Prostate biopsy sepsis prevention: external validation of an alcohol needle washing protocol.

PURPOSE: Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is associated with a 1-8% risk of post-biopsy sepsis (PBS). A recent study described an isopropyl alcohol needle washing protocol that significantly decreased PBS rates. The current study examined the efficacy of this technique in our clinic population. MATERIALS AND METHODS: Data were reviewed for 1250 consecutive patients undergoing TRUS-Bx at the Charlie Norwood VA Medical Center from January 2017 to January 2023. Needle washing was adopted in February 2021. Complications occurring within 30 days after TRUS-Bx were recorded. RESULTS: There were 912 patients in group 1 (without needle washing) and 338 in group 2 (with needle washing). Groups had equivalent demographic features, and men of African descent comprised 70% of patients. Standard 12 core biopsies were done in 83% and 82% in groups 1 and 2, respectively (p = 0.788). Total complication rates were 4% and 2% in groups 1 and 2, respectively (p = 0.077). There were 13 sepsis events in group 1 (1.4%) and none in group 2 (p = 0.027). Clavien-Dindo Grade I-III complications occurred in 25 (2.7%) and 7 (2.1%) patients in groups 1 and 2, respectively (p = 0.505). Standard antibiotic prophylaxis (PO fluoroquinolone and IM gentamicin) was given in 80% and 86% of patients in groups 1 and 2, respectively (p = 0.030). Subset analysis limited to patients who received standard prophylaxis showed a significant difference in sepsis rates (1.5% vs 0%; p = 0.036). CONCLUSIONS: Adoption of isopropyl alcohol needle washing was associated with a significant decrease in PBS events.

A novel exosome based therapeutic intervention against neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a highly lethal variant of castration-resistant prostate cancer (CRPC) with poor survival rates. Current treatment options for NEPC are limited to highly toxic platinum drugs highlighting the urgent need for new therapies. This study aimed to develop a novel therapeutic approach using engineered exosomes against NEPC. Exosomes were modified to target CEACAM5, an NEPC surface antigen, by attaching CEACAM5 antibodies to HEK293T exosomes. These exosomes were loaded with drugs inhibiting EZH2 and the androgen receptor (AR) as recent research shows a persistent role of AR in NEPC wherein it plays a concerted role with EZH2 in driving neuronal gene programs. In vitro experiments with NEPC cell lines demonstrated that CEACAM5-targeted exosomes were specifically taken up by NEPC cells, leading to reduced cellular viability and decreased expression of neuronal markers. Further in vivo tests using a NEPC patient-derived xenograft model (LuCaP145.1) showed significant tumor regression in mice treated with engineered exosomes compared to control mice receiving IgG-labeled exosomes. These results suggest that CEACAM5-engineered exosomes hold promise as a targeted therapy for NEPC. Importantly, our exosome engineering strategy is versatile and can be adapted to target various surface antigens in prostate cancer and other diseases.

Transgender patient undergoing Rezum therapy: a case report.

Rezum is a relatively new, minimally invasive approach that utilizes vaporized water to ablate prostatic tissue surrounding the proximal urethra in patients with benign prostatic hyperplasia. However, of the many notable studies involving Rezum's effectiveness in men, none have documented use of Rezum in the transgender community. With a growing population of transgender patients in the USA, prostate treatments will be offered for transgender women on a more regular basis. To the best of our knowledge, we introduce the first case of Rezum being utilized to treat benign prostatic hyperplasia in a patient self-identifying as a woman.

Therapeutic potential of pomegranate juice-derived nanovesicles in nude mouse benign prostatic hyperplasia (BPH) xenograft model.

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms affect a large percentage of the male population and places a substantial burden on the world health system. Current therapies include 5-alpha reductase inhibitors and alpha-blockers that are only partially effective and pose a huge economic burden, emphasizing the urgent need for effective, economical therapies. We isolated nanovesicles from pomegranate juice (Punica Granatum) (referred to as 'POM-NVs') and report to our knowledge for the first time, that these vesicles possess therapeutic potential against BPH. Following extensive characterization of POM-NVs, we tested their therapeutic potential in vitro using BPH1 cell line and identified a potential anti-proliferative and pro-apoptotic effect. We further tested these vesicles using a clinically relevant xenograft mouse BPH model derived from human BPH tissues. Remarkably, POM-NVs could reverse the BPH phenotype conferred by TGF-ß mediated signaling and induced epithelial-to-mesenchymal (EMT) reversal, leading to the restoration of prostate epithelial states in vivo and in vitro. Furthermore, these vesicles attenuated bone morphogenic protein 5 (BMP5) signaling, a cardinal alteration that is instrumental in driving BPH. Considering the large incidences of BPH and its associated economic burdens, our study has important implications and can potentially improve the clinical management of BPH.

miR-410 Is a Key Regulator of Epithelial-to-Mesenchymal Transition with Biphasic Role in Prostate Cancer.

The molecular basis of prostate cancer (PCa) progression from the primary disease to metastatic castration-resistant prostate cancer (CRPC) followed by therapy-induced neuroendocrine prostate cancer is not fully understood. In this study, we elucidate the role of miR-410, a little-studied microRNA located on chromosome 14q32.31 within the DLK1-DIO3 cluster, in PCa. miR-410 expression analyses in primary and metastatic PCa tissues and cell lines show that its levels are decreased in initial stages and increased in advanced PCa. Functional studies were performed in a series of PCa cell lines. In LNCaP cells, miR-410 overexpression led to decreases in cellular viability, proliferation, invasiveness, and migration. On the other hand, miR-410 overexpression in PC3 and C42B cells led to increased viability, proliferation, and invasiveness. Our data suggest that miR-410 represses epithelial-to-mesenchymal transition (EMT) in LNCaP cells by directly repressing SNAIL. However, it promotes EMT and upregulates PI3K/Akt signaling in PC3 and C42B cells. In vivo studies with PC3 xenografts support an oncogenic role of miR-410. These data suggest that miR-410 acts as a tumor suppressor in the initial stages of PCa and play an oncogenic role in advanced PCa. Our findings have important implications in understanding the molecular basis of PCa progression with potential translational implications.

Reduced Risk of Sepsis after Prostate Biopsy Using a Cephalosporin-Fluoroquinolone Antibiotic Regimen and Isopropyl Alcohol Needle Washing.

OBJECTIVE: To compare 3 prophylactic regimens to assess their impact on postbiopsy sepsis incidence. METHODS: Data were reviewed for 829 consecutive patients who underwent prostate biopsy in a community practice setting between January 2013 and October 2017. Group 1 patients received ciprofloxacin 500 mg two times a day orally for 4 days starting the day prior to biopsy and gentamicin 80 mg intramuscularly 20 minutes prior to biopsy. From April 2015 to October 2017, 2 groups of patients were followed in parallel in a randomized manner. Group 2 received ciprofloxacin 500 mg two times a day orally for 4 days starting the day prior to biopsy and ceftriaxone 1 g intramuscularly 20 minutes prior to biopsy. Group 3 received the same antibiotic regimen as group 2 and also underwent isopropyl alcohol needle washing. RESULTS: All study groups were demographically equivalent. Microscopic bacterial counts were substantially decreased after isopropyl alcohol needle washing. Incidence of postbiopsy sepsis in groups 1 (n = 313), 2 (n = 259), and 3 (n = 257) was 3.8%, 2%, and 0%, respectively (analysis of variance; P = .006). Risk factors for sepsis included elevated body mass index, Charlson Comorbidity Score, and presence of type 2 diabetes mellitus. CONCLUSION: There was a significant reduction in the incidence of sepsis after prostate biopsy using a combination of a ciprofloxacin-ceftriaxone antibiotic regimen and isopropyl alcohol needle washing. The technique for needle washing is inexpensive and quick, and can be easily adopted into current biopsy protocols.

Outcomes and Complications of Robotic-assisted Laparoscopic Prostatectomy in a Community Hospital Setting.

OBJECTIVE: To evaluate outcomes for 144 robotic-assisted laparoscopic prostatectomies (RALPs) conducted upon introduction of a robotic surgery program in a community hospital. METHODS: Patient data were reviewed for 144 patients who underwent RALP from January 2013 to February 2015. Complications and oncologic and functional outcomes were assessed. Student t test and analysis of variance were used to compare differences among study groups. RESULTS: Median age was 64 (IQR 60-68) and median prostate-specific antigen was 5.61 (interquartile range [IQR] 4.3-7.7). Stage pT2, pT3a, and 3b pathology was present at rates of 77%, 21%, and 8%, respectively. Median operative blood loss was 200 mL (IQR 150-300), median operative time was 1.75 hours (IQR 1.5-2.3), and median length of stay was 2 days (IQR 1-2). Overall, there were 9 complications (6.8%); 2 were classified as major and 7 as minor events. The overall positive surgical margin rate was 19%, with positive surgical margin rates of 11% and 46.8% in patients with pT2 and pT3 disease, respectively (P < .001). The overall biochemical recurrence rate at 12 months was 12.5% occurring in 10% and 20% of patients with pT2 and pT3 disease, respectively (P = .32). Continence success at 1, 6, and 12 months was 67%, 90%, and 93%, respectively. Potency success in men with normal to mild erectile dysfunction at baseline was 76% and 83% at 6 and 12 months, respectively. CONCLUSION: RALP in this community hospital practice was both safe and effective. Complication rates and oncologic and functional outcomes in this study were commensurate with those reported by high volume centers.

Genitourinary manifestations of sickle cell disease.

Sickle cell disease is a common genetic disorder characterized by sickling of red blood cells under conditions of reduced oxygen tension. In turn, sickling leads to intravascular hemolysis and vaso-occlusive events with subsequent tissue ischemia-reperfusion injury affecting multiple organs, including the genitourinary system. Our review of the genitourinary manifestations of sickle cell disease focuses on sickle cell nephropathy, priapism, and other genitourinary complications such as papillary necrosis and renal medullary carcinoma.

Analytical and biological validation of a multiplex immunoassay for acute kidney injury biomarkers.

BACKGROUND: Acute kidney injury (AKI) is a dynamic process that can involve inflammatory, hypoxic, and structural changes to the kidney. We evaluated a multiplex panel of markers representing different AKI mechanisms as a tool to provide integrated assessment of AKI status in a single assay. METHODS: Urinary cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) were measured by multiplex electrochemiluminescence immunoassay. Analytical performance was compared to the biological and pathological variation of these markers in human samples. RESULTS: Linearity was established over a 3- to 4-log range for all markers, which spanned the reference ranges established from healthy donors. Imprecision was below 15%, comparing favorably with the observed biological variation of these markers. Control patients fell within donor-derived reference ranges for most markers, but a subset of patients showed CysC and KIM-1 elevations in the absence of documented AKI. CONCLUSION: The multiplex assay is reliable for simultaneous quantitation of CysC, IL-18, KIM-1 and NGAL in human urine, and performs at levels sufficient for clinical application. The observed differences in biological variability and baseline levels suggest that clinical strategies to detect AKI will need to vary depending upon the specific markers used.

Association between warm ischemia time and renal parenchymal atrophy after partial nephrectomy.

PURPOSE: Renal parenchymal volume decrease after partial nephrectomy is associated with late functional outcomes. We examined the relative effects of resection related and atrophy related volume change on late kidney function. MATERIALS AND METHODS: Data were analyzed from a cohort of 187 patients who underwent open, laparoscopic or robotic partial nephrectomy between 2009 and 2011. Total change in kidney size after surgery was expressed as percent functional volume preservation measured using the cylindrical volume ratio method. Renal atrophy was expressed as parenchymal thickness preservation, and was assessed by measuring parenchymal thickness before and after partial nephrectomy in regions of the operated kidney distant from the site of resection. Standard statistical analyses were conducted to assess relationships among variables. RESULTS: Mean (± SD) percent functional volume preservation was 92% (± 8%), which correlated with a late percent glomerular filtration rate preservation of 91% (± 12%). Mean parenchymal thickness preservation for the cohort was 99% (± 4%). Minimal atrophy was observed in patients with warm ischemia time less than 40 minutes (parenchymal thickness preservation range 98% to 100%). Atrophy was more pronounced in patients with warm ischemia time greater than 40 minutes (parenchymal thickness preservation 96%). Multivariate regression analysis showed correlation of percent functional volume preservation with atrophy; correlation of warm ischemia time, diameter-axial-polar nephrometry score and atrophy with percent functional volume preservation; and correlation of Charlson score and diameter-axial-polar nephrometry score with percent decrease in glomerular filtration rate. CONCLUSIONS: In most patients with warm ischemia time less than 40 minutes the incidence of parenchymal atrophy was minimal, suggesting that the kidney volume decrease after partial nephrectomy was predominantly resection related. Kidney volume decrease after partial nephrectomy in patients with warm ischemia time greater than 40 minutes appeared to be due to a combination of resection related and atrophy related changes.

"Trifecta" in partial nephrectomy.

PURPOSE: We introduce the concept of trifecta outcomes during robotic/laparoscopic partial nephrectomy, in which the 3 key outcomes of negative cancer margin, minimal renal functional decrease and no urological complications are simultaneously realized. We report serial trifecta outcomes in patients treated with robotic/laparoscopic partial nephrectomy for tumor in a 12-year period. MATERIALS AND METHODS: A total of 534 patients had complete data available and were retrospectively divided into 4 chronologic eras, including the discovery era--139 from September 1999 to December 2003, conventional hilar clamping era--213 from January 2004 to December 2006, early unclamping era--104 from January 2007 to November 2008 and anatomical zero ischemia era--78 from March 2010 to October 2011. Renal functional decrease was defined as a greater than 10% reduction in the actual vs volume predicted postoperative estimated glomerular filtration rate. RESULTS: Across the 4 eras tumors trended toward larger size (2.9, 2.8, 3.1 and 3.3 cm, p = 0.08) and yet the estimated percent of kidney preserved was similar (89%, 90%, 90% and 88%, respectively, p = 0.3). Recent eras had increasingly complex tumors that were more often 4 cm or greater (p = 0.03), centrally located (p <0.009) or hilar (p <0.0001). Nevertheless, with significant technical refinement warm ischemia time decreased serially (36, 32, 15 and 0 minutes, respectively, p <0.0001). Renal functional outcomes were superior in recent eras with fewer patients experiencing a decrease (p <0.0001). Uniquely, actual estimated glomerular filtration rate outcomes exceeded volume predicted estimated glomerular filtration rate outcomes only in the zero ischemia cohort in regard to other eras (-9.5%, -11%, -0.9% and 4.2%, respectively, p <0.001). Positive cancer margins were uniformly low at less than 1%. Urological complications trended lower in recent eras (p = 0.01). Trifecta outcomes occurred more commonly in recent eras (45%, 44%, 62% and 68%, respectively, p = 0.0002). CONCLUSIONS: Trifecta should be a routine goal during partial nephrectomy. Despite increasing tumor complexity, trifecta outcomes of robotic/laparoscopic partial nephrectomy improved significantly in the last decade.

Comparative outcomes of laparoscopic and open adrenalectomy for adrenocortical carcinoma: single, high-volume center experience.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare and clinically aggressive cancer. Previous studies reported increased recurrence rates associated with laparoscopic adrenalectomy (LA). We evaluated a single-center experience of LA versus open adrenalectomy (OA) for the management of ACC. METHODS: Between 1993 and 2011, 44 consecutive patients with primary ACC were treated at our institution. Baseline patient characteristics and surgical and pathological outcomes were compared between OA and LA groups. Multivariable Cox proportional hazards analysis was used to estimate the association between OA versus LA with recurrence-free and overall survival. RESULTS: Eighteen and 26 patients underwent LA and OA, respectively. Patients who underwent OA had larger tumors and more advanced clinical stage compared with LA group. During a median follow-up of 22 months, 22 recurrences and 26 deaths were observed. The 2-year, recurrence-free and overall survivals for OA and LA were 60 vs. 39 % (P = 0.7) and 54 vs. 58 % (P = 0.6), respectively. After adjusting for clinical stage, OA was associated with lower risk of recurrence (hazard ratio (HR) 0.4; 95 % confidence interval (CI) 0.2-1.2; P = 0.099) and improved overall survival (HR 0.5; 95 % CI 0.2-1.2; P = 0.122) compared with LA, although differences were not statistically significant. CONCLUSIONS: A nonstatistically significant increase in recurrence and death was observed among patients undergoing LA versus OA after adjusting for clinical stage. The rarity of this disease limits the ability to assess for significant differences in a single-institution series. Patients with suspected ACC should be considered for OA.

Diameter-axial-polar nephrometry: integration and optimization of R.E.N.A.L. and centrality index scoring systems.

PURPOSE: The R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior) and centrality index nephrometry scores enable systematic, objective assessment of anatomical tumor features. We systematically compared these systems using item analysis test theory to optimize scoring methodology. MATERIALS AND METHODS: Analysis was based on 299 patients who underwent partial nephrectomy from 2007 to 2011 and met study inclusion criteria. Percent functional volume preservation, and R.E.N.A.L. and centrality index scores were measured. Late percent glomerular filtration rate preservation was calculated as the ratio of the late to the preoperative rate. Interobserver variability analysis was done to assess measurement error. All data were statistically analyzed. RESULTS: A novel scoring method termed DAP (diameter-axial-polar) nephrometry was devised using a data based approach. Mean R.E.N.A.L., centrality index and DAP scores for the cohort were 7.3, 2.5 and 6 with 84%, 90% and 95% interobserver agreement, respectively. The DAP sum score and all individual DAP scoring components were associated with the clinical outcome, including percent functional volume preservation, warm ischemia time and operative blood loss. DAP scoring criteria allowed for the normalization of score distributions and increased discriminatory power. DAP scores showed strong linear associations with percent functional volume preservation (r(2) = 0.97) and late percent glomerular filtration rate preservation (r(2) = 0.81). Each 1 unit change in DAP score equated to an average 4% change in kidney volume. CONCLUSIONS: DAP nephrometry integrates the optimized attributes of the R.E.N.A.L. and centrality index scoring systems. DAP scoring was associated with simplified methodology, decreased measurement error, improved performance characteristics, improved interpretability and a clear association with volume loss and late function after partial nephrectomy.

Nephrometry score is associated with volume loss and functional recovery after partial nephrectomy.

PURPOSE: Functional volume preservation after partial nephrectomy is a primary determinant of kidney function. We identified tumor features, including R.E.N.A.L. (radius for tumor size as maximal diameter, exophytic/endophytic tumor properties, nearness of deepest portion of tumor to collecting system or sinus, anterior/posterior descriptor and location relative to polar line) and centrality index nephrometry scores, associated with volume loss after partial nephrectomy. MATERIALS AND METHODS: A chart and imaging review was done for 237 patients who underwent partial nephrectomy from 2007 to 2010 and met study inclusion criteria. R.E.N.A.L. and centrality index nephrometry scores were measured in all patients. Percent functional volume preservation was estimated a median of 1.4 years after surgery using the cylindrical volume ratio method. Statistical analysis was done to study associations. RESULTS: Independent tumor features associated with percent functional volume preservation included tumor diameter (p < 0.001) and the distance from tumor periphery to kidney center (p = 0.02). R.E.N.A.L. and centrality index scores were associated with percent functional volume preservation (each p < 0.001). Nephrometry scores were also associated with nadir and late percent glomerular filtration rate preservation. Tumors classified as highly complex, with a centrality index score of 1.5 or less and a R.E.N.A.L. score of 10 or greater, were associated with an average 28% to 30% functional parenchymal volume loss of operated kidneys. A mean 8% difference in percent functional volume preservation was observed among low, intermediate and high tumor complexity categories for R.E.N.A.L. and centrality index scores. CONCLUSIONS: R.E.N.A.L. and centrality index nephrometry scores were associated with changes in the percent functional volume preservation and the perioperative functional decrease. Nephrometry scores performed better than diameter alone on statistical analysis. Nephrometry scores may be useful to estimate the likelihood of operative volume loss and by proxy the functional outcome.

Functional recovery after partial nephrectomy: effects of volume loss and ischemic injury.

PURPOSE: We used what is to our knowledge a new method to estimate volume loss after partial nephrectomy to assess the relative contributions of ischemic injury and volume loss on functional outcomes. MATERIALS AND METHODS: We analyzed the records of 301 consecutive patients who underwent conventional partial nephrectomy between 2007 and 2010 with available data to meet inclusion criteria. Percent functional volume preservation was measured at a median of 1.4 years after surgery. Modification of diet in renal disease-2 estimated glomerular filtration rate was measured preoperatively and perioperatively, and a median of 1.2 years postoperatively. Statistical analysis was done to study associations. RESULTS: Hypothermia or warm ischemia 25 minutes or less was applied in 75% of cases. Median percent functional volume preservation was 91% (range 38%-107%). Percent glomerular filtration rate preservation at nadir and late time points was 77% and 90% of preoperative glomerular filtration rate, respectively. On multivariate analysis percent functional volume preservation and warm ischemia time were associated with nadir glomerular filtration rate while only percent functional volume preservation was associated with late glomerular filtration rate (each p <0.001). Late percent glomerular filtration rate preservation and percent functional volume preservation were directly associated (p <0.001). Recovery of function to 90% or greater of percent functional volume preservation predicted levels was observed in 86% of patients. In patients with de novo postoperative stage 3 or greater chronic kidney disease, percent functional volume preservation and Charlson score were associated with late percent glomerular filtration rate preservation. Warm ischemia time was not associated with late functional glomerular filtration rate decreases in patients considered high risk for ischemic injury. CONCLUSIONS: In this cohort volume loss and not ischemia time was the primary determinant of ultimate renal function after partial nephrectomy. Technical modifications aimed at minimizing volume loss during partial nephrectomy while still achieving negative margins may result in improved functional outcomes.

Small renal masses: risk prediction and contemporary management.

The majority of kidney cancer tumors are small renal masses (SRMs). Partial nephrectomy is now established as the preferred treatment modality. In some patients the potential morbidity may outweigh the oncologic risk. Based on active surveillance studies, restriction of radical therapy to patients with aggressive tumors has been proposed. This has spurred renewed interest in development of radiologic and biopsy-based diagnostic techniques that can identify high-risk disease. This article discusses the natural history and pathologic features of SRMs, the evolving role of biopsy, and provides an overview of outcomes of various treatment approaches and current recommendations for management.