Adjuvant treatment of colorectal cancer in the elderly : where do we come from and where are we going?

Objective: Colorectal cancer is the third most commonly reported cancer in the world and about 50% of patients are diagnosed over the age of 70 years. The authors discuss age-related changes in organ function, comorbidities and frailty in the elderly, and their impact on chemotherapy toxicity. Methods: The authors review data from observational studies and subgroup analyses of randomized clinical trials on adjuvant chemotherapy in elderly colorectal cancer patients. Results: Several large population-based studies suggest that adjuvant chemotherapy is offered less frequently to elderly patients, although in recent years the prescription patterns tended to significantly increase. In fact, data from retrospective analyses of randomized trials indicate that elderly stage III colorectal cancer patients may get similar clinical advantage from adjuvant treatment with fluoropyrimidines, although major comorbidities may substantially limit life expectancy and minimize the survival benefits. The use of oxaliplatin-based regimens needs to take into account the individual risk/benefit profile due to lack of unequivocal evidence of positive literature data. Conclusions: Adjuvant chemotherapy of colorectal cancer should be investigated by prospective trials specifically designed for the elderly. Fit elderly patients should be offered standard adjuvant treatments, while modified schedule, attenuated doses or even treatment omission can be offered to more frail patients

Concomitant administration of proton pump inhibitors does not significantly affect clinical outcomes in metastatic breast cancer patients treated with ribociclib

Background: Gastric pH changes by proton-pump-inhibitors (PPIs) were found to affect progression-free survival (PFS) in metastatic breast cancer (mBC) patients treated with palbociclib. The current study was aimed at investigating whether the same effect could occur in patients treated with ribociclib. Patients and methods: Patients with hormone-positive/HER-2-negative mBC candidates for first-line treatment with ribociclib were enrolled in this retrospective-cohort study. Patients were classified as "no concomitant PPIs" or "concomitant PPIs"; PPI administration covered the entire or not less than 2/3 of treatment with ribociclib. All clinical interventions were made according to clinical practice. Results: A total of 128 patients were consecutively enrolled in the study; 78 belonged to the "no concomitant PPIs" group and 50 to the "concomitant PPIs" group. One hundred and six patients were endocrine-sensitive and received ribociclib and letrozole, while 22 were endocrine-resistant and were treated with ribociclib and ful-vestrant. The most prescribed PPI was lansoprazole. According to PFS, patients taking PPIs had a PFS almost superimposable to those assuming ribociclib and endocrine therapy alone (35.3 vs. 49.2 months, p = 0.594). No difference in PFS was observed in estrogen-sensitive or estrogen-resistant mBC in the presence or absence of concomitant PPI treatment (p = 0.852). No correlation with adverse events was found including grade>2 he-matological toxicities. Conclusions: The present study supports the hypothesis that the concomitant use of PPIs does not compromise the efficacy of ribociclib in a real-life setting

Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.ClinicalTrials.gov NCT00730509

Management of advanced genitourinary tumors

The management of advanced genitourinary tumors is rapidly evolving thanks to the clinical availability of several targeted drugs with different mechanisms of action. Among clinicians, in-depth knowledge of all the aspects of the disease, together with the capacity to interpret and accurately correlate clinical data and imaging findings, are strongly needed. Moreover, the optimization of treatment sequences might lead to better disease control with respect to prognostic categories, radiological monitoring and newer biomarkers. Among the genitourinary tumors, only few data are available on bladder, testicular and penile cancers. Our report is supported by scientific and clinical experience in renal cell carcinoma and prostate cancer

Amici miei. Fenomenologia delle relazioni amicali nella societ\ue0 del benessere.

Presentazione dei risultati di una ricerca empirica sulle relazioni amicali nel Nord est. pp.9-19; 39-52; 125-13