HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma.

BACKGROUND: Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4). METHODS/DESIGN: The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection. DISCUSSION: We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma. TRIAL REGISTRATION: NCT02614534 ( clinicaltrial.gov ) Nov-2015.

Comparison of a high-carbohydrate and a high-monounsaturated fat, olive oil-rich diet on the susceptibility of LDL to oxidative modification in subjects with Type 2 diabetes mellitus.

AIMS: To compare the effects of a high-carbohydrate (CHO) diet and a high-monounsaturated fatty acid (MUFA) diet on LDL oxidative resistance in free-living individuals with Type 2 diabetes mellitus. METHODS: Twenty-two men and women out-patients with Type 2 diabetes, with mean age 61 years and in fair metabolic control (HbA1c<8.0%), were enrolled at a university hospital lipid clinic in a randomized, crossover feeding trial comparing two isocaloric diets for 6 weeks each: CHO (fat, 28% energy) and MUFA (fat, 40% energy) based on virgin olive oil. Outcome measurements were changes in LDL susceptibility to oxidation, body weight, glycaemic control, and lipoprotein profiles. RESULTS: Planned and observed diets were well matched. Participants preferred the MUFA diet over the CHO diet. The lag time of conjugated diene formation during Cu2+-induced LDL oxidation was similar after the CHO and MUFA diets (36.4 +/- 12.2 min and 36.0 +/- 13.7 min, respectively). Body weight, glycaemic control, total triglycerides, and total, LDL- and HDL-cholesterol levels also were similar after the two diets. Compared with the CHO diet, the MUFA diet lowered VLDL-cholesterol by 35% (P=0.023) and VLDL triglyceride by 16% (P=0.016). CONCLUSIONS: Natural food-based high-CHO and high-MUFA diets have similar effects on LDL oxidative resistance and metabolic control in subjects with Type 2 diabetes. A MUFA diet is a good alternative to high-CHO diets for nutrition therapy of diabetes because it also has a beneficial effect on the lipid profile and superior patient acceptance.

High-monounsaturated fat, olive oil-rich diet has effects similar to a high-carbohydrate diet on fasting and postprandial state and metabolic profiles of patients with type 2 diabetes.

Whether metabolic control in type 2 diabetes mellitus (DM) is best achieved with the traditional high-carbohydrate (CHO), low-fat diet or a low-CHO, high-fat diet is still controversial. In a randomized crossover study, we compared the effects of a low-fat (30% of daily energy) diet and a high-fat (40% of daily energy), high-monounsaturated-fat diet for 6 weeks each on fasting and postprandial glucose, insulin, and lipoprotein concentrations in 12 patients with well-controlled type 2 DM (fasting blood glucose, 176 +/- 54 mg/dL; hemoglobin A1c, 6.4% +/- 0.7%) and no overt dyslipidemia (serum total cholesterol, 235 +/- 43 mg/dL; triglycerides, 180 +/- 63 mg/dL). Home-prepared foods were used and olive oil was the main edible fat, accounting for 8% and 25% of daily energy requirements in the low-fat and high-fat diets, respectively. For postprandial studies, the same mixed meal containing 36% fat was used in both dietary periods. Body weight and fasting and 6-hour postprandial blood glucose, insulin, and lipoprotein levels were similar after the two diets. The mean incremental area under the curve of serum triglycerides 0 to 6 hours after the challenge meal, adjusted for baseline levels, did not change significantly after the high-fat diet compared with the low-fat diet (1,484 +/- 546 v 1,714 +/- 709 mg x 6 h/dL, respectively, P = .099). Mean postprandial triglyceride levels at 6 hours were increased about 2 times over fasting levels and were still greater than 300 mg/dL after either diet. A diet high in total and monounsaturated fat at the expense of olive oil is a good alternative diet to the traditional low-fat diet for patients with type 2 DM. However, ongoing postprandial hypertriglyceridemia with either diet points to the need for other therapies to decrease triglyceride-rich lipoproteins (TRL) and the inherent atherogenic risk in type 2 diabetics.