Vitamin D Supplementation and Disease-Free Survival in Stage II Melanoma: A Randomized Placebo Controlled Trial.

Patients with newly resected stage II melanoma (n = 104) were randomized to receive adjuvant vitamin D3 (100,000 IU every 50 days) or placebo for 3 years to investigate vitamin D3 protective effects on developing a recurrent disease. Median age at diagnosis was 50 years, and 43% of the patients were female. Median serum 25-hydroxy vitamin D (25OHD) level at baseline was 18 ng/mL, interquartile range (IQ) was 13-24 ng/mL, and 80% of the patients had insufficient vitamin D levels. We observed pronounced increases in 25OHD levels after 4 months in the active arm (median 32.9 ng/mL; IQ range 25.9-38.4) against placebo (median 19.05 ng/mL; IQ range 13.0-25.9), constantly rising during treatment. Remarkably, patients with low Breslow score (<3 mm) had a double increase in 25OHD levels from baseline, whereas patients with Breslow score ≥3 mm had a significantly lower increase over time. After 12 months, subjects with low 25OHD levels and Breslow score ≥3 mm had shorter disease-free survival (p = 0.02) compared to those with Breslow score <3 mm and/or high levels of 25OHD. Adjusting for age and treatment arm, the hazard ratio for relapse was 4.81 (95% CI: 1.44-16.09, p = 0.011). Despite the evidence of a role of 25OHD in melanoma prognosis, larger trials with vitamin D supplementation involving subjects with melanoma are needed.

Neoadjuvant therapy and mini-invasive total mesorectal excision for rectal cancer: feasibility and outcome analysis from a single institution prospectively collected data base.

AIM AND BACKGROUND: Neoadjuvant treatment for rectal adenocarcinoma improves local control and represents the standard for locally advanced disease. Laparoscopic and robotic total mesorectal excision has been increasingly adopted. It provides magnified visualization of the pelvic cavity, thereby facilitating the mesorectal dissection. METHODS: Consecutive patients with locally advanced/ultralow rectal adenocarcinoma received neoadjuvant treatment and mini-invasive total mesorectal excision at our center. We retrospectively reviewed the clinical records by using a prospectively collected data base and focusing on feasibility, tumor response and treatment outcomes. RESULTS: In a 13-year period, 117 rectal adenocarcinoma patients (80 males and 37 females) received neoadjuvant treatment and mini-invasive total mesorectal excision. Median age at diagnosis was 67 years; pre-treatment stage was I in 10 (9%); IIA in 58 (50%); IIC in 5 (4%); IIIA in 10 (9%); IIIB in 31 (26%) and IV in 3 (2%) patients. All patients received external beam radiation therapy, 79 (67%) combined with fluorouracil-based chemotherapy. One-hundred and three patients underwent laparoscopic surgery and 14 robotic surgery. Overall, 90 patients (77%) had anterior resection and 27 (23%) had abdominoperineal resection. Down-staging was obtained in 70 patients (66%). No major intraoperative nor delayed surgical complications were observed. At a median follow up of 52 months, 8 patients (7%) had a local relapse, 7 of them along with distant relapse, and 16 (14%) had distant relapse. The 5-year relapse-free survival was 76.5%. CONCLUSIONS: Our data suggest that in a community hospital mini-invasive surgery after neoadjuvant treatment is feasible in real clinical practice and achieves consistent results in term of disease control rate.

Venous thromboembolism prophylaxis and treatment in cancer: a consensus statement of major guidelines panels and call to action.

PURPOSE: Venous thromboembolism (VTE) is an increasingly frequent complication of cancer and its treatments, and is associated with worsened mortality and morbidity in patients with cancer. DESIGN: The Italian Association of Medical Oncology, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, the French National Federation of the League of Centers Against Cancer, and the European Society of Medical Oncology have recently published guidelines regarding VTE in patients with cancer. This review, authored by a working group of members from these panels, focuses on the methodology and areas of consensus and disagreement in the various clinical guidelines as well as directions for future research. RESULTS: There is broad consensus regarding the importance of thromboprophylaxis in hospitalized patients with cancer, including prolonged prophylaxis in high-risk surgical patients. Prophylaxis is not currently recommended for ambulatory patients with cancer (with exceptions) or for central venous catheters. All of the panels agree that low molecular weight heparins are preferred for the long-term treatment of VTE in cancer. Areas that warrant further research include the benefit of prophylaxis in the ambulatory setting, the risk/benefit ratio of prophylaxis for hospitalized patients with cancer, an understanding of incidental VTE, and the impact of anticoagulation on survival. CONCLUSION: We call for a sustained research effort to investigate the clinical issues identified here to reduce the burden of VTE and its consequences in patients with cancer.

Optimizing use of opiates in the management of cancer pain.

Cancer pain is often suboptimally managed. The underestimation and undertreatment continues to be a problem despite the availability of consensus-based guidelines. Most patients with cancer develop pain. The prevalence and severity of pain among cancer patients varies according to primary and metastatic sites and stage of disease. Opioid therapy is the cornerstone of management of severe chronic pain in the field of cancer patients and in general in palliative care medicine. Since this class of drugs is the cornerstone of the treatment, optimizing its use may be useful in clinical practice. For this purpose we focused on 4 distinct issues: 1) How to implement the use the opioids in cancer patients; 2) How to optimise the use of morphine in cancer patients; 3) The management of side effects and opioid switching; 4) What is the role of other potent opioids. A holistic approach including an appropriate use of opioids may improve pain control in most cancer patients, particularly for those with advanced disease.

Growth Factors: Thrombopoietic Property of the Pineal Hormone Melatonin.

The recent advances in the psychoneuroimmunology have suggested that the hematopoiesis may be under a neuroendocrine regulation, mainly exerted by the pineal gland. In particular, melatonin (MLT), which is the main pineal hormone, has appeared to stimulate platelet generation, probably by promoting the megakaryocyte fragmentation and modulating the cytokine network involved in platelet production. On this basis, we have evaluated the effect of pharmacological doses of MLT on platelet number in patients with persistent thrombocytopenia due to different causes. The study included 200 patients, who were randomized to receive supportive care alone or MLT at 20 mg/day orally in the evening, for al least 1 month. No MLT-related toxicity occured. Platelet mean number rapidly and significantly increased in response to MLT, and a normalization of platelet number was achieved on MLT therapy in 71/98 (72%) patients. The least responsive form of thrombocytopenia was DIC. This study shows that the pineal hormone MLT may represent a well tolerable and effective therapy of thrombocytopenia due to different pathogenetic mechanisms.