alpha, 10 with the Delta, and five with the Omicron variant. Fecal microbiome analysis showed that α-diversity was reduced in the order of the Omicron, Delta, and Alpha variants (p = 0.07). Linear discriminant analysis revealed differences in the abundance of short-chain fatty acid-producing gut microbiota for each SARS-CoV-2 variant. Fecal metabolome analysis showed that the Omicron and Delta variants had markedly reduced propionic and lactic acid levels compared to the Alpha strain (p

Abstract Objectives Endoscopic ultrasonography is an important examination for periampullary diseases. The duodenum is filled with water to ensure a clear image and distend the duodenal wall without burying the papilla within duodenal folds; however, peristalsis frequently makes it difficult to maintain water within the duodenum. The gel immersion method (intestine is filled with viscosity gel) has recently been attracting attention. We evaluated the usefulness of using this method for endoscopic ultrasonography to detect and delineate the major duodenal papilla. Methods Fifty‐nine consecutive patients who underwent gel immersion‐endoscopic ultrasonography between February and March 2021 were included retrospectively. The papilla was observed by filling the duodenum with clear viscosity gel. Outcomes were the rate of duodenal distention, delineation rates of the papilla, the time required for delineation, volume of the gel used, and adverse events. Results Duodenal distention was excellent, good, and poor in 58%, 34%, and 7% of cases, respectively. The delineation rates of the papilla in the axial and longitudinal views were 98% and 66%, respectively. The median time required to delineate the papilla in each view was 3.1 (range, 1.0–1.4) and 7.9 (1.9–28.6) min; the median volume of the gel used was 80 (30–150) ml and 100 (50–200) ml, respectively. No adverse events were noted. Conclusions Gel immersion‐endoscopic ultrasonography provided sufficient duodenal distention, leading to high rates of detection and delineation of the papilla using a small volume of gel within a short time. This method may be useful for the evaluation of the ampullary region.

Background: Precut papillotomy is performed in cases of difficult biliary cannulation, but identification of the biliary orifice is difficult. Texture and color enhancement imaging (TXI) can enhance the structure, color, and brightness. This study compared TXI and white light imaging (WLI) in visibility of biliary orifices. Methods: We retrospectively examined 20 patients who underwent bile duct cannulation using both WLI and TXI after precut papillotomy at our center between 2021 and 2022. On WLI and TXI images displayed in random order, bile duct orifice on precut‐incision surface of each image was independently evaluated by eight evaluators. Single‐indication accuracy rate of biliary orifices, visibility score rated on a 4‐grade scale, and color difference between the biliary orifice and the surrounding tissue were examined. Results: The single‐indication accuracy rate was higher in TXI compared to WLI (50.6% vs. 35.6%, odds ratio 2.26 [95% CI: 1.32–3.89], p =.003). The time to indicate the biliary orifice was comparable between TXI and WLI (median, 9.7 s [range, 2.6–43] vs. 10.9 s [1.5–64], p =.086). Furthermore, the visibility score was higher in TXI than in WLI (median, 3 [interquartile range, 2–3] vs. 2 [2, 3], p <.001), and the color difference between the biliary orifice and surrounding tissue in TXI was more pronounced than in WLI (median, 22.9 [range, 9.39–55.2] vs. 18.0 [6.48–43.0]; p <.001). Conclusions: TXI enhanced the color difference and visibility of the biliary orifice after precut and improved single‐indication accuracy rate, suggesting that it could be useful for biliary cannulation after precut papillotomy. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim With the control of viral hepatitis, alcoholic hepatocellular carcinoma (HCC) is becoming increasingly important in Japan. In alcoholic cirrhosis, the impact of portal hypertension is significant. Thus, it may be difficult to predict prognosis accurately with the reported prognostic scores. Here we propose the platelet‐albumin‐bilirubin tumor nodes metastasis (TNM) score (PALBI‐T score) as a prognostic model for HCC in alcoholic liver disease, and investigate its usefulness. The PALBI‐T score is an integrated score based on the TNM stage and PALBI grade including platelets, reflecting portal hypertension. Methods This study included 163 patients with alcoholic HCC treated at our Center from 1997 to 2018. We compared the prognostic prediction abilities of the Japan Integrated Staging (JIS) score, ALBI‐T score, and PALBI‐T score. The PALBI‐T score was calculated similarly to the JIS and ALBI‐T scores. Areas under the receiver operating characteristic curve (AUC) were calculated for predicting overall survival (OS). Results In predicting the 1‐year survival, the JIS score had a larger AUC (AUC = 0.925) than the ALBI‐T score (AUC = 0.895) and PALBI‐T score (AUC = 0.891). On the other hand, there was no significant difference in predicting OS among the integrated scores. The PALBI‐T score (AUC = 0.740) had the largest AUC, and the JIS score (AUC = 0.729) and ALBI‐T score (AUC = 0.717) were not significantly different from the PALBI grade (AUC = 0.634). The PALBI grade reflected the degree of portal hypertension. Conclusion In patients with alcoholic HCC, the Japan Integrated Staging score is useful for predicting short‐term prognosis. The PALBI‐T score, which reflects portal hypertension, appears to be a more valid prognostic score for predicting long‐term prognosis.

Abstract Pancreatic duct stenting is a well-established method for reducing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, there is no consensus on the optimal type of plastic stent. This study aimed to evaluate the feasibility and safety of a new 4-Fr plastic stent for pancreatic duct stenting. Forty-nine consecutive patients who placed the 4-Fr stent into the pancreatic duct (4Fr group) were compared with 187 consecutive patients who placed a conventional 5-Fr stent (control group). The primary outcome was technical success. Complications rate, including post-ERCP pancreatitis (PEP) were the secondary outcomes. Propensity score matching was introduced to reduce selection bias. The technical success rate was 100% in the 4Fr group and 97.9% in the control group (p = 0.315). Post-ERCP amylase level was significantly lower in the 4-Fr group than the control group before propensity score matching (p = 0.006), though without statistical significance after propensity score matching (p = 0.298). The rate of PEP in the 4Fr group (6.1%) was lower than the control group (15.5%), though without statistical significance before (p = 0.088) and after (p = 1.00) propensity score matching. Pancreatic duct stenting using a novel 4-Fr plastic stent would be at least similar or more feasible and safe compared to the conventional plastic stent.

Abstract JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504–0.937) in the low CCr group. Although the total number of incidences of all Grade 3–4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.

Abstract Purpose Effective second‐line chemotherapy options are limited in treating advanced biliary tract cancers (BTCs). Resminostat is an oral histone deacetylase inhibitor. Such inhibitors increase sensitivity to fluorouracil, the active form of S‐1. In the phase I study, addition of resminostat to S‐1 was suggested to have promising efficacy for pre‐treated BTCs. This study investigated the efficacy and safety of resminostat plus S‐1 in second‐line therapy for BTCs. Methods Patients were randomly assigned to receive resminostat or placebo (200 mg orally per day; days 1–5 and 8–12) and S‐1 group (80–120 mg orally per day by body surface area; days 1–14) over a 21‐day cycle. The primary endpoint was progression‐free survival (PFS). Secondary endpoints comprised overall survival (OS), response rate (RR), disease control rate (DCR), and safety. Results Among 101 patients enrolled, 50 received resminostat+S‐1 and 51 received placebo+S‐1. Median PFS was 2.9 months for resminostat+S‐1 vs. 3.0 months for placebo+S‐1 (HR: 1.154, 95% CI: 0.759–1.757, p = 0.502); median OS was 7.8 months vs. 7.5 months, respectively (HR: 1.049, 95% CI: 0.653–1.684, p = 0.834); the RR and DCR were 6.0% vs. 9.8% and 70.0% vs. 78.4%, respectively. Treatment‐related adverse events (TrAEs) of grade ≥ 3 occurring more frequently (≥10% difference) in the resminostat+S‐1 than in the placebo+S‐1 comprised platelet count decreased (18.0% vs. 2.0%) and decreased appetite (16.0% vs. 2.0%). Conclusions Resminostat plus S‐1 therapy improved neither PFS nor OS for patients with pre‐treated BTCs. Addition of resminostat to S‐1 was associated with higher incidence of TrAEs, but these were manageable (JapicCTI‐183883).

Background: Endoscopic papillectomy (EP) is less invasive than surgery but procedure‐related adverse events (AEs) still frequently occur. This study compared the benefits of EP using a new optimal endoCUT setting on the VIO (Erbe) electrosurgical unit (VIO‐EP) with those using the conventional electrosurgical unit setting (ICC‐EP, Erbe). Methods: This multicenter, retrospective, comparative cohort study included 57 patients who underwent VIO‐EP and 91 who underwent ICC‐EP. The primary outcome was occurrence of EP‐related AEs. Secondary outcomes were pathological findings (the resection margins, the R0 resection, and residual lesions). Results: Pancreatitis tended to be less common in the VIO‐EP group (5.3% vs. 9.9%, p =.248). Evaluation of computed tomography images showed that pancreatitis was confined to the pancreatic head in 77.8% of cases in the ICC‐EP group and in 33.3% of those in the VIO‐EP group. After exclusion of cases of delayed bleeding, pancreatitis tended to be less common in the VIO‐EP group; this finding was not statistically significant (2.3% vs. 8.2%, p =.184). In pathological findings, residual lesions were significantly less common in the VIO‐EP group. Conclusions: The risks of pancreatitis and residual lesions after EP may be lower when the VIO electrosurgical unit is used with the optimal setting. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to clarify the clinical utility of measuring serum pancreatic enzymes after endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of predicting post‐ERCP pancreatitis (PEP) by a meta‐analysis of diagnostic test accuracy studies. Methods: Studies on the prediction accuracy of PEP by serum amylase or lipase measured at 2, 3, and 4 h after ERCP were collected. A literature search was performed in PubMed and the Cochrane Library database for studies published between January 1980 and March 2023. The quality of individual studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies‐2. Data were analyzed using Meta‐DiSc 2.0 software. Results: We searched the databases and identified 20 observational studies (12,313 participants). PEPs were defined according to criteria by Cotton or modified Cotton, revised Atlanta criteria, or the Japanese criteria. Meta‐analysis of eight studies (4389 participants) showed a pooled sensitivity of 71.1% (95% confidence interval [CI] 56.1–82.5) and pooled specificity of 91.2% (95% CI 85.9–94.6) for the serum amylase cut‐off value at 3 times the upper limit of normal (ULN). Another meta‐analysis of five studies (1970 participants) showed a pooled sensitivity of 85.8% (95% CI 61.9–95.7) and pooled specificity of 85.3% (95% CI 81.9–88.1) for the serum lipase cut‐off value at 3 times ULN. Conclusion: Despite a high risk of bias due to various reference standards, this updated meta‐analysis and the utility assessment by a decision tree showed the utility of serum amylase or lipase levels more than 3 times ULN measured 2–4 h after ERCP for predicting PEP. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study was to evaluate the safety and efficacy of partially covered self-expandable metallic stents (PCSEMS) in patients undergoing neoadjuvant chemo(radio) therapy (NAC) for pancreatic cancer (PC). Methods: This was a prospective multicenter study to evaluate the safety and efficacy of PCSEMS in patients receiving NAC for resectable and borderline resectable PC. The primary endpoint was the rate of recurrent biliary obstruction (RBO). Results: Twenty-six patients with PC (three with resectable PC and 23 with borderline resectable PC) who underwent NAC at seven Japanese centers were included in the analysis. Both the technical and functional success rates of PCSEMS placement were 100%. Early stent-related complications were observed in three patients (11.5%): mild pancreatitis (n=2) and mild liver abscess (n=1). The median time to surgery or palliation was 4.0 months. Surgical resection was eventually performed in 73.1% of patients, and stent removal during surgery was successful in all patients. RBO was observed in nine patients (34.6%): seven with stent occlusion, one with kinking and one with migration. The RBO rates in resected cases and nonresected cases were 36.8% and 28.6%, respectively. Conclusions: Biliary drainage by PCSEMS was safe and feasible in patients undergoing NAC for resectable and borderline resectable PC.

Introduction Neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy (NAC/NACRT) for resectable/borderline resectable pancreatic cancers was recently performed to improve clinical outcomes and led to good results, although it remains controversial whether NAC/NACRT is beneficial for resectable pancreatic cancer. A few recent studies revealed longer patency and lower cost related to the stent occlusion of a metal stent than those of a plastic stent during NAC/NACRT. It also remains controversial which type of self-expandable metal stent (SEMS) is the most suitable for patients with resectable/borderline resectable pancreatic cancer during NAC/NACRT: an uncovered SEMS (USEMS), a fully covered SEMS (FCSEMS) or a partially covered SEMS (PCSEMS). So far, two randomised controlled trials indicated that a USEMS and an FCSEMS were similar in preoperative stent dysfunction and adverse event rate. Thus, we aimed to verify the non-inferiority of a PCSEMS to a USEMS in this multicentre randomised controlled trial.Methods and analysis We designed a multicentre randomised controlled trial, for which we will recruit 100 patients with resectable/borderline resectable pancreatic cancer and distal biliary obstruction scheduled for NAC/NACRT from 13 high-volume institutions. Patients will be randomly allocated to the PCSEMS group or USEMS group. The primary outcome measure is the preoperative biliary event rate. Data will be analysed after completion of the study. We will calculate the 95% CIs of the incidence of preoperative biliary events in each group and analyse whether the difference between them is within the non-inferiority margin (10%).Ethics and dissemination This study has been approved by the institutional review board of Hokkaido University Hospital. The results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal.Trial registration number UMIN000041737; jRCT1012200002.