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Background: The G-protein-coupled receptor Class C Group 6 Member A (GPRC6A) is activated by multiple ligands and is important for the regulation of calcium homeostasis. Extracellular calcium is capable to increase NLRP3 inflammasome activity of the innate immune system and deletion of this proinflammatory pathway mitigated pancreatitis severity in vivo. As such this pathway and the GPRC6A receptor is a reasonable candidate gene for pancreatitis. Here we investigated the prevalence of sequence variants in the GPRC6A locus in different pancreatitis aetiologies., Methods: We selected 6 tagging SNPs with the SNPinfo LD TAG SNP Selection tool and the functional relevant SNP rs6907580 for genotyping. Cohorts from Germany, further European countries and China with up to 1,124 patients and 1,999 controls were screened for single SNPs with melting curve analysis., Results: We identified an association of rs1606365(G) with alcoholic chronic pancreatitis in a German (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.65-0.89, p = 8 × 10 -5 ) and a Chinese cohort (OR 0.78, 95% CI 0.64-0.96, p = 0.02). However, this association was not replicated in a combined cohort of European patients (OR 1.18, 95% CI 0.99-1.41, p = 0.07). Finally, no association was found with acute and non-alcoholic chronic pancreatitis., Conclusions: Our results support a potential role of calcium sensing receptors and inflammasome activation in alcoholic chronic pancreatitis development. As the functional consequence of the associated variant is unclear, further investigations might elucidate the relevant mechanisms., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/objectives: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP., Methods: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses., Results: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only., Conclusions: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/objectives: The elevation of insulin-like growth factor 1 (IGF-1) and adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the risk of many cancers. The aim of this study was to evaluate the serum concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis (CP)., Methods: The study included 43 patients with PDAC, 39 patients with CP and 10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA method (Corgenix UK Ltd R&D Systems). The study protocol was approved by the Bioethics Committee at the Medical University of Lodz., Results: In PDAC patients the serum IGF-1 level was significantly higher than in patients with CP (107.79 ± 66.40 ng/ml vs 89.91 ± 74.06 ng/ml; P < 0.05). Patients with both CP and diabetes mellitus (DM) were noted to have a significantly lower level of IGF-1 compared with those who only had CP (51.33 ± 24.30 ng/ml vs 108.42 ± 82.39 ng/ml; P = 0.01). The same result was obtained for men with and without DM (58.05 ± 32.44 ng/ml vs 98.79 ± 79.47 ng/ml, P = 0.05). As regards the serum level of RBP-4, the PDAC and CP groups were not significantly different from each other., Conclusions: Diabetes accompanying PDAC does not influence the level of IGF-1 as opposed to diabetes in the course of CP. The IGF-1 level can be useful for early diagnosis of PDAC. High concentration of RBP-4 is not specific to pancreatic cancer, so it does not appear to be a useful biomarker for PDAC., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/aims: Analysis of cystic fluid may be useful in distinguishing between benign and malignant cysts which has significant impact on their management. The aim of our study was to assess the diagnostic utility of carcinoembryonic antigen (CEA) and K-ras gene mutation in pancreatic cysts fluid., Methods: The study included 56 patients with pancreatic cystic fluid collected for analysis. The cysts were classified as benign (simple cysts, pseudocysts, serous cystadenoma) - 39 patients or premalignant/malignant (mucinous cystadenoma, IPMN, cystadenocarcinoma) - 17 patients. The patients history, CEA fluid concentrations and presence of K-ras mutation were analyzed., Results: CEA were higher in patients with malignant cysts (mean levels 238 ± 12.5 ng/ml; range 32.8-4985 ng/ml) compared to benign lesions (mean levels 34.5 ± 3.7 ng/ml; range 3.9-693 ng/ml; p < 0.001). K-ras mutation correctly classified 11 of 17 patients with premalignant/malignant lesions. It was also detected in 1 patient with final diagnosis of benign cyst (the sensitivity 64.7% and the specificity 97.4%; p < 0.01). If CEA and molecular analysis were combined in that cysts with either CEA level>45 ng/ml or presence of K-ras mutation, than 16 of 17 premalignant/malignant cysts were correctly identified (94.1%)., Conclusion: Molecular analysis of pancreatic cyst fluid adds diagnostic value to the preoperative diagnosis and should be considered when cyst cytologic examination is negative for malignancy., (Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Neopterin and tissue polypeptide-specific antigen (TPS) have been suggested to be useful in differential diagnosis between pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP). The aim of our study was to compare the clinical usefulness of CA19-9, neopterin and TPS serum levels in patients with PA and CP., Methods: The study included 85 patients with PA, 72 with CP and 50 healthy controls. The serum concentrations of neopterin, TPS and CA19-9 were measured (DRG International, USA). The associations of the analyzed markers and clinical data at diagnosis have been evaluated., Results: Serum levels of neopterin, TPS and CA19-9 were higher in PA patients compared to CP (p < 0.001). TPS and CA19-9 levels were also elevated in patients with CP compared to the control group (p < 0.001). In contrast, there was no difference between neopterin serum levels in CP patients and the control group (p > 0.05). Neopterin showed the best sensitivity and specificity (91.8 and 87.5%) in PA diagnosis compared to CA19-9 (respectively 83.5 and 75%) and TPS (75.3 and 65.3%)., Conclusion: Our results indicate that neopterin may be potentially useful in differential diagnosis between PA and CP. Assessment of TPS probably adds no significant information to that obtained with CA19-9 and neopterin. and IAP., (Copyright © 2011 S. Karger AG, Basel.)

Background: In chronic pancreatitis (CP), a debilitating, progressive and incurable disease, patients' wellbeing is considerably impaired, but the different factors affecting quality of life (QoL), have not been identified yet., Methods: 69 patients with CP were evaluated (M/F 55/14; mean age 46.6 +/- 10.05 years). Different degrees of pancreatic damage were defined using the Cambridge classification; pain intensity and frequency were assessed using pain index. QoL was measured using EORTC QLQ-C30 and the PAN26 questionnaire. Although developed for pancreatic cancer, the C30/PAN26 has been validated for chronic pancreatitis., Results: Digestive symptoms, financial difficulties, fear of future health and general pain scales showed considerable effects of CP on QoL. We observed significant negative correlation between mean QoL scores and pain index in almost all domains (p < 0.001, p < 0.05). Pain intensity affects QoL scales more often than pain frequency. BMI correlated positively with QoL in global health status, altered bowel habits, body image and satisfaction with health care domains (p < 0.01, p < 0.05)., Conclusion: Pain index, BMI, Cambridge classification and disease duration are the most important factors adversely affecting QoL in CP. Measurement of QoL is essential in the disease management and improves the knowledge of psychosocial functioning of these patients. and IAP.