Background: Surgical resection remains the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). The prognostic value of resection margin status following pancreatoduodenectomy (PD) remains controversial. Standardised pathological assessment increases positive margins but limited data is available on the significance of involved margins. We investigated the impact of resection margin status in PDAC on patient outcome. Method: We identified all patients with PD for PDAC at one pancreatic cancer centre between August 2008 and December 2014. Demographic, operative, adjuvant therapeutic and survival data was obtained. Pathology data including resection margin status of specific anatomic margins was collected and analysed. Results: 107 patients were included, all pathologically staged as T3 with 102 N1. 87.9% of patients were R1 of which 53.3% showed direct extension to the resection margin. Median survival for RO patients versus R1<1 mm and R1 = 0 mm was 28.4 versus 15.4 and 25.1 versus 13.4 months. R1 = 0 mm status remained a predictor of poor outcome on multivariate analysis. Evaluation of individual margins (R1<1 mm) showed the SMV and SMA margins were associated with poorer overall survival. Multiple involved margins impacted negatively on outcome. SMA margin patient outcome with R1 = 1-1.9 mm was similar to R1=>2 mm. Conclusion: Using an R1 definition of <1 mm and standardised pathology we demonstrate that R1 rates in PDAC can approach 90%. R1 = 0 mm remained an independent prognostic factor for overall survival. Using R1<1 mm we have shown that involvement of medial margins and multiple margins has significant negative impact on overall survival. We conclude that not all margin positivity has the same prognostic significance. Crown Copyright (C) 2020 Published by Elsevier B.V. on behalf of IAP and EPC. All rights reserved.

Background: Various descriptive terms are utilised in the radiological reporting of pancreatic tumours and their association with surrounding vasculature which in turn defines tumour resectability. This study aimed to generate and validate a radiological reporting proforma for borderline and locally advanced tumours in an effort to provide standardization, improve the ability to reliably define tumour resectability, and generate consistency when comparing institutional Results. Material and Methods: A group of HPB surgeons and radiologists formed a think tank to identify the key factors that determine tumour resectability, with emphasis on vascular involvement whilst considering current guidelines (MD Anderson and AHPBA/SSAT/SSO/NCCN). The PROTRACT (Pancreatic Tumour Radiological Assessment and Classification) proforma was subsequently generated. A validation analysis assessed concordance between 2 blinded radiologists reporting CT-Pancreas images of borderline and locally advanced tumours. Results: The PROTRACT proforma includes information on all aspects of pancreatic tumours, with a particular emphasis on avoiding descriptive terms of vessel involvement, and rather quantifying this (i.e. length, axial circumferential degree and 'compass position' of involvement, degree of stricturing, presence of occlusion/invasion). The validation study revealed the SMV to be the most commonly involved vessel (72.2%) followed by the PV (50%), with a mean length and degree of involvement across all vessels of 20.5mm and 221degrees. When analyzing concordance between the two reporters, the median concordance rate of vessel involvement, stricturing, occlusion and invasion was 69%, 80%, 100% and 100% respectively. Conclusions: We believe the PROTRACT proforma is a useful tool to improve consistency in the radiological reporting of pancreatic tumours. We hope the current pilot work may be built upon through constructive feedback to optimize the reporting process, and thus improve our ability to compare clinical care and ensure patients are reliably classified into the appropriate tumour category with respect to potential future resection +/- vascular reconstruction.

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Background: For unresectable pancreatic cancer a repeat tissue diagnosis is usually required for chemotherapy, even if the 1st tissue is ‘suspicious for cancer’. We aimed to determine whether ‘suspicious’ tissue alone or in combination with a suspicious imaging and/or elevated CA19-9 might be sufficient to confirm the diagnosis of cancer. Methods: Information was gathered from a prospective database (2005-2013)for all pancreatic head lesions that underwent an EUS(Endoscopic Ultrasound) guided tissue diagnosis. Data was analysed using Microsoft Excel and IBM SPSS21. Results: 772(69.5%) of 1125 EUS-FNA patients had a suspicious solid pancreatic head lesion on initial imaging. 238(21%) patients required >1 attempt at tissue diagnosis. Suspicious cytology/histology alone had 97.2% specificity for diagnosing malignancy. Suspicious imaging + Ca19-9≥100 + suspicious cytology/histology, was 99.8% specific. Suspicious pancreatic mass with metastasis + Ca19-9 ≥800, without any histology/cytology was 99.8% specific. All of the above had sensitivities of 13.8 – 78.2%. Conclusion: A combination of a strongly suspicious imaging, a suspicious cytology or histology and CA19-9 ≥100 is highly specific(99.8%) for pancreatic adenocarcinoma or cholangiocarcinoma. Therefore such patients may not require any further tissue diagnosis. Similarly the combination of a suspicious pancreatic mass with metastatic disease on imaging and CA19-9 ≥800 is also highly specific(99.8%) and therefore such patients may not require any tissue diagnosis at all.

BSTRACT Background Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. Methods DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). Results DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21–2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22–3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91–3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38–0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80–1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3–30.4] vs 29.2 [19.5–41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1–15.7] vs. 18.0 [7.6–15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant ( p = 0.303), but the interaction of treatment arm and hENT1 expression was ( p = 0.009). Conclusion DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.

Background: Mortality following pancreatoduodenectomy is related to centre volume although the optimal volume is not defined. Methods: Patients undergoing PD between 2001 and 2016 were identified from UK national databases. The effects of patient variables, centre volume and time period upon 90 day mortality were studied. Results: 90 day mortality (970/14,935,6.5%) was related to advanced age, comorbidity, diagnosis, ethnicity, deprivation, centre volume and time period. Mortality rates fell markedly from 10.0% in 2001-4 to 4.1% in 2013-16. There was no difference in 90 day mortality between high (36-60 PD per year) and very high volume (>60) centres. However, patients operated upon at very high volume centres were more elderly (66, 58 -73 vs 65, 56 -72; median, IQR; p = 0.006), deprived (38.7 vs 34.6%; p < 0.001) and co morbid (48.9 vs 46.1%; p = 0.027). Conclusion: Although a plateau in the centre volume and mortality relationship appears to have been demonstrated those patients treated at the highest volume centres were at higher risk of mortality. This data suggests therefore that to further understand outcomes from specialist centres characteristics of the patient population should be defined, not just centre volume.

BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.

Introduction Self-expanding metal stents (SEMS) are superior to plastic stents (PS) for pre-operative drainage of the common bile duct (CBD) and are increasingly preferred. Endoscopic ultrasound (EUS) has a role in staging particularly of tumours that are borderline operable on CT. Biliary stents can cause acoustic shadowing and artefacts thereby reducing the view of the posterior aspect of the tumour and its relationship to local vessels. SEMS have a larger cross-sectional profile and may cause more shadowing than PS. There are to date no published studies of the impact of biliary stents on EUS staging. The aim of this study is to assess whether the presence of a biliary stent impairs the accuracy of linear EUS staging. Method The study group comprised all patients with head of pancreas (HOP) mass undergoing EUS biopsy between January 2013 and June 2016. Staging information was obtained from the EUS report. Staging was considered accurate when EUS had the same staging with respect to the major vessels (SMV, SMA and PV) as per outcome of surgery or multidisciplinary consensus following imaging review. Any statement indicating inability to fully image the tumour margins due to stent was classified as indicative of inaccurate staging. Accuracy of vascular staging between the stented and unstented group was analysed using Chi-square test. Results A total of 835 patients underwent EUS for a solid pancreatic mass of which 382 had a mass in the HOP. Median age was 67 [25-86] yrs and 326 (85%) were male. At time of EUS, 232 of 382 (61%) patients had no stent and 150 (39%) patients had stents in the CBD; 97 (65%) SEMS and 53 (35%) PS. Staging wasn’t required in 74 patients and reports were not available in 14; 260 had documented EUS staging. Overall staging accuracy was 247/297 (83%); accurate in 39/76 (51%) SEMS patients, 37/43 (86%) with PS and 171/178 (96%) unstented patients. Staging outcomes were significantly different between SEMS compared to the PS group (p=0.0003) and the unstented group, p=0.0001. Difference in staging between plastic stent and the unstented group was also significant, p=0.03. Conclusion Our results show a significant impact of SEMS and plastic stents on EUS staging. The effect is greatest with SEMS. We therefore recommend that patients in whom EUS staging is indicated, who also require biliary drainage, should have EUS performed before stent placement and if biliary drainage must be performed before EUS, plastic stents should be considered. Disclosure of Interest None Declared

Introduction Biliary complications after liver transplantation (LT) are common and some risk factors have been identified. Optimum endoscopic management including use of fully covered self-expanding metal stents (fcSEMS) in patients following LT requires evaluation. We aimed to identify risk factors for biliary complications following LT and present our experience of endoscopic management. Method Retrospective analysis of adult LT’s performed at our centre. Patient demographics, donor characteristics, transplantation data (including graft type; donation after brain death (DBD) or cardiac death (DCD)), biliary complications and subsequent management were recorded and the DRI calculated. The cohort consisted of all DBD LT’s performed between 2013 and 2016 and all DCD LT’s performed between 2007 and 2016. Univariate and multivariable analysis was used to identify risk factors for biliary complications and ascertain factors associated with stricture resolution and ascertain factors associated with biliary stricture resolution. Results A total of 153 (n=122 DBD and n=31 DCD) patients were included of which 43 (28%) patients developed biliary complications. There was no difference in the rate of biliary leaks but biliary strictures were associated with DCD (16/31, 51.6%) compared to DBD (27/122, 22.1%) OR 3.1 (1.6–8.6, p=0.0017), higher donor risk index (2.08 vs. 1.85, p=0.017) and warm ischaemia time >40 min (p=0.033). Late biliary strictures (>1 year) occurred more frequently in DCD compared to DBD livers (4/11 vs. 1/15 respectively). Hepatic artery thrombosis rate was the same in both groups (9.3% vs. 7.2%, p=0.74). Multivariable analysis showed that only DCD was independently associated with biliary strictures (adjusted OR 6.4, 2.4–17.0, p=0.0002). 11/43 with biliary complications underwent surgical or radiological management. The remainder underwent ERCP; 24 patients had 60 procedures for strictures, 6 patients had 17 procedures for biliary leak and 2 had 4 procedures for stone disease (all DCD). There were no differences in stricture resolution between DCD and DBD (7/11 vs. 11/13, p=ns) or the number of procedures required (32 in DBD vs. 28 in DCD). However, stricture resolution rates were higher following fcSEMS insertion compared to plastic stents (8/10 vs. 10/39 respectively, p=0.006). Conclusion Biliary complications are associated with DCD livers, higher DRI and longer warm ischaemia time. Endoscopic management of biliary complications leads to high resolution rates but patients undergo a high volume of such procedures. fcSEMS appear to have improved efficacy for stricture resolution compared to plastic stents. Disclosure of Interest None Declared

Acute blood loss in trauma requires quick identification and action to restore circulating volume and save the patient. Massive transfusion protocols (MTPs) have become standard at Trauma Centers, in order to rapidly deliver blood products to bleeding patients. This literature review presents current standards of transfusion ratios, as well as insights into adjuncts during massive transfusions.PubMED was searched for articles from 2005 to 2020 on MTPs, the article were assessed for single vs. multi-institutional, mechanism of injury, type of MTP, timing in which blood products should be administered, timing of delivery of blood products to trauma bay, pre-hospital treatment and adjuncts, and outcomes.Eleven studies addressed transfusion ratios. Seven studies looked at timing of blood products. Nine studies addressed MTP pre-hospital treatment and adjuncts. Prior to 2015, studies supported the benefits of a balanced transfusion ratio, which was then confirmed by the PROPPR randomized controlled trial. The shorter the time to blood product delivery the better the outcomes. New advances in technology have allowed us to measure different patterns of coagulation, allowing more individualized approaches to the bleeding patient.Current massive transfusion protocols should utilize between 1:1:1 and 1:1:2 ratios of the 3 main products; plasma, platelets, and red blood cells. Massive transfusion protocols are effective in decreasing mortality. Better resuscitation efforts were seen when blood products were readily available in the trauma bay when the patient arrived and the faster the replacement of blood, the better the outcomes.

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