Objectives: 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. Methods: 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. Results: We identified rare pathogenic genotypes involving the SPINK1, PRSS1, CTRC, and/or CUR genes in 535 (50.42%) CP patients but in only 71 (5.94%) controls (odds ratio = 16.12; P < 0.001). Mutation-positive patients had significantly earlier median ages at disease onset and at diagnosis of pancreatic stones, diabetes mellitus and steatorrhea than mutation-negative ICP patients. Pathogenic genotypes were present in 57.1, 39.8, and 32.1% of the ICP, ACP, and SCP patients, respectively, and influenced age at disease onset and clinical outcomes in all subgroups. Conclusions: We provide evidence that rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes significantly influence the age of onset and clinical outcomes of CP. Extensive gene-environment interactions were also identified.

In their recent observational study, Zhao et al1Zhao Z.H. Hu L.H. Ren H.B. et al.Incidence and risk factors for post-ERCP pancreatitis in chronic pancreatitis.Gastrointest Endosc. 2017; 86: 519-524Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar found similar incidence rates of post-ERCP pancreatitis (PEP) in patients with chronic pancreatitis (CP) versus other biliary diseases, and they reported lower PEP incidence rates as the severity of CP increased. The authors state that they “identified other possible risk and protective factors not examined before. The reduced incidence of PEP in CP patients was correlated with the presence of diabetes mellitus, pancreatic stones, and the use of ESWL (extracorporeal shock wave lithotripsy).” We would like to point out that our group had formerly evaluated the influence of type 2 diabetes mellitus (T2DM) on the short-term adverse events after ERCP in an 11-year (2003-2013) observational study that included 126,885 therapeutic procedures (23,002 [18.1%] in people with T2DM) in the overall Spanish population.2de Miguel-Yanes J. Méndez-Bailón M. Jiménez-García R. et al.Tendencies and outcomes in endoscopic biliary sphincterotomies among people with or without type 2 diabetes mellitus in Spain, 2003-2013.Rev Esp Enferm Dig. 2016; 108: 386-393Crossref PubMed Scopus (3) Google Scholar We found lower crude incidence rates of PEP in people with T2DM than in people without T2DM (15.9% vs 18.3%, respectively). We additionally described decreasing numbers of PEP over time, but this trend reached statistical significance only for people without T2DM. In our study, T2DM was associated with lower in-hospital mortality after an endoscopic biliary sphincterotomy (odds ratio [OR] = 0.82 [0.74-0.92]). Last, time trend analyses from 2003 to 2013 showed significant reductions in in-hospital mortality over time only in people with T2DM (OR = 0.97 [0.94-1.00]). Despite some methodologic limitations inherent in observational studies, we believe that it is worth remembering our results at this point.3García-Cano J. If you suffer from type-2 diabetes mellitus, your ERCP is likely to have a better outcome.Rev Esp Enferm Dig. 2016; 108: 383-385Crossref PubMed Scopus (2) Google Scholar All authors disclosed no financial relationships relevant to this publication. Incidence and risk factors for post-ERCP pancreatitis in chronic pancreatitisGastrointestinal EndoscopyVol. 86Issue 3PreviewAlmost all studies on post-ERCP pancreatitis (PEP) have mainly involved patients with biliary diseases rather than chronic pancreatitis (CP), and the concept that CP seems to be a protective factor associated with PEP has not been studied in detail. The aim of this study was to determine the incidence of PEP in patients with CP at different clinical stages and to identify the predictive and protective factors of PEP in a large cohort. Full-Text PDF Response:Gastrointestinal EndoscopyVol. 87Issue 1PreviewWe highly appreciate the response from de Miguel-Yanes et al1 about the influence of diabetes mellitus (DM) on the incidence rate of post-ERCP pancreatitis (PEP). Because patients with chronic pancreatitis (CP) are at high risk for the development of DM, it is an important issue with significant implications for clinical practice.2 Full-Text PDF

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.

Rare functionally defective carboxypeptidase A1 (CPA1) variants have been reported to predispose to nonalcoholic chronic pancreatitis, mainly the idiopathic subtype. However, independent replication has so far been lacking, particularly in Asian cohorts where initial studies employed small sample sizes. Herein we performed targeted next-generation sequencing of the CPA1 gene in 1,112 Han Chinese idiopathic chronic pancreatitis (ICP) patientsthe largest ICP cohort so far analyzed in a single populationand 1,580 controls. Sanger sequencing was used to validate called variants, and the CPA1 activity and secretion of all newly found variants were measured. A total of 18 rare CPA1 variants were characterized, 11 of which have not been previously described. However, no significant association was noted with ICP irrespective of whether all rare variants [20 out of 1,112 (1.8%) in patients vs. 24 out of 1,580 (1.52%) in controls; P=0.57] or functionally impaired variants [three out of 1,112 (0.27%) in patients vs. two out of 1,580 (0.13%) in controls; P=0.68] were considered.

Background and Aims: Almost all studies on post-ERCP pancreatitis (PEP) have mainly involved patients with biliary diseases rather than chronic pancreatitis (CP), and the concept that CP seems to be a protective factor associated with PEP has not been studied in detail. The aim of this study was to determine the incidence of PEP in patients with CP at different clinical stages and to identify the predictive and protective factors of PEP in a large cohort.Methods: In this observational cohort study, medical records of patients with CP (CP group) and biliary diseases (BD group) in a tertiary hospital from January 2011 to May 2015 were examined. The difference in the incidence of PEP between CP group and BD group and the risk of PEP at different clinical stages of CP were calculated by the chi(2) test or the Fisher exact test. The predictive and protective factors for PEP were investigated by univariate and multivariate analysis.Results: In total, 2028 ERCP procedures were performed in 1301 patients with CP and 2000 procedures in 1655 patients with BD. The overall incidence of PEP in CP group (4.5%) was similar to that in the BD group (4.8%; P = .747). However, CP patients had significantly lower rates of moderate and severe attacks (0% vs 1.3%, P < .01). According to the M-ANNHEIM classification, the PEP incidences of CP at stages 0, I, II, III, and IV were 4.4%, 5.1%, 3.8%, 2.0%, and 2.0%, respectively. CP patients at stage Ia had the highest PEP incidence (8.0%) among all CP patients, significantly higher than that at stages Ib + Ic (3.9%) and II (3.8%). Female gender, history of acute pancreatitis, and prior PEP were independent risk factors of PEP, whereas extracorporeal shock wave lithotripsy was a protective factor.Conclusions: Compared with BD patients, CP patients had similar incidence of PEP overall but lower grades of severity. The incidence of PEP in CP patients decreased significantly with disease progression.

内镜下逆行胰胆管造影术（ ERCP）是胆胰疾病一项重要的诊断与治疗技术，具有诊断确切、疗效好、创伤小、不良反应少及费用低等优点。但其作为有创操作，术后有一定并发症，包括ERCP术后胰腺炎（ post-ERCP pancreatitis ， PEP）、出血、感染等，其中，PEP是最常见、最严重的并发症，一旦并发重症胰腺炎，患者的生命会受到严重威胁。为了有效预防PEP，国内外学者对其发病机制、危险因素及防治措施等方面进行了广泛而深入的研究。迄今为止，直肠给予非甾体类抗炎药及胰管支架置入的效果是比较明确的，但仍未有效解决这一世界性的难题。本文就PEP的定义、发生率、危险因素尤其是预防治疗的最新研究作一综述。

Objective To investigate the clinical application value of magnetically guided capsule endoscopy ( MGCE) to stomach examination. Methods Data of 500 patients who received MGCE examina?tion from January 2014 to February 2016 in our hospital were retrospectively analyzed. The feasibility and safety of MGCE were studied by analyzing the detection rate of gastric lesions, transit time, adverse events, clarity and visibility, in comparison with esophagogastroduodenoscopy( EGD) . Results The lesion detecting rate was 57?8%(289/500), the average transit time was (106?0±101?1)min. Overall effective rate of cleanliness was 91?8%. The visibility satisfaction rate was 98?8%. Compared with EGD, MGCE had good detection ability in stomach focal lesions. The sensitivity,specificity and accuracy were 92?0%, 85?7% and 88?3%,respectively. Except for capsule retention occurred in one patient, no other complication happened. Conclusion MGCE, stable and safe, shows high detection and accuracy rates for gastric diseases, and can be used as an effective examination tool.

Objective To detect the changing discipline of detection rate of gastric and duodenal ulcers varied by season based on the database of Digestive Endoscopy Center of Changhai Hospital of 10 years and the trend of the number of upper endoscopies in Changhai Hospital,and to figure out the detection rate of peptic ulcer in different genders,age groups and patient status.Methods All endoscopy data were listed by season.The number of endoscopic procedures and diagnosis were obtained.The analysis of detection rate of peptic ulcer disease in different seasons in different gender,age group and patient status was conducted using the chi square test.One-Way-ANOVA test was used to validate the time trends of the number of endoscopic procedures and diagnosis,while binary logistic regression was used for detection rate of peptic ulcer disease.Results A total of 215 692 endoscopic reports were derived from the database,among which 33 559 were diagnosed as peptic ulcer,with 18 270 as gastric ulcer and 15 289 as duodenal ulcer.There were significant differences in detection rates of peptic ulcer disease in different seasons in different gender,age group and patient status.The detection rates of gastric ulcer(P＜0.01,OR =0.983,95％ CI:0.976-0.987) and duodenal ulcer (P＜0.05,OR =0.992,95％CI:0.986-0.997)decreased along the time trend.The detection rates of gastric ulcer (P＜0.01,OR=1.04,95％CI:1.03-1.06) and duodenal ulcer(P＜0.01,OR=1.05,95％ CI:1.03-1.06) showed a significant seasonal variation.The detection rate of gastric ulcer was higher in winter (9.26％) and lower in spring (8.16％).As for duodenal ulcer,the detection rate is also higher in winter (8.38％),but lower in autumn (5.88％).Conclusion From 2004 January to 2014 February,the number of endoscopic procedures increased and showed a significant seasonal variation.Although the number of endoscopic diagnosis increased in the past 10 years,the overall detection rate of the two kinds of peptic ulcer declined.The time trends of detection rate of both ulcer showed a significant seasonal variation,higher in winter.

Objective To culture C57BL/6 mouse pancreatic stellate cells (PSCs) with a modified method,and to establish a simple cultivation method with a high yield of PSCs.Methods Pancreatic tissues in C57BL/6 mice were collected,washed by fetal bovine serum,minced into 0.5 ～ 1 mm3,and cultured in sterile culture flasks.After 4days,primary PSCs were collected and passed on.The changes in intracellular lipid droplets were identified by oil red O staining;α-SMA,desmin expression was detected by immunocytochemical or immunocytofluorescent staining,and Western blot.Results Outgrowth cells in the fourth day were oval or star with abundant lipid droplets and fewer cells expressed c-SMA and desmin protein.PSCs turned into bigger,more pseudopodial ones with decreasing lipid droplets and significantly increasing expression of o-SMA and desmin protein after the passage.Protein expression of α-SMA in primary and passage PSCs were 0.653 ± 0.071,2.290 ± 0.055,respectively;and the expression in passage PSCs was significantly higher than that in primary PSCs (P ＜0.05),and the number of cells expressing desmin protein was significantly increased.Conclusions Modified tissue culture is a high yield and high purity method for both quiescent and activated PSCs,which can meet the need of in-vitro studies.

Pancreas is a retroperitoneally located organ, and thus general CT and MRI have a very limited specificity and sensitivity in diagnosing pancreatic diseases. However, endoscopic ultrasonography (EUS) with a better differential diagnostic capability of detecting pancreatic morphology and properties through gastric wall has been widely accepted by physicians and become one of the first-line methods compared with other techniques. Currently, common technologies used in the diagnosis and treatment of pancreatic diseases include EUS-guided fine needle aspiration (EUS-FNA), EUS-guided drainage, EUS-guided pancreatic cysts ablation, EUS-assisted radiotherapy, and EUS-guided celiac plexus neurolysis (EUS-CPN), etc. Recent innovative applications include contrast-enhanced EUS with Doppler mode, contrast-enhanced harmonic EUS, and EUS elastography. The clinical application of EUS in pancreatic diseases has been overviewed. Keywords: Diagnosis, endoscopic ultrasonography (EUS), endoscopy, pancreatic diseases, therapy.