Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.

The pan-cancer analysis of whole genomes The expansion of whole-genome sequencing studies from individual ICGC and TCGA working groups presented the opportunity to undertake a meta-analysis of genomic features across tumour types. To achieve this, the PCAWG Consortium was established. A Technical Working Group implemented the informatics analyses by aggregating the raw sequencing data from different working groups that studied individual tumour types, aligning the sequences to the human genome and delivering a set of high-quality somatic mutation calls for downstream analysis (Extended Data Fig. 1). Given the recent meta-analysis

The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.

No abstract

Background and Aims: Autoimmune pancreatitis seems to be a disease with a heterogeneous appearance. Our intention was to establish key diagnostic criteria, define grades of severity and activity, identify features of potential subtypes and evaluate the diagnostic relevance of biopsy specimens. Methods: Histopathological criteria and clinical features were recorded in pancreatic resection specimens from 53 patients who were found to have chronic pancreatitis lacking pseudocysts, calculi, irregular duct dilatations, pancreas divisum and/or duodenal wall inflammation. The severity of the chronic inflammation was graded, and the activity of the acute inflammatory component and the granulocytic epithelial lesion (GEL) were determined. Additionally, pancreatic biopsy specimens from 9 patients with suspected AIP were assessed. Results: Periductal lymphoplasmacytic infiltration was identified in all cases, followed in order of frequency by periductal fibrosis and venulitis. These changes were absent in 147 pancreatic specimens that showed chronic pancreatitis associated with pseudocysts, calculi, pancreas divisum and/or duodenal wall inflammation. In 90% of the cases, these chronic changes were graded as 3 or 4. In 81%, the inflammatory process resided in the head of the pancreas and involved the common bile duct. GELs were present in 42% of the patients, who had a mean age of 40.5 years, an almost equal male-female ratio and a high coincidence of ulcerative colitis or Crohn's disease. Patients without GELs were older (mean age 64 years), showed a male preponderance, commonly had Sjögren's syndrome and often developed recurrent bile-duct stenosis. Diagnostically relevant lesions were present in two of five wedge biopsy specimens and three of four fine-needle specimens. Conclusions: Periductal lymphoplasmacytic infiltration and fibrosis, preferential occurrence in the pancreatic head and venulitis characterize autoimmune pancreatitis. GELs predominantly occur in a subset of patients who are younger, more commonly have ulcerative colitis and Crohn's disease and seem to have fewer recurrences than patients without GELs. Pancreatic biopsy material proved to be a very helpful adjunct for establishing the diagnosis.