Consistent predictive ability of prostate-specific antigen density prediction model for clinically significant prostate cancer across age strata.

BACKGROUND: Prebiopsy prostate-specific antigen density (PSAD) is a well-known predictor of clinically significant prostate cancer (csPCa). Since prostate-specific antigen (PSA) and prostate volume (PV) increase normally with aging, PSAD thresholds may vary. The purpose of the study was to determine if PSAD was predictive of csPCa in different age strata. METHODS: We retrospectively reviewed our institutional database for patients who underwent multiparametric magnetic resonance imaging (MRI) between January 2016 and December 2021. We included patients who had post-MRI prostate biopsies. Based on age, we divided our cohort into four subgroups (groups 1-4): <55, 55-64, 65-74, and ≥75 years old. PSAD accuracy was estimated by the area under the curve (AUC) as a predictive model for differentiating csPCa between the groups. CsPCa was defined as a Gleason Grade Group 2 or higher. Three different PSAD thresholds (0.1, 0.15, and 0.2) were tested across the groups for sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV). Chi-square and analysis of variance tests were used for bivariate analysis. All analys were completed using R 4.3 (R Core Team, 2023). RESULTS: Among 1913 patients, 883 (46.1%) had prostate biopsies. In groups 1, 2, 3, and 4, there were 62 (7%), 321 (36.4%), 404 (45.8%), and 96 (10.9%) patients, respectively. Median PSA was 5.6 (interquartile range 3.4-8.1), 6.2 (4.8-9), 6.8 (5.1-9.7), and 9 (5.6-13), respectively (p < 0.01). Median PV was 42.3 (30-62), 51 (36-77), 55.5 (38-85.9), and 59.3 (42-110) mL, respectively (p < 0.01). No difference was observed in median PSAD between age groups 1-4 (0.1 [0.07-0.16], 0.11 [0.08-0.18], 0.1 [0.07-0.19], and 0.1 [0.07-0.2]), respectively (p = 0.393). CsPCa was diagnosed in 241 (27.3%) patients, of which 10 (16.1%), 65 (20.2%), 121 (30%), and 45 (46.7%) were in groups 1-4, respectively (p < 0.001). For groups 1-4, the PSAD AUC for predicting csPCa was 0.75, 0.68, 0.71, and 0.74. While testing PSAD threshold of 0.15 across the different age groups (1-4), the PPV vs. NPV was 39.1 vs. 93.2, 33.6 vs. 87, 50.9 vs. 80.8, and 66.1 vs. 64.7, respectively. CONCLUSIONS: PSAD prediction model was found to be similar among different age groups. In young patients, PSAD had a high NPV but low PPV. With increasing age, the opposite trend was observed, likely due to higher disease prevalence. While PSAD thresholds may be less useful in older patients to rule out higher-grade prostate cancer, the clinical consequences of these diagnoses require a case-by-case evaluation.

Comparing the lifespan of virgin artificial urinary sphincters in radiated patients: transcorporal vs. standard placement.

PURPOSE: To compare the lifespan of first transcorporal cuff (TC) placement of an artificial urinary sphincter (AUS) versus standard placement (SP) in patients with prior radiotherapy (RT) for prostate cancer (PCa). METHODS: We reviewed first (virgin) AUS placements from two high-volume care centers between 1/2011 and 1/2021, including PCa patients with RT history. AUS lifespan was assessed via the hazard ratio of device explantation and/or revision within a ten-year timeframe for the TC vs. SP approaches. Chi-square, Fisher's exact, and t-tests compared clinicodemographic variables. Kaplan-Meier curve compared TC and SP lifespan. RESULTS: 85/314 men with AUS met inclusion criteria, with 38.8% (33/85) in the TC group and 61.2% (52/85) in the SP group. Median ages were 69.8 (IQR = 65.2-73.6) and 67.1 (61.6-72.9), respectively, p = 0.17. Over a median follow up of 51.9 (15.8-86.1) and 80.4 (28.1-128.3) months for the TC and SP, overall, 12 (36.4%) TC devices were removed (four [12.1%] due to mechanical failures; eight [24.2%] erosions, and two [6.1%] infections) vs. 29 (55.8%) in the SP group (14 [26.9%] mechanical failures; 11 [21.1%] erosions, and five [9.6%] infections). No statistically significant differences were observed between the two approaches, with HR = 0.717, 95% CI 0.37-1.44, p = 0.35. The calculated device survival probabilities for the TC vs. SP at one, five, and 10 years were 78.8% vs. 76.9%, 69.3% vs. 58.7%, and 62.1% vs. 46.7%, respectively. CONCLUSIONS: TC cuff insertion for the first AUS implantation in pre-radiated patients showed to be comparable to SP when it comes to device survival, with comparable complication rates. Current guidance for approach selection is primarily based on patient selection and surgeon preference.

Frequent Telomerase Reverse Transcriptase Promoter and Fibroblast Growth Factor Receptor 3 Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder.

The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.

Epidemiology of and Risk Factors in Postoperative Complications from Robotically Assisted Laparoscopic Radical Prostatectomy in Contemporary National Surgical Quality Improvement Program Data.

Introduction: For localized clinically significant prostate cancer (csPCa), robotically assisted laparoscopic radical prostatectomy (RALP) is the gold standard surgical treatment. Despite low overall complication rate, continued quality assurance (QA) efforts to minimize complications of RALP are important, particularly given movement toward same-day discharge. In 2019, National Surgical Quality Improvement Program (NSQIP) began collecting RALP-specific data. In this study, we assessed pre- and perioperative factors associated with postoperative complications for RALP to further QA efforts. Materials and Methods: Surgical records of csPCa patients who underwent RALP were retrieved from the 2019 to 2021 NSQIP database, including new RALP-specific data. Multivariate logistic regression evaluated the association between risk factors and outcomes specific to RALP and pelvic lymph node dissection (PLND). Input variables included American Society of Anesthesiologists (ASA) class, age, operative time, and body mass index (BMI). Variables from the extended dataset with PLND information included number of nodes evaluated, perioperative antibiotics, postoperative venous thromboembolism (VTE) prophylaxis, history of prior pelvic surgery, and history of prior radiotherapy (RT). Outcomes of interest were any surgical complication, infection, pulmonary embolism, deep venous thrombosis, acute kidney injury, pneumonia, lymphocele, and urinary/anastomotic leak (UAL). Results: A total of 11,811 patients were included with 6.1% experiencing any complication. Prior RT, prior pelvic surgery, older age, higher BMI, lack of perioperative antibiotic therapy, longer operative time, PLND, and number of lymph nodes dissected were associated with higher risk of postoperative complications. Regarding procedure-specific complications, there were increased odds of UAL with prior RT, prior pelvic surgery, longer operative time, and higher BMI. Odds of developing lymphocele increased with prior pelvic surgery, performance of PLND, and increased number of nodes evaluated. Conclusion: In contemporary NSQIP data, RALP is associated with low complication rates; however, these rates have increased compared with historical studies. Attention to and counseling regarding risk factors for peri- and postoperative complications are important to set expectations and minimize risk of unplanned return to a health care setting after discharge.

Transurethral Resection of the Prostate in Younger Men: Effectiveness and Long-term Outcomes.

OBJECTIVES: This study aims to investigate the efficacy and outcomes of transurethral resection of the prostate (TURP) in the context of younger male patients. METHODS: Males aged ≤55 who underwent TURP at Rambam Health Care Campus from January 2011 to August 2023 were retrospectively reviewed. Clinicodemographic characteristics, indications for surgery, uroflowmetry, pressure-flow study, and early and late postoperative outcomes were collected. Patients with urethral or bladder abnormalities were excluded. Chi-square and Fisher's exact tests were employed for bivariate analysis. RESULTS: Inclusion criteria were met by 58 men who underwent TURP at a median age of 52 years (interquartile range [IQR] 49.5-54). Median prostate size was 35 mL (24.5-56), with median prostate-specific antigen of 1.4 ng/mL (0.65-3.1). A total of 60% of patients used α-blockers, and 19% used 5α-reductase inhibitors pre-surgery. Overall, 54 (93.1%) had severe lower urinary tract symptoms (LUTS), with 34 (59%) being predominantly emptying and 20 (35%) storage. Most surgeries were performed for refractory LUTS in 38 (66%), followed by urinary retention in 16 (28%). At 6 weeks, 57 (98%) patients were catheter-free. The maximum flow rate and residual volume showed significant improvement from a median of 6.85 mL/s to 17.9 mL/s (P<0.001), and from 120 mL to 10 mL (P=0.0142), respectively. Pathology revealed benign prostatic hyperplasia in 53 (91.4%), and inflammation in 5 (8.5%). A total of 13 auxiliary procedures were required in 12 patients (20.7%) during follow-up: 7 transurethral bladder neck incisions, 3 re-TURP, 1 meatus widening, and 1 patient required artificial urinary sphincter implantation followed by simple cystectomy for end-stage bladder. CONCLUSIONS: In young men, TURP showed short-term gains in flowmetry and catheter removal rates, but a sustained need for subsequent procedures in the long run. In this unique population, patients should be carefully selected, and alternative, less aggressive, interventions should be considered.

Investigation of Disparity of Urologic Fellowship Match Rates by Gender and US Versus International Medical Graduates Over the Past Decade.

OBJECTIVE: To investigate the influence of postgraduate medical education (US vs. international) and gender on applicant matching for postgraduate training across different urologic sub-specialties. METHODS: Match statistics of five societies that participated in the AUA fellowship match between 2010-2024 were retrospectively reviewed. Societies included: Endourology Society (EUS), Society for Urological oncology (SUO), American Society of Andrology (AMA), Society of Genitourinary Reconstructive Surgeons (GURS), and Society of Pediatric Urology (SPU). Candidates were classified based on gender (male/female) and their postgraduate medical education: local graduates from the United States or Canada (US/Ca) and international medical graduates (IMG). The match odds were analyzed using the Chi-square test, while trends were assessed through the Mann-Kendall test. RESULTS: Overall, 2429 applicants applied for 1627 programs from 2010 to 2024, comprising 1998 males (81.8%), 399 females (16.4%), and 42 undisclosed (1.7%). There were 1486 US/Ca graduates (60.8%) and 953 IMGs (39.2%). 1471 (60.6%) applicants were matched with a program, compared to 958 (39.4%) unmatched. The likelihood of US/Ca graduates matching (83.8%) was significantly higher than IMGs (23.3%), OR = 17.5, 95% CI: (14.3, 21.5), p < 0.001. IMGs had the highest match rate with GURS (33.8%, 47/118) and the lowest with SPU (7%, 1/14). Female applicants had a significantly higher chance of matching 324/399 (81.2%) than male applicants 1139/1998 (57%), OR = 3.26, 95% CI: (2.5, 4.3), p < 0.001. US/Ca-to-IMGs ratios and the male-to-female ratios were stable throughout the match years. CONCLUSIONS: Compared to IMGs, U.S./Ca graduates had remarkably higher matching rates. Matching outcomes were also significantly better for female applicants. Further assessment of international involvement and diversity in urological subspecialty roles is warranted.

"Shared decision-making" for prostate cancer screening: Is it a marker of quality preventative healthcare?

BACKGROUND: "Shared decision-making" (SDM) is a cornerstone of prostate cancer (PCa) screening guidelines due to tradeoffs between clinical benefits and concerns for over-diagnosis and over-treatment. SDM requires effort by primary-care-providers (PCP) in an often busy clinical setting to understand patient preferences with the backdrop of patient risk factors. We hypothesized that SDM for PCa screening, given its prominence in guidelines and practical challenges, may be associated with quality preventative healthcare in terms of other appropriate cancer screening and encouragement of other preventative health behaviors. METHODS: From the 2020 Behavioral Risk Factor Surveillance Survey, 50-75 year old men who underwent PSA screening were assessed for their participation in SDM, PCa and colorectal cancer (CRC) screening, and other preventative health behaviors, like vaccination, exercise, and smoking status. Adjusted odds ratio of likelihood of PSA testing as a function of SDM was calculated. Likelihoods of SDM and PSA testing as a function of preventative health behaviors were also calculated. RESULTS: Screening rates were 62 % for PCa and 88 % for CRC. Rates of SDM were 39.1 % in those with PSA screening, and 16.2 % in those without. Odds of PSA screening were higher when SDM was present (AOR = 2.68). History of colonoscopy was associated with higher odds of SDM (AOR = 1.16) and PSA testing (AOR = 1.94). Health behaviors, like regular exercise, were associated with increased odds of SDM (AOR = 1.14) and PSA testing (AOR = 1.28). History of flu vaccination (AOR = 1.29) and pneumonia vaccination (AOR = 1.19) were associated with higher odds of SDM. Those who received the flu vaccine were also more likely to have PSA testing (AOR = 1.36). Smoking was negatively associated with SDM (AOR = 0.86) and PSA testing (AOR = 0.93). Older age was associated with higher rates of PSA screening (AOR = 1.03, CI = 1.03-1.03). Black men were more likely than white men to have SDM (AOR = 1.6, CI = 1.59 - 1.6) and decreased odds of PSA testing (AOR = 0.94, CI = 0.94 - 0.95). CONCLUSIONS: SDM was associated with higher odds of PSA screening, CRC screening, and other appropriate preventative health behaviors. Racial disparities exist in both SDM and PSA screening usage. SDM may be a trackable metric that can lead to wider preference-sensitive care and improved preventative care.

Optimising postoperative care: Same-day discharge after transurethral resection of the prostate.

INTRODUCTION: This study aims to assess the feasibility and safety of same-day discharge after transurethral resection of the prostate. MATERIALS AND METHODS: Five years of records were retrospectively analysed. Length of stay categorised patients into Groups 1 (same-day discharge) and 2 (standard-length discharge). Logistic regression analysis was performed, controlling for clinicodemographic factors. Student's t-test compared continuous bladder irrigation and catheter dwell times. RESULTS: A total of 459 patients were identified between 2016 and 2021, 280 in Group 1 and 179 in Group 2, with median ages of 71.0 (interquartile range 36-92) and 72.0 (interquartile range 47-101) years (p = 0.067), respectively. Same-day discharge rates notably increased post-2018 (p = 0.025). Median prostate tissue resected in Group 2 was 7.1g (3.4-12.4g) and in Group 1 was 4.9g (2.4-10.2g; p = 0.034). While continuous bladder irrigation >1 hour was significantly lower in Group 1 than Group 2 (96.8% versus 27.4%; p = 0.0001), catheter dwell times were comparable (70.1 and 70.8 hours, respectively). Control-adjusted results showed a 40% reduction in emergency department representation odds for Group 1 compared with Group 2 (odds ratio = 0.60; 95% confidence interval = 0.37-0.99; p = 0.04). Length of stay was not significantly associated with hospital readmissions (p = 0.11). Continuous bladder irrigation for <1 hour in Group 1 was associated with a reduced emergency department representation (odds ratio = 0.43; 95% confidence interval = 0.197-0.980) but not readmission (odds ratio = 0.413; 95% confidence interval = 0.166-1.104). CONCLUSIONS: Same-day discharge post-transurethral resection of the prostate may be a viable and safe option for carefully selected patients.

Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.

Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.

Highlighting Gender Differences in RLS: Analysis of Gender in Robotic and Laparoscopic Surgical Volume in Urology Vs Other Subspecialties.

OBJECTIVE: To evaluate the involvement of women surgeons in RLS over time and across fields. While women are an increasing proportion of the urological workforce, the overall percentage of women urologists remains low. As robotic/laparoscopic surgery (RLS) has become first-line for many surgical problems, we hypothesized that women in urology may have lower participation than other specialties. MATERIALS AND METHODS: We obtained country-wide data by surgeon from the Data.CMS.gov database for 2014-2019 for major RLS procedures in colorectal surgery, gynecology, thoracic surgery, and urology. Data were sorted by gender and CPT code. Temporal trends were assessed, and estimation was performed by exponential regression comparing means and rates of change between departments and surgeon genders. RESULTS: Surgeons across disciplines and genders showed increases in RLS volume over time (P <.05). There were significant differences between men and women surgeons between specialties in average number of surgeons (P <.0001) and rate of change over time (P = .0035). The difference of the rate of increase in the number of surgeons performing RLS between genders was significant for all disciplines, suggesting women were entering RLS surgery faster than men across specialties (P <.05). CONCLUSION: There is a disparity in RLS procedure performance in men vs women across surgical disciplines. The greatest discrepancy in participation between genders existed in Urology, despite the field having a higher percentage of women physicians than other some subspecialties. Targeted action to address barriers to women surgeons' participation in RLS will increase diversity of thought and improve clinical care.

Preoperative planning using virtual reality and computed tomography angiogram in deep inferior epigastric perforator flap breast reconstruction.

The gold standard for preoperative planning of deep inferior epigastric perforator (DIEP) flap breast reconstruction uses computed tomography angiography (CTA). Virtual reality (VR) circumnavigates the limitations of CTA by reconstructing a fully immersive and interactive 3D representation of the scan. Scans of 44 patients who underwent DIEP flap breast reconstruction were retrospectively reviewed and compared using CTA and VR imaging modalities. The objective of this research was to compare perforators found using VR to the ones identified using conventional CTA. A correlation was found between the imaging modalities for unilateral (R = 0.96 (CI = 0.92, 0.98)) and bilateral (R = 0.93, (CI = 0.83, 0.97)) DIEP flap surgeries when comparing perforator location related to the umbilicus. Multivariable ordinal logistic regression found that higher intramuscular course length (IMC) is associated with the number of perforators found per side (OR = 1.79 (CI = 1.24, 2.6)), and medial location (OR = 2.85 (CI = 1.38, 5.87)). Larger vessel caliber (VC) is associated with shorter IMC (T2 vs. T3, OR = 3.34 (CI = 1.49, 7.49)), and branching in adipose tissue (AB) is associated with higher VC (T1 vs. T3, OR = 0.02 (CI = 0.007, 0.08); T2 vs. T3, OR = 0.24 (CI = 0.11, 0.55)). Overall, preoperative planning using VR was easy to use, safe, more intuitive, and provided in a time-efficient manner, more information about perforant characteristics. VR can improve the surgeon's decision accuracy, relating to the best perforators for harvesting, in a shorter time period.

Evolution of the HIF targeted therapy in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, affecting hundreds of thousands of people worldwide and can affect people of any age. The pathogenesis of ccRCC is most commonly due to biallelic loss of the tumor suppressor gene VHL. VHL is the recognition subunit of an E3-ubiquitin-ligase-complex essential for degradation of the hypoxia-inducible factors (HIF) 1α and 2α. Dysfunctional degradation of HIF results in overaccumulation, which is particularly concerning with the HIF2α subunit. This leads to nuclear translocation, dimerization, and transactivation of numerous HIF-regulated genes responsible for cell survival and proliferation in ccRCC. FDA-approved therapies for RCC have primarily focused on targeting downstream effectors of HIF, then incorporated immunotherapeutics, and now, novel approaches are moving back to HIF with a focus on interfering with upstream targets. This review summarizes the role of HIF in the pathogenesis of ccRCC, novel HIF2α-focused therapeutic approaches, and opportunities for ccRCC treatment.

Appendicocecal Loop Urinary Diversion in a Transplant Kidney: Case Report, Literature Review.

Urinary diversion in renal transplant patients can take a variety of forms - bladder augmentation, continent cutaneous pouch, or intestinal conduits, to name a few. Herein, we present a unique case of an appendicocecal urinary diversion in a patient with history of end stage renal disease, pelvic radiation, and complex surgical history who underwent deceased-donor renal transplantation. During the renal transplant, the transplant ureterovesical anastomosis could not be performed due to inherent anatomical hindrances. A temporary modified cutaneous ureterostomy using a single-J stent was therefore used for drainage of the transplant kidney. Given that the cutaneous ureterostomy was not a durable, long-term option, we sought to develop a creative surgical solution. This report presents a unique case of urinary diversion post renal transplant and reviews the literature of renal transplantation in patients with anatomical abnormalities.

Targeting Bladder Urothelial Carcinoma with pHLIP-ICG and Inhibition of Urothelial Cancer Cell Proliferation by pHLIP-amanitin.

Acidity is a useful biomarker for the targeting of metabolically active-cells in tumors. pH Low Insertion Peptides (pHLIPs) sense the pH at the surfaces of tumor cells and can facilitate intracellular delivery of cell-permeable and cell-impermeable cargo molecules. In this study we have shown the targeting of malignant lesions in human bladders by fluorescent pHLIP agents, intracellular delivery of amanitin toxin by pHLIP for the inhibition of urothelial cancer cell proliferation, and enhanced potency of pHLIP-amanitin for cancer cells with 17p loss, a mutation frequently present in urothelial cancers. Twenty-eight ex-vivo bladder specimens, from patients undergoing robotic assisted laparoscopic radical cystectomy for bladder cancer, were treated via intravesical incubation for 15-60 minutes with pHLIP conjugated to indocyanine green (ICG) or IR-800 near infrared fluorescent (NIRF) dyes at concentrations of 4-8 µM. White light cystoscopy identified 47/58 (81%) and NIRF pHLIP cystoscopy identified 57/58 (98.3%) of malignant lesions of different subtypes and stages selected for histopathological processing. pHLIP NIRF imaging improved diagnosis by 17.3% (p < 0.05). All carcinoma-in-situ cases missed by white light cystoscopy were targeted by pHLIP agents and were diagnosed by NIRF imaging. We also investigated the interactions of pHLIP-amanitin with urothelial cancer cells of different grades. pHLIP-amanitin produced concentration- and pH-dependent inhibition of the proliferation of urothelial cancer cells treated for 2 hrs at concentrations up to 4 µM. A 3-4x enhanced cytotoxicity of pHLIP-amanitin was observed for cells with a 17p loss after 2 hrs of treatment at pH6. Potentially, pHLIP technology may improve the management of urothelial cancers, including imaging of malignant lesions using pHLIP-ICG for diagnosis and surgery, and the use of pHLIP-amanitin for treatment of superficial bladder cancers via intravesical instillation.

Direct Oral Anticoagulants for Venous Thromboembolism Prophylaxis Following Robot-assisted Radical Cystectomy: A Retrospective Feasibility Study at a Single Academic Medical Center.

OBJECTIVES: To evaluate the use of direct oral anticoagulants following radical cystectomy for venous thromboembolism prophylaxis. We compared the experience of those who received venous thromboembolism prophylaxis following a robot-assisted radical cystectomy with either a direct oral anticoagulant or enoxaparin. METHODS: Medical records of 66 patients who underwent robot-assisted radical cystectomy between July 2017 and May 2020 at a single academic institution were reviewed retrospectively. Patients received extended prophylaxis with either a direct oral anticoagulant or enoxaparin before or following surgical discharge. Venous thromboembolic events and complications resulting in emergency department visits and readmissions were reviewed over a 90-day postoperative period. RESULTS: A total of 4 venous thromboembolic events within 90 days of surgery were observed. Among patients taking enoxaparin, 5% (2/37) developed a deep vein thrombosis and 3% (1/37) developed a pulmonary embolism. Among patients taking direct oral anticoagulants, 3% (1/29) developed a deep vein thrombosis. Zero patients in the enoxaparin group and 3% (1/29) of patients in the direct oral anticoagulant group experienced bleeding that required an emergency department visit. CONCLUSION: Direct oral anticoagulants performed comparably to enoxaparin in this feasibility study following robot-assisted radical cystectomy in 66 patients. No significant differences in the number of venous thromboembolisms or bleeding complications were observed. These data encourage future studies and support the prospect of direct oral anticoagulants as a potentially suitable oral alternative to injectable low molecular weight heparins for venous thromboembolism prophylaxis following radical cystectomy.

p53 Expression, Programmed Death Ligand 1, and Risk Factors in Urinary Tract Small Cell Carcinoma.

Introduction: Small cell carcinoma of the urinary tract (SCCUT) is a rare finding with poor clinical course. This study sheds light on the molecular subtype and identifies risk factors in patients diagnosed with SCCUT. Methods: Immunohistochemical expression of immunotherapy target programmed death ligand 1 (PD-L1) and luminal (GATA3), basal (p63), and p53 markers are assessed in patients diagnosed with SCCUT. Univariate analysis identified risk factors. Overall survival (OS) is computed using the Kaplan-Meier method. Results: Tissue was available for 70.2% (33/47). All showed a high PD-L1 expression phenotype. p53 is seen in 93.9% (31/33), mostly as overexpression, GATA3 in 45.5% (15/33), and p63 in 57.6% (19/33). For the entire cohort (n = 47), 1-year survival was 59.6%, and the median OS was 17 months. Univariate analysis shows that chemotherapy [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.14-0.61, p = 0.001], radical surgery (HR = 0.37, 95% CI = 0.18-0.76, p = 0.007), and diagnosis of non-pure SCCUT (HR = 0.44, 95% CI = 0.22-0.86, p = 0.02) are favorable prognostic features. Metastasis had negative associations with survival (HR = 2.1, 95% CI = 1.1-4.2, p = 0.03). Conclusions: In this series, pure and mixed SCCUT are characterized by p53 overexpression and a high PD-L1 phenotype. Histology of non-pure SCCUT is a positive prognosticator, and radical cystectomy or chemotherapy can improve OS. These findings demonstrate that SCCUT may be eligible for PD-L1 immunotherapy.

Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe.

OBJECTIVE: To improve visualization of upper tract urothelial carcinomas. Previous studies using the novel pH low insertion peptide (pHLIP) variant 3 (Var3) conjugated to indocyanine green (ICG) have demonstrated high sensitivity and specificity for imaging of bladder urothelial carcinoma. Here, we describe a novel approach for the imaging of upper tract urothelial carcinomas using ICG-Var3 pHLIP. METHODS: Twelve ex-vivo upper urinary tract specimens were irrigated with ICG-Var 3 pHLIP for 15 minutes and then examined using a white light laparoscopic camera followed by near infrared fluorescent (NIRF) imaging using a Stryker 1588 AIM imaging system. Standard histopathologic evaluation was performed and findings were correlated with white light and ICG-Var3 NIRF imaging. One patient who underwent radical nephrectomy for renal cell carcinoma was used as a negative control. RESULTS: Nineteen lesions were identified on histopathologic evaluation in 10 patients, including 82% high-grade urothelial carcinoma and 18% low-grade urothelial carcinoma. Nineteen (100%) malignant lesions were identified using NIRF imaging, while 15 (78.9%) lesions were identified using conventional white light examination. The sensitivity of ICG-Var3 pHLIP NIRF imaging was 100% compared to 78.9% white light examination. Both modalities are 100% specific. Benign collecting systems and ureters did not show uptake of the pHLIP construct. CONCLUSION: In this feasibility study, the ICG-Var3 pHLIP imaging agent demonstrated superior diagnostic performance compared to conventional white light examination. While additional studies are required for validation and in-vivo translation, pHLIP-based imaging represents a promising tool to improve the evaluation and management of upper tract urothelial carcinoma.