GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases.

BACKGROUND: The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies. METHODS: GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1-10; 11-15; 16-20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values. DISCUSSION: HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years. TRIAL REGISTRATION: EudraCT number: 2019-004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).

Serum Bioavailable Vitamin D Concentrations and Bone Mineral Density in Women After Obesity Surgery.

INTRODUCTION: Low bone mass after obesity surgery may arise as a consequence of chronic malabsorption of calcium and vitamin D. However, we have not found any role of serum 25-hydroxyvitamin D or of polymorphisms in the vitamin D receptor gene in previous studies. PURPOSE: To investigate the circulating bioavailable 25-hydroxyvitamin D in women after bariatric procedures and its association with bone mass. PATIENTS AND METHODS: The study consisted of 91 women on follow-up for 7 ± 2 years after bariatric surgery. We measured bone mineral density (BMD), serum parathormone (PTH), 25-hydroxyvitamin D, and vitamin D binding protein (VDBP). All patients were genotyped for two variants in the coding region of VDBP (rs4588 and rs7041). Bioavailable 25-hydroxyvitamin D was calculated in double homozygotes. RESULTS: We found a negative correlation between bioavailable 25-hydroxyvitamin D and PTH (r = -0.373, P = 0.018), but not with BMD at lumbar spine (r = -0.065, P = 0.682) or hip (r = -0.029, P = 0.857). When adjusting by age, similar results were found for PTH (r = -0.441, P = 0.005), BMD at lumbar spine (r = -0.026, P = 0.874) and hip (r = -0.096, P = 0.561). After multivariate linear regression, forcing bioavailable 25-hydroxyvitamin D into the model resulted in a weak significant association with BMD at the lumbar spine (ß = - 0.247, P = 0.025). CONCLUSIONS: Serum bioavailable 25-hydroxyvitamin D concentrations are not associated with bone mass loss after bariatric surgery in women. The negative association with serum PTH levels suggests that vitamin D supplementation partly improves secondary hyperparathyroidism, yet other mechanisms may contribute to low bone mass after bariatric surgery.