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.

Influence of immunosuppression and effect of hepatitis C virus on new onset of diabetes mellitus in liver transplant recipients.

INTRODUCTION: New-onset posttransplantation diabetes mellitus (PTDM), with an incidence of 10% to 30%, increased graft and patient morbidity and mortality. Such causal factors as age, obesity, therapy, immunosuppression, and hepatitis C virus (HCV) contribute to this disease. OBJECTIVE: We sought to determine the incidence of PTDM and impaired fasting glucose (IFG) concentration in transplant recipients to define the causal variables. MATERIAL AND METHODS: The study included 127 patients. Patients with pretransplantation diabetes and those with less than 6 months of follow-up were excluded. A descriptive observational study to assess the association between PTDM and IFG and the immunosuppression therapy used was performed by monitoring the potential confounding variables of age, obesity, and HCV. RESULTS: During mean follow-up of 73.7 months (range, 7-120 mo), 93 patients received cyclosporine A (CyA) and 34 received tacrolimus (Tac) therapy. Thirty patients (23.6%) developed PTDM or IFG including 15 (16%; PTDM, six IFG, nine) in the CyA group and 15 (PTDM, seven; IFG, eight) in the Tacrolimus group (P = .001; odds ratio [OR], 4.1). They were homogeneous with respect to confounding variables except for HCV (P = .01). Of the 55 patients with HCV infection, 12 developed PTDM or IFG, including three in the CyA group and nine in the tacrolimus group (P = .03; OR, 7.7), whereas in the 72 patients without HCV infection, the CyA or tacrolimus association with PTDM or IFG was significant (P = .05), Mantel-Haenszel test; OR, 4.9). The interaction between HCV and immunosuppression therapy was primarily produced in the IFG group (HCV-positive; P = .008; OR, 8). CONCLUSION: We observed an association between the use of tacrolimus and the development of PTDM or IFG. There is greater risk in HCV-positive patients, in particular in relation to IFG. The choice of immunosuppressive treatment might be decided on the basis of the patient's pretransplantation status.