Nicholas Power

Lymph Node–Positive Bladder Cancer Treated With Radical Cystectomy and Lymphadenectomy: Effect of the Level of Node Positivity

BACKGROUND The extent of lymphadenectomy needed to optimize oncologic outcomes after radical cystectomy (RC) for patients with regionally advanced bladder cancer (BCa) is unclear. OBJECTIVE Evaluate the effect of the location of lymph node metastasis on recurrence-free survival (RFS) and cancer-specific survival (CSS) for patients undergoing RC with a mapping pelvic lymph node dissection (PLND). DESIGN, SETTING, AND PARTICIPANTS A study of 591 patients undergoing RC with mapping PLND was completed between 2000 and 2010. Median follow-up was 30 mo. INTERVENTION RC with mapping PLND. MEASUREMENTS We evaluated the impact of lymph node involvement by location on disease outcomes using the 2010 TNM staging system. Survival estimates were described using Kaplan-Meier methods. Gender, age, pathologic stage, histology, number of positive nodes, location of positive nodes, node density, use of perioperative chemotherapy, and grade were evaluated as predictors of RFS and CSS using multivariate Cox proportional hazard regression. RESULTS AND LIMITATIONS Overall, 114 patients (19%) had lymph node involvement, and 42 patients (7%) had pN3 disease. On multivariate analysis, the number of positive lymph nodes (one or two or more) was significantly associated with increased risk of cancer-specific death (hazard ratio [HR]: 1.9 [95% confidence interval (CI), 1.04-3.46], p=0.036; versus HR: 4.3 [95% CI, 2.25-8.34], p<0.0005). Positive lymph node location was not an independent predictor of RFS or CSS. Five-year RFS for pN3 patients undergoing RC with PLND was 25% (95% CI, 10-42). This finding was not statistically different from our pN1 and pN2 patients (38% [95% CI, 22-54] and 35% [95% CI, 11-60], respectively). This study is limited by the lack of prospective randomization and a control group. CONCLUSIONS The outcome for patients with involved common iliac lymph nodes was similar to the outcome for patients with primary nodal basin disease. These data support inclusion of the common iliac lymph nodes (pN3) in the nodal staging system for BCa. Lymph node location was not an independent predictor of outcome, whereas the number of positive lymph nodes was an independent predictor of worse oncologic outcome (pN1, pN2). Further refinements of the TNM system to provide improved prognostication are warranted.

Comparison of Open and Minimally Invasive Partial Nephrectomy for Renal Tumors 4-7 Centimeters

BACKGROUND Indications for partial nephrectomy (PN) in the treatment of renal cell carcinoma are evolving, particularly for larger, more complex tumors. OBJECTIVE Compare single-institution outcomes for minimally invasive partial nephrectomy (MIPN) and open partial nephrectomy (OPN) for tumors>4-7 cm. DESIGN, SETTING, AND PARTICIPANTS A total of 2290 patients underwent PN from 2002 to 2010 at Memorial Sloan-Kettering Cancer Center; 280 had >4-7 cm renal cortical tumors. Of these 280 patients, 230 had pT1b, 48 had pT3a, and 2 had angiomyolipomas; 226 underwent OPN and 54 underwent MIPN (16 robot-assisted and 37 laparoscopic procedures). Perioperative management was uniform on the clinical pathway. Perioperative data, clinicopathologic variables, complications within 30 d, and oncologic outcomes were reviewed. MEASUREMENTS Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Complications were reported from prospectively collected data based on a modified Clavien system. The Fisher exact and Mann-Whitney U tests were used for descriptive statistical analysis. Kaplan-Meier methods were used to estimate survival. RESULTS AND LIMITATIONS Median follow-up for OPN and MIPN was 29 and 13 mo, respectively. There were no statistically significant differences in age, gender, preoperative American Society of Anesthesiologists score, laterality, histologic subtype, tumor size, tumor stage, or margin status between procedures. Univariate analysis revealed significantly greater values in the OPN group for preoperative eGFR, renal artery clamp time, estimated blood loss, use of renal hypothermia, and length of stay. Differences in overall survival and recurrence-free survival were not statistically significant; however, short median follow-up times limit comparison. There was no significant difference in the number of complications grade≥3 (p=0.1) or urine leaks requiring intervention (p=0.7). Limitations include the retrospective nature of the study and the possibility of selection bias. CONCLUSIONS OPN and MIPN procedures performed in patients with tumors>4-7 cm offer acceptable and comparable results in terms of operative, functional, and convalescence measures, regardless of approach.

Reverse Stage Shift at a Tertiary Care Center: Escalating Risk in Men Undergoing Radical Prostatectomy

The objective of this study was to evaluate changes in clinical and pathologic characteristics of prostate cancer in patients who underwent surgery at a large tertiary care center in the context of increased use of active surveillance (AS) and minimally invasive surgery (MIS).

Pelvic Lymph Node Dissection for Patients with Elevated Risk of Lymph Node Invasion During Radical Prostatectomy: Comparison of Open, Laparoscopic and Robot-Assisted Procedures

BACKGROUND AND PURPOSE Published outcomes of pelvic lymph node dissection (PLND) during robot-assisted laparoscopic prostatectomy (RALP) demonstrate significant variability. The purpose of the study was to compare PLND outcomes in patients at risk for lymph node involvement (LNI) who were undergoing radical prostatectomy (RP) by different surgeons and surgical approaches. PATIENTS AND METHODS Institutional policy initiated on January 1, 2010, mandated that all patients undergoing RP receive a standardized PLND with inclusion of the hypogastric region when predicted risk of LNI was ≥ 2%. We analyzed the outcomes of consecutive patients meeting these criteria from January 1 to September 1, 2010 by surgeons and surgical approach. All patients underwent RP; surgical approach (open radical retropubic [ORP], laparoscopic [LRP], RALP) was selected by the consulting surgeon. Differences in lymph node yield (LNY) between surgeons and surgical approaches were compared using multivariable linear regression with adjustment for clinical stage, biopsy Gleason grade, prostate-specific antigen (PSA) level, and age. RESULTS Of 330 patients (126 ORP, 78 LRP, 126 RALP), 323 (98%) underwent PLND. There were no significant differences in characteristics between approaches, but the nomogram probability of LNI was slightly greater for ORP than RALP (P=0.04). LNY was high (18 nodes) by all approaches; more nodes were removed by ORP and LRP (median 20, 19, respectively) than RALP (16) after adjusting for stage, grade, PSA level, and age (P=0.015). Rates of LNI were high (14%) with no difference between approaches when adjusted for nomogram probability of LNI (P=0.15). Variation in median LNY among individual surgeons was considerable for all three approaches (11-28) (P=0.005) and was much greater than the variability by approach. CONCLUSIONS PLND, including hypogastric nodal packet, can be performed by any surgical approach, with slightly different yields but similar pathologic outcomes. Individual surgeon commitment to PLND may be more important than approach.

Renal Function and Oncologic Outcomes of Parenchymal Sparing Ureteral Resection Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

PURPOSE We compared renal function and oncologic outcomes of parenchymal sparing ureteral resection with radical nephroureterectomy for the treatment of upper tract urothelial carcinoma confined to the ureter. MATERIALS AND METHODS Review of a large institutional database identified 367 patients treated for primary upper tract urothelial carcinoma with radical nephroureterectomy or parenchymal sparing ureteral resection from 1994 to 2009. Patients with known renal pelvis tumors, muscle invasive urothelial carcinoma, prior cystectomy, contralateral upper tract urothelial carcinoma, metastatic disease or chemotherapy were excluded, leaving 120 patients for analysis. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Recurrence-free, cancer specific and overall survival were estimated using Kaplan-Meier analysis. RESULTS Radical nephroureterectomy was performed in 87 patients and parenchymal sparing ureteral resection in 33. Median age at surgery was 73 years in the radical nephroureterectomy group (IQR 64-76) vs 70 years (IQR 59-77) in the parenchymal sparing ureteral resection group (p = 0.5). The radical nephroureterectomy and parenchymal sparing ureteral resection cohorts had several disparate clinicopathological variables including preoperative hydronephrosis (80% vs 45%, p = 0.0006), stage (pT3 or greater 26% vs 9%, p = 0.01) and baseline estimated glomerular filtration rate (51 vs 63 ml/minute/1.73 m(2), p = 0.009). Patients who underwent radical nephroureterectomy experienced a significantly greater decrease in estimated glomerular filtration rate after surgery (median -7 vs 0 ml/minute/1.73 m(2), p <0.001). Median followup was 4.2 years. Of the patients 79 experienced cancer recurrence and 44 died (28 of upper tract urothelial carcinoma). There were no obvious differences in the rates of recurrence, cancer specific death or overall death by procedure type. However, due to the limited number of events we cannot exclude the possibility that there are large differences in oncologic outcomes by procedure type. CONCLUSIONS Parenchymal sparing ureteral resection is associated with superior postoperative renal function. However, the impact on cancer control cannot be determined conclusively due to the small sample size and putative selection bias.

Intraoperative Mannitol Use Does Not Improve Long-term Renal Function Outcomes After Minimally Invasive Partial Nephrectomy

OBJECTIVE To evaluate intravenous mannitol during minimally invasive partial nephrectomy (PN) by comparing the renal function outcomes of the patients who received it versus those who did not. METHODS Of 285 consecutive elective minimally invasive PN cases from February 2005 to July 2010, 164 patients (58%) were treated with mannitol. We compared the renal function recovery using a multivariate generalized estimating equation linear model of estimated glomerular filtration rate (eGFR) controlling for nephrometry complexity, preoperative eGFR, American Society of Anesthesiologists score, ischemia time, estimated blood loss, age, and sex. Sensitivity analyses were performed to adjust for cold ischemia and individual surgeon differences corrected for year of surgery. RESULTS Of the 285 patients who underwent minimally invasive treatment, 164 received mannitol and 121 did not. Those who received mannitol had a better preoperative eGFR (median 72 vs 69 mL/min/m(2), P = .046), less complex nephrometry scores (P = 0.051), and were less likely to have an American Society of Anesthesiologists score of ≥ 3 (42% vs 54%, P = .005). Renal function recovery was similar in both groups (estimated effect of mannitol -0.7 mL/min/m(2), 95% confidence interval -3.6-2.2, P = .6). At no point in the postoperative period did mannitol make a significant difference in the eGFR according to the generalized estimating equation model after adjusting for multiple potential renal function confounders. CONCLUSION Mannitol use did not influence renal function recovery within 6 months of minimally invasive PN as measured by the eGFR in our analysis. An appropriately designed prospective study of mannitol is being conducted to validate its use during PN.

Comparison of Guidelines on Non-Muscle Invasive Bladder Cancer (EAU, CUA, AUA, NCCN, NICE)

Background: Non-muscle invasive bladder cancer (NMIBC) represents a considerably diverse patient group and the management of this complex disease is debatable. A number of panels from Europe and North America have convened on the topic and recently released guideline documents. Objective: The purpose was to compare and contrast the NMIBC guideline recommendations from the EAU (Europe), CUA (Canada), NCCN (United States), AUA (United States), and NICE (United Kingdom). Methods: All unabridged guideline documents were reviewed by the authors and comparisons were completed according to major topics in NMIBC. Results: Despite a paucity of high level evidence regarding the majority of management topics in NMIBC, there was general agreement among the various guideline panels. Differences mainly centered on the categories of evidence synthesized and grades of recommendations. Each document offers a unique presentation of the available literature and guideline recommendation. Conclusions: The guidelines for NMIBC from the EAU, CUA, AUA, NCCN, and NICE provide considerable consensus regarding the management of this often difficult disease. Clinicians are encouraged to familiarize themselves with all of the guidelines in order to determine which style of presentation would be most useful to their current practice.

Urine Neutrophil Gelatinase-Associated Lipocalin as a Marker of Acute Kidney Injury After Kidney Surgery

PURPOSE We evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls. MATERIALS AND METHODS Using patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m(2) or greater. RESULTS Of 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m(2) in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m(2), respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) had higher urine NGAL postoperatively than those with a higher preoperative estimated rate. CONCLUSIONS Urine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry

Background Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Patients and Methods Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/μL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. Results PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. Conclusions PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

Intravenous Mannitol Versus Placebo During Partial Nephrectomy in Patients with Normal Kidney Function: A Double-blind, Clinically-integrated, Randomized Trial

BACKGROUND Mannitol is currently used as a renal protective agent to mitigate the effects of renal ischemia during nephron-sparing surgery (NSS). This routine practice lacks rigorous methodological study. OBJECTIVE To assess the effect on renal function outcomes after surgery of mannitol infusion prior to renal ischemia during NSS. DESIGN, SETTING, PARTICIPANTS This prospective, randomized, placebo-controlled, double-blind trial included 199 patients with a preoperative estimated glomerular filtration rate (eGFR) >45ml/min/1.73m2 scheduled for NSS; the trial was conducted between July 2012 and July 2015. INTERVENTION Patients undergoing NSS were randomized to receive mannitol (12.5g) or placebo intravenously within 30min prior to renal vascular clamping. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was the difference in eGFR (renal function) between the two groups at 6 mo following surgery assessed with an analysis of covariance model using preoperative eGFR, treatment group, and surgical approach as covariates. RESULTS AND LIMITATIONS At baseline, the median age of the patients was 58 yr, and the median eGFR was 88ml/min/1.73m2. Comparing placebo with mannitol infusion, the adjusted difference of 0.2 eGFR units at 6 mo was not significant (p=0.9), with the upper bound of the 95% confidence interval (-3.1 to 3.5) excluding a clinically relevant effect of mannitol. Limitations include evaluation of a single mannitol dose and patients all had excellent preoperative renal function. CONCLUSIONS Intraoperative 12.5g mannitol infusion during NSS has no demonstrable clinical benefit when compared with standardized fluid hydration in patients with normal preoperative renal function, and its use in this setting is not warranted. PATIENT SUMMARY In this randomized trial, patients with normal kidney function who received mannitol during surgery to remove part of their kidney had no better kidney function 6 mo after surgery than those who did not receive mannitol. We conclude that this routine practice should be discontinued.