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Purpose A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. Methods An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. Results A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score >= 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. Conclusion Patients with a Shin score

Naturally occurring anthocyanins possess colorectal cancer chemopreventive properties in rodent models. We investigated whether mirtocyan, an anthocyanin-rich standardized bilberry extract, causes pharmacodynamic changes consistent with chemopreventive efficacy and generates measurable levels of anthocyanins in blood, urine, and target tissue. Twenty-five colorectal cancer patients scheduled to undergo resection of primary tumor or liver metastases received mirtocyan 1.4, 2.8, or 5.6 grams (containing 0.5-2.0 grams anthocyanins) daily for 7 days before surgery. Bilberry anthocyanins were analyzed by high performance liquid chromatography (HPLC) with visible or mass spectrometric detection. Proliferation was determined by immunohistochemistry of Ki-67 in colorectal tumor. Concentrations of insulin-like growth factor (IGF)-I were measured in plasma. Mirtocyan anthocyanins and methyl and glucuronide metabolites were identified in plasma, colorectal tissue, and urine, but not in liver. Anthocyanin concentrations in plasma and urine were roughly dose-dependent, reaching ∼179 ng/gram in tumor tissue at the highest dose. In tumor tissue from all patients on mirtocyan, proliferation was decreased by 7% compared with preintervention values. The low dose caused a small but nonsignificant reduction in circulating IGF-I concentrations. In conclusion, repeated administration of bilberry anthocyanins exerts pharmacodynamic effects and generates concentrations of anthocyanins in humans resembling those seen in ApcMin mice, a model of FAP adenomas sensitive to the chemopreventive properties of anthocyanins. Studies of doses containing

Perspective on this Article from Pilot Study of Oral Anthocyanins for Colorectal Cancer Chemoprevention

The Gallbladder Reporting and Data System (GB-RADS) ultrasound (US) risk stratification is proposed to improve consistency in US interpretations, reporting, and assessment of risk of malignancy in gallbladder wall thickening in non-acute setting. It was developed based on a systematic review of the literature and the consensus of an international multidisciplinary committee comprising expert radiologists, gastroenterologists, gastrointestinal surgeons, surgical oncologists, medical oncologists, and pathologists using modified Delphi method. For risk stratification, the GB-RADS system recommends six categories (GB-RADS 0–5) of gallbladder wall thickening with gradually increasing risk of malignancy. GB-RADS is based on gallbladder wall features on US including symmetry and extent (focal vs. circumferential) of involvement, layered appearance, intramural features (including intramural cysts and echogenic foci), and interface with the liver. GB-RADS represents the first collaborative effort at risk stratifying the gallbladder wall thickening. This concept is in line with the other US-based risk stratification systems which have been shown to increase the accuracy of detection of malignant lesions and improve management. Graphical abstract: [Figure not available: see fulltext.].

Background There is increasing evidence that peri-operative glucocorticosteroid can ameliorate the systemic response following major surgery. Preliminary evidence suggests peri-operative usage of glucocorticosteroid may decrease post-operative complications. These positive associations have been observed in a range of different operations including intra-abdominal, thoracic, cardiac, and orthopaedic surgery. This review aims to investigate the impact of peri-operative glucocorticosteroid in major pancreatic resections. Methods A systematic review based on a search in Medline and Embase databases was performed. PRISMA guidelines for systematic reviews were followed. Results A total of five studies were analysed; three randomised controlled trials and two retrospective cohort studies. The total patient population was 1042. The glucocorticosteroids used were intravenous hydrocortisone or dexamethasone. Three studies reported significantly lower morbidity in the peri-operative glucocorticosteroid group. The number needed to treat to prevent one major complication with hydrocortisone is four patients. Two studies demonstrated that dexamethasone was associated with a statistically significantly improved median overall survival in pancreatic cancer. Conclusion This is the first systematic review conducted to investigate the significance of peri-operative glucocorticosteroid in patients undergoing pancreatic resection. This review shows a correlation of positive outcomes with the administration of glucocorticosteroid in the peri-operative setting following a major pancreatic resection.. More randomised clinical trials are required to confirm if this is a true effect, as it would have significant implications.

Background There is a well-documented scarcity of the availability of healthy human livers for transplantation. The majority of discarded donor livers are used for organ preservation studies in the context of liver transplantation. Hemi-hepatectomies are a common procedure performed in tertiary hepatobiliary units. The specimen, also consisting of healthy liver, is eventually discarded despite the presence of healthy human liver tissue which would be invaluable for research. In 1959, Russel and Burch described the “3Rs” of animal research as replacement, reduction, and refinement (Flecknell, 2002). Optimising the use of hemi-hepatectomy human liver tissue for research would reduce the need for live animals and provide a more economical and physiological model to study invasive hepatic disease. Ex vivo perfusion of human hepatic segments has enormous potential and we are currently investigating this tool to be used as a translational model for invasive disease, including macrophage response to the earliest phases of infection, as demonstrated in porcine organs by Wanford et al (2021). Methods This retrospective service evaluation project was registered locally with audit registration numbers 11852 and 11852a. All liver resections booked electronically over a six month period, between 1/10/20 and 31/3/21, were assessed. Patient records, including intra-operative notes, were reviewed to identify which patients had a partial hepatectomy (left hemi-hepatectomy, right hemi-hepatectomy, or left lateral segmentectomy). The data was then compared against histology reports to identify which segments from the specimen were pathological and which segments were disease-free. A prospective Research Ethics Committee-approved clinical trial was registered by the name of “Tissue Models for Liver Disease” or TIMOLD (ClinicalTrials.gov Identifier: NCT05255042; 8/9/2021). Patients recruited were those aged eighteen or over undergoing elective liver resections. Exclusion criteria included those with acute invasive infection, children and vulnerable groups. A re-audit was performed following implementation of the TIMOLD study for the same time period the following year, between 1/10/21 and 31/3/22. Data analysis was performed using GraphPad Prism. Results Between 1/10/20 and 31/3/21, 43 liver resections were listed. Intra-operatively, 3/43 patients had inoperable disease and 2/43 did not require a resection. Of the 38 liver resections performed, 30 (79%) were for colorectal liver metastases (CRLM), 4/38 (11%) were for hepatocellular carcinoma (HCC), and the remainder for cholangiocarcinoma, neuroendocrine tumours and adenomas. 19/38 (50%) liver resections were a hemi-hepatectomy or left lateral segmentectomy. Histology review found that 11/19 (58%) specimens contained at least one healthy liver segment which was eventually discarded. Between 1/10/21 and 31/3/22, following implementation of the TIMOLD study, 57 liver resections were listed. 6/57 patients were found to have inoperative disease and 1/57 did not require a resection. Of 50 liver resections, 32/50 (64%) were for CRLM, 9/50 (18%) were for HCC and the remainder for cholangiocarcinoma, neuroendocrine tumours, IPMN and benign disease. 27/50 (54%) had a hemi-hepatectomy or left lateral segmentectomy. 17/27 (63%) partial hepatectomies were found to contain at least one healthy liver segment with potential for research use. As part of the TIMOLD trial, 8/17 healthy liver segments were retrieved and used for research during a six-month period, in comparison to none the previous year (p Conclusions We demonstrate that at least 50% of patients undergoing liver resection at a tertiary HPB unit require a hemi-hepatectomy or left lateral segmentectomy over 12 months. Furthermore, at least half of these partial resections involve healthy anatomical liver segments as part of the specimen. Over six months, eight disease-free human liver segments, which would otherwise have been discarded, were perfused ex vivo in an attempt to develop a model representing human hepatic physiology at the organ level. Expanding this research model to other hepatobiliary units provides scientists an invaluable model for pre-clinical research, negating the need for live animal experimentation.

Background This survey took a ‘'snapshot’’ of prevailing attitudes towards minimally invasive HPB surgery from a consultant and trainee perspective. Methods Between November 2020 and January 2021, two google surveys were emailed to all HPB tertiary centres in the UK. The questionnaire contained 33 and 31 questions respectively regarding minimally invasive practice and training. Results Thirty-five HPB consultants completed the survey. The most common indications for conversion were failure to progress (91.4%), excessive blood loss (85.7%), access issues (85.7%). The majority (78.8%) of HPB surgeons undertook minimally invasive distal pancreatectomy (MIDP). One consultant undertook minimally invasive pancreaticoduodenectomy (MIPD), 48.4% declared not performing MIPDs due to uncertainty of its superiority. Eighty-five-point seven percent performed minimally invasive minor liver resection and segementectomy (MImLRS), 70.6% reported better outcomes with this approach; 28.6% of consultants performed minimally invasive major liver resection (MIMLR), 23.3% reported better outcomes with MIMLR. Half of HPB trainees did not have access to complex laparoscopic HPB procedures; 72.2% desired fellowship training. Conclusions MImLRS and MIDP are accepted approaches by most HPB consultants correlating with a perception that outcomes are better/comparable to open approaches, in contrast to MIPD and MIMLR. HPB trainees lack laparoscopic HPB exposure leading them to seek further experience with fellowships.

Background Ex vivo perfusion techniques for human organs, in particular for the human liver, have been extensively studied for decades. Although ex vivo perfusion of human organs has been widely studied in the context of organ preservation and transplantation, it has also proven to be an invaluable tool in the development of novel models for translational pre-clinical research. Not only do these models allow more accurate study of human organ response to noxious external stimuli, but they also represent a far more ethical alternative to live animal experimentation.Although split-liver perfusion of the left or right hepatic lobe is well described in literature, ex vivo perfusion of isolated liver segments has not been previously attempted. A successful hepatic segmental perfusion model would provide a unique opportunity to study inflammation, response to infection and novel therapeutic approaches.The overall aim of this study was to establish an experimental ex vivo hepatic perfusion model on surgically resected human liver segments as a platform to evaluate and study organ preservation and function. The development of an ex vivo perfusion model of human liver segments would produce the ideal platform to study treatment effects without needing to sacrifice animals. Methods Patients were recruited as part of the TIMOLD (Tissue Models for Liver Disease) clinical trial (ClinicalTrials.gov Identifier: NCT05255042; 8/9/2021). Patients recruited were those aged eighteen or over undergoing elective liver resections at a single hepatobiliary unit. Nine human liver segments were retrieved following hemi-hepatectomy for colorectal liver metastases or hepatocellular carcinoma. A healthy segment was resected from the diseased specimen in theatre and a segmental hepatic artery and portal vein was cannulated immediately and flushed with ice cold heparinised preservation solution. Four segments were perfused with 600ml O negative expired red blood cells (HL-RBC) and five segments were perfused with 250ml Oxyglobin diluted with 250ml Volplex (HL-OXY). All segments were administered several drugs to provide metabolic support and optimise perfusion owing to their anticoagulant, antioxidant, and anti-inflammatory properties. Segments were perfused on a bespoke normothermic machine perfusion circuit for 4–6 hours. Perfusion parameters were monitored throughout perfusion and hourly hepatic venous blood gases were taken to monitor glucose and lactate levels. Hourly core biopsies were also taken for H&E staining and interpreted by a consultant histopathologist. Data is reported as the median (range) and statistical analysis has been performed using the Mann-Whitney U test on Graphpad Prism. Results HL-RBC (n=4) had a median pre-perfusion weight of 216 (146–1330) grams whilst HL-OXY (n=5) had a median weight of 269(128–367) grams (p>0.05). HL-RBC segments had a median warm ischaemic (WI) time of 76.5(68–81) minutes and a median cold ischaemic (CI) time of 97 (35–119) minutes. HL-OXY segments had a median WI time of 5 (3–80) minutes and a median CI time of 38 (28–63) minutes (p>0.05). Median portal venous resistance was lower for the HL-OXY group (0.076mmHg/ml/min) in comparison to the HL-RBC group (0.62mmHg/ml/min); p0.05). HL-OXY had a lower median lactate of 4.54mmol/L in comparison to HL-RBC (14.7mmol/L) throughout perfusion (p Conclusions We present here, for the first time, the development of a successful ex vivo isolated hepatic segmental perfusion model. We demonstrate, in the development of this model, that bovine haemoglobin glutamer-200 (Oxyglobin) is a superior oxygen carrier to expired O negative red blood cells in the ex vivo perfusion of isolated human hepatic segments. The HL-OXY group demonstrated a significantly lower portal venous resistance in comparison to HL-RBC, although there was no difference in arterial resistance. Furthermore, HL-OXY segments had lower median glucose and lactate levels during perfusion compared to HL-RBC segments. 4 of 5 segments perfused with Oxyglobin demonstrated viable hepatocytes on histopathological analysis after 6 hours of perfusion. The segment demonstrating early necrosis was one with established cirrhosis on pre-perfusion histology. We describe a protocol for the successful ex vivo perfusion of non-cirrhotic human hepatic segments. Human liver is routinely resected in tertiary hepatobiliary units and much of the specimen discarded. The paradigm presented here identifies a readily available ethical source of human liver with minimal warm ischaemia. This facilitates optimal conditions for translational research, is cost-effective and avoids animal experimentation.

Meta-analysis aimed to quantify the relationship between intraductal papillary mucinous neoplasm (IPMN) and increased incidence of extra-pancreatic malignancy (EPM) previously reported in qualitative observational cohort studies. Study protocol was registered with PROSPERO (CRD42020169614) and conducted to the Meta-analysis Of Observational Studies in Epidemiology and systematic review reported with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Assessing the Methodological Quality of Systematic Reviews guidelines. Sixteen studies (total of 8240 patients) were included in the pooled, and 7399 patients in the subgroup meta-analyses. The odds ratio (OR) for any EPM in the presence of IPMN was 57.9 (95% confidence interval 40.5–82.7), fixed effects, I2 = 59% (p

Background The clinical significance of indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma (PDAC) is unknown. The rate of detection on IPN has risen due to enhanced staging investigations to determine resectability. IPNs detected on preoperative imaging represent a clinical dilemma and complicate decision-making. Currently, there are no recommendations on the management of IPN. This review provides a comprehensive overview of the current knowledge on the natural history of IPN detected among patients with resectable PDAC. Methods A systematic review based on a search in Medline and Embase databases was performed. All clinical studies evaluating the significance of IPN in patients with resectable PDAC were included. PRISMA guidelines were followed. Results Five studies met the inclusion criteria. The total patient population was 761. The prevalence of IPN reported ranged from 18 to 71%. The median follow-up duration was 17 months. The median overall survival was 19 months. Patients with pre-operative IPN which subsequently progressed to clinically recognizable pulmonary metastases, ranged from 1.5 to 16%. Four studies found that there was no significant difference in median overall survival in patients with or without IPNs. Conclusion This is a first review on the significance of IPN in patients with resectable PDAC. The preoperative presence of IPN does not demonstrate an association with overall survival after surgery. The identification of IPN is a significant finding however it should not preclude patients with resectable PDAC from undergoing curative resection.

Background With the rising prevalence of obesity, there is a plethora of literature discussing the relationship between obesity and acute pancreatitis (AP). Evidence has shown a possible correlation between visceral adipose tissue (VAT) and AP incidence and severity. This systematic review explores these associations. Methods Eligible articles were searched and retrieved using Medline and Embase databases. Clinical studies evaluating the impact of VAT as a risk factor for AP and the association of the severity of AP and VAT were included. Results Eleven studies, with a total of 2529 individuals were reviewed. Nine studies showed a statistically significant association between VAT and the severity of AP. Only four studies found VAT to be a risk factor for acute pancreatitis. Two studies showed VAT to be associated with an increased risk of local complications and two studies showed a correlation between VAT and mortality. Conclusion This is the first systematic review conducted to study the association between VAT and AP. The existing body of evidence demonstrates that VAT has a clinically relevant impact and is an important prognostic indicator of the severity of AP. However, it has not shown to be an independent risk factor to the risk of developing AP. The impact of VAT on the course and outcome of AP needs to be profoundly explored to confirm these findings which may fuel earlier management and better define the prognosis of patients with AP. VAT may need to be incorporated into prognostic scores of AP to improve accuracy.

Background: The International Study Group for Pancreatic Surgery provides globally accepted definitions for reporting of complications after pancreatic surgery. This International Study Group for Pancreatic Surgery project aims to provide a standardized framework for reporting of the results of operative treatment for chronic pancreatitis. Methods: An International Study Group for Pancreatic Surgery project circulation list was created with pre-existing and new members and including gastroenterologists in addition to surgeons. A computerized search of the literature was undertaken for articles reporting the operative treatment of chronic pancreatitis. The results of the literature search were presented at the first face-to-face meeting of this International Study Group for Pancreatic Surgery project group. A document outlining proposed reporting standards was produced by discussion during an initial meeting of the International Study Group for Pancreatic Surgery. An electronic questionnaire was then sent to all current members of the International Study Group for Pancreatic Surgery. Responses were collated and further discussed at international meetings in North America, Europe, and at the International Association of Pancreatology World Congress in 2019. A final consensus document was produced by integration of multiple iterations. Results: The International Study Group for Pancreatic Surgery consensus standards for reporting of surgery in chronic pancreatitis recommends 4 core domains and the necessary variables needed for reporting of results: clinical baseline before operation; the morphology of the diseased gland; a new, standardized, operative terminology; and a minimum outcome dataset. The 4 domains combine to give a comprehensive framework for reports. Conclusion: Adoption of the 4 domains of the International Study Group for Pancreatic Surgery reporting standards for surgery for chronic pancreatitis will facilitate comparison of results between centers and help to improve the care for patients with this debilitating disease.

Percutaneous cholecystostomy (PC) is often performed for patients with acute cholecystitis who are too high risk for cholecystectomy. The purpose of this retrospective study was to evaluate the outcomes of this cohort of patients over a 5-year period. A retrospective analysis of all patients treated with PC for acute cholecystitis in a tertiary centre teaching hospital was conducted. The study period ranged from January 2010 to December 2015. Clinical data were extracted from the hospitals′ electronic database system, as well as reviewing clinical notes and imaging reports. The aims of this study were to detect the reason PC was undertaken as opposed to surgery, the subsequent definitive management of patients initially treated with PC, the incidence of common bile duct stones (CBDS), the complications from PC, and the 30-day mortality. A total of 96 patients were identified. The total number of patients with CBDS was 27 (28.1%). Fourteen (14.6%) patients were shown to have CBDS on initial imaging. CBDS was detected in 12 patients (12.5%) at cholangiogram during their PC procedure. One patient had CBDS detected during a check cholangiogram at 6 weeks, which was not seen on initial imaging. Twenty-eight patients (29.2%) underwent an endoscopic retrograde cholangiopancreatography (ERCP), during their index admission. The main reasons for PC were a high American Society of Anaesthesiologists (ASA) score (49%), sepsis requiring organ support (19.8%), empyema of the gallbladder (29.1%), failed external biliary drainage for biliary obstruction (2.1%), and concomitant palliative malignancy (5.2%). Interval cholecystectomy was performed in 24 patients (25%). The total 30-day in-hospital mortality was 16.7%. PC is an effective and safe alternative as salvage therapy in high-risk elderly patients who have multiple comorbidities. It is valuable as a temporising measure before definitive treatment in high-risk patients. A high index of suspicion for CBDS (and further imaging with MRCP or a check cholangiogram) is warranted to detect missed CBDS. This is particularly relevant in this vulnerable group of patients where CBDS may represent a future source of recurrent sepsis.

Background The human immune response to bacterial and viral pathogens has been the focus of intense research, but details on the earliest phases of infection remain unclear. Better knowledge regarding the response of immune cells in the liver is important for the treatment of severe bacterial disease. Ex vivo perfusion which mimics physiological conditions of the liver may provide useful models for this research. An ex vivo model which perfuses hepatic segments would allow translational research on a physiological and reliable model in the scarce resource of human organs. Here we describe the extra-corporeal perfusion of a porcine hepatic segment. Methods Whole porcine livers were retrieved from animals slaughtered according to UK laws for food production and connected to a normothermic extracorporeal perfusion circuit. Constant perfusion via the hepatic artery and portal vein with heparinized autologous blood was established. Sodium bicarbonate, epoprostanol sodium and calcium chloride were also added to the perfusate to regulate acid-base status and reduce vasospasm. Functionality was assessed by monitoring blood-gases, perfusion pressures and flow rate. A segmental ex-vivo liver resection was performed to leave hepatic segment IV in circuit and isolated segment IV perfusion was maintained for one hour. Results Portal venous pressure was maintained between 8-16mmHg and hepatic arterial pressure between 80-90mmHg. Metabolic acidosis resolved with addition of sodium bicarbonate to the circuit with a pH of 7.42 after segmental perfusion for 1 hour. The lactate increased over the course of the perfusion to 20mmol/L after 1 hour of perfusion, however glucose levels were found to improve with the addition of sodium bicarbonate to the circuit. Conclusions Isolated segmental perfusion via ex-vivo resection of porcine hepatic segments is technically challenging. Ischaemic-reperfusion injury coupled with progressive metabolic acidosis may limit model viability. However, addition of sodium bicarbonate to the perfusate aids reduction of glucose levels and improves acidosis. Successful perfusion of a porcine hepatic segment provides the potential for segmental perfusion of human hepatic segments such as those resected during hemi-hepatectomies (HRA approved; REC 21/PR/0287). This is an important milestone leading to the creation of a model to study the early changes in human liver tissue for example during infection.

Background Isolated splenic vein thrombosis (iSVT) is a common complication of pancreatic disease. Whilst patients remain asymptomatic, there is a risk of sinistral portal hypertension and subsequent bleeding from gastric varices if recanalization does not occur. There is a wide variation of iSVT treatment, even within single centres. We report outcomes of iSVT from tertiary referral hepatobiliary and pancreatic (HPB) units including the impact of anticoagulation on recanalization rates and subsequent variceal bleeding risk. Methods A retrospective cohort study including all patients diagnosed with iSVT on CT scan abdomen and pelvis between 2011 and 2019 from two institutions. Patients with both SVT and portal vein thrombosis at diagnosis, and isolated splenic vein thrombosis secondary to malignancy were excluded. The outcomes of anticoagulation, recanalization rates, risk of bleeding, and progression to portal vein thrombosis were examined. Results Ninety-eight patients with iSVT were included; of which thirty-nine patients received anticoagulation (40%). The most common cause of iSVT was acute pancreatitis n = 88 (90%). The recanalization rate in the anticoagulation group was 46% vs 15% in patients receiving no anticoagulation (p = 0.0008, OR = 4.7, 95% CI 1.775 to 11.72). Upper abdominal vascular collaterals (demonstrated on CT scan angiography) were significantly less among patients who received anticoagulation treatment (p = 0.03, OR = 0.4, 95% CI 0.1736 to 0.9288). The overall rate of upper GI variceal related bleeding was 3% (n = 3/98) and it was independent of anticoagulation treatment. Two of the patients received therapeutic anticoagulation. Conclusions The current data support that therapeutic anticoagulation is associated with a statistically significant increase in recanalization rates of the splenic vein; with a subsequent reduction in radiological left-sided portal hypertension. However, all patients had a very low risk of variceal bleeding regardless of anticoagulation. The findings from this retrospective study should merit further investigation in large-scale randomized clinical trials.

Background Since the second surge of SARS-COVID-19 on 18th of September, additional several measures were introduced, and pathways created in order to execute safe surgical practices and protect both patients and staff from SARS-COVID-19. Despite these measures, there have been reported cases of outbreaks in various parts of UK amongst patients and clinical staff. Method Three outbreaks in the past 6 weeks (10, September 2020 to 21, October 2020) were reported in our surgical wards and we compiled the timing, initial source, number of affected individuals and immediate management steps taken. Results Following the first outbreak on wards, 28-day surveillance helped us understand responsible variants. Several staff members were found walking out of hospital, in groups once they had removed their PPEs. Communal lunching with inadequate social distancing, attending work with symptoms (albeit atypical for COVID), sharing cars to/from work or not wearing PPE correctly were highlighted in the subsequent investigations. The reduction in number of affected individuals during the last two incidents reflected a degree of efficacy of the implemented preventative measures, which were reviewed again following the subsequent incidents. Conclusions In the present climate, a robust and prompt response to outbreaks is required. Continual iteration with regards to the need for PPE, adequate social distancing and avoiding over-crowding in communal areas is paramount to reduce the probability of ward outbreaks and inter-professional transmission. Asymptomatic staff testing, particularly in high-risk areas could also be considered but would require adequate laboratory capacity and rapid turnaround of test results.

BACKGROUND Within the last decade, advances and availability in radiological imaging have led to an increase in the detection of incidental liver lesions (ILLs) in the asymptomatic patient population. This poses a diagnostic conundrum. This study was undertaken to review the outcome of liver lesions labelled as 'indeterminate' in asymptomatic patients without a biopsy-proven concomitant primary tumour. The secondary aim was to assess the impact on healthcare resources and cost-effectiveness with regards to the frequency and modality of radiological scans, multidisciplinary team discussions and clinic reviews. METHODS The study consisted of a retrospective analysis of prospectively collected data from the University Hospitals of Leicester multidisciplinary team database. The study period ranged from 2010 to 2015. All patients were followed-up for 3 years to ensure no late re-occurrences with malignancy. RESULTS A total of 92 patients with ILL were identified. The median age was 72 years. The median size of these ILLs was 10 mm. Eighty-seven patients required supplementary imaging and 42 required a third imaging. Ninety-one patients had benign lesions. Only one case was biopsy proven to be malignant. CONCLUSION Small (

Background Epidural analgesia is conventionally used as the mainstay of analgesia in open abdominal surgery but has a small life-changing risk of complications (epidural abscesses or haematomas). Local wound-infusion could be a viable alternative and are associated with fewer adverse effects. Methods A retrospective observational analysis of individuals undergoing open hepato-pancreato-biliary surgery over 1 year was undertaken. Patients either received epidural analgesia (EP) or continuous wound infusion (WI) + IV patient controlled anaesthesisa (PCA) with an intraoperative spinal opiate. Outcomes analyzed included length of stay, commencement of oral diet and opioid use. Results Between Jan 2016- Dec 2016, 110 patients were analyzed (WI n=35, EP n=75). The median length of stay (days) was 8 in both the WI and EP group (p=0.846), the median time to commencing oral diet (days) was 3 in WI group and 2 in EP group (p=0.455). There was no significant difference in the amount of oromorph, codeine or tramadol (mg) between WI and EP groups (p=0.829, p=0.531, p=0.073, respectively). Conclusions Continuous wound infusion + IV PCA provided adequate analgesia to patients undergoing open hepato-pancreato-biliary surgery. It was non-inferior to epidural analgesia with respect to hospital stay, commencement of oral diet and opioid use.

BACKGROUND: The initial response to islet transplantation and the subsequent acute inflammation is responsible for significant attrition of islets following both autologous and allogenic procedures. This multicentre study compares this inflammatory response using cytokine profiles and complement activation. METHODS: Inflammatory cytokine and complement pathway activity were examined in two cohorts of patients undergoing total pancreatectomy followed either by autologous (n=11) or allogenic (n=6) islet transplantation. Two patients who underwent total pancreatectomy alone (n=2) served as controls. RESULTS: The peak of cytokine production occurred immediately following induction of anaesthesia and during surgery. There was found to be a greater elevation of the following cytokines: TNF-alpha (P

Introduction Malnutrition is a common sequela of chronic pancreatitis (CP). Alterations in body composition and the assessment of sarcopenia have gained the interest of clinicians in recent years. There is a scarcity of data currently available concerning sarcopenia in patients with CP. This review aims to investigate the prevalence and impact of sarcopenia in CP. Methods Embase and Medline databases were used to identify all studies that evaluated sarcopenia and outcomes in patients with chronic pancreatitis. Due to paucity of data, conference abstracts were included. PRISMA guidelines for systematic reviews were followed. Results Six studies, with a total of 450 individuals were reviewed. Three full-text studies and three conference abstracts met the predetermined eligibility criteria. The prevalence of sarcopenia in CP from all studies ranged from 17–62%. Pancreatic exocrine insufficiency was associated as an independent and significant risk factor for sarcopenia. Sarcopenia was found to be associated with a reduced quality of life, increased hospitalisation, and reduced survival. It was associated with significantly lower islet yield following total pancreatectomy with islet auto transplantation in CP. Conclusion The review of these existing studies amalgamates the limited data on sarcopenia and its impact on CP. It has shown that sarcopenia is exceedingly prevalent and an important risk factor in CP patients. The data presented emphasises that sarcopenia has a significant prognostic value and should be included in future prospective analyses in the outcomes of CP.

As data and metadata from the SARS-CoV-2 pandemic mature, the true impact on non-cancer, non-emergency surgical practice is becoming apparent. The authors present data on the impact of gallstone disease in their unit during 5 months of the COVID-19 pandemic (March 2020 to August 2020) compared with the equivalent period in 2019. Although the total number of patients presenting with gallstone disease was comparable, there was a decrease in patients with cholecystitis and perforation (although it is possibly too early for these to have presented), and there was a small but worrying increase in patients with gallstone pancreatitis. With the recent increase in alert level to 4 and increased government restrictions in an attempt to avoid a second national lockdown, a consistent national approach is required to mitigate these risks.

Introduction: \ud The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic.\ud \ud Methods: \ud A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved.\ud \ud Results: \ud Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic.\ud \ud Conclusion: \ud The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised.

Objective –To assess the efficacy of a pilot Chronic Pancreatitis (CP) Multidisciplinary (MDT) clinic. Methods – 60 patients referred to a pilot MDT CP clinic were analysed. Anthropometric data, nutrition status, malabsorption evidence, glycaemic control, opiate use, bone mineral density (BMD) assessment and quality of life (QoL) were examined. Results –The average age was 51.27 (±12.75). The commonest aetiology was alcohol (55%). Ninety one point five percent had evidence of ongoing pancreatic exocrine insufficiency, with 88.1% requiring initiation or up-titration of pancreatic enzyme replacement (PERT). Up to half of the patients exhibited micronutrient deficiency. Twenty eight percent were diagnosed with type IIIc diabetes. There was an average daily reduction of 6 mg of morphine usage per patient with a concurrent decline in median pain scores from 83.3 to 63.3, which was non-significant. The median QoL score was 33.3 compared to a score of 75 from the reference population. QoL scores increased from 31.0 to 37.3 at follow up appointments. Seventy two point five percent of patients had undiagnosed low BMD. Conclusion The data suggest that CP patients have significant nutritional deficiencies as well as undiagnosed diabetes, poor pain and glycaemic control which negatively impacts QoL. Assessment in a multi-disciplinary clinic ensures appropriate management.

BACKGROUND: Numerous factors influence pancreatic islet survival following auto-transplantation. Of these, the host immune response in the early peri-operative period is one of the most important. In this study we investigated the role of the mannose-binding lectin (MBL)-dependent pathway in a group of total pancreatectomy (TP) islet auto-transplantation (TPIAT) patients and classified them as competent or deficient in MBL activity. Complement pathway activities, MBL protein and inflammatory cytokine concentrations were evaluated from eleven pancreatic islet auto-transplant patients from two institutions. METHODS: Eleven patients from two institutions were prospectively recruited. Serum was screened at different time points for 29 different cytokines and compared according to their MBL deficient or competent status. Twelve patients from previous TPIAT patients also underwent screening of MBL pathway activity. RESULTS: A total nine of twenty three patients (39%) were MBL pathway deficient. MCP-1, IL-7 and IL-1a concentrations were significantly lower in the MBL deficient cohort compared to the normal MBL group (P=0.0237, 0.0001 and 0.0051 respectively). IL-6 and IL-8 concentrations were significantly raised in the normal MBL group. MBL functional activity was lower in insulin-independent group compared to the insulin-dependent group. CONCLUSIONS: Complement activation is an important, possibly damaging response during intra-portal islet infusion. MBL pathway deficiency appears common in this population and the cytokine response was attenuated in MBL pathway deficient patients. Therapeutic MBL pathway blockade during and following islet auto-transplantation (IAT) may improve islet survival and function and thereby clinical outcome.

Intraductal tubulopapillary neoplasms (ITPNs) of the pancreas and bile duct are contemporary entities. It is unclear on how to best manage patients with this diagnosis because little is known about its progression to cancer. This review provides an update on the current knowledge of ITPN of the pancreas and bile duct with an overview of clinical, radiological, histopathological, and molecular features, as well as the prognosis and management. Embase and Medline databases search were performed to identify studies that evaluated ITPN of the pancreas and bile duct. The infrequent exposure to this variant poses a diagnostic challenge. The diagnosis of ITPN is almost always made postoperatively because there are no characteristics on radiological studies to distinguish it from other cystic neoplasms of the pancreas. As ITPN has a favorable prognosis, it is crucial to establish an accurate diagnosis and differentiate it from other pancreatic and biliary variants. These neoplasms are considered to be precursor lesions to carcinomas, hence, surgery and close clinical surveillance are recommended. Further studies are essential to elucidate the natural history of ITPN, guide best treatment strategy and determine disease recurrence and survival.

The effect of COVID on surgical admissions was investigated by comparing such admissions from March to August 2020 with those in the same period in 2019. A significant reduction was noted in surgical admissions. The majority of this reduction was seen in the group with non-specific abdominal pain. It is presumed that public adherence to authorities’ message and effective ambulatory care are behind this decrease., we investigated the COVID effect on surgical admissions by comparing surgical admissions to the same period in 2019. significant reduction was noted of surgical admissions. interestingly, the majority of this reduction was seen in the non specific abdominal pain group. it is presumed that public adherence to authorities message and effective ambulatory care are behind this decrease.

Purpose The aim of this study was to compare the prognostic value of established scoring systems with early warning scores in a large cohort of patients with acute pancreatitis. Methods In patients presenting with acute pancreatitis, age, sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score, Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for the first 72 h following admission. These variables were compared between survivors and non-survivors, between patients with mild/moderate and severe pancreatitis (based on the 2012 Atlanta Classification) and between patients with a favourable or adverse outcome. Results A total of 629 patients were identified. EWS was the best predictor of adverse outcome amongst all of the assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1, 2 and 3, respectively) and was the most accurate predictor of mortality on both days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis revealed that an EWS ≥2 was independently associated with severity of pancreatitis, adverse outcome and mortality. Conclusion This study confirms the usefulness of EWS in predicting the outcome of acute pancreatitis. It should become the mainstay of risk stratification in patients with acute pancreatitis.

Up to three‐quarters of patients undergoing liver resection for colorectal liver metastases (CRLM) develop intrahepatic recurrence. Repeat hepatic resection appears to provide the optimal chance of cure for these patients. The aim of this study was to analyze short‐ and long‐term outcomes following index and repeat hepatectomy for CRLM. Clinicopathological data were obtained from a prospectively maintained database. Perioperative variables and outcomes were compared using the Chi‐squared test. Variables associated with long‐term survival following index and second hepatectomy were identified by Cox regression analyses. Over the study period, 488 patients underwent hepatic resection for CRLM, with 71 patients undergoing repeat hepatectomy. There was no significant difference in rates of morbidity (P = 0.135), major morbidity (P = 0.638), or mortality (P = 0.623) when index and second hepatectomy were compared. Performance of repeat hepatectomy was independently associated with increased overall and cancer‐specific survival following index hepatectomy. Short disease‐free interval between index and second hepatectomy, number of liver metastases >1, and resection of extrahepatic disease were independently associated with shortened survival following repeat resection. Repeat hepatectomy for recurrent CRLM offers short‐term outcomes equivalent to those of patients undergoing index hepatectomy, while being independently associated with improved long‐term patient survival.

BACKGROUND Clinical risk scores (CRS) within the context of neoadjuvant chemotherapy for colorectal liver metastases (CRLM) has not been validated. The predictive value of clinical risk scoring in patients administered neoadjuvant chemotherapy prior to liver surgery for CRLM is evaluated. METHODS A prospective database over a 15-year period (April 1999 to March 2014) was analysed. We identified two groups: A, neoadjuvant chemotherapy prior to CRLM surgery; and B, no neoadjuvant chemotherapy. RESULTS Overall median survival in groups A and B were 36 (2-137) months and 33 (2-137) months. In group A, nodal status, size, number of metastases and carcinoembryonic antigen levels were not found to be independent predictors of overall survival (OS). However, patients with a shorter disease-free interval of less than 12 months had an increased OS (P = 0.0001). Multivariate analysis of high- and low-risk scores compared against survival in group B (P < 0.05) confirms the applicability of the scoring system in traditional settings. CONCLUSION Traditional CRS are not a prognostic predictive tool when applied to patients receiving neoadjuvant chemotherapy for CRLM. Disease-free interval may be one independent variable for use in future risk score systems specifically developed for the neoadjuvant chemotherapy era.

Despite increasingly mixed communities in large cities, there remains a paucity of absolute and comparative data concerning the treatment, access and survival of British Asians with pancreatic cancer. A prospective database of 1038 patients with a diagnosis of pancreatic cancer from 2003 to 2012 was analysed. Asian/Asian British was defined as patients identifying themselves as originating from India, Bangladesh or Pakistan. No significant difference was observed in gender split for both Asian/Asian British and White British (AAB and WB). The incidence of pancreas cancer was also equivalent between the two groups at 8.1 versus 8.8 per 100,000 of the population. Age at presentation was significantly younger in AABs when compared to WBs (67 vs. 70 years, p = 0.003). Whilst median maximal tumour diameter, node status and the incidence of metastases were not different between AABs and WBs, the AABs had a significantly greater median T-stage (3.0 versus 2.5, p = 0.0024). The percentage of patients referred for chemotherapy was significantly higher in the AAB group (70.5 vs. 47.7 %, p = 0.0015). Overall survival and survival for patients having palliative treatment were significantly greater in AABs (4.6 vs. 6.1 months and 3.7 vs. 5.1 months). This study demonstrates that AAB patients are present with pancreatic cancer at a younger age and that when receiving palliative chemotherapy their survival is significantly better. Further studies and larger data sets over a longer period are required. It is important to examine further the complexity of incidence and survival in ethnic minorities and investigate the underlying reasons when differences are demonstrated.

To determine the accuracy and safety of the percutaneous biopsy of pancreatic mass lesions.Over a 12-year period clinical parameters, imaging, pathologic results, and complications were assessed in patients undergoing percutaneous biopsies pancreatic lesions.One hundred fifty-three patients underwent pancreatic biopsy. The preferred modality for performing the biopsy was ultrasound (93%, n=143) followed by computerized tomography (7%, n=10). Histologic diagnosis was achieved in 147 patients, of which 3 (2%) were benign and 144 (94%) were malignant. Complications included a single death from overwhelming hemorrhage and 2 patients with morbidity (hematoma and cerebrovascular accident). The sensitivity and specificity of percutaneous biopsies was 90% and 95%, respectively.Ultrasound-guided and computerized tomographic-guided percutaneous biopsy of pancreatic lesions is an effective and safe method to confirm or refute malignancy in suspicious pancreatic lesions. Endoscopic ultrasound-guided Tru-Cut may have the added advantage of avoiding the risk of peritoneal soiling.

BACKGROUND Within the last decade, advances and availability in radiological imaging have led to an increase in the detection of incidental liver lesions (ILLs) in the asymptomatic patient population. This poses a diagnostic conundrum. This study was undertaken to review the outcome of liver lesions labelled as 'indeterminate' in asymptomatic patients without a biopsy-proven concomitant primary tumour. The secondary aim was to assess the impact on healthcare resources and cost-effectiveness with regards to the frequency and modality of radiological scans, multidisciplinary team discussions and clinic reviews. METHODS The study consisted of a retrospective analysis of prospectively collected data from the University Hospitals of Leicester multidisciplinary team database. The study period ranged from 2010 to 2015. All patients were followed-up for 3 years to ensure no late re-occurrences with malignancy. RESULTS A total of 92 patients with ILL were identified. The median age was 72 years. The median size of these ILLs was 10 mm. Eighty-seven patients required supplementary imaging and 42 required a third imaging. Ninety-one patients had benign lesions. Only one case was biopsy proven to be malignant. CONCLUSION Small (

The introduction of endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy (ES) has changed the treatment of choledocholithiasis. An increasing number of young patients are requiring ES, and this raises concern regarding any potential long-term complications arising from irreversibly altering the anatomy of the sphincter of Oddi. In particular, concern has been raised regarding the risk of late cholangiocarcioma. A review was performed evaluating the relationship between ES for benign disease and the subsequent development of late complications, including biliary tract malignancy, the formation of primary duct stones, and recurring cholangitis. A systematic review of articles published between 1970 and 2013 was undertaken. Current evidence shows that ES is a safe and effective treatment for common bile duct stones. The long-term risk of subsequent cholangiocarcinoma has not been convincingly proven although in many of these studies the follow-up period was inadequate. There does appear to be an associated increased incidence of cholangiocarcinomas following sphincterotomy although this is not proven to be causative. If there is an increased risk of cholangiocarcinoma following ES, it is likely to be small in western populations. However, until longer follow-up studies are published, it may be prudent to avoid ES in the very young.

Background To date, no studies have sought to determine the frequency of malignancy in patients presenting with a putative biliary stricture and normal liver function tests (LFTs). The primary aim of this retrospective cohort study was to determine the likelihood of malignancy in patients presenting with a biliary stricture and normal LFTs, a normal bilirubin level either alone or in combination with normal levels of liver enzymes [alkaline phosphatase (ALP) and alanine transaminase (ALT)]. A secondary aim was to determine any clinical/biochemical/sonographic features that may be associated with malignancy. Methods Patients presenting over a 10‐year period were included. Fifteen variables were analysed to determine their association with malignant disease. Results Eight hundred and thirty patients with putative biliary strictures were included. Primary hepatopancreaticobiliary (HPB) cancers presented with a normal bilirubin and normal liver enzymes (ALP and ALT) in 6% of cases. Patients with a putative biliary stricture and a normal bilirubin level whose final diagnoses were pancreatic cancer, ampullary cancer, distal cholangiocarcinoma and hilar cholangiocarcinoma represented 21%, 13%, 7% and 9% of individuals diagnosed with these pathologies, respectively. Hypoalbuminaemia and isolated intrahepatic duct dilatation on ultrasound were significantly associated with malignancy in patients with normal bilirubin and completely normal LFTs. Conclusions This study has shown that patients with a putative biliary stricture and completely normal LFTs are unlikely to have a primary HPB malignancy. Those presenting with a normal bilirubin level, but deranged liver enzymes (ALP and/or ALT), are more likely to have malignant disease, and this should necessitate a higher degree of clinical suspicion.

INTRODUCTION This study assessed the safety and efficacy of acute laparoscopic cholecystectomy (ALC) in patients presenting with biliary pathology. The potential savings plus income generation for the hospital were calculated. METHODS All patients undergoing emergency cholecystectomy were identified from computerized and hand-written theater records to ensure complete capture. Length of stay, procedure time, patient demographics, and postoperative complications were recorded. Tariffs for conservative versus acute management were calculated. Total admissions and readmissions with biliary pathology (acute cholecystitis, biliary colic, gallstone pancreatitis, and obstructive jaundice) over a 12-month period were recorded. RESULTS Eighty-four patients undergoing ALC were identified. There was only 1 major complication (1 postoperative bleed managed laparoscopically). ALC for all admissions would result in savings of £ 695,918 over 12 months. The implementation of ALC for all patients would result in a small loss in revenue when compared with elective laparoscopic cholecystectomy (£ 15,495) provided that all operations could be accommodated on established operating lists. Implementing ALC on all appropriate biliary admissions could generate up to 3 cholecystectomies daily for a population base of 1 million. CONCLUSIONS ALC is cost-effective and safe. It can be offered to all patients with biliary pathology provided they are fit enough for surgery.