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The high geochemical reactivity of boron and the large relative mass difference between10B and11B lead to significant boron isotope fractionation in nature. So far the measured range of boron isotope composition (δ11B) varies between –70 and +75‰. The negative δ11B values are found in non-marine evaporite borate minerals and tourmalines, whereas positive δ11B values are common in salt lake brines and evaporated seawater. Since the 1980s, with improved measurement methods, applications of boron isotope analysis have increased rapidly. At present, boron isotopes are successfully applied to reconstruct ancient marine environments, to determine depositional environments and ore genesis, to trace groundwater pollution and seawater intrusion, and to study continental erosion. This paper summarises the methods for boron isotope analysis, the mechanisms of boron isotope fractionation and the distribution of boron isotopes in nature, reviews the achievements and the problems of boron isotopes in geochemical applications, and proposes research directions of boron isotopes in geochemical fields. [ABSTRACT FROM PUBLISHER]

Objective: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment., Methods: ApoE -/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation., Results: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36., Conclusion: Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level., Competing Interests: Conflict of Interest: No conflict of interest declared. Declaration of Figures Authenticity: All figures submitted have been created by the authors who confirm that the images are original with no duplication and have not been previously published in whole or in part., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: In this study we aimed to comprehensively evaluate the clinical features and treatment outcomes of Chinese patients with autoimmune pancreatitis (AIP) through a single-center real-world study., Methods: Patients diagnosed with AIP in Changhai Hospital, Naval Medical University from January 2014 to December 2021 were included. Baseline characteristics, laboratory test results, cross-sectional imaging and endoscopic ultrasound (EUS) findings, and long-term follow-up data were obtained. The differences in these characteristics between type 1 and type 2 AIP patients were analyzed., Results: Among all 320 patients, 271 (84.7%) and 49 (15.3%) had type 1 and type 2 AIP, respectively. The most common initial symptom was abdominal discomfort (58.1%), followed by obstructive jaundice (32.5%). Extrapancreatic organ involvement was identified in 126 (39.4%) patients, with the biliary system being the most commonly involved (36.6%). Elevated serum IgG4 level was rare in type 2 AIP patients. The diagnostic accuracy of computed tomography (CT), magnetic resonance imaging (MRI), and EUS for definitive and probable AIP were 78.0%, 68.7%, and 80.5%, respectively. EUS-guided tissue acquisition with immunohistochemical staining helped establish a final diagnosis in 39.7% of patients. During the follow-up period of 60 months, 18.6% of patients experienced relapse. The 1-, 3-, and 5-year relapse rates were higher in type 1 AIP patients, with an accumulated rate of 8.0%, 12.6%, and 15.1%, when compared with those with type 2 AIP., Conclusions: Type 2 AIP is not uncommon in Chinese population. The diagnostic accuracy of CT and EUS for AIP might be superior to that of MRI., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background and Objective: To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 ( 125 I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer., Methods: We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS- 125 I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups., Results: EUS-CPN and 125 I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS- 125 I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS- 125 I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure., Conclusions: Both EUS-CPN and EUS- 125 I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS- 125 I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different., Competing Interests: Zhen-Dong Jin is an Associate Editor of the journal. This article was subject to the journal's standard procedures, with peer review handled independently of the editor and his research group., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Scholar Media Publishing.)

The geochemistry of Li and Li isotopes is a promising tracer of chemical weathering processes for both modern and ancient times. Therefore, accurate and precise determination of the isotopic composition of Li is required for a large variety of complex geological samples with different Li concentrations and matrix/Li ratios. Especially, geochemical studies of precious geological samples with ultra-low lithium content and high matrix. In this study, the accuracy and the precision corresponding to Li isotopic measurements of low-level samples using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) with membrane desolvation introduction system was evaluated. The method of MC-ICP-MS with membrane desolvation and a high-sensitivity X-skimmer cone, together with a simple one-step column separation enabled the high-precision isotopic analysis of Li quantities as small as 2 ng. The long-term instrumental external reproducibility of δ 7 Li values for the L-SVEC and SPEX-Li were 0.0 ± 0.1‰ ( n = 20) and 12.1 ± 0.4‰ ( n = 20), respectively. Based on the measurements on a series of international reference materials over the last two years. The measured δ 7 Li values for the standards with a variety of matrices, including BHVO-2, AGV-2 and seawater (NASS-6). The δ 7 Li values of BHVO-2 (4.58 ± 0.35‰), AGV-2 (6.85 ± 0.40‰) and NASS-6 (30.88 ± 0.20‰) are in agreement with the published data within the uncertainty. We also present analytical results for South China Sea surface seawater water, meteorite, limestones and rain water. These results demonstrate the validity of the method for obtaining highly precise and accurate outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Introduction: Evidence on the comparative diagnostic performance of endoscopic ultrasound (EUS)-based techniques for pancreatic cystic lesions (PCLs) is limited. This network meta-analysis comprehensively compared EUS-based techniques for PCL diagnosis., Methods: A comprehensive literature search was performed for all comparative studies assessing the accuracy of 2 or more modalities for PCL diagnosis. The primary outcome was the diagnostic efficacy for mucinous PCLs. Secondary outcomes were the diagnostic efficacy for malignant PCLs, diagnostic success rate, and adverse event rate. A network meta-analysis was conducted using the ANOVA model to assess the diagnostic accuracy of each index., Results: Forty studies comprising 3,641 patients were identified. The network ranking of the superiority index for EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) and EUS-guided through-the-needle biopsy (EUS-TTNB) were significantly higher than other techniques for differentiating mucinous PCLs; besides, EUS-TTNB was also the optimal technique in identifying malignant PCLs. The evidence was inadequate for EUS-nCLE diagnosing malignant PCLs and contrast-enhanced harmonic EUS diagnosing both mucinous and malignant PCLs. Glucose showed a high sensitivity but low specificity, and molecular analysis (KRAS, GNAS, and KRAS + GNAS mutations) showed a high specificity but low sensitivity for diagnosing mucinous PCLs. Satisfactory results were not obtained during the evaluation of the efficiency of pancreatic cyst fluid (PCF) biomarkers in detecting malignant PCLs., Discussion: For centers with relevant expertise and facilities, EUS-TTNB and EUS-nCLE were better choices for the diagnosis of PCLs. Further studies are urgently required for further improving PCF biomarkers and validating the diagnostic performance of the index techniques., (Copyright © 2022 by The American College of Gastroenterology.)

Background and Objectives: EUS has recently gained attraction in mainland China. This study aimed to evaluate the development of EUS from results of two national surveys., Methods: EUS-related information, including infrastructure, personnel, volume, and quality indicator, was extracted from the Chinese Digestive Endoscopy Census. Data from 2012 and 2019 were compared, and differences among various hospitals and regions were analyzed. The EUS rates (EUS annual volume per 100,000 inhabitants) between China and developed countries were also compared., Results: The number of hospitals performing EUS in mainland China increased from 531 to 1236 (2.33-fold), and 4025 endoscopists performed EUS in 2019. The volumes of all EUS and interventional EUS increased from 207,166 to 464,182 (2.24-fold) and 10,737 to 15,334 (1.43-fold), respectively. The EUS rate in China was lower than that in developed countries but showed a higher growth rate. EUS rate varied substantially among different provincial regions (in 2019: 4.9-152.0 per 100,000 inhabitants) and showed significant positive association with gross domestic product per capita (in 2019: r = 0.559, P = 0.001). The EUS-FNA-positive rate in 2019 was comparable between hospitals in terms of annual volume (≥50 or < 50: 79.9% vs. 71.6%, P = 0.704) and practice duration (starting EUS-FNA before or after 2012: 78.7% vs. 72.6%, P = 0.565)., Conclusion: EUS has developed considerably in China in recent years but still needs substantial improvement. More resources are in demand for hospitals in less-developed regions and with low EUS volume., Competing Interests: None

Background and Objectives: It remains unclear whether the use of the stylet slow-pull (SP) and wet suction (WS) can improve the yield of endoscopic ultrasound-guided fine-needle biopsy compared to standard suction (SS). The aim of this study was to compare the diagnostic efficacy of the three sampling techniques when using 25G ProCore needles for solid pancreatic lesions., Materials and Methods: This multicenter single-blind randomized crossover superiority trial enrolled patients with solid pancreatic lesions (n = 300) from four digestive endoscopic centers in China. All three sampling techniques were performed on each patient using a 25G ProCore needle in a randomized sequence. The diagnostic efficacy, the specimen yield, and quality of each technique, the overall technical success rate and diagnostic yield of the 25G ProCore needle, and rate of adverse events were evaluated., Results: A total of 291 patients were analyzed. No significant difference was found in diagnostic efficiency among the three techniques (sensitivity, 82.14% vs. 75.00% vs. 77.86, P = 0.1186; accuracy, 82.82% vs. 75.95% vs. 78.69%, P = 0.1212). The SP had an inferior tissue integrity compared to the SS and WS techniques (71.82% vs. 62.55% vs. 69.76%, P = 0.0096). There was no significant difference in the degree of blood contamination among the three groups (P = 0.2079). After three passes, the overall sensitivity was 93.93%, and the accuracy was 94.16%., Conclusions: SS and WS techniques are better choices than SP technique for 25G ProCore needle, for they could provide higher specimen adequacy without increasing the amount of blood contamination. The 25G ProCore needle can provide a satisfactory diagnostic yield for solid pancreatic lesions., Competing Interests: None

Background: There is huge shortage of ERCP practitioners (ERCPists) in China, and ERCP training is urgently needed. ChangHai Advanced eNdoscopy Courses for ERCP (CHANCE) is a 4-month program for ERCP training since 2004. This study evaluated the efficiency of this short-term training model, and reported on the ERCP careers of the trainees following completion of the CHANCE program., Methods: This study was a retrospective investigation included all the CHANCE trainees from Jan 2004 to Dec 2014. Questionnaires were sent to all trainees. The career competence percentage, ERCP careers and predictive factors of career competence were investigated and analyzed., Results: A total of 413 trainees participated in the CHANCE program over 11 years covered by the survey and 258 questionnaires were valid for the study. The mean (SD) age of the trainees was 35.36 (4.17), and the male to female ratio was 4.4:1. The average follow-up time was 7.77 (3.44) years. A total of 173 (67.1%) trainees had achieved career competence. In terms of ERCP careers, the mean annual ERCP volume was 120.60 (96.67), with a complication percentage of 8.2%. Hospital qualification, compliance with follow-up learning guidance, participating academic activity, and practitioner type were identified predictive factors of career competence., Conclusions: As a short-term training program, the CHANCE achieved an acceptable career competence percentage, providing endoscopists more chances to learn ERCP and giving them appropriate training guidance for career competence. This training mode is worth promoting in developing countries with shortage of ERCPists., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Esophagogastroduodenoscopy (EGD) is fundamental for detecting upper gastrointestinal (GI) neoplasms. However, the impact of sedation on small neoplasm detection during EGD has not been evaluated. The aim of this study was to investigate whether EGD with sedation could improve small upper GI neoplasm detection., Methods: This propensity score-matched retrospective study analyzed the medical records of outpatients undergoing diagnostic EGD at a large tertiary center between January 2013 and December 2018. The primary outcome was the detection rate of small upper GI neoplasms (≤10 mm). The secondary outcomes were biopsy rate and small neoplasms in different anatomic subsites., Results: After propensity score matching, 20,052 patients undergoing diagnostic EGD with or without propofol sedation were identified. A higher detection rate of small upper GI neoplasms was observed in the sedation group (2.80% vs. 2.02%; p < .001). In particular, the detection rate of small cancers in the sedation group was 3-fold higher than that in the no-sedation group (0.16% vs. 0.05%; p = .023). Small neoplasms were more likely identified at the gastric antrum (1.60% vs. 1.09%; p = .002) and angulus (0.66% vs. 0.45%; p = .044) in the sedation group. In addition, endoscopists were more likely to take biopsies when performing sedated EGD (41.4% vs. 36.4%, p < .001), and a higher biopsy rate was associated with an increased detection rate of small neoplasms., Conclusions: Sedation was significantly associated with a higher detection rate of small upper GI neoplasms and might be recommended for improving the quality of EGD.

Background and Objects: An atypical cytologic diagnosis arises from inflammation or early neoplastic process. It is commonly found in EUS-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) tissue sampling of pancreatic malignancies. The aims of this study were to evaluate the diagnostic performance of EUS-FNA/FNB in patients with cytologic diagnosis of atypical cells and to develop a prediction model for malignant tumors of the pancreas in the atypical cytologic diagnostic category., Methods: Two hundred and twenty-six patients in the atypical cytologic diagnostic category were analyzed. Multivariate logistic regression analyses were performed to determine predictive factors for pancreatic malignancies. The final diagnoses were confirmed by repeat biopsy; surgical pathology, or clinical follow-up for at least 6 months., Results: The atypical cytologic diagnosis using EUS-FNA/FNB was associated with an absolute risk of malignancy (82.3%). Multivariate logistic regression analyses revealed that older age, long axis of the mass, and increased carbohydrate antigen 19-9 (CA19-9) were independent risk factors for true malignant pancreatic tumors among patients in the atypical cytologic diagnostic category. The calibration curve had a slope of 0.96, and a regression coefficient (R 2 ) of 0.91. The area under the receiver operating characteristic curve of the validation group was 0.803., Conclusions: Atypical lesions of EUS-FNA/FNB have a higher risk of malignancy. Older age, the long axis of the mass, and elevated serum CA19-9 level were identified as independent risk factors for true malignant pancreatic tumors among patients in the atypical cytologic diagnostic category., Competing Interests: None

Background: Pancreatitis is the most common complication of pancreatic extracorporeal shock wave lithotripsy (ESWL). There has been little research into effective prevention of post-ESWL pancreatitis. Therefore, we aimed to assess the efficacy of prophylactic rectal indometacin in preventing post-ESWL pancreatitis., Methods: In this double-blind, randomised, placebo-controlled trial done at Changhai Hospital (Shanghai, China), patients aged 18 years or older with chronic pancreatitis and pancreatic stones (>5 mm in diameter) who were eligible for treatment with ESWL were randomly allocated using a computer-generated randomisation table, in a 1:1 ratio, to receive 100 mg rectal indometacin or identical glycerin (placebo) suppositories 30 min before ESWL. Patients, endoscopists, and outcome assessors were masked to group allocation. The primary outcome was the incidence of post-ESWL pancreatitis within 24 h of ESWL, analysed by the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02797067., Findings: Between May 31, 2016, and June 26, 2019, 1370 patients were enrolled, with 685 patients randomly assigned to the rectal indometacin group and 685 patients to the placebo group. All patients received their allocated intervention and completed final follow-up, and were included in the intention-to-treat analysis. Post-ESWL pancreatitis occurred in 60 (9%) patients in the rectal indometacin group and 84 (12%) patients in the placebo group (relative risk 0·71, 95% CI 0·52-0·98; p=0·042). Transient adverse events occurred in 235 (34%) patients in the rectal indometacin group and 252 (37%) patients in the placebo group, with asymptomatic hyperamylasaemia being the most common (189 [28%] patients vs 197 [29%] patients). No difference was noted between groups in the incidence of other complications and transient adverse events., Interpretation: Pre-procedural administration of rectal indometacin is an efficacious and safe means of reducing the incidence of post-ESWL pancreatitis., Funding: Programs of Shanghai Municipal Government and the "Ten Thousand Plan"-National High Level Talents Special Support Plan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that mainly affects young women., Aim: To evaluate the impact of parenchyma-preserving surgical methods (PPMs, including enucleation and central pancreatectomy) in the treatment of SPN patients., Methods: From 2013 to 2019, patients who underwent pancreatectomy for SPNs were retrospectively reviewed. The baseline characteristics, intraoperative index, pathological outcomes, short-term complications and long-term follow-up data were compared between the PPM group and the conventional method (CM) group., Results: In total, 166 patients were included in this study. Of them, 33 patients (19.9%) underwent PPM. Most of the tumors (104/166, 62.7%) were found accidentally. Comparing the parameters between groups, the hospital stay d (12.35 vs 13.5 d, P = 0.49), total expense (44213 vs 54084 yuan, P = 0.21), operation duration (135 vs 120 min, P = 0.71), and intraoperative bleeding volume (200 vs 100 mL, P = 0.49) did not differ between groups. Regarding pathological outcomes, tumor size (45 vs 32 mm, P = 0.07), Ki67 index ( P = 0.53), peripheral tissue invasion (11.3% vs 9.1%, P = 0.43) and positive margin status (7.5% vs 6%, P = 0.28) also did not differ between groups. Moreover, PPM did not increase the risk of severe postoperative pancreatic fistula (3.8% vs 3.0%, P = 0.85) or tumor recurrence (3.0% vs 6.0%, P = 0.39). However, the number of patients who had exocrine insufficiency during follow-up was significantly lower in the PPM group (21.8% vs 3%, P = 0.024). CM was identified as an independent risk factor for pancreatic exocrine insufficiency (odds ratio = 8.195, 95% confident interval: 1.067-62.93)., Conclusion: PPM for SPN appears to be feasible and safe for preserving the exocrine function of the pancreas., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: This study aimed to examine the effects of a training program combining formal cytological curriculum and practical assessments on endosonographers and to determine how many operations were needed for training through learning curves., Methods: A formal cytological curriculum was implemented in November 2019 for four endosonographers. The competency of endosonographers before and after the curriculum was judged by quantitative scores. From December 2019 to October 2020, trainees independently examined the adequacy and atypia grade of pancreatic specimens acquired by EUS-guided-fine-needle biopsy based on specific atypical grading criteria. The accuracy of the adequacy and atypia assessment of each trainee was calculated, and learning curves were drawn to evaluate the improvement., Results: The median posttraining score improved by 87% from 49 to 91.5 out of 100. Ninety patients were enrolled in the practical assessments. The accuracy for specimen adequacy and atypia assessment of each trainee was 91.7%, 92.8%, 91.0%, and 89.3% and 80.0%, 82.1%, 81.0%, and 78.9%. The learning curves of each trainee showed a steady and significant improvement, and ninety cases were sufficient for satisfactory adequacy assessment., Conclusions: Basic knowledge of on-site cytopathologic evaluation can be gained through standardized and systematic training. Practical assessments showed that, at the completion of ninety cases, trained endosonographers reached a satisfactory level of recognizing specimen adequacy, but continue practice was needed for atypia assessment., Competing Interests: None

Background: Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice., Aim: To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies., Methods: With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital., Results: The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time ( P = 0.32; P = 0.16, respectively)., Conclusion: CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted., Competing Interests: Conflict-of-interest statement: Wu JR, Chen LZ, Chang J and Song P were staff of Tencent Healthcare (Shenzhen) Co. LTD, which supported the work with provision of research grants, prototype software, prototype PC and GPU units. The other authors have no conflicts of interest to declare. The sponsor had no involvement in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, and approval of the manuscript; or the decision to submit the manuscript for publication., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Although endoscopic ultrasound (EUS) features and criteria have been described in chronic pancreatitis, challenges remain with interoperator variability and ease of adoption. The aim of this study was to define and validate the EUS features of chronic pancreatitis in a multicenter prospective study in Asia., Method: The study was divided into two parts: the first part was conducted to derive the EUS features of chronic pancreatitis with adequate interoperator agreement; the second was to prospectively evaluate these features in a multicenter cross-sectional study and determine the optimal combination of features for the diagnosis of chronic pancreatitis. Prospectively enrolled cases had standard internationally validated radiologic or histologic features of chronic pancreatitis, and controls were patients without chronic pancreatitis who underwent EUS examination., Results: The top six EUS features that had good interobserver agreement (mean kappa 0.73, range 0.60 - 0.90) were selected to be further evaluated in part II of the study. These included: hyperechoic foci with shadowing, lobularity with honeycombing, cysts, dilated main pancreatic duct, dilated side branches, and calculi in the main pancreatic duct. A total of 284 subjects (132 cases, 152 controls) were enrolled from 12 centers in Asia. All six features had high accuracy ranging from 63.3 % to 89.1 %. Two or more of these six EUS features accurately defined chronic pancreatitis (sensitivity 94.7 %, specificity 98.0 %), with an area under the receiver operating curve of 0.986., Conclusion: This multicenter Asian study characterized and defined the EUS features of chronic pancreatitis. This provides a useful tool in clinical practice and further research in pancreatic cancer surveillance., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Early detection of advanced cystic mucinous neoplasms [(A-cMNs), defined as high-grade dysplasia or malignancy] of the pancreas is of great significance. As a simple and feasible detection method, serum tumor markers (STMs) may be used to predict advanced intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). However, there are few studies on the usefulness of STMs other than carbohydrate antigen (CA) 19-9 for early detection of A-cMNs., Aim: To study the ability of five STMs-CA19-9, carcinoembryonic antigen (CEA), CA125, CA724, and CA242 to predict A-cMNs and distinguish IPMNs and MCNs., Methods: We mainly measured the levels of each STM in patients pathologically diagnosed with cMNs. The mean levels of STMs and the number of A-cMN subjects with a higher STM level than the cutoff were compared respectively to identify the ability of STMs to predict A-cMNs and distinguish MCNs from IPMNs. A receiver operating characteristic curve with the area under curve (AUC) was also created to identify the performance of the five STMs., Results: A total of 187 patients with cMNs were identified and 72 of them showed A-cMNs. We found that CA19-9 exhibited the highest sensitivity (SE) (54.2%) and accuracy (76.5%) and a moderate ability (AUC = 0.766) to predict A-cMNs. In predicting high-grade dysplasia IPMNs, the SE of CA19-9 decreased to 38.5%. The ability of CEA, CA125, and CA724 to predict A-cMNs was low (AUC = 0.651, 0.583, and 0.618, respectively). The predictive ability of CA242 was not identified. The combination of STMs improved the SE to 62.5%. CA125 may be specific to the diagnosis of advanced MCNs., Conclusion: CA19-9 has a moderate ability, and CEA, CA125, and CA724 have a low ability to predict A-cMNs. The combination of STM testing could improve SE in predicting A-cMNs., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Various modalities are applied for pathological diagnosis of malignant biliary strictures (MBS), including brush cytology (BC), forceps biopsy (FB) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). We aimed to assess the value of these modalities in a repeated tissue acquisition process for biliary strictures with initially inconclusive pathological outcomes., Methods: Patients who were suspected of having MBS and underwent a BC in two large teaching hospitals were retrospectively included. The sensitivity, specificity, positive and negative predictive values, and accuracy of the initial and repeated BC, FB and EUS-FNA were analyzed. Their performances were compared to determine which modality was superior in repeated tissue acquisition., Results: In total, 476 patients were included. The sensitivity, specificity and accuracy in diagnosing MBS for the initial BC were 30.3%, 100% and 55.0%, respectively. Altogether 39, 27 and 44 patients underwent a repeat BC, FB and EUS-FNA, respectively. The sensitivity for repeated BC, FB and EUS-FNA was 41.2%, 61.1% and 44.4%, respectively, whereas their specificity all reached 100%. When comparing diagnostic accuracy, none of the modalities was superior (74.4% vs 74.1% vs 54.5%, P = 0.173). In the repeated process, one patient who underwent BC and two underwent FB developed mild pancreatitis., Conclusions: Repeated tissue acquisition achieves a conclusive diagnosis of MBS in nearly half patients who have an initially inconclusive cytological diagnosis. None of the tissue acquisition methods is significantly superior in the repeated process., (© 2020 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background and Objectives: The sensitivity of EUS-guided fine-needle biopsy (EUS-FNB) varies considerably. The optimal number of passes through a solid pancreatic lesion with a 22G FNB needle during EUS-FNB is controversial. This prospective randomized controlled study aimed to determine the optimal number of needle passes during EUS-FNB of solid pancreatic lesions, with 22G FNB needles and different sampling techniques., Methods: Pancreatic masses were sampled using 22G FNB needles with either the stylet slow-pull (SP) technique or the standard-suction (SS) technique. We determined the number of needle passes required to obtain a diagnostic accuracy of >90%. Differences between the two techniques in terms of technical success rate, cytological acquisition, core tissue acquisition, sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and complications were analyzed., Results: A total of 120 patients were randomly assigned to either SP or SS group. Three patients who were lost to follow-up and one who did not complete 5 passes due to bent needle head were excluded from the study. Fifty-six cases in the SP group and 60 cases in the SS group were included in the analysis. For SP technique, the cumulative accuracy of passes 1, 2, 3, 4, and 5 was 44.83%, 76.79%, 87.50%, 92.86%, and 94.64%, respectively. For SS technique, the cumulative accuracy of passes 1, 2, 3, 4, and 5 was 71.67%, 85.0%, 90.0%, 93.33%, and 95.0%, respectively. For each group, there was no statistically significant difference in accuracy after 3 and 4 passes. After 4 passes, the pooled sensitivity (92.59% vs. 93.10%), accuracy (92.86% vs. 93.10%), and specificity (100% vs. 100%) were similar (P > 0.05) in the SP and SS groups, respectively. In addition, positive cytological diagnoses (83.9% vs. 85.0%) and positive histological diagnoses (71.4% vs. 78.3%) were comparable (P > 0.05) in the SP and SS groups, respectively. No statistically significant factor was found associated with diagnostic sensitivity for each group., Conclusion: When on-site cytological evaluation is unavailable, we recommend that at least 3 passes with 22G ProCore needles be performed during EUS-FNB using the SS technique, at least 4 passes when using SP technique. The SS technique showed potential advantages over SP technique in tissue acquisition and diagnostic capabilities., Competing Interests: None

For a definitive diagnosis of fine-needle aspiration (FNA)/biopsy, one of the reliable techniques to determine the adequacy and accuracy rapid on-site evaluation (ROSE) of cytological samples is preferable. Because of the lack of trained pathologists, alternatives have to be explored. This study is primarily conducted to determine the diagnostic sensitivity and specificity of full-field optical coherence tomography (FF-OCT) and secondarily to evaluate the possibility of FF-OCT differentiating different types of pancreatic diseases. The diagnostic coherence of FF-OCT by a trained assistant (endoscopist) and trained pathologist is also compared. This is a single-center, prospective, observation trial. Eighty patients would be enrolled in the study. The tissue samples acquired by endoscopic ultrasound fine-needle biopsy (EUS-FNB) would be imaged by the FF-OCT system, interpreted by a trained endoscopist and a pathologist. The results of the image interpretation would be verified with histological findings. This study determines the diagnostic capability of FF-OCT as a ROSE technique while performing EUS-FNB, and whether endoscopists can implement the assessment., Competing Interests: None

Objective: Ring finger protein 6 (RNF6) has been identified to be associated with the progression of colorectal cancer, gastric cancer and breast cancer. Its role in hepatocellular carcinoma (HCC), however, remains largely unclear. This study aims to illustrate the prognostic potential of RNF6 in nonalcoholic fatty liver disease (NAFLD)-HCC., Patients and Methods: A total of 162 eligible NAFLD-HCC patients treated in our hospital from May 2017 to May 2019 were recruited. RNF levels in the collected tumor tissues and paracancerous tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and immunohistochemistry (IHC). Then, the influences of RNF6 on overall survival (OS) and recurrence-free survival (RFS) in NAFLD-HCC patients were explored. Potential clinical factors for the prognosis in NAFLD-HCC were finally analyzed., Results: RNF6 was upregulated in NAFLD-HCC tissues. Highly expressed RNF6 at both mRNA and protein levels predicted poor OS and RFS in NAFLD-HCC. RNF6 level, metastasis, tumor node metastasis (TNM) staging, and tumor grade were correlated with the prognosis in NAFLD-HCC., Conclusions: Great effects have been made on improving the diagnostic rate. Here, highly expressed RNF6 was unfavorable to OS and RFS in NAFLD-HCC. As a result, RNF6 not only contributed to the diagnosis of NAFLD-HCC, but also predicted its prognosis and recurrence.

Background: How suction technique affects endoscopic ultrasound-guided tissue acquisition (EUS-TA) remains unclear. A standardized protocol is currently lacking, with most previous studies being restricted to EUS-guided fine-needle aspiration (EUS-FNA). The research related to EUS-guided fine-needle biopsy (EUS-FNB) is sparse., Aims: The aim of this study is to evaluate the diagnostic efficacy, cellularity, tissue acquisition, blood contamination and adverse event rate of three common suction techniques (standard suction, slow-pull, and wet suction) used for EUS-FNB of solid pancreatic masses., Methods: This is a multicenter single-blind randomized cross-over superiority trial. A total of 300 patients with suspected pancreatic malignancy will be enrolled from digestive endoscopic centers at five large tertiary hospitals in China. All three suction techniques will be performed on each patient using a 25G ProCore needle, with the sequence of suction techniques determined by randomization. Cytological and histological specimens obtained with each of the three techniques will be assessed independently. Outcomes among the three suction techniques will be compared., Discussion: To the best of our knowledge, this is the largest multicenter randomized cross-over trial designed to determine the optimal suction technique for the diagnosis of solid pancreatic masses. This study may contribute to standardizing the suction technique for EUS-FNB., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Endoscopic retrograde cholangiopancreatography (ERCP) for extraction of common bile duct (CBD) stones in Billroth II anatomy patients is still a technical challenge and factors affecting stone extraction have not yet been clarified. This study aimed to analyze our experience and evaluate potential factors affecting CBD stone extraction., Methods: A retrospective analysis of CBD stones patients with a history of Billroth II gastrectomy, who underwent therapeutic ERCP for stone extraction at our center from August 1999 to December 2017, was conducted. The outcomes of ERCP and potential factors affecting stone extraction were examined., Results: A total of 227 patients were enrolled, and 176 patients (77.5%) achieved technical success. The success rate of duodenal ampullary access and selective biliary cannulation was 84.1% (191/227) and 92.1% (176/191), respectively. The mean CBD diameter was 15 mm (range 6-35 mm), and the largest stone size was 13 mm (range 4-36 mm). CBD stones were ultimately removed in 137 patients (77.8%), and 105 patients (59.7%) for the first session. Mechanical lithotripsy was used in 17 patients (9.7%). The overall ERCP-related complication rate was 6.3% (11/176), including bleeding in 3 patients (1.7%) and mild pancreatitis in 6 patients (3.4%). The multivariate analysis indicated that CBD stone number ≥ 2 (OR 2.171; 95% CI 1.095-4.306; p = 0.027), and the largest CBD stone size ≥ 12 mm (OR 3.646; 95% CI 1.833-7.251; p < 0.001) were patient-related risk factors for failed stone removal; while the use of endoscopic papillary (large) balloon dilation (EPBD/EPLBD) (OR 0.291; 95% CI 0.147-0.576; p < 0.001) was a procedure-related protective factor for successful stone extraction., Conclusions: ERCP is safe and effective for extraction of CBD stones in Billroth II anatomy patients. The number and the largest size of CBD stones, and the use of EPBD/EPLBD are predictive factors for CBD stone extraction.

Background and Aims: Studies comparing the diagnostic efficacy of liquid-based cytology (LBC) and smear cytology (SC) of pancreatic tissue sampling obtained via EUS-guided FNA (EUS-FNA) are still insufficient, mainly because results were controversial. We compared the diagnostic efficiency of LBC and SC of EUS-FNA of pancreatic lesions in one of the largest tertiary hospitals in China., Methods: A retrospective database search (January 2015 to January 2019) was performed for patients who underwent EUS-FNA with both LBC and SC. Demographic, cytologic, and endosonographic data were collected from 819 patients; 514 cases met the inclusion criteria. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were compared. Rapid on-site evaluation was not available in all cases., Results: Three hundred eighty-five cases (74.90%) had confirmed malignancy, and 40 cases (7.78%) confirmed benign neoplasm. Adequate tissue sampling rates showed no significant difference between the 2 groups. The sensitivity, accuracy, and negative predictive value (NPV) of LBC were higher than those of SC with statistical significance (71.4% vs 55.1%, 76.1% vs 61.6%, and 40.6% vs 27.7%, respectively). The sensitivity, accuracy, and NPV of combined SC and LBC were higher than those of LBC alone with statistical significance (83.9% vs 71.4%, 86.5% vs 76.1%, and 56.8% vs 40.6%, respectively). Multivariate analysis revealed that pancreatic neck/body/tail lesions (P = .003), solid lesions (P < .001), 22-gauge needle size (P < .001), and number of needle passage >3 (P = .041) were associated with higher diagnostic sensitivity in all participants using LBC, whereas number of needle passage >3 (P = .017) was associated with higher diagnostic sensitivity using SC., Conclusions: LBC was more accurate and sensitive than SC in EUS-FNA of pancreatic lesions with higher NPV when rapid on-site evaluation is unavailable. Pancreatic neck/body/tail lesions, solid lesions, 22-gauge needle, and more than 3 passes were associated with higher sensitivity when using LBC. Performing more than 3 passes is associated with higher sensitivity when using SC., (Copyright © 2020. Published by Elsevier Inc.)

Background/aims: Endoscopic retrograde cholangiopancreatography (ERCP) in Billroth II gastrectomy patients is technically demanding and factors affecting its technical difficulty have not yet been clarified. This study aimed to investigate the outcomes of ERCP in Billroth II gastrectomy patients and identify potential factors affecting its technical failure., Patients and Methods: A large retrospective study of 308 consecutive patients (391 procedures) with Billroth II gastrectomy-who underwent ERCP from January 2002 to December 2016-was conducted. The outcomes of ERCP and potential factors affecting its technical failure were analyzed., Results: The success rate of duodenal ampullary access, selective duct cannulation and the accomplishment of expected procedures was 81.3% (318/391), 86.5% (275/318) and 97.3% (256/263), respectively, and the technical success rate was 70.3% (275/391). The overall ERCP-related complication rate was 15.3% (60/391). The multivariate analysis indicated that first-time ERCP attempt [odds ratio (OR) 4.29, 95% confidence interval (CI) 2.34-7.85, P < 0.001], Braun anastomosis (OR 3.65, 95% CI 1.38-9.64, P < 0.009), and no cap-assisted gastroscope (OR 3.05, 95% CI 1.69-5.51, P < 0.001) were significantly associated with technical failure., Conclusions: ERCP is safe, effective and feasible for Billroth II gastrectomy patients. Previous ERCP history, absence of Braun anastomosis and the use of a cap-assisted gastroscope are the predictive factors for its technical success., Competing Interests: None

During the Last Glacial Maximum (LGM; ~20,000 years ago), the global ocean sequestered a large amount of carbon lost from the atmosphere and terrestrial biosphere. Suppressed CO 2 outgassing from the Southern Ocean is the prevailing explanation for this carbon sequestration. By contrast, the North Atlantic Ocean-a major conduit for atmospheric CO 2 transport to the ocean interior via the overturning circulation-has received much less attention. Here we demonstrate that North Atlantic carbon pump efficiency during the LGM was almost doubled relative to the Holocene. This is based on a novel proxy approach to estimate air-sea CO 2 exchange signals using combined carbonate ion and nutrient reconstructions for multiple sediment cores from the North Atlantic. Our data indicate that in tandem with Southern Ocean processes, enhanced North Atlantic CO 2 absorption contributed to lowering ice-age atmospheric CO 2 .

With the digestive endoscopic tunnel technique (DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria (MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal (GI) tract. At present, the tunnel technique application range covers the following: (1) Treatment of lesions originating from the mucosal layer, e.g ., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis; (2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc .; and (3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment. The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism, and significance of DETT, prevention of infection and concepts of DETT-associated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract (indications and contraindications, procedures, pre- and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations)., Competing Interests: Conflict-of-interest statement: All authors have no financial relationships to disclose.

Background: Endoscopic ultrasonography (EUS)-guided drainage has become the first-line therapy for late peri-pancreatic fluid collection (PFC). Double pigtail plastic stents (DPPS) and lumen-apposing metal stents (LAMS) are commonly used for PFC drainage. Recently, a multi-institutional consensus on PFC drainage has recommended that LAMS should be the standard care for patients with walled-off necrosis (WON). However, given the poor quality of evidence, we aim to perform a large-scale randomized controlled trial to determine whether LAMS is superior to DPPS for WON drainage., Methods/design: The study is an open-label, prospective, parallel-group, superiority, multicenter randomized controlled trial. Two hundred and fifty-six patients with WON who will attend 18 tertiary hospitals in China will be randomly allocated to the LAMS or DPPS group before the procedure. The primary endpoint is the clinical success at one month after drainage (reduction in the size of WON to < 2 cm). Secondary endpoints include technical success, operation time, recurrence, adverse events, and secondary interventions., Discussion: The LVPWON trial is designed to determine whether LAMS is effective, safe, and superior to DPPS for WON drainage., Trial Registration: ClinicalTrials.gov, NCT03027895 . Registered on 14 January 2017.

Background: Rat renal transplantation is an essential experimental model for studies of transplantation immunobiology. Harvesting both kidneys from one donor rat for transplantation is widely used to reduce the number of experimental animals. Using the conventional method, both kidneys of the donor rat are harvested simultaneously, which leads to the prolonged warm ischemic times during transplantation of the second donor kidney. Prolonged warm ischemia time is the main risk factor for delayed graft function., Methods: Two different approaches are compared. Method 1, conventional method: both kidneys of the donor rat are harvested simultaneously and then transplanted into two recipients. During transplantation, the first and second donor kidneys were regarded as Group 1 and 2, respectively. Method 2, step-by-step method: after left nephrectomy, the donor rat survives, and we perform left renal transplantation (Group 3). Then, the right kidney of the surviving donor rat is incised and transplanted into the left side of the second recipient (Group 4)., Results: The success rates were 86.7, 93.3, 93.3 and 86.7% in groups 1, 2, 3 and 4, respectively. The warm ischemia times increased significantly in group 2 compared with the other 3 groups (p < 0.05) but differed non-significantly between groups 3 and 4 (p > 0.05). Serum creatinine levels, blood urea nitrogen and 24-h urine protein level obviously increased after kidney transplantation in group 2 compared with other groups (p < 0.05)., Conclusions: We developed an optimized method for reducing warm ischemia time, thereby minimizing delayed graft function.

Objectives: Interventional endoscopic ultrasonography (EUS) procedures are gaining popularity and the most commonly performed procedures include EUS-guided drainage of pancreatic pseudocyst, EUS-guided biliary drainage, EUS-guided pancreatic duct drainage and EUS-guided celiac plexus ablation. The aim of this paper is to formulate a set of practice guidelines addressing various aspects of the above procedures., Methods: Formulation of the guidelines was based on the best scientific evidence available. The RAND/UCLA appropriateness methodology (RAM) was used. Panellists recruited comprised experts in surgery, interventional EUS, interventional radiology and oncology from 11 countries. Between June 2014 and October 2016, the panellists met in meetings to discuss and vote on the clinical scenarios for each of the interventional EUS procedures in question., Results: A total of 15 statements on EUS-guided drainage of pancreatic pseudocyst, 15 statements on EUS-guided biliary drainage, 12 statements on EUS-guided pancreatic duct drainage and 14 statements on EUS-guided celiac plexus ablation were formulated. The statements addressed the indications for the procedures, technical aspects, pre- and post-procedural management, management of complications, and competency and training in the procedures. All statements except one were found to be appropriate. Randomised studies to address clinical questions in a number of aspects of the procedures are urgently required., Conclusions: The current guidelines on interventional EUS procedures are the first published by an endoscopic society. These guidelines provide an in-depth review of the current evidence and standardise the management of the procedures., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Pancreatic cancer is a lethal disease and usually is diagnosed at advanced stages of disease. This study assessed the effects of intratumoral ethanol injection using an endoscopic ultrasound (EUS) probe on the control of pancreatic cancer in a mouse orthotopic xenograft model., Materials and Methods: The subcutaneous and orthotopic human pancreatic cancer cell mouse xenograft models were established. Different concentrations of ethanol (0-95%) were injected into subcutaneous xenograft tumors. In the orthotopic tumor model, ethanol was injected into the tumor lesions under the guidance of a high-frequency EUS probe. Tumor volume, relative tumor volume (RTV), and histopathology were evaluated. The serum amylase level was analyzed at baseline and 24 h after treatment in the orthotopic tumor model., Results: Injection of 40-95% ethanol induced tumor necrosis in the subcutaneous tumor model, while there was no statistical difference between the RTVs of the two groups ( P = 0.81). In the orthotopic tumor model, the RTV of the 80% ethanol treatment group was less than that of the saline injection group ( P < 0.01); and histologically, there was a large area of necrosis observed in the 80% ethanol group. The serum amylase level was slightly elevated at 24 h after injection and returned to the baseline level at 7 days., Conclusion: Injection of 80% ethanol into xenograft tumor lesions of orthotopic pancreatic cancer resulted in tumor necrosis, and the procedure was safe and effective. Future studies will further confirm its antitumor activity as well as assess its safety and feasibility.

Background: Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is the first-line therapy for large pancreatic duct stones. Although it is a highly effective and safe procedure for the fragmentation of pancreatic stones, it is still not complication-free. Just like endoscopic retrograde cholangiopancreatography (ERCP), pancreatitis is the most common complication. To date, nonsteroidal anti-inflammatory drugs (NSAIDs) have proven to be the only effective prophylactic medication for post-ERCP pancreatitis and the European, American and Japanese Society for Gastrointestinal Endoscopy guidelines have recommended prophylactic rectally administered indomethacin for all patients undergoing ERCP. Given the little research about effective prevention for post P-ESWL pancreatitis, we aim to determine whether rectally administered indomethacin can reduce post-ESWL-pancreatitis., Methods/design: The RIPEP study is a prospective, randomized, double-blinded, placebo-controlled trial. One thousand three hundred and seventy patients with chronic pancreatitis and pancreatic stones (>5 mm in diameter) treated with P-ESWL at Changhai Hospital will be randomly allocated to rectally administered indomethacin or placebo therapy before the procedure. The primary endpoint is the incidence of post-ESWL pancreatitis. Secondary endpoints include the severity of pancreatitis, occurrence rate of asymptomatic hyperamylasemia and other complications., Discussion: The RIPEP trial is designed to show that rectally administered indomethacin reduces the development and severity of post-ESWL pancreatitis and benefits patients treated with P-ESWL., Trial Registration: ClinicalTrials.gov, ID: NCT02797067 . Registered on 17 November 2016.

Background: We describe a simple and reliable orthotopic kidney transplantation method in rats with the use of sleeve arterial anastomosis and a modified stenting technique for anastomosis of the renal vein (RV)., Methods: Male Fischer and Lewis rats were used as kidney donors and recipients, respectively, and their left kidneys were harvested in situ. In the control rats (n = 30), the renal artery (RA) and RV anastomoses were performed end-to-end with interrupted sutures by means of the conventional technique. In the experimental animals (n = 30), revascularization of the RA was fashioned end-in-end with the use of a modified sleeve anastomosis, the RV was anastomosed end-to-end with the use of a modified stenting technique and interrupted sutures, and the ureter was anastomosed with the use of the end-to-end interrupted suture technique., Results: The arterial anastomosis time in the control group was 8.52 ± 1.1 minutes, and that in the experimental group was 4.7 ± 0.6 minutes (P < .05). The venous anastomosis time in the experimental group was 9.2 ± 1.3 minutes, which also was less than in the control group (11.19 ± 0.78 minutes; P < .05). The warm ischemia time decreased from 26.8 ± 1.3 minutes in the control group to 20.7 ± 0.5 minutes in the experimental group (P < .05). The success rate of 93% at 21 days after grafting was identical in the experimental and control groups., Conclusions: We developed a modified model of orthotopic kidney transplantation that can significantly reduce the warm ischemia time., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Single nucleotide polymorphisms (SNPs) in mismatch repair genes, especially in the MLH1 gene, are closely associated with susceptibility to hereditary nonpolyposis colorectal cancer. However, few relevant findings are available regarding the association between sporadic colorectal cancer (SCRC) and SNPs of MLH1 in Chinese patients. Therefore, the present study aimed to describe the pathogenic association between three important MLH1 polymorphisms and SCRC in the Chinese population. Peripheral blood samples from 156 SCRC patients and 311 healthy controls were collected. DNA was purified from peripheral blood, and the V384D, R217C, and I219V polymorphisms were evaluated using high-resolution melting analysis and direct sequencing. The association between the three important MLH1 polymorphisms and clinical pathological features of the SCRC patients was analyzed. In addition, PMS2-MLH1 protein interactions were determined by co-immunoprecipitation (Co-IP) to determine the protein functional alteration induced by these SNPs. Among the three polymorphisms, V384D was significantly associated with the risk of SCRC (OR = 31.36, P < 0.0001). The allele frequencies were 4.81 and 0.16% in the SCRC group. No association was found between SCRC and R217C, or between SCRC and I219V. Moreover, the allele frequency of R217C was significantly higher in the SCRC patients younger than 60 years than in those older than 60 years. Co-IP showed that the MLH1 R217C, V384D, and I219V variants had relative binding abilities with PMS2 of 0.59, 0.70, and 0.80, respectively, compared with the wild-type. These findings suggest that MLH1 V384D could be a promising genetic marker for susceptibility to SCRC.

Aim: To perform a systematic review comparing the outcomes of endoscopic, percutaneous and surgical pancreatic pseudocyst drainage., Methods: Comparative studies published between January 1980 and May 2014 were identified on PubMed, Embase and the Cochrane controlled trials register and assessed for suitability of inclusion. The primary outcome was the treatment success rate. Secondary outcomes included were the recurrence rates, re-interventions, length of hospital stay, adverse events and mortalities., Results: Ten comparative studies were identified and 3 were randomized controlled trials. Four studies reported on the outcomes of percutaneous and surgical drainage. Based on a large-scale national study, surgical drainage appeared to reduce mortality and adverse events rate as compared to the percutaneous approach. Three studies reported on the outcomes of endoscopic ultrasound (EUS) and surgical drainage. Clinical success and adverse events rates appeared to be comparable but the EUS approach reduced hospital stay, cost and improved quality of life. Three other studies compared EUS and esophagogastroduodenoscopy-guided drainage. Both approaches were feasible for pseudocyst drainage but the success rate of the EUS approach was better for non-bulging cyst and the approach conferred additional safety benefits., Conclusion: In patients with unfavorable anatomy, surgical cystojejunostomy or percutaneous drainage could be considered. Large randomized studies with current definitions of pseudocysts and longer-term follow-up are needed to assess the efficacy of the various modalities.

Historical reconstruction of atmospheric black carbon (BC, in the form of char and soot) is still constrained for inland areas. Here we determined and compared the past 150-yr records of BC and polycyclic aromatic compounds (PACs) in sediments from two representative lakes, Huguangyan (HGY) and Chaohu (CH), in eastern China. HGY only receives atmospheric deposition while CH is influenced by riverine input. BC, char, and soot have similar vertical concentration profiles as PACs in both lakes. Abrupt increases in concentrations and mass accumulation rates (MARs) of soot have mainly occurred since ~1950, the establishment of the People's Republic of China, when energy usage changed to more fossil fuel contributions reflected by the variations in the concentration ratios of char/soot and individual PACs. In HGY, soot MARs increased by ~7.7 times in the period 1980-2012 relative to the period 1850-1950. Similar increases (~6.7 times) were observed in CH. The increase in soot MARs is also in line with the emission inventory records in the literature and the fact that the submicrometer-sized soot particles can be dispersed regionally. The study provides an alternative method to reconstruct the atmospheric soot history in populated inland areas.

Background and Aim: A major reason impeding the growth of endoscopic ultrasound (EUS) in Asia is the lack of training availability. We aimed to prospectively evaluate the effectiveness of a short-term structured EUS training program in improving the knowledge and skill of EUS among trainees., Methods: The study was conducted in six workshops in six countries including Sri Lanka, Pakistan, Thailand, Vietnam, Singapore and Philippines, within a year. Trainees were evaluated using written and skill tests before and after completion of the training., Results: Pre- and post-workshop written tests from a total of 62 trainees were analyzed. Compared with pre-training, the trainees improved significantly in the overall mean (± SD) scores after the training (66.0 ± 0.3% to 77.5 ± 0.2%, P < 0.0001). Thirty-one trainees were randomly selected to undergo a skill test before and after the course. Compared with pre-training, the proportions of trainees who succeeded in locating each structure post-training were: celiac axis (36-80.5%), pancreatic body (51.5-80.5%), pancreatic body and tail (42-77.5%), splenic vein and artery (48.5-84%), left kidney (60-83%), and spleen (47-83%). Overall, there was a significant improvement in the proportion of trainees' successful localization of structures post-training compared to before training (P < 0.0001)., Conclusion: Following a structured training program, trainees' knowledge and skills in EUS improved significantly. Structured training courses appear to be an effective way of imparting EUS knowledge and skills to aspiring endosonographers in the Asian region., (© 2015 The Authors. Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.)

Objective: To quantify the expressions of Smad7 and Smad ubiquitin regulatory factor 2 (Smurf2) in the pancreas in rats with chronic pancreatitis (CP)., Methods: A total of 16 male Wistar rats were randomly divided into the control group and the CP group, with 8 rats in each group. CP was induced in vivo with dibutyltin dichloride (DBTC). Four weeks after DBTC administration, histological assessment and the measurement of hydroxyproline content in the pancreatic tissues were performed to assess the inflammation and fibrosis of the pancreas. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) for transforming growth factor (TGF)-β1 and α-smooth muscle actin (α-SMA) were applied to assess activated pancreatic stellate cells (PSC) and TGF-β1 expression. Smad7 and Smurf2 expressions in the pancreas were measured using Western blot and RT-PCR., Results: Typical histopathological characteristics of DBTC-induced CP in the rats with extensively activated PSC. Compared with the control group, the expressions of TGF-β1, α-SMA and hydroxyproline content in the pancreatic tissues in the CP group were significantly increased. Meanwhile, the mRNA and protein expressions of Smad7 and Smurf2 were significant increased in the fibrotic pancreas, in which the expressions of Smad7 proteins showed an obvious reduction compared with controls., Conclusion: The dysregulation of Smad7 and Smurf2 may be associated with the pathogenesis of pancreatic fibrosis through the TGF-β signaling pathway., (© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Elemental carbon (EC) and polycyclic aromatic compounds (PACs) are potential proxies for the reconstruction of change in human activities and the origin of air masses in historic times. In this study, the historic deposition of char and soot (the two subtypes of EC) and PACs in a 150-year sediment core from different topographic subbasins of Lake Qinghai on the Qinghai Tibetan Plateau (QTP) were reconstructed. The objective was to explore how the variations in the concentrations of EC and PACs, in the ratios of char to soot and of oxygenated polycyclic aromatic hydrocarbons (OPAHs) to parent PAHs, and in the composition of the PAC mixtures reflect historical changes in climate and human activity and the origin of air masses arriving at the QTP. The deposition fluxes of soot in the different subbasins were similar, averaging 0.18 (range of 0.15-0.25) and 0.16 (0.13-0.23) g m(-2) year(-1), respectively, but they varied for char (averaging 0.11 and 0.22 g m(-2) year(-1), respectively), suggesting ubiquitous atmospheric deposition of soot and local river inputs of char. The different vertical distributions of the char/soot ratios in the different subbasins can be interpreted in terms of the different transport mechanisms of char and soot. An abrupt increase in soot concentrations since 1980 coincides with results from the QTP ice cores that were interpreted to be indicative of soot transport from South Asia. Similar concentration patterns of PAHs with soot and 9,10-anthraquinone/anthracene (9,10-AQ/ANT) ratios all >2.0 suggest regional PAC sources. Increasing PAH/soot ratios and decreasing 9,10-AQ/ANT ratios since the beginning of the 1970s indicate increasing local emissions. The historical trends of these diagnostic ratios indicate an increase in the fossil-fuel contribution since the beginning of the 1970s. The increase of perylene concentrations with increasing core depth and the ratio of perylene to its penta-aromatic isomers indicate that perylene originates mainly from in situ biogenic diagenesis. We demonstrate that the concentrations of EC, char, soot, and PACs in sediments can be used to reconstruct local, regional, and remote sources and transport pathways of pollutants to the QTP.

Background: There is a lack of consensus on how endoscopic ultrasound (EUS) guided pseudocyst drainage should be performed. This survey was carried out amongst members of the Asian Endoscopic Ultrasonography Group (AEG) to describe their practices in performing this procedure., Methods: This was an Asia wide multi-institutional survey amongst members of the Asian EUS group conducted between November and December 2013. The responses to a 19-question survey with regard to the practice of pseudocyst drainage were obtained., Results: In total, 19 endoscopists responded to the questionnaire and the mean (SD) number of procedures performed by each endoscopist was 87.95 (40); 42.2 % believed that prior endoscopic retrograde cholangiopancreatography (ERCP) is required and pancreatic duct stenting is indicated in patients with pancreatic duct disruption; 47.4 % used tapered catheters for track dilation and 42.1 % used the cystotome; 84.1 % would dilate the track up to 8 to 10 mm in size. Metallic stents were used by 10.5 % of the respondents and transcystic catheters were employed by 26.3 %. Those who were more experienced in the procedure tended to use the cystotome more frequently (P = 0.02) and removed the stents in less than 3 months after insertion (P = 0.011)., Conclusion: This was the first Asia wide survey in the practice of pseudocyst drainage. There were wide variations in practice and randomized studies are urgently needed to establish the best approach for management of this condition. There is also a pressing need for establishment of a consensus for safe practices.

The knowledge of the association of polycyclic aromatic hydrocarbons (PAHs) with organic matter and carbonaceous materials is critical for a better understanding of their environmental transport, fate, and toxicological effects. Extensive studies have been done with regard to the relationship of PAHs with total organic carbon (TOC) and elemental carbon (EC) in different environmental matrices. The relationship between PAHs and the two subtypes of EC, char (combustion residues) and soot (produced via gas-to-particle conversion) also has been tested in field and laboratory experiments using reference materials. However, a direct comparison of associations of PAHs between with char and with soot in real environmental matrices has to our knowledge not yet been reported because of a lack of methodology to differentiate them. In this study, char and soot were measured using the IMPROVE method to test their associations with 12 EPA priority PAHs measured in topsoil samples (N=22, top 10 cm) collected from the Guanzhong Plain and in surface sediment samples (N=32, top 5 cm) from the Wei River (central China). In both soils and sediments, ∑12PAHs were more strongly associated with soot than with char, mainly due to the fact that soot and PAHs were produced in the same gas phase during combustion, had a strong affinity for each other, and were transported and deposited together, while char, the combustion residue, was transported differently to PAHs due to its large particle size. Stronger correlations between PAHs and the different carbon fractions (TOC, soot, and char) in sediments than in soils were observed, which is associated with the redistribution of PAHs among the organic matter pools in water because of the processes during soil erosion and sedimentation in the river., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Autoimmune pancreatitis (AIP) is increasingly recognized as a unique subtype of pancreatitis. This study aimed to analyze the diagnosis and treatment of AIP patients from a tertiary care center in China., Methods: One hundred patients with AIP who had been treated from January 2005 to December 2012 in our hospital were enrolled in this study. We retrospectively reviewed the data of clinical manifestations, laboratory tests, imaging examinations, pathological examinations, treatment and outcomes of the patients., Results: The median age of the patients at onset was 57 years (range 23-82) with a male to female ratio of 8.1:1. The common manifestations of the patients included obstructive jaundice (49 patients, 49.0%), abdominal pain (30, 30.0%), and acute pancreatitis (11, 11.0%). Biliary involvement was one of the most extrapancreatic manifestations (64, 64.0%). Fifty-six (56.0%) and 43 (43.0%) patients were classified into focal-type and diffuse-type respectively according to the imaging examinations. The levels of serum IgG and IgG4 were elevated in 69.4% (43/62) and 92.0% (69/75) patients. Pathological analysis of specimens from 27 patients supported the diagnosis of lymphoplasmacytic sclerosing pancreatitis, and marked (>10 cells/HPF) IgG4 positive cells were found in 20 (74.1%) patients. Steroid treatment and surgery as the main initial treatments were given to 41 (41.0%) and 28 (28.0%) patients, respectively. The remission rate after the initial treatment was 85.0%. Steroid was given as the treatment after relapse in most of the patients and the total remission rate at the end of follow-up was 96.0%., Conclusions: Clinical manifestations, laboratory tests, imaging and pathology examinations in combination could increase the diagnostic accuracy of AIP. Steroid treatment with an initial dose of 30 or 40 mg prednisone is effective and safe in most patients with AIP.