Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients.

BACKGROUND: Several studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors' interplay remains unknown. METHODS: 74 CRC patients after standard treatment were randomized to 1-year 2000 IU/day vitD or placebo.  Baseline and post-treatment fecal microbiota for shotgun metagenomics sequencing was collected. Coda-lasso and Principal Component Analysis were used to select and summarize treatment-associated taxa and pathways. Associations between vitD and taxa/pathways were investigated with logistic regression. Mediation analysis was performed to study if treatment-associated taxa mediated the effect of supplementation on 25(OH)D levels. Cox proportional-hazards model was used for disease-free survival (DFS). RESULTS: 60 patients were analyzed. Change in alpha diversity (Shannon: p = 0.77; Simpson: p = 0.63) and post-treatment beta diversity (p = 0.70) were comparable between arms. Post-treatment abundances of 63 taxa and 32 pathways differed between arms. The 63 taxa also mediated the effect of supplementation on 25(OH)D (p = 0.02). There were sex differences in vitD levels, microbiota and pathways. Pathways of essential amino acids' biosynthesis were more abundant in supplemented women. Fusobacterium nucleatum presence at baseline was associated with worse DFS (p = 0.02). Those achieving vitD sufficiency (25(OH)D≥30 ng/ml) had lower post-treatment abundances (p = 0.05). Women were more likely to have F. nucleatum post-treatment (p = 0.02). CONCLUSIONS: VitD supplementation may contribute shaping the gut microbiota and the microbiota may partially mediate the effect of supplementation on 25(OH)D. The observed sex-specific differences highlight the necessity of including sex/gender as a variable in microbiome studies.

Laryngeal dysplasia: Oncological outcomes in a large cohort of patients treated in a tertiary comprehensive cancer centre.

PURPOSE: Laryngeal dysplasia represents a series of precancerous lesions, observed as laryngeal leukoplakia. General agreement has been lacking for their management and treatment ranging from simple biopsy to complete excision with cold blade/laser. In this work, we aim at providing the oncological outcomes of patients affected by laryngeal dysplasia, treated with a single modality, and at identifying clinical parameters predictive of malignant transformation. MATERIALS AND METHODS: We performed a retrospective analysis of patients treated with transoral laser microsurgery between January 2005 and December 2015 in a tertiary comprehensive cancer centre. Data were collected about smoke and alcohol habits, site of the laryngeal lesion, surgical outcomes and progression to invasive squamous cell carcinoma. RESULTS: The grade of dysplasia, margins' status and smoke habit were not associated with a significantly worse DFS and a higher risk of invasive SCC. We identified three parameters (supraglottic involvement, multifocality and history of more than one recurrence of dysplasia) that have a significant prognostic value. CONCLUSIONS: On the base of these clinical parameters, a more intensive follow-up might be warranted for high-risk patients.