Robotic versus laparoscopic versus open nephrectomy for live kidney donors.

BACKGROUND: Waiting lists for kidney transplantation continue to grow. Live kidney donation significantly reduces waiting times and improves long-term outcomes for recipients. Major disincentives to potential kidney donors are the pain and morbidity associated with surgery. This is an update of a review published in 2011. OBJECTIVES: To assess the benefits and harms of open donor nephrectomy (ODN), laparoscopic donor nephrectomy (LDN), hand-assisted LDN (HALDN) and robotic donor nephrectomy (RDN) as appropriate surgical techniques for live kidney donors. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 31 March 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing LDN with ODN, HALDN, or RDN were included. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Thirteen studies randomising 1280 live kidney donors to ODN, LDN, HALDN, or RDN were included. All studies were assessed as having a low or unclear risk of bias for selection bias. Five studies had a high risk of bias for blinding. Seven studies randomised 815 live kidney donors to LDN or ODN. LDN was associated with reduced analgesia use (high certainty evidence) and shorter hospital stay, a longer procedure and longer warm ischaemia time (moderate certainty evidence). There were no overall differences in blood loss, perioperative complications, or need for operations (low or very low certainty evidence). Three studies randomised 270 live kidney donors to LDN or HALDN. There were no differences between HALDN and LDN for analgesia requirement, hospital stay (high certainty evidence), duration of procedure (moderate certainty evidence), blood loss, perioperative complications, or reoperations (low certainty evidence). The evidence for warm ischaemia time was very uncertain due to high heterogeneity. One study randomised 50 live kidney donors to retroperitoneal ODN or HALDN and reported less pain and analgesia requirements with ODN. It found decreased blood loss and duration of the procedure with HALDN. No differences were found in perioperative complications, reoperations, hospital stay, or primary warm ischaemia time. One study randomised 45 live kidney donors to LDN or RDN and reported a longer warm ischaemia time with RDN but no differences in analgesia requirement, duration of procedure, blood loss, perioperative complications, reoperations, or hospital stay. One study randomised 100 live kidney donors to two variations of LDN and reported no differences in hospital stay, duration of procedure, conversion rates, primary warm ischaemia times, or complications (not meta-analysed). The conversion rates to ODN were 6/587 (1.02%) in LDN, 1/160 (0.63%) in HALDN, and 0/15 in RDN. Graft outcomes were rarely or selectively reported across the studies. There were no differences between LDN and ODN for early graft loss, delayed graft function, acute rejection, ureteric complications, kidney function or one-year graft loss. In a meta-regression analysis between LDN and ODN, moderate certainty evidence on procedure duration changed significantly in favour of LDN over time (yearly reduction = 7.12 min, 95% CI 2.56 to 11.67; P = 0.0022). Differences in very low certainty evidence on perioperative complications also changed significantly in favour of LDN over time (yearly change in LnRR = 0.107, 95% CI 0.022 to 0.192; P = 0.014). Various different combinations of techniques were used in each study, resulting in heterogeneity among the results. AUTHORS' CONCLUSIONS: LDN is associated with less pain compared to ODN and has comparable pain to HALDN and RDN. HALDN is comparable to LDN in all outcomes except warm ischaemia time, which may be associated with a reduction. One study reported kidneys obtained during RDN had greater warm ischaemia times. Complications and occurrences of perioperative events needing further intervention were equivalent between all methods.

Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinoma.

PURPOSE: Patients with resected localized clear-cell renal cell carcinoma (ccRCC) remain at variable risk of recurrence. Incorporation of biomarkers may refine risk prediction and inform adjuvant treatment decisions. We explored the role of tumor genomics in this setting, leveraging the largest cohort to date of localized ccRCC tissues subjected to targeted gene sequencing. EXPERIMENTAL DESIGN: The somatic mutation status of 12 genes was determined in 943 ccRCC cases from a multinational cohort of patients, and associations to outcomes were examined in a Discovery (n = 469) and Validation (n = 474) framework. RESULTS: Tumors containing a von-Hippel Lindau (VHL) mutation alone were associated with significantly improved outcomes in comparison with tumors containing a VHL plus additional mutations. Within the Discovery cohort, those with VHL+0, VHL+1, VHL+2, and VHL+≥3 tumors had disease-free survival (DFS) rates of 90.8%, 80.1%, 68.2%, and 50.7% respectively, at 5 years. This trend was replicated in the Validation cohort. Notably, these genomically defined groups were independent of tumor mutational burden. Amongst patients eligible for adjuvant therapy, those with a VHL+0 tumor (29%) had a 5-year DFS rate of 79.3% and could, therefore, potentially be spared further treatment. Conversely, patients with VHL+2 and VHL+≥3 tumors (32%) had equivalent DFS rates of 45.6% and 35.3%, respectively, and should be prioritized for adjuvant therapy. CONCLUSIONS: Genomic characterization of ccRCC identified biologically distinct groups of patients with divergent relapse rates. These groups account for the ∼80% of cases with VHL mutations and could be used to personalize adjuvant treatment discussions with patients as well as inform future adjuvant trial design.

The current status of robotic colorectal surgery training programmes.

Robotic-assisted colorectal surgery (RACS) is steadily increasing in popularity with an annual growth in the number of colorectal procedures undertaken robotically. Further upscaling of RACS requires structured and standardised robotic training to safeguard high-quality clinical outcomes. The aims of this systematic review were to assess the structure and assessment metrics of currently established RACS training programmes. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines was performed. Searches were performed of the Ovid Medline, Embase and Web of Science databases between 2000 and 27th November 2021 to identify studies reporting on training curricula in RACS. Core components of training programmes and their relevant outcome assessment metrics were extracted. Thirteen studies were identified, with all training programmes designed for the da Vinci platform (Intuitive Surgical, Inc., Sunnyvale, CA, USA). Common elements of multimodal programmes included theoretical knowledge (76.9%), case observation (53.8%), simulation (100%) and proctored training (76.9%). Robotic skills acquisition was assessed primarily during the simulation phase (n = 4, 30.1%) and proctoring phase (n = 10, 76.9%). Performance metrics, consisting of time or assessment scores for VR simulation were only mandated in four (30.1%) studies. Objective assessment following proctored training was variably reported and employed a range of assessment metrics, including direct feedback (n = 3, 23.1%) or video feedback (n = 8, 61.5%). Five (38.4%) training programmes used the Global Assessment Score (GAS) forms. There is a broad consensus on the core multimodal components across current RACS training programmes; however, validated objective assessment is limited and needs to be appropriately standardised to ensure reproducible progression criteria and competency-based metrics are produced to robustly assess progression and competence.

A Delphi consensus statement for digital surgery.

The use of digital technology is increasing rapidly across surgical specialities, yet there is no consensus for the term 'digital surgery'. This is critical as digital health technologies present technical, governance, and legal challenges which are unique to the surgeon and surgical patient. We aim to define the term digital surgery and the ethical issues surrounding its clinical application, and to identify barriers and research goals for future practice. 38 international experts, across the fields of surgery, AI, industry, law, ethics and policy, participated in a four-round Delphi exercise. Issues were generated by an expert panel and public panel through a scoping questionnaire around key themes identified from the literature and voted upon in two subsequent questionnaire rounds. Consensus was defined if >70% of the panel deemed the statement important and <30% unimportant. A final online meeting was held to discuss consensus statements. The definition of digital surgery as the use of technology for the enhancement of preoperative planning, surgical performance, therapeutic support, or training, to improve outcomes and reduce harm achieved 100% consensus agreement. We highlight key ethical issues concerning data, privacy, confidentiality and public trust, consent, law, litigation and liability, and commercial partnerships within digital surgery and identify barriers and research goals for future practice. Developers and users of digital surgery must not only have an awareness of the ethical issues surrounding digital applications in healthcare, but also the ethical considerations unique to digital surgery. Future research into these issues must involve all digital surgery stakeholders including patients.

Feasibility and safety of radical prostatectomy for oligo-metastatic prostate cancer: the Testing Radical prostatectomy in men with prostate cancer and oligo-Metastases to the bone (TRoMbone) trial.

OBJECTIVES: To test the feasibility of randomisation to radical prostatectomy (RP) plus pelvic lymphadenectomy in addition to standard-of-care (SOC) systemic therapy in men with newly diagnosed oligo-metastatic prostate cancer. PATIENTS AND METHODS: A prospective, randomised, non-blinded, feasibility clinical trial with an embedded QuinteT Recruitment Intervention (QRI) to optimise recruitment was conducted in nine nationwide tertiary care centres undertaking high-volume robotic surgery. We aimed to randomise 50 men with synchronous oligo-metastatic prostate cancer within an 18-month recruitment period to SOC systemic therapy vs SOC plus RP (intervention arm). The main outcome measures were: ability to randomise patients, optimised by a QRI; EuroQoL five Dimensions five Levels (EQ-5D-5L) questionnaires to capture quality-of-life (QoL) data at baseline and 3 months post-randomisation; routine clinicopathological assessment to capture adverse events and prostate-specific antigen in both arms, plus standard perioperative parameters in the surgical arm. RESULTS: A total of 51 men were randomised within 14 months (one was subsequently deemed ineligible), with 60-83% accrual rate in centres that recruited at least two patients. All patients completed the trial follow-up; one patient in the intervention arm subsequently did not undergo the surgical intervention and one in the SOC arm refused all therapies. The QRI positively impacted recruitment. QoL data showed similarly high functioning in both study arms. Surgery for men with oligo-metastatic prostate cancer was found to be safe and had similar impact on early functional outcomes as surgery for standard indication. CONCLUSION: It is feasible to randomise men with synchronous oligo-metastatic prostate cancer to a surgical intervention in addition to standard systemic therapies. While surgery appeared safe with no substantial impact on QoL in this feasibility study, a large randomised controlled trial is now warranted to examine treatment effectiveness of this additional component in the multimodality management of oligo-metastatic prostate cancer.

Ten-year survival outcomes after radical nephroureterectomy with a risk-stratified approach using prior diagnostic ureteroscopy: a single-institution observational retrospective cohort study.

OBJECTIVES: To evaluate the long-term oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) and the impact of diagnostic ureteroscopy (URS) on survival outcomes. MATERIALS AND METHODS: A retrospective analysis of all consecutive patients undergoing RNU for suspected UTUC at a UK tertiary referral centre from a prospectively maintained database was conducted. The primary outcome measures were 5- and 10-year cancer-specific survival (CSS). The secondary outcomes were: overall survival (OS), recurrence-free survival (RFS), impact of prior diagnostic URS on OS, CSS and intravesical RFS (intravesical-RFS), and predictors of intravesical recurrence. Statistical analysis was performed in R using the 'survminer' and 'survival' packages. The Kaplan-Meier method was used to calculate survival functions and these were expressed in graphical form. Uni-/multivariate survival analyses were performed using the Cox proportional hazard regression model. Statistical significance in this study was set at P < 0.05. RESULTS: A total of 422 patients underwent RNU with confirmed UTUC. The median (interquartile range) follow-up of patients with confirmed UTUC was 9.2 (5.6-12.7) years. The 5- and 10-year CSS rates were 70.5% (95% confidence interval [CI] 65.9-74.9) and 67.1% (95% CI 62.4-71.6), respectively. OS (HR 1.04 [95% CI 0.78-1.38]; P = 0.46) and CSS (HR 0.96 [95% CI 0.68-1.34]; P = 0.81) were similar in the diagnostic URS and the direct RNU cohorts. intravesical RFS was superior for the direct RNU cohort (HR 1.94 [95% CI 1.19-3.17]; P = 0.008). In multivariate analysis, prior URS, T2 stage, proximal ureter tumour and bladder cancer history were predictors of metachronous bladder recurrence. CONCLUSION: This single-centre retrospective cohort study reports the long-term oncological outcomes of RNU with a median follow-up of 9.2 years, serving as a reference standard in counselling patients undergoing RNU. Stage and grade of the RNU specimen were the only two studied factors that appeared to adversely impact long-term CSS and OS. Our results suggest that the risk of intravesical recurrence is increased nearly twofold in patients who have undergone diagnostic URS prior to RNU. Prior URS, however, does not appear to adversely impact long-term CSS and OS. The authors suggest that a risk-stratified approach be adopted, wherein diagnostic URS is offered only in equivocal cases.

Contemporary application of artificial intelligence in prostate cancer: an i-TRUE study.

Artificial intelligence (AI) involves technology that is able to emulate tasks previously carried out by humans. The growing incidence, novel diagnostic strategies and newer available therapeutic options have had resource and economic impacts on the healthcare organizations providing prostate cancer care. AI has the potential to be an adjunct to and, in certain cases, a replacement for human input in prostate cancer care delivery. Automation can also address issues such as inter- and intra-observer variability and has the ability to deliver analysis of large volume datasets quickly and accurately. The continuous training and testing of AI algorithms will facilitate development of futuristic AI models that will have integral roles to play in diagnostics, enhanced training and surgical outcomes and developments of prostate cancer predictive tools. These AI related innovations will enable clinicians to provide individualized care. Despite its potential benefits, it is vital that governance with AI related care is maintained and responsible adoption is achieved.

Can the Use of Serial Multiparametric Magnetic Resonance Imaging During Active Surveillance of Prostate Cancer Avoid the Need for Prostate Biopsies?-A Systematic Diagnostic Test Accuracy Review.

CONTEXT: The role of multiparametric magnetic resonance imaging (mp-MRI) during active surveillance (AS) of prostate cancer needs evaluation. It remains unclear whether mp-MRI can replace prostate biopsies completely during AS. OBJECTIVE: To evaluate the diagnostic performance of mp-MRI for disease progression in men on AS for prostate cancer. EVIDENCE ACQUISITION: This systematic review was performed in accordance with the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Cross-sectional studies that evaluate the diagnostic performance of mp-MRI (index test) for disease progression compared with systematic and targeted prostate/template biopsies or a composite of this (reference standard) were included. A meta-analysis was performed using STATA with "metandi" and "midas" commands. EVIDENCE SYNTHESIS: Seven studies with 800 patients were included in this systematic review. The pooled pathological progression rate was 27%. The pooled sensitivity and specificity of mp-MRI for disease progression were 0.61 (95% confidence interval [CI]: 0.46-0.74) and 0.78 (95% CI: 0.54-0.91), respectively. Adjusting for a prevalence of disease progression of 30% results in a positive predictive value of 0.43 (95% CI: 0.39-0.46) and a negative predictive value of 0.81 (95% CI: 0.78-0.84). Significant heterogeneity was observed. The meta-regression analysis did not demonstrate any significant outliers. CONCLUSIONS: It is not possible to supplant prostate biopsies with mp-MRI in AS protocols with the current level of evidence. There is significant institutional variation in the diagnostic performance of mp-MRI during AS. Institutions must internally audit the diagnostic performance of mp-MRI in the AS setting. AS protocols must be based on local diagnostic performance, rather than on international AS protocols that may have limited applicability at individual settings. PATIENT SUMMARY: In this review, we explored the accuracy of multiparametric magnetic resonance imaging in diagnosing disease progression for patients who were enrolled in active surveillance programmes for prostate cancer.

Recipient outcomes in total laparoscopic live donor nephrectomy with multiple renal vessels.

INTRODUCTION: In kidney transplantation, total laparoscopic live donor nephrectomy (TLLDN) in the presence of multiple renal arteries (MRA) is technically challenging and has traditionally been associated with higher complication rates. We report our experience of using MRA grafts procured by TLLDN. MATERIALS AND METHODS: Patients undergoing TLLDN at our center (2004-2014) was identified from a prospectively maintained database and divided into single renal arteries (SRA) or MRA groups. Recipient perioperative parameters, postoperative complications, and long-term graft survival were analyzed. RESULTS: Of 465 patients, 106 had MRA and 359 had an SRA. There were six vascular complications in the SRA group and two in the MRA group (1.7% vs. 1.8%). There were eight ureteric complications requiring intervention in the SRA group compared to three in the MRA group (4% vs. 3%; P = 0.45). Acute rejection was observed in 12% of the SRA group compared to 9% in the MRA group (P = 0.23). One-, 5- and 10-year graft survivals were 98.2%, 91.3%, and 89.8% in the MRA group versus 98.0%, 90.4%, and 77.5% in the SRA group (log-rank P = 0.13). CONCLUSION: The use of MRA grafts procured by TLLDN has comparable complication rates to SRA grafts and should not preclude selection for renal transplantation.

Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer.

OBJECTIVES: To describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis. DESIGN: Multicentre prospective observational cohort study. SETTING AND PARTICIPANTS: Eleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected. OUTCOMES: Type and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival. RESULTS: Of 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC. CONCLUSIONS: Raising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers.

Trans-peritoneal vs. retroperitoneal robotic assisted partial nephrectomy in posterior renal tumours: need for a risk-stratified patient individualised approach. A systematic review and meta-analysis.

To systematically review world literature and compare peri-operative outcome including operating time (OT), estimated blood loss (EBL), warm ischemia time (WIT), length of stay (LOS) and complications between retroperitoneal robotic assisted partial nephrectomy (RP-RAPN) and trans-peritoneal robotic assisted partial nephrectomy (TP-RAPN) for posteriorly located renal masses. All randomised trials and observational studies comparing RP-RAPN and TP-RAPN for posteriorly located renal masses were considered. The GRADE approach (Grading of Recommendations Assessment, Development and Evaluation, GRADE) was used to rate the quality of evidence. 82 potential publications were identified. 3 were included in the review. All three studies were observational comparative studies. 347 and 550 patients underwent RP-RAPN and TP-RAPN, respectively, for posteriorly located tumours. There was statistically significant difference in LOS between the 2 techniques, favouring the RP-RAPN cohort: risk ratio (M-H, random, 95% CI), - 0.42 [- 0.67, - 0.18], p < 0.0006. There was no statistically significant difference in overall complication rates between the two techniques: risk ratio (M-H, fixed, 95% CI), 0.80 [0.49, 1.30], p = 0.37. There was no statistically significant difference in ≥ Clavien 3a complication rates between the two t echniques: risk ratio (M-H, fixed, 95% CI), 1.17 [0.62, 2.19], p = 0.63. OT, EBL, WIT and positive margin rates were similar for both approaches. The quality of evidence for complications, LOS and remaining outcomes were 'moderate', 'low' and 'very low', respectively, on GRADE approach. The current review suggests that the LOS with RP-RAPN are significantly lesser than TP-RAPN for posterior tumours. The RP-RAPN does not appear to offer any advantage over TP-RAPN for other peri-operative outcomes such as WIT, OT and EBL. The surgical margin rates and morbidity between the two approaches appear to be similar.

UK Multicenter Prospective Evaluation of the Leibovich Score in Localized Renal Cell Carcinoma: Performance has Altered Over Time.

OBJECTIVE: To examine changes in outcome by the Leibovich score using contemporary and historic cohorts of patients presenting with renal cell carcinoma (RCC) PATIENTS AND METHODS: Prospective observational multicenter cohort study, recruiting patients with suspected newly diagnosed RCC. A historical cohort of patients was examined for comparison. Metastasis-free survival (MFS) formed the primary outcome measure. Model discrimination and calibration were evaluated using Cox proportional hazard regression and the Kaplan-Meier method. Overall performance of the Leibovich model was assessed by estimating explained variation. RESULTS: Seven hundred and six patients were recruited between 2011 and 2014 and RCC confirmed in 608 (86%) patients. Application of the Leibovich score to patients with localized clear cell RCC in this contemporary cohort demonstrated good model discrimination (c-index = 0.77) but suboptimal calibration, with improved MFS for intermediate- and high-risk patients (5-year MFS 85% and 50%, respectively) compared to the original Leibovich cohort (74% and 31%) and a historic (1998-2006) UK cohort (76% and 37%). The proportion of variation in outcome explained by the model is low and has declined over time (28% historic vs 22% contemporary UK cohort). CONCLUSION: Prognostic models are widely employed in patients with localized RCC to guide surveillance intensity and clinical trial selection. However, the majority of the variation in outcome remains unexplained by the Leibovich model and, over time, MFS rates among intermediate- and high-risk classified patients have altered. These findings are likely to have implications for all such models used in this setting.

Detailed analysis of patient-reported lower urinary tract symptoms and effect on quality of life after robotic radical prostatectomy.

OBJECTIVE: To prospectively evaluate short- to medium-term patient-reported lower urinary tract symptoms (LUTS) and their effect on health-related quality of life (HRQoL) using validated questionnaires in a large cohort of patients following robotic-assisted radical prostatectomy (RARP) for prostate cancer. MATERIALS AND METHODS: HRQoL and LUTS outcomes were prospectively assessed in 357 consecutive men undergoing RARP at a single center from 2012 to 2015 using the functional assessment of cancer therapy-prostate (FACT-P) and the international consultation on incontinence modular questionnaire-male LUTS (ICIQ-MLUTS). Questionnaires were administered at baseline, 6, 12, and 18 months. Data were analyzed using paired t-tests and ANOVA. RESULTS: Questionnaire completion rates were high (over 60% of eligible men completed 18-month follow-up). Mean Total FACT-P did not significantly change after RARP: 125.95 (standard deviation [SD] = 19.82) at baseline and 125.86 (SD = 21.14) at 18-months (P = 0.55). Mean total ICIQ-MLUTS also remained unchanged: 18.69 (SD = 10.70) at baseline and 18.76 (SD = 11.33) at 18-months (P = 0.11). Mean voiding score significantly reduced from 10.34 (SD = 5.78) at baseline to 6.33 (SD = 3.99) at 6 months after RARP (P<0.001). A reciprocal significant increase in storage score was observed: 5.34 (SD = 4.26) at baseline, 9.65 (SD = 5.71) at 6 months (P<0.001). Subanalyses of ICIQ-MLUTS scores revealed increases in storage symptoms were exclusively within urinary incontinence domains and included significant increases in both urge and stress urinary incontinence scores. CONCLUSION: Overall, patient-reported outcome measures evaluating HRQoL and LUTS do not significantly change after RARP. Detailed analysis reveals significant changes within LUTS domains do occur after surgery which could be overlooked if only total LUTS scores are reported.

Surveillance versus ablation for incidentally diagnosed small renal tumours: the SURAB feasibility RCT.

BACKGROUND: There is uncertainty around the appropriate management of small renal tumours. Treatments include partial nephrectomy, ablation and active surveillance. OBJECTIVES: To explore the feasibility of a randomised trial of ablation versus active surveillance. DESIGN: Two-stage feasibility study: stage 1 - clinician survey and co-design work; and stage 2 - randomised feasibility study with qualitative and economic components. METHODS: Stage 1 - survey of radiologists and urologists, and development of patient information materials. Stage 2 - patients identified across eight UK centres with small renal tumours (< 4 cm) were randomised (1 : 1 ratio) to ablation or active surveillance in an unblinded manner. Randomisation was carried out by a central computer system. The primary objective was to determine willingness to participate and to randomise a target of 60 patients. The qualitative and economic data were collected separately. RESULTS: The trial was conducted across eight centres, with a site-specific period of recruitment ranging from 3 to 11 months. Of the 154 patients screened, 36 were eligible and were provided with study details. Seven agreed to be randomised and one patient was found ineligible following biopsy results. Six patients (17% of those eligible) were randomised: three patients received ablation and no serious adverse events were recorded. The 3- and 6-month data were collected for four (67%) and three (50%) out of the six patients, respectively. The qualitative substudy identified factors directly impacting on the recruitment of this trial. These included patient and clinician preferences, organisational factors (variation in clinical pathway) and standard treatment not included. The health economic questionnaire was designed and piloted; however, the sample size of recruited patients was insufficient to draw a conclusion on the feasibility of the health economics. CONCLUSIONS: The trial did not meet the criteria for progression and the recruitment rate was lower than hypothesised, demonstrating that a full trial is presently not possible. The qualitative study identified factors that led to variation in recruitment across the sites. Implementation of organisational and operational measures can increase recruitment in any future trial. There was insufficient information to conduct a full economic analysis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN31161700. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 81. See the NIHR Journals Library website for further project information.

Positive surgical margins and biochemical recurrence following minimally-invasive radical prostatectomy - An analysis of outcomes from a UK tertiary referral centre.

BACKGROUND: Positive surgical margins are a strong prognostic marker of disease outcome following radical prostatectomy, though prior evidence is largely from a PSA-screened population. We therefore aim to evaluate the biochemical recurrence in men with positive surgical margins (PSM) after minimally-invasive radical prostatectomy (MIRP) in a UK tertiary centre. METHODS: Retrospective study of men undergoing laparoscopic or robotic-assisted radical prostatectomy between 2002 and 2014. Men with positive surgical margins (PSM) were identified and their biochemical recurrence (BCR) rate compared with men without PSM. The primary outcome measures were BCR rates and time to BCR. Cox regression was used to estimate adjusted hazard ratios for biochemical recurrence rate (BCR), accounting for potential confounders. RESULTS: Five hundred ninety-two men were included for analysis. Pre-operative D'Amico risk stratification showed 37.5%, 53.3% and 9.3% of patients in the low, intermediate and high-risk groups, respectively. On final pathological analysis, the proportion of patients with local staging pT2, pT3a and pT3b was 68.8%, 25.2% and 6.1% respectively. Overall positive margin rate was 30.6%. On multivariate analysis, the only pre-operative factor associated with PSM was age >65years. Patients with PSM were more likely to have higher tumour volume and more advanced pathological local stage. The BCR rate was 10.7% in margin-positive patients and 5.1% in margin-negative patients, at median 4.4-year follow-up. Upon multivariate analysis, high pre-operative PSA and high Gleason group were the only significant predictors of BCR (P<0.05). CONCLUSIONS: In comparison to patients with negative surgical margins, those with PSM do not translate into worse medium-term oncological outcomes in the majority of cases amongst our cohort. We found that high pre-operative PSA and high Gleason group were the only significant predictors of BCR.

Early surgical outcomes and oncological results of robot-assisted partial nephrectomy: a multicentre study.

OBJECTIVE: To describe a multicentre experience of robot-assisted partial nephrectomy (RAPN) in northern England, with focus on early surgical outcomes and oncological results. PATIENTS AND METHODS: All consecutive patients undergoing RAPN at four tertiary referral centres in northern England in the period 2012-2015 were included for analysis. RAPN was performed via a transperitoneal approach using a standardized technique. Prospective data collection was performed to capture preoperative characteristics (including R.E.N.A.L. nephrometry score), and peri-operative and postoperative data, including renal function. Correlations between warm ischaemia time (WIT), positive surgical margin (PSM) rate, complication rates, R.E.N.A.L. nephrometry scores and learning curve were assessed using univariate and multivariate analyses. RESULTS: A total of 250 patients (mean age 58.1 ± 13 years, mean ± sd body mass index 27.3 ± 7 kg/m2 ) were included, with a median (range) follow-up of 12 (3-36) months. The mean ± sd tumour size was 30.6 ± 10 mm, mean R.E.N.A.L. nephrometry score was 6.1 ± 2 and 55% of tumours were left-sided. Mean ± sd operating console time was 141 ± 38 min, WIT 16.7 ± 8 min and estimated blood loss 205 ± 145 mL. There were five conversions (2%) to open/radical nephrectomy. The overall complication rate was 16.4% (Clavien I, 1.6%; Clavien II, 8.8%; Clavien III, 6%; Clavien IV/V; 0%). Pathologically, 82.4% of tumours were malignant and the overall PSM rate was 7.3%. The mean ± sd preoperative and immediate postoperative estimated glomerular filtration rates were 92.8 ± 27 and 80.8 ± 27 mL/min/1.73 m2 , respectively (P = 0.001). In all, 66% of patients remained in the same chronic kidney disease category postoperatively, and none of the patients required dialysis during the study period. 'Trifecta' (defined as WIT < 25 min, negative surgical margin status and no peri-operative complications) was achieved in 68.4% of patients overall, but improved with surgeon experience. PSM status and long WIT were significantly associated with early learning curve. CONCLUSION: This is the largest multicentre RAPN study in the UK. Initial results show that RAPN is safe and can be performed with minimal morbidity. Early oncological outcomes and renal function preservation data are encouraging.

Feasibility study of a randomized controlled trial comparing docetaxel chemotherapy and androgen deprivation therapy with sequential prostatic biopsies from patients with advanced non-castration-resistant prostate cancer.

BACKGROUND AND OBJECTIVE: Sequential tissue biopsies taken during clinical trials of novel systemic anticancer therapies for advanced prostate cancer (PCa) may aid pharmacodynamic evaluation and biomarker discovery. We conducted a single institution phase-II open-labeled randomized study to assess the safety, tolerability, and early efficacy of docetaxel chemotherapy plus androgen deprivation therapy (ADT) vs. ADT alone for patients with advanced non-castration-resistant PCa with sequential prostatic biopsies. PATIENTS AND METHODS: We randomized 30 patients with newly diagnosed high-grade locally advanced or metastatic (cT3-4/N0-1/M0-1) PCa to receive ADT with (n = 15) or without (n = 15) docetaxel. Transrectal ultrasound-guided prostatic biopsies were taken at randomization and ~22 weeks after treatment initiation. Primary end point: biochemical response rate. Secondary end points: time to progression and tumor profiling. RESULTS: Both treatments appear to be well tolerated, and there was no difference in mean nadir prostate-specific antigen and time to prostate-specific antigen relapse between treatment arms (P>0.05). No adverse effects of pre- and post-treatment prostatic biopsies were observed. The study was neither designed nor sufficiently powered to demonstrate statistically significant differences in oncological outcomes or safety profiles between the 2 treatment arms. CONCLUSIONS: Despite the lack of statistical power, our study suggests that docetaxel and ADT in combination may be well tolerated with apparently similar short-term efficacy compared with ADT alone for high-grade locally advanced or metastatic non-castration-resistant PCa, Sequential prostatic biopsies may provide tissue for tumor profiling to yield mechanistic or prognostic insights relating to novel systemic anticancer therapies.

A Prospective Randomised Paired Trial of Sirolimus versus Tacrolimus as Primary Immunosuppression following Non-Heart Beating Donor Kidney Transplantation.

INTRODUCTION: With calcineurin inhibitors potentiating damage from ischaemia-reperfusion injury in kidneys from donors after cardiac death we wanted to investigate the role of substituting sirolimus for tacrolimus in the delayed introduction of calcineurin inhibitor regime used in our centre. METHOD: A prospective randomised paired open-label study was performed taking pairs of kidneys from each donor and randomising one to a tacrolimus-based regime and the other to a similar regime based on sirolimus. Graft function at one year was the primary endpoint. RESULTS: Total 31 pairs of kidneys were randomised to each group, with 19 pairs of recipients available for analysis after post-randomisation study exclusions. Despite a higher incidence of biopsy proven acute rejection in the sirolimus group, renal allograft function was similar in both groups at three-monthly intervals up to one year post-transplant. All episodes of acute rejection in the sirolimus group occurred in the first three months. Graft and patient survival at one year was 100% in the tacrolimus group, with one death with functioning graft in the sirolimus group (95% survival). Unfortunately, 10 of the 19 patients in the sirolimus arm required switch of medication to tacrolimus due to acute rejection or intolerable drug side effects. CONCLUSIONS: Graft survival and function were very similar in the two groups despite the higher rate of acute rejection in the sirolimus arm, raising the possibility that the damage done by acute rejection was adequately offset by the nephron-sparing effect of sirolimus compared to tacrolimus. Sirolimus may have a role as a longer-term maintenance immunosuppressant after initial treatment with a different agent such as tacrolimus or belatacept.

Renal differentiation from adult spermatogonial stem cells.

There is considerable interest in the use of multi-potent stem cells in kidney tissue regeneration. We studied if spermatogonial stem cells have the ability to undergo kidney differentiation. Spermatogonial stem cell differentiation was induced using in vitro and ex vivo co-culture techniques. Conditioned media from human kidney fibroblasts induced the expression of epithelial and endothelial lineages in spermatogonial stem cells, consistent with nephrogenesis. Furthermore, we showed that these cells up-regulated renal tubular-specific markers alkaline phosphatase, mineralocorticoid receptor, renal epithelial sodium channel and sodium-glucose transporter-2 (p<0.05). GFP-labeled spermatogonial stem cells were engrafted into metanephric kidney organ cultures harvested from E12.5 mouse embryos. After 5 days of organ culture, focal anti-GFP staining was detectable in all inoculated kidneys demonstrating integration of spermatogonial stem cells into the developing kidney (p<0.01). Histological assessment showed early nephron-like architecture. In summary, we show that spermatogonial stem cells have the potential to generate renal tissue and lay the foundations for further investigations into a novel therapeutic approach for renal insufficiency.

Physiologic and anesthetic considerations in octogenarians undergoing laparoscopic partial nephrectomy.

The number of small renal tumors detected is increasing as imaging becomes both more available and advanced, and as the population ages, with a greater proportion of patients in their 80s emerging with small and treatable renal tumors. The technique of laparoscopic partial nephrectomy is emerging and becoming ever more popular in some centers, and is potentially a safer alternative for the elderly due to improved postoperative pain, shorter hospital stay with faster return to preoperative activities, and lower rates of morbidity and mortality. We present a systematic review of the physiologic and anesthetic considerations in octogenarians undergoing the procedure, highlighting special considerations and the need for expertise throughout the multidisciplinary team when dealing with these patients, in order to minimize risk and optimize outcome.