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Background & AimsPancreatic ductal adenocarcinoma (PDAC) is often lethal because it is highly invasive and metastasizes rapidly. The actin-bundling protein fascin has been identified as a biomarker of invasive and advanced PDAC and regulates cell migration and invasion in vitro. We investigated fascin expression and its role in PDAC progression in mice.MethodsWe used KRasG12D p53R172H Pdx1-Cre (KPC) mice to investigate the effects of fascin deficiency on development of pancreatic intraepithelial neoplasia (PanIn), PDAC, and metastasis. We measured levels of fascin in PDAC cell lines and 122 human resected PDAC samples, along with normal ductal and acinar tissues; we associated levels with patient outcomes.ResultsPancreatic ducts and acini from control mice and early-stage PanINs from KPC mice were negative for fascin, but approximately 6% of PanIN3 and 100% of PDAC expressed fascin. Fascin-deficient KRasG12D p53R172H Pdx1-Cre mice had longer survival times, delayed onset of PDAC, and a lower PDAC tumor burdens than KPC mice; loss of fascin did not affect invasion of PDAC into bowel or peritoneum in mice. Levels of slug and fascin correlated in PDAC cells; slug was found to regulate transcription of Fascin along with the epithelial−mesenchymal transition. In PDAC cell lines and cells from mice, fascin concentrated in filopodia and was required for their assembly and turnover. Fascin promoted intercalation of filopodia into mesothelial cell layers and cell invasion. Nearly all human PDAC samples expressed fascin, and higher fascin histoscores correlated with poor outcomes, vascular invasion, and time to recurrence.ConclusionsThe actin-bundling protein fascin is regulated by slug and involved in late-stage PanIN and PDAC formation in mice. Fascin appears to promote formation of filopodia and invasive activities of PDAC cells. Its levels in human PDAC correlate with outcomes and time to recurrence, indicating it might be a marker or therapeutic target for pancreatic cancer.

Evidence before this study: Acute appendicitis is the most common general surgical emergency in children. Its diagnosis remains challenging and children presenting with acute right iliac fossa (RIF) pain may be admitted for clinical observation or undergo normal appendicectomy (removal of a histologically normal appendix). A search for external validation studies of risk prediction models for acute appendicitis in children was performed on MEDLINE and Web of Science on 12 January 2017 using the search terms ["appendicitis" OR "appendectomy" OR "appendicectomy"] AND ["score" OR "model" OR "nomogram" OR "scoring"]. Studies validating prediction models aimed at differentiating acute appendicitis from all other causes of RIF pain were included. No date restrictions were applied. Validation studies were most commonly performed for the Alvarado, Appendicitis Inflammatory Response Score (AIRS), and Paediatric Appendicitis Score (PAS) models. Most validation studies were based on retrospective, single centre, or small cohorts, and findings regarding model performance were inconsistent. There was no high quality evidence to guide selection of the optimum model and threshold cutoff for identification of low-risk children in the UK and Ireland. Added value of this study: Most children admitted to hospital with RIF pain do not undergo surgery. When children do undergo appendicectomy, removal of a normal appendix (normal appendicectomy) is common, occurring in around 1 in 6 children. The Shera score is able to identify a large low-risk group of children who present with acute RIF pain but do not have acute appendicitis (specificity 44%). This low-risk group has an overall 1 in 30 risk of acute appendicitis and a 1 in 270 risk of perforated appendicitis. The Shera score is unable to achieve a sufficiently high positive predictive value to select a high-risk group who should proceed directly to surgery. Current diagnostic performance of ultrasound is also too poor to select children for surgery. Implications of all the available evidence: Routine pre-operative risk scoring could inform shared decision making by doctors, children, and parents by supporting safe selection of lowrisk patients for ambulatory management, reducing unnecessary admissions and normal appendicectomy. Hospitals should ensure seven-day-a-week availability of ultrasound for medium and high-risk patients. Ultrasound should be performed by operators trained to assess for acute appendicitis in children. For children in whom diagnostic uncertainty remains following ultrasound, magnetic resonance imaging (MRI) or low-dose computed tomography (CT) are second-line investigations.

Backgrounds and AimsLong term central venous access for Home Parenteral Nutrition (HPN) is associated with catheter related complications. The most studied and well known of these is Catheter Related Blood Stream Infection (CRBSI).This paper looks at other venous access complications, including blocked and damaged catheters, catheter related thrombosis and CRBSI. This paper will also present treatment outcomes for each of these complications. This paper will also examine if there are any correlating patient or catheter related factors that can help predict future catheter related complications. By demonstrating the treatment outcomes for each line complication, it is hoped this will contribute to the literature that could be used for standard setting in complications related to long term central venous access. MethodsHPN data was analysed from the Greater Glasgow and Clyde (GGC) Home Parenteral Nutrition Database (HPN) which is a comprehensive, prospectively maintained electronic record of all HPN patients treated in GGC. The time period of data collection was 1998-2017. Descriptive statistics were used to report data frequency, age, and catheter days' distributions. Data were not normally distributed and so non-parametric tests were used.Spearman's Rho correlation was used to measure correlation between two numeric groups. Catheter complications were reported as a rate in count data, meaning that more than one event could be recorded per patient, with 1,000 catheter days as the person-time denominator. Poisson means test and Fisher exact tests were used to compare different rates, as complications were treated as count data increasing over variable total time periods. P < 0.05 with 95% confidence interval (CI) was considered significant in all tests. Comparisons between binary data sets used 2 sample t-test to compare the groups. ResultsFrom 169 patients, 101 (59.8%) were female and 68 (40.2%) were male. The age when first starting HPN ranged from 16 to 79 years old with a median of 56 years. Total catheter days was 173,151 derived from 408 catheter insertions on 169 patients. 282 complications occurred in 85 patients over the study period. An overall catheter complication rate of 1.62/1000 days was found. 84 patients did not experience a single complication. There were 171 proven catheter infections in 66 patients over the study period. Infection rate from the entire period of report was 1.35 infections/1000 catheter days. This decreased over time. Infection was found to be correlated with length of time on HPN, catheter location, catheter diameter and use of Taurolock-Hep100. Thrombosis (n=16) was associated with total time on HPN(r 2 = 0.187, P <0.05) and the number of infections (r 2 = 0.207 P <0.05). Damage was strongly associated with increasing time on HPN with (r 2 of 0.494 and P <0.005). Blockage was not associated with any patient or catheter factors. Overall catheter salvage rate for CRBSI by antibiotic treatment was 61.87%.Success varied according to organism cultured. Catheter salvage was less succe...

SummaryThe actin bundling protein fascin 1 is not expressed in adult epithelial tissues, but during development it is transiently expressed in many different cell types, and later in adults it is expressed in a subset of immune cells, nervous tissues, endothelial cells, smooth muscle cells and pericytes. In contrast to the wealth of knowledge about the role of fascin 1 in cancer cell migration and invasion, little is known about the involvement of fascin 1 in angiogenesis. We speculated that as angiogenesis involves migration and invasion of tissues by endothelial cells, fascin 1 might have a role in both normal and tumour angiogenesis. Here, we provide evidence that loss of fascin 1 causes relatively minor reductions to angiogenesis during embryonic, postnatal and cancerous development by examining E12.5 hindbrains, postnatal retinas and B16F0 tumour cell allografts in fascin 1-null mice. We also find that in fascin 1 null tissues, endothelial cells display reduced filopodia formation during sprouting. We thus propose that fascin 1 expression promotes angiogenesis via filopodia formation, but is largely dispensable for both normal and tumour angiogenesis.

The aim of this study was to directly compare the prognostic value of cumulative scores and composite ratios in patients with operable rectal cancer. Within a single surgical unit preoperative differential blood cell results including neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, as well as CRP (C) and albumin (A) levels were recorded. These results were used to construct a series of composite ratios (NLR, PLR, LMR, CAR) and cumulative scores (NLS, PLS, LMS, NPS, mGPS). The relationship between composite ratios and the cumulative scores and clinicopathological characteristics, cancer specific survival (CSS) and overall survival (OS) were examined. A total of 413 patients were included. When adjusted for TNM stage, surgical approach, time of surgery and margin involvement mGPS (p < 0.05) was associated with CSS. In addition, most composite ratios/scores showed correlations with neoadjuvant therapy (p < 0.001). When a direct comparison between NPS (myeloid) and mGPS (liver) was carried out they showed similar associations with both CSS and OS. Therefore, both composite ratios and cumulative scores have been shown to be prognostic in patients with operable rectal cancer.

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