Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy for High Risk Renal Tumors.

PURPOSE: The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features.

Robotic-assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes.

PURPOSE: Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). METHODS: We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan-Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. RESULTS: One hundred and eight patients (6 %) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11-24), and median follow-up was 26 months (IQR 14-43). Ninety-one (84 %) patients did not receive adjuvant ADT of whom 60 % had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 %, respectively. Patients with ≤2 LN+ had significantly better biochemical-free estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 % CI 1.01-1.2, p = 0.04) and Gleason 8-10 (HR = 1.96; 95 % CI 1.1-3.4, p = 0.02) were predictors of BCR on multivariate analysis. CONCLUSION: Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.

Does robot-assisted laparoscopic ileocystoplasty (RALI) reduce peritoneal adhesions compared with open surgery?

OBJECTIVES: To compare perioperative outcomes between open ileocystoplasty and robot-assisted laparoscopic ileocystoplasty (RALI) in a porcine model, as objective data comparing outcomes between these two approaches in children with neurogenic bladder are lacking. We specifically examined differences in postoperative peritoneal adhesion formation between the groups. MATERIALS AND METHODS: In all, 20 pigs were assigned to an open ileocystoplasty or RALI study arm. All the pigs underwent an initial urodynamic study (UDS). In the RALI arm, reconstructive steps were performed intracorporeally using a standard da Vinci(®) system. Postoperatively, variables including first stool, weight gain, and complications were recorded. After 42 days, the pigs underwent a final UDS followed by adhesion assessment. Intraperitoneal adhesions were quantified by a third-party 'blinded' surgeon according to previously described objective scoring systems. RESULTS: Preoperative variables including UDS were similar in both groups. Overall operating time was significantly shorter for open ileocystoplasty than for RALI (149 vs 287 min, P < 0.001, respectively). Postoperatively, all variables including time to first stool, weight gain, and urodynamic parameters were similar amongst the groups. Pigs in the open arm developed significantly more adhesions (P = 0.02) and adhesions with a higher complexity (P = 0.04). CONCLUSIONS: In this porcine model, RALI achieved similar functional outcomes as the open approach, but required longer procedural times. The number and complexity of surgical adhesions among the groups favoured the RALI cohort. This may be of clinical significance in the paediatric spina bifida population, who generally undergo multiple surgical procedures in their lifetime, with increased risk for development of adhesions and subsequent intestinal obstruction.

Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer.

BACKGROUND: Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC. METHODS: More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis. RESULTS: On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals. CONCLUSIONS: A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance.

Extraprostatic Extension Is Extremely Rare for Contemporary Gleason Score 6 Prostate Cancer.

BACKGROUND: A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. OBJECTIVE: To assess pathologic stage of pure GS6 at radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: In the period 2003-2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a-b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. RESULTS AND LIMITATIONS: Of the 60 GS6 pT3a-b cases identified in the period 2003-2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. CONCLUSIONS: In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. PATIENT SUMMARY: GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles.

Prognostic Model for Predicting Survival in Patients with Disease Recurrence Following Radical Cystectomy.

BACKGROUND: Although the natural history of urothelial carcinoma of the bladder (UCB) from radical cystectomy (RC) to disease recurrence (DR) has been investigated intensively, the course of patients who have experienced DR after RC for UCB remains poorly understood. OBJECTIVE: To evaluate the prognostic value of the Bajorin criteria that consists of two risk factors: Karnofsky performance status (KPS) and the presence of visceral metastases (VMs) in patients with DR after RC for UCB. Furthermore, to identify additional factors associated with cancer-specific mortality (CSM) and thus build a multivariable model to predict survival after DR. DESIGN, SETTING, AND PARTICIPANTS: We identified 967 patients with UCB who underwent RC at 17 centers between 1979 and 2012 and experienced DR. Of these, 372 patients had complete data we used for analysis. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable Cox regressions analysis was performed. We used a forward stepwise selection process for our final multivariable model. RESULTS AND LIMITATIONS: Within a median follow-up of 18 mo, 266 patients died of disease. Cancer-specific survival at 1 yr was 79%, 76%, and 47% for patients with no (n=105), one (n=180), and two (n=87) risk factors (p<0.001; c-index: 0.604). On multivariable analyses, we found that KPS <80%, higher American Society of Anesthesiologists score, anemia, leukocytosis, and shorter time to DR (all p values <0.034) were independently associated with increased CSM. The combination of time to DR and KPS resulted in improved discrimination (c-index: 0.694). CONCLUSIONS: We confirmed the prognostic value of KPS and VMs in patients with DR following RC for UCB. We also found several other clinical variables to be associated with worse CSM. We developed a model for predicting survival after DR inclusive of time to DR and KPS assessed at DR. If validated, this model could help clinical trial design. PATIENT SUMMARY: We developed a model to predict survival following disease recurrence after radical cystectomy for urothelial carcinoma of the bladder, based on time to disease recurrence and Karnofsky performance status.

Is pelvic plexus nerve documentation feasible during robotic assisted laparoscopic ureteral reimplantation with extravesical approach?

PURPOSE: Urinary retention is a known complication of using an extravesical approach for ureteral reimplantation, especially in bilateral cases. The etiology may be secondary damage to pelvic nerves during ureteral dissection. Recent literature suggests that it is possible to visually identify these nerves during a robotic assisted laparoscopic approach. We performed an exploratory study to identify and document them in pediatric patients by means of electrophysiologic recordings. MATERIAL AND METHODS: Seven consecutive patients undergoing robotic assisted laparoscopic ureteral reimplantation with extravesical approach were prospectively enrolled in the study. Following dissection of the ureter below the level of vas deferens in male and the uterine artery in female, staying close to the adventitia and approaching the ureterovesical junction, the fibers as described in human cadaveric studies were identified dorsomedial to the ureter and preserved. Stimulating and recording electrodes were passed through to record post-synaptic compound muscle action potentials of the bladder. RESULTS: Even though the nerve fibers were visually identified, we were unable to consistently and reproducibly record compound muscle action potentials after stimulation of putative pelvic plexus fibers at the distal ureter, despite modulation in stimulation intensity, pulse characteristics, signal recording sensitivity and stimulator probe variation. CONCLUSIONS: In this pilot study, the inconsistent findings raise questions about the exact location of the neurovascular bundle, nature of bladder smooth muscle electrophysiology and the appropriate methodology of evaluation. This may provide a reason to reexamine the intraoperatively expected location of pelvic plexus nerve fibers.

Impact of prostate weight on probability of positive surgical margins in patients with low-risk prostate cancer after robotic-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To evaluate the impact of prostate weight (PW) on probability of positive surgical margin (PSM) in patients undergoing robotic-assisted radical prostatectomy (RARP) for low-risk prostate cancer. METHODS: The cohort consisted of 690 men with low-risk prostate cancer (clinical stage T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason score ≤6) who underwent RARP with bilateral nerve-sparing at our institution by 1 of 2 surgeons from 2003 to 2009. PW was obtained from the pathologic specimen. The association between probability of PSM and PW was assessed with univariate and multivariate logistic regression analysis. RESULTS: A PSM was identified in 105 patients (15.2%). Patients with PSM had significant higher prostate-specific antigen (P = .04), smaller prostates (P = .0001), higher Gleason score (P = .004), and higher pathologic stage (P < .0001). After logistic regression, we found a significant inverse relation between PSM and PW (OR 0.97%; 95% confidence interval [CI] 0.96, 0.99; P = .0003) in univariate analysis. This remained significant in the multivariate model (OR 0.98%; 95% CI 0.96, 0.99; P = .006) adjusting for age, body mass index, surgeon experience, pathologic Gleason score, and pathologic stage. In this multivariate model, the predicted probability of PSM for 25-, 50-, 100-, and 150-g prostates were 22% (95% CI 16%, 30%), 13% (95% CI 11%, 16%), 5% (95% CI 1%, 8%), and 1% (95% CI 0%, 3%), respectively. CONCLUSIONS: Lower PW is independently associated with higher probability of PSM in low-risk patients undergoing RARP with bilateral nerve-sparing.

Clinical and histologic predictors of renal function decline after laparoscopic partial nephrectomy.

BACKGROUND AND PURPOSE: Clinical and surgical factors predict renal function decline after laparoscopic partial nephrectomy (LPN). Additional histopathologic predictors may be found in the specimen's nonneoplastic tissue but were not studied. This study investigated the significance of histologic findings in addition to other known predictors of renal function after LPN. PATIENTS AND METHODS: Data of 150 patients who underwent LPN was analyzed. Renal function changes (median follow-up 15 months) were correlated with perioperative and histopathologic parameters. Three histopathologic features were evaluated and graded in the nonneoplastic parenchyma: Glomerulosclerosis, arteriosclerosis (AS), and interstitial fibrosis/tubular atrophy. Estimated GFR (eGFR) and percent decline on postoperative day 1 (POD1) and at the last follow-up were measured. RESULTS: Median eGFR percent decline at POD1 and last follow-up was -17 and -10, respectively (P<0.001). New-onset ≥stage III chronic kidney disease developed in only 7% of the patients. Three factors independently predicted POD1 eGFR decline: Artery and vein clamping vs artery only clamping (P=0.002), male sex (P=0.015), and larger tumor (P=0.02). Long-term loss of renal function was associated with POD1 eGFR decline (P=0.002) and the percentage of AS (P=0.01). The study limitations include a retrospective analysis leading to variability in the follow-up length and a small size cohort. CONCLUSIONS: LPN is associated with a favorable renal function outcome in most patients. Pathologic findings in the nonneoplastic tissue, in addition to clinical parameters, can be used to predict which patients are more likely to experience renal function impairment.

Drilling through impacted ureteral stones: use of the atherectomy rotablator device for urolithiasis.

BACKGROUND AND PURPOSE: The Rotablator is an angioplasty device that is passed over a wire. It uses a high-speed rotational "burr" (2 mm in diameter) that is coated with microscopic diamond particles and cooled by saline. It rotates at high speed (approximately 200,000 rpm) breaking up endovascular blockage into minute (smaller than red blood cells) fragments. We investigated, in vitro and ex vivo, the possible use of the Rotablator for urinary stone disease. MATERIALS AND METHODS: Human stones of different sizes and composition were used for the experiment. Stone impaction in vitro was modeled by wedging the stones into the proximal part of a 16F silicone Foley catheter. Likewise, an ex-vivo study was performed on stones placed into a freshly harvested swine ureter using a nitinol basket. Data regarding the drill time, remaining stone size, and ureteral damage were collected. RESULTS: Overall, 15 stones were treated (10 in vitro and 5 ex vivo). The device successfully drilled through all the stones, along the path of the guidewire, allowing complete passage of the burr. The pretreatment mean stone size for the silicone and ureteral testing was 65 mm(3) and 34 mm(3), respectively (both P < 0.01). The post-treatment size was 54 mm(3) and 24 mm(3), respectively. Average treatment time was 100 seconds. No visual macroscopic ureteral damage or perforation was observed. CONCLUSIONS: In vitro, the Rotablator is capable of drilling through stones with minimal damage. Drilling, however, occurred alongside the stone in which the guidewire was located and, thus, stone fragmentation appears to be minimal. Further studies are necessary to investigate other burr configurations and the use of the Rotablator for the fluoroscopic-guided passage of ureteral impaction in difficult clinical settings.