Oral estrogen receptor PROTAC® vepdegestrant (ARV-471) is highly efficacious as monotherapy and in combination with CDK4/6 or PI3K/mTOR pathway inhibitors in preclinical ER+ breast cancer models.

PURPOSE: Estrogen Receptor (ER) alpha signaling is a known driver of ER-positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Combining endocrine therapy (ET) such as fulvestrant with CDK4/6, mTOR or PI3K inhibitors is now a central strategy for the treatment of ER+ advanced breast cancer. However, suboptimal ER inhibition and resistance resulting from ESR1 mutation dictates that new therapies are needed. EXPERIMENTAL DESIGN: A medicinal chemistry campaign identified vepdegestrant (ARV-471), a selective, orally bioavailable, potent small molecule PROteolysis-TArgeting Chimera (PROTAC®) degrader of ER. We used biochemical and intracellular target engagement assays to demonstrate the mechanism of action of vepdegestrant, and ESR1 wild-type and mutant ER+ preclinical breast cancer models to demonstrate ER degradation-mediated tumor growth inhibition. RESULTS: Vepdegestrant induced ≥90% degradation of wild-type (WT) and mutant ER, inhibited ER-dependent breast cancer cell line proliferation in-vitro and achieved significant tumor growth inhibition (TGI) (87-123%) in MCF7 orthotopic xenograft models, better than the ET agent fulvestrant (31-80% TGI). In the hormone-independent ER Y537S patient derived xenograft (PDX) breast cancer model ST941/HI, vepdegestrant achieved tumor regressions and was similarly efficacious in the ST941/HI/PBR palbociclib-resistant model (102% TGI). Vepdegestrant induced robust tumor regressions in combination with each of the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib, the mTOR inhibitor everolimus, and the PI3K inhibitors alpelisib and inavolisib. CONCLUSIONS: Vepdegestrant achieved greater ER degradation in-vivo compared to fulvestrant, which correlated with improved tumor growth inhibition, suggesting vepdegestrant could be a more effective backbone ET for patients with ER+/HER2- breast cancer.

PROTACs Targeting BRM (SMARCA2) Afford Selective In Vivo 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. In vivo experiments performed with a subset of compounds identified PROTACs that potently and selectively degraded BRM in the Calu6 and/or the HCC2302 BRG1 mutant NSCLC xenograft models and also afforded antitumor efficacy in the latter system. Subsequent PK/PD analysis established a need to achieve strong BRM degradation (>95%) in order to trigger meaningful antitumor activity in vivo. Intratumor quantitation of mRNA associated with two genes whose transcription was controlled by BRM (PLAU and KRT80) also supported this conclusion.

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 surgical group was included to assess the feasibility of randomization. The primary endpoint was complete response to intravesical MMC in the chemoablation arm at 3 months, reported with exact 95% confidence intervals (CIs). Secondary endpoints included time to subsequent recurrence, summarized by Kaplan-Meier methods. RESULTS: Between February 2015 and August 2017, 82 patients with visual diagnosis of recurrent low-risk NMIBC were enrolled from 24 UK hospitals (chemoablation, n = 54; surgical management, n =28). The median follow-up was 24 months. Complete response at 3 months was 37.0% (20/54; 95% CI 24.3-51.3) with chemoablation and 80.8% (21/26; 95% CI 60.6-93.4) with surgical management. Amongst patients with complete response at 3 months, a similar proportion was recurrence-free by 12 months in both groups (84%). Amongst those with residual disease at 3 months, the 12-month recurrence-free proportion was lower in the surgical management group (40.0%) than in the chemoablation group (84%). Recruitment stopped early as chemoablation did not meet the prespecified threshold of 45% complete responses at 3 months. CONCLUSION: Intravesical chemoablation in low-risk NMIBC is feasible and safe, but did not demonstrate sufficient response in the present trial. After chemoablation there may be a reduction in recurrence rate, even in non-responders, that is greater than with surgery alone. Further research is required to investigate the role and optimal schedule of neoadjuvant intravesical chemotherapy prior to surgery for NMIBC.

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. Success was defined as freedom from failure in all three. RESULTS: Patients undergoing secondary pyeloplasty had better outcomes than endopyelotomy for symptomatic success (87.5% vs 74%), resolution of obstruction on MAG3 renography (96% vs 74%), and no need for further intervention (96% vs 71%). Overall success was 87.5% for pyeloplasty compared with 44% after secondary endopyelotomy. CONCLUSION: Outcomes of pyelopasty for secondary PUJO were superior when compared with endopyelotomy.

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 (27.8 %) had undergone URS after prior ESWL failed to achieve stone clearance (Salvage group). These patients were matched with a group of patients who underwent URS as first-line modality (Primary group). Stone-free rates and adjuvant procedures represented the primary points for comparison. Secondary points for comparison included complications, procedure duration, total laser energy used and length of hospitalization. Matching was possible in all cases. Stone clearance rates were 73.6 and 82.8 % for the Salvage and Primary group, respectively. The difference in stone clearance rates between the two groups was not statistically significant (p = 0.186). A total of 11 patients (12.6 %) in the Primary group and 18 patients (20.7 %) in the Salvage group underwent an adjuvant procedure (p = 0.154). No statistically significant differences were noted in terms of complications, procedure duration and length of hospitalization. In the Primary group, the laser energy used for stone fragmentation was higher (p = 0.043). The rate of ureteric stenting at the end of the procedure was higher for the Salvage group (p = 0.030). Previous failed ESWL is not a predictor for unfavorable outcome of URS. Salvage URS is associated, however, with an increased need for ureteric stenting at the end of the procedure.

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. In this prospective, randomized study we compared symptoms and quality of life after stent insertion to determine whether this stent is better tolerated than the InLay® stent. MATERIALS AND METHODS: Between September 2002 and September 2006 we randomized 159 patients requiring stent insertion for stone disease to receive the InLay or the Polaris ureteral stent. Patients were asked to complete the validated Ureteral Stent Symptom Questionnaire 2 weeks after stent insertion and 1 week after removal. RESULTS: A total of 98 patients completed and returned each questionnaire, including 45 with the InLay and 53 with the Polaris. There were no significant differences between the groups on any health domain assessed. In the InLay and Polaris groups 91% and 94% of patients experienced pain with the stent in situ, which decreased to 40% and 43%, respectively, after stent removal. The urinary symptom score with the stent in situ was equal in the 2 groups (32, maximum 55). Of the InLay and Polaris groups 60% and 66% of patients, respectively, would be against receiving a further stent due to symptoms (p = 0.79). CONCLUSIONS: The Polaris stent, designed with the specific aim of improving urinary symptoms and pain associated with ureteral stents, continues to have a significant detrimental effect on patient quality of life.

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. Patient tolerability was noted. At follow-up, any recurrence was recorded. RESULTS: Eighty patients (30%) had 91 procedures showing one or more recurrences. Fifty-one of the 80 patients (64%) were treated with cystodiathermy under LA. All completed treatment. Forty-five (88%) tolerated the procedure well. Forty-seven (92%) treatments were completed within 5 min. At a median follow-up of 15 weeks, 30 (59%) treated patients had no recurrence and three (6%) had recurrence at the site of treatment. CONCLUSIONS: LA cystodiathermy is an effective and well-tolerated alternative to general anaesthetic cystodiathermy that enables treatment at the time of detection and may, thereby, reduce patient anxiety.

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. Despite recent work promoting the use of pharmacological agents to improve stone passage rates, NSAIDs do not appear to reduce the time to stone passage or increase the likelihood of stone passage in renal colic.

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. RESULTS: A total of 100 patients were recruited, of whom 71 completed all questionnaires, including 38 in the laparoscopic group and 33 in the open group. In the 2 groups mean patient age was the same (56.8 years) and there was a similar sex distribution. The laparoscopic group had improved quality of life scores with significantly higher physical component scores 1 month postoperatively vs the open group (-5.7% vs -22.2%, p = 0.009). The laparoscopic group also had significantly higher mental component scores 2 days postoperatively vs the open group compared to baseline (6.0% vs -6.6%, p = 0.009). The laparoscopic group had significantly lower pain visual analog scale scores 1 month postoperatively compared to baseline. Patients with higher Comorbidity Symptom Scale scores were more likely to undergo a laparoscopic approach (p = 0.036). Despite this they had a significantly shorter hospital stay (4 vs 6 days, p <0.001). CONCLUSIONS: Quality of life benefits of laparoscopic over open nephrectomy were found in the early postoperative period despite more comorbidities in the laparoscopic group. This provides further evidence of the benefits of the laparoscopic approach over open surgery.

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. RESULTS: All procedures were performed for renal pathology. BMI values were similar in both groups. The mean time to insertion of the 12 mm Hasson and Bladeless trocars were 443 and 125 seconds, respectively (p < 0.0001). The incision in the bladeless group was only closed when the defect exceeded 12 mm (38%) or extended for specimen removal (23%), resulting in a mean time to closure of 203 seconds. In the Hasson group, entry into the abdominal cavity could not be confirmed in two patients (7.4%) due to multiple adhesions. In the Bladeless group, there was one failed placement (3%) requiring conversion to the Hasson technique and two injuries to intraabdominal structures (peritoneal minor bruising, liver injury requiring conversion to open procedure, 6%), There was one incidence of gas leakage (3%). There were no reports of port site herniation at a mean follow up of 9 months. CONCLUSION: Direct placement of a bladeless trocar under direct vision in a desufflated abdomen can reduce port placement time when compared to the Hasson technique. The benefits are maximised by using the bladeless trocar for procedures not requiring intact specimen removal. However, despite visualisation of tissue layers, this port cannot prevent serious intra abdominal injuries that can occur in a higher percentage of cases in comparison to the Hasson technique.

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. RESULTS: A total of 45 patients underwent antegrade stenting, 53 had retrograde stenting, 20 patients already had a stent in place, and 8 patients had retrograde pyelography followed by antegrade stenting. Operative time in patients with antegrade stent placement was significantly faster than in those with retrograde stent placement (median 185 v 245 min, P < 0.0001 [two-way analysis of variance]), even when the variability of the operative surgeon was taken into account. There was no difference in the complication rates. CONCLUSION: Antegrade stent placement results in a significantly faster overall operative time when compared with retrograde stent placement.

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. The catheter was inserted into the contralateral ureter following ureteroscopy for stone disease. Contraction frequency, pressure and velocity measurements were recorded at 24 h. Each patient was randomly allocated to receive oral diclofenac, nifedipine or tamsulosin. Measurements were taken following drug administration. Eighteen patients (mean age 50 years) were recruited. Two patients were excluded intraoperatively and three required early removal of the catheter. Prior to drug administration, the mean number of contractions recorded was 0-4.1/min and the peak contraction pressure ranged from 11 to 35 mmHg. Conduction velocity ranged from 1.5 to 2.6 cm/s. Ureteric peristalsis persisted in all patients despite these drugs. Diclofenac and nifedipine produced inconsistent ureteric pressure responses but had little effect on contraction frequency. Tamsulosin significantly reduced ureteric pressure but had no effect on contraction frequency. There are many limitations associated with the use of ureteric catheters, however, they may provide some useful information when used to record the response to an intervention in the same patient. These preliminary results suggest a reduction in pressure generation may be the essential factor in the promotion of stone passage. More work is required but these drugs may work by preventing the increased, uncoordinated muscular activity seen in renal colic whilst maintaining peristalsis, thereby promoting stone passage.

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 plain abdominal x-ray was performed and the size of any residual fragments was noted. Four patients were lost to followup, 1 in the 60 shock waves per minute group and 3 in the 120 shock waves per minute group. RESULTS: Of the 100 patients with complete followup 49 were treated at 60 shock waves per minute and 51 at 120 shock waves per minute. There was no statistically significant difference between mean stone area treated (p = 0.32) or additional analgesic use in the form of patient controlled alfentanil (p = 0.82). A successful outcome was defined by fragments smaller than 4 mm or stone-free status. At 60 shock waves per minute 59% of patients had a successful outcome compared with 61% at 120 shock waves per minute (p = 0.87) following a single treatment. Post-treatment complications were similar in both groups at 8% for 120 shock waves per minute and 10% for 60 shock waves per minute (p = 0.68). CONCLUSIONS: There was no significant difference in patient controlled analgesia use, complications or outcome between rates 60 and 120. Contrary to previous studies these results suggest that a slower rate of shock wave delivery during extracorporeal shock wave lithotripsy for renal calculi does not improve treatment efficacy with the Dornier Lithotripter S.

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. The ureter was obtained at open nephrectomy or cystectomy. Potassium-enriched Krebs' solution was used to evoke maximal muscle tone, followed by adding each drug in increasing concentrations to determine the percentage reduction in tone. The drugs used to represent each group were nifedipine, 5-methylurapidil (5-MU) and diclofenac. In all, 201 ureteric strips were obtained from 39 patients. RESULTS: At all drug concentrations, the in vitro relaxant effect of nifedipine and 5-MU was greater than that of diclofenac. At 10(-5) M the median reduction in proximal and distal ureteric tone to diclofenac, nifedipine and 5-MU were 18%, 5% and 47%, vs 57%, 33% and 65%, respectively. CONCLUSION: Nifedipine and 5-MU produced greater ureteric relaxation in vitro than diclofenac; they predominantly relax distal ureter. This suggests that a reduction in ureteric muscle tone, as opposed to complete ablation of activity, might be the promoting factor for stone passage.

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. In the first 18 procedures retrograde endopyelotomy was performed using diathermy. In the most recent 30 procedures the incision was made using holmium laser. Endoluminal ultrasound was used in 78% of retrograde endopyelotomy and in 5% of antegrade endopyelotomy. RESULTS: The retrograde endopyelotomy patients demonstrated significantly lower complication rates (12.5% vs. 42%) and shorter hospital stay (1.5 vs. 7 days) than the antegrade endopyelotomy patients. The mean follow up of the patients who remained free from disease recurrence during the study period was 46 and 24 months for the antegrade and retrograde endopyelotomy group, respectively. The overall success rate (mean time to failure) of antegrade and retrograde endopyelotomy was 56% (31 months) and 70% (17 months), respectively. There was no statistically significant increase in the overall success rate of retrograde endopyelotomy using endoluminal ultrasound per se. Stratifying retrograde endopyelotomy by the type of energy used for the incision, the overall success rate (mean time to failure) was 80% (10 months) and 53% (21 months) for Holmium laser and diathermy, respectively (p = 0.0626). CONCLUSIONS: The overall success of antegrade and retrograde endopyelotomy in this series appears to be largely a factor of lead-time bias and is similar enough to recommend retrograde endopyelotomy with holmium laser on the basis of its relative safety and shorter hospital stay.

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. The indications for surgery, and data during and after surgery are collected. Since 2001, data were reported on 1294 laparoscopic nephrectomies. RESULTS: Over the 3 years, the number of centres returning data has increased from 25 to 48. In 2002, data on 263 nephrectomies were returned; by 2004, this had increased to 598. In all three audits, most cases were for nonfunctioning kidneys and renal cell carcinoma, with transitional cell carcinoma and stones forming a smaller proportion. Over the 3 years, the mean (range) operative duration has reduced from 173 (89-335) to 166 (42-395) min. The median postoperative stay remained at 4-5 days, with a wide range reflecting other than clinical reasons for delayed discharge. The mortality rate remained low, at 0.7% and 0.2%, respectively, for 2002 and 2004. The mean conversion rate remained at 6-8% and the mean complication rate at 17-2%, but the proportion of major complications reduced from 10% to 4%. The transfusion rate also reduced from 10% to 7%. The operative duration, transfusion and conversion rates were higher in those centres performing fewer than 12 cases/year than in those performing at least one case per month. CONCLUSION: The BAUS laparoscopic nephrectomy audit is an effective method for ensuring both the safe and widespread implementation of this relatively new technique to the UK, and compliance with internationally accepted standards. This audit has shown differences in clinical outcomes in favour of high-volume centres, which may help to inform decisions about the centralization of urological laparoscopy services.

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. Over an eleven-year period, 176 procedures were performed. Eighty-three procedures were dismembered laparoscopic pyeloplasties, of which two retroperitoneal procedures were converted to open. The first 17 procedures were performed via the retroperitoneal approach and the following 66 via the transperitoneal route. Thirty-one procedures were open pyeloplasty. RESULTS: The retroperitoneal group had a mean follow up of 35 (16-66) months. Five patients (33%) developed recurrent symptoms with evidence of obstruction seen on the renogram within 4 months and required further surgery. The transperitoneal group had a mean follow up of 15 (3-38) months. Five patients were classified as failures (mean time to failure 4.6 months) resulting in a success rate of 92% for the transperitoneal route. Both groups had a mean post-operative hospital stay of 3.6 days. Open pyeloplasty at our institution has a success rate of 88% at a mean follow up of 85 months (range 3-260 months) and a mean length of post-operative stay of 6 days. CONCLUSION: Overall our success rate following laparoscopic pyeloplasty is 88%. However, our preferred approach is transperitoneal, which is associated with a success rate of 92%. This is equivalent, if not better than that seen following open pyeloplasty with the additional benefits of reduced hospital stay and time to recovery. There are many possible explanations for this difference in success rates between approaches, however equivalent results are reported in the literature and therefore the learning curve is likely to be the major factor in this series.