Active surveillance: does serial prostate biopsy increase histological inflammation?

BACKGROUND: Active surveillance (AS) is an appropriate management strategy for men with low-risk prostate cancer. Most protocols recommend repeated prostate biopsy every 12-24 months. The purpose of this paper is to describe histological inflammation patterns in men on AS who underwent serial prostate biopsy for disease monitoring. METHODS: We reviewed records of men on AS from January 1999 through February 2011 who had a diagnostic plus ≥1 repeat transrectal ultrasound-guided biopsies performed at our institution. The type and degree of inflammatory infiltrate were grossly reviewed and scored for each patient's biopsy by a single pathologist. Relationship of inflammation severity and number of serial biopsies was assessed using a repeated measures mixed model. Unpaired t-test and χ(2)-square analysis assessed variance in degree of inflammation and location of inflammation relative to cancer grade progression defined as Gleason sum increase. RESULTS: Fifty-six men met study inclusion criteria. Mean age was 62.1 (6.5) years, 71% were stage cT1c, 79% had a PSA level <10 ng ml(-1), and 98% had diagnostic Gleason sum ≤6. A small, statistically significant increase in maximum chronic inflammation (CI) scores with greater number of repeat biopsies was observed. CI scores were not associated with number of biopsies based on upgrade status. The main limitation to our study is our small sample size. Potential unmeasured confounders, such as unreported antibiotic use or symptomatic prostatitis, may have also affected our findings. CONCLUSIONS: In this pilot study of 56 men on AS for localized prostate cancer, degree of chronic histological inflammation increased with greater number of prostate biopsies, but was not associated with subsequent risk of grade progression.

Screening for mutations in synaptotagmin XI in Parkinson's disease.

Parkinson's disease (PD) is characterized by selective degeneration of neurons in the substantia nigra and subsequent dysfunction of dopaminergic neurotransmission. Genes identified in familial forms of PD encode proteins that are linked to the ubiquitin-proteasome system indicating the pathogenic relevance of disturbed protein degradation in PD. Some of them, i.e. alpha-synuclein, parkin and synphilin-1, have been implicated in presynaptic neurotransmission based on their localization in synaptic vesicles. Synaptotagmin XI is linked to the pathogenesis of PD based on its identification as a substrate of the ubiquitin-E3-ligase parkin. Moreover synaptotagmin XI is involved in the maintainance of synaptic function and represents a component of Lewy bodies (LB) in brains of PD patients. Therefore, we performed a detailed mutation analysis of the synaptotagmin XI gene in a large sample of 393 familial and sporadic PD patients. We did not find any disease causing mutations arguing against a major role of mutations in the synaptotagmin XI gene in the pathogenesis of PD.