Hiten D. Patel

Trends in Renal Surgery: Robotic Technology is Associated with Increased Use of Partial Nephrectomy

PURPOSE Underuse of partial vs radical nephrectomy for renal tumors was noted in recent population based analyses. An explanation is the learning curve associated with laparoscopic partial nephrectomy. We analyzed state trends in renal surgery and their relationship to the introduction of robotic technology. MATERIALS AND METHODS We used the Maryland HSCRC (Health Services Cost Review Commission) database to identify patients who underwent radical or partial nephrectomy, or renal ablation from 2000 to 2011. Utilization trends, and associated patient and hospital factors were analyzed using multivariate logistic regression. ICD-9 robotic modifier codes were established in October 2008. RESULTS Of the 14,260 patients included in analysis 11,271 (79.0%), 2,622 (18.4%) and 367 (2.6%) underwent radical and partial nephrectomy, and renal ablation, respectively. Partial nephrectomy increased from 8.6% in 2000 to 27% in 2011. Open radical nephrectomy decreased by 33%, while minimally invasive radical nephrectomy increased by 15%. Robot-assisted laparoscopic partial nephrectomy increased from 2008 to 2011, attaining a 14% rate at university and 10% at nonuniversity hospitals (p = 0.03). It was associated with increased partial nephrectomy (OR 9.67, p <0.001). Younger age, male gender and low patient complexity predicted partial nephrectomy on overall analysis, while higher hospital volume and university status were predictors only in earlier years. CONCLUSIONS Partial nephrectomy use increased in Maryland from 2001 to 2011, which was facilitated by robotic technology. Associations with hospital factors decreased with time. These data suggest that robotic technology may enable surgeons across practice settings to more frequently perform nephron sparing surgery.

Robotic-assisted Versus Traditional Laparoscopic Partial Nephrectomy: Comparison of Outcomes and Evaluation of Learning Curve

OBJECTIVES To examine the transition to robot-assisted laparoscopic partial nephrectomy (RALPN) from pure laparoscopic partial nephrectomy (LPN) and investigate the learning curve (LC). RALPN has emerged as a minimally invasive alternative to nephron-sparing surgery. METHODS A total of 150 consecutive patients were identified who underwent LPN or RALPN in the initial experience of a single surgeon since 2006. The perioperative data were evaluated using appropriate comparative tests. The LC was investigated by examining the operative times, warm ischemia times (WITs), and estimated blood loss (EBL) in groups of 25 consecutive patients. To account for laparoscopic LC, the outcomes of patients who underwent surgery in 2009 or later were also compared. RESULTS Of the 150 patients, 102 and 48 underwent LPN and RALPN, respectively. The patient and tumor characteristics were similar. The mean operative time (193 vs 152 minutes, P < .001), WIT (18.0 vs 14.0, P < .001), and EBL (245 vs 122 mL, P = .001) favored RALPN. Improvements in the operative time (P = .01), WIT (P = .006), and EBL (P = .01) were noted as experience increased in the LPN cohort and was most pronounced after the first 25 LPN patients. Since 2009, 55 and 44 patients underwent LPN and RALPN, respectively. Although the absolute differences were less, the operative time (182 vs 150, P < .001), WIT (15.3 vs 13.3, P < .001), and EBL (206 vs 118, P = .005) favored RALPN. CONCLUSIONS RALPN appears to have shorter operative and ischemia times and less blood loss compared with LPN. After a LC of approximately 25 cases, the transition from LPN to RALPN can be undertaken without an additional LC and can be associated with immediate benefits.

Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis

PURPOSE Several options exist for management of clinically localized renal masses suspicious for cancer, including active surveillance, thermal ablation and radical or partial nephrectomy. We summarize evidence on effectiveness and comparative effectiveness of these treatment approaches for patients with a renal mass suspicious for localized renal cell carcinoma. MATERIALS AND METHODS We searched MEDLINE®, Embase® and the Cochrane Central Register of Controlled Trials from January 1, 1997 through May 1, 2015. Paired investigators independently screened articles to identify controlled studies of management options or cohort studies of active surveillance, abstracted data sequentially and assessed risk of bias independently. Strength of evidence was graded by comparisons. RESULTS The search identified 107 studies (majority T1, no active surveillance or thermal ablation stratified outcomes of T2 tumors). Cancer specific survival was excellent among all management strategies (median 5-year survival 95%). Local recurrence-free survival was inferior for thermal ablation with 1 treatment but reached equivalence to other modalities after multiple treatments. Overall survival rates were similar among management strategies and varied with age and comorbidity. End-stage renal disease rates were low for all strategies (0.4% to 2.8%). Radical nephrectomy was associated with the largest decrease in estimated glomerular filtration rate and highest incidence of chronic kidney disease. Thermal ablation offered the most favorable perioperative outcomes. Partial nephrectomy showed the highest rates of urological complications but overall rates of minor/major complications were similar among interventions. Strength of evidence was moderate, low and insufficient for 11, 22 and 30 domains, respectively. CONCLUSIONS Comparative studies demonstrated similar cancer specific survival across management strategies, with some differences in renal functional outcomes, perioperative outcomes and postoperative harms that should be considered when choosing a management strategy.

Diagnostic Accuracy and Risks of Biopsy in the Diagnosis of a Renal Mass Suspicious for Localized Renal Cell Carcinoma: Systematic Review of the Literature

PURPOSE Clinical practice varies widely on the diagnostic role of biopsy for clinically localized renal masses suspicious for renal cell carcinoma. Therefore, we performed a systematic review of the available literature to quantify the accuracy and rate of adverse events of renal mass biopsy. MATERIALS AND METHODS MEDLINE®, Embase® and the Cochrane databases were searched (January 1997 to May 2015) for relevant studies. The systematic review process established by the Agency for Healthcare Research and Quality was followed. Nondiagnostic biopsies were excluded from diagnostic accuracy calculations. RESULTS A total of 20 studies with 2,979 patients and 3,113 biopsies were included in the study. The overall nondiagnostic rate was 14.1% with 90.4% of those undergoing surgery found to have malignancy. Repeat biopsy led to diagnosis in 80% of patients. The false-positive rate was low (4.0%), histological and renal cell carcinoma subtype concordance was substantial, and Fuhrman upgrading notable (16%) from low grade (1 to 2) to high grade (3 to 4). Core biopsy was highly sensitive (97.5%, CI 96.5-98.5) and specific (96.2%, CI 90.7-100) when a diagnostic result was obtained, but most patients (∼80%) did not undergo surgery after a benign biopsy. Among patients undergoing extirpation 36.7% with a negative biopsy had malignant disease on surgical pathology (negative predictive value 63.3%, CI 52.4-74.2). Direct complications included hematoma (4.9%), clinically significant pain (1.2%), gross hematuria (1.0%), pneumothorax (0.6%) and hemorrhage (0.4%). CONCLUSIONS Diagnostic accuracy was generally high for biopsy of localized renal masses with a low complication rate, but the nondiagnostic rate and negative predictive value were concerning. Renal mass sampling should be used judiciously as further research will determine its true clinical utility.

Comparative Analysis of Minimally Invasive Partial Nephrectomy Techniques in the Treatment of Localized Renal Tumors

OBJECTIVE To report our initial experience with robot-assisted laparoscopic partial nephrectomy compared with traditional laparoscopic partial nephrectomy. METHODS A retrospective review of the Johns Hopkins minimally invasive urologic surgery database identified 207 consecutive patients who had undergone laparoscopic or robotic-assisted laparoscopic partial nephrectomy from 2007 to 2011 by a single surgeon. The patient demographics and pathologic, operative, and perioperative outcomes were compared between the surgical techniques. The early oncologic outcomes are reported for the entire cohort. RESULTS A total of 102 and 105 patients underwent laparoscopic partial nephrectomy and robotic-assisted laparoscopic partial nephrectomy, respectively. The demographic data were comparable between the 2 groups. The clinical and pathologic tumor characteristics were similar between the 2 groups, and a significant proportion (≥48%) of patients in each group had moderate to high complexity tumors. Patients undergoing robotic-assisted laparoscopic partial nephrectomy had decreased warm ischemia times, estimated blood loss, and operative times on univariate and multivariate analysis. No difference was seen in the total perioperative or significant urologic complications between the 2 groups. A review of the early oncologic outcomes revealed no local recurrences and 1 case of metastatic renal cell carcinoma. CONCLUSION Minimally invasive partial nephrectomy is associated with favorable perioperative outcomes and low morbidity. Robotic-assisted laparoscopic partial nephrectomy appears to be associated with favorable warm ischemia times compared with laparoscopic partial nephrectomy.

Frailty as a marker of adverse outcomes in patients with bladder cancer undergoing radical cystectomy

OBJECTIVE To investigate the modified frailty index (mFI) as a preoperative predictor of postoperative complications following radical cystectomy (RC) in patients with bladder cancer. MATERIALS AND METHODS Patients undergoing RC were identified from the National Surgical Quality Improvement Program participant use files (2011-2013). The mFI was defined in prior studies with 11 variables based on mapping the Canadian Study of Health and Aging Frailty Index to the National Surgical Quality Improvement Program comorbidities and activities of daily livings. The mFI groups were determined by the number of risk factors per patient (0, 1, 2, and≥3). Univariable and multivariable regression were performed to determine predictors of Clavien 4 and 5 complications, and a sensitivity analysis was performed to determine the mFI value that would be a significant predictor of Clavien 4 and 5 complications. RESULTS Of the 2,679 cystectomy patients identified, 843 (31%) of patients had an mFI of 0, 1176 (44%) had an mFI of 1, 555 (21%) had an mFI of 2, and 105 (4%) had an mFI≥3. Overall, 1585 (59%) of patients experienced a Clavien complication. When stratified at a cutoff of mFI≥2, the overall complication rate was not different (61.7% vs. 58.3%, P = 0.1), but the mFI2 or greater group had a significantly higher rate of Clavien grade 4 or 5 complications (14.6% vs. 8.3%, P<0.001) and overall mortality rate (3.5% vs. 1.8%, P = 0.01) in the 30-day postoperative period. The multivariate logistic regression model showed independent predictors of Clavien grade 4 or 5 complications were age>80 years (odds ratio [OR] = 1.58 [1.11-2.27]), mFI2 (OR = 1.84 [1.28-2.64]), and mFI3 (OR = 2.58 [1.47-4.55]). CONCLUSIONS Among patients undergoing RC, the mFI can identify those patients at greatest risk for severe complications and mortality. Given that bladder cancer is increasing in prevalence particularly among the elderly, preoperative risk stratification is crucial to inform decision-making about surgical candidacy.

A Prospective, Comparative Study of Quality of Life among Patients with Small Renal Masses Choosing Active Surveillance and Primary Intervention

PURPOSE To our knowledge quality of life has not been evaluated in rigorous fashion in patients undergoing active surveillance for small renal masses. The prospective, multi-institutional DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry was opened on January 1, 2009, enrolling patients with cT1a (4.0 cm or less) small renal masses who elected primary intervention or active surveillance. MATERIALS AND METHODS Patients were enrolled following a choice of active surveillance or primary intervention. The active surveillance protocol includes imaging every 4 to 6 months for 2 years and every 6 to 12 months thereafter. The SF12® quality of life questionnaire was completed at study enrollment, at 6 and 12 months, and annually thereafter. MCS (Mental Component Summary), PCS (Physical Component Summary) and overall score were evaluated among the groups and with time using ANOVA and linear regression mixed modeling. RESULTS At 82 months among 3 institutions 539 patients were enrolled with a mean ± SD followup of 1.8 ± 1.7 years. Of the patients 254 were on active surveillance, 285 were on primary intervention and 21 were on active surveillance but crossed over to delayed intervention. A total of 1,497 questionnaires were completed. Total and PCS quality of life scores were better for primary intervention at enrollment through 5 years. There were generally no differences in MCS scores among the groups and there was a trend of improving scores with time. CONCLUSIONS In a prospective registry of patients undergoing active surveillance or primary intervention for small renal masses those undergoing primary intervention had higher quality of life scores at baseline. This was due to a perceived benefit in the physical health domain, which persisted throughout followup. Mental health, which includes the domains of depression and anxiety, was not adversely affected while on active surveillance, and it improved with time after selecting a management strategy.

Fluoroquinolone Resistance in the Rectal Carriage of Men in an Active Surveillance Cohort: Longitudinal Analysis

PURPOSE Rectal swabs can identify men with fluoroquinolone resistant bacteria and decrease the infection rate after transrectal ultrasound guided prostate biopsy by targeted antimicrobial prophylaxis. We evaluated the rate of fluoroquinolone resistance in an active surveillance cohort with attention to factors associated with resistance and changes in resistance with time. MATERIALS AND METHODS We evaluated 416 men with prostate cancer on active surveillance who underwent rectal swabs to assess the rate of fluoroquinolone resistance compared to that in men undergoing diagnostic transrectal ultrasound guided prostate biopsy. The chi-square test and Student t-test were used to compare categorical and continuous variables, respectively. Poisson regression analysis was used for multivariate analysis. RESULTS On the initial swab fluoroquinolone resistance was found in 95 of 416 men (22.8%) on active surveillance compared to 54 of 221 (24.4%) in the diagnostic biopsy cohort (p = 0.675). Diabetes was found in 4.0% of the fluoroquinolone sensitive group vs 14.7% of the resistant group (p <0.001). Biopsy history was not associated with resistance. Of those with a resistant first swab 62.9% had a resistant second swab and 88.9% of those with 2 resistant swabs showed resistance on the third swab. Of men with a sensitive first swab 10.6% showed resistance on the second swab and 10.6% of those with 2 sensitive swabs had resistant third swabs. CONCLUSIONS One of 4 men who present for surveillance and diagnostic transrectal ultrasound guided prostate biopsy have rectal flora resistant to fluoroquinolone. Resistance is significantly associated with diabetes but the number of prior biopsies is not. Men with fluoroquinolone resistant flora tend to remain resistant with time.

Prostate Specific Antigen Velocity Risk Count Predicts Biopsy Reclassification for Men with Very Low Risk Prostate Cancer

PURPOSE Prostate specific antigen velocity is an unreliable predictor of adverse pathology findings in patients on active surveillance for low risk prostate cancer. However, to our knowledge a new concept called prostate specific antigen velocity risk count, recently validated in a screening cohort, has not been investigated in an active surveillance cohort. MATERIALS AND METHODS We evaluated a cohort of men from 1995 to 2012 with prostate cancer on active surveillance. They had stage T1c disease, prostate specific antigen density less than 0.15 ng/ml, Gleason score 6 or less, 2 or fewer biopsy cores and 50% or less involvement of any core with cancer. The men were observed by semiannual prostate specific antigen measurements, digital rectal examinations and an annual surveillance biopsy. Treatment was recommended for biopsy reclassification. Patients with 30 months or greater of followup and 3 serial prostate specific antigen velocity measurements were used in primary analysis by logistic regression, Cox proportional hazards, Kaplan-Meier analysis and performance parameters, including the AUC of the ROC curve. RESULTS Primary analysis included 275 of 668 men who met very low risk inclusion criteria, of whom 83 (30.2%) were reclassified at a median of 57.1 months. Reclassification risk increased with risk count, that is a risk count of 3 (HR 4.63, 95% CI 1.54-13.87) and 2 (HR 3.73, 95% CI 1.75-7.97) compared to zero. Results were similar for Gleason score reclassification (HR 7.45, 95% CI 1.60-34.71 and 3.96, 95% CI 1.35-11.62, respectively). On secondary analysis the negative predictive value (risk count 1 or less) was 91.5% for reclassification in the next year. Adding the prostate specific antigen velocity risk count improved the AUC in a model including baseline prostate specific antigen density (0.7423 vs 0.6818, p = 0.025) and it outperformed the addition of overall prostate specific antigen velocity (0.7423 vs 0.6960, p = 0.037). CONCLUSIONS Prostate specific antigen velocity risk count may be useful for monitoring patients on active surveillance and decreasing the frequency of biopsies needed in the long term.

Comorbidities and causes of death in the management of localized T1a kidney cancer

The objectives of the present study were analyze specific comorbidities associated with survival and actual causes of death for patients with small renal masses, and to suggest a simplified measure associated with decreased overall survival specific to this population.