Intravenous omega-3 fatty acids are associated with better clinical outcome and less inflammation in patients with predicted severe acute pancreatitis: A randomised double blind controlled trial.

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).

A case of recurrent hepatic haemangioendothelioma.

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.

Retrospective Analysis of Outcomes Following Percutaneous Cholecystostomy for Acute Cholecystitis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Improved outcomes of islet autotransplant after total pancreatectomy by combined blockade of IL-1ß and TNFα.

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.

Indeterminate Pulmonary Nodules in Resected Liver Metastases from Colorectal Cancer: A Comparison of Patient Outcomes.

AIMS: Hepatic metastasectomy remains the only potentially curative treatment for colorectal liver metastases (CRLM). Some of these patients develop indeterminate pulmonary nodules (IPNs). This study aimed to compare outcomes of patients with and without IPN undergoing resection of CRLM to ascertain whether their presence is clinically significant. METHODS: Cases and controls were identified from a prospectively maintained database of CRLM resections. Patients with staging radiology demonstrating IPNs were included as cases. Controls were matched to the cases by four primary factors: age, type of resection (primary or redo), clinical risk score (CRS) and chemotherapy. RESULTS: The median disease-free survival (DFS) and overall survival (OS) for the cases were 7.0 months (95% CI 4.8-9.2) and 28.6 months (95% CI 21.2-36.0), respectively, and 12.0 months (95% CI 10.7-13.2) and 30.5 months (95% CI 19.4-41.6) for the controls. The 1-, 3- and 5-year survival rates were 92.7, 39.7 and 0.0% for the IPN group, and 92.4, 32.9 and 21.9% for those without. In total, 60.7% of IPN patients progressed to lung metastases, of which 39.3% underwent pulmonary resections. DFS was significantly shorter in the IPN group (p = 0.022), but OS was not significantly different (p = 0.421). The presence of IPN was independently associated with a shortened DFS (p = 0.027), as was a CRS of 3 or greater (p = 0.007). CONCLUSION: This study suggests that IPN does not significantly affect OS, but may predict earlier disease recurrence. IPN presence alone should not preclude radical resection but could be used to prompt more careful post-operative surveillance to detect lung metastases at a potentially operable stage.

Plasma and erythrocyte uptake of omega-3 fatty acids from an intravenous fish oil based lipid emulsion in patients with advanced oesophagogastric cancer.

BACKGROUND: It has been demonstrated that short term intravenous (IV) administration of omega-3 polyunsaturated fatty acids (PUFAs) is more effective than oral supplementation at promoting incorporation of the bioactive omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma, blood cells and tissues. The effect of repeated short term IV infusion of omega-3 PUFAs was investigated in patients with advanced oesophagogastric cancer during palliative chemotherapy. METHODS: Patients with advanced oesophagogastric cancer (n = 21) were recruited into a phase II pilot clinical trial. All patients were scheduled for an intravenous infusion of Omegaven® (fish oil supplement containing EPA and DHA) at a rate of 2 ml/kg body weight for 4 h once a week for up to six months. Blood samples were collected to assess omega-3 PUFA uptake into plasma non-esterified fatty acids (NEFAs) and phosphatidylcholine (PC) and into red blood cell (RBC) membranes. Fatty acid profiles were analysed by gas chromatography. RESULTS: Twenty patients received at least one Omegaven® treatment and were included in the analysis. Each infusion of omega-3 PUFAs resulted in increased EPA and DHA in plasma NEFAs, but there was little effect on PUFAs within plasma PC during the infusions. However, with repeated weekly infusion of omega-3 PUFAs, the EPA content of plasma PC and of RBC membranes increased. CONCLUSION: Repeated weekly omega-3 PUFA infusion is effective in enriching plasma PC and RBC membranes in EPA in patients with advanced oesophagogastric cancer receiving palliative chemotherapy. TRIAL REGISTRATION: Clinical Trials.Gov NCT01870791.

Treatment Access and Survival Amongst British Asians with Pancreatic Cancer.

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.

Potential applications of fish oils rich in omega-3 polyunsaturated fatty acids in the management of gastrointestinal cancer.

BACKGROUND & AIMS: Despite advances in chemotherapeutic agents and surgical approaches for its management, gastrointestinal cancer still accounts for 27% of new cancer cases and 35% of cancer related mortality worldwide. Omega-3 polyunsaturated fatty acids (PUFAs) specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory and anticancer activities and are used as immuno-nutrients. METHODS: A literature search was conducted to identify primary research reporting on applications of the omega-3 PUFAs in gastrointestinal cancer. RESULTS: Reported laboratory studies indicate a clear role for omega-3 PUFAs in preventing cancer development at various stages including cancer cell proliferation, survival, angiogenesis, inflammation and metastasis. In clinical settings, omega-3 PUFAs have been reported to improve the immune response, maintain lean body mass, improve quality of life and improve overall survival in patients with colorectal and pancreatic cancer. In contrast to other GI cancers, there is a strong connection between inflammation and oesophageal cancer. CONCLUSIONS: Little work has been done exploring the role for omega-3 PUFAs in oesophageal cancer prevention and management. The authors are conducting a clinical trial investigating the use of parenteral omega-3 PUFAs supplementary to the standard of care (epirubicin, oxaliplatin and capecitabine palliative chemotherapy) in patients with advanced oesophagogastric cancer as a promising new therapeutic approach.

Is Abdominal Fat Distribution Measured by Axial CT Imaging an Indicator of Complications and Mortality in Acute Pancreatitis?

BACKGROUND: Obesity is an important risk-stratifying co-morbidity for many pathological conditions. Controversy exists about its influence in outcomes after acute pancreatitis (AP). This study assessed abdominal fat distribution (subcutaneous, retroperitoneal and intra-abdominal) measured using computer tomography (CT) images and related it to outcomes in patients with AP. METHODS: The case notes of patients admitted with AP were identified from computerised records from 2008 to the 2013. Image analysis software was used to assess the individual abdominal fat distributions from CT images. RESULTS: A total of 79 patients were included. There was no relationship between fat distribution and either severity of, or mortality from, AP. Fat distribution was not found to be an independent risk factor on multivariate analysis. There was, however, a positive correlation between retroperitoneal and intra-abdominal fat with APACHE II scores, Ranson and Glasgow score and Multiple Organ Dysfunction score (MODS) on various days following admission (r = 0.421, p = 0.0008; r = 0.469, p < 0.0001; r = 0.398, p = 0.007; r = 0.336, p = 0.011, respectively). On multiple logistical regression analysis, the only variables associated with mortality were Balthazar Severity Index, MODS and EWS with a p value of <0.0001, 0.0019 and 0.0481, respectively. CONCLUSIONS: Obese patients have worse predicted outcomes as measured by the EWS, MODS and Ranson scores. Abdominal fat distribution, however, was not shown to be directly related to AP severity or mortality. The addition of fat parameters may be of use in prognostic CT severity index models, but from this data, it does not appear to be an independent risk factor of adverse outcome.

Ablation for recurrent hepatocellular carcinoma: a systematic review of clinical efficacy and prognostic factors.

BACKGROUND: Hepatocellular carcinoma (HCC) typically recurs following primary treatment. The primary objective of this systematic review was to evaluate the safety and efficacy of ablative therapies for recurrent HCC. The secondary objective was to identify any factors associated with prognosis following ablation for recurrent disease. METHODS: A systematic search of the literature published between January 2000 and December 2013 was undertaken using the PubMed, Medline and Scopus databases. Reference lists from selected studies were manually searched to ensure complete capture of any relevant data. RESULTS: A total of 19 studies were included in the review. The median age of patients undergoing ablation for recurrent HCC was 58 years (range 52-69 years) and 85 % of patients had cirrhosis (range 56-100 %). HCC recurred as a single nodule in 79 % of those treated with ablation (range 46-100 %). There were few significant complications associated with any form of ablation. Sufficient data were only available to allow analysis of survival outcomes following radiofrequency ablation (RFA). After RFA the median, 1, 3 and 5-year survivals were 84 % (73-99 %), 51 % (42-84 %) and 40 % (28-83 %), respectively. The only factor consistently associated with overall survival following ablation for recurrence was the alpha-fetoprotein (AFP) level. CONCLUSION: Comparable survival figures from previously published systematic reviews suggest that hepatic resection is the most effective treatment for recurrent HCC. However, ablation can be a safe and effective option for the majority of patients with recurrent disease who are unsuitable for surgery. Elevated levels of AFP suggest a poorer prognosis following ablation.

Serology and ultrasound for diagnosis of choledocholithiasis.

INTRODUCTION: Magnetic resonance cholangiopancreatography (MRCP) is not a routine investigation to exclude choledocholithiasis unless there is clinical or biochemical suspicion of common bile duct (CBD) stones. This study attempted to determine which radiological or serological parameters best predicted CBD stones. METHODS: All patients undergoing MRCP from 2005 to 2011 were selected. Patients with pancreatitis were excluded. Liver function tests (LFTs) at admission and prior to MRCP were recorded, as was abdominal ultrasonography and MRCP results. Parameters measured routinely on LFTs included alkaline phosphatase (ALP), alanine transaminase (ALT) and bilirubin. Receiver operating characteristic curve area analysis (area under the curve [AUC]) and chi-squared analysis were undertaken. RESULTS: Overall, 195 patients were identified, 71 of whom had CBD stones on MRCP. Raised ALP levels on admission demonstrated a correlation with CBD stones (AUC: 0.619, odds ratio [OR]: 3.16, p=0.06). At ultrasonography, a dilated CBD (OR: 3.76, p<0.001) and intrahepatic duct dilation (OR: 5.56, p<0.001) were highly significant predictors. However, only 37% of patients had a dilated CBD on ultrasonography. Ongoing elevation of LFT parameters, particularly ALP (AUC: 0.707, OR: 4.64, p<0.001) and ALT (AUC: 0.646, OR: 5.40, p<0.001), displayed a significant correlation with CBD stones. CONCLUSIONS: Ongoing (even if minor) elevations of liver function test parameters should prompt the need to exclude CBD stones even in the presence of a normal CBD diameter on ultrasonography.

Role of preoperative carbohydrate loading: a systematic review.

INTRODUCTION: Surgical stress in the presence of fasting worsens the catabolic state, causes insulin resistance and may delay recovery. Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects. A systematic review was undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance, gastric emptying, gastric acidity, patient wellbeing, immunity and nutrition following surgery. METHODS: All studies identified through PubMed until September 2011 were included. References were cross-checked to ensure capture of cited pertinent articles. RESULTS: Overall, 17 randomised controlled trials with a total of 1,445 patients who met the inclusion criteria were identified. Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient comfort following surgery, especially hunger, thirst, malaise, anxiety and nausea. No definite conclusions could be made regarding preservation of muscle mass. Following ingestion of carbohydrate drinks, no adverse events such as apparent or proven aspiration during or after surgery were reported. CONCLUSIONS: Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive influence on a wide range of perioperative markers of clinical outcome. Further studies are required to determine its cost effectiveness.

Cellular and plasma uptake of parenteral omega-3 rich lipid emulsion fatty acids in patients with advanced pancreatic cancer.

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.

The role of magnetic resonance cholangiopancreatography in the management of acute gallstone pancreatitis.

INTRODUCTION: The aim of this study was to identify whether magnetic resonance cholangiopancreatography (MRCP) can be used selectively in patients with acute gallstone pancreatitis to detect choledocholithiasis, based on liver function tests (LFTs) and ultrasonography appearance. METHODS: All patients admitted between January 2008 and January 2011 with gallstone pancreatitis (amylase >300u/l) who underwent MRCP were included in the study. LFTs and radiology reports were obtained from the respective computer systems. RESULTS: Overall, 173 patients with acute gallstone pancreatitis underwent MRCP and 30% (52/173) showed choledocholithiasis. The mean bilirubin level was significantly higher in those with choledocholithiasis (46 ±5µmol/l vs 36 ±3µmol/l, p=0.0388) although there was no significant difference in alkaline phosphatase (276 ±25iu/l vs 229 ±16iu/l, p=0.1154). However, sensitivity of abnormal bilirubin (>21µmol/l) for choledocholithiasis was only 62% and specificity was 41%. Sensitivity of abnormal alkaline phosphatase (>140iu/l) for choledocholithiasis was only 75% and specificity was 37%. There was a significant association between biliary dilatation on ultrasonography and choledocholithiasis on MRCP (p=0.0099) although the sensitivity of biliary dilatation for choledocholithiasis was only 44% and the specificity was 79%. Furthermore, there was no difference in the incidence of choledocholithiasis on MRCP for those patients with persistently deranged LFTs versus those whose LFTs returned to normal (relative risk: 1.07, 95% confidence interval: 0.61-1.89, p=1.00). Overall, 10% of patients with choledocholithiasis on MRCP had entirely normal LFTs on admission and no biliary dilatation or choledocholithiasis on ultrasonography. CONCLUSIONS: All patients with acute gallstone pancreatitis should undergo specific imaging, preferably MRCP, to exclude choledocholithiasis as LFTs and ultrasonography are inaccurate in predicting common bile duct stones.