The aim of the present study was to evaluate clinical activity, and the pharmacodynamic and pharmacokinetic profiles, of oral metronomic vinorelbine (VNR) plus dexamethasone (DEX) in metastatic castration-resistant prostate cancer (mCRPC) patients. Fourty-one patients (92 % chemotherapy-resistant) received 30 mg/day VNR p.o. thrice a week plus 1 mg/day DEX p.o. until disease progression. Plasma soluble B cell antigen 7 homolog 3 (sB7-H3), vascular endothelial growth factor (VEGF), and thrombospondin-1 (TSP-1), were measured by ELISA. Plasma VNR was detected using a LC-MS-MS system. The fraction of patients free of progression, defined by criteria of the Prostate Cancer Clinical Trials Working Group 2, at 3 months was 61 %. PSA decrease ≥50 % from baseline was observed in 35 % of patients. Median PFS and OS were 4 months (95 % CI, 2.8-6.9) and 17.5 months (95 % CI, 10.8-24.5), respectively. Toxicity was mild, and no grade 4 toxicities were found. The mean plasma VNR C ranged from 1 to 2.7 ng/ml (T 1.1 h) and no evidence of drug accumulation was found. A moderate relationship was found between plasma sB7-H3 and PSA values (r = 0.565; P = 0.0094) at the baseline. Increased PFS (11.3 vs. 2.8 months; P = 0.0298) was observed in patients with sB7-H3 levels <30.25 ng/mL. Plasma VEGF AUC increased in non-responders (P < 0.0001), whereas responders maintained higher plasma TSP-1 AUC (P = 0.0063). In conclusion, metronomic VNR plus DEX showed favourable activity, and a low toxicity profile, in mCRPC patients. Plasma sB7-H3, VEGF and TSP-1 levels are potential pharmacodynamic markers at the reached low plasma concentrations of vinorelbine metronomically administered.

Urinary lithiasis after renal transplantation is a relatively uncommon disease; the predisposing factors and the composition of calculi are identical to those of patients with native kidneys. We present a case of a 45-year-old woman with a staghorn stone in a left-sided transplanted kidney who was treated successfully by percutaneous nephrolithotomy (PCNL). After reviewing the literature, we conclude that PCNL in transplanted kidney is a feasible and safe procedure. The technical aspects of the procedure, such as patient position and the use of the ultrasound-guided caliceal puncture, are stressed.

The aim of the present study was to assess the effects of ipriflavone administration in the prevention of the rapid bone loss that follows ovariectomy in women. After 10-30 days from bilateral ovariectomy, patients received either the sole calcium supplementation (500 mg/day, n = 16) or ipriflavone (600 mg/day, n = 16) in addition to the same daily calcium supplement for 12 months. In calcium-treated subjects urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels showed a substantial (p < 0.01) increase, while radial bone density significantly (p < 0.01) decreased 6 months after surgery. In ipriflavone treated group the patterns of biochemical markers indicated that ipriflavone can restrain the bone remodeling processes and radial bone density showed no significant modification during the 12 month study period. These results demonstrate that ipriflavone administration prevents the rapid bone loss that follows ovariectomy. Thus, ipriflavone can represent an attractive alternative for the prevention of osteoporosis in postmenopausal women who present contraindications to the estrogen replacement therapy.

The mineral content of bone was measured in 134 male patients who underwent ureterosigmoidostomy within the past 18 years. Moreover, the principal humoral indices of bone metabolism, together with hematic pH and alkaline reserve (BE) values were evaluated. This study showed that after approximately 6 years from a ureterosigmoidostomy there was significant bone demineralization. These data, supported by a parallel increase of serum osteocalcin, show that ureterosigmoidostomy represents a risk factor for osteoporosis especially in those patients who already have below normal values of bone mineral density prior to surgery.

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