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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.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.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%;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 Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown. Methods Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis. Results In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-β2-glycoprotein I (β2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum β2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P

International audience; In the human genome, most 5 ' splice sites (similar to 99%) employ the canonical GT dinucleotide whereas a small minority (similar to 1%) use the noncanonical GC dinucleotide. The functionality and pathogenicity of 5 ' splice site GT>GC (+2T>C) variants have been extensively studied but we know very little about 5 ' splice site GC>GT (+2C>T) variants. Herein, we have addressed this deficiency by performing a meta-analysis of reported +2C>T "pathogenic" variants together with a functional analysis of engineered +2C>T substitutions using a cell culture-based full-length gene splicing assay. Our results establish proof of concept that +2C>T variants are qualitatively different from +2T>C variants in terms of their functionality and suggest that, in sharp contrast to +2T>C variants, most if not all +2C>T variants have no pathological relevance. Our findings have important implications for interpreting the clinical relevance of +2C>T variants and understanding the evolutionary switching between GT and GC 5 ' splice sites in mammalian genomes.

Introduction: 5' splice site GT>GC or +2T>C variants have been frequently reported to cause human genetic disease and are routinely scored as pathogenic splicing mutations. However, we have recently demonstrated that such variants in human disease genes may not invariably be pathogenic. Moreover, we found that no splicing prediction tools appear to be capable of reliably distinguishing those +2T>C variants that generate wild-type transcripts from those that do not. Methodology: Herein, we evaluated the performance of a novel deep learning-based tool, SpliceAI, in the context of three datasets of +2T>C variants, all of which had been characterized functionally in terms of their impact on pre-mRNA splicing. The first two datasets refer to our recently described “in vivo” dataset of 45 known disease-causing +2T>C variants and the “in vitro” dataset of 103 +2T>C substitutions subjected to full-length gene splicing assay. The third dataset comprised 12 BRCA1 +2T>C variants that were recently analyzed by saturation genome editing. Results: Comparison of the SpliceAI-predicted and experimentally obtained functional impact assessments of these variants (and smaller datasets of +2T>A and +2T>G variants) revealed that although SpliceAI performed rather better than other prediction tools, it was still far from perfect. A key issue was that the impact of those +2T>C (and +2T>A) variants that generated wild-type transcripts represents a quantitative change that can vary from barely detectable to an almost full expression of wild-type transcripts, with wild-type transcripts often co-existing with aberrantly spliced transcripts. Conclusion: Our findings highlight the challenges that we still face in attempting to accurately identify splice-altering variants.

We have read with interest the recent publication of Hegyi and Sahin-Toth1 reporting that chronic pancreatitis (CP)-predisposing CPA1 mutations function through the misfolding pathway rather than through loss of CPA1 protein/activity. Herein, we explore an additional insight gleaned from this study beyond those discussed in an accompanying Editorial.2 In the original study reporting the association of CPA1 variants with CP, all unambiguous loss-of-function (LoF) variants (eg, nonsense mutations) were lumped together with missense mutations that functionally impaired the CPA1 protein.3 However, unlike missense mutations, unambiguous LoF variants often result in transcripts that contain premature termination codons (PTC) and are thus prone to nonsense-mediated RNA decay (NMD). NMD detects and degrades PTC-containing transcripts, thereby preventing the accumulation of truncated proteins.4 5 This implies that most unambiguous LoF CPA1 variants would not be able to elicit endoplasmic reticulum (ER) stress and hence, in light of the Hegyi and Sahin-Toth study, will not predispose …

Background/objectives Carboxyl ester lipase is a pancreatic enzyme encoded by CEL, an extremely polymorphic human gene. Pathogenic variants of CEL either increases the risk for chronic pancreatitis (CP) or cause MODY8, a syndrome of pancreatic exocrine and endocrine dysfunction. Here, we aimed to characterize a novel duplication allele of CEL (CEL-DUP2) and to investigate whether it associates with CP or pancreatic cancer. Methods The structure of CEL-DUP2 was determined by a combination of Sanger sequencing, DNA fragment analysis, multiplex ligation-dependent probe amplification and whole-genome sequencing. We developed assays for screening of CEL-DUP2 and analyzed cohorts of idiopathic CP, alcoholic CP and pancreatic cancer. CEL protein expression was analyzed by immunohistochemistry. Results CEL-DUP2 consists of an extra copy of the complete CEL gene. The allele has probably arisen from non-allelic, homologous recombination involving the adjacent pseudogene of CEL. We found no association between CEL-DUP2 carrier frequency and CP in cohorts from France (cases/controls: 2.5%/2.4%; P = 1.0), China (10.3%/8.1%; P = 0.08) or Germany (1.6%/2.3%; P = 0.62). Similarly, no association with disease was observed in alcohol-induced pancreatitis (Germany: 3.2%/2.3%; P = 0.51) or pancreatic cancer (Norway; 2.5%/3.2%; P = 0.77). Notably, the carrier frequency of CEL-DUP2 was more than three-fold higher in Chinese compared with Europeans. CEL protein expression was similar in tissues from CEL-DUP2 carriers and controls. Conclusions Our results support the contention that the number of CEL alleles does not influence the risk of pancreatic exocrine disease. Rather, the pathogenic CEL variants identified so far involve exon 11 sequence changes that substantially alter the protein’s tail region.

GT>GC 5’ splice site (or +2T>C) variants have been frequently reported to cause human genetic disease. However, although we have demonstrated that GT>GC variants in human disease genes may not invariably be pathogenic, none of the currently available splicing prediction tools appear to be capable of reliably distinguishing those GT>GC variants that generate wild-type transcripts from those that do not. Recently, SpliceAI, a novel deep residual neural network tool, has been developed for splicing prediction. Methodologically distinct from previous approaches that either rely on human-engineered features and/or which focus on short nucleotide windows adjoining exon-intron boundaries, SpliceAI assesses splicing determinants by evaluating 10,000 nucleotides of flanking contextual sequence to predict the functional role in splicing of each position in the pre-mRNA transcript. Herein, we evaluated the performance of SpliceAI in the context of three datasets of GT>GC variants, all of which had been characterized functionally in terms of their impact on mRNA splicing. The first two datasets refer to our recently described “in vivo” dataset of 45 disease-causing GT>GC variants and the “in vitro” dataset of 103 GT>GC substitutions. The third dataset comprised 12 BRCA1 GT>GC variants that were recently analyzed by saturation genome editing. We processed all GT>GC variants using the default settings of SpliceAI. Comparison of the SpliceAI-predicted and experimentally obtained functional impact assessments of the analyzed GT>GC variants revealed that although SpliceAI performed rather better than other prediction tools, it was still far from perfect. A key issue is that the impact of GT>GC (as well as GT>GA or +2T>A) variants that generated wild-type transcripts represents a quantitative change that can vary from barely detectable to almost full expression of wild-type transcripts, with wild-type transcripts often co-existing with aberrantly spliced transcripts. Our findings highlight the challenges that we still face in attempting to accurately identify splice-altering variants.

Objectives The aim of this study was to establish a standard to describe the spatial distribution of pancreatic stones in chronic pancreatitis (CP). Methods Two hundred forty-seven CP patients with pancreatic stones from June to December 2012 were enrolled. Two-dimensional images from coronal projection of 3-dimensional computed tomography images of pancreatic stones were gained. The number (n) of all stones and the geometric standard deviation (σ) of distances between the centroid of all stones and the centroids of every stone that represented the spatial distribution nonuniformity were calculated by Stone Reconstruction and Identification Programming System. Results The mean value of n and σ were 13.6 and 22.5; n > 13.6 and σ > 22.5 were determined as "multistones" and "nonuniform," respectively. Compared with alcoholic CP, idiopathic CP was less prone to multistones (odds ratio [OR], 0.310) and more prone to nonuniform (OR, 3.247). Pancreatic pseudocyst (OR, 2.211) in CP course was a risk factor of multistones, whereas diabetes mellitus in first-/second-/third-degree relatives (OR, 0.382) was a protective factor. Age at diagnosis of pancreatic stones (OR, 1.022) was a risk factor of nonuniformity. Conclusions Compared with idiopathic CP, alcoholic CP patients were prone to more pancreatic stones that distribute more uniformly.

In the human genome, most 5’ splice sites (~99%) employ the canonical GT dinucleotide whereas a small minority (~1%) use the non-canonical GC dinucleotide. The functionality and pathogenicity of 5’ splice site GT>GC (i.e., +2T>C) variants have been extensively studied but we still know very little about 5’ splice site GC>GT (+2C>T) variants. Herein, we sought to address this deficiency by performing a meta-analysis of identified +2C>T pathogenic variants together with a functional analysis of +2C>T substitutions using a cell culture-based full-length gene splicing assay. Our results establish a proof of concept that +2C>T variants are qualitatively different from +2T>C variants in terms of their functionality and pathogenicity and suggest that, in sharp contrast with +2T>C variants, most if not all +2C>T variants have no pathological relevance. Our findings have important implications for interpreting the clinical relevance of +2C>T variants but might also improve our understanding of the evolutionary basis of switching between GT and GC 5’ splice sites in mammalian genomes.

Pediatric patients suffer from chronic pancreatitis (CP), especially those with diabetes mellitus (DM). This study aimed to identify the incidence of and risk factors for DM in pediatric CP. CP patients admitted to our center from January 2000 to December 2013 were assigned to the pediatric (

International audience; It has long been known that canonical 5' splice site (5'SS) GT>GC variants may be compatible with normal splicing. However, to date, the actual scale of canonical 5'SSs capable of generating wild-type transcripts in the case of GT>GC substitutions remains unknown. Herein, combining data derived from a meta-analysis of 45 human disease-causing 5'SS GT>GC variants and a cell culture-based full-length gene splicing assay of 103 5'SS GT>GC substitutions, we estimate that ~15-18% of canonical GT 5'SSs retain their capacity to generate between 1% and 84% normal transcripts when GT is substituted by GC. We further demonstrate that the canonical 5'SSs in which substitution of GT by GC-generated normal transcripts exhibit stronger complementarity to the 5' end of U1 snRNA than those sites whose substitutions of GT by GC did not lead to the generation of normal transcripts. We also observed a correlation between the generation of wild-type transcripts and a milder than expected clinical phenotype but found that none of the available splicing prediction tools were capable of reliably distinguishing 5'SS GT>GC variants that generated wild-type transcripts from those that did not. Our findings imply that 5'SS GT>GC variants in human disease genes may not invariably be pathogenic.

Objectives The objective of this study was to evaluate the safety and efficacy of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in chronic pancreatitis (CP) patients with pancreatic stones after previous pancreatic surgery. Methods This is a single-center study prospectively conducted in pained CP patients undergoing P-ESWL. Patients with a pancreatic surgery history (PSH) were included in the PSH group, and patients without a PSH during the same period were assigned to the control group. The primary outcomes included complications associated with P-ESWL and pain relief. Secondary outcomes included stone clearance and improved quality-of-life scores. Results From March 2011 to October 2014, P-ESWLs were performed on 1017 patients (50 in the PSH group, 967 in the control group). No significant difference was observed in the frequency of occurrence of P-ESWL complications between the PSH group and control group (14.0% vs 13.2%, P = 0.877). At follow-up (2.6 years; range, 1.0-4.5 years), pain relief was achieved in 36 patients (75.0%), and 37 patients (77.1%) experienced complete stone clearance. No significant differences were observed between these patients and the matched controls. Conclusions For CP patients who develop painful stones after pancreatic surgery, P-ESWL safely achieves significant pain relief and stone clearance, preventing the need for a repeat surgery.

Background and Aim Pancreatic pseudocyst is a common complication of chronic pancreatitis. The identification of risk factors and development of a nomogram for pancreatic pseudocysts in chronic pancreatitis patients may contribute to the early diagnosis and intervention of pancreatic pseudocysts. Methods Patients with chronic pancreatitis admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic pseudocysts after the onset of chronic pancreatitis and after the diagnosis of chronic pancreatitis were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. Results With a total of 1,998 patients, pancreatic pseudocysts were detected in 228 (11.41%) patients. Age at the onset of chronic pancreatitis, smoking, and severe acute pancreatitis were identified risk factors for pancreatic pseudocysts development while steatorrhea and pancreatic stones were protective factors. Incorporating these 5 factors, the nomogram achieved good concordance indexes of 0.735 and 0.628 in the training and validation cohorts, respectively, with well-fitted calibration curves. Conclusion The nomogram achieved an individualized prediction of pancreatic pseudocysts development in chronic pancreatitis. It may help the early diagnosis and management of pancreatic pseudocysts.

Background and aims Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is recommended as the first-line treatment for pancreatic stones. However, how well P-ESWL performs in pediatric patients remains unclear. We aimed to evaluate the safety and efficacy of P-ESWL for pediatric patients with chronic pancreatitis. Methods This prospective observational study was conducted in patients with painful chronic pancreatitis who underwent P-ESWL. Patients aged under 18 years were included in the pediatric group; patients aged over 18 years who underwent P-ESWL in the same period were assigned to the control group. For investigation of long-term follow-up, the pediatric group were matched with patients from the control group in a 1:1 ratio. The primary outcomes were P-ESWL complications and pain relief. The secondary outcomes included: stone clearance, physical and mental health, quality of life score, and growth and developmental state. Results From March 2011 to March 2015, P-ESWL was performed in 1135 patients (72 in the pediatric group, 1063 in the control group). No significant differences were observed in the occurrence of P-ESWL complications between the two groups (11.1 % vs. 12.8 %; P = 0.68). Among the 67 pediatric patients (93.1 %) who underwent follow-up for 3.0 years (range 1.3 – 5.2), complete pain relief was achieved in 52 patients (52 /67; 77.6 %); this value was not significantly different from that of the matched controls (55 /69; 79.7 %; P = 0.94). Conclusions P-ESWL is safe and effective for pediatric patients with chronic pancreatitis. It can promote significant pain relief and stone clearance, and can benefit growth and development.

Background and aim Diabetes mellitus (DM) is a common complication of idiopathic chronic pancreatitis (ICP), which impairs the quality of life for patients. This study aimed to identify risk factors and develop nomogram for DM in ICP to help early diagnosis. Methods Idiopathic chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were included. Cumulative rates of DM were calculated by Kaplan-Meier method. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on training cohort, risk factors for DM were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. Results Totally, 1633 patients with ICP were finally enrolled. The median follow-up duration was 9.8 years. DM was found in 26.3% (430/1633) of patients after the onset of CP. Adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct were identified risk factors for DM development. The nomogram achieved good concordance indexes in the training and validation cohorts, respectively, with well-fitted calibration curves. Conclusions Risk factors were identified, and nomogram was developed to determine the risk of DM in ICP patients. Patients with one or more of the risk factors including adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct have higher incidence of DM.

Background The clinical significance of SPINK1 intronic variants in chronic pancreatitis has been previously assessed by various approaches including a cell culture-based full-length gene assay. A close correlation between the results of this assay and in silico splicing prediction was apparent. However, until now, a clinical diagnostic pipeline specifically designed to classify SPINK1 intronic variants accurately and efficiently has been lacking. Herein, we present just such a pipeline and explore its efficacy and potential utility in potentiating the classification of newly described SPINK1 intronic variants. Results We confirm a close correlation between in silico splicing prediction and results from the cell culture-based full-length gene assay in the context of three recently reported pathogenic SPINK1 intronic variants. We then integrated in silico splicing prediction and the full-length gene assay into a stepwise approach and tested its utility in the classification of two novel datasets of SPINK1 intronic variants. The first dataset comprised 16 deep intronic variants identified in 52 genetically unexplained Chinese chronic pancreatitis patients by sequencing the entire intronic sequence of the SPINK1 gene. The second dataset comprised five novel rare proximal intronic variants identified through the routine analysis of the SPINK1 gene in French pancreatitis patients. Employing a minor allele frequency of > 5% as a population frequency filter, 6 of the 16 deep intronic variants were immediately classified as benign. In silico prediction of the remaining ten deep intronic variants and the five rare proximal intronic variants with respect to their likely impact on splice site selection suggested that only one proximal intronic variant, c.194 + 5G > A, was likely to be of functional significance. Employing the cell culture-based full-length gene assay, we functionally analyzed c.194 + 5G > A, together with seven predicted non-functional variants, thereby validating their predicted effects on splicing in all cases. Conclusions We demonstrated the accuracy and efficiency of in silico prediction in combination with the cell culture-based full-length gene assay for the classification of SPINK1 intronic variants. Based upon these findings, we propose an operational pipeline for classifying SPINK1 intronic variants in the clinical diagnostic setting. Electronic supplementary material The online version of this article (10.1186/s40246-019-0193-7) contains supplementary material, which is available to authorized users.

Background: Pancreatic stones are pathognomonic of chronic pancreatitis (CP). This study aimed to determine the incidence, identify risk factors, and develop a nomogram for pancreatic stones in CP patients. Methods: Patients with CP admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic stones after the onset of CP and after the diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. Results: With a total of 2,153 CP patients, pancreatic stones were detected in 1,626 (75.5%) patients, with a median follow-up of 7.8 years. Age at the onset of CP, body mass index, smoking, diabetes mellitus, pancreatic pseudocyst, biliary stricture, severe acute pancreatitis, and type of pain were identified risk factors for pancreatic stones development. The nomogram with these 8 factors achieved good accuracy. Conclusions: The nomogram achieved an individualized prediction of pancreatic stones development in CP. It may help the management of pancreatic stones.

Background Pediatric patients always suffer from chronic pancreatitis (CP), especially those with steatorrhea. This study aimed to identify the incidence of and risk factors for steatorrhea in pediatric CP. To our best knowledge, there is no pediatric study to document the natural history of steatorrhea in CP. Methods CP patients admitted to our center from January 2000 to December 2013 were enrolled. Patients were assigned to the pediatric (

It has long been known that canonical 5’ splice site (5’SS) GT>GC mutations may be compatible with normal splicing. However, to date, the true scale of canonical 5’SS GT>GC mutations generating wild-type transcripts, both in the context of the frequency of such mutations and the level of wild-type transcripts generated from the mutation alleles, remain unknown. Herein, combining data derived from a meta-analysis of 45 informative disease-causing 5’SS GT>GC mutations (from 42 genes) and a cell culture-based full-length gene splicing assay of 103 5’SS GT>GC mutations (from 30 genes), we estimate that ∼15-18% of the canonical GT 5’SSs are capable of generating between 1 and 84% normal transcripts as a consequence of the substitution of GT by GC. We further demonstrate that the canonical 5’SSs whose substitutions of GT by GC generated normal transcripts show stronger complementarity to the 5’ end of U1 snRNA than those sites whose substitutions of GT by GC did not lead to the generation of normal transcripts. We also observed a correlation between the generation of wild-type transcripts and a milder than expected clinical phenotype but found that none of the available splicing prediction tools were able to accurately predict the functional impact of 5’SS GT>GC mutations. Our findings imply that 5’SS GT>GC mutations may not invariably cause human disease but should also help to improve our understanding of the evolutionary processes that accompanied GT>GC subtype switching of U2-type introns in mammals.

Objectives\ud \ud Rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort.\ud \ud Methods\ud \ud We performed targeted next-generation sequencing of the four CP-associated genes in 1061 Han Chinese CP patients and 1196 controls. To evaluate gene–environment interactions, the patients were divided into three subgroups, idiopathic CP (ICP; n = 715), alcoholic CP (ACP; n = 206), and smoking-associated CP (SCP; n = 140). The potential impact of rare pathogenic variants on the age of onset of CP and clinical outcomes was evaluated using the Kaplan–Meier model.\ud \ud Results\ud We identified rare pathogenic genotypes involving the SPINK1, PRSS1, CTRC, and/or CFTR genes in 535 (50.42%) CP patients but in only 71 (5.94%) controls (odds ratio = 16.12; P

Background and AimsWe aimed to investigate outcomes of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) for the removal of large pancreatic stones coexisting with pancreatic pseudocysts (PPCs) in chronic pancreatitis (CP).MethodsThis is a prospective study performed in CP patients with at least 1 stone (≥5 mm). Patients were divided into the PPC group (stones coexisting with PPCs) or the control group (stones alone). Patients were initially subjected to successive P-ESWL treatments, followed by ERCP. Primary outcomes were P-ESWL adverse events, and secondary outcomes were stone clearance, long-term pain relief, improved quality-of-life scores, and PPC regression.ResultsA total of 849 patients (59 in the PPC group and 790 in the control group) was subjected to P-ESWL between March 2011 and October 2013. Occurrences of P-ESWL adverse events were similar between the PPC group and the control group (11.86% vs 12.41%, P = .940). After the treatment of initial P-ESWL combined with ERCP, the complete, partial, and nonclearance of stones occurred in 67.24%, 20.69%, and 12.07%, respectively, of patients in PPC group, with no significant difference from the control group (complete, partial, and nonclearance: 83.17%, 10.40%, and 11.39%, respectively; P = .106). Fifty-five of 59 patients (93.22%) with PPCs were followed for a median period of 21.9 months (range, 12.0-45.1). PPCs disappeared in 56.36% (31/55) and 76.36% (42/55) of patients after 3 months and 1 year of follow-up visits, respectively. Moreover, complete and partial pain relief were achieved in 63.64% (35/55) and 25.45% (14/55) of patients, respectively. The scores for quality of life (P < .001), physical health (P < .001), and weight loss (P < .001) improved.ConclusionsIn our multispecialty tertiary center, initial P-ESWL followed by ERCP was safe in patients with coexisting pancreatic stones and PPCs and effective for stone clearance, main pancreatic duct drainage, and pain relief.

The ingestion of foreign bodies is a common emergency in clinical practice, representing about 4% of all emergency endoscopies. If not treated promptly, ingested foreign bodies may cause serious complications, even result in death. Currently, the international guidelines and consensuses on the management of foreign bodies in the upper gastrointestinal tract mainly include Management of ingested foreign bodies and food impactions by the American Society for Gastrointestinal Endoscopy (ASGE), Management of ingested foreign bodies in children: a clinical report of the NASPGHAN Endoscopy Committee by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), Pediatric button battery injuries: 2013 task force update by the American Broncho-Esophagological Association (ABEA); Management of ingested magnets in children by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and NASPGHAN; and Clinical guidelines for imaging and reporting ingested foreign bodies by the American Roentgen Ray Society (ARRS). But no guideline or consensus on the endoscopic management of foreign bodies in the upper gastrointestinal tract is available in China. Thus, the Chinese Society of Digestive Endoscopy has led and organized experts from various disciplines, including gastroenterology, digestive endoscopy, thoracic surgery, gastrointestinal surgery, otorhinolaryngology, emergency medicine, pediatrics, and radiology, to co-develop this consensus based on the current status of management for upper gastrointestinal foreign bodies in China, with reference to the latest international guidelines and consensuses. This article is protected by copyright. All rights reserved.

Background: Although variants in the three trypsin-dependent pathway genes, PRSS1, SPINK1 and CTRC, have been firmly associated with a risk of developing chronic pancreatitis, their potential impact on the clinical course of the disease remains unclear. Methods: We performed targeted next-generation sequencing of the PRSS1, SPINK1 and CTRC genes in 2 257 Han Chinese subjects, including 715 idiopathic chronic pancreatitis (ICP) patients, 206 alcoholic chronic pancreatitis (ACP) patients, 140 smoking-associated chronic pancreatitis (SCP) patients, and 1 196 controls. All called rare variants were subjected to Sanger sequencing; all validated variants were assigned as being either pathogenic or non-pathogenic in accordance with stringent criteria. The potential impact of pathogenic variants on disease onset and progression of ICP, ACP and SCP was evaluated using the Kaplan-Meier model. Findings: We identified rare pathogenic genotypes involving the PRSS1, SPINK1 and CTRC genes in 388 (54·27%) of ICP patients but in only 52 (4·35%) of controls (odds ratio=26·10; p

BackgroundChronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas. This study aimed to compare the natural course of alcoholic chronic pancreatitis (ACP) and idiopathic chronic pancreatitis (ICP).MethodsCP patients admitted to our center from January 2000 to December 2013 were enrolled. Characteristics were compared between ACP and ICP patients. Cumulative rates of diabetes mellitus (DM), steatorrhea, pancreatic stone, pancreatic pseudocyst, biliary stricture, and pancreatic cancer after the onset and the diagnosis of CP were calculated, respectively. The cumulative rates of DM and steatorrhea after diagnosis of pancreatic stone were also calculated.ResultsA total of 2,037 patients were enrolled. Among them, 19.8% (404/2,037) were ACP and 80.2% (1,633/2,037) were ICP patients. ACP and ICP differs in many aspects, especially in gender, age, smoking, complications, morphology of pancreatic duct, and type of pain. The development of DM, steatorrhea, PPC, pancreatic stone, and biliary stricture were significantly earlier and more common in ACP patients. No significant difference was observed for pancreatic cancer development. There was a rather close correlation between exocrine/endocrine insufficiency and pancreatic stone in ACP patients, which was much less correlated in ICP patients.ConclusionThe long-term profile of ACP and ICP differs in some important aspects. ACP patients usually have a more severe course of CP. These differences should be recognized in the diagnosis and treatment of CP.

Vascular invasion is one of the most important prognostic factors for patients with hepatocellular carcinoma (HCC). The objective of the current, retrospective study was to determine the associations of ascites and hepatitis B viral factors (HBeAg and anti-HBe status and HBV DNA levels), as well as tumor-related factors (size, tumor number, grade, and location) with micro- or macroscopic vascular invasion in patients with HCC that developed as a result of hepatitis B virus (HBV)-related cirrhosis. A total of 336 consecutive patients were included. Potential factors associated with micro- or macroscopic vascular invasion were analyzed by logistic regression. Ascites were more commonly detected in patients with micro- or macroscopic vascular invasion, and the presence of ascites was independently associated with vascular invasion. Among patients with mild-to-moderate or severe ascites, the odds ratio for macroscopic vascular invasion was 4.83 (95 % confidence interval [CI] 2.29-10.16) and 11.87 (95 % CI 4.53-31.07), respectively. Similarly, the presence of ascites was associated with microscopic vascular invasion (OR 5.00; 95 % CI 1.23-20.31). In contrast, hepatitis B viral factors were not significantly associated with vascular invasion. The presence of ascites was associated with vascular invasion in patients with HBV-related cirrhotic HCC. Thus, patients with ascites, vascular invasion should be considered and more frequent surveillance should be performed after curative treatment.

To identify the risk factors and develop nomograms for common bile duct (CBD) stricture in chronic pancreatitis (CP) patients.CBD stricture is a common complication in CP and has a variable clinical presentation ranging from asymptomatic to overt jaundice and cholangitis.Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of CBD stricture after onset and diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. On the basis of the training cohort, risk factors for CBD stricture and symptomatic CBD stricture were identified through Cox proportional hazards regression model, and nomograms was developed, respectively. Internal and external validations were performed based on the training and validation cohort, respectively.With a total of 2153 patients, the median duration of follow-up was 7.0 years. CBD strictures were detected in 340 (15.8%) patients, whereas 159 of them were symptomatic. Male gender, age at onset of CP, smoking, body mass index, and morphology of main pancreatic duct were identified risk factors for CBD stricture development. Age at onset of CP, body mass index, and type of pain were identified risk factors for symptomatic CBD stricture development. Both nomograms achieved good concordance indexes with well-fitted calibration curves.The nomogram achieved an individualized prediction of symptomatic CBD stricture development in CP patients. It may help the early diagnosis and intervention of symptomatic CBD stricture and reduce the rates of severe adverse events.

Background Risk of pancreatic cancer may increase in chronic pancreatitis patients. Aims This study aimed to identify the incidence of and risk factors for pancreatic cancer in chronic pancreatitis patients. Methods Chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic cancer and survival rates were calculated. The standardized incidence ratio was calculated based on the pancreatic cancer incidence in general population of China. Risk factors for pancreatic cancer were identified. Results In a total of 1656 patients, the median follow-up duration was 8.0 years. Pancreatic cancer was detected in 21 patients (1.3%). The expected number of cases of pancreatic cancer was 1.039, yielding a standardized incidence ratio of 20.22. The standardized incidence ratios for patients with a >60 pack-year smoking history were much higher (145.82). Two risk factors for pancreatic cancer were identified: age at the onset of chronic pancreatitis (hazard ratio, 1.05) and a >60 pack-year smoking history (hazard ratio, 11.83). Conclusion The risk of pancreatic cancer is markedly increased in chronic pancreatitis patients compared with the general population, especially in patients with an older age at onset and a >60 pack-year smoking history. The high-risk populations were suggested to be followed up closely.

Chronic pancreatitis (CP) is an inflammatory disease characterized by progressive fibrosis of pancreas. Early diagnosis will improve the prognosis of patients. This study aimed to obtain serum miRNA biomarkers for early diagnosis of CP. In the current study, we analyzed the differentially expressed miRNAs (DEmiRs) of CP patients from Gene Expression Omnibus (GEO), and the DEmiRs in plasma of early CP patients (n = 10) from clinic by miRNA microarrays. Expression levels of DEmiRs were further tested in clinical samples including early CP patients (n = 20), late CP patients (n = 20) and healthy controls (n = 18). The primary endpoints were area under curve (AUC) and expression levels of DEmiRs. Four DEmiRs (hsa-miR-320a-d) were obtained from GEO CP, meanwhile two (hsa-miR-221 and hsa-miR-130a) were identified as distinct biomarkers of early CP by miRNA microarrays. When applied on clinical serum samples, hsa-miR-320a-d were accurate in predicting late CP, while hsa-miR-221 and hsa-miR-130a were accurate in predicting early CP with AUC of 100.0% and 87.5%. Our study indicates that miRNA expression profile is different in early and late CP. Hsa-miR-221 and hsa-miR-130a are biomarkers of early CP, and the panel of the above 6 serum miRNAs has the potential to be applied clinically for early diagnosis of CP.

Six cases with various clinical manifestations and treatments are presented in this chapter.

It is difficult to some extent to make the definitive diagnosis of chronic pancreatitis, especially if the disease is not recognized by the physicians treating the patients. Basing on the presence of several different diagnostic characters of the CP, the Zurich workshop on alcoholic chronic pancreatitis proposed a classification in which CP was divided into ‘probable’ and ‘definite’ (Ammann 1997). There is a similar grading recommended by the Japan Pancreas Society (Homma et al. 1997). In 2007, Schneider and his colleagues established a new MANNHEIM classification system referring to the understandings of the Zurich workshop, but they decided to include smaller amounts of alcohol intake as risk factors for the development of CP than before, as well as a subgroup of ‘borderline’ CP into the classification system. The M-ANNHEIM diagnostic criteriaof CP are listed in Table 7.1 (Schneider et al. 2007).

Pancreatic pseudocyst is a common complication of chronic pancreatitis. The identification of risk factors and development of a nomogram for pancreatic pseudocysts in chronic pancreatitis patients may contribute to the early diagnosis and intervention of pancreatic pseudocysts.Patients with chronic pancreatitis admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic pseudocysts after the onset of chronic pancreatitis and after the diagnosis of chronic pancreatitis were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively.With a total of 1998 patients, pancreatic pseudocysts were detected in 228 (11.41%) patients. Age at the onset of chronic pancreatitis, smoking, and severe acute pancreatitis were identified risk factors for pancreatic pseudocysts development while steatorrhea and pancreatic stones were protective factors. Incorporating these five factors, the nomogram achieved good concordance indexes of 0.735 and 0.628 in the training and validation cohorts, respectively, with well-fitted calibration curves.The nomogram achieved an individualized prediction of pancreatic pseudocysts development in chronic pancreatitis. It may help the early diagnosis and management of pancreatic pseudocysts.

This study aimed to investigate the occurrence of and determine the risk factors for steatorrhea in chronic pancreatitis (CP). It was based on analysis of both retrospectively and prospectively acquired database for CP patients admitted to our center from January 2000 to December 2013. Demographic data, course of disease, medical history and follow-up evaluations of patients were documented in detail. Cumulative rate of steatorrhea was calculated by using the Kaplan–Meier method. For risk factor analysis, multivariate analysis by Cox proportional hazards regression model was performed. A total of 2,153 CP patients were included with a mean follow-up duration of 9.3 years. Approximately 14% (291/2,153) of CP patients presented with steatorrhea at diagnosis of CP. Cumulative rates of steatorrhea at 1, 5, 10 and 20 years after diagnosis of CP were 4.27% (95% CI: 3.42%–5.34%), 12.53% (95% CI: 10.74%–14.59%), 20.44% (95% CI: 17.37%–23.98%) and 30.82% (95% CI: 20.20%–45.21%), respectively. Male gender (HR = 1.771, p = 0.004), diabetes (HR = 1.923, p

Supplemental Digital Content is available in the text, Background: The aim of this study was to explore the underlying molecular mechanism and potential molecular biomarkers of chronic pancreatitis (CP) and construct a miRNA-mRNA regulation network. Methods: To explore the involvement of miRNAs in CP, we downloaded the miRNA and mRNA expression profiles of CP patients and healthy controls and identified the differentially expressed miRNAs and genes. Functional analysis was conducted and significant pathways were utilized. Finally, the miRNA-mRNA regulation network of CP was constructed. Results: A total of 44 miRNA risk gene pathway relationships were identified, and a complex regulation network was constructed with 3 genes (ABL1, MYC, and ANAPC13) having the highest degree in affecting the network of CP. Importantly, 4 risk genes (NOTCH3, COX5A, THBS1, and KARS) and 1 risk miRNA (hsa-miR-324-5p) were identified with high prediction accuracy. Conclusions: In conclusion, we analyzed miRNAs and mRNAs expression profiles in CP, 1 risk miRNA, and 4 risk genes were identified with high prediction accuracy as biomarkers of CP. Although further evaluation in clinical study is needed, our findings provide new insights into the pathogenesis of CP and may improve the diagnosis and therapy by identifying novel targets.