Asymmetric Hsp90 N domain SUMOylation recruits Aha1 and ATP-competitive inhibitors.

The stability and activity of numerous signaling proteins in both normal and cancer cells depends on the dimeric molecular chaperone heat shock protein 90 (Hsp90). Hsp90's function is coupled to ATP binding and hydrolysis and requires a series of conformational changes that are regulated by cochaperones and numerous posttranslational modifications (PTMs). SUMOylation is one of the least-understood Hsp90 PTMs. Here, we show that asymmetric SUMOylation of a conserved lysine residue in the N domain of both yeast (K178) and human (K191) Hsp90 facilitates both recruitment of the adenosine triphosphatase (ATPase)-activating cochaperone Aha1 and, unexpectedly, the binding of Hsp90 inhibitors, suggesting that these drugs associate preferentially with Hsp90 proteins that are actively engaged in the chaperone cycle. Importantly, cellular transformation is accompanied by elevated steady-state N domain SUMOylation, and increased Hsp90 SUMOylation sensitizes yeast and mammalian cells to Hsp90 inhibitors, providing a mechanism to explain the sensitivity of cancer cells to these drugs.

Mohs micrographic surgery for male genital tumors: Local recurrence rates and patient-reported outcomes.

BACKGROUND: Local recurrence rates (LRRs) after Mohs micrographic surgery (MMS) for male genital cancers have been reported in only a few small case series, and patient-reported outcomes (PROs) have not been studied. OBJECTIVE: To determine the LRR and PROs after MMS for male genital skin cancers. METHODS: Retrospective review of all male genital skin cancers removed with MMS between 2008 and 2019 at an academic center. LRR was determined by chart review and phone calls. PROs were assessed by survey. RESULTS: A total of 119 skin cancers in 108 patients were removed with MMS. Tumors were located on the penis (90/119) and scrotum (29/119). Diagnoses included squamous cell carcinoma in situ (n = 71), invasive squamous cell carcinoma (n = 32), extramammary Paget disease (n = 13), melanoma (n = 2), and basal cell carcinoma (n = 1). The LRR was 0.84% (1/119), with a mean follow-up time of 3.25 years (median, 2.36 years). The majority of survey respondents reported no changes in urinary (66%) or sexual functioning (57.5%) after surgery. LIMITATIONS: Retrospective single-center experience; short follow-up time; low survey response rate; no baseline functional data. CONCLUSION: MMS for male genital skin cancer has a low LRR and high patient-reported satisfaction with urinary and sexual function.

Associations between Hospital Volume and Outcomes of Robot-Assisted Radical Prostatectomy.

PURPOSE: Robot-assisted radical prostatectomy has become the predominant surgical modality to manage localized prostate cancer in the U.S. However, there are few studies focusing on the associations between hospital volume and outcomes of robot-assisted radical prostatectomy. MATERIALS AND METHODS: We identified robot-assisted radical prostatectomies for clinically localized (cT1-2N0M0) prostate cancer diagnosed between 2010 and 2014 in the National Cancer Database. We categorized annual average hospital robot-assisted radical prostatectomy volume into very low, low, medium, high and very high by most closely sorting the final included patients into 5 equal-sized groups (quintiles). Outcomes included 30-day mortality, 90-day mortality, conversion (to open), prolonged length of stay (more than 2 days), 30-day (unplanned) readmission, positive surgical margin and lymph node dissection rates. RESULTS: A total of 114,957 patients were included in the study, and hospital volume was categorized into very low (3 to 45 cases per year), low (46 to 72), medium (73 to 113), high (114 to 218) and very high (219 or more). Overall 30-day mortality (0.12%), 90-day mortality (0.16%) and conversion rates (0.65%) were low. Multivariable logistic regressions showed that compared with the very low volume group, higher hospital volume was associated with lower odds of conversion to open surgery (OR 0.23, p <0.001 for very high), prolonged length of stay (OR 0.25, p <0.001 for very high), 30-day readmission (OR 0.53, p <0.001 for very high) and positive surgical margins (OR 0.61, p <0.001 for very high). Higher hospital volume was also associated with higher odds of lymph node dissection in the intermediate/high risk cohort (OR 3.23, p <0.001 for very high). CONCLUSIONS: Patients undergoing robot-assisted radical prostatectomy at higher volume hospitals are likely to have improved perioperative and superior oncologic outcomes compared to lower volume hospitals.

Hospital-specific antibiograms and antibiotic prophylaxis for prostate biopsies: a reexamination of AUA recommendations.

INTRODUCTION: To assess whether standard American Urological Association (AUA) and other recommendations for prostate biopsy prophylaxis provide sufficient coverage of common urinary organisms responsible for post biopsy infections by comparing local antibiograms in Philadelphia-area hospitals. MATERIALS AND METHODS: De-identified culture results derived from antibiograms were collected from six academic and community hospitals in the Philadelphia region. Analysis specifically focused on four major bacterial causes of urinary tract infection following prostate biopsy (Escherichia coli (E. coli), Klebsiella pneumoniae, Proteus mirabilis and Enterococcus faecalis) along with commonly recommended antibiotics including fluoroquinolones (FQ's), trimethoprim/sulfamethoxazole, ceftriaxone, and gentamicin. RESULTS: Bacterial sensitivities to each antibiotic across institutions showed variation in E.coli sensitivities to FQs (p < 0.001), trimethoprim/sulfamethoxazole (p < 0.001), ceftriaxone (p < 0.001) and gentamicin (p < 0.001). Klebsiella pneumoniae and Proteus mirabilis exhibited similar variations. Sensitivity comparisons for Enterococcus faecalis was unable to be performed due to absent or incomplete data across institutions. CONCLUSION: Institutional antibiograms vary within our regional hospitals. Standardized recommendations for commonly used antibiotic prophylaxis such as fluoroquinolones may be inadequate for peri-procedural prostate biopsy prophylaxis based on local resistance patterns. Valuable information about the potential effectiveness of antibiotic prophylaxis for prostate biopsies can be found in local institutional antibiograms, and should be consulted when considering antibiotic prophylaxis for prostate biopsy procedures.

Next-day discharge after minimally invasive partial nephrectomy: an analysis of the US National Surgical Quality Improvement Program.

PURPOSE: Clinical care pathways and new technologies have decreased the length of stay after many surgeries. However, doubt exists about the safety of shorter hospital stays. We sought to evaluate the feasibility of next-day discharge after minimally invasive partial nephrectomy in a national cohort of US patients and surgeons. METHODS: Using the National Surgical Quality Improvement Program database, we analyzed patients who underwent minimally invasive partial nephrectomy from 2012 to 2016. Patients were grouped into discharge on post-operative day 1, or discharge on days 2 and 3. Propensity score matching was used to balance patient characteristics and univariable analysis was used to determine the effect of next-day discharge on readmission, post-discharge complications, and major post-discharge complications. RESULTS: A total of 8153 patients were included in the analysis and 4430 were matched. The matched cohort was balanced on all patient and peri-operative characteristics. On univariable analysis, no increase in odds were observed in the next-day discharge group for readmission (odds ratio 0.8; 95% confidence interval 0.6-1.4; p = 0.2), post-discharge complications (odds ratio 1.0; 95% confidence interval 0.7-1.4; p = 0.9), or post-discharge major complications (odds ratio 0.9; 95% confidence interval 0.5-1.4; p = 0.6). CONCLUSIONS: Next-day discharge in select patients after minimally invasive partial nephrectomy is effectively being utilized by a large, nationwide cohort of surgeons. This approach is feasible in certain patient populations though further research must determine selection criteria for safe next-day discharge.

Hospital volume and outcomes of robot-assisted partial nephrectomy.

OBJECTIVE: To evaluate the impact of hospital volume on outcomes of robot-assisted partial nephrectomy (RAPN). MATERIALS AND METHODS: Patients with renal cell carcinoma who underwent RAPN between 2010 and 2013 were identified in the National Cancer Database. Hospital yearly RAPN volume was categorized into groups by sorting patients as closely as possible into five groups of equal size (quintiles): very low; low; medium; high; and very high volume. Outcomes included 30-day mortality, 90-day mortality, open conversion, prolonged length of hospital stay (PLOS; defined as >3 days), 30-day readmission rate, and positive surgical margin (PSM) rate. Unadjusted analyses and multivariable logistic regressions were used to compare outcomes. Sensitivity analyses with hospital volume considered as a continuous variable were also performed. RESULTS: A total of 18 724 RAPN cases were included. Hospital volume quintiles were: very low volume, 1-7 cases (n = 3 693); low volume, 8-14 cases (n = 3 719); medium volume, 15-23 cases (n = 3 833); high volume, 24-43 cases (n = 3 649); and very high volume, ≥44 cases (n = 3 830). There was no significant difference in 30-day or 90-day mortality among the five groups. Multivariable logistic regression analysis (reference: very low volume) showed that higher hospital volume was associated with lower odds of conversion (low [odds ratio {OR}: 0.88; P = 0.377]; medium [OR: 0.60; P = 0.001]; high [OR: 0.57; P < 0.001]; very high [OR: 0.47; P < 0.001]), lower odds of PLOS (low [OR: 0.93; P = 0.197], medium [OR: 0.75; P < 0.001]; high [OR: 0.62; P < 0.001]; very high [OR: 0.45; P < 0.001]), and lower odds of PSMs (low [OR: 0.76; P < 0.001]; medium [OR: 0.76, P < 0.001]; high [OR: 0.59; P < 0.001]; very high [OR: 0.34; P < 0.001]). Sensitivity analyses confirmed increasing hospital volume (per 1-case increase) was associated with lower odds of conversion (OR: 0.986; P < 0.001), PLOS (OR: 0.989; P < 0.001) and PSMs (OR: 0.984; P < 0.001). A difference in 30-day readmission rate was found in unadjusted analysis but not in adjusted analyses. CONCLUSION: Undergoing RAPN at higher-volume hospitals may have better peri-operative outcomes (conversion to open and LOS) and lower PSM rates. Future studies are needed to explore the detailed components that lead to the superior outcomes in higher-volume hospitals.

Hospital volume and short-term outcomes after cytoreductive nephrectomy.

PURPOSE: To investigate the impact of hospital volume on short-term outcomes after cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). METHODS: We identified mRCC patients who underwent CN from 2006 to 2013 in the National Cancer Database. Annual hospital CN volume was categorized as high (top 20th percentile) and low. Multivariable logistic regressions were used to compare 30-day mortality, 90-day mortality, prolonged length of stay (PLOS, ≥7 days), and 30-day readmission rates. Sensitivity analyses were performed with hospital volume considered as a continuous variable. RESULTS: A total of 9789 patients were included with high-volume (n = 1916) defined as ≥8 cases and low-volume (n = 7873) as 1-7 cases annually. Multivariable logistic regression showed that high-volume was associated with lower odds of 30-day mortality (OR = 0.69, P = 0.013), 90-day mortality (OR = 0.65, P < 0.001), PLOS (OR = 0.82, P = 0.002), and 30-day readmission (OR = 0.78, P = 0.028). Sensitivity analyses showed that increasing hospital volume (per case) was associated with lower odds of 30-day mortality (OR = 0.965, P = 0.008), 90-day mortality (OR = 0.966, P < 0.001), PLOS (OR = 0.982, P = 0.001), and 30-day readmission (OR = 0.975, P = 0.012). CONCLUSION: Higher hospital volume was associated with better short-term outcomes after CN. Future studies are needed to validate our findings and explore the potential components leading to better outcomes in the higher volume hospitals.

Lack of Impact of Robotic Assisted Laparoscopic Radical Prostatectomy on Intraoperative Levels of Prostate Cancer Circulating Tumor Cells.

PURPOSE: While the significance of circulating tumor cells in clinically localized cancer remains controversial, it has been reported that surgical tumor manipulation can increase circulating tumor cells, including during open prostatectomy. To our knowledge it is unknown whether this cell shedding also occurs during minimally invasive prostatectomy, which minimizes tumor palpation and uses earlier vascular control. We tested the impact of robotic assisted laparoscopic radical prostatectomy on intraoperative circulating tumor cell levels. MATERIALS AND METHODS: Circulating tumor cell counts were compared in peripheral blood specimens from 25 patients treated with robotic assisted laparoscopic radical prostatectomy preoperatively vs intraoperatively after prostate excision, in addition to 11 healthy blood donors. Circulating tumor cell detection was performed using EpCAM immunomagnetic enrichment and multiparametric flow cytometry quantification of viable EpCAM positive/prostate specific membrane antigen positive/CD45 negative cells. Intraoperative cell counts and increases were tested in univariable analyses for associations with perioperative variables, histopathology and postoperative progression. RESULTS: Circulating tumor cells were detected in 0% of healthy controls compared to 48% and 52% of prostatectomy cases preoperatively and intraoperatively, respectively (range 1 to 8 cells). There was no difference in the incidence or mean number of circulating tumor cells preoperatively vs intraoperatively. Of the patients 60% had no intraoperative change from preoperative levels. Intraoperative cell increases vs decreases were equally infrequent (each 20%) with no intraoperative increase greater than 1 circulating tumor cell. Intraoperative circulating tumor cell detection was not significantly associated with prostatectomy operative characteristics, histopathology or early postoperative progression at a median 21-month followup. CONCLUSIONS: Robotic assisted laparoscopic radical prostatectomy does not cause significant intraoperative increases in circulating tumor cells in contrast to historical reports of open prostatectomy. These findings may aid urologists in counseling candidates for robotic assisted laparoscopic radical prostatectomy regarding the possibility of intraoperative tumor cell shedding.

Prostate Cancer Diagnosis on Repeat Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsy of Benign Lesions: Recommendations for Repeat Sampling.

PURPOSE: Urologists face a dilemma when a lesion identified on multiparametric magnetic resonance imaging is benign on image guided fusion biopsy. We investigated the detection rate of prostate cancer on repeat fusion biopsy in multiparametric magnetic resonance imaging lesions initially found to be pathologically benign on fusion biopsy. MATERIALS AND METHODS: We reviewed the records of all patients from 2007 to 2014 who underwent multiparametric magnetic resonance imaging and image guided fusion biopsy. We identified men who underwent rebiopsy of the same discrete lesion after initial fusion biopsy results were benign. Data were documented on a per lesion basis. We manually reviewed UroNav system (Invivo, Gainesville, Florida) needle tracking to verify accurate image registration. Multivariate analysis was used to identify clinical and imaging factors predictive of prostate cancer detection at repeat fusion biopsy. RESULTS: A total of 131 unique lesions were rebiopsied in 90 patients. Of these 131 resampled lesions 21 (16%) showed prostate cancer, which in 13 (61.9%) was Gleason 3 + 3. On multivariate analysis only lesion growth on repeat multiparametric magnetic resonance imaging was significantly associated with prostate cancer detection at repeat biopsy (HR 3.274, 95% CI 1.205-8.896, p = 0.02). CONCLUSIONS: Pathologically benign multiparametric magnetic resonance imaging lesions on initial image guided fusion biopsy are rarely found to harbor clinically significant prostate cancer on repeat biopsy. When prostate cancer was identified, most disease was low risk. An increase in lesion diameter was an independent predictor of prostate cancer detection. While these data are retrospective, they may provide some confidence in the reliability of negative initial image guided fusion biopsies despite a positive multiparametric magnetic resonance imaging finding.

Reproducibility of Multiparametric Magnetic Resonance Imaging and Fusion Guided Prostate Biopsy: Multi-Institutional External Validation by a Propensity Score Matched Cohort.

PURPOSE: As the adoption of magnetic resonance imaging/ultrasound fusion guided biopsy expands, the reproducibility of outcomes at expert centers becomes essential. We sought to validate the comprehensive NCI (National Cancer Institute) experience with multiparametric magnetic resonance imaging and fusion guided biopsy in an external, independent, matched cohort of patients. MATERIALS AND METHODS: We compared 620 patients enrolled in a prospective trial comparing systematic biopsy to fusion guided biopsy at NCI to 310 who underwent a similar procedure at Long Island Jewish Medical Center. The propensity score, defined as the probability of being treated outside NCI, was calculated using the estimated logistic regression model. Patients from the hospital were matched 1:1 for age, prostate specific antigen, magnetic resonance imaging suspicion score and prior negative biopsies. Clinically significant disease was defined as Gleason 3 + 4 or greater. RESULTS: Before matching we found differences between the cohorts in age, magnetic resonance imaging suspicion score (each p <0.001), the number of patients with prior negative biopsies (p = 0.01), and the overall cancer detection rate and the cancer detection rate by fusion guided biopsy (each p <0.001). No difference was found in the rates of upgrading by fusion guided biopsy (p = 0.28) or upgrading to clinically significant disease (p = 0.95). A statistically significant difference remained in the overall cancer detection rate and the rate by fusion guided biopsy after matching. On subgroup analysis we found a difference in the overall cancer detection rate and the rate by fusion guided biopsy (p <0.001 and 0.003) in patients with prior negative systematic biopsy but no difference in the 2 rates (p = 0.39 and 0.51, respectively) in biopsy naïve patients. CONCLUSIONS: Improved detection of clinically significant cancer by magnetic resonance imaging and fusion guided biopsy is reproducible by an experienced multidisciplinary team consisting of dedicated radiologists and urologists.

Genomic Evolution of Oligometastatic Clear Cell Renal Cell Carcinoma Presenting Two Decades Following Radical Nephrectomy.

Metachronous oligometastatic clear cell renal cell carcinoma may take many years before becoming clinically apparent. Herein we report regional lymph node recurrence of clear cell renal cell carcinoma more than two decades following radical nephrectomy. Chromosomal microarray analysis demonstrated multiple chromosomal alterations, including 3pq deletion shared by the original and recurrent tumors, and 17p deletion containing the TP53 gene present only in the latter. Sequencing of 1550 genes revealed mutations of VHL in both the primary and metastasis and BAP1 only in the metastatic lesion. These findings genetically link the original and recurrent tumors and suggest that VHL, TP53, and BAP1 alterations played an evolutionary role in recurrence decades after initial resection.

Oncologic control and predictors of urologic reconstruction after Mohs micrographic surgery for low-risk penile malignancy.

PURPOSE: Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients' short-term oncologic control and preoperative characteristics predicting reconstruction needs are undefined. This study assesses MMS's oncologic efficacy for low-risk penile cancer and identifies baseline predictors of post-resection reconstruction referral. METHODS: We retrospectively reviewed 73 adult males with 78 penile cutaneous malignancies treated with MMS from 2005 to 2019. Patients underwent MMS with or without surgical reconstruction. Demographic information, MMS operative details, lesion pathology, and short-term outcomes were recorded. Descriptive statistics for all variables were calculated, and logistic regression identified predictive factors for urologic referral for complex reconstruction. RESULTS: Seventy-three men with 78 lesions, all staged ≤ cT1a prior to MMS, were identified. Twenty-one men were found to have invasive SCC. Median follow-up was 2.0 years (IQR 0.8-5.2 years). MMS was able to clear the disease in 90.4% of cases. One patient had disease related death following progression. Dermatology closed primarily in 68% of patients. Twenty percent of patients had a complication, most commonly poor wound healing. On univariate and multivariate linear regression analysis, lesion size > 3 cm and involvement of the glans independently predicted the need for referral to a reconstructive surgeon. CONCLUSIONS: MMS for penile cancer appears to provide sound oncologic control in the properly selected patient. Involvement of a reconstructive surgeon may be needed for glandular and large lesions, necessitating early referral to a comprehensive multidisciplinary care team.

Diminished Short-Term Efficacy of Reduced-Dose Induction BCG in the Treatment of Non-Muscle Invasive Bladder Cancer.

The ongoing Bacillus Calmette-Guérin (BCG) shortage has created challenges for the treatment of non-muscle invasive bladder cancer (NMIBCa). Our objective was to evaluate the efficacy of reduced-dose induction BCG (RD-iBCG) compared to full-dose induction BCG (FD-iBCG) regarding recurrence rates. We hypothesized that patients receiving RD-iBCG may recur at a higher rate compared to those who received FD-iBCG therapy. A retrospective review of all patients with NMIBCa treated with intravesical therapy at our institution between 2015-2020 was conducted. Inclusion criteria consisted of having a diagnosis of AUA intermediate or high-risk NMIBCa with an indication for a six-week induction course of FD or RD-BCG with at least 1 year of documented follow up. The data were censored at one year. Propensity score matching for age, sex, tumor pathology, and initial vs. recurrent disease was performed. The primary endpoint was bladder cancer recurrence, reported as recurrence-free survival. A total of 254 patients were reviewed for this study. Our final cohort was 139 patients after exclusion. Thirty-nine percent of patients had HGT1 disease. 38.6% of patients receiving RD-BCG developed a recurrence of bladder cancer within a one-year follow-up as compared to 33.7% of patients receiving FD therapy. After propensity matching, this value remained statistically significant (p = 0.03). In conclusion, RD-iBCG for NMIBCa is associated with a significantly greater risk of recurrence than full-dose induction therapy, suggesting that RD-iBCG may not be equivalent or non-inferior to full-dose administration in the short term.

Fluorescence-guided radical prostatectomy.

Robotic-assisted laparoscopic radical prostatectomy represents one of the most common operations in urologic oncology and involves several critical technical steps including pelvic lymph node dissection, cavernous nerve sparing and vesicourethral anastomosis. The quality of performing these steps is linked to functional and oncological outcomes. Indocyanine green [ICG] is a non-radioactive, water-soluble compound which allows for enhanced visualization with near-infrared fluorescence of both anatomical structures and vasculature during complex abdominal operations such as prostatectomy. During the last decade, several investigators have examined the value and role of ICG fluorescence during prostatectomy. In this review, we sought to evaluate the body of evidence for fluorescence-guided robotic prostatectomy as well as assess potential future areas of investigation with this technology.

Spontaneous rupture of a bladder diverticulum with delayed open surgical repair.

Spontaneous rupture of a bladder diverticulum is a rare entity typically associated with tissue weakness, bladder outlet obstruction, increased intra-abdominal pressure, or inflammation. Diagnosis is most often achieved via cystogram with a reported role for pelvic ultrasound. Extraperitoneal ruptures are typically treated with catheterization and antibiosis while intraperitoneal ruptures are most frequently treated with immediate surgical intervention. In this case, an adult female presented with an intraperitoneal rupture with no clear inciting event with diagnosis confirmed by pelvic transvaginal ultrasound following a non-diagnostic cystogram. The patient was treated successfully with delayed open surgical repair.

Longitudinal Changes in Quality of Life After Ureteroscopy for Nephrolithiasis.

OBJECTIVE: To assess alterations in health-related quality of life (HRQOL) in patients with nephrolithiasis, given the limited prospective data on patient reported outcomes following surgical intervention with ureteroscopy. METHODS: Adults with either a renal or ureteral calculus who underwent ureteroscopy (URS) were recruited prospectively from 2017-2020. Participants completed the PROMIS-29 profile which measures the dimensions of physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance at enrollment, 1-, 6-, and 12-months. Scores are reported as T-scores (normalized to US-population) and were compared at each time point against the mean for the US-population (50) using one-sample Welch's t'test and between each pairwise time point comparison using a Wilcoxon signed rank test. RESULTS: At enrollment, a total of 69 participants completed the PROMIS-29 survey. As compared to the US-population mean, participants at enrollment had significantly different scores in physical function, fatigue, pain interference, depressive symptoms, anxiety, and sleep disturbance (all P<.05), but not ability to participate in social roles and activities. In pairwise comparisons, improvement was only observed from enrollment to 1-month in pain interference (P<.01) and fatigue (P = .03). However, there was improvement at a longer interval from enrollment to 12-months in all dimensions (pairwise comparisons, all P<.05) except depressive symptoms. CONCLUSION: The PROMIS-29 profile is responsive to changes in HRQOL for patients with nephrolithiasis undergoing URS, with improvement of PROMIS scores up to 12-months. This information can be utilized for patient counseling to guide expectations during the recovery period.

Prognostic significance of sarcomatoid features in metastatic renal cell carcinoma treated with cytoreductive nephrectomy and targeted therapy.

INTRODUCTION: The presence of sarcomatoid features in localized renal cell carcinoma (RCC) is associated with worse outcomes. We sought to use a national database to evaluate the outcomes and prognosis of metastatic RCC (mRCC) with sarcomatoid features treated with cytoreductive nephrectomy (CN) and targeted therapy (TT). METHODS: The National Cancer Database (2010-2013) was used to identify patients with mRCC at diagnosis. Only patients who underwent CN followed by TT were included. Kaplan-Meier curves, log-rank test, and multivariate Cox regression analysis were used to compare overall survival (OS) between mRCC with and without sarcomatoid features. Subgroup analysis in patients with clear cell RCC (ccRCC) was performed. RESULTS: A total of 1,427 patients with mRCC treated with CN followed by TT were included of which 364 (26%) had mRCC with sarcomatoid features. mRCC with sarcomatoid features were more likely to have Fuhrman grade 4 cancer. mRCC with sarcomatoid features had worse OS than mRCC without sarcomatoid features (24.6 vs 12.0 months, P < 0.001). For the clear cell cohort, mRCC with sarcomatoid features had worse OS than mRCC without sarcomatoid features (26.2 vs 14.0 months, P < 0.001). Multivariate Cox regression showed sarcomatoid features was significantly associated with worse OS in the overall cohort (hazard ratio [HR] =1.63, 95% confidence interval [CI] =1.38-1.91, P < 0.001) and the ccRCC subcohort (HR=1.53, 95% CI=1.23-1.90, P < 0.001). DISCUSSION/CONCLUSION: mRCC with sarcomatoid features treated with CN and TT has a very poor and drastically different prognosis compared with mRCC without sarcomatoid features. With the expansion of systemic RCC therapies, investigation is needed to optimize treatment in this high-risk cohort.

Post-cystectomy Enterocele: A Case Series and Review of the Literature.

OBJECTIVE: To present a case series and literature review on post radical cystectomy (RC) pelvic organ prolapse (POP) to heighten awareness of the symptoms, imaging findings, and risk factors associated with this complication and discuss opportunities for prevention. Women with muscle invasive bladder cancer undergo RC with anterior exenteration, significantly disrupting the pelvic floor. These women are at risk for POP. METHODS: We present 4 cases of high-grade POP in women who underwent RC for bladder cancer. We reviewed the literature by conducting a Boolean search in PubMed with the terms "("radical cystectomy") AND ("enterocele" OR "pelvic organ prolapse" OR "rectocele" OR "vaginal vault prolapse")." RESULTS: All 4 women reported a bulge sensation in the vagina and physical exam confirmed POP. Three had radiographic findings consistent with high-grade enterocele at rest. Three experienced prolonged intra-abdominal pressure rise post-RC that may have further weakened pelvic floor support, while the fourth had a history of surgery for high-grade POP. Nine articles on POP following RC were identified. Four focused on treatment and 3 focused on prevention. CONCLUSION: Administration of a single validated question would have identified all 4 cases of postoperative enterocele and is sensitive to detect most women who are experiencing POP. Attention to the pelvic floor on cross-sectional imaging with identification of features that indicate POP, such as herniation of intestinal contents below the pubo-coccygeal line, will identify and/or confirm high-grade enterocele. Familiarity with risk factors for POP and identification of weakened vaginal wall support opens up the opportunity for prevention.

Contemporary National Trends and Variations of Pelvic Lymph Node Dissection in Patients Undergoing Robot-Assisted Radical Prostatectomy.

INTRODUCTION: Previous studies showed suboptimal adherence to clinical practice guidelines for pelvic lymph node dissection (PLND) during radical prostatectomy (RP). Robot-assisted RP (RARP) has become the predominant surgical management for localized prostate cancer in the United States but contemporary national data on PLND adherence during RARP are still lacking. METHODS: RARPs for clinically localized (cT1-2N0M0) intermediate-risk and high-risk prostate cancer diagnosed between 2010 and 2016 in National Cancer Database were identified. Outcome of interest was PLND and multivariable logistic regressions were used to identify whether patient demographics and facility characteristics were associated with the outcome. RESULTS: We included 115,355 patients in the final cohort (intermediate-risk = 86,314, high-risk = 29,041). From 2010 to 2016, there was an increasing trend of PLND in the overall, intermediate-risk, and high-risk cohorts. In 2016, PLND was performed in 79.7% of the intermediate-risk and 93.5% of the high-risk patients. Multivariable logistic regressions showed Hispanic race/ethnicity (vs. white) (odds ratio [OR] = 0.90, P = .010), lowest socioeconomic status (vs. highest) (OR = 0.85, P < .001), rural area (vs. metro area) (OR=0.61, P < .001), and community facility (vs. academic) (OR = 0.56, P < .001) were some of the factors associated with lower PLND rate. Variations of PLND rate among reporting facility's locations were also identified. CONCLUSION: Contemporary national data showed significantly increased PLND rate in patients who underwent RARP for intermediate-risk and high-risk prostate cancer in recent years. However, there were still some variations in PLND rate among different patient populations and facilities. Continued efforts need to be made to further increase PLND rate and narrow or eliminate disparities we identified.

Outcomes of mohs microgrpahic resection for cutaneous malignancy involving the scrotum.

INTRODUCTION: Squamous cell carcinoma (SCC) and extramammary Paget's Disease (EMPD) of the scrotum are exceedingly rare. Given their propensity for local invasion and treatment with wide local excision, they can be highly morbid conditions. Outcomes of Mohs Micrographic Surgery (MMS) for scrotal cutaneous malignancy is not well described in current literature. We hypothesized that MMS for scrotal cutaneous malignancy would provide equivalent or improved oncologic outcomes while limiting the morbidity associated with wide excision. MATERIALS/METHODS: This is a retrospective review and analysis of a prospectively maintained database spanning entries from 2005 to 2019. Collected data included general patient characteristics and surgical characteristics reported on a per lesion basis. MMS was performed by our institution's department of dermatology using their standard technique. RESULTS: Overall, a total of 26 consecutive patients with 28 lesions (SCC or EMPD) were analyzed. Out of our cohort of 15 patients with 16 scrotal SCC lesions, 10 (66%) patients were current or former smokers, 4 (26%) were immunosuppressed, and 2 (13%) had HPV infections. The median preoperative and postoperative size of SCC lesions were 5.7cm [2] and 20.2cm [2] respectively. There was one (6%) oncologic recurrence of SCC of the scrotum and one (6%) local wound complication. Our cohort also included 11 patients with 12 scrotal EMPD lesions. One patient (9%) had an underlying associated malignancy (prostate cancer). The preoperative and postoperative area of lesions were 50.6cm [2] and 96.4cm [2] respectively. One (9%) EMPD lesion had a positive final margin at resection requiring reoperation. After achieving negative surgical margins, no patients in this cohort had an oncologic recurrence. 3 (26%) scrotal EMPD cases had local wound postoperative complications, only one required reoperation. CONCLUSION: To our knowledge, this is the first case series focused on MMS for both SCC and EMPD with scrotal involvement. Our data suggests that MMS for scrotal cutaneous malignancy may improve oncologic outcomes and may decreases local post-operative reconstructive issues when compared to reported outcomes of treatment with wide local excision. When able, scrotal cutaneous malignancy patients should be referred to urologists at centers with MMS capabilities as it likely will improve their outcomes. The urologist should maintain active involvement with these patients to coordinate this complex and advanced pattern of care.