A. Arshad

Potential applications of fish oils rich in n -3 fatty acids in the palliative treatment of advanced pancreatic cancer

The palliative treatment of patients with advanced pancreatic cancer (APC) has undergone little advancement in the last 15 years. Novel therapies that have been investigated to extend survival have shown little benefit over existing chemotherapy regimens. Patients with APC often experience significant weight loss, which is one of the primary factors involved in declining quality of life. Recently, the ability of n-3 fatty acid rich oral preparations to attenuate or reverse tumour-related weight loss has been investigated in this patient group with encouraging results. Laboratory investigation has also yielded promising results suggesting a potential direct tumouricidal effect of n-3 fatty acids as well as the putative potentiation of existing chemotherapy regimes. The present review aims to examine the potential applications of fish oils rich in n-3 fatty acids in patients with APC, present a selection of the studies carried out to date and outline avenues of possible further clinical investigation.

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 cohorts 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 development of a multiorgan ex vivo perfused model: results with the porcine liver-kidney circuit over 24 hours.

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 organs vitality and functionality throughout the experiments.

Potential for Proteomic Approaches in Determining Efficacy Biomarkers Following Administration of Fish Oils Rich in Omega-3 Fatty Acids Application in Pancreatic Cancers

Pancreatic cancer is a disease with a significantly poor prognosis. Despite modern advances in other medical, surgical, and oncologic therapy, the outcome from pancreatic cancer has improved little over the last 40 years. To improve the management of this difficult disease, trials investigating the use of dietary and parenteral fish oils rich in omega-3 (ω-3) fatty acids, exhibiting proven anti-inflammatory and anticarcinogenic properties, have revealed favorable results in pancreatic cancers. Proteomics is the large-scale study of proteins that attempts to characterize the complete set of proteins encoded by the genome of an organism and that, with the use of sensitive mass spectrometric-based techniques, has allowed high-throughput analysis of the proteome to aid identification of putative biomarkers pertinent to given disease states. These biomarkers provide useful insight into potentially discovering new markers for early detection or elucidating the efficacy of treatment on pancreatic cancers. Here, our review identifies potential proteomic-based biomarkers in pancreatic cancer relating to apoptosis, cell proliferation, angiogenesis, and metabolic regulation in clinical studies. We also reviewed proteomic biomarkers from the administration of ω-3 fatty acids that act on similar anticarcinogenic pathways as above and reflect that proteomic studies on the effect of ω-3 fatty acids in pancreatic cancer will yield favorable results.

OP004 EVALUATION OF THE CYTOKINES RESPONSE TO OMEGA-3 FATTY ACIDS IN PATIENTS WITH SEVERE ACUTE PANCREATITIS: A RANDOMISED CONTROLLED TRIAL

Rationale: A progressive decrease of renal function has been described in patients on home parenteral nutrition (HPN) for benign intestinal failure. The occurrence of frequent and severe episodes of dehydration potentially causing chronic renal failure (CRF) on HPN, was considered an indication for intestinal transplantation (ITx ), even though ITx is the solid organ transplant at higher risk for developing CRF. We investigated the renal function before and after HPN or ITx in patients currently cared at the same Hospital. Methods: A cross-sectional and retrospective follow up study was carried out in patients meeting the following criteria: age >18 and 60 yrs, duration of treatment 6 months, living at home. Renal function was evaluated at time of enrollment (cross sectional) and was compared with that observed at time of starting HPN or ITx (retrospective follow up): serum creatinine concentration (mg/dL) and glomerular filtration rate (GFR), estimated according to the MDRD equation (ml/min/1.73m2). CRF was defined as GFR <60. Duration of follow up was from time of starting HPN or ITx to time of cross sectional. Analysis by Student’s T and X2 test. Results: Thirty-three HPN patients and 22 ITx recipients were enrolled. At starting treatment, mean creatinine was 0.82 and 0.83 (P= 0.88), mean GFR was 101 and 115 (p = 0.21), and frequency of CRF was 6% and 9% (P= 0.67), in HPN and ITx respectively. Mean duration of follow up was 101 months in HPN and 74 in ITx (p = 0.15). At time of cross sectional, creatinine was higher (P= 0.00), GFR was lower (P= 0.03), %decrease of GFR was higher (p = 0.00) and frequency of CRF was higher (p = 0.10) in ITx. The yearly decline of GFR was 2.8% in HPN and 14.5% in ITx (p = 0.02). Conclusion: The decrease of renal function and the risk of developing CRF are greater after ITx than during long-term HPN.