Early detection of urothelial premalignant lesions using hexaminolevulinate fluorescence cystoscopy in high risk patients

<p>Abstract</p> <p>Background</p> <p>To evaluate fluorescence cystoscopy with hexaminolevulinate (HAL) in the early detection of dysplasia (DYS) and carcinoma in situ (CIS) in select high risk patients.</p> <p>Methods</p> <p>We selected 30 consecutive bladder cancer patients at high risk for progression. After endoscopic resection, all patients received (a) induction BCG schedule when needed, and (b) white light and fluorescence cystoscopy after 3 months. HAL at doses of 85 mg (GE Healthcare, Buckinghamshire, United Kingdom) dissolved in 50 ml of solvent to obtain an 8 mmol/L solution was instilled intravesically with a 12 Fr catheter into an empty bladder and left for 90 minutes. The solution was freshly prepared immediately before instillation. Cystoscopy was performed within 120 minutes of bladder emptying. Standard and fluorescence cystoscopy was performed using a double light system (Combilight PDD light source 5133, Wolf, Germany) which allowed an inspection under both white and blue light.</p> <p>Results</p> <p>The overall incidence was 43.3% dysplasia, 23.3% CIS, and 13.3% superficial transitional cell cancer. In 21 patients, HAL cystoscopy was positive with one or more fluorescent flat lesions. Of the positive cases, there were 4 CIS, 10 DYS, 2 association of CIS and DYS, 4 well-differentiated non-infiltrating bladder cancers, and 1 chronic cystitis. In 9 patients with negative HAL results, random biopsies showed 1 CIS and 1 DYS. HAL cystoscopy showed 90.1% sensitivity and 87.5% specificity with 95.2% positive predictive value and 77.8% negative predictive value.</p> <p>Conclusion</p> <p>Photodynamic diagnosis should be considered a very important tool in the diagnosis of potentially evolving flat lesions on the bladder mucosa such as DYS and CIS. Moreover, detection of dysplasic lesions that are considered precursors of CIS may play an important role in preventing disease progression. In our opinion, HAL cystoscopy should be recommended in the early follow-up of high risk patients.</p

ESUR prostate MR guidelines 2012

The aim was to develop clinical guidelines for multi-parametric MRI of the prostate by a group of prostate MRI experts from the European Society of Urogenital Radiology (ESUR), based on literature evidence and consensus expert opinion. True evidence-based guidelines could not be formulated, but a compromise, reflected by “minimal” and “optimal” requirements has been made. The scope of these ESUR guidelines is to promulgate high quality MRI in acquisition and evaluation with the correct indications for prostate cancer across the whole of Europe and eventually outside Europe. The guidelines for the optimal technique and three protocols for “detection”, “staging” and “node and bone” are presented. The use of endorectal coil vs. pelvic phased array coil and 1.5 vs. 3 T is discussed. Clinical indications and a PI-RADS classification for structured reporting are presented

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Active Surveillance for Prostate Cancer: A Systematic Review of the Literature

Context: Prostate cancer (PCa) remains an increasingly common malignancy worldwide. The optimal management of clinically localized, early-stage disease remains unknown, and profound quality of life issues surround PCa interventions. Objective: To systematically summarize the current literature on the management of low-risk PCa with active surveillance (AS), with a focus on patient selection, outcomes, and future research needs. Evidence acquisition: A comprehensive search of the PubMed and Embase databases from 1980 to 2011 was performed to identify studies pertaining to AS for PCa. The search terms used included prostate cancer and active surveillance or conservative management or watchful waiting or expectant management. Selected studies for outcomes analysis had to provide a comprehensive description of entry characteristics, criteria for surveillance, and indicators for further intervention. Evidence synthesis: Data from seven large AS series were reviewed. Inclusion criteria for surveillance vary among studies, and eligibility therefore varies considerably (4-82%). PCa-specific mortality remains low (0-1%), with the longest published-median follow-up being 6.8 yr. Up to one-third of patients receive secondary therapy after a median of about 2.5 yr of surveillance. Surveillance protocols and triggers for intervention vary among institutions. Most patients are treated for histologic Conclusions: AS for PCa offers an opportunity to limit intervention to patients who will likely benefit the most from radical treatment. This approach confers a low risk of disease-specific mortality in the short to intermediate term. An early, confirmatory biopsy is essential for limiting the risk of underestimating tumor grade and amount. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved