Publications by authors named "Faiz Mumtaz"

42 Publications

Perioperative impact of body mass index on upper urinary tract and renal robot-assisted surgery: a single high-volume centre experience.

J Robot Surg 2021 Jul 27. Epub 2021 Jul 27.

Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, Hampstead, London, UK.

To assess the impact of body mass index (BMI) on peri-operative outcomes of kidney and upper tract robot-assisted surgery. Medical audit of patients who underwent robot-assisted kidney and upper tract cancer surgery at a single institution between 2017 and 2019, categorized on BMI into obese patients with a BMI ≥ 30 kg/m and a control group with BMI < 25 kg/m. Patient and tumour characteristics, surgery time, intraoperative blood loss, intraoperative adverse events (AE) according to the European Association of Urology Intraoperative Adverse Incidents Classification (EAUiaiC), conversion- to-open/radical rate as well as 30-day postoperative AE according to Clavien-Dindo (CD) and length of inpatient stay were analyzed. 366 patients were identified, 141 with a BMI < 25 (normal-weight) and 225 BMI ≥ 30 (obesity). There were no significant differences between the groups in terms of age, gender, comorbidities, tumour size, TNM stage and type of surgery. Obese patients had a higher estimated blood loss (198.05 ml), surgery time (171.75 min), intraoperative AE (all grades) (14.67%, 95% CI (0.10-0.19) as well as adherent perinephric fat (APF) (14.22%, 95% CI (0.09-0.19)) in contrast to the control group (86.85 ml, 148.29 min, 7.04% and 2.12%, respectively). Hospital stay, major intraoperative AE (≥ 3) and major postoperative AE (CD > 2) distributed equally between groups. Robotic kidney and upper tract surgery in obese patients showed an increase in surgery time and blood loss potentially related to APF. However, obesity was not associated with conversion to open surgery or radical nephrectomy in nephron-sparing procedures, length of stay, major intraoperative AE or postoperative complications.
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http://dx.doi.org/10.1007/s11701-021-01285-6DOI Listing
July 2021

Growth and renal function dynamics of renal oncocytomas on active surveillance.

BJU Int 2021 May 28. Epub 2021 May 28.

Division of Surgery and Interventional Science, University College London.

Objectives: To study the natural history of renal oncocytomas and address indications for intervention by determining how growth associates with renal function over time, the reasons for surgery and ablation, and disease-specific survival.

Patients And Methods: Retrospective cohort of consecutive patients with renal oncocytoma on active surveillance reviewed at the Specialist Centre for Kidney Cancer at Royal Free London NHS Foundation Trust (2012 to 2019). Comparison between groups was tested using the Mann-Whitney U and the Chi-square tests. A mixed-effects model with a random intercept for patient was used to study the longitudinal association between tumour size and estimated glomerular filtration rate (eGFR).

Results: Longitudinal data from 98 patients with 101 lesions was analysed. Most patients were male (68.3%), median age was 69 years (IQR 13). The median follow-up was 29 months (IQR 26). Most lesions were small renal masses, 24% measured over 4 cm. Over half (64.4%) grew at a median rate of 2 mm per year (IQR 4). No association was observed between tumour size and eGFR over time (p=0.871). Nine lesions (8.9%) were subsequently treated. Two deaths were reported, neither were related to the diagnosis of renal oncocytoma.

Conclusion: Natural history data from the largest active surveillance cohort of renal oncocytomas to date show that renal function does not seem to be negatively impacted by growing oncocytomas, and confirms clinical outcomes are excellent after a median follow up of over 2 years. Active surveillance should be considered the gold standard management of renal oncocytomas up to 7cm.
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http://dx.doi.org/10.1111/bju.15499DOI Listing
May 2021

The European Association of Urology COVID Intermediate-priority Group is Poorly Predictive of Pathological High Risk Among Patients with Renal Tumours.

Eur Urol 2021 Aug 20;80(2):265-267. Epub 2021 May 20.

UCL Medical School, University College London, London, UK; Specialist Centre For Kidney Cancer, Royal Free London NHS Foundation Trust, London, UK. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2021.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136273PMC
August 2021

Impact of the first surge of the COVID-19 pandemic on a tertiary referral centre for kidney cancer.

BJU Int 2021 May 8. Epub 2021 May 8.

Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, London, UK.

Objective: To analyse the impact of the COVID-19 pandemic on a centralized specialist kidney cancer care pathway.

Materials And Methods: We conducted a retrospective analysis of patient and pathway characteristics including prioritization strategies at the Specialist Centre for Kidney Cancer located at the Royal Free London NHS Foundation Trust (RFH) before and during the surge of COVID-19.

Results: On 18 March 2020 all elective surgery was halted at RFH to redeploy resources and staff for the COVID-19 surge. Prioritizing of patients according to European Association of Urology guidance was introduced. Clinics and the specialist multidisciplinary team (SMDT) meetings were maintained with physical distancing, kidney surgery was moved to a COVID-protected site, and infection prevention measurements were enforced. During the 7 weeks of lockdown (23 March to 10 May 2020), 234 cases were discussed at the SMDT meetings, 53% compared to the 446 cases discussed in the 7 weeks pre-lockdown. The reduction in referrals was more pronounced for small and asymptomatic renal masses. Of 62 low-priority cancer patients, 27 (43.5%) were deferred. Only one (4%) COVID-19 infection occurred postoperatively, and the patient made a full recovery. No increase in clinical or pathological upstaging could be detected in patients who underwent deferred surgery compared to pre-COVID practice.

Conclusion: The first surge of the COVID-19 pandemic severely impacted diagnosis, referral and treatment of kidney cancer at a tertiary referral centre. With a policy of prioritization and COVID-protected pathways, capacity for time-sensitive oncological interventions was maintained and no immediate clinical harm was observed.
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http://dx.doi.org/10.1111/bju.15441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239749PMC
May 2021

Pattern, timing and predictors of recurrence after surgical resection of chromophobe renal cell carcinoma.

World J Urol 2021 Apr 13. Epub 2021 Apr 13.

Division of Surgery and Interventional Science, University College London, London, UK.

Purpose: Currently there are no specific guidelines for the post-operative follow-up of chromophobe renal cell carcinoma (chRCC). We aimed to evaluate the pattern, location and timing of recurrence after surgery for non-metastatic chRCC and establish predictors of recurrence and cancer-specific death.

Methods: Retrospective analysis of consecutive surgically treated non-metastatic chRCC cases from the Royal Free London NHS Foundation Trust (UK, 2015-2019) and the international collaborative database RECUR (15 institutes, 2006-2011). Kaplan-Meier curves were plotted. The association between variables of interest and outcomes were analysed using univariate and multivariate Cox proportional hazards regression models with shared frailty for data source.

Results: 295 patients were identified. Median follow-up was 58 months. The five and ten-year recurrence-free survival rates were 94.3% and 89.2%. Seventeen patients (5.7%) developed recurrent disease, 13 (76.5%) with distant metastases. 54% of metastatic disease diagnoses involved a single organ, most commonly the bone. Early recurrence (< 24 months) was observed in 8 cases, all staged ≥ pT2b. 30 deaths occurred, of which 11 were attributed to chRCC. Sarcomatoid differentiation was rare (n = 4) but associated with recurrence and cancer-specific death on univariate analysis. On multivariate analysis, UICC/AJCC T-stage ≥ pT2b, presence of coagulative necrosis, and positive surgical margins were predictors of recurrence and cancer-specific death.

Conclusion: Recurrence and death after surgically resected chRCC are rare. For completely excised lesions ≤ pT2a without coagulative necrosis or sarcomatoid features, prognosis is excellent. These patients should be reassured and follow-up intensity curtailed.
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http://dx.doi.org/10.1007/s00345-021-03683-9DOI Listing
April 2021

Perioperative therapy in renal cancer in the era of immune checkpoint inhibitor therapy.

Curr Opin Urol 2021 05;31(3):262-269

Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust.

Purpose Of Review: Immune checkpoint inhibitor (ICI) combination therapy has revolutionized therapy of metastatic renal cancer. The success of immunotherapy has renewed an interest to study these agents in adjuvant and neoadjuvant settings and prior to cytoreductive nephrectomy. This narrative review will give an overview of ongoing trials and early translational research outcomes.

Recent Findings: In nonmetastatic renal cell carcinoma (RCC), five phase 3 adjuvant and neoadjuvant trials with ICI monotherapy or combinations are ongoing with atezolizumab (IMmotion 010; NCT03024996), pembrolizumab (KEYNOTE-564; NCT03142334), nivolumab (PROSPER; NCT03055013), nivolumab with or without ipilimumab (CheckMate 914; NCT03138512) and durvalumab with or without tremelimumab (RAMPART; NCT03288532). Phase 1b/2 neoadjuvant trials demonstrate safety, efficacy and dynamic changes of immune infiltrates and provide rationales for neoadjuvant trial concepts as well as prediction of response to therapy. In primary metastatic RCC, two phase 3 trials investigate the role of deferred cytoreductive nephrectomy following pretreatment with ICI combination (NORDICSUN; NCT03977571 and PROBE; NCT04510597).

Summary: The outcomes of the major phase 3 trials are awaited as early as 2023. Meanwhile, translational data from phase 1b/2 studies enhance our understanding of the tumour immune microenvironment and its dynamic changes.
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http://dx.doi.org/10.1097/MOU.0000000000000868DOI Listing
May 2021

Safety and feasibility of early single-dose mitomycin C bladder instillation after robot-assisted radical nephroureterectomy.

BJU Int 2020 12 9;126(6):739-744. Epub 2020 Aug 9.

Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, London, UK.

Objectives: To assess the safety and feasibility of early single-dose mitomycin C (MMC) bladder instillation after robot-assisted radical nephroureterectomy (RARNU) at a tertiary kidney cancer centre. RARNU with bladder cuff excision and subsequent MMC bladder instillation to reduce recurrence risk is the 'gold standard' for high-risk upper urinary tract urothelial carcinoma (UUTUC). We adapted a RARNU technique with precise distal ureteric dissection, bladder cuff excision and watertight bladder closure.

Patients And Methods: We retrospectively reviewed all patients undergoing RARNU for UUTUC at our centre performed as a standardised transperitoneal procedure comprising of: bladder cuff excision, two-layer watertight closure and intraoperative bladder leak test; without re-docking/re-positioning of the robotic surgical system. Patient demographics, the timing of MMC instillation, adverse events (surgical and potentially MMC-related) and length of stay (LOS) were assessed according to the Clavien-Dindo classification.

Results: A total of 69 patients underwent a RARNU with instillation of MMC. The median (interquartile range [IQR]) age was 70 (62-78) years. The median (IQR) day of MMC instillation was 2 (1-3) days and the median (IQR) LOS was 2 (2-4) days, with urethral catheter removal on day of discharge in all cases. Only Grade I Clavien-Dindo complications occurred in seven patients (10%); five had ileus, one a wound infection and one a self-limiting delirium, all managed conservatively. No adverse events potentially related to MMC instillation were noted within 30 days postoperatively.

Conclusion: The use of intravesical MMC instillation given in the immediate postoperative period appears feasible and safe in patients undergoing RARNU with intraoperative confirmation of a water-tight closure ensuring early catheter-free discharge, with no significant adverse events. The potential reduction in intravesical recurrence in patients receiving early MMC needs to be assessed with longitudinal follow-up studies.
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http://dx.doi.org/10.1111/bju.15162DOI Listing
December 2020

Complex Open Pyeloplasty in a Pelvic Kidney.

Urology 2020 Jul 16;141:e47-e48. Epub 2020 Apr 16.

Division of Surgery and Interventional Science, University College London, London, United Kingdom; Specialist centre for kidney cancer, Royal Free Hospital, London, United Kingdom. Electronic address:

A pelvic kidney occurs in between 1 in 2200 and 1 in 3000 people, due to failure of ascent during development. It is commonly asymptomatic and usually functions normally. Pelvic ureteral junction obstruction can either be congenital or acquired, and is characterized by intrinsic stenosis or extrinsic compression of the ureter at the junction with the pelvicalyceal renal system. This can cause symptomatic or asymptomatic hydronephrosis. We describe the complex case and management of a patient with a massive pelvic ureteral junction obstruction in a pelvic kidney.
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http://dx.doi.org/10.1016/j.urology.2020.03.048DOI Listing
July 2020

Will three-dimensional models change the way nephrometric scoring is carried out?

BJU Int 2019 12;124(6):898-899

Royal Free London NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1111/bju.14907DOI Listing
December 2019

Guideline adherence for the surgical treatment of T1 renal tumours correlates with hospital volume: an analysis from the British Association of Urological Surgeons Nephrectomy Audit.

BJU Int 2020 01 18;125(1):73-81. Epub 2019 Aug 18.

Netherlands Cancer Institute, Amsterdam, The Netherlands.

Objective: To assess European Association of Urology guideline adherence on the surgical management of patients with T1 renal tumours and the effects of centralisation of care.

Patients And Methods: Retrospective data from all kidney tumours that underwent radical nephrectomy (RN) or partial nephrectomy (PN) in the period 2012-2016 from the British Association of Urological Surgeons Nephrectomy Audit were retrieved and analysed. We assessed total surgical hospital volume (HV; RN and PN performed) per centre, PN rates, complication rates, and completeness of data. Descriptive analyses were performed, and confidence intervals were used to illustrate the association between hospital volume and proportion of PN. Chi- squared and Cochran-Armitage trend tests were used to evaluate differences and trends.

Results: In total, 13 045 surgically treated T1 tumours were included in the analyses. Over time, there was an increase in PN use (39.7% in 2012 to 44.9% in 2016). Registration of the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) complexity score was included in March 2016 and documented in 39% of cases. Missing information on postoperative complications appeared constant over the years (8.5-9%).  A clear association was found between annual HV and the proportion of T1 tumours treated with PN rather than RN (from 18.1% in centres performing <25 cases/year [lowest volume] to 61.8% in centres performing ≥100 cases/year [high volume]), which persisted after adjustment for PADUA complexity. Overall and major (Clavien-Dindo grade ≥III) complication rate decreased with increasing HV (from 12.2% and 2.9% in low-volume centres to 10.7% and 2.2% in high-volume centres, respectively), for all patients including those treated with PN.

Conclusion: Closer guideline adherence was exhibited by higher surgical volume centres. Treatment of T1 tumours using PN increased with increasing HV, and was accompanied by an inverse association of HV with complication rate. These results support the centralisation of kidney cancer specialist cancer surgical services to improve patient outcomes.
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http://dx.doi.org/10.1111/bju.14862DOI Listing
January 2020

Protocol for a feasibility study of a cohort embedded randomised controlled trial comparing phron paring reatment (NEST) for small renal masses.

BMJ Open 2019 06 11;9(6):e030965. Epub 2019 Jun 11.

Department of Surgical Biotechnology, Division of Surgery and Interventional Science, University College London, London, UK.

Introduction: Small renal masses (SRMs; ≤4 cm) account for two-thirds of new diagnoses of kidney cancer, the majority of which are incidental findings. The natural history of the SRM seems largely indolent. There is an increasing concern regarding surgical overtreatment and the associated health burden in terms of morbidity and economy. Observational data support the safety and efficacy of percutaneous cryoablation but there is an unmet need for high-quality evidence on non-surgical management options and a head-to-head comparison with standard of care is lacking. Historical interventional trial recruitment difficulties demand novel study conduct approaches. We aim to assess if a novel trial design, the cohort embedded randomised controlled trial (RCT), will enable carrying out such a comparison.

Methods And Analysis: Single-centre prospective cohort study of adults diagnosed with SRM (n=200) with an open label embedded interventional RCT comparing nephron sparing interventions. Cohort participants will be managed at patient and clinicians' discretion and agree with longitudinal clinical data and biological sample collection, with invitation for trial interventions and participation in comparator control groups. Cohort participants with biopsy-proven renal cell carcinoma eligible for both percutaneous cryoablation and partial nephrectomy will be randomly selected (1:1) and invited to consider percutaneous cryoablation (n=25). The comparator group will be robotic partial nephrectomy (n=25). The primary outcome of this feasibility study is participant recruitment. Qualitative research techniques will assess barriers and recruitment improvement opportunities. Secondary outcomes are participant trial retention, health-related quality of life, treatment complications, blood transfusion rate, intensive care unit admission and renal replacement requirement rates, length of hospital stay, time to return to pre-treatment activities, number of work days lost, and health technologies costs.

Ethics And Dissemination: Ethical approval has been granted (UK HRA REC 19/EM/0004). Study outputs will be presented and published.

Trial Registration: ISRCTN18156881; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2019-030965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6577353PMC
June 2019

Robot-assisted partial nephrectomy: How to minimise renal ischaemia.

Arab J Urol 2018 Sep 7;16(3):350-356. Epub 2018 Jul 7.

Specialist Centre for Renal Cancer, Royal Free Hospital, London, UK.

Renal ischaemia research has shown an increase in renal damage proportional to ischaemic time. Therefore, we assessed the importance of renal ischaemic times for warm and cold ischaemia approaches, and explored the different surgical techniques that can help to minimise renal ischaemia in robot-assisted partial nephrectomy (RAPN). Minimising renal ischaemia during nephron-sparing surgery (NSS) is a key factor in preserving postoperative renal function. Current data support a safe warm ischaemia time (WIT) of ≤25 min and cold ischaemic time of ≤35 min, resulting in no significant deterioration in renal function. In general, patients undergoing NSS have increased comorbidities, including chronic kidney disease, and in these patients it is difficult to predict their postoperative renal function recovery. With RAPN, efforts should be made to keep the WIT to <25 min, as minimising the ischaemic time is vital for preservation of overall renal function and remains a modifiable risk factor. Parenchymal or segmental artery clamping, early unclamping or off-clamp techniques can be adopted when ischaemic times are likely to be >25 min, but may not lead to superior functional outcome. Careful preoperative planning, tumour factors, and meticulous surgical technique are critical for optimum patient outcome.
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http://dx.doi.org/10.1016/j.aju.2018.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105361PMC
September 2018

Contemporary surgical management of renal oncocytoma: a nation's outcome.

BJU Int 2018 06 2;121(6):893-899. Epub 2018 Mar 2.

Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, London, UK.

Objective: To report on the contemporary UK experience of surgical management of renal oncocytomas.

Patients And Methods: Descriptive analysis of practice and postoperative outcomes of patients with a final histological diagnosis of oncocytoma included in The British Association of Urological Surgeons (BAUS) nephrectomy registry from 01/01/2013 to 31/12/2016. Short-term outcomes were assessed over a follow-up of 60 days.

Results: Over 4 years, 32 130 renal surgical cases were recorded in the UK, of which 1202 were oncocytomas (3.7%). Most patients were male (756; 62.9%), the median (interquartile range [IQR]) age was 66.8 (13) years. The median (IQR; range) lesion size was 4.1 (3; 1-25) cm, 43.5% were ≤4 cm and 30.3% were 4-7 cm lesions. In all, 35 patients (2.9%) had preoperative renal tumour biopsy. Most patients had minimally invasive surgery, either radical nephrectomy (683 patients; 56.8%), partial nephrectomy (483; 40.2%) or other procedures (36; 3%). One in five patients (243 patients; 20.2%) had in-hospital complications: 48 were Clavien-Dindo classification grade ≥III (4% of the total cohort), including three deaths. Two additional deaths occurred within 60 days of surgery. The analysis is limited by the study's observational nature, not capturing lesions on surveillance or ablated after biopsy, possible underreporting, short follow-up, and lack of central histology review.

Conclusion: We report on the largest surgical series of renal oncocytomas. In the UK, the complication rate associated with surgical removal of a renal oncocytoma was not negligible. Centralisation of specialist services and increased utilisation of biopsy may inform management, reduce overtreatment, and change patient outcomes for this benign tumour.
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http://dx.doi.org/10.1111/bju.14159DOI Listing
June 2018

Robotic-assisted Laparoscopic Partial Nephrectomy in a Horseshoe Kidney. A Case Report and Review of the Literature.

Urology 2018 Apr 27;114:e3-e5. Epub 2017 Dec 27.

Department of Urology, Royal Free Hospital, London, United Kingdom. Electronic address:

Horseshoe kidney is a rare renal fusion anomaly, and because of limited mobilization of the kidney and its multiple arterial blood supplies, minimally invasive surgery for renal tumors can be challenging. We describe a case of a right-side oncocytoma in a horseshoe kidney managed robotically and review the literature of robotic-assisted laparoscopic surgical resection of kidney tumors in renal fusion anomalies. Robotic-assisted laparoscopic partial nephrectomy in a horseshoe kidney is feasible. Fusion-related limited mobility during the procedure, as well as an extremely variable blood supply, require meticulous planning. Multi-phase computed tomography and interactive 3D anatomical models are helpful tools to prepare for surgery.
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http://dx.doi.org/10.1016/j.urology.2017.12.003DOI Listing
April 2018

Cascade Fumarate Hydratase mutation screening allows early detection of kidney tumour: a case report.

BMC Med Genet 2017 07 26;18(1):79. Epub 2017 Jul 26.

Centre for Nephrology, University College London, Royal Free Hospital, London, UK.

Background: Fumarate hydratase (FH) deficiency is a rare autosomal recessive disorder which results in a major defect in cellular metabolism. It presents in infancy with progressive encephalopathy, hypotonia, seizures and failure to thrive and is often fatal in childhood. It is caused by mutations in the FH gene (1q42.1) that result in deficiency of the citric acid cycle enzyme fumarate hydratase, resulting in accumulation of fumaric acid. Heterozygous germline mutations in the FH gene predispose to an aggressive autosomal dominant inherited early-onset kidney cancer syndrome: hereditary leiomyomatosis and renal cell cancer (HLRCC).

Case Presentation: Cascade FH mutation screening enabled the early diagnosis of a renal tumour in an asymptomatic parent of a child with fumarate hydratase deficiency, resulting in timely and possibly life-saving treatment.

Conclusion: While the theoretical risk of kidney cancer in parents of children with recessive fumarate hydratase deficiency is well recognized, to our knowledge this is the first report of a kidney tumour being detected in a parent by screening performed for this indication. This underscores the importance of offering lifelong kidney surveillance to such parents and other heterozygous relatives of children born with fumarate hydratase deficiency.
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http://dx.doi.org/10.1186/s12881-017-0436-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530463PMC
July 2017

Optimising renal cancer patients for nephron-sparing surgery: a review of pre-operative considerations and peri-operative techniques for partial nephrectomy.

Urologia 2017 Feb 16;84(1):20-27. Epub 2017 Jan 16.

Department of Urology, Royal Free London NHS Foundation Trust, London - UK.

Nonmodifiable factors including pre-operative renal function and amount of healthy renal tissue preserved are the most important predictive factors that determine renal function after partial nephrectomy. Ischaemia time is an important modifiable risk factor and cold ischaemia time should be used if longer ischaemia time is anticipated. New techniques may have a role in maximising postoperative kidney function, but more robust studies are required to understand their potential benefits and risks.
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http://dx.doi.org/10.5301/uro.5000208DOI Listing
February 2017

Hepatitis and Solitary Left Renal Mass: Renal Hepatocellular Carcinoma.

Urology 2016 Oct 18;96:114-115. Epub 2016 Jul 18.

Royal Free NHS Foundation Trust, London, United Kingdom.

Solitary renal tumours are often primary clear cell carcinoma. A 48-year-old man with chronic hepatitis, hepatocellular carcinoma (HCC), and orthotropic liver transplant 6 years ago presented with a solitary left renal mass. Histology revealed metastatic HCC of the left kidney with extensive reactive changes in lymph nodes. Interestingly, biopsy of the transplanted liver showed no evidence of HCC recurrence. Metastatic disease to the kidney often disseminate locally through transcelomic spread, or hematogenous affecting both kidneys. It is important to recognize extrahepatic HCC metastases to the contralateral kidney, especially in patients with active hepatitis, and radical lymph node clearance is needed.
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http://dx.doi.org/10.1016/j.urology.2016.07.008DOI Listing
October 2016

Sign of the times: be careful what you say in the operating room.

Lancet 2016 Feb;387(10018):536

The Renal Cancer Center, Royal Free Hospital, Pond Street, London NW3 2QG, UK.

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http://dx.doi.org/10.1016/S0140-6736(16)00224-5DOI Listing
February 2016

Angiotensin II increases corpus cavernosal contractility and oxidative stress in partial bladder outlet obstructed rabbits: relevance to erectile dysfunction.

J Sex Med 2013 May 21;10(5):1251-8. Epub 2012 May 21.

Department of General Surgery, Division of Interventional Science, University College London Medical School, London, UK.

Introduction: We investigated the effect angiotensin II (Ang II), a corpus cavernosal smooth muscle (CCSM) constrictor peptide, has on tissue taken from rabbits following chronic partial bladder outlet obstruction (PBOO), as this model is characterized by an increase in corpus cavernosal collagen deposition and a marked reduction and impaired relaxation of CCSM cells.

Aim: To determine the interaction between Ang II and nitric oxide (NO) and the development of oxidative stress (OS) in a rabbit model of chronic PBOO.

Methods: Corpus cavernosal tissue was obtained from 12 sham-operated and 20 PBOO rabbits. Organ bath studies determined Ang II/NO interaction on CCSM function using losartan (AT1 receptor antagonist), sodium nitroprusside (SNP, NO donor), electrical field stimulation (EFS), and vardenafil (phosphodiesterase type 5 inhibitor). The role of OS in the Ang II response was also determined using diphenylene iodonium chloride (DPI), the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, which inhibits superoxide production and superoxide dismutase (SOD, the enzyme that accelerates the breakdown of superoxide).

Main Outcome Measure: Action of Ang II and AT1 receptor antagonist, as well as SOD and DPI on CCSM function.

Results: Ang II caused a dose-dependent contraction of CCSM strips that was enhanced in PBOO rabbits and inhibited by losartan, DPI, and SOD. CCSM relaxation induced by SNP/EFS was impaired in this model and improved by vardenafil and losartan.

Conclusions: These findings imply that the increased Ang II contractile response is a pathological consequence of PBOO and that AT1 receptor inhibition may be a therapeutic approach to treat ED associated with PBOO.
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http://dx.doi.org/10.1111/j.1743-6109.2012.02768.xDOI Listing
May 2013

Effect of angiotensin II and its receptor antagonists on human corpus cavernous contractility and oxidative stress: modulation of nitric oxide mediated relaxation.

J Urol 2011 Jun 21;185(6):2414-20. Epub 2011 Apr 21.

Division of Interventional Science, Department of Clinical Biochemistry, University College London Medical School, Royal Free Campus, Enfield, United Kingdom.

Purpose: To our knowledge the interaction between angiotensin II and nitric oxide in the control of human corpus cavernous function has not been assessed previously. We determined the presence and role of angiotensin II and its receptors in human penile function.

Materials And Methods: Corpus cavernous tissue was obtained from 35 patients undergoing gender reassignment surgery. Immunohistochemical analysis was done to determine angiotensin II peptide tissue distribution. Organ bath studies were done to determine the angiotensin II/nitric oxide interaction on corpus cavernous smooth muscle function. The role of oxidative stress in the angiotensin II response was also examined using the nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin.

Results: Angiotensin II was distributed in arteriolar endothelium, endothelium lining sinusoids and smooth muscle cells, and caused dose dependent contraction of human corpus cavernous smooth muscle strips that was inhibited by the angiotensin type 1 receptor antagonist losartan. Relaxation of corpus cavernous smooth muscle induced by the nitric oxide donor sodium nitroprusside or electrical field stimulation was potentiated by losartan. Apocynin decreased angiotensin II induced corpus cavernous contraction.

Conclusions: Angiotensin II and nitric oxide interact to modulate human cavernous function since losartan potentiated sodium nitroprusside and electrical field stimulation mediated corpus cavernous smooth muscle relaxation. The angiotensin II response involves the production of superoxide and the development of oxidative stress. These findings support the role of angiotensin II in the regulation of human penile smooth muscle tone and suggest that angiotensin type 1 receptor inhibition may be a therapeutic approach to erectile dysfunction.
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http://dx.doi.org/10.1016/j.juro.2011.02.2645DOI Listing
June 2011

Serotonin induces a biphasic response in rabbit cavernosal smooth muscle: relevance to the erectile process.

Urol Int 2007 ;79(3):255-61

Department of Urology, Royal Free Hospital and University College Medical School, University College London, London, UK.

Introduction: Serotonin (5-hydroxytryptamine; 5-HT) can cause contraction in cavernosal smooth muscle. We further evaluated this effect of 5-HT.

Methods: Organ bath studies were used.

Results: 5-HT induced a sustained contraction occasionally accompanied by a transient relaxation (in 30% of rabbit cavernosal tissues) that preceded the contraction. Ondansetron and Y-25130 (both 5-HT3 receptor antagonists) but not SB-269970 (a 5-HT7 receptor antagonist) significantly inhibited or abolished this transient relaxation. Doxazosin (dox, an alpha1-receptor antagonist) and ketanserin (ketan, a 5-HT2A receptor antagonist) significantly inhibited or abolished the sustained contraction. The effects of dox on 5-HT-mediated contraction were concentration-dependent.

Conclusions: Our findings further confirm that the peripheral serotonergic pathway may play a part in the erectile process via 5-HT2A receptor-mediated contractile and 5-HT3 receptor-mediated relaxant activities. Our results also support the findings of human studies, which suggest that both ketan and dox may exert beneficial effects on the erectile process.
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http://dx.doi.org/10.1159/000107959DOI Listing
November 2007

Patterns of urethral injury and immediate management.

Curr Opin Urol 2007 Nov;17(6):383-9

Derriford Hospital, Plymouth, Devon, UK.

Purpose Of Review: The management of urethral trauma remains controversial. The purpose of this review is to provide a concise account of the patterns of urethral injury and the current trends of its immediate management.

Recent Findings: Recent studies have identified types of pelvic fractures associated with a higher risk of urethral injury. Recognition of these fractures coupled with timely radiographic imaging has facilitated the earlier diagnosis of urethral injury and ensured that serious long-term sequelae are minimized. In highly selected cases of complete anterior and posterior urethral disruption primary realignment by a combined antegrade and retrograde endoscopic approach is increasingly being considered as a management option to restore early urethral continuity. Urethral trauma secondary to penetrating gunshot wounds and penile fracture requires immediate surgical exploration and repair.

Summary: The urologist involved in the management of genitourinary tract trauma needs to recognize the patterns of urethral injury, especially those associated with certain pelvic fractures. A judicious and systematic approach coupled with a conscious effort to minimize short and long-term sequelae of all urethral injuries will ensure optimal results. There is a need for a consensus on the optimal management of each of the vast arrays of urethral injuries.
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http://dx.doi.org/10.1097/MOU.0b013e3282f0d5fdDOI Listing
November 2007

Modernising urological careers: the 'numbers game'.

BJU Int 2007 May 16;99(5):969-71. Epub 2007 Jan 16.

The Monash Medical Centre, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/j.1464-410X.2006.06692.xDOI Listing
May 2007

Laparoscopic nephroplication and nephropexy as an adjunct to pyeloplasty in UPJO with giant hydronephrosis.

Int Urol Nephrol 2006 ;38(3-4):443-6

Department of Urology, All India Institute of Medical Sciences, 110029, New Delhi, India.

Giant hydronephrosis due to uretero-pelvic junction obstruction (UPJO) is rare and usually the treatment is nephrectomy. When renal salvage is required, reconstruction of the UPJ alone is usually inadequate to improve drainage from the pelvicalyceal system. Various open surgical techniques have been described to improve gravity-assisted drainage from the giant hydronephrotic kidney. We describe, for the first time, a complete laparoscopic approach for pyeloplasty combined with nephroplication and nephropexy.
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http://dx.doi.org/10.1007/s11255-005-4975-6DOI Listing
September 2007

Minimally invasive treatment of ureteropelvic junction obstruction: optimizing outcomes with concomitant cost reduction.

J Endourol 2006 Sep;20(9):663-8

Barnet and Chase Farm NHS Trust, Chase Farm Hospital, Enfield, UK.

With the seemingly exponential increase in the use of minimally invasive techniques in urology, cost-benefit comparisons will continue to play a major part in establishing services and in improving those that already exist. The management of ureteropelvic junction obstruction is a focus of significant attention. An effective way of optimizing the economy of management is to understand the implications in terms of the success of each mode of treatment. Subsequently, costing models should be developed and applied in large-scale multicenter studies with the aid of health economists. The long-term benefits can then be assessed by also including patient's perceived quality of life. Economic assessment will not be enough to promote cost-effective practices. The take-up of any techniques will always be influenced not only by patient preference and surgeon expertise but also, perhaps ironically, by the way hospitals and surgeons are remunerated. In addition, the impact of the time taken to train a surgeon to carry out laparoscopic dismembered pyeloplasty competently may play a significant role. Until these issues are resolved, definitive recommendation for the treatment of ureteropelvic junction obstruction will continue to be made on an individual basis.
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http://dx.doi.org/10.1089/end.2006.20.663DOI Listing
September 2006

The role of serotonin (5-hydroxytryptamine1A and 1B) receptors in prostate cancer cell proliferation.

J Urol 2006 Oct;176(4 Pt 1):1648-53

Department of Urology, Royal Free Hospital and University College Medical School, University College, London, United Kingdom.

Purpose: Serotonin (5-hydroxytryptamine), a monoamine neurotransmitter released by prostate neuroendocrine cells, has a fundamental role in tumor growth, differentiation and gene expression. We investigated the effect of 5-hydroxytryptamine and 5-hydroxytryptamine antagonists on the growth of prostate cancer cells and we identified 5-hydroxytryptamine receptor expression in PC3 cells and in human hormone refractory prostate cancer tissue.

Materials And Methods: A total of 12 preparations of hormone refractory PC3 human prostate cancer cells were incubated with 5-hydroxytryptamine, or the 5-hydroxytryptamine receptor antagonists 5-hydroxytryptamine1A, 1B, 1D, 2, 3 or 4. After 72 hours cell viability was assessed using the crystal violet assay. PC3 cells treated with 5-hydroxytryptamine1A and 1B antagonists were investigated for apoptosis using flow cytometry. PC3 cells and sections of hormone refractory human prostate cancer tissue were studied by immunohistochemistry and Western blot analysis.

Results: In PC3 cells 5-hydroxytryptamine caused dose dependent proliferation with a maximum increase of 15% in 12 preparations at a concentration of 10(-8) M at 72 hours compared to controls (p < 0.0001). At a concentration of 10(-4) M at 72 hours the 5HT1A antagonist NAN-190 hydrobromide and the 5-hydroxytryptamine1B antagonist SB224289 HCl (Tocris Laboratories, Bristol, United Kingdom) induced a 20% and 78% inhibitory effect, respectively, on PC3 cell growth compared to that in controls (p < 0.0001). In PC3 cells 5-hydroxytryptamine1A and 1B antagonists demonstrated apoptosis after 24 and 48 hours of incubation. Immunostaining for 5-hydroxytryptamine1A and 1B receptors was seen in PC3 cells and prostate cancer tissue. Western blot analysis demonstrated 5-hydroxytryptamine1A and 1B receptor proteins with 46 and 43 kDa bands, respectively.

Conclusions: In PC3 prostate cancer cells 5-hydroxytryptamine1A and to a greater extent 5-hydroxytryptamine1B antagonists significantly inhibit growth and induce apoptosis. To our knowledge growth inhibition caused by the 5-hydroxytryptamine1B antagonist SB224289 HCl is a novel finding, as is apoptosis caused by the 2 antagonists 5-hydroxytryptamine1A and 1B. This effect is most likely mediated via 5-hydroxytryptamine1A and 1B receptors. Therefore, our results imply that 5-hydroxytryptamine1A and in particular 5-hydroxytryptamine1B receptor antagonists warrant further investigations as potential anti-neoplastic agents.
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http://dx.doi.org/10.1016/j.juro.2006.06.087DOI Listing
October 2006

Gene therapy and erectile dysfunction: the current status.

Asian J Androl 2007 Jan 4;9(1):8-15. Epub 2006 Aug 4.

Department of Urology, Royal Free Hospital and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2QG, UK.

Current available treatment options for erectile dysfunction (ED) are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 (PDE5) inhibitors (i.e. sildenafil, tadalafil and vardenafil) has revolutionized the treatment of ED, these oral medications require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Future ED therapies might consider the application of molecular technologies such as gene therapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means for altering intracavernous pressure "on demand" without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined (lacunar) spaces. This review provides a brief insight of the current role of gene therapy in the management of ED.
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http://dx.doi.org/10.1111/j.1745-7262.2007.00224.xDOI Listing
January 2007

Doxazosin and serotonin (5-HT) receptor (1A, 2A, and 4) antagonists inhibit 5-HT-mediated human cavernosal contraction.

J Androl 2006 Sep-Oct;27(5):679-85. Epub 2006 May 25.

Department of Urology, Royal Free Hospital and University College Medical School, University College London, United Kingdom.

Penile erection results from the balance between relaxation and contractile mechanisms of the corpus cavernosum. Only a few studies suggest a role for endogenous contractile agents such as 5-hydroxytryptamine (5-HT). Our aim was to confirm the possible role of 5-HT in human erection. The effect of 5-HT on human cavernosal tissues, as well as those of doxazosin (shown previously to have 5-HT inhibitory action), ketanserin (5-HT (2A) receptor antagonist), NAN-190 (5-HT (1A) receptor antagonist), and SB 203186 (5-HT (4) receptor antagonist) on 5-HT-mediated effects, were assessed using the organ bath technique, including electrical field stimulation study (EFS). Results are presented as median (mg/mg = mg contraction/mg of tissue). Consistent 5-HT-mediated (10(-3) M) contractions were demonstrated (n = 18; 63 mg/mg). These contractions were inhibited with ketanserin by 90% (n = 8), NAN-190 by 68% (n = 12), and SB 203186 by 55% (n = 12). Doxazosin showed a similar 5-HT inhibitory action in a concentration-dependent manner (10(-4) M; 94% reduction; n = 8, 10(-6) M; 68.3% reduction; n = 8). Our EFS studies indicated the presence of neuronally derived 5-HT and that a majority of the nonnoradrenogenic contraction (54%) was mediated via 5-HT(2A) receptors. These findings suggest that 5-HT may play a role in the human detumescence process via 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors. Neuronally released 5-HT is probably an important contractile neurotransmitter in the erectile process. Doxazosin, ketanserin, and 5-HT(1A) and 5-HT(4) receptor antagonists may be useful as part of combination therapy used to treat erectile dysfunction.
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http://dx.doi.org/10.2164/jandrol.106.000547DOI Listing
November 2006

Pharmacological properties of endothelin-1 in the rabbit corpus cavernosum.

In Vivo 2006 Mar-Apr;20(2):243-6

Department of Urology, Royal Free Hospital and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.

Background: Endothelin (ET-1) may play a role in the regulation of erection but this has not been conclusively demonstrated. Augmented cavernosal smooth muscle (CSM) contraction in the rat occurs following exposure to both ET-1 and phenylephrine (PE; alpha-1 agonist). The aim of this study was to assess the effect of ET-1 and its possible role in the alpha1-adrenergic pathway during the erectile process.

Materials And Methods: Organ bath studies were performed on CSM strips of penises obtained from 12 age-matched New Zealand White rabbits. The effect of ET-1 and PE alone on CSM tone in the absence and presence of ETA (BQ123) and ETB (BQ788) antagonists was assessed. Tissue responses were measured as tension (newton, N). EC50 values are expressed as mean +/- S.E.M.

Results: PE (10(8) - 10(-4) M) and ET-1 (10(-10) - 10(-6) M) produced a concentration-dependent contraction in rabbit CSM strips. The EC50 values were 1.7 x 10(-7) M +/- 1.1 and 3.4 x 10(-9) M +/- 1.5, respectively. BQ123 10(-5) M significantly inhibited ET-1-mediated CSM contractions more than BQ788 10(-5) M (both ANOVA p<0.01). The EC50 were 1.3 x 10(-6) M +/- 2.6 and 2.0 x 10(-7) M +/- 2.1, respectively. Neither the ETA or ETB receptor antagonist had a significant influence on alpha1-adrenergic receptor-mediated CSM contraction.

Conclusion: ETA receptors may play a greater role than ETB receptors in ET-1-induced rabbit CSM contraction and the detumescence process. The a1-adrenergic-dependent pathway does not involve the ETA or ETB receptors.
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May 2006
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