Prostate cancer detection through unbiased capture of methylated cell-free DNA.

Prostate cancer screening using prostate-specific antigen (PSA) has been shown to reduce mortality but with substantial overdiagnosis, leading to unnecessary biopsies. The identification of a highly specific biomarker using liquid biopsies, represents an unmet need in the diagnostic pathway for prostate cancer. In this study, we employed a method that enriches for methylated cell-free DNA fragments coupled with a machine learning algorithm which enabled the detection of metastatic and localized cancers with AUCs of 0.

A comparative study of peri-operative outcomes for 100 consecutive post-chemotherapy and primary robot-assisted and open retroperitoneal lymph node dissections.

Purpose: To describe and compare differences in peri-operative outcomes of robot-assisted (RA-RPLND) and open (O-RPLND) retroperitoneal lymph node dissection performed by a single surgeon where chemotherapy is the standard initial treatment for Stage 2 or greater non-seminomatous germ cell tumour.

Methods: Review of a prospective database of all RA-RPLNDs (28 patients) and O-RPLNDs (72 patients) performed by a single surgeon from 2014 to 2020. Peri-operative outcomes were compared for patients having RA-RPLND to all O-RPLNDs and a matched cohort of patients having O-RPLND (20 patients).

Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells.

BRCA1 deficiencies cause breast, ovarian, prostate and other cancers, and render tumours hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. To understand the resistance mechanisms, we conducted whole-genome CRISPR-Cas9 synthetic-viability/resistance screens in BRCA1-deficient breast cancer cells treated with PARP inhibitors. We identified two previously uncharacterized proteins, C20orf196 and FAM35A, whose inactivation confers strong PARP-inhibitor resistance.

Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer.

Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT).

Investigating upper urinary tract urothelial carcinomas: a single-centre 10-year experience.

Objectives: Evidence of the accuracy of predictive tests in confirming the presence and grade of upper urinary tract urothelial carcinomas (UUTUC) is limited. We present the largest series evaluating the diagnostic value of pre- and intra-operative parameters in the detection of UUTUC.

Materials And Methods: We retrospectively analysed records of patients who underwent diagnostic ureteroscopy between 2005 and 2014 for suspected UUTUC.

The importance of surgical margins in prostate cancer.

Positive surgical margins (PSM) after radical prostatectomy (RP) are a predictor of biochemical recurrence (BCR), and highly dependent on surgeon, experience, and skill. The length and location PSMs are important, with significant differences between open and robotic RP. The impact of PSMs on BCR remains secondary to other clinico-pathologic variables: Gleason Score, pathologic stage, and baseline PSA.

Vancomycin resistant enterococci in urine cultures: Antibiotic susceptibility trends over a decade at a tertiary hospital in the United Kingdom.

Purpose: Enterococci are a common cause of urinary tract infection and vancomycin-resistant strains are more difficult to treat. The purpose of this surveillance program was to assess the prevalence of and determine the risk factors for vancomycin resistance in adults among urinary isolates of Enterococcus sp. and to detail the antibiotic susceptibility profile, which can be used to guide empirical treatment.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae in hospital urinary tract infections: incidence and antibiotic susceptibility profile over 9 years.

Purpose: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are an increasing concern regarding antibiotic resistance and their potential to cause serious infections which are difficult to treat. The purpose of this surveillance programme was to assess the incidence of ESBL in adults amongst urinary isolates, identify risk factors, and detail the antibiotic susceptibility profile in order to guide empirical treatment.

Methods: From 2006 to 2014, we reviewed 21,414 positive urine cultures for E.

Surgical margin length and location affect recurrence rates after robotic prostatectomy.

Background: Robotic-assisted laparoscopic radical prostatectomy is a current standard treatment for localized prostate cancer, with treatment failure defined by biochemical recurrence (BCR). Open radical prostatectomy series have identified the presence of a positive surgical margin (PSM) as a predictor of long-term recurrence, a measure that is affected by the surgeon׳s skill. We evaluate the effect of PSM parameters on BCR rates from robotic-assisted laparoscopic radical prostatectomy, across 3 high-volume institutions.

Optimizing radical prostatectomy for the early recovery of urinary continence.

Radical prostatectomy remains the gold-standard treatment for clinically localized prostate cancer. Although cancer control is the primary goal, secondary outcomes such as continence recovery are of great importance to patients. Thus, it is a challenge for prostate cancer surgeons to optimize continence outcomes without compromising oncologic results.

Detailed analysis of operating time learning curves in robotic prostatectomy by a novice surgeon.

Objectives: Structured mentor-led training programmes permit the safe introduction of novice trainees to robotic-assisted laparoscopic prostatectomy (RALP). We outline the first description of parallel learning curves for individual surgical steps and quantify the relative difficulty of each step to propose an order of training in our structured mentoring programme.

Patients And Methods: A prospective ethically approved database was used to evaluate the operating times of each individual surgical step, in the first 150 RALP cases performed independently by a robotic-naive laparoscopic surgeon.

Pathological outcomes and strategies to achieve optimal cancer control during robotic radical prostatectomy in Asian-Indian men.

Introduction And Objectives: There is a paucity of information in the literature about the characteristics of prostate cancer in the Asian-Indian population. We wanted to evaluate the oncological outcomes of Asian-Indians and Caucasians. We also derived a nomogram for prediction of extraprostatic extension (EPE) and presented biochemical recurrence (BCR) rates in the Asian-Indian population.

Is robotic technology facilitating the minimally invasive approach to partial nephrectomy?

Objective: • To establish its current status, this study reviews the literature, and reports developments in robotic-assisted partial nephrectomy (RPN), highlighting results from various studies that investigate the oncological and functional efficacy of RPN. Partial nephrectomy has become the standard therapy for the management of small renal masses. In an effort to overcome the perioperative morbidity associated with an open approach, and the extended warm ischaemia times associated with a laparoscopic approach, robotic platforms have been introduced.

Biobanking after robotic-assisted radical prostatectomy: a quality assessment of providing prostate tissue for RNA studies.

Background: RNA quality is believed to decrease with ischaemia time, and therefore open radical prostatectomy has been advantageous in allowing the retrieval of the prostate immediately after its devascularization. In contrast, robotic-assisted laparoscopic radical prostatectomies (RALP) require the completion of several operative steps before the devascularized prostate can be extirpated, casting doubt on the validity of this technique as a source for obtaining prostatic tissue. We seek to establish the integrity of our biobanking process by measuring the RNA quality of specimens derived from robotic-assisted laparoscopic radical prostatectomy.

LESSons in minimally invasive urology.

Since the introduction of laparoscopic surgery, the promise of lower postoperative morbidity and improved cosmesis has been achieved. LaparoEndoscopic Single Site (LESS) surgery potentially takes this further. Following the first human urological LESS report in 2007, numerous case series have emerged, as well as comparative studies comparing LESS with standard laparoscopy.

The dramatic effects of Galantamine in a patient with early-onset Alzheimer's disease.

Introduction: We discuss the case of a 51 year old former mid-wife presented to the NHS Luton and Bedfordshire psychiatric services with a 2 year history of increasing forgetfulness with significant impairment to her daily function. She was diagnosed with non-familial early-onset Alzheimer's Disease (EOAD) and started on 8mg daily of the acetylcholinesterase inhibitor Galantamine.

Methods: The information for this study was gathered from patient notes, consultant, collateral and personal accounts.

Direct visualization of the trimeric structure of the ASIC1a channel, using AFM imaging.

There has been confusion about the subunit stoichiometry of the degenerin family of ion channels. Recently, a crystal structure of acid-sensing ion channel (ASIC) 1a revealed that it assembles as a trimer. Here, we used atomic force microscopy (AFM) to image unprocessed ASIC1a bound to mica.