Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors.

Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI. Here, we performed protein tyrosine kinase (PTK) profiling using PamChip® technology. The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib. Briefly, our results showed that 36 kinase substrates differs (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer. Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. In our assay, tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients.

The quality of medical autopsy reports. / Kvaliteten på medisinske obduksjonsrapporter.

BACKGROUND: Medical autopsies are rarely made subject to quality assurance. We have investigated the quality of autopsy reports in Norway and assessed the impact of errors on the cause of death statistics. MATERIAL AND METHOD: Every fifth medical autopsy report for adults (> 2 years) in 2014 was reviewed. The significance of the autopsy result for the registration of cause of death was studied by comparing the death certificate issued by the clinician with the coding in the Cause of Death Registry after the autopsy. RESULTS: A total of 389 autopsy reports from 15 departments of pathology were reviewed. The autopsy request, as well as the death certificate and the codes for the cause of death from the Cause of Death Registry were available for 339 and 360 cases respectively. Ninety-five requests had specified clinical questions, but were commented on by the pathologist in 33 cases. Obesity was rarely reported as a finding, even in cases of pathological deviations from a normal weight. A post-mortem virus examination or toxicology had been performed in 1 and 28 autopsies respectively. The average turnaround time for autopsies without and with a neuropathological examination was 99 and 138 days respectively. Errors in reporting the cause of death or inadequate reporting were evident in 69 cases (18 %), most frequently for deaths from cardiovascular diseases. The autopsy result led to a change to the cause of death in the Cause of Death Registry in 206 out of 360 (57 %) cases for which coding data were available. Errors in the formulation of the autopsy result resulted in erroneous coding of the cause of death in 22 out of 47 (47 %) of cases with errors. INTERPRETATION: The proportion of autopsy reports with errors in the formulation of the cause of death was unexpectedly high and may have consequences for the cause of death statistics. Long turnaround times for autopsies complicate communication with the clinician about the findings.

Photodynamic therapy with methyl aminolevulinate for atypial carcinoma in situ of the penis.

OBJECTIVE: Photodynamic therapy (PDT) has been investigated as an alternative treatment for cutaneous squamous cell carcinoma in situ (CIS), also known as Bowen's disease. Atypia of the squamous epithelium is graded, with the most severe atypia being equivalent to CIS. CIS on the penis is regarded as a premalignant condition and is seen either in isolation or in conjunction with carcinoma of the penis. MATERIAL AND METHODS: A group of 10 patients with atypia/CIS were treated with PDT between December 2002 and April 2005. The group consisted of five patients with primary lesions and five with atypia after an organ-preserving operation for carcinoma of the penis. RESULTS: Eight patients were treated once, one twice and one six times. When complete remission was not achieved, a biopsy was taken for diagnosis. Three of the 10 patients had histopathological residual disease after a median follow-up period of 20 months (range 15-36 months). The first week after treatment could be painful but the cosmetic results were excellent. There was almost no loss of substance or fibrosis in the treated area, and sensitivity was restored to normal after approximately 1 month. CONCLUSIONS: In our experience, PDT for CIS seems to be a promising treatment modality with regard to cancer control, organ preservation, cosmetics and functional results. As with laser therapy of these lesions, careful follow-up is mandatory. Larger studies are needed and are planned.