A. Eltweri

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

BACKGROUND & AIMSnDespite 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.nnnMETHODSnA literature search was conducted to identify primary research reporting on applications of the omega-3 PUFAs in gastrointestinal cancer.nnnRESULTSnReported 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.nnnCONCLUSIONSnLittle 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.

The “kidney–liver” multiorgan ex vivo perfused model improves the circuit’s biochemical milieu during perfusion compared to the “liver–kidney” counterpart

The multiorgan ex vivo perfused liver–kidney model allows studying the hepatic pathophysiology and purifying waste products. We tested if the addition of the kidney first followed by the liver (KL circuit) produces better results compared to the classic liver-first approach (LK). Intact livers and kidneys were obtained post mortem from ten female domestic white pigs, five experiments were conducted with the KL circuit and five with the LK. Bile, urine production, arterial blood gases, glucose, renal and liver tests were collected hourly during the perfusions. The KL circuit had values more close to physiological ranges, more stable over time and showed less variability compared to the LK circuit for urine production, glucose, PH, anion gap, lactate, urea, sodium, potassium and Alanine Transaminase (ANOVA test for repeated measures pxa0<xa00.05). The KL circuit produced a more physiological and reliable biochemical milieu.

Steps for the Autologous Ex vivo Perfused Porcine Liver-kidney Experiment

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.

PWE-169 Treatment of oesophageal cell lines with docosahexaenoic fatty acid (DHA) and oxaliplatin: effects on proliferation, expression of vascular endothelial growth factor and IL-6

Introduction Oesophageal cancer is a very aggressive disease, and despite advances in cancer treatment, the prognosis is still poor. Growth factors such as vascular endothelial growth factor (VEGF) and pro-inflammatory markers have a major role in cancer progression, survival and metastasis. We examined anti-proliferative effects of DHA and oxaliplatin on two oesophageal cancer cell lines, in addition to assessing effects on VEGF and the inflammatory cytokine IL-6. Method Two Oesophageal cell lines (OE33 and OE19) were treated with either DHA or Oxaliplatin (0–50 µM) and incubated for up to 144 h. Cell counts were measured using a Z2 particle size analyser and expression of VEGF and IL-6 measured in cell culture supernatant using MSD ELISA kits. Three way ANOVA was used to analyse the data using StataIC 13 software. Results DHA reduced proliferation of OE33 and OE19 cell lines by 59% (p < 0.001) and 26% (p = 0.019) respectively. Oxaliplatin reduced proliferation by 77% (p < 0.001) and 76% (p < 0.001) respectively, growth curve demonstrated in the Figure 1. Down regulation of VEGF expression in OE33 cells after 144 h DHA treatment (50 µM) was highly significant (p < 0.0001, 95% CI -664.04 to -544.27) as was Oxaliplatin treatment (50 µM) (p < 0.0001, 95% CI -803.97 to -581.70). OE19 cells exhibited sensitivity to both drugs at lower concentrations at this same time point; DHA (30 µM) (p = 0.005, 95% CI -63.88 to -19.57) and Oxaliplatin (20 µM) (p = 0.026 95% CI -73.1 to -6.54). The two drugs had no statistically significant inhibition of IL-6 expression in both cell lines despite inhibition of cell growth.Abstract PWE-169 Figure 1 Conclusion The data provide evidence that the DHA and Oxaliplatin have statistically significant down regulation effect of VEGF in the two oesophageal cell lines but didn’t alter expression of pro-inflammatory markers such as IL-6. Disclosure of interest None Declared.

A Systematic Review of the Randomised Phase III Clinical Trials Employing Palliative Chemotherapy in the Management of Advanced Esophagogastric Adenocarcinoma

Background: Two-thirds of patients with esophagogastric cancer will be treated with palliative intent, with palliative chemotherapy being the most widely applied therapy. Just over half of those scheduled to receive this treatment will complete treatment as planned, with other patients failing to complete either because of disease progression or treatment side effects. The aim of this review was to report response rates, survival and toxicity of palliative chemotherapy for esophagogastric adenocarcinoma. Methods: Forty-three randomised phase III clinical trials, reporting on 12,945 patients during the years indicate 1990-2016 were evaluated and information on response rate, survival and treatment related toxicity extracted. Thirty-three studies described patients receiving 1 st line therapy and ten studies described patients receiving 2 nd line therapy. Results: Combination regimens were the most widely applied treatment worldwide as first line, with response rates in the order of 20-62%, and median overall survival in the order of 7.2-14.1 months. 30-85% of patients went on to receive second line therapy, generally single agent therapy, with reported response rates in the order of 7-22%, and median overall survival in the range 4.0-13.9 months. With the exception of trastuzumab, the effects of biological agents have been largely disappointing. The principal toxicities for chemotherapy were gastrointestinal (0-58%) and neutropenia (1-39% single agent, 12-82% combination therapy). Conclusions: At the current time, combination therapy remains the standard of care for patients with advanced esophagogastric adenocarcinoma.

PWE-168 Omega-3 fatty acid infusion reduces gastrointestinal toxicity and prevents thromboembolism in patients with advanced oesophagogastric cancer treated with palliative platinum based chemotherapy: Abstract PWE-168 Table 1

Introduction The omega-3 fatty acids, EPA and DHA have proven anticancer activity in laboratory and clinical cancer studies. This clinical trial evaluated whether adding omega-3 fatty acids to palliative platinum based chemotherapy influenced the outcome of patients with oesophagogastric cancer compared to those given chemotherapy alone Method 21 participants in the 1st stage of a phase II single arm trial received palliative chemotherapy, intravenous (IV) epirubicin (50mg/m2) and oxaliplatin (130mg/m2) every 21 days, oral capecitabine (1250mg/m2) daily for 21 days and IV omega-3 fatty acids (2ml/Kg/4 h) (Omegaven® Fresenius-Kabi). The Omegaven infusion was given immediately after the chemotherapy on days 1, 8 and 15 of each cycle (intervention). Clinical outcomes were compared to outcomes in 37 patients treated with chemotherapy alone (control). Toxicities were graded using the CTCAE v4.03. Clinical response rate was assessed by RECIST v1.1 criteria. Results Fifty-six patients eligible participants were screened for inclusion, 35 were excluded principally because of poor performance status. Twenty one patients were enrolled in the study, 20 received at least one treatment and they form the basis of this report. The radiological response and toxicity of the intervention and control groups are indicated (Table 1). The mean baseline and 7 day post treatment triglyceride levels were 1.7 mmol/l (95% CI 1.6- 1.79) and 1.66 mmol/l (95% CI 1.56–1.75) respectively. The highest recorded triglyceride level was 4.84 mmol/l. No patient experienced fat overload syndrome or grade 3/4 hypertriglyceridemia. Mean platelet counts were 217 X109/l in the intervention group (95% CI 207–226 X109/l) compared to 332 X109/l in the control group (95% CI 316–348 X109/l).Abstract PWE-168 Table 1 EOX chemotherapy and Omegaven (n = 21) EOX chemotherapy (n = 37) p-value Radiological responseCompletePartialStable diseaseProgressive disease 0 (0%)11 (73%)3 (20%)1 (7%) 1 (4%)11 (39%)11 (39%)5 (18%) 0.470.030.240.34 Grade 3/4 toxicityDiarrhoeaNausea/vomitingThromboembolismInfectionPeripheral neuropathy 2/20 (10%)0/20 (0%)0/20 (0%)4/20 (20%)2/20 (10%) 10/37 (27%)7/37 (19%)7/37 (19%)1/37 (3%)5/37 (13%) 0.180.040.040.751.0 Toxicity related hospital admission 11/20 (55%) 29/37 (78%) 0.06 Overall survival at 6 months (95% CI) 0.71 (047–0.86) 0.68 (0.50–0.80) Conclusion Compared to patients treated with chemotherapy alone, those treated with supplementary omega-3 fish oils had reduced chemotherapy related toxicity, notably fewer gastrointestinal and thromboembolic adverse effects. Omega-3 fatty acids have the potential to ameliorate the toxicity associated with chemotherapeutic agents. Disclosure of interest A. Eltweri Grant/ Research Support from: Fresenius-Kabi, A. Thomas Grant/ Research Support from: Fresenius-Kabi, A. Dennison Grant/ Research Support from: Fresenius-Kabi, M. Metcalfe Grant/ Research Support from: Fresenius-Kabi, D. Bowrey Grant/ Research Support from: Fresenius-Kabi, Nutricia

Case Report of Mannose-Binding Lectin (MBL) Deficiency and Postoperative Sepsis and Coagulopathy in a Patient Following Total Pancreatectomy for Chronic Pancreatitis

CONTEXTnComplement 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.nnnCASE REPORTnA 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.nnnCONCLUSIONnThis 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.