PROTACs Targeting BRM (SMARCA2) Afford Selective Degradation over BRG1 (SMARCA4) and Are Active in BRG1 Mutant Xenograft Tumor Models.

The identification of VHL-binding proteolysis targeting chimeras (PROTACs) that potently degrade the BRM protein (also known as SMARCA2) in SW1573 cell-based experiments is described. These molecules exhibit between 10- and 100-fold degradation selectivity for BRM over the closely related paralog protein BRG1 (SMARCA4). They also selectively impair the proliferation of the H1944 "BRG1-mutant" NSCLC cell line, which lacks functional BRG1 protein and is thus highly dependent on BRM for growth, relative to the wild-type Calu6 line.

CALIBER: a phase II randomized feasibility trial of chemoablation with mitomycin-C vs surgical management in low-risk non-muscle-invasive bladder cancer.

Objectives: To evaluate the activity of intravesical mitomycin-C (MMC) to ablate recurrent low-risk non-muscle-invasive bladder cancer (NMIBC) and assess whether it may enable patients to avoid surgical intervention for treatment of recurrence.

Patients And Methods: CALIBER is a phase II feasibility study. Participants were randomized (2:1) to treatment with four once-weekly MMC 40-mg intravesical instillations (chemoablation arm) or to surgical management.

The management of secondary pelvi-ureteric junction obstruction - a comparison of pyeloplasty and endopyelotomy.

Objective: To review our experience in the management of secondary pelvi-ureteric junction obstruction (PUJO) comparing endopyelotomy with pyeloplasty.

Patients And Methods: We retrospectively analysed our database of 58 patients having undergone operative management of PUJO after failed primary management, including 41 with failed pyeloplasty and 17 failed endopyelotomy. Outcomes included mercapto-acetyltriglycine (MAG3) drainage capacity, symptomatic control and need for further intervention.

Does previous failed ESWL have a negative impact of on the outcome of ureterorenoscopy? A matched pair analysis.

This study aims to evaluate the outcome of ureteroscopy/ureterorenoscopy (URS) as a salvage procedure for stones resistant to extracorporeal shock wave lithotripsy (ESWL). Between January 2009 and January 2012, 313 patients with upper tract lithiasis were treated by URS. Among them, 87 (27.

New ureteral stent design does not improve patient quality of life: a randomized, controlled trial.

Purpose: Ureteral stents result in significant morbidity in many patients. Manufacturers have altered stent design and composition to minimize symptoms. The Polaris™ stent is made of a Percuflex® combination, providing a firm proximal aspect with a softer distal aspect to minimize symptoms.

Audit of safety, efficacy, and cost-effectiveness of local anaesthetic cystodiathermy.

Introduction: The aim of this study was to audit our experience of cystodiathermy under local anaesthetic (LA) at the time of flexible cystoscopy for recurrent superficial bladder transitional cell carcinoma (TCC).

Patients And Methods: A total of 264 flexible cystoscopies were performed on patients with a past history of TCC. The number and site of recurrences were recorded and selected patients were offered cystodiathermy.

The Role of Non-Steroidal Anti-Inflammatory Drugs in Renal Colic.

NSAIDs provide optimal analgesia in renal colic due to the reduction in glomerular filtration and renal pelvic pressure, ureteric peristalsis and ureteric oedema. Prevention of glomerular afferent arteriolar vasodilatation renders these patients at risk of renal impairment. NSAIDs have the additional benefit of reducing the number of new colic episodes and preventing subsequent readmission to hospital.

A comparative study of quality of life issues relating to open versus laparoscopic nephrectomy: a prospective pragmatic study.

Purpose: We determined whether laparoscopic nephrectomy confers improved health related quality of life in the early postoperative period compared with open nephrectomy.

Materials And Methods: Patients undergoing open or laparoscopic nephrectomy were prospectively recruited. Patients completed the Comorbidity Symptom Scale preoperatively as well as the SF-36(R) quality of life health survey and pain visual analog scale preoperatively, and 2 days and 1 month postoperatively.

Prospective study comparing the bladeless optical access trocar versus Hasson open trocar for the establishment of pneumoperitoneum in laparoscopic renal procedures.

Introduction: To present a single centre prospective randomized study on the use of the bladeless Optiview system (Ethicon Endosurgery, Cincinnati, OH) to create the pneumoperitoneum in laparoscopic renal procedures reporting the results with regards safety, efficacy and complications and comparing it with the Hasson open technique.

Patients And Methods: Sixty patients were randomly recruited, 27 to the open and 33 to the bladeless group at the Bristol Urological Institute, UK. Time to insertion, time to closure and any intraoperative and postoperative complication related to trocar insertion was recorded.

Antegrade versus retrograde stenting in laparoscopic pyeloplasty.

Purpose: To compare operative times between retrograde and antegrade ureteral stenting as part of laparoscopic pyeloplasty.

Patients And Methods: Laparoscopic pyeloplasty procedures from January 2002 to January 2007 were identified through a prospective database. Procedures on 126 patients were performed using the same transperitoneal technique apart from the method of stent placement, which was performed in either a retrograde manner before laparoscopy or an antegrade manner during the laparoscopic portion of the procedure.

Effect of smooth muscle relaxant drugs on proximal human ureteric activity in vivo: a pilot study.

Drugs are increasingly being used to promote stone passage in renal colic. Diclofenac, nifedipine and tamsulosin cause ureteric smooth muscle relaxation in vitro; however, in clinical trials nifedipine and tamsulosin promote stone passage whereas diclofenac has no apparent benefit. We adapted a ureteric pressure transducer catheter in an attempt to compare the human ureteric response to these drugs in vivo.

Does rate matter? The results of a randomized controlled trial of 60 versus 120 shocks per minute for shock wave lithotripsy of renal calculi.

Purpose: In this study we prospectively compared 2 rates of shock wave delivery, 60 and 120 shock waves per minute, to determine whether rate affects outcome with the Dornier Lithotripter S, a lithotriptor with an electromagnetic shock wave source, for renal calculi.

Materials And Methods: A total of 104 patients with uncomplicated single renal calculus were randomized and treated. Following a single treatment patients were reviewed at 3 months to determine outcome.

A comparative in vitro study to determine the beneficial effect of calcium-channel and alpha(1)-adrenoceptor antagonism on human ureteric activity.

Objective: To compare the in vitro human ureteric muscle response to calcium-channel and alpha-adrenoceptor antagonists, to determine the promoting factor for stone passage. Clinical trials suggest that stone passage in renal colic can be promoted by ureteric relaxation using these agents, however nonsteroidal anti-inflammatory drugs appear to reduce ureteric activity in vitro but do not promote stone passage when used in clinical trials.

Materials And Methods: Human ureteric muscle strips were used to record the effect that each drug had on muscle tone in vitro.

A reminder of the association between Clostridium septicum and colonic adenocarcinoma.

We present the case of a patient, with previously unknown liver metastases, presenting with a liver abscess and Clostridium septicum septicaemia. C. septicum is known to be associated with both malignancy and immunosuppression and therefore in patients where this organism is isolated, efforts must be made to exclude an occult underlying malignancy or haematological disorder.

Antegrade versus retrograde endopyelotomy for pelvi-ureteric junction (PUJ) obstruction.

Objectives: To compare complication and success rates of antegrade and retrograde endopyelotomy performed over 10 years and to define possible risk factors associated with treatment failure.

Methods: From 1994 to 2004, 61 patients underwent a total of 68 endoscopic treatments: 19 antegrade and 49 retrograde endopyelotomy procedures. Antegrade endopyelotomy was always performed using diathermy.

A 3-year review of The British Association of Urological Surgeons Section of Endourology Laparoscopic Nephrectomy Audit.

Objective: To report and compare the data obtained from the BAUS UK national laparoscopic nephrectomy audit over the past 3 years.

Methods: Each year, consultants performing laparoscopic nephrectomy are invited to submit prospectively collected data on all patients so treated at their centres. The data from each centre is entered into a nationally established database using a standard data-collection sheet.

Our experience with retroperitoneal and transperitoneal laparoscopic pyeloplasty for pelvi-ureteric junction obstruction.

Objective: Laparoscopic dismembered pyeloplasty has been quoted to have equivalent success rates to the traditional open procedure in the treatment of pelvi-ureteric junction obstruction (PUJO). The aim of this study was to report our experience with laparoscopic pyeloplasty.

Patients And Methods: All patients with PUJO are entered into a database to record patient, operative and post-operative details.