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Acute pancreatitis (AP) is one of the most common diseases requiring hospitalization with increasing incidence. This pathology has variable severity and is associated with significant morbidity and mortality. Early diagnosis, including prognosis of clinical course of the disease is key in the initial clinical management. However, currently available prognostic markers have variable efficacy and the limited utility. Adipokines that are released from the peripancreatic adipose tissue during AP may represent the easy to use and practical AP prognostic markers. This review discusses the current state of knowledge concerning the clinical value of the adipokines in AP, such as adiponectin, ghrelin, interleukin 6, interleukin 8, interleukin 18, leptin, neutrophil gelatinase associated lipocalin, obestatin, resistin, visfatin. Among described adipokines, interleukin 6, neutrophil gelatinase associated lipocalin and resistin seem to be the most valuable as the diagnostic and prognostic markers in AP.

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.)

Objectives: Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). Our objective was to assess the efficacy and safety of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules (CREON) in patients with EPI due to CP or PS., Methods: This was a double-blind, randomized, multicountry, placebo-controlled, parallel-group trial enrolling patients ≥18 years old with confirmed EPI due to CP or PS conducted in clinical research centers or hospitals. After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units per meal; 36,000 per snack) or placebo for 7 days. All patients received an individually designed diet to provide at least 100 g of fat per day. The primary efficacy measure was the change in coefficient of fat absorption (CFA) from baseline to end of the double-blind period, analyzed using non-parametric analysis of covariance. Secondary outcomes included the coefficient of nitrogen absorption (CNA), clinical symptoms, and safety parameters., Results: In total, 25 patients (median age of 54 years, 76% male) received pancrelipase and 29 patients (median age of 50 years, 69% male) received placebo. Th e mean ± s.d. change from baseline in CFA was significantly greater with pancrelipase vs. placebo: 31.9 ± 18.6 vs. 8.7 ± 12.4 % ( P < 0.0001) [corrected]. Similarly, the mean ± s.d. change from baseline in CNA was greater for pancrelipase vs. placebo: 35.2 ± 29.1 vs. 8.9 ± 28.0 % ( P = 0.0005) [corrected].Greater improvements from baseline in stool frequency, stool consistency, abdominal pain, and flatulence were observed with pancrelipase vs. placebo. Treatment-emergent adverse events (TEAEs) were reported in five patients (20.0%) in the pancrelipase group and in six (20.7%) in the placebo group; the most common were gastrointestinal (GI) events and metabolism/nutrition disorders. There were no treatment discontinuations due to TEAEs., Conclusions: Pancrelipase delayed-release 12,000-lipase unit capsules were effective in treating fat and nitrogen maldigestion with a TEAE rate similar to that of placebo in patients with EPI due to CP or PS.

Background/aims: Pancreatic adenocarcinoma (PA) has a very poor prognosis. In patients suffering from chronic pancreatitis (CP) the risk for the PA development is higher than in the general population. The purpose of the study was to compare the prevalence of p53 mutations in PA and CP in order to evaluate their usefulness in differential diagnosis of those diseases., Methodology: We examined 49 patients who underwent Whipple resection or distal pancreatectomy for pancreatic adenocarcinoma (26 subjects) or chronic pancreatitis (23 subjects). DNA from pancreatic tissue was analyzed for p53 mutations with PCR/SSCP methods., Results: The p53 gene mutation has been shown in 16 (61.5%) of the PA patients (9 in exon 5 and 7 in exon 7) and in 2 (8.6%) of CP patients (1 in exon 5 and 1 in exon 8; p < 0.001). There was a significant correlation between p53 mutation and G3 tumor differentiation (p < 0.01). Overall median survival in patients with PA was 8.5 months. No relationship between presence of p53 mutation and survival time in PA patients has been observed., Conclusions: The specificity of p53 mutation for pancreatic cancer is very high. Our results indicate that p53 gene mutation may provide an additional tool in differential diagnosis of CP and PC.

Background: The differentiation of chronic pancreatitis (CP) from pancreatic adenocarcinoma (PA) remains the great challenge for clinicians. The purpose of this study was to compare the prevalence of K-ras and c-erbB-2 mutations in PA and CP in order to evaluate their usefulness in differential diagnosis of those diseases., Methods: The study included 49 patients who underwent Whipple resection or distal pancreatectomy for pancreatic adenocarcinoma (26 subjects) or chronic pancreatitis (23 subjects). DNA from pancreatic tissue was analyzed for K-ras codon 12 and c-erbB-2 mutations with PCR amplifications., Results: The K-ras gene mutation has been shown in 20 (76.9%) PA cases and in 8 (34.8%) CP cases (p<0.01). Prevalence of c-erbB-2 amplification in patients with PA was 17 (65.3%), which was not different from CP, 16 (56.5%) (p=0.58). There was a significant correlation between K-ras mutation and lymph node metastases (p=0.025) as well as between K-ras mutation and G3 tumor differentiation (p=0.037). Overall median survival in patients with PA was 9.5 mo. There was no relationship between presence of K-ras (p=0.58) or c-erbB-2 (p=0.17) mutation and survival time in PA patients., Conclusion: Those results may indicate that both K-ras and c-erbB-2 play a role in pancreatic carcinogenesis, however only K-ras may provide an additional tool in differential diagnosis of CP and PC.

Background/aims: The incidence of carbohydrate tolerance disorders in patients after acute pancreatitis has not been clearly established yet. The aim of the study was to estimate the frequency of endocrine pancreatic function impairment in patients after acute pancreatitis and its correlation with acute pancreatitis etiology and clinical course., Methodology: 82 patients (27 women and 55 men), aged between 28-65 (mean: 47 +/- 8.3), 1-7 (mean: 4.7 +/- 3.6) years after acute pancreatitis were evaluated. Control group consisted of 15 healthy volunteers. Oral glucose tolerance test with RIA insulin level was performed in all examined patients. Patients with any sign of chronic pancreatitis, based on clinical, functional (stool chymotrypsin test) and imaging (US and CT) findings, were excluded from the study., Results: Impaired glucose tolerance was found in 4 patients (4.9%) and overt diabetes in 13 patients (15.8%) recovered from acute pancreatitis, which was not significantly different from those values in the local general population. Mean insulin values fasting and 30, 60 and 90 min after administration of 75 g glucose were significantly lower in patients after acute pancreatitis than in controls (p < 0.001). Endocrine pancreatic function impairment was found significantly more often in patients after severe acute pancreatitis clinical course (p < 0.0001), than in patients after mild pancreatitis. The frequency of impaired glucose tolerance and diabetes after acute alcoholic pancreatitis was 13 (36%), which was significantly higher (p < 0.05), than in cases of gallstone etiology (14%) and other causes (0%)., Conclusions: Pancreatic endocrine function impairment following acute pancreatitis is associated with the decreased plasma insulin levels fasting and after glucose stimulus. Overall, the incidence of diabetes mellitus in patients after acute pancreatitis is similar to the reported values for the general population in this area. Alcoholic pancreatitis is more often complicated with impaired glucose tolerance and diabetes mellitus as regards to other causes of pancreatitis. Endocrine pancreatic function impairment is significantly more common after severe than after mild acute pancreatitis.