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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)., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: 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., Methods: 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., Results: 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)., Conclusion: 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.

Introduction: Death from sepsis in the intensive care unit (ITU) is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with ω-3 has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial., Method: A randomized control trial investigating the effects of parenteral ω-3 was carried out. Consecutive patients diagnosed with sepsis were entered into the study and randomized to receive either parenteral ω-3 or standard medical care only. The primary outcome measure was a reduction in organ dysfunction using the Sequential Organ Failure Assessment (SOFA) score as a surrogate marker. The secondary outcome measures were mortality, length of stay, mean C-reactive protein (CRP), and days free of organ dysfunction/failure., Results: Sixty patients were included in the study. The baseline demographics were matched for the two cohorts. Patients treated with parenteral ω-3 were associated with a significant reduction in new organ dysfunction (Δ-SOFA 2.2 ± 2.2 vs. 1.0 ± 1.5, P = .005 and maximum-SOFA 10.1 ± 4.2 vs. 8.1 ± 3.2, P = .041) and maximum CRP (186.7 ± 78 vs. 141.5 ± 62.6, P = .019). There was no significant reduction in the length of stay between cohorts. Patients treated with ω-3 in the strata of less severe sepsis had a significant reduction in mortality (P = .042)., Conclusion: The treatment of critically ill septic patients with parenteral ω-3 is safe. It is associated with a significant reduction in organ dysfunction. It may be associated with a reduction in mortality in patients with less severe sepsis., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Background & Aims: Omega-3 rich fatty acids (n-3FA) have powerful anti-inflammatory and anti-neoplastic properties. Previous studies have investigated plasma and cellular uptake of oral and parenteral n-3FA regimens. These have shown that n-3FA undergo rapid uptake into cells which is sustained for the length of the treatment course. The aim of this study was to investigate long-term uptake of prolonged, regular treatment courses of parenteral n-3FA which has not been previously reported., Methods: As part of a phase II single-arm trial, patients with advanced pancreatic cancer were treated with gemcitabine plus parenteral n-3FA rich lipid emulsion (up to 100 g) each week for three consecutive weeks with a subsequent rest week. This was repeated for up to six months in total for each patient. Pre-treatment serum and erythrocyte cell membrane (ECM) pellet samples were obtained each week for the entire treatment course of each patient. Post-treatment samples were obtained for the first two cycles only to assess rapid uptake. Fatty acid methyl esters (FAME) were produced and analysed using gas chromatography. FAME proportions as a total of sample lipid composition for each class were plotted and the results analysed using a linear regression coefficient model., Results: There was rapid and significant uptake of EPA and DHA FAME into plasma Non-Esterified Fatty Acids (NEFA) and EPA into ECM pellets in post-treatment samples (median increase of 1.06%, 0.65% and 0.05% respectively). There was significant reduction in n-6 fatty acid FAMEs and DHA in ECM pellets (decrease of 0.31% and 0.8% respectively- p = 0.031 for all). There was significant sustained uptake of EPA and DHA FAME into ECM pellets over the cohort's pooled treatment course with corresponding reduction in the n-6:n-3 ratio., Conclusions: Prolonged regular parenteral n-3FA administration results in rapid and sustained cellular uptake. This regimen is appropriate for therapies aimed at increasing n-3FA content of cellular membranes and reduction of the n-6:n-3 ratio., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a very poor prognosis. To date patient outcomes have not improved principally due to the limited number of patients suitable for surgical resections and the radiation and chemotherapy resistance of these tumours. In the last decade, a failure of conventional therapies has forced researchers to re-examine the environment of PDAC. The tumour environment has been demonstrated to consist of an abundance of stroma containing many cells but predominantly pancreatic stellate cells (PSCs). Recent research has focused on understanding the interaction between PSCs and PDAC cells in vitro and in vivo. It is believed that the interaction between these cells is responsible for supporting tumour growth, invasion and metastasis and creating the barrier to delivery of chemotherapeutics. Novel approaches which focus on the interactions between PDAC and PSCs which sustain the tumour microenvironment may achieve significant patient benefits. This manuscript reviews the current evidence regarding PSCs, their interaction with PDAC cells and the potential implication this may have for future therapies., Methods: A PubMed search was carried out for the terms 'pancreas cancer' OR 'pancreatic cancer', AND 'pancreatic stellate cells', NOT 'hepatic stellate cells'. All studies were screened and assessed for their eligibility and manuscripts exploring the relationship between PSCs and PDAC were included. The studies were subdivided into in vitro and in vivo groups., Results: One hundred and sixty-six manuscripts were identified and reduced to seventy-three in vitro and in vivo studies for review. The manuscripts showed that PDAC cells and PSCs interact with each other to enhance proliferation, reduce apoptosis and increase migration and invasion of cancer cells. The pathways through which they facilitate these actions provide potential targets for future novel therapies., Conclusion: There is accumulating evidence supporting the multiple roles of PSCs in establishing the tumour microenvironment and supporting the survival of PDAC. To further validate these findings there is a need for greater use of physiologically relevant models of pancreatic cancer in vitro such as three dimensional co-cultures and the use of orthotopic and genetically engineered murine (GEM) models in vivo., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Context: Complement plays a central role against infection and coordinates the activity of coagulation and fibrinolysis. In this report we present a patient that underwent total pancreatectomy experienced sepsis, coagulopathy and bleeding that endangered the postoperative course., Case Report: A sixty-five-year-old woman underwent total pancreatectomy for intractable pain without islet transplant, this patient was diagnosed as AP and MBL deficient from a blood test performed preoperatively. On the postoperative course she experienced severe haemorrhages and sepsis for 3 weeks postoperatively. An analysis of serial perioperative serum samples conducted which showed further depletion of the alternate and MBL complement pathway without restoration to baseline levels., Conclusion: This is the first reported case of alternative and mannose-binding lectin pathways depletion associated with major postoperative bleeding and sepsis following pancreatic surgery. Future research should examine the relationship between complement pathways activity and postoperative complications in order to possibly introduce it as a preoperative screening and possible replacement therapy prior to any major surgical intervention.

Purpose: This study compared 2 methods of palliative stent placement, 6-monthly interval stent changes (RS), or a single-stent policy with no planned stent change (SS)., Results: A total of 460 patients were identified. There were no significant differences in the proportion of patients requiring unplanned stent changes in the RS or SS group (22.3% vs. 22.8%). Median survival was not significantly different between the RS and SS groups, for both benign disease (96 vs. 92 mo) and malignant disease (9 vs. 6 mo). Patients undergoing unplanned stent changes had the poorest survival and the highest stent change-related complication rate. Patients with a blocked stent episode were more likely to develop further problems with stent patency, within a median interval of 2.5 months., Conclusions: In carefully selected patients, a single stent may be adequate with no planned change of stent. There appears to be a clearly defined subgroup of patients who have recurrent problems with stent patency; these should have their interval exchange brought forward on a 3-monthly basis, or a self-expanding metal stent should be used.

Rationale, Aims and Objectives: Chronic pancreatitis (CP) is a progressive inflammatory disorder with pain being the most frequent symptom. It is associated with loss of function, pancreatogenic diabetes and digestive enzyme deficiency. The impact of local complications and loss of pancreatic function results in unknown and unreported costs. This study attempts to identify both the direct and indirect costs associated with CP., Methods: A MEDLINE literature review was performed for all relevant articles relating to any aspect of direct and indirect costs as a result of CP., Results: In the UK, there are 12,000 admissions per annum of patients with CP at an estimated cost of £55.8 million. The costs for loss of pancreatic function are estimated at £45-90 million and $75.1 million for endocrine and exocrine function, respectively. Chronic pain contributes $638 million per year in costs. The protracted course of CP and paucity of monetary data make quantifying direct and indirect costs difficult. An estimate of direct and indirect costs is at £285.3 million per year. This equates to £79,000 per person per year., Conclusions: Patients with CP consume a disproportionately high volume of resources., (© 2014 John Wiley & Sons, Ltd.)

The use of ex vivo perfused models can mimic the physiological conditions of the liver for short periods, but to maintain normal homeostasis for an extended perfusion period is challenging. We have added the kidney to our previous ex vivo perfused liver experiment model to reproduce a more accurate physiological state for prolonged experiments without using live animals. Five intact livers and kidneys were retrieved post-mortem from sacrificed pigs on different days and perfused for a minimum of 6 hr. Hourly arterial blood gases were obtained to analyze pH, lactate, glucose and renal parameters. The primary endpoint was to investigate the effect of adding one kidney to the model on the acid base balance, glucose, and electrolyte levels. The result of this liver-kidney experiment was compared to the results of five previous liver only perfusion models. In summary, with the addition of one kidney to the ex vivo liver circuit, hyperglycemia and metabolic acidosis were improved. In addition this model reproduces the physiological and metabolic responses of the liver sufficiently accurately to obviate the need for the use of live animals. The ex vivo liver-kidney perfusion model can be used as an alternative method in organ specific studies. It provides a disconnection from numerous systemic influences and allows specific and accurate adjustments of arterial and venous pressures and flow.

Introduction: There are plausible biological mechanisms for how statins may prevent pancreatic cancer, although the evidence from epidemiological studies in the general population is conflicting. This study aims to clarify whether statins exert their effects in specific sub-groups, namely, gender, smoking status and diabetes., Methods: A matched case-control study was conducted in patients diagnosed with pancreatic cancer, and a group of dermatology patients of similar ages and gender, diagnosed with basal cell carcinoma. Participants' medical records were reviewed for information on statin use prior to diagnosis. Odds ratios and 95 % CIs for the development of pancreatic cancer were estimated using conditional logistic regression. Subgroup analysis was performed in men, women, smokers and those with type 2 diabetes., Results: Two hundred fifty-two cases (median age 71 years, range 48-73 years, 51 % women) and 504 controls were identified, of which 23 % of cases were regular statin users versus 21 % of controls. In the general study population there was no association between pancreatic cancer and regular statin use (OR 0.82, 95 % CI 0.53-1.23, p = 0.33). However, in male smokers, regular statin use was associated with significantly reduced odds of pancreatic cancer compared to male smokers not prescribed a statin (OR 0.11, 95 % CI 0.01-0.96, p = 0.05). In patients with type 2 diabetes statins use was not associated with reduced odds (OR 0.92, 95 % CI 0.35-2.45, p = 0.80), with no gender effects., Conclusions: In male smokers, statins may reduce the odds of pancreatic cancer. Statin use should be measured in aetiological studies of pancreatic cancer but analysed in specific sub-groups. Future work should investigate statins as chemopreventative agents in this high risk sub-group.

Aim: National Institute for Clinical Excellence guidelines suggest that patients who have undergone potentially curative treatment for colorectal cancer (CRC) should be followed up for 3 years. The aim of this study was to investigate whether the time to presentation with colorectal liver metastases (CRLM) has changed over time. This information, which is currently unknown, may inform future decisions regarding follow-up., Methods: Patients presenting with metachronous isolated liver metastases between 1997 and 2011 were included. Timings of presentation with CRLM, rates of liver resection, survival data and factors associated with delayed presentation were investigated., Results: 269 patients were included in the study. Those having their primary CRC resection between 1997 and 2007 presented earlier with liver metastases over time (r = -0.33, 95% CI -0.45 to -0.20). However, 26% of patients who developed CRLM did so beyond 3 years. There was no significant difference in rates of liver resections for those presenting within, or beyond, 3 years (p = 0.21). There was no significant difference in survival for those presenting with resectable CRLM within, or beyond, 3 years (Exp(b) = 0.60, 95% CI 0.28-1.28). No factors associated with late presentation were identified., Conclusions: These results suggest that CRC follow-up should be extended to 5 years. Follow-up interventions should be more frequent in the early stages reflecting the trend towards earlier presentation with CRLM. The economic implications of extending follow-up compare favourably to other NHS funded initiatives., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: Accurate preoperative radiological staging of hilar cholangiocarcinoma remains difficult, and a number of patients are found to have irresectable advanced tumours or occult metastases at exploration. Staging laparoscopy can improve the detection of irresectable disease, avoiding unnecessary laparotomy. This study examines the role of staging laparoscopy in hilar cholangiocarcinoma, with a focus on yield over different time periods and identification of preoperative factors increasing the risk of irresectable disease., Methods: Retrospective case note review of all patients undergoing staging laparoscopy for radiologically resectable hilar cholangiocarcinoma, identified from the hepatobiliary multidisciplinary team database, was performed., Results: One hundred consecutive patients underwent staging laparoscopy between 1998 and 2011. Of these, 34 patients were found to be irresectable due to metastatic disease, and 11, due to extensive local disease. Fifty patients proceeded to exploratory laparotomy following staging laparoscopy, and 36 % (18/50) of whom were found to have irresectable disease: 12 patients due to advanced local disease and 6 patients due to metastases. The overall yield of laparoscopy was 45 %, and the accuracy was 71 %. There was no significant difference in age, preoperative bilirubin, neutrophil/lymphocyte ratio, Ca19-9 levels or T stage between patients with resectable disease and with irresectable disease on laparoscopy. There was also no change in the yield of laparoscopy over time, despite advances in radiological imaging., Conclusion: In this series, staging laparoscopy avoided unnecessary laparotomy in 45 % of patients with radiologically resectable hilar cholangiocarcinoma. No factor was able to predict positive yield, and therefore, all patients with potentially resectable hilar cholangiocarcinoma should undergo staging laparoscopy.

Background: Pancreatic cystic lesions are an increasing problem and investigation of these cysts can be fraught with difficulty. There is currently no gold standard for diagnosis or surveillance. This review was undertaken to determine the present reliability of the characterisation, assessment of malignant potential and diagnosis of pancreatic cystic lesions using available imaging modalities., Methods: A Medline search using the terms 'pancreatic', 'pancreas', 'cyst', 'cystic', 'lesions', 'imaging', 'PET'. 'CT', 'MRI' and 'EUS' was performed. Publications were screened to include studies examining the performance of CT, MRI, MRCP, EUS and 18-FDG PET in the determination of benign or malignant cysts, cyst morphology and specific diagnoses., Results: Nineteen studies were identified that met the inclusion criteria. 18-FDG PET had a sensitivity and specificity of 57.0-94.0% and 65.0-97.0% and an accuracy of 94% in determining benign versus malignant cysts. CT had a sensitivity and specificity of 36.3-71.4% and 63.9-100% in determining benign disease but had an accuracy of making a specific diagnosis of 39.0-44.7%. MRI had a sensitivity and specificity of 91.4-100.0% and 89.7% in assessing main pancreatic duct communication., Conclusion: CT is a good quality initial investigation to be used in conjunction with clinical data. MRCP can add useful information regarding MPD communication but should be used judiciously. PET may have a role in equivocal cases to determine malignancy. Further examination of CT-PET in this patient group is warranted., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Introduction: Mediators derived from the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid oxidation have been shown to have tumour promoting effects in experimental models, while n-3 PUFAs are thought to be protective. Here we report fatty acid concentrations in hepatic colorectal metastases compared to liver tissue without tumour in humans., Methods: Twenty patients with colorectal liver metastasis were randomized to receive a 72 h infusion of parenteral nutrition with or without n-3 PUFAs. Histological samples from liver metastases and liver tissue without tumour were obtained from 15 patients at the time of their subsequent liver resection (mean 8 days (range 4-12) post-infusion) and the fatty acid composition determined by gas chromatography., Results: There were no significant differences in fatty acid composition between the two intervention groups. When data from all patients were combined, liver tissue without tumour had a higher content of both n-3 and n-6 PUFAs and a lower content of oleic acid and total n-9 fatty acids compared with tumour tissue (p<0.0001, 0.0002,<0.0001 and <0.0001, respectively). The n-6/n-3 PUFA ratio was found to be higher in tumour tissue than tissue without tumour (p<0.0001)., Conclusions: Hepatic colorectal adenocarcinoma metastases have a higher content of n-9 fatty acids and a lower content of n-6 and n-3 PUFAs than liver tissue without tumour., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Pancreatic cancer is a rapidly progressive disease which is often only amenable to palliative treatment. Few patients respond to palliative chemotherapy, so surrogate markers indicating which patients are likely to respond to treatment are required. There is a well-established link between pro-inflammatory circulating cytokines and growth factors (CAF), and the development of neoplasia. Agents that may modulate these factors are of interest in developing potential novel therapeutic applications., Methods: As part of a single-arm phase II trial in patients with advanced pancreatic cancer (APC) treated with gemcitabine and intravenous (i.v.) omega-3 rich lipid emulsion (n-3FA), serum samples were analysed for 14 CAF using a multiplex cytokine array. Baseline serum concentrations were correlated with overall (OS) and progression-free survival (PFS), and changes in concentration correlated with time and outcomes for CAF responders were analysed., Results: Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) concentrations reduced significantly with treatment over time. Low baseline interleukin (IL)-6 and -8 were correlated with improved OS. PDGF responders showed a tendency towards improved OS and FGF responders a significantly improved PFS., Discussion: Treatment with gemcitabine plus i.v. n-3FA may reduce concentrations of CAF which may be associated with an improved outcome. Baseline IL-6 and -8 may be surrogate markers for outcome in patients with APC treated with this regimen., (© 2012 International Hepato-Pancreato-Biliary Association.)

Ex vivo perfused porcine livers have been used for temporary support during acute liver failure. The aim of this study was to assess both the histological changes and temporal pattern of the changes that occur during extracorporeal liver perfusions and to correlate these with factors that may influence them. Five porcine livers were harvested, preserved in cold ice and reperfused for 6 h in an extracorporeal circuit using autologous normothermic blood. Tissue biopsies were collected hourly. The Ishak score was used to quantify hepatic necrosis, and immunohistochemistry was used to evaluate apoptosis and regeneration. Liver weight, perfusion parameters, arterial blood gases and blood samples were also collected. The Ishak score peaked immediately before and 4 h after the start of reperfusion. Scattered necrosis, microvesicular steatotic vacuolization, sinusoidal dilatation and red cell extravasation were present. Anion gap acidosis was associated with the Ishak score. An inverse correlation was present between liver regeneration and necrosis, and between liver weight and regeneration. No changes were observed for apoptosis. Among the inflammatory cytokines evaluated, interleukin-6 and -8 levels increased significantly during the perfusions. Hepatic necrosis was always present during the extracorporeal perfusions, followed a definite pattern and was inversely correlated with regeneration. Apoptosis did not increase over baseline levels. The meaning of these findings and their correlation with clinical outcomes during acute hepatic failures deserve further investigation.

We already developed an ex vivo liver-kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid-base parameters. In the combined liver-kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19-23 h of perfusions) than the kidney (9-13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organ's vitality and functionality throughout the experiments., (© 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Preoperative biliary drainage (PBD) for distal bile duct obstruction may increase post-operative complications. This study examined the effect of PBD on positive bile culture (PBC) rates and complications after biliary bypass or pancreaticoduodenectomy. Bilirubin levels in the non-PBD cohort were also analysed to determine the impact on outcome., Methods: A retrospective case-note analysis from 2005 to the present day was undertaken. Statistical analysis was undertaken using Students's t-test, chi-squared test, receiver operator characteristics, correlation coefficient and relative risk ratios., Results: A total of 422 patients were identified undergoing pancreaticoduodenectomy or biliary bypass for either benign or malignant distal biliary obstruction. One hundred ninety-six patients had complete data regarding PBD and bile cultures. PBD resulted in a significantly higher relative risk of both infectious complications and positive bile cultures. Overall complication rate was greater in patients undergoing PBD. The major complication rate was equivalent between the two groups. Bilirubin levels in the non-PBD cohort did not correlate or predict length of stay, high-dependency stay, and mortality or complication rate., Conclusion: There seems to be little value in PBD for patients with distal biliary obstruction other than to defer definitive surgery to a non-emergency setting. For most hepato-pancreato-biliary units, avoidance of PBD will prove logistically difficult., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Objectives: Chronic pancreatitis (CP) results in an extremely poor quality of life and substantially increases health care utilization. Few data exist regarding the cost-effectiveness of surgical treatment for CP., Methods: This article examined the cost-effectiveness of total pancreatectomy (TP) with islet cell autotransplantation (IAT) for CP., Results: Sixty patients undergoing TP + IAT and 37 patients undergoing TP were identified. Surgery resulted in significant reduction in opiate use, frequency of hospital admissions, and length of stay as well as visual analog scale scores for pain. Total pancreatectomy + IAT resulted in longer survival than TP alone (16.6 vs 12.9 years); 21.6% of patients with TP + IAT were insulin-independent, and those requiring insulin have reduced daily requirements compared with those having TP alone (22 vs 35 IU). The cost of TP + IAT with attendant admission and analgesia costs over the 16-year survival period was £110,445 compared with £101,608 estimated 16-year costs if no TP + IAT was undertaken., Conclusions: Total pancreatectomy + IAT is effective in improving pain and reducing analgesia. Islet cell transplantation offers the chance of insulin independence and results in lower insulin requirements, as well as conferring a survival advantage when compared with TP alone. Total pancreatectomy + IAT is cost-neutral when compared with nonsurgical or segmental surgical therapy.

Omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid, and docosahexaenoic acid have been shown to have multiple beneficial antitumour actions that affect the essential alterations that dictate malignant growth. In this review we explore the putative mechanisms of action of omega-3 polyunsaturated fatty acid in cancer protection in relation to self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion, and how these will hopefully translate from bench to bedside.

Background: Histological abnormalities in the non-tumour-bearing liver (NTBL) may influence outcome following hepatectomy. Effects will be most pertinent following right trisectionectomy but have yet to be specifically examined in this context. This study aimed to investigate the influence of perioperative factors, including NTBL histology, on outcome following right trisectionectomy., Methods: Pathological review of the NTBL of 103 consecutive patients undergoing right trisectionectomy between January 2003 and December 2009 was performed using established criteria for steatosis, non-alcoholic steatohepatitis (NASH), sinusoidal injury (SI), fibrosis and cholestasis. Perioperative and pathological factors were correlated with post-operative outcome (morbidity, major morbidity, hepatic insufficiency and mortality)., Results: Morbidity, hepatic insufficiency and major morbidity occurred in 37.9 %, 14.6 % and 22.3 % of cases, respectively. Ninety-day mortality rate was 5.8 %. NASH (P = 0.007) and perioperative blood transfusion (P = 0.001) were independently associated with hepatic insufficiency following trisectionectomy. NASH (P = 0.028), perioperative transfusion (P = 0.016), diabetes mellitus (P = 0.047) and coronary artery disease (P = 0.036) were independently associated with major morbidity. Steatosis, SI, fibrosis and cholestasis in the NTBL demonstrated no association with any adverse outcome., Conclusion: NASH, but not steatosis or SI, is associated with adverse outcome following right trisectionectomy and caution must be exerted when considering major hepatectomy in patients with NASH.

Electrolytic ablation (EA) destroys the liver by releasing toxic radicles and producing modifications in the local pH without increasing the tissue temperature. We assessed the histological changes produced by EA using an ex-vivo perfused model. Five porcine livers were harvested, preserved in ice and reperfused for six hours in an extracorporeal circuit using autologous normothermic blood. One hour after reperfusion EA was performed and liver biopsies collected at the end of the experiments. The main necrotic zone consisted of coagulative necrosis, sinusoidal dilatation and haemorrhage with an unusual morphological pattern. The coagulative necrosis and haemorrhage affected mainly the peripheral area of the lobule with relative sparing of the area surrounding the centrilobular vein. Contrasting with this sinusoidal dilatation appeared to be more prominent in the centrilobular area. EA produces patterns of tissue destruction that have not been observed with the more commonly used thermal techniques. Further studies should obtain more information about the influence of adjacent biliary and vascular structures so that appropriate clinical trials can be designed.

Background: The ex vivo porcine liver perfused model isolates the organ from extrinsic regulatory mechanisms, facilitating an improved understanding of the organ physiology and reaction to various conditions. We have assessed the influence of the addition of a porcine kidney to the circuit., Methods: Eight livers were harvested and perfused for 6 hours. In 5 additional experiments a kidney also was connected in parallel. Hourly arterial blood gases were collected to analyze glucose, acid base, and renal parameters. The primary end point was an evaluation of the influence of the kidney on glucose, pH, and electrolyte levels., Results: In the combined porcine liver-kidney circuit all the parameters significantly improved compared with the liver circuit alone. This was particularly evident for glucose values because normoglycemia was reached by the end of the perfusion, and for pH and electrolyte values that were maintained at initial levels., Conclusions: The addition of a porcine kidney to the perfusion circuit improves the biochemical milieu. This might produce more consistent and reliable results, particularly during studies requiring a steady-state environment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The addition of a kidney to the ex vivo liver perfused model may facilitate the circuit homeostatic balance of important biochemical parameters (i.e. pH changes, urea and creatinine, or glucose levels) but might also increase the inflammatory reaction produced. In this study, we compared the production of various cytokines between liver-kidney and liver-alone circuits. Seven livers were harvested from female pigs and perfused for 6 h. In five additional experiments, a kidney was also harvested and connected in parallel. Blood samples for interleukins (IL) 1, 2, 4, 6, 8, 10, and 12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were collected before perfusion and at hours 1, 2, 4 and 6 postperfusion. In the combined liver-kidney circuit, a significant increase was present only for IL-6 and IL-8, but this did not differ significantly from those recorded in the liver-alone circuit. All other cytokines were not modified from baseline levels. The addition of a kidney to the perfusion circuit does not stimulate a greater inflammatory reaction than that of the liver alone and therefore further confirms the safety of the experimental setups in view of more delicate experiments requiring strict homeostatic conditions.

Objectives: The role of laparoscopy in staging periampullary malignancies is to detect small-volume metastatic disease not visible on preoperative imaging. Owing to improvements in preoperative imaging, some centers no longer undertake routine laparoscopic staging, whereas others still find it a useful pre-exploration tool., Methods: This study investigated the diagnostic yield of staging laparoscopies in 137 consecutive potentially resectable patients with periampullary malignancies. Serology on presentation, tumor size on computed tomography and proinflammatory markers such as C-reactive protein, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and Glasgow Prognostic Score were also examined to see if they were able to identify patients more likely to benefit from staging laparoscopy., Results: Laparoscopy identified occult disease in 16.1% of the patients. Only tumor diameter on cross-sectional imaging was related to an increase in diagnostic yield on staging laparoscopy. Area-under-curve values for tumor size and occult disease at laparoscopy were 0.8, with P = 0.0001., Conclusion: Staging laparoscopy is a useful adjunct to computed tomography in staging periampullary cancers. Tumor size (especially >45 mm) is the only preoperative marker predictive of unexpected occult disease and may be used to select high-risk patients for laparoscopic staging.

Introduction: Differentiating between chronic pancreatitis and pancreatic adenocarcinoma can be difficult due to considerable overlap in disease presentation and radiological signs and the frequent co-existence of the two conditions. In this situation, surgeons may have to proceed to "blind" pancreaticoduodenectomy or attempt to confirm malignancy intraoperatively with frozen section (FS) histology., Methods: This study attempted to ascertain the false-negative and false-positive rates of undertaking pancreaticoduodenectomies (PD) based on clinical suspicion (CS) or after intraoperative confirmation of malignancy using FS histology., Results: Of patients, 13.6% (nine out of 66) underwent a benign PD in the CS group; 6.7% of patients had a missed malignancy in the FS group (n = 62), but intraoperative histology prevented PD in 35% of patients with benign disease in the FS group. Specificity and sensitivity of intraoperative FS in detecting malignancy was 100% and 89.7%, respectively. Sensitivity of clinical assessment in detecting malignancy was 86.4%., Conclusions: In experienced hands, intraoperative confirmation of malignancy is effective and will avoid resection in patients with benign disease. However, for many surgeons the chance of missing a small tumour with a false-negative biopsy will be unacceptable and they would prefer to undertake a "blind" resection and accept the mortality risk of pancreaticoduodenectomy for benign disease.

Background: This review examines histological modifications obtained after liver radiofrequency ablation (RFA)., Methods: A literature search has been undertaken for all pre-clinical and clinical studies involving RFA and in which ablation zones have been excised for a complete histological examination., Results: Two main histological areas are present, a central zone of coagulative necrosis and a peripheral rim of congestion and extravasation. Both corresponded to specific microscopic characteristics that evolved over time and that are influenced by the proximity of patent vessels and the liver perfusion status. Viable cells are not present in the central zone but have been described in the ischemic peripheral rim where they survive the ischemia and inflammation process. These correspond in clinical studies to residual viable tumor cells that lead to failure of the procedure., Conclusions: Histological changes following RFA are complex and interactions take place at both a cellular and tissue level. Changes in the peripheral zone must be considered in future studies in order to extend the volume of reliable tumor destruction and increase the effectiveness of the procedure., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Variations in the porcine hepatic vasculature may contribute to the outcome of experiments based on liver perfusion models. We studied the hepatic artery (HA), variations of its branches, and the correlation with the resultant perfusion., Materials and Methods: Nineteen animals were used. After 6 h of perfusion, dissection of the HA and its branches was conducted up to the insertion in the liver parenchyma. Data about the macroscopic appearance of lobes and the pattern of branching were recorded., Results: In all cases, the HA bifurcated into two constant branches, one for the LL/LM lobes (further divided in two vessels for each lobe) and one for the RM lobe. Five main patterns were identified involving vessels for the RL and the CL lobes. Two variations produced complete and uniform perfusion of the entire liver in all cases, while in the remaining cases, only part of them were completely perfused., Conclusions: Some variants of the porcine HA and its branches are associated with the risk of incomplete perfusion if the perfusion cannula placement does not take the individual hepatic arterial anatomy into account. Understanding of the hepatic arteries branching patterns is essential when ex vivo perfusion models are being established., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Electrolytic ablation (EA) is a treatment that destroys tissues through electrochemical changes in the local microenvironment. This review examined studies using EA for the treatment of liver and pancreatic tumours, in order to define the characteristics that could endow the technique with specific advantages compared with other ablative modalities., Methods: Literature search of all studies focusing on liver and pancreas EA., Results: A specific advantage of EA is its safety even when conducted close to major vessels, while a disadvantage is the longer ablation times compared to more frequently employed techniques. Bimodal electric tissue ablation modality combines radiofrequency with EA and produced significant larger ablation zones compared to EA or radiofrequency alone, reducing the time required for ablation. Pancreatic EA has been investigated in experimental studies that confirmed similar advantages to those found with liver ablation, but has never been evaluated on patients. Furthermore, few clinical studies examined the results of liver EA in the short-term but there is no appropriate follow-up to confirm any survival advantage., Conclusions: EA is a safe technique with the potential to treat lesions close to major vessels. Specific clinical studies are required to confirm the technique's safety and eventually demonstrate a survival advantage., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

Background: Serological proinflammatory markers such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been associated with reduced survival for many different types of cancer. This study determined the prognostic value of the preoperative value of these markers in patients with resectable pancreatic adenocarcinoma., Methods: Consecutive patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma were entered into our database from 2001 to the present day. CRP, NLR, and PLR at the time of presentation were recorded as well as overall and disease-free survival., Results: Seventy-four patients were identified. Overall median survival was 35.0 months and median disease-free survival was 27.0 months. Follow-up ranged from 1 to 125.8 months. Preoperative NLR was significantly greater in those patients who developed recurrence in the follow-up period (4.5 vs. 3.1). CRP and PLR were not found to differ significantly between the two groups. Kaplan-Meier survival analysis of patients with NLR > 5 demonstrated a disease-free survival of 12 months compared with 52 months for those patients with NLR < 5 (p < 0.001)., Conclusion: Preoperative NLR offers important prognostic information regarding disease-free survival following curative resection of pancreatic ductal adenocarcinoma.

Background: Recently randomized controlled trials have been advocated to compare radiofrequency ablation (RFA) and hepatic resection (HR) in resectable tumours and determine whether differences in observed survivals result from the heterogeneity in previous studies between RFA (treating unresectable lesions) and HR (treating lesions deemed resectable). We reviewed the literature that directly compares the treatments and employed an evidence-based approach to examine the data., Materials and Methods: All studies comparing RFA and HR were included. Primary outcomes were the overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. A subgroup analysis was conducted for solitary or small tumors (<4 cm for colorectal metastases (CRM) or <5 cm for hepatocellular carcinoma (HCC))., Results: Most studies were retrospective. For CRM, HR was markedly superior to RFA in respect of 3- and 5-year OS as well as 5-year DFS including tumours smaller than 4 cm and solitary lesions. For HCC, HR was markedly superior to RFA for 3- and 5-year OS as well as 3-year DFS, and produced a better OS at 3 years for solitary lesions and DFS at 3 years for small tumours., Conclusions: Multiple factors determine outcomes following treatment of liver tumours. Small or solitary lesions seem the most appropriate ones to study as this reduces the number of confounding variables, but even in these cases HR confers a better OS and DFS than RFA for both CRM and HCC. If our data are confirmed it will be important to examine other factors influencing the response.

Introduction: Laparoscopic splenectomy has emerged as a safe and effective treatment for a variety of haematological conditions. The objective was to review the results from a large personal series from the perspective of outcomes according to operative time, conversion to open operation, complications and mortality. The application of laparoscopic splenectomy to cases of splenomegaly without hand assistance is examined., Patients and Methods: A retrospective review of 140 patients undergoing laparoscopic splenectomy at a single university hospital by one surgeon during 1994-2006. Case notes were reviewed and data collected on operative time, conversion to open procedure, morbidity and mortality. Particular reference was made towards the results of cases of splenomegaly., Results: In total 140 laparoscopic splenectomies were performed with a complication rate of 15% and no mortality. The median operative time was 100 min and conversion to open procedure was necessary in 2.1%. Conversion for cases of splenomegaly was only 5.7%. The median hospital stay was 3 days., Conclusions: Laparoscopic splenectomy is a safe procedure with acceptable morbidity. A laparoscopic approach for splenomegaly is feasible.

Background: The inflammatory response following hepatic ablation depends on different factors including the method used, the duration and intensity of the treatment and the presence or absence of ischemia. Debate continues about the use of different modalities and whether some aspects of the response may be advantageous by releasing immunological active substances. Little data have been published concerning the cytokine response elicited by hepatic electrolytic ablation (EA). Study of an ex vivo liver model could allow for the evaluation of this response without the influence of confounding systemic factors., Methods: Livers explanted from 11 pigs were perfused extracorporeally with normothermic autologous blood. Four of them underwent EA after 1 h of reperfusion. Serum samples were obtained up to 6 h after the reperfusion and assayed for IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha., Results: Significant changes in the control group were observed for IL-6 after the second hour and IL-8 after the first hour compared with baseline levels (P < 0.001). In the EA group, IL-6 and IL-12 were raised after the second hour and IL-8 and IL-10 after the first hour (P < 0.001). The comparison between groups showed significant differences for IL-2, IL-4 (decreased in the EA group compared with controls), IL-10 and TNF-alpha (EA group increased compared with controls; P < 0.001)., Conclusions: The ex vivo perfused liver model demonstrated changes in levels of IL-2, IL-4, IL-10 and TNF-alpha following hepatic EA.

Background: The liver has a complex hormonal and nervous control mechanism leading to difficulty in the interpretations of its responses to chronic hypoxia. Theoretically an ex vivo perfused model of the liver should, by dissociating the organ from the extrinsic regulatory mechanisms, allow a better and unequivocal analysis of changes obtained., Materials and Methods: Twelve livers were harvested from female pigs and perfused for 6 h. Hypoxia was produced by means of isovolemic hemodilution with hemoglobin and hematocrit reduced to 40% of the baseline value. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. Every hour, physiological parameters (arterial/portal venous pressures and flows) were measured and blood samples were collected for the analysis of hemoglobin, red blood cells, hematocrit, lactate, glucose, albumin, alanine aminotransferase, alkaline phosphatase, and total bilirubin, arterial and venous blood gases. The arterio-venous oxygen and carbon dioxide differences, and the hepatic metabolic rate for oxygen, were also calculated. Primary endpoint of the study was the glucose response of the liver to acute hypoxia. Secondary endpoints were eventual changes of markers for hepatic viability and functionality., Results: Most parameters showed significant variability during the first h of perfusion but subsequently normalized and remained stable at baseline values for the following 5 h. A strong and significant hyperglycemic response was present throughout the experiment (P < 0.001). Lactate rose steadily throughout the study period and after 6 h of perfusion there was a significant deviation from initial values (P < 0.05). Albumin did not change significantly throughout the study although a trend towards decreasing values was observed (Friedman test, P = NS). After an initial rise in levels of alanine transaminase and alkaline phosphatase following perfusion (P < 0.01), values remained constant without any further increase., Conclusions: Following reperfusion in an ex vivo model, the liver reacts to low oxygen concentrations mobilizing glycogen deposits. This mechanism depends on an intrinsic sensibility of hepatocytes to hypoxia, as demonstrated by the ex vivo liver perfusion. These findings improve our knowledge in organ preservation for liver transplantation., (Copyright 2010 Elsevier Inc. All rights reserved.)

Pancreatic surgery is still associated with a relatively high morbidity and mortality compared with other specialties. This is a result of the complex nature of the organ, the difficult access as a result of the retroperitoneal position and the number of technically challenging anastomoses required. Nevertheless, the past two decades have witnessed a steady improvement in morbidity and a decrease in mortality achieved through alterations of technique (particularly relating to the pancreatic anastomoses) together with hormonal manipulation to decrease pancreatic secretions. Recently minimally invasive pancreatic surgery has been attempted by several centres around the world which has stimulated considerable interest in this approach. The majority of the cases attempted have been distal pancreatectomies, because of the more straightforward nature of the resection and the lack of a pancreatic ductal anastomosis, but more recently reports of laparoscopic pancreaticoduodenectomy have started to appear. The reports of the series to date have been difficult to interpret and although the results are claimed to be equivalent or better than those associated with a traditional approach a careful examination of the literature and comparison with the best results previously reported does not presently support this. In the present review we examined all the reports of pancreatic procedures performed laparoscopically and compared the results with those previously achieved at open surgery.

Ablative techniques may provide an alternative to resection in treating awkwardly placed hepatic malignancy adjacent to major vascular and biliary structures. The heat-sink effect may reduce efficacy adjacent to major vascular structures. Vascular occlusion improves efficacy but is associated with increased vascular and biliary complications. The safety and efficacy of ablation in these situations remain to be defined. Further studies comparing both safety and efficacy are needed.