Intra-operative fluorescence-based detection of positive surgical margins during radical prostatectomy: Lessons learned from a pilot ex vivo translational study.

OBJECTIVES: Nerve-sparing techniques during radical prostatectomy have been associated with an increased risk of positive surgical margins. The intra-operative detection of residual prostatic tissue could help mitigate this risk. The objectives of the present study were to assess the feasibility of using an anti-prostate-specific membrane antigen (anti-PSMA) antibody conjugated with a fluorophore to characterize fresh prostate tissue as prostatic or non-prostatic for intra-operative surgical margin detection. METHODS: Fresh prostatic tissue samples were collected from transurethral resections of the prostate (TURP) or prostate biopsies, and either immunolabelled with anti-PSMA antibody conjugated with Alexa Fluor 488 or used as controls. A dedicated, laparoscopy-compliant fluorescence device was developed for real-time fluorescence detection. Confocal microscopy was used as the gold standard for comparison. Spectral unmixing was used to distinguish specific, Alexa Fluor 488 fluorescence from nonspecific autofluorescence. RESULTS: The average peak wavelength of the immuno-labeled TURP samples (n = 4) was 541.7 ± 0.9 nm and of the control samples (n = 4) was 540.8 ± 2.2 nm. Spectral unmixing revealed that these similar measures were explained by significant autofluorescence, linked to electrocautery. Three biopsy samples were then obtained from seven patients and also displayed significant nonspecific fluorescence, raising questions regarding the reproducibility of the fixation of the anti-PSMA antibodies on the samples. Comparing the fluorescence results with final pathology proved challenging due to the small sample size and tissue alterations. CONCLUSIONS: This study showed similar fluorescence of immuno-labeled prostate tissue samples and controls, failing to demonstrate the feasibility of intra-operative margin detection using PSMA immuno-labeling, due to marked tissue autofluorescence. We successfully developed a fluorescence device that could be used intraoperatively in a laparoscopic setting. Use of the infrared range as well as newly available antibodies could prove interesting options for future research.

Superselective Ischemia in Robotic Partial Nephrectomy Does Not Provide Better Long-term Renal Function than Renal Artery Clamping in a Randomized Controlled Trial (EMERALD): Should We Take the Risk?

BACKGROUND: Superselective clamping of tumor-targeted arteries aims to eliminate ischemia of the remnant kidney while keeping tumor bed bloodless during excision. OBJECTIVE: To evaluate the impact of superselective clamping on long-term renal function, compared with renal artery early unclamping. DESIGN, SETTING, AND PARTICIPANTS: A randomized monocentric single-blind trial (1:1) was conducted from February 2018 to August 2019. Patients with a single renal tumor were candidates for a robot-assisted partial nephrectomy (RAPN) in a referral center. EMERALD (NCT03679572) was powered to include 50 patients with an interim analysis after 30 cases. INTERVENTION: Superselective RAPN (SS-RAPN) with near-infrared fluorescence (NIRF) or conventional RAPN with renal artery early unclamping. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the percent change of estimated glomerular filtration rate (eGFR) in the operated kidney after 6 mo (combination of eGFR and relative function on 99mTc-DMSA scintigraphy). Secondary endpoints assessed feasibility and safety of the technique. RESULTS AND LIMITATIONS: Relative eGFR reduction in the operated kidney at 6 mo did not differ significantly (-21.4% vs -23.4%, p=0.66). This absence of difference remained after adjusting on percentage of kidney volume preserved, which was an independent predictor of functional preservation. There were no significant differences in terms of blood loss, change in hemoglobin, postoperative complications, transfusion, and conversion to radical nephrectomy (two vs zero) or to open surgery (one vs zero). Despite a good accrual, the steering committee interrupted the trial after the interim analysis for futility given the absence of trend in favor of SS-RAPN. CONCLUSIONS: SS-RAPN using NIRF does not provide better renal function preservation than renal artery clamping, questioning the interest of this technique at a higher risk of bleeding. PATIENT SUMMARY: In this randomized controlled trial, superselective clamping of tumor feeding arteries did not show any advantage in terms of long-term renal function compared with conventional artery clamping.

Super-selective robot-assisted partial nephrectomy using near-infrared flurorescence versus early-unclamping of the renal artery: results of a prospective matched-pair analysis

ABSTRACT Introduction Super-selective clamping of tumor-specific segmental arteries was developed to eliminate ischemia of the remnant kidney while limiting hemorrhage during partial nephrectomy. The objective is to evaluate the benefice of super-selective clamping on renal functional outcome, compared to early-unclamping of the renal artery. Materials and Methods From March 2015 to July 2016, data from 30 patients undergoing super-selective robot-assisted PN (RAPN) for a solitary tumor by a single surgeon were prospectively collected. Tumor devascularization was assessed using indocyanine green near-infrared fluorescence. A matched-pair analysis with a retrospective cohort undergoing early-unclamping was conducted, adjusting on tumor complexity and preoperative eGFR. Perioperative, oncologic and functional outcomes using DMSA-renal scintigraphy were assessed. Multivariate analysis was performed to identify predictors of postoperative renal function and de novo chronic kidney disease (CKD). Results Super-selective RAPN was successful in 23/30 patients (76.7%), 5 requiring secondary main artery clamping due to persistent tumor fluorescence. Matched-pair analysis showed similar operating time, blood loss, positives margins and complication rates. Super-selective clamping was associated with an improved eGFR variation at discharge (p=0.002), 1-month (p=0.01) and 6-month post-op (-2%vs-16% p=0.001). It also led to a better relative function on scintigraphy (46%vs40% p=0.04) and homolateral eGFR (p=0.04), and fewer upstaging to CKD stage ≥3 (p=0.03). On multivariate analysis, super-selective clamping was a predictor of postoperative renal function. Conclusion Super-selective RAPN leads to an improved preservation of renal function and a reduced risk of de novo CKD stage≥3, while keeping the benefit of main artery clamping on perioperative outcomes.

Super-selective robot-assisted partial nephrectomy using near-infrared flurorescence versus early-unclamping of the renal artery: results of a prospective matched-pair analysis.

INTRODUCTION: Super-selective clamping of tumor-specific segmental arteries was developed to eliminate ischemia of the remnant kidney while limiting hemorrhage during partial nephrectomy. The objective is to evaluate the benefice of super-selective clamping on renal functional outcome, compared to early-unclamping of the renal artery. MATERIALS AND METHODS: From March 2015 to July 2016, data from 30 patients undergoing super-selective robot-assisted PN (RAPN) for a solitary tumor by a single surgeon were prospectively collected. Tumor devascularization was assessed using indocyanine green near-infrared fluorescence. A matched-pair analysis with a retrospective cohort undergoing early-unclamping was conducted, adjusting on tumor complexity and preoperative eGFR. Perioperative, oncologic and functional outcomes using DMSA-renal scintigraphy were assessed. Multivariate analysis was performed to identify predictors of postoperative renal function and de novo chronic kidney disease (CKD). RESULTS: Super-selective RAPN was successful in 23/30 patients (76.7%), 5 requiring secondary main artery clamping due to persistent tumor fluorescence. Matched-pair analysis showed similar operating time, blood loss, positives margins and complication rates. Super-selective clamping was associated with an improved eGFR variation at discharge (p=0.002), 1-month (p=0.01) and 6-month post-op (-2%vs-16% p=0.001). It also led to a better relative function on scintigraphy (46%vs40% p=0.04) and homolateral eGFR (p=0.04), and fewer upstaging to CKD stage ≥3 (p=0.03). On multivariate analysis, super-selective clamping was a predictor of postoperative renal function. CONCLUSION: Super-selective RAPN leads to an improved preservation of renal function and a reduced risk of de novo CKD stage≥3, while keeping the benefit of main artery clamping on perioperative outcomes.

Active Surveillance for Favorable Risk Prostate Cancer in African Caribbean Men: Results of a Prospective Study.

PURPOSE: Active surveillance is a treatment option for favorable risk prostate cancer. However, data are missing on populations of African descent. We evaluated the safety and benefit of active surveillance in an African Caribbean cohort with favorable risk prostate cancer. MATERIALS AND METHODS: Between 2005 and 2016, a single center, prospective cohort study was performed in Guadeloupe, French West Indies, including patients on active surveillance who had low risk prostate cancer (prostate specific antigen 10 ng/ml or less and Gleason score 6 or less) or favorable intermediate risk prostate cancer (prostate specific antigen 10 to 20 ng/ml, Gleason score 3 + 4 or less and life expectancy less than 10 years). Treatment was recommended in case of grade progression, increased tumor volume, prostate cancer doubling time less than 36 months or patient wish. Overall survival, disease specific survival and duration of active surveillance were calculated with the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards model to identify predictors of active surveillance termination. RESULTS: A total of 234 patients with a median age of 64 years were enrolled in study. Median followup was 4 years (IQR 2.3-5.5). Overall survival at 30 months, 5 years and 10 years was 99.5%, 98.5% and 90.7%, respectively. Disease specific survival at 30 months, and 5 and 10 years was 100%. At 30 months, 5 years and 10 years 72.7%, 52.6% and 40.4% of patients, respectively, remained untreated and on active surveillance. Age (HR 0.96 per additional year, 95% CI 0.93-0.99) and prostate specific antigen density (HR 1.52 per additional 0.1 ng/ml, 95% CI 1.20-1.89) were found to be independent predictors of active surveillance termination. CONCLUSIONS: Active surveillance is safe and beneficial for highly selected African Caribbean patients. It seems to be feasible for patients at low risk and intermediate favorable risk. Prostate specific antigen density could help better select these patients.

Partial nephrectomy versus ablative therapy for the treatment of renal tumors in an imperative setting.

PURPOSE: To compare partial nephrectomy (PN) and percutaneous ablative therapy (AT) for renal tumor in imperative indication of nephron-sparing technique (NST). MATERIALS AND METHODS: Between 2000 and 2015, 284 consecutive patients with a kidney tumor in an imperative indication of NST were retrospectively included in a multicenter study. PN [open (n = 146), laparoscopic (n = 9), or robotic approach (n = 17)] and AT [radiofrequency ablation (n = 104) or cryoablation (n = 8)] were performed for solitary kidney (n = 146), bilateral tumor (n = 78), or chronic kidney disease (CKD) (n = 60). RESULTS: Patients in the PN group had larger tumors and a higher RENAL score. There were no differences between the two groups with respect to age, reasons for imperative indication, and preoperative eGFR. Patients in the AT group had a higher ASA and CCI. PN had worse outcomes than AT in terms of transfusion rate, length of stay, and complication rate. Local radiological recurrence-free survival was better for PN, but metastatic recurrence was similar. Percentage of eGFR decrease was similar in the two groups. Temporary or permanent dialysis was not significantly different. On multivariate analysis, PN and AT had a similar eGFR change when adjusted for tumor complexity, reason of imperative indication and CCI. CONCLUSION: In imperative indication of nephron-sparing treatment for a kidney tumor, either PN or AT can be proposed. PN offers the ability to manage larger and more complex tumors while providing a better local control and a similar renal function loss.

Augmented Reality Using Transurethral Ultrasound for Laparoscopic Radical Prostatectomy: Preclinical Evaluation.

PURPOSE: To guide the surgeon during laparoscopic or robot-assisted radical prostatectomy an innovative laparoscopic/ultrasound fusion platform was developed using a motorized 3-dimensional transurethral ultrasound probe. We present what is to our knowledge the first preclinical evaluation of 3-dimensional prostate visualization using transurethral ultrasound and the preliminary results of this new augmented reality. MATERIALS AND METHODS: The transurethral probe and laparoscopic/ultrasound registration were tested on realistic prostate phantoms made of standard polyvinyl chloride. The quality of transurethral ultrasound images and the detection of passive markers placed on the prostate surface were evaluated on 2-dimensional dynamic views and 3-dimensional reconstructions. The feasibility, precision and reproducibility of laparoscopic/transurethral ultrasound registration was then determined using 4, 5, 6 and 7 markers to assess the optimal amount needed. The root mean square error was calculated for each registration and the median root mean square error and IQR were calculated according to the number of markers. RESULTS: The transurethral ultrasound probe was easy to manipulate and the prostatic capsule was well visualized in 2 and 3 dimensions. Passive markers could precisely be localized in the volume. Laparoscopic/transurethral ultrasound registration procedures were performed on 74 phantoms of various sizes and shapes. All were successful. The median root mean square error of 1.1 mm (IQR 0.8-1.4) was significantly associated with the number of landmarks (p = 0.001). The highest accuracy was achieved using 6 markers. However, prostate volume did not affect registration precision. CONCLUSIONS: Transurethral ultrasound provided high quality prostate reconstruction and easy marker detection. Laparoscopic/ultrasound registration was successful with acceptable mm precision. Further investigations are necessary to achieve sub mm accuracy and assess feasibility in a human model.

High Grade Blunt Renal Trauma: Predictors of Surgery and Long-Term Outcomes of Conservative Management. A Prospective Single Center Study.

PURPOSE: The management of major renal trauma has shifted in the last decade in favor of a nonoperative approach. Our level 1 trauma center promotes this approach with the objective of renal function preservation. However, certain situations still require surgery. In this study we analyze predictors of surgery and long-term outcomes after conservative management. MATERIALS AND METHODS: From January 2004 to March 2015 we prospectively collected data from all patients admitted to our institution for high grade blunt renal trauma (grades IV and V). Nonoperative management was considered successful when patients did not undergo surgical exploration, regardless of angioembolization or endoscopic treatment. RESULTS: Of 306 patients with renal trauma 151 presented with major injuries, including 124 grade IV and 27 grade V. Nonoperative management was successful in 110 (89%) cases of grade IV and 14 (52%) cases of grade V lesions. Deceleration mechanism (p=0.03), associated lesions (p=0.001), percentage of devitalized parenchyma (p=0.012), angioembolization (p <0.001), hemodynamic instability (p <0.001) and low hemoglobin (p=0.001) were more frequent in patients treated surgically. On multivariate analysis grade (OR 7.36, p=0.01) and hemodynamic instability (OR 4.18, p=0.04) were the only independent predictors of surgical treatment. Long-term followup of preserved kidneys revealed a remaining 40% and 0% relative renal function after grade IV and V injuries, respectively. Only devascularized parenchyma greater than 25% predicted the decline of long-term renal function. CONCLUSIONS: Nonoperative management can and should be performed safely in cases of grade IV injuries whenever possible, with valuable long-term renal function. It can also be initiated in grade V cases. However, surgeons should consider nephrectomy with the onset of any suspicious symptoms.

The role for surgery in high-risk prostate cancer.

High-risk prostate cancer (PCa) refers to a very heterogeneous subgroup of disease. Recent series have shown very promising results of radical prostatectomy (RP)-alone or part as a multimodality approach-in patients with high-risk PCa, with satisfactory survival curves even though biochemical recurrence rate was high. Adjuvant treatment (radiotherapy (RT) alone or combined with androgen deprivation) was necessary in 20 to 54 % of patients, notably in cases with positive surgical margins. As for functional outcomes, urinary continence was preserved in about 92 % of cases and overall potency in 60 %. When comparing RP versus RT as primary treatment for high-risk PCa, a recent meta-analysis found surgery to be associated with an improved cancer-specific mortality compared with RT. In selected high-risk PCa young patients, surgery appears to be a valid option. Patients should however be informed of the possibility of adjuvant treatment, as part of a multimodal approach.

First clinical experience in urologic surgery with a novel robotic lightweight laparoscope holder.

PURPOSE: To report the feasibility and the safety of a surgeon-controlled robotic endoscope holder in laparoscopic surgery. PATIENTS AND METHODS: From March 2010 to September 2010, 20 patients were enrolled prospectively to undergo a laparoscopic procedure using an innovative robotic endoscope holder. Two surgeons performed six adrenalectomies, four sacrocolpopexies, five pyeloplasties, four radical prostatectomies, and one radical nephrectomy. Demographic data, overall setup time, operative time, number of assistants needed were reviewed. Surgeon satisfaction regarding the ergonomics was assessed using a 10-point scale. Postoperative clinical outcomes were reviewed at day 1 and 1 month postoperatively. RESULTS: The per-protocol analysis was performed on 17 patients for whom the robot was effectively used for surgery. Median age was 63 years; 10 (59%) patients were female. Median body mass index was 26.8. Surgical procedures were completed with the robot in 12 (71%) cases. Median number of surgical assistant was 0. Overall setup time with the robot was 19 minutes; operative time was 130 minutes during which the robot was used 71% of the time. Mean hospital stay was 6.94 ± 2.3 days. Median score regarding the easiness of use was 7. Median pain level was 1.5/10 at day 1 and 0 at 1 month postoperatively. Open conversion was needed in one (6%) case, and four minor complications occurred in two (12%) patients. CONCLUSION: This use of this novel robotic laparoscope holder is safe, feasible, and provides good comfort to the surgeon.