SPINK1 mutations and risk of pancreatic cancer in a Chinese cohort.

OBJECTIVE: The relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP). METHODS: This is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients' demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status. RESULTS: PC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14-1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04-0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered. CONCLUSIONS: CP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP.

Optimal Timing of Endoscopic Intervention After Extracorporeal Shock-Wave Lithotripsy in the Treatment of Chronic Calcified Pancreatitis.

OBJECTIVES: The interval between extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) may cause differences in cannulation and stone removal. This study was to investigate the optimal timing of ERCP after ESWL. METHODS: Patients with chronic calcified pancreatitis, who underwent ESWL and subsequent ERCP in Changhai Hospital from February 2012 to February 2015, were retrospectively analyzed. The interval between ESWL and ERCP was used to divide patients into groups A (<12 hours), B (12-36 hours), and C (>36 hours). Cannulation success, stone clearance, and post-ESWL/ERCP complications were compared. RESULTS: A total of 507 patients were enrolled. There were no significant differences regarding the successful cannulation and stone removal rates between the 3 groups. In patients without prior ERCP, the successful cannulation rates were 71.4%, 81.9%, and 90.9% (P = 0.004), and the successful clearance rates were 76.2%, 85.1%, and 90.9% (P = 0.031) for these 3 groups, respectively, showing significant differences. There were no differences in the successful cannulation and stone extraction rates for patients with prior ERCP. CONCLUSIONS: The interval between ESWL and ERCP in chronic calcified pancreatitis patients with prior ERCP is not relevant, while delaying endoscopic intervention is recommended in those with native papilla.

Factors associated with prior acute pancreatitis episodes among patients with chronic pancreatitis.

BACKGROUND: The relationship between chronic pancreatitis (CP) and acute pancreatitis (AP) is complex and not well understood. CP could be preceded by antecedent episodes of AP. AIMS: The aim of this study was to explore both genetic and environmental factors associated with AP episodes before the diagnosis of CP. METHODS: This was a cross-sectional study including 1022 patients. Detailed demographic, genetic, and clinical data were collected. Based on the presence of AP episode(s) before diagnosis of CP, patients were divided into AP group (further classified into single episode of AP group and recurrent AP group) and non-AP group. Related factors among these groups were assessed using multivariate logistic regression model. RESULTS: Before diagnosis of CP, 737 patients (72.1%) had a history of AP. Smoking(P = 0.005) and heavy alcohol consumption(P = 0.002) were risk factors for AP while age at CP onset(P < 0.001), harboring the SPINK1 mutation(P < 0.001), diabetes(P < 0.001) and steatorrhea(P < 0.001) were protective factors. Further, alcoholic CP(P = 0.019) was the only independent risk factor for recurrent AP attacks while age at onset of CP(P < 0.001), pancreatic stones(P = 0.024). and pseudocysts(P = 0.018) served as protective factors. CONCLUSIONS: SPINK1 mutations served as protective factor for AP episodes, suggesting SPINK1 mutation might play a pathogenic role in CP occurrence with occult clinical manifestations.

Risk factors for sinistral portal hypertension and related variceal bleeding in patients with chronic pancreatitis.

OBJECTIVES: Sinistral portal hypertension (SPH) is an uncommon complication of chronic pancreatitis (CP) and can result in severe gastrointestinal bleeding. The aim of this study was to determine the prevalence and the potential risk factors for SPH and related gastrointestinal variceal bleeding in patients with CP. METHODS: We retrospectively reviewed all patients with SPH due to CP admitted to our hospital from July 2014 to June 2019 in this case-control study. Patients with CP without SPH were randomly selected as controls during the study period (case: control  =  1:2). The characteristics, medical history, course of CP, characteristics associated with SPH, and follow-up evaluations of the patients were documented in detail. The prevalence rate of SPH in patients with CP and related gastrointestinal bleeding was calculated. Risk factors for SPH and related variceal bleeding were analyzed using univariate or multivariate logistic regression analysis. RESULTS: The prevalence of SPH was 2.7% (89/3358) in patients with CP. Independent risk factors for SPH included alcohol consumption (P = 0.030), history of acute pancreatitis (P = 0.010), diabetes mellitus (P < 0.001), and pseudocysts (P < 0.001). Overall 17 (19.1%) patients suffered from related gastrointestinal bleeding. Between the bleeding and non-bleeding groups, there were significant differences in the types of CP, existence of stones, gastric varices diagnosed before bleeding, splenomegaly and hypersplenism by univariate analysis. CONCLUSION: SPH is a rare complication of CP that is associated with a relatively low risk of variceal bleeding.