Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

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In this paper we present and analyse a technique for applying minimum variance distortionless response (MVDR) beamforming to a coherent plane-wave compounding (CPWC) acquisition system. In the past, this has been done using a spatial smoothing approach that reduces the effective size of the receive aperture and degrades the image resolution. In this paper, we apply the MVDR algorithms in a novel way to the acquired data from the individual transducer elements, before any summation or other compounding. This enables us to propose a new approach for estimation of the covariance matrix that decorrelates the coherence among the components at all the different acquisition angles. This results in a new approach to receive beamforming for CPWC acquisition. The new beamformer is demonstrated on imaging data acquired with a research scanner. We find the new beamformer offers substantial improvements over the DAS method. It also significantly outperforms the previously published MVDR/CPWC beamformer on phantom studies where the signal from the main target is dominated by noise and interference. These improvements motivate further study in this new approach for enhancing image quality.

Gastrointesinal: Colonic amyloidosis causing submucosal haematoma and bleeding from strainingAmyloidosis is a rare disorder of extracellular deposition of an abnormal fibrillar protein, disrupting tissue structure and function. Primary amyloidosis (monoclonal immunoglobulin light chains, AL) is the most common form, which can be idiopathic or associated with plasma cell dyscrasias. Involvement in the gastrointestinal (GI) tract is very common among patients with primary amyloidosis, with the small and large intestines being the most frequently affected organs. Amyloid deposition is dominant in the muscularis mucosa, submucosa and muscularis propria, leading to polypoid protrusions, thickened folds or mucosal ulceration. As a result, GI manifestations of AL amyloidosis range widely from diarrhoea, constipation, intestinal obstruction (mechanical or ileus) to GI bleeding, including submucosal haematoma. The risk of GI bleeding in primary amyloidosis is further potentiated by the presence of a thrombin inhibitor and a deficiency of factor X. These coagulopathies can be found in up to 20% of patients with AL amyloidosis. As treatment of these coagulopathies with conventional fresh frozen plasma, platelets, or even plasma exchange is ineffective, great caution must be taken in the decision of mucosal biopsy in patients with AL amyloidosis to avoid a potentially refractory, difficult to treat GI bleeding.A 50-year old lady with a history of primary amyloidosis developed peri-rectal bleeding in the context of known gastro-intestinal involvement, proven on colonic biopsies obtained 1-year prior (Figure 1a-b, arrow indicates Congo stain positive). On this occasion, the patient described a 4-day history of severe constipation and the passage of frequent, large volume motions of bright red blood mixed with stool after significant straining. On examination, the patient had a resting pulse rate of 105 and blood pressure of 70/50 mmHg. Laboratory investigations revealed a haemoglobin drop from 102g/L to 87g/L over 3-days. Following resuscitation with packed red blood cells and fresh frozen plasma, a flexible sigmoidoscopy was performed that revealed a tubular, eccentric, semi-circumferential bluish submucosal abnormality that extended for 15cm in the proximal descending colon (Figure 2a-b). Mucosal pit pattern of colonic mucosa was noted on the slough overlying the bluish abnormality (Figure 2b). Oozing fresh blood was also noted from the edge of this abnormality, which is thought to be a colonic sub-mucosal haematoma from amylodosis ( Figure 2b). Biopsies were deemed unsafe as it can precipitate further bleeding. The bleeding stopped spontaneously after 3 days, with complete resolution of the haematoma on repeat flexible sigmoidoscopy performed 2 weeks later. Contributed by

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