Matthew S. Metcalfe

The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential.

Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. This review explores the evidence and the mechanisms by which omega-3 FA may act as angiogenesis inhibitors and identifies opportunities for original research trialling omega-3 FAs as anti-cancer agents in humans. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases and beta-catenin.

Case-matched comparison of long-term results of non-heart beating and heart-beating donor renal transplants.

Function and survival of non‐heart‐beating donor (NHBD) renal transplants have been shown to be comparable to those from heart‐beating donors (HBDs) up to 10 years after transplantation. However, there are few data on outcome after 10 years, particularly from uncontrolled NHBD donors.

Prediction of Mortality in Acute Pancreatitis: A Systematic Review of the Published Evidence

Objective: In this review, we focus on studies that examined such prognostic indices in relation to predicting a fatal outcome from pancreatitis. Summary Background Data: Acute pancreatitis (AP) is a common emergency, and early identification of high-risk patients can be difficult. For this reason, a plethora of different prognostic variables and scoring systems have been assessed to see if they can reliably predict the severity of pancreatitis and/or subsequent mortality. Methods: All studies that focused on AP, including retrospective series and prospective trials, were retrieved and analysed for factors that could influence mortality. Articles that analysed factors influencing the severity of the disease or the manifestation of disease-related complications were excluded. Results: 58 articles meeting the inclusion criteria were identified. Among the various factors investigated, APACHE II seemed to have the highest positive predictive value (69%). However, most prognostic variables and scores showed high negative predictive values but suboptimal values for positive predictive power. Conclusions: Despite the proliferation of scoring systems for grading AP, none are ideal for the prediction of mortality. With the exception of the APACHE II, the other scores and indexes do not have a high degree of sensitivity, specificity and predictive values.

A case-control comparison of the results of renal transplantation from heart-beating and non-heart-beating donors.

Introduction. The decline in heart-beating brainstem dead organ donors has necessitated the search for other organ sources. In the field of renal transplantation one alternative source currently available, but little used, is that of kidneys from non-heart-beating donors (NHBD). Reticence to use NHBD kidneys is in part due to concerns over the effect that warm ischemic may have subsequent graft function. Presented here are the results of the NHBD renal transplants at the Leicester transplant unit, and compared with matched heart-beating donor transplants as a case control analysis. Methods. In order to analyze any differences in graft performance between the two organ sources, the confounding effect of other variables known to influence the outcome of renal transplantation was minimized by matching NHBD and HBD transplants for the following criteria: donor age and sex, first or re-transplant, anastomosis and cold times, tissue match and PRA sensitisation. Transplant performance was assessed primarily by graft survival, the statistical evaluation of which was by log rank analysis of Kaplan-Meier curves. Results. 72 NHBD and 192 HBD transplants were performed over an eight year period. Of the 192 HBD transplants, 105 matched one or more of the NHBD by the criteria outlined above, and thus constituted the control group for comparison. There was no significant difference in overall graft survival between the two groups. The 5 year survival for the NHBD was 73% compared with 65% for HBD kidneys. When death with a functioning graft is treated as censored data, then these figures become 75% and 81% respectively, again without statistical significance. Conclusion. NHBD kidneys are a valuable additional source of organs for transplantation, with long-term survival, comparable to transplants from HBD.

Management of acute non-cirrhotic and non-malignant portal vein thrombosis: a systematic review.

BackgroundNo definitive evidence exists regarding the treatment of acute portal vein thrombosis (PVT). Treatment modalities described include conservative management, anticoagulation, thrombolysis, and thrombectomy. This review examines the impact of such treatment, its outcomes, and the complications resulting from the resultant portal hypertension.MethodsA Medline literature search was undertaken using the keywords portal vein thrombosis, anticoagulation, thrombolysis, and thrombectomy. The primary end point was portal vein recanalization. Secondary outcome measures were morbidity and the development of portal hypertension and its sequelae, including variceal bleeding. Data from articles relating to PVT in the context of cirrhosis, malignancy, or liver transplant were excluded.ResultsEarly systemic anticoagulation results in complete portal vein recanalization in 38.3% of cases and partial recanalization in 14.0% of cases. Spontaneous recanalization without treatment can only be expected in up to 16.7% of patients. Frequently this is only when associated with self-limiting underlying pathology and/or minimal thrombus extension. Thrombolysis can be associated with major complications in up to 60% of patients.ConclusionsThe natural history of acute PVT is poorly described. Spontaneous resolution of acute portal vein thrombosis is uncommon. Early anticoagulation results in a satisfactory rate of recanalization with minimal procedure-associated morbidity. Thrombolysis should be used with caution and only considered if the disease is progressive and signs of mesenteric ischemia are present. Further well-designed trials with precise outcome reporting are needed to improve our understanding of the disease.

Efficacy and safety of microwave ablation for primary and secondary liver malignancies: A systematic review

This article reviews the therapeutic efficacy and complications of microwave ablation (MWA) in the treatment of primary and secondary liver malignancies. A PubMed search using keywords ‘microwave’, ‘liver’, ‘malignancy’, ‘cancer’ and ‘tumour’ was performed to identify articles related to MWA of liver malignancies published in English from 1975 to February 2008. MWA is an effective treatment options for both primary and secondary liver malignancies with survivals comparable with those of liver resections. Local recurrences can be managed with further ablation. Small tumour size, well-differentiated tumour and a reduced number of lesions are factors associated with good prognosis. Temporary occlusion of the portal venous and hepatic arterial flow may increase the size of ablation but the safety aspect requires further validation. MWA is a minimally invasive technique that has broadened the therapeutic option for patients with conventionally unresectable liver tumours with promising survival data. Future advances in the applicator design and treatment monitoring may further improve its efficacy and widen the indications.

Hepatic microwave ablation: a review of the histological changes following thermal damage

Microwave (MW) ablation therapy is a local treatment by which tumours are destroyed by coagulation from the passage of MWs into cells. The aim of this review is to examine histological results obtained from preclinical and clinical studies. A literature search was undertaken for all studies focusing on MW therapy and in which lesions were excised for a complete histopathological examination after treatment. Two main zones were described after ablative therapy (central and transitional). Both corresponded to specific microscopic characteristics and evolved over time in a precise manner. No viable cells even up to 6 cm in diameter were demonstrated in 93% of lesions after treatment. Microwave therapy is a reliable technique under a variety of clinical situations. Future investigations are needed to compare MW with other ablative techniques to identify factors that influence the effectiveness of the various techniques and to determine specific indications.

Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy

Highlights • Curcumin + FOLFOX inhibits growth of primary cancer stem cell (CSC) spheroid models.• Curcumin + FOLFOX decreases expression of CSC markers in primary CSC spheroid models.• Curcumin enhances proapoptotic effects of chemotherapy in explant culture.• Curcumin is safe and tolerable in combination with FOLFOX chemotherapy.• Curcumin is perceived by patients as an acceptable daily adjunct to chemotherapy.

Single-incision laparoscopic cholecystectomy: a systematic review.

OBJECTIVES To compare the morbidity, pain, cosmesis, and cost-effectiveness of single-incision laparoscopic cholecystectomy (SILC) with standard laparoscopic cholecystectomy (SLC). DATA SOURCES Existing literature in MEDLINE through July 31, 2011. STUDY SELECTION We reviewed all studies identified through MEDLINE. References were cross-checked to ensure capture of cited pertinent articles. Case reports and series of less than 4 cases were excluded. DATA SYNTHESIS In total we analyzed 49 studies, including 2336 patients. Seven studies consisted of randomized trials and 11 of case-matched control series (compared with SLC). The technical aspects of SILC were not standardized. Median follow-up time was 4 weeks, although 27 studies (55.1%) reported no follow-up. The overall median complication rate was 7.37% (range, 0-28.6%), and the overall rate of biliary duct complications was 0.39%. Postoperative pain was similar or worse in SILC compared with SLC in 10 of 13 articles reporting pain outcomes (76.9%). Six articles investigating cosmesis after SILC compared outcomes with those of SLC. Three articles demonstrated significantly improved cosmesis after SILC. CONCLUSIONS The perceived benefits of SILC compared with SLC are improved cosmesis and reduced surgical trauma. No definitive evidence suggests that such improvements can be gained by SILC. Complications are more common, may be underestimated owing to the lack of sufficient follow-up, and may be associated with a shift from safe practice.

Useless and dangerous—fine needle aspiration of hepatic colorectal metastases

Fine needle aspiration cytology (FNAC) is an established tool for diagnosing liver tumours. It has recognised complications, however. Use of the procedure in abdominal tumours is fatal in 0.006 to 0.031% of cases.1 2 Most deaths occur with liver tumours and are due to haemorrhage. Another complication is that metastases can seed along biopsy needle tracts, although this has been reported to be rare, with an incidence of 0.003% to 0.07%, mostly from pancreatic tumours.1 2 More recently, much higher rates (0.4% to 5.1%) of needle tract metastases have been reported when FNAC is used in liver lesions, usually for primary liver tumours.3–7 Only 13 cases of needle tract colorectal metastases caused by FNAC in liver lesions are described in journals listed in Medline.7–13 Several authors have commented that the procedure should be avoided because of the risk of this complication. A further similar case is reported here, extending the contraindication of FNAC in hepatic tumours to include lesions for which no primary malignancy has been found. Therefore in Western populations, in which primary liver malignancy is rare, the diagnosis of apparently malignant liver lesions should centre on searching for the primary tumour, rather than on FNAC of the lesion. A 78 year old man presenting with back pain was found on computed tomography of his abdomen to have a lesion in the right lobe of his liver. FNAC of the lesion was done without referral to a surgeon, …