Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome‐wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I‐II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 × 10−4). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta‐analysis supported the association (P = 1.15 × 10−4). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.

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IntroductIon Biliary and pancreatic diseases, especially choledocholithiasis and neoplastic diseases, are commonly seen in elderly patients. Endoscopic retrograde cholangiopancreatography (ERCP) is a diagnostic and therapeutic procedure performed more and more frequently also in elderly patients. objEctIvEs The aim of this study was to evaluate the utility and safety of ERCP in patients >80 years of age. PAtIEnts And mEthods We retrospectively analyzed 821 ERCP performed in the Department of Gastrointestinal Diseases, Medical University of Łódź in the years 2005-2007. We compared age, sex, clinical symptoms, laboratory findings, ERCP efficacy and safety in patients >80 years of age versus younger subjects.

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Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P=7.14×10 -10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumor cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P=3.56×10 -6). This SNP is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.

Unweighted score for the subject: sum of the scores of each SNPs. e Average unweighted score for the subject: average of the scores of each SNPs.f Weighted score for the subject: sum of the scores of each SNPs. g Average weighted score for the subject: average of the scores of each SNPs. h Allele associated with longer telomeres. i Beta coefficients for association of each SNP with telomere length, providing an estimate of the relative importance of each SNP. j Estimates of the per-allele effect on LTL in base pairs, following ref. 52.

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 Autoimmune pancreatitis (AIP) is an uncommon inflammatory disorder that may accompany inflammatory bowel disease (IBD). The clinical relevance of AIP-IBD coexistence, therapeutic strategies, and long-term outcomes are scarcely known. Methods In this ECCO COllaborative Network For Exceptionally Rare case reports project (ECCO-CONFER) we included cases of AIP diagnosed in patients with IBD. Data on the diagnostic criteria, clinical characteristics, and patient outcomes were retrospectively collected and analysed. Results The cohort included 82 patients [54% males, 77% with ulcerative colitis (UC), age at IBD and AIP diagnosis 32±16 and 35±16 years, respectively]. Of all AIP patients, 71% were classified as type 2, 21% as type 1, and 8% as undefined type. Detailed characteristics of the study group are shown in Table 1. In 57% of the individuals, IBD was diagnosed before AIP. In the remaining cases, IBD was diagnosed simultaneously (20%) or afterwards (23%). Half of the patients required immunomodulators and 43% biological therapy to control their IBD. Twenty-two percent of UC and 6% of Crohn’s disease (CD) required surgical intervention during a mean follow-up of 3.6±3.4 years. Histological confirmation was used in 38% of cases, while the remaining were diagnosed as probable AIP based on clinical, biochemical, and radiologic criteria. Magnetic resonance was the most frequently used imaging modality (61%). Eighty percent of patients received steroids for AIP. Thiopurines were used for AIP in 16 (19%) patients, 81% of them responded to treatment. One patient was successfully treated for AIP with infliximab. AIP complications occurred in 27%, including pancreatic exocrine insufficiency (19%) and diabetes (13%). Five patients underwent surgery due to suspected pancreatic cancer. Patients with complicated AIP were significantly older at AIP and IBD diagnosis, were more frequently males and presented with weight loss at AIP diagnosis, and had less frequently a family history of IBD (Table 1). Colonic IBD (i.e. UC, isolated colonic IBD-unclassified or colonic CD) was seen in a higher proportion of individuals with complicated vs benign AIP course (91% vs 33%, p&lt;0.0001). At the end of follow-up, 75 (91%) and 73 (89%) patients were in remission of AIP and IBD, respectively. No IBD or AIP-related deaths were reported. Conclusion In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign, and long-term outcomes are favourable. Older age, male gender, isolated colonic IBD location, and weight loss at AIP presentation were seen in higher proportions of patients with a complicated course of AIP.