Automated Identification of Key Steps in Robotic-Assisted Radical Prostatectomy Using Artificial Intelligence.

PURPOSE: The widespread use of minimally invasive surgery generates vast amounts of potentially useful data in the form of surgical video. However, raw video footage is often unstructured and unlabeled, thereby limiting its use. We developed a novel computer-vision algorithm for automated identification and labeling of surgical steps during robotic-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Surgical videos from RARP were manually annotated by a team of image annotators under the supervision of 2 urologic oncologists. Full-length surgical videos were labeled to identify all steps of surgery. These manually annotated videos were then utilized to train a computer vision algorithm to perform automated video annotation of RARP surgical video. Accuracy of automated video annotation was determined by comparing to manual human annotations as the reference standard. RESULTS: A total of 474 full-length RARP videos (median 149 minutes; IQR 81 minutes) were manually annotated with surgical steps. Of these, 292 cases served as a training dataset for algorithm development, 69 cases were used for internal validation, and 113 were used as a separate testing cohort for evaluating algorithm accuracy. Concordance between artificial intelligence‒enabled automated video analysis and manual human video annotation was 92.8%. Algorithm accuracy was highest for the vesicourethral anastomosis step (97.3%) and lowest for the final inspection and extraction step (76.8%). CONCLUSIONS: We developed a fully automated artificial intelligence tool for annotation of RARP surgical video. Automated surgical video analysis has immediate practical applications in surgeon video review, surgical training and education, quality and safety benchmarking, medical billing and documentation, and operating room logistics.

A luminal non-coding RNA-based genomic classifier confirms favourable outcomes in patients with clinically organ-confined bladder cancer treated with radical cystectomy.

OBJECTIVE: To further evaluate a genomic classifier (GC) in a cohort of patients undergoing radical cystectomy (RC), as long non-coding RNA (lncRNA)-based genomic profiling has suggested utility in identifying a distinct tumour subgroup corresponding to a favourable prognosis in patients with bladder cancer. PATIENTS AND METHODS: Transcriptome-wide expression profiling using Decipher Bladder was performed on transurethral resection of bladder tumour samples from a cohort of patients with high-grade, clinically organ-confined (cTa-T2N0M0) urothelial carcinoma (UC) who subsequently underwent RC without any neoadjuvant therapy (n = 226). The lncRNA-based luminal favourable status was determined using a previously developed GC. The primary endpoint was overall survival (OS) after RC. Secondary endpoints included cancer-specific mortality and upstaging at RC. RESULTS: In the study, 134 patients were clinical non-muscle-invasive bladder cancer (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favourable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On multivariate analysis, patients with the luminal favourable subtype (vs without) were significantly associated with lower odds of upstaging to pathological (p)T3+ disease (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.12-0.82; P = 0.02), any upstaging (OR 0.41, 95% CI 0.20-0.83; P = 0.01), and any upstaging and/or pN+ (OR 0.50, 95% CI 0.25-1.00; P = 0.05). Luminal favourable bladder cancer was significantly associated with better OS (hazard ratio 0.33, 95% CI 0.15-0.74; P = 0.007). CONCLUSIONS: This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.

Intraoperative Blood Transfusion Is Associated With Increased Risk of Venous Thromboembolism After Radical Cystectomy.

PURPOSE: Our objective was to examine whether perioperative blood transfusion is associated with venous thromboembolism following radical cystectomy adjusting for both patient- and disease-related factors. MATERIALS AND METHODS: Patients who underwent radical cystectomy for bladder cancer from 1980-2020 were identified in the Mayo Clinic cystectomy registry. Blood transfusion during the initial postoperative hospitalization was analyzed as a 3-tiered variable: no transfusion, postoperative transfusion alone, or intraoperative with or without postoperative transfusion. The primary outcome was venous thromboembolism within 90 days of radical cystectomy. Associations between clinicopathological variables and 90-day venous thromboembolism were assessed using multivariable logistic regression, with transfusion analyzed as both a categorical and a continuous variable. RESULTS: A total of 3,755 radical cystectomy patients were identified, of whom 162 (4.3%) experienced a venous thromboembolism within 90 days of radical cystectomy. Overall, 2,112 patients (56%) received a median of 1 (IQR: 0-3) unit of blood transfusion, including 811 (38%) with intraoperative transfusion only, 572 (27%) with postoperative transfusion only, and 729 (35%) with intraoperative and postoperative transfusion. On multivariable analysis, intraoperative with or without postoperative blood transfusion was associated with a significantly increased risk of venous thromboembolism (adjusted OR 1.73, 95% CI 1.17-2.56, P = .002). Moreover, when analyzed as a continuous variable, each unit of blood transfused intraoperatively was associated with 7% higher odds of venous thromboembolism (adjusted OR 1.07, 95% CI 1.01-1.13, P = .03). CONCLUSIONS: Intraoperative blood transfusion was significantly associated with venous thromboembolism within 90 days of radical cystectomy. To ensure optimal perioperative outcomes, continued effort to limit blood transfusion in radical cystectomy patients is warranted.

Complete and Uneventful Recovery in a Case of Lymphocytic Hypophysitis Causing a Third Nerve Palsy.

Lymphocytic hypophysitis (LH) is a neuroendocrine disorder characterised by autoimmune inflammation of the pituitary gland with resultant pituitary dysfunction. Rarely, the presenting symptom can be diplopia due to irritation of the third, fourth, or sixth cranial nerves secondary to cavernous sinus involvement of the mass or increased intracranial pressure. We describe the case of a healthy, 20-year-old female with a pupillary sparing third nerve palsy, who was subsequently diagnosed with LH after an endoscopic transsphenoidal biopsy of the mass. She was treated with hormone replacement therapy and corticosteroids, resulting in full resolution of symptoms with no recurrence to date. To our knowledge, this is the first report of a third nerve palsy due to definitive biopsy proven LH. Despite its rarity, the unique presentation and favourable evolution of this case should aid clinicians in its timely recognition, appropriate workup, and treatment.

A Contemporary Analysis of Urethral Recurrence following Radical Cystectomy.

PURPOSE: Oncologic outcomes following urethral recurrence (UR) remain incompletely described, with reports limited by small cohort sizes. We evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. MATERIALS AND METHODS: We reviewed our institutional radical cystectomy (RC) registry to identify patients with UR. Cox proportional hazards regression was used to assess risk factors for UR. Kaplan-Meier and Cox models were used to assess the relationship between UR and CSS/OS as well as to compare outcomes following symptomatic vs asymptomatic presentation of UR. RESULTS: Overall, 2,930 patients underwent RC from 1980 to 2018, with a median postoperative followup of 7.1 years (IQR 2.8-13.1), of whom 144 (4.9%) were subsequently diagnosed with UR. Carcinoma in situ (HR 1.98, 95% CI 1.30-3.04), multifocal disease (HR 1.59, 95% CI 1.07-2.36) and prostatic urethral involvement at RC (HR 3.01, 95% CI 1.98-4.57) were associated with increased risk of UR. UR was associated with decreased CSS (HR 7.30, 95% CI 5.46-9.76) and OS (HR 1.86, 95% CI 1.54-2.24). A total of 63/144 patients were diagnosed with UR based on symptoms, while 104/144 patients with UR underwent urethrectomy. Patients with symptomatic UR had higher tumor stage at urethrectomy (≥pT2 in 13.1% vs 3.1%, p=0.007), while patients with asymptomatic UR experienced longer median CSS (12.1 vs 6.1 years) and OS (8.30 vs 4.82 years; p=0.05 for both). CONCLUSIONS: We identified pathological risk factors for UR after RC and report adverse subsequent survival outcomes for these patients. Presentation with symptomatic UR was associated with higher tumor stage and poorer prognosis, supporting a value to continued urethral surveillance after RC.

Comparison of Pediatric and Adult Ambulatory Blood Pressure Monitoring Criteria for the Diagnosis of Hypertension and Detection of Left Ventricular Hypertrophy in Adolescents.

OBJECTIVE: To compare pediatric ambulatory blood pressure monitoring (ABPM) criteria with adult ABPM criteria for the diagnosis of hypertension and detection of left ventricular hypertrophy (LVH) in adolescents. STUDY DESIGN: ABPM and echocardiography reports from adolescents age 13-21 years from 2015 to 2019 were analyzed. The concordance of hypertension based on pediatric criteria (American Heart Association 2014) was compared with adult criteria from American College of Cardiology/American Heart Association 2017 (overall BP ≥125/75 mm Hg, wake BP ≥130/80 mm Hg, sleep BP ≥110/65 mm Hg) using the Cohen kappa statistic. Logistic regression, adjusted for body mass index z score, and receiver operating characteristic curves (ROCs) compared pediatric criteria vs adult criteria in predicting LVH (left ventricular mass index >95th percentile reference values and left ventricular mass index >51 g/m2.7). RESULTS: Of 306 adolescents, 140 (45.8%) had hypertension based on pediatric criteria vs 228 (74.5%) based on adult criteria; the agreement was poor (59.3%, n = 137, kappa = 0.41). A higher prevalence of LVH was captured by adult criteria only (n = 91) compared with pediatric criteria only (n = 3). Logistic regression found no significant differences between pediatric and adult criteria in the detection of LVH >95th percentile (OR 1.24, CI 0.66, 2.31, P = .51) or >51 g/m2.7 (OR 1.06, CI 0.47, 2.40, P = .89). ROCs for pediatric criteria were not significant for detecting LVH >95th percentile (0.50, P = .91) or >51 g/m2.7 (0.55, P = .45), whereas the ROC for adult criteria was significant for detecting LVH >95th percentile (0.59, P = .045) but not >51 g/m2.7 (0.63, P = .07). Although all individuals with LVH >51 g/m2.7 were hypertensive by adult criteria, 8 of these individuals were missed by pediatric criteria. CONCLUSIONS: Adult criteria captured a higher prevalence of LVH and appeared to predict better LVH than pediatric criteria. A consideration to align ABPM criteria for diagnosing hypertension in adolescents with adult guidelines is warranted.

Adding carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in postsecond generation hormone therapy setting: Impact on treatment response and survival outcomes.

BACKGROUND: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting. METHODS: We retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo-naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate-specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30-month overall survival. RESULTS: Patients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15-5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04-8.54) (P = .0442). 30-month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31-7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58-11.06; P = .0037) between patients in group (C) compared to those in group (B) CONCLUSION: This data demonstrates improved response and overall survival in treatment-refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

Complete Surgical Metastasectomy of Renal Cell Carcinoma in the Post-Cytokine Era.

PURPOSE: Data supporting complete metastasectomy of metastatic renal cell carcinoma were derived primarily from the era of cytokine therapy. Whether complete metastasectomy remains beneficial in patients who receive more recently approved systemic therapies has not been well studied. The objective of this study was to examine survival outcomes among patients treated with complete metastasectomy in the era of targeted therapy and checkpoint blockade availability. MATERIALS AND METHODS: We queried our institutional nephrectomy registry and identified 586 patients who underwent partial or radical nephrectomy of unilateral, sporadic renal cell carcinoma with a first occurrence of metastasis between 2006 and 2017. Of these patients 158 were treated with complete metastasectomy. Associations of complete metastasectomy with cancer specific and overall survival were assessed using Cox proportional hazards models. RESULTS: Median followup after the diagnosis of metastasis was 3.9 years, during which 403 patients died, including 345 of renal cell carcinoma. Of the patients treated with complete metastasectomy 147 (93%) did not receive any systemic treatment of the index metastatic lesion(s). Two-year cancer specific survival was significantly greater in patients with vs without complete metastasectomy (84% vs 54%, p <0.001). After adjusting for age, gender, and the timing, number and location of metastases complete metastasectomy was associated with a significantly reduced likelihood of death from renal cell carcinoma (HR 0.47, 95% CI 0.34-0.65, p <0.001). CONCLUSIONS: Complete surgical resection of metastases of renal cell carcinoma was associated with improved cancer specific survival in the post-cytokine era. It may be considered in appropriate patients after a process of shared decision making.

Association of Partial versus Radical Nephrectomy with Subsequent Hypertension Risk Following Renal Tumor Resection.

PURPOSE: We investigated the risks of new onset and worsened hypertension after radical vs partial nephrectomy. MATERIALS AND METHODS: Using a national administrative database of privately and Medicare insured patients we performed a retrospective cohort study of 9,207 and 4,686 patients who underwent radical and partial nephrectomy, respectively, for a renal mass between January 1, 2007 and December 31, 2016. One-to-one propensity score matching was done to balance the surgical groups based on patient demographics, baseline comorbidities, current medications and surgery year. Primary outcomes included new onset hypertension among patients with no history of hypertension and worsened hypertension among patients with baseline hypertension. We performed subgroup analyses stratified by patient age (75 or greater vs less than 75 years) and the presence of baseline kidney disease. Incidence rates and Cox proportional hazards models were used to compare outcomes in matched cohorts. RESULTS: Among 3,106 propensity matched patients without preexisting hypertension radical nephrectomy was associated with a higher risk of new onset hypertension compared to partial nephrectomy (HR 1.40, 95% CI 1.22-1.60, p <0.001). Similarly among 6,250 propensity matched patients with hypertension prior to surgery radical nephrectomy was associated with a higher risk of worsening baseline hypertension (HR 1.18, 95% CI 1.10-1.26, p <0.001). Subgroup analyses were consistent with the main study findings of worsened hypertension (p for interaction ≥0.05). CONCLUSIONS: Radical nephrectomy was associated with a higher risk of new onset and worsened hypertension compared to partial nephrectomy, including among elderly patients and individuals with normal kidney function. Given prior noted associations between hypertension and noncancer related morbidity, our results further encourage the preferential use of partial nephrectomy to manage localized renal masses when technically feasible.

Prognostic evaluation of perinephric fat, renal sinus fat, and renal vein invasion for patients with pathological stage T3a clear-cell renal cell carcinoma.

OBJECTIVE: To investigate the prognostic significance of various patterns of extrarenal extension that comprise pathological stage T3a clear-cell renal cell carcinoma (ccRCC) amongst patients undergoing nephrectomy for non-metastatic disease. PATIENTS AND METHODS: A retrospective review of 563 patients who underwent radical nephrectomy for pathologically confirmed T3aN0/NxM0 ccRCC between 1970 and 2011 was performed. All pathological slides were re-reviewed by one urological pathologist. Associations of patterns of extrarenal extension (perinephric fat [PF], renal sinus fat [SF], and renal vein [RV], in isolation or in any combination) with disease progression, cancer-specific mortality (CSM), and all-cause mortality were evaluated on multivariable analyses. RESULTS: Overall, PF invasion, renal SF invasion, and RV tumour thrombus were present in 144 (26%), 51 (9%), and 163 (29%) patients, respectively, with multiple patterns of extrarenal extension identified in 205 (36%) patients. There were no significant differences in survival outcomes for isolated involvement of PF, renal SF, or RV. However, patients with multiple patterns of extrarenal extension were at significantly increased risk of disease progression (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.04-1.65; P = 0.020), CSM (HR 1.64, 95% CI 1.27-2.12; P < 0.001), and all-cause mortality (HR 1.32, 95% CI 1.08-1.61; P = 0.008). CONCLUSIONS: The presence of multiple patterns of extrarenal extension is associated with a higher risk of disease progression and cancer-related death after radical nephrectomy compared to isolated involvement of the PF, renal SF, or RV, which carry similar prognostic weight. If validated, these findings may help refine risk stratification of non-metastatic T3a RCC by distinguishing patients with multiple vs one pattern of extrarenal extension.

Implementation of multiparametric magnetic resonance imaging technology for evaluation of patients with suspicion for prostate cancer in the clinical practice setting.

OBJECTIVES: To investigate the impact of implementing magnetic resonance imaging (MRI) and ultrasonography fusion technology on biopsy and prostate cancer (PCa) detection rates in men presenting with clinical suspicion for PCa in the clinical practice setting. PATIENTS AND METHODS: We performed a review of 1 808 consecutive men referred for elevated prostate-specific antigen (PSA) level between 2011 and 2014. The study population was divided into two groups based on whether MRI was used as a risk stratification tool. Univariable and multivariable analyses of biopsy rates and overall and clinically significant PCa detection rates between groups were performed. RESULTS: The MRI and PSA-only groups consisted of 1 020 and 788 patients, respectively. A total of 465 patients (45.6%) in the MRI group and 442 (56.1%) in the PSA-only group underwent biopsy, corresponding to an 18.7% decrease in the proportion of patients receiving biopsy in the MRI group (P < 0.001). Overall PCa (56.8% vs 40.7%; P < 0.001) and clinically significant PCa detection (47.3% vs 31.0%; P < 0.001) was significantly higher in the MRI vs the PSA-only group. In logistic regression analyses, the odds of overall PCa detection (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.29-2.35; P < 0.001) and clinically significant PCa detection (OR 2.04, 95% CI 1.48-2.80; P < 0.001) were higher in the MRI than in the PSA-only group after adjusting for clinically relevant PCa variables. CONCLUSION: Among men presenting with clinical suspicion for PCa, addition of MRI increases detection of clinically significant cancers while reducing prostate biopsy rates when implemented in a clinical practice setting.

A risk-stratified approach to neoadjuvant chemotherapy in muscle-invasive bladder cancer: implications for patients classified with low-risk disease.

PURPOSE: To validate published risk criteria for informing use of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC), and to examine outcomes of low-risk (LR) patients treated with immediate radical cystectomy (RC). METHODS: We identified 1931 patients who underwent RC for MIBC from 1980 to 2016. Patients were considered high risk (HR) with hydronephrosis, lymphovascular invasion, variant histology and/or cT3/4 disease. Kaplan-Meier survival estimates were compared to patients classified as LR, and logistic regression was used to examine factors associated with pathologic downstaging. RESULTS: A total of 1025 LR and 906 HR patients were identified. Median follow-up was 6.3 years (IQR 2.6-12), during which time 1321 (68%) patients died, 753 (39%) from bladder cancer. HR patients had significantly lower 5-year CSS than LR patients (50% vs. 68%, p = 0.001). Of 561 cisplatin-eligible LR patients treated with RC without NAC, 293 (52%) had pathologic non-organ confined disease; of these, 81 (14%) received adjuvant chemotherapy; 78 (14%) did not due to a perioperative event, while 134 (24%) did not due to patient/provider choice. NAC in LR patients was associated with greater odds of pT0 (OR 3.05; p < 0.001) and < pT2 (OR 2.53; p < 0.001) disease, but was not significantly associated with CSS (p = 0.31). CONCLUSIONS: Our results validate the proposed risk groups. Among LR patients treated without NAC, 52% experienced pathologic upstaging, and 14% were unable to receive adjuvant chemotherapy due to a perioperative event. These data support offering NAC to both HR and LR MIBC patients, and may be useful for patient counseling.

Symptomatic Venous Thromboembolism is Associated with Inferior Survival among Patients Undergoing Nephrectomy with Inferior Vena Cava Tumor Thrombectomy for Renal Cell Carcinoma.

PURPOSE: We investigated the incidence and survival impact of symptomatic venous thromboembolism after nephrectomy with inferior vena cava tumor thrombectomy. MATERIALS AND METHODS: We retrospectively reviewed the records of 183 patients who underwent nephrectomy with inferior vena cava tumor thrombectomy (level I-IV) for renal cell carcinoma between 2000 and 2010. Postoperative venous thromboembolism was defined as symptomatic bland thrombus or embolism confirmed on imaging. The cumulative incidence of venous thromboembolism was estimated by the Kaplan-Meier method. Associations of clinicopathological features with time to thromboembolism after surgery and all cause mortality were evaluated on multivariable analysis with Cox models. RESULTS: Symptomatic venous thromboembolism developed in 55 patients a median of 23 days (IQR 5-142) postoperatively, including pulmonary thrombosis in 24, deep venous thrombosis in 17, bland inferior vena cava thrombosis in 13 and portal vein thrombosis in 1. The cumulative incidence of thromboembolism 30, 90 and 365 days following surgery was 17%, 22% and 27%, respectively. A history of smoking (HR 2.15, 95% CI 1.09-4.24, p = 0.028), ECOG (Eastern Cooperative Oncology Group) performance status 1 or greater (HR 2.15, 95% CI 1.17-3.93, p = 0.013), hypercoagulability disorder (HR 5.12, 95% CI 1.93-13.59, p = 0.001) and bulky lymphadenopathy at surgery (HR 4.84, 95% CI 1.87-12.51, p = 0.001) was significantly associated with an increased risk of venous thromboembolism on multivariable analysis. Postoperative venous thromboembolism was significantly associated with an increased risk of all cause mortality (HR 1.53, 95% CI 1.04-2.23, p = 0.029). CONCLUSIONS: Venous thromboembolism after nephrectomy and tumor thrombectomy is common within 90 days of surgery. Symptomatic venous thromboembolism in this population is independently associated with a greater risk of mortality.

The Association of Aspirin Use with Survival Following Radical Cystectomy.

PURPOSE: Aspirin may have antineoplastic properties through the inhibition of inflammatory cytokines that regulate cell proliferation, angiogenesis and apoptosis. In patients with nonmuscle invasive bladder cancer aspirin use has been linked to a reduced risk of recurrence. We evaluated the association of aspirin with survival following radical cystectomy. MATERIALS AND METHODS: A total of 1,061 patients underwent radical cystectomy at our institution between 2007 and 2016, of whom 461 (43%) were aspirin users at the time of surgery. Survival estimates were assessed by the Kaplan-Meier method. The Cox proportional hazards model was applied to evaluate associations between patient features and survival. RESULTS: Median followup after radical cystectomy among survivors was 4.2 years (IQR 2-6.2). During this time 442 patients died, including 331 of bladder cancer. Aspirin users were significantly older, more likely to have a history of cardiovascular disease and diabetes, and more likely to use metformin or statin (each p <0.05). Nevertheless, we found that patients who ingested a daily aspirin had significantly higher 5-year cancer specific survival (68% vs 60%, p = 0.02) and overall survival (59% vs 52%, p = 0.03) compared to nonusers. Moreover, after multivariable adjustment aspirin use remained independently associated with lower cancer specific mortality (HR 0.64, 95% CI 0.45-0.89, p = 0.01) as well as all cause mortality (HR 0.70, 95% CI 0.53-0.93, p = 0.02) but not with distant metastasis (p >0.05). CONCLUSIONS: Daily aspirin use was associated with significantly improved survival outcomes following radical cystectomy. Further research is warranted to evaluate the potential underlying biological mechanisms and investigate causality.

The Temporal Association of Robotic Surgical Diffusion with Overtreatment of the Small Renal Mass.

PURPOSE: We evaluated contemporary practice patterns in the management of small renal masses. MATERIALS AND METHODS: We identified 52,804 patients in the NCDB (National Cancer Database) who were diagnosed with a small renal mass (4 cm or less) between 2010 and 2014. Utilization trends of active surveillance, ablation and robotic, laparoscopic and open surgical techniques were compared among all comers, elderly patients 75 years old or older and individuals with competing health risks, defined as a Charlson index of 2 or greater. Multivariable logistic regression models were used to assess factors associated with robotic renal surgery and active surveillance. RESULTS: Surgery remained the primary treatment modality across all years studied, performed in 75.0% and 74.2% of cases in 2010 and 2014, respectively. Although increases in active surveillance from 4.8% in 2010 to 6.0% in 2014 (p <0.001) and robotic renal surgery (22.1% in 2010 to 39.7% in 2014, p <0.001) were observed, the increase in the proportion of small renal masses treated with robotic partial and radical nephrectomy was greater than that of active surveillance (82.0% and 63.0%, respectively, vs 25.0%). Subgroup analyses in individuals 75 years old or older, or with a Charlson index of 2 or greater likewise revealed preferential increases in robotic surgery vs active surveillance. On multivariable analysis later year of diagnosis was associated with increased performance of robotic renal surgery compared to active surveillance (2014 vs 2010 OR 1.44, 95% CI 1.20-1.72, p <0.001) and nonrobotic procedural interventions (2014 vs 2010 OR 2.59, 95% CI 2.30-2.93, p <0.001). CONCLUSIONS: Robotic surgical extirpation has outpaced the adoption of active surveillance of small renal masses. This raises concern that the diffusion of robotic technology propagates overtreatment, particularly among elderly and comorbid individuals.

Neer Award 2018: Platelet-derived growth factor receptor α co-expression typifies a subset of platelet-derived growth factor receptor ß-positive progenitor cells that contribute to fatty degeneration and fibrosis of the murine rotator cuff.

BACKGROUND AND HYPOTHESIS: After massive tears, rotator cuff muscle often undergoes atrophy, fibrosis, and fatty degeneration. These changes can lead to high surgical failure rates and poor patient outcomes. The identity of the progenitor cells involved in these processes has not been fully elucidated. Platelet-derived growth factor receptor ß (PDGFRß) and platelet-derived growth factor receptor α (PDGFRα) have previously been recognized as markers of cells involved in muscle fibroadipogenesis. We hypothesized that PDGFRα expression identifies a fibroadipogenic subset of PDGFRß+ progenitor cells that contribute to fibroadipogenesis of the rotator cuff. METHODS: We created massive rotator cuff tears in a transgenic strain of mice that allows PDGFRß+ cells to be tracked via green fluorescent protein (GFP) fluorescence. We then harvested rotator cuff muscle tissues at multiple time points postoperatively and analyzed them for the presence and localization of GFP+ PDGFRß+ PDGFRα+ cells. We cultured, induced, and treated these cells with the molecular inhibitor CWHM-12 to assess fibrosis inhibition. RESULTS: GFP+ PDGFRß+ PDGFRα+ cells were present in rotator cuff muscle tissue and, after massive tears, localized to fibrotic and adipogenic tissues. The frequency of PDGFRß+ PDGFRα+ cells increased at 5 days after massive cuff tears and decreased to basal levels within 2 weeks. PDGFRß+ PDGFRα+ cells were highly adipogenic and significantly more fibrogenic than PDGFRß+ PDGFRα- cells in vitro and localized to adipogenic and fibrotic tissues in vivo. Treatment with CWHM-12 significantly decreased fibrogenesis from PDGFRß+ PDGFRα+ cells. CONCLUSION: PDGFRß+ PDGFRα+ cells directly contribute to fibrosis and fatty degeneration after massive rotator cuff tears in the mouse model. In addition, CWHM-12 treatment inhibits fibrogenesis from PDGFRß+ PDGFRα+ cells in vitro. Clinically, perioperative PDGFRß+ PDGFRα+ cell inhibition may limit rotator cuff tissue degeneration and, ultimately, improve surgical outcomes for massive rotator cuff tears.

Partial Nephrectomy is Associated with Higher Risk of Relapse Compared with Radical Nephrectomy for Clinical Stage T1 Renal Cell Carcinoma Pathologically Up Staged to T3a.

PURPOSE: We studied recurrence-free survival after partial vs radical nephrectomy for clinical stage T1 renal cell carcinoma in all patients and in those up staged to pathological stage T3a. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,250 patients who underwent partial or radical nephrectomy for clinically localized T1 renal cell carcinoma between 2006 and 2014. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of nephrectomy type with the log rank test and Cox models, adjusting for clinical, radiological and pathological characteristics. RESULTS: A total of 86 recurrences (7%) were observed during a median followup of 37 months. No difference in recurrence-free survival between partial and radical nephrectomy was found among all clinical stage T1 renal cell carcinomas. T3a up staging was noted in 140 patients (11%) and recurrent disease was observed in 44 (31.4%) during a median followup of 38 months. Among up staged T3a cases partial nephrectomy was associated with shorter recurrence-free survival compared to radical nephrectomy on univariable analysis (recurrence HR 2.04, 95% CI 1.12-3.68, p = 0.019) and multivariable analysis (recurrence HR 5.39, 95% CI 1.94-14.9, p = 0.001). CONCLUSIONS: In a subgroup of patients clinically staged T1 renal cell carcinoma will be pathologically up staged to T3a. Among these patients those who undergo partial nephrectomy appear to have inferior recurrence-free survival relative to those who undergo radical nephrectomy.

Active surveillance for incidental renal mass in the octogenarian.

OBJECTIVE: To evaluate the oncologic outcomes among a large cohort of octogenarian patients placed on active surveillance for a localized renal mass. METHODS: We retrospectively reviewed patients ≥80 years of age presenting for asymptomatic, incidentally detected clinically localized stage T1 renal mass between 2006 and 2013 who were followed by active surveillance (AS). The primary endpoint was development of metastatic renal cell carcinoma. Secondary outcomes included intervention-free survival, cancer-specific survival, and overall survival. RESULTS: Eighty-nine octogenarians (median age = 83.4 years) were placed on AS for a median 29.9 months. Median Charlson Comorbidity Index and Katz Index of Independence in Activities of Daily Living scores were 2 and 5, respectively. For all comers, median initial tumor size was 2.4 cm with median growth rate of 0.20 cm/year. Eight (9.0%) patients failed AS due to delayed intervention and three (1.1%) due to systemic progression after median follow-up of 27.8 and 39.9 months, respectively. Two (2.2%) patients in the delayed intervention cohort developed metastasis after treatment. Tumor growth rate was significantly higher among those undergoing intervention versus no intervention (0.60 vs. 0.15 cm/year, P = 0.05) and among patients with systemic progression versus no metastasis (1.28 vs. 0.18 cm/year, P = 0.001). Five-year intervention-free, metastasis-free, cancer-specific, and overall survivals were 90.6, 95.6, 95.6, and 85.7%, respectively. CONCLUSION: AS represents an effective management strategy in octogenarians given low overall risk of metastasis. Tumor growth kinetics may identify patients at risk of systemic progression in whom treatment should be considered.

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.

Outcomes of Laparoscopic Partial Nephrectomy in Patients Continuing Aspirin Therapy.

PURPOSE: A clinical dilemma surrounds the use of aspirin therapy during laparoscopic partial nephrectomy. Despite reduced cardiac morbidity with perioperative aspirin use, fear of bleeding related complications often prompts discontinuation of therapy before surgery. We evaluate perioperative outcomes among patients continuing aspirin and those in whom treatment is stopped preoperatively. MATERIALS AND METHODS: A total of 430 consecutive cases of laparoscopic partial nephrectomy performed between January 2012 and October 2014 were reviewed. Patients on chronic aspirin therapy were stratified into on aspirin and off aspirin groups based on perioperative status of aspirin use. Primary end points evaluated included estimated intraoperative blood loss and incidence of bleeding related complications, major postoperative complications, and thromboembolic events. Secondary outcomes included operative time, transfusion rate, length of hospital stay, rehospitalization rate and surgical margin status. RESULTS: Among 101 (23.4%) patients on chronic aspirin therapy, antiplatelet treatment was continued in 17 (16.8%). Bleeding developed in 1 patient in the on aspirin group postoperatively and required angioembolization. Conversely 1 myocardial infarction was observed in the off aspirin cohort. There was no significant difference in the incidence of major postoperative complications, intraoperative blood loss, transfusion rate, length of hospital stay and rehospitalization rate. Operative time was increased with continued aspirin use (181 vs 136 minutes, p=0.01). CONCLUSIONS: Laparoscopic partial nephrectomy is safe and effective in patients on chronic antiplatelet therapy who require perioperative aspirin for cardioprotection. Larger, prospective studies are necessary to discern the true cardiovascular benefit derived from continued aspirin therapy as well as better characterize associated bleeding risk.