5-Alpha reductase inhibitors induce a prostate luminal to club cell transition in human benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.

PSA density is associated with BPH cellular composition.

BACKGROUND: Current AUA guidelines recommend 5 alpha reductase inhibitor (5ARI) treatment for patients with obstructive benign prostatic hyperplasia (BPH) that display prostate volume ≥30 cc and total prostate specific antigen (PSA) ≥1.5 ng/ml. However, BPH is highly pleomorphic and response to 5ARIs is highly variable. An understanding of cellular composition based on a noninvasive PSA density test could lead to improved clinical decision making. METHODS: The histological composition of 307 BPH specimens was scored by a pathologist for stromo-glandular content and associated with total PSA, prostate volume, PSA density and other clinical variables using univariate and multivariate linear regression. RESULTS: The percentage of glandular composition in prostates of 5ARI-naïve men was positively and independently associated with PSA and PSA density. It was determined through statistical modeling that a PSA density ≤0.05 ng/ml2 associated with a glandular composition of ≤30% with 76% sensitivity. CONCLUSIONS: PSA density could provide a decisive variable for estimating BPH cellular content and may eventually improve selection of patients for 5ARI treatment. Further work is needed to demonstrate that patients with higher glandular content are more responsive to 5ARI treatment.

Single-cell analysis of mouse and human prostate reveals novel fibroblasts with specialized distribution and microenvironment interactions.

Stromal-epithelial interactions are critical to the morphogenesis, differentiation, and homeostasis of the prostate, but the molecular identity and anatomy of discrete stromal cell types is poorly understood. Using single-cell RNA sequencing, we identified and validated the in situ localization of three smooth muscle subtypes (prostate smooth muscle, pericytes, and vascular smooth muscle) and two novel fibroblast subtypes in human prostate. Peri-epithelial fibroblasts (APOD+) wrap around epithelial structures, whereas interstitial fibroblasts (C7+) are interspersed in extracellular matrix. In contrast, the mouse displayed three fibroblast subtypes with distinct proximal-distal and lobe-specific distribution patterns. Statistical analysis of mouse and human fibroblasts showed transcriptional correlation between mouse prostate (C3+) and urethral (Lgr5+) fibroblasts and the human interstitial fibroblast subtype. Both urethral fibroblasts (Lgr5+) and ductal fibroblasts (Wnt2+) in the mouse contribute to a proximal Wnt/Tgfb signaling niche that is absent in human prostate. Instead, human peri-epithelial fibroblasts express secreted WNT inhibitors SFRPs and DKK1, which could serve as a buffer against stromal WNT ligands by creating a localized signaling niche around individual prostate glands. We also identified proximal-distal fibroblast density differences in human prostate that could amplify stromal signaling around proximal prostate ducts. In human benign prostatic hyperplasia, fibroblast subtypes upregulate critical immunoregulatory pathways and show distinct distributions in stromal and glandular phenotypes. A detailed taxonomy of leukocytes in benign prostatic hyperplasia reveals an influx of myeloid dendritic cells, T cells and B cells, resembling a mucosal inflammatory disorder. A receptor-ligand interaction analysis of all cell types revealed a central role for fibroblasts in growth factor, morphogen, and chemokine signaling to endothelia, epithelia, and leukocytes. These data are foundational to the development of new therapeutic targets in benign prostatic hyperplasia. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Identifying predictors of antispasmodic use following robotic assisted simple prostatectomy.

INTRODUCTION: Anticholinergic or ß-3 agonist use following robotic simple prostatectomy (RASP) is not well described. We describe rates of antispasmodic use following RASP and identify potential predictors of medication use. MATERIALS AND METHODS: A retrospective review of all RASP patients from 2/2016 - 1/2020 was conducted. Patients with no preoperative International Prostate Symptom Score (IPSS) were excluded. Demographics, clinical data, and postoperative medication use were collected by electronic medical record review. Multivariable logistic regression analysis using a priori variables was performed to identify independent factors associated with antispasmodic use. RESULTS: A total of 255 patients underwent RASP at a mean age of 70.0 years ± 7.3 and mean body mass index (BMI) of 28.6 kg/m2 ± 5.0. Median preoperative prostate volume was 132.3 cc ± 45.0. Rates of preoperative diabetes, obstructive sleep apnea (OSA), smoking and alcohol use were 19.6%, 6.3%, 3.1%, and 11.8% respectively; 8.6% of patients (n = 22) initiated antispasmodics at a median of 2.5 months (IQR 1.3-4.2) postoperatively. Median duration of antispasmodic use was 6.5 months (IQR 1.7-14.7). Mirabegron was most commonly prescribed (31.8%). On multivariable logistic regression analysis, OSA was independently associated with postoperative antispasmodic use (OR 8.13, 95% CI 2.02-32.67, p = 0.003); 68.8% of OSA patients were treated with continuous positive airway pressure (CPAP). Treatment was not significantly associated with postoperative antispasmodic use (p = 0.61). CONCLUSION: Patients with OSA are over 8 times more likely to require antispasmodic medications following RASP in the short term. These patients may benefit from more tailored preoperative counseling.

Clinical and radiographic outcomes following salvage intervention for ureteropelvic junction obstruction.

PURPOSE: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). MATERIALS AND METHODS: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. RESULTS: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. CONCLUSIONS: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.

Urethral luminal epithelia are castration-insensitive cells of the proximal prostate.

BACKGROUND: Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors. METHODS: Here, we use single-cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes. Pan-transcriptomic comparison to human prostate cell types identified a mouse equivalent of human urethral luminal cells, which highly expressed putative prostate progenitor markers. Validation of the urethral luminal cell cluster was performed using immunostaining and flow cytometry. RESULTS: Our data reveal that previously identified facultative progenitors marked by Trop2, Sca-1, KRT4, and PSCA are actually luminal epithelial cells of the urethra that extend into the proximal region of the prostate, and are resistant to castration-induced androgen deprivation. Mouse urethral luminal cells were identified to be the equivalent of previously identified human club and hillock cells that similarly extend into proximal prostate ducts. Benign prostatic hyperplasia (BPH) has long been considered an "embryonic reawakening," but the cellular origin of the hyperplastic growth concentrated in the periurethral region is unclear. We demonstrate an increase in urethral luminal cells within glandular nodules from BPH patients. Urethral luminal cells are further increased in patients treated with a 5-α reductase inhibitor. CONCLUSIONS: Our data demonstrate that cells of the proximal prostate that express putative progenitor markers, and are enriched by castration in the proximal prostate, are urethral luminal cells and that these cells may play an important role in the etiology of human BPH.

Natural history of 'second' biochemical failure after salvage radiation therapy for prostate cancer: a multi-institution study.

OBJECTIVES: To describe the natural history of prostate cancer in men who experience a second biochemical recurrence (BCR) after salvage radiotherapy (SRT) after prostatectomy. PATIENTS AND METHODS: After undergoing SRT at one of two institutions between 1986 and 2013, 286 patients experienced a second BCR, defined as two rises in prostate-specific antigen (PSA) of ≥0.2 ng/mL above nadir. Event rates for distant metastasis (DM) or freedom from DM (FFDM), castration-resistant prostate cancer (CRPC), prostate cancer-specific survival (PCSS), and overall survival (OS) were estimated using the Kaplan-Meier method. Cox regression was used for comparative analyses. RESULTS: At a median of 6.1 years after second BCR, DM, CRPC, PCSS and OS rates were 41%, 27%, 83% and 73%, respectively. On multivariable analysis, interval to second BCR <1 year (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.71-4.14; P < 0.001], Gleason score 8-10 (HR 1.65, 95% CI 1.07-2.54; P = 0.022), and concurrent ADT during SRT (HR 1.76, 95% CI 1.08-2.88; P = 0.024) were associated with FFDM, while PCSS was associated with interval to second BCR <1 year (HR 3.00, 95% CI 1.69-5.32; P < 0.001) and concurrent ADT during SRT (HR 2.15, CI 1.13-4.08; P = 0.019). These risk factors were used to stratify patients into three groups, with 6-year FFDM rates of 71%, 59% and 33%, and PCSS rates of 89%, 79%, and 65%, respectively. CONCLUSION: Following second BCR after SRT, clinical progression is enriched in a subgroup of patients with prostate cancer, while others remain without DM for long intervals. Stratifying patients into risk groups using prognostic factors may aid counselling and future trial design.

Comparison of Robot-Assisted Versus Open Simple Prostatectomy for Benign Prostatic Hyperplasia.

PURPOSE OF REVIEW: Recent advancements in minimally invasive approaches for prostate surgery have provided numerous options for surgical management of benign prostatic hyperplasia (BPH). In the setting of a large prostate, an open simple prostatectomy was previously considered the gold standard surgical treatment. However, the recently updated American Urological Association (AUA) guidelines on surgical management of BPH now consider both open and minimally invasive approaches to simple prostatectomy viable alternatives for treating large glands, depending on expertise with the techniques. The purpose of our review is to discuss the minimally invasive robot-assisted approach and compare it to the classic open approach to simple prostatectomy. RECENT FINDINGS: Despite longer operative times, the robotic approach is associated with shorter hospital stay and lower morbidity profile. The morbidity of an open approach remains significant. Blood transfusions are 3-4 times as likely compared to a robotic approach and major complications are twice as likely. Consistent with previous literature, our review shows functional outcome improvements like flow rate and symptom score to be comparable between the robotic and open approach. The amount of adenoma resected and PSA decline is also similar among robotic and open cases. Robot-assisted simple prostatectomy is a safe and effective procedure for BPH secondary to a large prostate gland. Appropriately, it is no longer deemed "investigational" by the latest AUA guidelines on BPH and recommended as an alternative to the open approach.

Axial Abdominal Imaging after Partial Nephrectomy for T1 Renal Cell Carcinoma Surveillance.

PURPOSE: The overall recurrence rate of T1 renal cell carcinoma is low. We evaluated abdominal imaging after partial nephrectomy based on current guidelines for T1 renal cell carcinoma surveillance. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with T1 renal cell carcinoma who underwent partial nephrectomy between 2006 and 2012 followed by abdominal imaging at our institution. Primary and secondary outcomes were the incidence and timing, respectively, of imaging diagnosed abdominal recurrences. A literature review was performed to summarize prior reports of recurrence incidence and timing after partial nephrectomy for T1 disease. RESULTS: A total of 160 patients with stage T1a and 37 with T1b underwent partial nephrectomy. Seven patients had an abdominal recurrence, including 3 with local and distant recurrences, and 4 with a metachronous contralateral kidney recurrence. The incidence of abdominal recurrence detected by imaging was higher in the T1b than in the T1a group (10.8% vs 1.9%, p = 0.024). Although it was not significant, median time to recurrence was earlier in T1b vs T1a cases (13 vs 37 months, p = 0.480). In each group recurrences developed after 3 years of suggested guideline surveillance. In the literature combined with the current study the time to median recurrence for T1b vs T1a was 24 vs 29 months (p = 0.226). CONCLUSIONS: Recurrences detected by abdominal imaging developed earlier and more frequently in T1b than in T1a cases. Future recommendations for surveillance strategies after partial nephrectomy should distinguish T1a from T1b with less intense frequency of imaging for T1a. A longer period of surveillance should be considered since recurrences can develop beyond 3 years.

Likelihood of Incomplete Kidney Tumor Ablation with Radio Frequency Energy: Degree of Enhancement Matters.

PURPOSE: Larger size and clear cell histopathology are associated with worse outcomes for malignant renal tumors treated with radio frequency ablation. We hypothesize that greater tumor enhancement may be a risk factor for radio frequency ablation failure due to increased vascularity. MATERIALS AND METHODS: A retrospective review of patients who underwent radio frequency ablation for renal tumors with contrast enhanced imaging available was performed. The change in Hounsfield units (HU) of the tumor from the noncontrast phase to the contrast enhanced arterial phase was calculated. Radio frequency ablation failure rates for biopsy confirmed malignant tumors were compared using the chi-squared test. Multivariate logistic analysis was performed to assess predictive variables for radio frequency ablation failure. Disease-free survival was calculated using Kaplan-Meier analysis. RESULTS: A total of 99 patients with biopsy confirmed malignant renal tumors and contrast enhanced imaging were identified. The incomplete ablation rate was significantly lower for tumors with enhancement less than 60 vs 60 HU or greater (0.0% vs 14.6%, p=0.005). On multivariate logistic regression analysis tumor enhancement 60 HU or greater (OR 1.14, p=0.008) remained a significant predictor of incomplete initial ablation. The 5-year disease-free survival for size less than 3 cm was 100% vs 69.2% for size 3 cm or greater (p <0.01), while 5-year disease-free survival for HU change less than 60 was 100% vs 92.4% for HU change 60 or greater (p=0.24). CONCLUSIONS: Biopsy confirmed malignant renal tumors, which exhibit a change in enhancement of 60 HU or greater, experience a higher rate of incomplete initial tumor ablation than tumors with enhancement less than 60 HU. Size 3 cm or greater portends worse 5-year disease-free survival after radio frequency ablation. The degree of enhancement should be considered when counseling patients before radio frequency ablation.

The Usefulness of Chest X-Rays for T1a Renal Cell Carcinoma Surveillance.

PURPOSE: The overall incidence of pulmonary metastasis of T1 renal cell carcinoma is low. We evaluated the usefulness of chest x-rays based on the current AUA (American Urological Association) guidelines and NCCN Guidelines® for T1a renal cell carcinoma surveillance. MATERIALS AND METHODS: Between 2006 and 2012, 258 patients with T1a renal cell carcinoma were treated with partial nephrectomy, radical nephrectomy or radio frequency ablation with surveillance followup at our institution. A retrospective chart review was performed to identify demographics, pathological findings and surveillance records. The primary outcome was the incidence of asymptomatic pulmonary recurrences diagnosed by chest x-ray in cases of T1a disease. Our secondary outcome was a comparison of diagnoses by treatment modality (partial nephrectomy, radical nephrectomy or radio frequency ablation). RESULTS: Pulmonary metastases developed in 3 of 258 patients (1.2%) but only 1 (0.4%) was diagnosed by standard chest x-ray surveillance. Median followup in the entire cohort was 36 months (range 6 to 152) and 193 of 258 patients (75%) had greater than 24 months of followup. A mean of 3.3 surveillance chest x-rays were completed per patient. When assessed by treatment type, there was no significant difference in the recurrence rate for partial nephrectomy (0 of 191 cases), radical nephrectomy (0 of 22) or radio frequency ablation (1 of 45 or 2.2%) (p = 0.09). CONCLUSIONS: Chest x-rays are a low yield diagnostic tool for detecting pulmonary metastasis in patients treated for T1a renal cel carcinoma. Treatment mode does not appear to influence the need for chest x-ray surveillance.

Equivocal ureteropelvic junction obstruction on diuretic renogram--should minimally invasive pyeloplasty be offered to symptomatic patients?

PURPOSE: Equivocal ureteropelvic junction obstruction refers to clinical symptoms and/or other radiological suggestions of possible ureteropelvic junction obstruction but with inconclusive results of obstruction on diuretic renogram. We evaluated long-term outcomes in patients with equivocal ureteropelvic junction obstruction treated with minimally invasive pyeloplasty. MATERIALS AND METHODS: We retrospectively analyzed the records of 125 consecutive patients who underwent minimally invasive pyeloplasty as performed by a single surgeon from May 2004 to July 2013. Of 98 patients with followup those with more than 6-month followup were included in analysis. Equivocal ureteropelvic junction obstruction, defined as half-life less than 20 minutes on diuretic renogram, was identified in 23 patients. All patients underwent transperitoneal minimally invasive pyeloplasty. We evaluated patient demographics, preoperative and postoperative symptoms and renal function. RESULTS: The 16 female and 7 male patients with equivocal ureteropelvic junction obstruction had flank pain and associated hydronephrosis on imaging. At a median followup of 20.2 months (range 7 to 75) 95.7% of patients with equivocal obstruction achieved complete symptom resolution. Mean ± SD preoperative and postoperative half-life was 14.1 ± 3.7 and 7.4 ± 4.2 minutes, respectively, for an improvement of 6.7 minutes (p < 0.001). In 1 patient (4.3%) with equivocal obstruction of a complicated iatrogenic etiology treatment ultimately failed postoperatively and endopyelotomy was required. There was no statistically significant difference in clinical or radiological success between the equivocal obstruction group and the 75 patients treated with minimally invasive pyeloplasty for definitive ureteropelvic junction obstruction (p = 0.44 and 0.07, respectively). CONCLUSIONS: In patients with radiographic equivocal ureteropelvic junction obstruction and flank pain minimally invasive pyeloplasty efficaciously provides symptomatic relief and functional preservation. Results are comparable to those in patients with high grade obstruction.

Oncologic Efficacy of Radio Frequency Ablation for Small Renal Masses: Clear Cell vs Papillary Subtype.

PURPOSE: Current radio frequency ablation series do not distinguish renal cell carcinoma subtypes when reporting oncologic efficacy. Papillary neoplasms may be more amenable to radio frequency ablation than clear cell carcinoma because they are less vascular, which may limit heat energy loss. We report the long-term outcomes of patients treated with radio frequency ablation for small renal masses by renal cell carcinoma subtype. MATERIALS AND METHODS: The records of patients undergoing radio frequency ablation for small renal masses (cT1a) at 2 institutions from March 2007 to July 2012 were retrospectively reviewed. Patients were included in analysis if they had biopsy confirmed clear cell or papillary renal cell carcinoma histology. Patients had at least 1 contrast enhanced cross-sectional image following radio frequency ablation. Demographic data between tumor subtypes were compared using the paired t-test. Oncologic outcomes were determined by Kaplan-Meier survival analysis and survivor curves were compared with the log rank test. RESULTS: A total of 229 patients met study inclusion criteria. There were 181 clear cell tumors and 48 papillary tumors. Median followup was 33.2 months. There was no difference between tumor groups based on patient age, tumor size or grade, or months of followup. Five-year disease-free survival was 89.7% for clear cell tumors and 100% for papillary tumors (p = 0.041). There was no significant difference in overall survival (88.4% vs 89.6%, p = 0.764). CONCLUSIONS: Radio frequency ablation outcomes seem to be determined in part by renal cell carcinoma subtype with clear cell renal tumors having less favorable outcomes. We hypothesize that this is due to differences in tumor vascularity. Our experience suggests that future tumor ablation studies should consider reporting outcomes based on tumor cell types.

Single- versus dual-console robot-assisted radical prostatectomy: impact on intraoperative and postoperative outcomes in a teaching institution.

OBJECTIVE: To compare the outcomes of robotic-assisted laparoscopic prostatectomy (RALP) using a dual versus single-console system in a resident training program using intraoperative, perioperative and postoperative measures. METHODS: Patients with PCa who underwent RALP prior to and after implementing a dual-console system at an academic institution were reviewed from 2006-2012. All surgeries were performed by a single-faculty surgeon well after the learning curve was established. In all cases, chief residents participated in the surgery and performed progressively more portions. Demographic, intraoperative and pathologic parameters were obtained. Continence and erectile function were assessed at 6 and 12 months. Postoperative complications were graded using the Clavien-Dindo classification. Predictors of outcomes on univariate analysis were included in multivariate logistic or linear models. RESULTS: Of 381 patients, 185 and 196 underwent single- or dual-console RALP, respectively. There was a significant decrease in mean operative time using the dual-console system (222 vs. 171 min, p < 0.0001) as well as in the incidence of intraoperative complications (8.65 vs. 1.53%, p < 0.0001) and postoperative complications (14.1 vs. 6.63%, p = 0.03.) Complications of Clavien grade ≥3a occurred more frequently with a single-console system (7 vs. 1%, p = 0.003.) Differences persisted when controlling for potential confounders by multivariate regression. Postoperative measures of continence, erectile function and the rate of biochemical recurrence were similar between cohorts. CONCLUSIONS: When training resident surgeons to perform RALP, a dual-console system may improve intraoperative and perioperative outcomes. The dual-console may represent a safer, more efficient modality for robotic surgical education as compared to a single-console system.

Prompt management of anastomotic leak or acute obstruction after minimally invasive pyeloplasty with percutaneous nephrostomy preserves outcomes.

PURPOSE: Urine leak or obstruction in the early postoperative period is a worrisome complication of pyeloplasty. Suboptimal management may risk long-term success. We evaluated percutaneous nephrostomy to manage complications of minimally invasive pyeloplasty. MATERIALS AND METHODS: We retrospectively analyzed the records of 125 patients who underwent minimally invasive pyeloplasty performed by a single surgeon from May 2004 to May 2013. All complications were catalogued and patients with anastomotic urine leakage or postoperative obstruction were identified. Less than 7 days postoperatively percutaneous nephrostomy was done in each case. Surgical success was defined as resolution of flank pain and/or improved half-time (less than 20 minutes) on diuretic renogram. RESULTS: Early percutaneous nephrostomy placement was required in 12 patients (9.6%) for symptomatic obstruction (6) or anastomotic urine leakage (6) a median of 4.5 days (range 2 to 7) postoperatively. Percutaneous nephrostomies remained in place a median of 9.5 days (range 5 to 42). Median followup was 15 months (range 2 to 80). Mean half-time was 36.4 minutes preoperatively and 11.1 minutes postoperatively. Continued postoperative obstruction (half-time greater than 20 minutes) was documented in 1 (8%) and 13 patients (11.5%) who did and did not require percutaneous nephrostomy placement, respectively. There was no statistical difference in radiological and clinical success rates between the percutaneous nephrostomy group and the 113 patients in whom minimally invasive pyeloplasty was uncomplicated (p = 0.74 and 0.28, respectively). CONCLUSIONS: In patients treated with minimally invasive pyeloplasty aggressive management of acute urinary complications with percutaneous nephrostomy placement preserved radiographic and symptomatic outcomes that were comparable to those in patients without complications.

Long-term outcomes in healthy adults after radiofrequency ablation of T1a renal tumours.

OBJECTIVE: To report the long-term oncological and renal function outcomes in healthy adults treated with radiofrequency ablation (RFA) for small renal masses. MATERIALS AND METHODS: We retrospectively analysed the medical records of otherwise healthy patients (those with American Society of Anesthesiologists symptom score 1 or 2) with clinical T1a renal tumours who underwent RFA at our institution between March 2001 and July 2012. Radiographic follow-up with contrast imaging was performed at 6 weeks, 6 months, 1 year and annually thereafter. Local recurrence was defined as any new enhancing lesion (>10 HU) after the initial negative post-treatment computed tomography results. The estimated glomerular filtration rates (eGFRs) before and after RFA were calculated using the Cockgroft-Gault equation. RESULTS: We performed RFA on 58 renal tumours in 52 patients. The mean tumour size was 2.2 cm with a median (interquartile range) follow-up of 60 (48-90) months. Three (5.1%) of the treated masses had tumour recurrence after initial RFA. The 5- and 10-year recurrence-free survival rate was 94.2%. There were no recurrences after 3 years. Three (5.1%) patients died during the follow-up, which gave 5- and 10-year overall survival rates of 95.7% and 91.1%. No patient developed metastatic renal cell carcinoma (RCC) and none died from RCC. Paired analysis showed that the eGFR values at a median follow-up of 40 months did not differ significantly from those before RFA. CONCLUSION: With long-term follow-up, RFA provides durable oncological and functional outcomes for selected T1a renal tumours in otherwise healthy patients.

A dual-camera hyperspectral laparoscopic imaging system.

Minimally invasive surgery (MIS) has expanded broadly in the field of abdominal and pelvic surgery. However, there are still prevalent issues surrounding intracorporeal surgery, such as iatrogenic injury, anastomotic leakage, or the presence of positive tumor margins after resection. Current approaches to address these issues and advance laparoscopic imaging techniques often involve fluorescence imaging agents, such as indocyanine green (ICG), to improve visualization, but these have drawbacks. Hyperspectral imaging (HSI) is an emerging optical imaging modality that takes advantage of spectral characteristics of different tissues. Various applications include tissue classification and digital pathology. In this study, we developed a dual-camera system for high-speed hyperspectral imaging. This includes the development of a custom application interface and corresponding hardware setup. Characterization of the system was performed, including spectral accuracy and spatial resolution, showing little sacrifice in speed for the approximate doubling of the covered spectral range, with our system acquiring 29 spectral images from 460-850 nm. Reference color tiles with various reflectance profiles were imaged and a RMSE of 3.56 ± 1.36% was achieved. Sub-millimeter resolution was shown at 7 cm working distance for both hyperspectral cameras. Finally, we image ex vivo tissues, including porcine stomach, liver, intestine, and kidney with our system and use a high-resolution, radiometrically calibrated spectrometer for comparison and evaluation of spectral fidelity. The dual-camera hyperspectral laparoscopic imaging system can have immediate applications in various surgeries.

Retzius-sparing vs. posterior urethral suspension: similar early-phase post-robotic radical prostatectomy continence outcomes.

Stress urinary incontinence (SUI) is a risk of robotic-assisted radical prostatectomy (RP) which can be a frustrating problem for both surgeons and patients. We aim to compare short-term continence outcomes between patients undergoing Retzius Sparing RP (RS-RP) and those undergoing standard RP with the inclusion of a PUS suture technique and suprapubic tube (PUS-RP). A retrospective review of 105 consecutive patients who underwent RP was performed, comparing patients who underwent RS-RP and PUS-RP. Our main outcome was pad usage as a surrogate for SUI. Patients were evaluated 4 weeks following RP and again at approximately 3 months. Continence was defined as no pad usage or up to one safety pad per day. Risk factors associated with not being continent were identified using univariate and multivariate analyses. In our cohort, 52 patients underwent RS-RP and 53 patients underwent PUS-RP. The two groups had similar patient demographics. Although not statistically significant, there was a higher rate of a positive surgical margin in the RS-RP compared to PUS-RP (25% vs 15%, p = 0.204). At one month follow-up for PUS-RP and RS-RP, there was no significant difference in the frequency of continent men (69.2% vs. 76.9%, p = 0.302). At 3-month follow-up for the two groups of patients, again, there was no significant difference in the frequency of continence for PUS-RP and RS-RP (86.2% vs 88%, p = 0.824). Patients who underwent RS-RP had similar rates of continence to those patients undergoing PUS-RP in the short-term post-operative period.

Mapping Cellular Interactions from Spatially Resolved Transcriptomics Data.

Cell-cell communication (CCC) is essential to how life forms and functions. However, accurate, high-throughput mapping of how expression of all genes in one cell affects expression of all genes in another cell is made possible only recently, through the introduction of spatially resolved transcriptomics technologies (SRTs), especially those that achieve single cell resolution. However, significant challenges remain to analyze such highly complex data properly. Here, we introduce a Bayesian multi-instance learning framework, spacia, to detect CCCs from data generated by SRTs, by uniquely exploiting their spatial modality. We highlight spacia's power to overcome fundamental limitations of popular analytical tools for inference of CCCs, including losing single-cell resolution, limited to ligand-receptor relationships and prior interaction databases, high false positive rates, and most importantly the lack of consideration of the multiple-sender-to-one-receiver paradigm. We evaluated the fitness of spacia for all three commercialized single cell resolution ST technologies: MERSCOPE/Vizgen, CosMx/Nanostring, and Xenium/10X. Spacia unveiled how endothelial cells, fibroblasts and B cells in the tumor microenvironment contribute to Epithelial-Mesenchymal Transition and lineage plasticity in prostate cancer cells. We deployed spacia in a set of pan-cancer datasets and showed that B cells also participate in PDL1/PD1 signaling in tumors. We demonstrated that a CD8+ T cell/PDL1 effectiveness signature derived from spacia analyses is associated with patient survival and response to immune checkpoint inhibitor treatments in 3,354 patients. We revealed differential spatial interaction patterns between γδ T cells and liver hepatocytes in healthy and cancerous contexts. Overall, spacia represents a notable step in advancing quantitative theories of cellular communications.

A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.