Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer.

OBJECTIVES: To describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis. DESIGN: Multicentre prospective observational cohort study. SETTING AND PARTICIPANTS: Eleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected. OUTCOMES: Type and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival. RESULTS: Of 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC. CONCLUSIONS: Raising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers.

UK Multicenter Prospective Evaluation of the Leibovich Score in Localized Renal Cell Carcinoma: Performance has Altered Over Time.

OBJECTIVE: To examine changes in outcome by the Leibovich score using contemporary and historic cohorts of patients presenting with renal cell carcinoma (RCC) PATIENTS AND METHODS: Prospective observational multicenter cohort study, recruiting patients with suspected newly diagnosed RCC. A historical cohort of patients was examined for comparison. Metastasis-free survival (MFS) formed the primary outcome measure. Model discrimination and calibration were evaluated using Cox proportional hazard regression and the Kaplan-Meier method. Overall performance of the Leibovich model was assessed by estimating explained variation. RESULTS: Seven hundred and six patients were recruited between 2011 and 2014 and RCC confirmed in 608 (86%) patients. Application of the Leibovich score to patients with localized clear cell RCC in this contemporary cohort demonstrated good model discrimination (c-index = 0.77) but suboptimal calibration, with improved MFS for intermediate- and high-risk patients (5-year MFS 85% and 50%, respectively) compared to the original Leibovich cohort (74% and 31%) and a historic (1998-2006) UK cohort (76% and 37%). The proportion of variation in outcome explained by the model is low and has declined over time (28% historic vs 22% contemporary UK cohort). CONCLUSION: Prognostic models are widely employed in patients with localized RCC to guide surveillance intensity and clinical trial selection. However, the majority of the variation in outcome remains unexplained by the Leibovich model and, over time, MFS rates among intermediate- and high-risk classified patients have altered. These findings are likely to have implications for all such models used in this setting.

Lead optimization toward proof-of-concept tools for Huntington's disease within a 4-(1H-pyrazol-4-yl)pyrimidine class of pan-JNK inhibitors.

Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole.

A case of asymptomatic renal pseudoaneurysm post partial nephrectomy treated successfully.

Pseudoaneurysm remains one of the rare complications of partial nephrectomy with reported rates of 0.4-1.4%. We add to the literature a case of asymptomatic pseudoaneurysm post laparoscopic partial nephrectomy (LPN) that was successfully treated with embolisation.

Subfrontal schwannoma: a case report and literature review.

Subfrontal schwannomas are rare and usually misdiagnosed preoperatively. We present the third reported case of a schwannoma arising from the olfactory nerve. The neuroradiological and pathological features of the case, as well as the origin of the tumour are discussed.