Aims: The study aimed to determine the current trends in urolithiasis-related admissions and associated interventions in England between 2006/2007 and 2013/2014 utilizing Hospital Episode Statistics (HES) online data. Material and Methods: Data was extracted from the online HES data set for each year from 2006/2007 to 2013/2014 inclusive. Admissions and procedural interventions were identified from their corresponding OPCS-4 and ICD-10 codes. Results: Finished consultant episodes (FCEs) for urolithiasis have increased by 20% over the last 7 years, with 93,039 FCEs in the year 2013/2014. Based on English population statistics, the lifetime prevalence of urolithiasis based on hospital-related admission/intervention data for 2013/2014 is 14%. The biggest increases were seen in those aged ≥75 years (up by 51%, n = 2,853). Total interventions have increased from 28,624 to 42,068, with increased rates of shock wave lithotripsy (26%), ureteroscopy (URS; 86%) and percutaneous nephrolithotomy (149%). Emergency URS procedures have increased by 38%. Day-case rates for ureteric and renal URS, in 2013/2014, were 22 and 21%, respectively. Conclusions: Over the last 7 years, there is a rising prevalence of kidney stone disease with associated increase in the number of interventions related to it. Both elective and emergency URS procedures are increasing, with a rising trend for day-case URS. Similar trends are seen worldwide and future resource planning for urolithiasis is needed to match the increase in demand.

Background The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued Phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify potential biomarkers. Methods We evaluated baseline clinical data, needle biopsies and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center. Pathology review, tumor and germline targeted DNA sequencing (n=72 genes), and expression profiling using Nanostring platform (n=163 genes) were performed to explore changes in critical prostate cancer pathways linked to aggression and resistance. Results 3/52 patients had only microfocal residual cancer at prostatectomy. The most common alterations included TMPRSS2-ERG fusion (n=32), TP53 mutation or deletion (n=11), PTEN deletion (n=6), FOXA1 (n=6), SPOP (n=4) mutation, with no significant enrichment in post-treated specimens. We did not observe AR amplification or mutations. The degree of AR signaling suppression varied among treated tumors and there was up-regulation of both AR and AR-V7 expression as well as a subset of neuroendocrine and plasticity genes. Conclusions These data support the feasibility of targeted and temporal genomic and transcriptome profiling of neoadjuvant-treated prostate cancer with limited formalin-fixed paraffin embedded tissue requirement. Characterization of the heterogeneity of treatment response and molecular outliers that arise post-treatment provides new insight into potential early markers of resistance.

Small-cell prostate carcinoma (SCPC) is an aggressive malignancy that is managed similarly to small-cell lung cancer. SCPC can evolve from prostate adenocarcinoma in response to androgen deprivation therapy, but, in rare cases, is present at initial cancer diagnosis. The molecular aetiology of de novo SCPC is incompletely understood, owing to the scarcity of tumour tissue and the short life-expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology, and the remainder had some admixed adenocarcinoma foci, but all were treated with first-line platinum-based chemotherapy. The median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin-embedded archival tumour tissue. We observed frequent biallelic deletion and/or mutation of the tumour suppressor genes TP53, RB1, and PTEN, similarly to what was found in treatment-related SCPC. Indeed, at the RNA level, pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes, including BRCA1, BRCA2, ATM, and MSH2/6, potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harboured ETS gene rearrangements involving androgen-driven promoters, consistent with the evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape that underlies this unusual pathological variant, and suggest opportunities for targeted therapy strategies in a disease with few treatment options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Introduction Radiation dose to the rectum in prostate brachytherapy (PBT) can be reduced by the use of polyethylene glycol (PEG) hydrogel spacers. This reduces the rate of rectal toxicity and allows dose escalation to the prostate. Our objectives were to provide an overview of technique for injection of a PEG hydrogel spacer, reduction in rectal dosimetry, gastrointestinal toxicity and potential complications. Methods We systematically reviewed the role of PEG hydrogel spacers in PBT using the Cochrane and PRISMA methodology for all English-language articles from January 2013 to December 2019. Data was extracted for type of radiotherapy, number of patients, type of PEG-hydrogel used, mean prostate-rectum separation, rectal dosimetry, acute and late GI toxicity, procedure-related complications and the technique used for hydrogel insertion. Results Nine studies (671 patients and 537 controls) met our inclusion criteria. Of these 4 used DuraSeal ® and 5 used SpaceOAR ®. The rectal spacing achieved varied between 7.7-16 mm. Failure of hydrogel insertion was seen only in 12 patients, mostly related to failure of hydrodissection in patients undergoing salvage PBT. Where reported, the rectal D2 cc was reduced by between 21.6 and 52.6% and the median rectal V75% cc was reduced by between 91.8-100%. Acute GI complications were mostly limited to grade 1 or 2 toxicity (n = 153, 33.7%) with low levels of grade 3 or 4 toxicity (n = 1, 0.22%). Procedure-related complications were limited to tenesmus (0.14%), rectal discomfort (1.19%), and bacterial prostatitis (0.44%). Conclusions PEG hydrogel spacers are safe to insert. Gel insertion is easy, fast and has a low rate of failure. These studies convincingly demonstrate a significant reduction in rectal dosimetry. Although the results of spacers in reducing rectal toxicity is promising, these need to be confirmed in prospective randomised trial.

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