This study identified and characterised 21 novel FH mutations and demonstrated that PRCCII can be the only one manifestation of HLRCC. Due to the incomplete penetrance of HLRCC, the authors propose to extend the FH mutation analysis to every patient with PRCCII occurring before 40 years of age or when renal tumour harbours characteristic histologic features, in order to discover previously ignored HLRCC affected families.

The aim of this study was to evaluate the efficacy of helical CT using a combination of CT-attenuation values and visual assessment of stone density as well as discriminant linear analysis to predict the chemical composition of urinary calculi. One hundred human urinary calculi were obtained from a stone-analysis laboratory and placed in 20 excised pig kidneys. They were scanned at 80, 120 and 140 kV with 3-mm collimation. Average, highest and lowest CT-attenuation values and CT variability were recorded. The internal calculus structure was assessed using a wide window setting, and visual assessment of stone density was recorded. A stepwise discriminant linear analysis was performed. The following three variables were discriminant: highest CT-attenuation value, visual density, and highest CT-attenuation value/area ratio, all at 80 kV. The probability of correctly classifying stone composition with these three variables was 0.64, ranging from 0.54 for mixed calculi to 0.69 for pure calculi. The probabilities of correctly classifying calculus composition were: 0.91 for calcium oxalate monohydrate and brushite, 0.89 for cystine, 0.85 for uric acid, 0.11 for calcium oxalate dihydrate, 0.10 for hydroxyapatite, and 0.07 for struvite calculi. When the first two ranks of highest probability for the accurate classification of each calculus type were taken into account, 81% of the calculi were correctly classified. Assessment at 80 kV of the highest CT-attenuation value, visual density and the highest CT-attenuation value/area ratio accurately predicts the chemical composition of 64-81% of urinary calculi. When the first two ranks of highest probability for the accurate classification of each calculus type were taken into account, all cystine, calcium oxalate monohydrate and brushite calculi were correctly classified.

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Purpose: This multicenter, open-label, phase II study evaluated the safety and clinical activity of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, 2, and 3, in patients with metastatic melanoma.Experimental Design: Thirty-two patients with a maximum of one prior systemic therapy received axitinib at a starting dose of 5 mg twice daily. The primary endpoint was objective response rate.Results: Objective response rate was 18.8% [95% confidence interval (CI), 7.2-36.4], comprising one complete and five partial responses with a median response duration of 5.9 months (95% CI, 5.0-17.0). Stable disease at 16 weeks was noted in six patients (18.8%), with an overall clinical benefit rate of 37.5%. Six-month progression-free survival rate was 33.9%, 1-year overall survival rate was 28.1%, and median overall survival was 6.6 months (95% CI, 5.2-9.0). The most frequently (>15%) reported nonhematologic, treatment-related adverse events were fatigue, hypertension, hoarseness, and diarrhea. Treatment-related fatal bowel perforation, a known class effect, occurred in one patient. Axitinib selectively decreased plasma concentrations of soluble VEGFR (sVEGFR)-2 and sVEGFR-3 compared with soluble stem cell factor receptor (sKIT). No significant association was noted between plasma levels of axitinib and response. However, post hoc analyses indicated potential relationships between efficacy endpoints and diastolic blood pressure of 90 mm Hg or higher as well as baseline serum lactate dehydrogenase levels.Conclusions: Axitinib was well tolerated, showed a selective VEGFR-inhibitory profile, and showed single-agent activity in metastatic melanoma. Further evaluations of axitinib, alone and combined with chemotherapy, are ongoing. Clin Cancer Res; 17(23); 7462-9. Ó2011 AACR.