Search

Superior patient outcomes rely on surgical training being optimized. Accordingly, we conducted an international, prospective, cross-sectional study determining relative impacts of COVID-19, gender, race, specialty and seniority on mental health of surgical trainees.Trainees across Australia, New Zealand and UK enrolled in surgical training accredited by the Royal Australasian College of Surgeons or Royal College of Surgeons were included. Outcomes included the short version of the Perceived Stress Scale, Oxford Happiness Questionnaire short scale, Patient Health Questionnaire-2 and the effect on individual stress levels of training experiences affected by COVID-19. Predictors included trainee characteristics and local COVID-19 prevalence. Multivariable linear regression analyses were conducted to assess association between outcomes and predictors.Two hundred and five surgical trainees were included. Increased stress was associated with number of COVID-19 patients treated (P = 0.0127), female gender (P = 0.0293), minority race (P = 0.0012), less seniority (P = 0.001), and greater COVID-19 prevalence (P = 0.0122). Lower happiness was associated with training country (P = 0.0026), minority race (P = 0.0258) and more seniority (P 0.0001). Greater depression was associated with more seniority (P 0.0001). Greater COVID-19 prevalence was associated with greater reported loss of training opportunities (P = 0.0038), poor working conditions (P = 0.0079), personal protective equipment availability (P = 0.0008), relocation to areas of little experience (P 0.0001), difficulties with career progression (P = 0.0172), loss of supervision (P = 0.0211), difficulties with pay (P = 0.0034), and difficulties with leave (P = 0.0002).This is the first study to specifically describe the relative impacts of COVID-19 community prevalence, gender, race, surgical specialty and level of seniority on stress, happiness and depression of surgical trainees on an international scale.

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.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC., Circulating tumour cells can be useful for monitoring disease progression but how they survive in the circulatory system is unclear. Here, the authors use single-cell sequencing of circulating tumour cells from multiple vascular sites in liver cancer patients and identify genes that may help the cells survive.

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.

Summary Background and aims Omega-3 fatty acids (FA) can ameliorate the hyper-inflammatory response that occurs in conditions such as severe acute pancreatitis (SAP) and this may improve clinical outcome. We tested the hypothesis that parenteral omega-3 FA from a lipid emulsion that includes fish oil could be beneficial in patients with predicted SAP by reducing C-reactive protein (CRP) concentration (primary outcome), and modulating the inflammatory response and improving clinical outcome (secondary outcomes). Methods In a phase II randomized double-blind single-centre controlled trial, patients with predicted SAP were randomised to receive a daily infusion of fish oil containing lipid emulsion (Lipidem® 20%, BBraun) for 7 days (n = 23) or a daily infusion of a lipid emulsion without fish oil (Lipofundin® MCT 20%, BBraun) (n = 22). Results On admission, both groups had comparable pancreatitis predicted severity and APACHE II scores. Administration of fish oil resulted in lower total blood leukocyte number (P = 0.04), CRP (P = 0.013), interleukin-8 (P = 0.05) and intercellular adhesion molecule 1 (P = 0.01) concentrations, multiple organ dysfunction score, sequential organ failure assessment score (P = 0.004), early warning score (P = 0.01), and systemic inflammatory response syndrome (P = 0.03) compared to the control group. The fish oil group had fewer new organ failures (P = 0.07), lower critical care admission rate (P = 0.06), shorter critical care stay (P = 0.03) and shorter total hospital stay (P = 0.04). Conclusions It is concluded that intravenous administration of a fish oil containing lipid emulsion, a source of omega-3 FA, improves clinical outcomes in patients with predicted SAP, benefits that may be linked to reduced inflammation. ClinicalTrials.gov number NCT01745861 . EU Clinical Trials Register EudraCT (2010-018660-16).

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 Administration of intravenous ω-3 fatty acid (ω-3FA) in advanced pancreatic adenocarcinoma patients receiving gemcitabine chemotherapy shows disease stabilization and improved progression-free survival. Using high-definition plasma proteomics, the underlying biological mechanisms responsible for these clinical effects are investigated. METHODS AND RESULTS A pilot study involving plasma that was collected at baseline from 13 patients with histologically confirmed, unresectable pancreatic adenocarcinoma (baseline group) after 1-month treatment with intravenous gemcitabine and ω-3FA (treatment group) and intravenous gemcitabine only (control group) and was prepared for proteomic analysis. A 2-arm study comparing baseline vs treatment and treatment vs control was performed. Proteins were isolated from plasma with extensive immunodepletion, then digested and labeled with isobaric tandem mass tag peptide tags. Samples were then combined, fractionated, and injected into a QExactive-Orbitrap Mass-Spectrometer and analyzed on Proteome Discoverer and Scaffold with ensuing bioinformatics analysis. Selective reaction monitoring analysis was performed for verification. In total, 3476 proteins were identified. Anti-inflammatory markers (C-reactive protein, haptoglobin, and serum amyloid-A1) were reduced in the treatment group. Enrichment analysis showed angiogenesis downregulation, complement immune systems upregulation, and epigenetic modifications on histones. Pathway analysis identified direct action via the Pi3K-AKT pathway. Serum amyloid-A1 significantly reduced (P < .001) as a potential biomarker of efficacy for ω-3FA. CONCLUSIONS This pilot study demonstrates administration of ω-3FA has potential anti-inflammatory, antiangiogenic, and proapoptotic effects via direct interaction with cancer-signaling pathways in patients with advanced pancreatic adenocarcinoma. Further studies in a larger sample size is required to validate the clinical correlation found in this preliminary study.

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 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 (

Numerous techniques have been described for fashioning gastrojejunostomy (GJ) in a Roux-en-Y gastric bypass. These include hand-sewn anastomosis (HSA) and mechanical anastomosis; the latter includes circular stapled anastomosis (CSA) or manual linear stapled anastomosis (mLSA). More recently, this list also includes powered linear stapled anastomosis (pLSA). The aim of this study was to analyse if addition of power to stapling would improve the integrity of GJ anastomosis in ex vivo porcine models.The present study included five groups - mLSA1, mLSA2, HSA, CSA, and pLSA. Sequential infusions of methylene blue-coloured saline were performed into the GJ models. Pressure readings were recorded till the point of leak denoting burst pressure (BP). Total volume (TV) and site of leak were recorded. Compliance was calculated from the equation ΔTV/ΔBP.Differences in pouch and intestinal thickness were not statistically significant between the models. BPs were higher in the mechanical anastomosis groups, i.e., pLSA 21 ± 9.85 mmHg, CSA 20.33 ± 5.78 mmHg, mLSA1 18 ± 4.69 mmHg and mLSA2 11 ± 2.94 mmHg, when compared to HSA 9.67 ± 3.79 mm Hg, which was found to be statistically significant (Kruskal-Wallis test, P = 0.03). Overall, the highest BP was recorded for powered stapling followed by circular, and then, linear stapling; however, this difference was not statistically significant (P = 0.86). There was no statistically significant difference among groups with regard to compliance (Kruskal-Wallis test, P = 0.082).Despite the limited number of samples, mechanical anastomosis showed a statistically higher BP when compared to HSA, suggesting better anastomotic integrity. The pLSA group showed promising results with the highest BP recorded among all groups; however, this did not reach statistical significance.

Classical in vivo infection models are oftentimes associated with speculation due to the many physiological factors that are unseen or not accounted for when analyzing experimental outputs, especially when solely utilizing the classic approach of tissue-derived colony-forming unit (CFU) enumeration. To better understand the steps and natural progression of bacterial infection, the pathophysiology of individual organs with which the bacteria interact in their natural course of infection must be considered. In this case, it is not only important to isolate organs as much as possible from additional physiological processes, but to also consider the dynamics of the bacteria at the cellular level within these organs of interest. Here, we describe in detail two models, ex vivo porcine liver and spleen coperfusion and a murine infection model, and the numerous associated experimental outputs produced by these models that can be taken and used together to investigate the pathogen-host interactions within tissues in depth.

Summary Background Hypervirulent Klebsiella pneumoniae (hvKp) strains of capsule type K1 and K2 cause invasive infections associated with hepatic abscesses, which can be difficult to treat and are frequently associated with relapsing infections. Other K pneumoniae strains (non-hvKp), including lineages that have acquired carbapenem resistance, do not manifest this pathology. In this work we aimed to test the hypothesis that within-macrophage replication is a key mechanism underpinning abscess formation in hvKp infections. Methods In this exploratory investigation, to study the pathophysiology of abscess formation, mice were intravenously infected with 106 colony forming units (CFU) of either hvKp isolates (six strains) or non-hvKp isolates (seven strains). Intracellular bacterial replication and neutrophil influx in liver and spleen was quantified by fluorescence microscopy of sliced cryopreserved organs of mice collected 30 min, 6 h, and 24 h after infection with the aim to provide data of bacterial association to Kupffer cells in the liver and to the different tissue macrophages in the spleen. Microbiological and microscopy analysis of an ex-vivo model of pig liver and spleen infection were used to confirm within-macrophage replication. Pig organs were perfused with heparinised, autologous pig's blood and injected with 6·5 × 107 CFU of hvKp K2 sequence type 25 strain GMR151. Blood and tissue biopsies collected before infection and 30 min, 1 h, 2 h, 3 h, 4 h, and 5 h after infection were used to measure bacterial counts and to identify the subcellular localisation of bacteria by immunohistochemistry analysis. Findings We show that hvKp resisted phagocyte-mediated clearance and replicated in mouse liver macrophages to form clusters 6 h after infection, with a mean of 7·0 bacteria per Kupffer cell (SD 6·2); however, non-hvKp were efficiently cleared (mean 1·5 bacteria per cell [SD 1·1]). HvKp infection promoted neutrophil recruitment to sites of infection, which in the liver resulted in histopathological signs of abscess formation as early as 24 h post-infection. Experiments in pig organs which share a high functional and anatomical resemblance to human organs, provided strong evidence for the propensity of hvKp to replicate within the hepatic macrophages. Interpretation These findings show subversion of innate immune processes in the liver by K pneumoniae and resistance to Kupffer cell mediated clearance as an explanation for the propensity of hvKp strains to cause hepatic abscesses. Funding University of Oxford and a Royal Society Wolfson grant funded biosafety facility.

Klebsiella, macrophage, abscess Background: Hypervirulent Klebsiella pneumoniae (hvKp) strains of capsule type K1 and K2 cause invasive infections associated with hepatic abscesses, which can be difficult to treat and are frequently associated with relapsing infections. Other K pneumoniae strains (non-hvKp), including lineages that have acquired carbapenem resistance, do not manifest this pathology. In this work we aimed to test the hypothesis that within-macrophage replication is a key mechanism underpinning abscess formation in hvKp infections. Methods: In this exploratory investigation, to study the pathophysiology of abscess formation, mice were intravenously infected with 106 colony forming units (CFU) of either hvKp isolates (six strains) or non-hvKp isolates (seven strains). Intracellular bacterial replication and neutrophil influx in liver and spleen was quantified by fluorescence microscopy of sliced cryopreserved organs of mice collected 30 min, 6 h, and 24 h after infection with the aim to provide data of bacterial association to Kupffer cells in the liver and to the different tissue macrophages in the spleen. Microbiological and microscopy analysis of an ex-vivo model of pig liver and spleen infection were used to confirm within-macrophage replication. Pig organs were perfused with heparinised, autologous pig's blood and injected with 6·5 × 107 CFU of hvKp K2 sequence type 25 strain GMR151. Blood and tissue biopsies collected before infection and 30 min, 1 h, 2 h, 3 h, 4 h, and 5 h after infection were used to measure bacterial counts and to identify the subcellular localisation of bacteria by immunohistochemistry analysis. Findings: We show that hvKp resisted phagocyte-mediated clearance and replicated in mouse liver macrophages to form clusters 6 h after infection, with a mean of 7·0 bacteria per Kupffer cell (SD 6·2); however, non-hvKp were efficiently cleared (mean 1·5 bacteria per cell [SD 1·1]). HvKp infection promoted neutrophil recruitment to sites of infection, which in the liver resulted in histopathological signs of abscess formation as early as 24 h post-infection. Experiments in pig organs which share a high functional and anatomical resemblance to human organs, provided strong evidence for the propensity of hvKp to replicate within the hepatic macrophages. Interpretation: These findings show subversion of innate immune processes in the liver by K pneumoniae and resistance to Kupffer cell mediated clearance as an explanation for the propensity of hvKp strains to cause hepatic abscesses. Funding: University of Oxford and a Royal Society Wolfson grant funded biosafety facility.

Classical in vivo infection models are oftentimes associated with speculation due to the many physiological factors that are unseen or not accounted for when analyzing experimental outputs, especially when solely utilizing the classic approach of tissue-derived colony-forming unit (CFU) enumeration. To better understand the steps and natural progression of bacterial infection, the pathophysiology of individual organs with which the bacteria interact in their natural course of infection must be considered. In this case, it is not only important to isolate organs as much as possible from additional physiological processes, but to also consider the dynamics of the bacteria at the cellular level within these organs of interest. Here, we describe in detail two models, ex vivo porcine liver and spleen coperfusion and a murine infection model, and the numerous associated experimental outputs produced by these models that can be taken and used together to investigate the pathogen-host interactions within tissues in depth.

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 Cavernous hepatic haemangiomas are benign liver tumours and although common when small, giant haemangiomas (usually accepted as being greater than 10cm) are infrequent. Treatment is indicated in patients who are symptomatic or if diagnosis is unclear, although with giant haemangiomas, many support expectant management of asymptomatic lesions due to the risk of major complications. Traditionally hepatic resection has been the primary treatment option for these lesions, but a variety of other techniques, including enucleation, have been described as safe and effective alternatives. There remains equipoise in respect of the best management of giant haemangiomas above 10cm. Cases of such size are rare and so there is a paucity of data available. Case presentation We present a case of a 65-year-old male who underwent successful anatomical liver resection for a 5kg giant cavernous haemangioma of 26cm diameter following its incidental identification during an ultrasound scan. We also discuss and compare the role of resection and enucleation for the treatment of haemangiomata greater than 20cm in diameter. Conclusions This case demonstrates successful resection of an unusually giant haemangioma which, in contrast to the majority of literature, provides a valuable addition to the limited evidence base for management of this condition by anatomical resection.

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

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a limited number of effective treatments. Using emerging technologies such as artificial intelligence (AI) to facilitate the earlier diagnosis and decision-making process represents one of the most promising areas for investigation. The integration of AI models to augment imaging modalities in PDAC has made great progression in the past 5 years, especially in organ segmentation, AI-aided diagnosis, and radiomics based individualized medicine. In this article, we review the developments of AI in the field of PDAC and the present clinical position. We also examine the barriers to future development and more widespread application which will require increased familiarity of the underlying technology among clinicians to promote the necessary enthusiasm and collaboration with computer professionals.

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.

A 28-year-old male with infra-cardiac totally anomalous pulmonary venous connection (TAPVC) repaired as new-born presented in adulthood with right heart strain and very large left atrium to portal vein vessel. Residual connections from pulmonary veins to systemic circulation are believed to represent persistent ‘vertical veins’ (VV) not ligated at the time of the initial surgery. In our patient, since endovascular occlusion was not judged suitable, the anomalous vessel was surgically ligated and resected. A review of the literature failed to find such a procedure reported in an adult patient and analyzed the intra-operative ligation of VV during repair of TAPVC.

Summary Background Acute pancreatitis (AP) is marked by a strong pro-inflammatory response, which may cause a systemic inflammatory response syndrome (SIRS), organ failure, and death. Early administration of omega-3 fatty acids (FA) may reduce the pro-inflammatory response and improve outcome in AP. A systematic review focusing on the safety and efficacy of omega-3 FA in AP is lacking. Aim Evaluate the safety and efficacy of an intervention with omega-3 FA in acute pancreatitis and additionally in sepsis. Methods A systematic review and meta-analysis was performed using the PubMed, Embase, and Cochrane databases including only randomized controlled trials in AP and, for safety endpoints, in sepsis investigating intervention including omega-3 FA without other active components (e.g. addition of glutamine to the intervention). The primary outcome was mortality. Results After screening 1186 studies, five randomized trials (n = 229) with omega-3 FA in AP were included. In AP patients treated with omega-3 FA within 48 h after hospitalization, a non-significant reduction of mortality was seen (OR 0∙50, 95%CI 0∙13–1∙99, p = 0∙33), compared to controls. In two studies (n = 85), omega-3 FA reduced the risk of new onset of organ failure (OR 0∙33, 95%CI 0∙12–0∙93, p = 0∙04). Nine randomized trials with 312 patients suffering from sepsis (not pancreatitis related) demonstrated a reduced mortality (OR 0∙52, 95%CI 0∙28–0∙97, p = 0·04). None of these 14 randomized trials reported safety concerns. Conclusions Administration of omega-3 FA could reduce the risk of new-organ failure in patients with AP. There were no safety issues reported of the early administration of omega-3 FA in any of the included studies. To show the real clinical benefit of omega-3 FA in AP, a large and pragmatic randomized controlled trial is needed.

The last 3 years have seen the emergence of promising targeted therapies for the treatment of hepatocellular carcinoma (HCC). Sorafenib has been the mainstay of treatment for a decade and newer modalities were ineffective and did not confer any increased therapeutic benefit until the introduction of lenvatinib which was approved based on its non-inferiority to sorafenib. The subsequent success of regorafenib in HCC patients who progress on sorafenib treatment heralded a new era of second-line treatment and was quickly followed by ramucirumab, cabozantinib, and the most influential, immune checkpoint inhibitors (ICIs). Over the same period combination therapies, including anti-angiogenesis agents with ICIs, dual ICIs and targeted agents in conjunction with surgery or other loco-regional therapies, have been extensively investigated and have shown promise and provided the basis for exciting clinical trials. Work continues to develop additional novel therapeutic agents which could potentially augment the presently available options and understand the underlying mechanisms responsible for drug resistance, with the goal of improving the survival of patients with HCC.

Hepatic haemangioendothelioma is a rare (1:1,000,000) mesenchymal tumour of the liver of vascular origin. Metastatic malignancies, other primary liver tumours and cholangiocarcinomas all have significantly worse prognoses and may mimic hepatic haemangioendothelioma. Hence, careful pathological assessment with appropriate tumour markers and immunohistochemistry are essential. We present a rare case of recurrence of hepatic haemangioendothelioma after 10 years post-hemihepatectomy. Surgical approaches include liver resection, liver transplantation and ablative techniques with chemotherapy and radiotherapy reserved for patients where a surgical approach is not possible. Hepatic haemangioendothelioma has an unpredictable course that is generally indolent and it is associated with a significantly better long-term survival. Consequently, it is important that these tumours are recognised and the approach to the diagnosis should be methodical. Owing to the protracted course of the disease, a prolonged duration of surveillance and an aggressive approach towards disease recurrence are essential for long-term survival.

Background Cystic lesions of the pancreas (PCLs) may be inflammatory or proliferative and making an accurate and timely pre-operative diagnosis remains a significant clinical challenge. This is principally due to the heterogeneity of the pathological processes involved. PCLs constitute an entity with diverse histology and although infrequent, the possible potential for malignant transformation of these lesions and the opportunity for curative surgery mandates that our diagnostic approaches are up to date and evidence based. In addition, improved diagnostic accuracy is crucial to prevent unnecessary surgical procedures with the inevitable associated morbidity. Methods This narrative review examines the current diagnostic benchmarks and identifies novel diagnostic techniques that warrant further consideration, a number of which are beginning to be included in routine clinical practice when these PCLs are being investigated. A computerized search was made of MEDLINE, EMBASE and PubMed using the search words 'diagnostic approaches to pancreatic cystic lesions'. All relevant articles in English language or with an English abstract were retrieved and additionally cross referenced. Conclusion The increasing accuracy of available imaging techniques together with the wider availability of endoluminal ultrasound and the development of additional novel methods to assess PCLs presents an opportunity to significantly improve the pre-operative diagnosis rate. This is essential to classify the type of PCL and hence guide the management particularly with lesions where there is a likelihood of progression to more serious pathology. We have highlighted the need for a comprehensive and standardized algorithm for the diagnosis and management of PCLs.

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.

Variants of hepatic duct anomalies are widely discussed in the literature. Duplication producing a double and/or aberrant extrahepatic bile duct is one of the rarest congenital variants that have been sparingly reported. A 71-year-old female presented with right-sided abdominal pain. Computerized tomography demonstrated an enhancing soft tissue thickening in the gastric pylorus with extension into the left lobe of the liver and invasion of the left intrahepatic bile ducts and dilatation of the left intra- and extrahepatic biliary tract. Further examination led to a diagnosis of a double common bile duct with ectopic drainage into the gastric antrum. Recognition of this rare anomaly is of great importance because of the implications in respect of concomitant pathology, the potential short- and long-term sequelae and crucially for operative planning. Failing to appreciate the extent of anomalies may result in significant complications with the attendant morbidity.

Background: Numerous techniques have been described for fashioning gastrojejunostomy (GJ) in a Roux-en-Y gastric bypass. These include hand-sewn anastomosis (HSA) and mechanical anastomosis; the latter includes circular stapled anastomosis (CSA) or manual linear stapled anastomosis (mLSA). More recently, this list also includes powered linear stapled anastomosis (pLSA). The aim of this study was to analyse if addition of power to stapling would improve the integrity of GJ anastomosis in ex vivo porcine models. Subjects and Methods: The present study included five groups – mLSA1, mLSA2, HSA, CSA, and pLSA. Sequential infusions of methylene blue-coloured saline were performed into the GJ models. Pressure readings were recorded till the point of leak denoting burst pressure (BP). Total volume (TV) and site of leak were recorded. Compliance was calculated from the equation ΔTV/ΔBP. Results: Differences in pouch and intestinal thickness were not statistically significant between the models. BPs were higher in the mechanical anastomosis groups, i.e., pLSA 21 ± 9.85 mmHg, CSA 20.33 ± 5.78 mmHg, mLSA1 18 ± 4.69 mmHg and mLSA2 11 ± 2.94 mmHg, when compared to HSA 9.67 ± 3.79 mm Hg, which was found to be statistically significant (Kruskal–Wallis test, P = 0.03). Overall, the highest BP was recorded for powered stapling followed by circular, and then, linear stapling; however, this difference was not statistically significant (P = 0.86). There was no statistically significant difference among groups with regard to compliance (Kruskal–Wallis test, P = 0.082). Conclusion: Despite the limited number of samples, mechanical anastomosis showed a statistically higher BP when compared to HSA, suggesting better anastomotic integrity. The pLSA group showed promising results with the highest BP recorded among all groups; however, this did not reach statistical significance.

The efficacy of islet transplant is compromised by a significant loss of islet mass posttransplant due to an innate inflammatory reaction. We report the use of a combination of etanercept and anakinra (ANA+ETA) to block inflammatory islet damage in 100 patients undergoing total pancreatectomy with islet autotransplant. The patients were divided into 3 groups: no treatment (control [CTL]), etanercept alone (ETA), or a combination of etanercept and anakinra (ANA+ETA). Peritransplant serum samples were analyzed for protein markers of islet damage and for inflammatory cytokines. Graft function was assessed by fasting blood glucose, basal C-peptide, secretory unit of islet transplant objects (SUITO) index, and hemoglobin A1c . Administration of both antiinflammatory drugs was well tolerated without any major adverse events. Reductions in interleukin-6, interleukin-8, and monocyte chemoattractant protein 1 were observed in patients receiving ANA+ETA compared with the CTL group, while also showing a modest improvement in islet function as assessed by basal C-peptide, glucose, hemoglobin A1c , and SUITO index but without differences in insulin dose. These results suggest that double cytokine blockade (ANA+ETA) reduces peritransplant islet damage due to nonspecific inflammation and may represent a promising strategy to improve islet engraftment, leading to better transplant outcomes.

Chronic pancreatitis (CP) is an inflammatory disease that causes progressive damage to the pancreatic parenchyma with irreversible morphological changes and fibrotic replacement of the gland. The risk factors associated with developing CP have been described as toxic (e.g., alcohol and tobacco); idiopathic (e.g., unknown); genetic, autoimmune, recurrent acute pancreatitis, and obstructive (the TIGAR-O system). Upon histological screening of the pancreata from a cohort of CP patients who had undergone pancreatectomy for the treatment of intractable pain in Leicester, UK, one sample showed a striking change in the morphological balance toward an endocrine phenotype, most notably there was evidence of substantial α cell genesis enveloping entire cross sections of ductal epithelium and the presence of α cells within the ductal lumens. This patient had previously undergone a partial pancreatectomy, had severe sclerosing CP, an exceptionally low body mass index (15.2), and diabetes at the time the pancreas was removed, and although these factors have been shown to induce tissue remodeling, such high levels of α cells was an unusual finding within our series of patients. Due to the fact that α cells have been shown to be the first endocrine cell type that emerges during islet neogenesis, future research profiling the factors that caused such marked α cell genesis may prove useful in the field of islet transplantation.

Background There is limited evidence assessing the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oesophageal adenocarcinoma, both in vitro and in vivo. We evaluated the effects of the omega-3 PUFA and oxaliplatin on OE33 and OE19 cells. Method The two oesophageal cells were treated with Omegaven® (fish oil emulsion), EPA, DHA and oxaliplatin and incubated for up to 144 h. Results The following inhibitory effects were observed on OE33 cells: EPA reduced cell growth by 39% (p = 0.001), DHA by 59% (p

Background Severe community-acquired pneumococcal pneumonia is commonly associated with bacteraemia. Although it is assumed that the bacteraemia solely derives from pneumococci entering the blood from the lungs it is unknown if other organs are important in the pathogenesis of bacteraemia. Using three models, we tested the relevance of the spleen in pneumonia-associated bacteraemia. Methods We used human spleens perfused ex vivo to explore permissiveness to bacterial replication, a non-human primate model to check for splenic involvement during pneumonia and a mouse pneumonia-bacteraemia model to demonstrate that splenic involvement correlates with invasive disease. Findings Here we present evidence that the spleen is the reservoir of bacteraemia during pneumonia. We found that in the human spleen infected with pneumococci, clusters with increasing number of bacteria were detectable within macrophages. These clusters also were detected in non-human primates. When intranasally infected mice were treated with a non-therapeutic dose of azithromycin, which had no effect on pneumonia but concentrated inside splenic macrophages, bacteria were absent from the spleen and blood and importantly mice had no signs of disease. Interpretation We conclude that the bacterial load in the spleen, and not lung, correlates with the occurrence of bacteraemia. This supports the hypothesis that the spleen, and not the lungs, is the major source of bacteria during systemic infection associated with pneumococcal pneumonia; a finding that provides a mechanistic basis for using combination therapies including macrolides in the treatment of severe community-acquired pneumococcal pneumonia. Funding Oxford University, Wolfson Foundation, MRC, NIH, NIHR, and MRC and BBSRC studentships supported the work.

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.