Robotic Bladder Autotransplantation: Preclinical Studies in Preparation for First-in-human Bladder Transplant.

PURPOSE: Human urinary bladder transplantation has never been performed. From a technical standpoint, challenges include the complex deep pelvic vascular anatomy, limited intraoperative visualization, and high procedural complexity. In preparation for a first-in-human clinical trial, we report preclinical studies to develop the technique of robotic retrieval and autotransplantation of vascularized composite bladder allograft. MATERIALS AND METHODS: Institutional Animal Care and Use Committee, Institutional Review Board, and UNOS (United Network for Organ Sharing) approvals were obtained, and IDEAL (Idea, Development, Exploration, Assessment, Long-term Study) Reporting Guidelines were followed. Robotic vascularized composite bladder allograft recovery, back-table graft preparation, and robotic autotransplantation were performed in 3 vascularized model settings: living porcine (n=3), pulsatile human cadavers (n=2), and heart-beating brain-dead deceased research human donors (n=5). Our primary objective was to develop a reproducible technique for robotic vascularized composite bladder allograft transplantation. Technical success was defined by adequate, sustained vascularized composite bladder allograft reperfusion. Secondary objectives were intraoperative parameters, including operative time, graft ischemia time, and blood loss. RESULTS: Successful robotic vascularized composite bladder allograft autotransplantation was achieved in 2 porcine, 1 cadaver, and 3 brain-dead research donors. In the heart-beating research donors, console time decreased with successive surgeries, and visual inspection revealed healthy revascularized autografts with prompt, global indocyanine green immunofluorescence uptake. In 1 heart-beating donor who was hemodynamically maintained for 12 hours postoperatively, reinspection confirmed excellent maintained global vascularized composite bladder allograft vascularity and bladder mucosal integrity. CONCLUSIONS: To our knowledge, the first preclinical experience of bladder autotransplantation in vascularized models is reported, including robotic vascularized composite bladder allograft recovery, back-table reconstruction, and autotransplantation. This experience represents the essential preclinical work required to build toward the first-in-human trial of bladder transplantation, performed under a UNOS-approved genitourinary vascularized composite bladder allograft program (NCT No. 05462561).

Hyperandrogenism and Hyperestrogenism Secondary to Mixed Germ-Cell Testicular Tumor.

Testicular cancer with androgen and estrogen secretion is classically associated with Leydig cell tumors. Rare case reports have described this finding in germ-cell tumors along with signs of androgen and estrogen excess including gynecomastia and infertility. We report the case of a 19-year-old male with a non-seminomatous testicular germ-cell tumor found to have hyperandrogenism, hyperestrogenism, and suppression of central sex hormones. Similar findings may be underreported in the literature, and males with suspected testicular malignancy should be appropriately screened for signs of androgen and/or estrogen excess so they can be offered appropriate monitoring and counseling.

Partial Gland Ablation of Prostate Cancer: Effects of Repeat Treatment.

OBJECTIVE: To evaluate the near-term clinical and pathological effects of repeat partial gland ablation (PGA) in men with intermediate-risk prostate cancer (PCa). MATERIALS AND METHODS: One hundred seventy men with focal lesions of PCa (all GG2 or GG3) underwent PGA with high-intensity focused ultrasound (HIFU) or cryotherapy (CRYO) in prospective trials. Residual PCa in or near the ablation zone was found in 37 men after a first PGA; 30 went on to receive a second PGA and were the subjects of study. At 3 timepoints, baseline and 6 months after first and second ablations, quality-of-life (QOL) questionnaires (IIEF, IPSS) and MRI-guided biopsies (MRGB) were performed. Biopsies were targeted and systematic at baseline and in follow-up, comprehensively about the ablation zone. RESULTS: All 30 patients completed QOL questionnaires and 26 had MRGB at the 3 timepoints. Mean QOL scores were not significantly different from the baseline after the first or second PGA. No operative complications were encountered; and "decisional regret" was reported in only 2/29 men after the repeat ablation. A decrease in semen volume was reported by 25% of patients. Repeat ablation was successful (absence of csPCa on MRGB) in 14/26 (53%) of men. PSA levels decreased and MRI lesions resolved after ablations, but neither was a reliable predictor of biopsy outcomes. CONCLUSION: When initial PGA fails, repeat PGA is a reasonable consideration, because in near-term follow-up, secondary procedures appear to be safe, causing only minimal detriment to urinary and sexual function, with csPCa becoming undetectable by MRGB in approximately half the patients.

A Radiomic-based Machine Learning Algorithm to Reliably Differentiate Benign Renal Masses from Renal Cell Carcinoma.

BACKGROUND: A substantial proportion of patients undergo treatment for renal masses where active surveillance or observation may be more appropriate. OBJECTIVE: To determine whether radiomic-based machine learning platforms can distinguish benign from malignant renal masses. DESIGN, SETTING, AND PARTICIPANTS: A prospectively maintained single-institutional renal mass registry was queried to identify patients with a computed tomography-proven clinically localized renal mass who underwent partial or radical nephrectomy. INTERVENTION: Radiomic analysis of preoperative scans was performed. Clinical and radiomic variables of importance were identified through decision tree analysis, which were incorporated into Random Forest and REAL Adaboost predictive models. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the degree of congruity between the virtual diagnosis and final pathology. Subanalyses were performed for small renal masses and patients who had percutaneous renal mass biopsies as part of their workup. Receiver operating characteristic curves were used to evaluate each model's discriminatory function. RESULTS AND LIMITATIONS: A total of 684 patients met the selection criteria. Of them, 76% had renal cell carcinoma; 57% had small renal masses, of which 73% were malignant. Predictive modeling differentiated benign pathology from malignant with an area under the curve (AUC) of 0.84 (95% confidence interval [CI] 0.79-0.9). In small renal masses, radiomic analysis yielded a discriminatory AUC of 0.77 (95% CI 0.69-0.85). When negative and nondiagnostic biopsies were supplemented with radiomic analysis, accuracy increased from 83.3% to 93.4%. CONCLUSIONS: Radiomic-based predictive modeling may distinguish benign from malignant renal masses. Clinical factors did not substantially improve the diagnostic accuracy of predictive models. Enhanced diagnostic predictability may improve patient selection before surgery and increase the utilization of active surveillance protocols. PATIENT SUMMARY: Not all kidney tumors are cancerous, and some can be watched. We evaluated a new method that uses radiographic features invisible to the naked eye to distinguish benign masses from true cancers and found that it can do so with acceptable accuracy.

Gluteal Necrotizing Soft Tissue Infection and Hip Osteomyelitis due to Candida Glabrata.

BACKGROUND: Necrotizing soft tissue infection (NSTI) is a rapidly progressive and often fatal infection of the soft tissue. Classically, it is attributed to bacterial infection and immunocompromised patients are particularly vulnerable. However, NSTI due to fungal infection rarely does occur, including from Candida species, and can pose a diagnostic challenge for unfamiliar providers. Expedient clinical recognition, surgical debridement, fungal tissue culture, and initiation of antifungal therapy are key. CASE PRESENTATION: We report a 39-year-old obese male with long-standing history of poorly controlled diabetes who presented to a community hospital, noted to have NSTI of the sacrum, bilateral buttocks, and left hip, and was treated only with antibiotics. After transfer to an academic center, the patient underwent aggressive debridement and tissue diagnosis of Candida glabrata NSTI was made. He received broad-spectrum antibiotic and antifungal therapy for several months. Over the course of 4 months, his infection was cleared, and his large tissue defects were reconstructed with rotation flaps and the patient was discharged home. CONCLUSIONS: Fungal NSTI is a rare entity, especially when due to Candida species. It can be exceedingly difficult to diagnose and manage, as these patients may suffer higher mortality than those with NSTI due to bacteria. A high index of suspicion for the entity, rapid debridement, intraoperative tissue culture, and treatment with appropriate antifungal therapy offers the greatest chance of survival.

Voucher-Based Kidney Donation and Redemption for Future Transplant.

Importance: Policy makers, transplant professionals, and patient organizations agree that there is a need to increase the number of kidney transplants by facilitating living donation. Vouchers for future transplant provide a means of overcoming the chronological incompatibility that occurs when the ideal time for living donation differs from the time at which the intended recipient actually needs a transplant. However, uncertainty remains regarding the actual change in the number of living kidney donors associated with voucher programs and the capability of voucher redemptions to produce timely transplants. Objective: To examine the consequences of voucher-based kidney donation and the capability of voucher redemptions to provide timely kidney allografts. Design, Setting, and Participants: This multicenter cohort study of 79 transplant centers across the US used data from the National Kidney Registry from January 1, 2014, to January 31, 2021, to identify all family vouchers and patterns in downstream kidney-paired donations. The analysis included living kidney donors and recipients participating in the National Kidney Registry family voucher program. Exposures: A voucher was provided to the intended recipient at the time of donation. Vouchers had no cash value and could not be sold, bartered, or transferred to another person. When a voucher was redeemed, a living donation chain was used to return a kidney to the voucher holder. Main Outcomes and Measures: Deidentified demographic and clinical data from each kidney donation were evaluated, including the downstream patterns in kidney-paired donation. Voucher redemptions were separately evaluated and analyzed. Results: Between 2014 and 2021, 250 family voucher-based donations were facilitated. Each donation precipitated a transplant chain with a mean (SD) length of 2.3 (1.6) downstream kidney transplants, facilitating 573 total transplants. Of those, 111 transplants (19.4%) were performed in highly sensitized recipients. Among 250 voucher donors, the median age was 46 years (range, 19-78 years), and 157 donors (62.8%) were female, 241 (96.4%) were White, and 104 (41.6%) had blood type O. Over a 7-year period, the waiting time for those in the National Kidney Registry exchange pool decreased by more than 3 months. Six vouchers were redeemed, and 3 of those redemptions were among individuals with blood type O. The time from voucher redemption to kidney transplant ranged from 36 to 155 days. Conclusions and Relevance: In this study, the family voucher program appeared to mitigate a major disincentive to living kidney donation, namely the reluctance to donate a kidney in the present that could be redeemed in the future if needed. The program facilitated kidney donations that may not otherwise have occurred. All 6 of the redeemed vouchers produced timely kidney transplants, indicating the capability of the voucher program.

Evaluation of Bowel Function Following Radical Cystectomy and Urinary Diversion Using Two Validated Questionnaires: What Are the Effects on Quality of Life?

OBJECTIVE: To assess both short- and long-term constipation symptoms and their impact on quality of life in patients who underwent radical cystectomy (RC) with three different types of urinary diversion: orthotopic neobladder (ONB), continent cutaneous diversion (CCD), and ileal conduit (IC). MATERIALS AND METHODS: The validated Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires were administered to all patients at follow-up greater than 30 days from surgery. Clinical and pathological characteristics were prospectively recorded in an institutional review board approved bladder cancer database. Using multivariable linear regression analyses, we determined significant predictors of improved constipation symptoms and quality of life scores. RESULTS: A total of 198 patients completed 255 PAC-SYM and PAC-QOL questionnaires with a median follow-up time of 1.7 years (IQR: 0.7 - 3.0 years). ONB, CCD, and IC were performed in 78%, 5.5%, and 16.5% of patients, respectively. Higher bowel function scores (i.e. worse symptoms) were noted at 3 months post-operatively, while these scores significantly improved over time for PAC-SYM total score (P = .004), abdominal subscore (P = .001), and rectal subscore (P = .018). On multivariable analysis, we found that patients <70 years old (B -2.1, P = .004), with follow-up >1 year (B -4.8, P = .001), and who received an IC (B -2.4, P = .02) had significantly lower PAC-SYM scores. CONCLUSION: Patients have few constipation symptoms and are overall satisfied with their bowel function at long-term follow-up after RC. While patients with IC have significantly fewer constipation symptoms compared to those with ONB or CCD, all patients had significant improvement one year after the surgery.

Imaging of vascular malformations with a high-intensity focused ultrasound probe for treatment planning.

OBJECTIVE: We aimed to investigate whether a current commercially available high-intensity focused ultrasound (HIFU) probe can adequately image targeted vascular malformations (VMs) in anticipation of HIFU treatment planning and delivery. METHODS: We enrolled 10 consecutive patients who were scheduled to undergo treatment of symptomatic peripheral VMs confirmed by routine preoperative contrast-enhanced magnetic resonance imaging and soft tissue duplex ultrasound. The lesions were situated no more than 6 cm from the skin. After induction of general anesthesia and before surgical intervention, we prepared and positioned the Sonablate HIFU probe (SonaCare Medical, LLC, Charlotte, NC) to obtain multiple B-mode images of the targeted VM in the transverse and longitudinal dimensions. We then rated the quality of the images and the feasibility of the imaging process itself using a previously devised questionnaire aimed at evaluating the adequacy of the images for potential HIFU treatment planning and delivery. The patients subsequently underwent surgical intervention and clinical follow-up for their VM per the standard protocol. RESULTS: The study included 10 participants aged 21 to 67 years (mean ± standard deviation, 36.5 ± 16.5 years). Six patients (60%) identified as female. The VMs imaged consisted of eight venous (80%), one lymphatic (10%), and one combined lymphovenous (10%) malformation. The lesions were in the extremities only (50%), trunk only (20%), trunk and extremities (20%), or neck and extremities (10%). Pain related to the VM was present in all 10 patients (100%). In all 10 patients, the boundary and location of the VM could be visualized via the HIFU probe despite the diminished B-mode imaging resolution. The absence of Doppler functionality in the HIFU probe did not prevent the identification of the VMs in any patient up to a depth of 6 cm. The results from the postimaging survey showed that difficulty in preparing the study device for imaging was 1.1 ± 0.3 and difficulty in use was 1.1 ± 0.1, with a score of 1 equal to easy and 5 to difficult. The stability of the acoustic coupling to the patient was 1.3 ± 0.2, with a score of 1 representing very stable. CONCLUSIONS: We were able to ultrasonically identify and outline all targeted peripheral VMs using a commercially available HIFU probe in anticipation of treatment planning and delivery. Baseline magnetic resonance imaging and soft tissue duplex ultrasound remain essential tools for guiding probe placement and HIFU imaging.

Impact of Pelvic Lymph Node Dissection and Its Extent on Perioperative Morbidity in Patients Undergoing Radical Prostatectomy for Prostate Cancer: A Comprehensive Systematic Review and Meta-analysis.

CONTEXT: Pelvic lymph node dissection (PLND) yields the most accurate staging in patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), although it can be associated with morbidity. OBJECTIVE: To systematically evaluate the impact of PLND extent on perioperative morbidity in patients undergoing RP. A new PLND-related complication assessment tool is proposed. EVIDENCE ACQUISITION: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was conducted. MEDLINE/PubMed, Scopus, Embase and Web of Science databases were searched to yield studies discussing perioperative complications following RP and PLND. The extent of PLND was classified according to the European Association of Urology PCa guidelines. Studies were categorized according to the extent of PLND. Intra- and postoperative complications were classified as "strongly," "likely," or "unlikely" related to PLND. Anatomical site of perioperative complications was recorded. A cumulative meta-analysis of comparative studies was conducted using Review Manager 5.3 (Cochrane Collaboration, Oxford, UK). EVIDENCE SYNTHESIS: Our search generated 3645 papers, with 176 studies meeting the inclusion criteria. Details of 77 303 patients were analyzed. Of these studies, 84 (47.7%), combining data on 28 428 patients, described intraoperative complications as an outcome of interest. Overall, 534 (1.8%) patients reported one or more intraoperative complications. Postoperative complications were reported in 151 (85.7%) studies, combining data on 73 629 patients. Overall, 10 401 (14.1%) patients reported one or more postoperative complication. The most reported postoperative complication strongly related to PLND was lymphocele (90.6%). The pooled meta-analysis revealed that RP + limited PLND/standard PLND had a significantly decreased risk of experiencing any intraoperative complication (risk ratio [RR]: 0.55; p = 0.01) and postoperative complication strongly related to PLND (RR: 0.46; p = <0.00001), particularly for lymphocele formation (RR: 0.52; p = 0.0003) and thromboembolic events (RR: 0.59; p = 0.008), when compared with extended/superextended PLND. The extent of PLND was confirmed to be an independent predictor of lymphocele formation (RR: 1.77; p < 0.00001). CONCLUSIONS: The perioperative morbidity of PLND in patients undergoing RP and PLND for PCa significantly correlates with the extent of PLND. More standardized reporting of intra- and postoperative complications is needed to better estimate the direct impact of PLND extent on perioperative morbidity. PATIENT SUMMARY: Pelvic lymph node dissection (PLND) is the most accurate method for staging in patients undergoing radical prostatectomy for prostate cancer, although it can be associated with complications. This study aims to systematically evaluate the impact of PLND extent on perioperative complications in these patients. We found that intra- and postoperative complications correlate significantly with the extent of PLND. A more rigorous assessment and thorough reporting of perioperative complications are recommended.

Consulting 'Dr. Google' for minimally invasive urological oncological surgeries: A contemporary web-based trend analysis.

PURPOSE: To determine web-based public interest in minimally invasive surgery (MIS) specifically for urological oncological surgical procedures and how interest in robotics and laparoscopy compares over time. MATERIALS AND METHODS: Worldwide search-engine trend analysis included electronic Google queries of MIS urologic options from January 2004 to August 2019, worldwide. Join-point regression was performed. Comparison of annual relative search volume (ARSV) and average annual percentage change (AAPC) were analysed to assess loss or gain of interest. Evaluations were made regarding 1) penetrance of interest for MIS in Urology; 2) how MIS urologic procedures compared over time; and 3) which were the top related queries to searches for urologic oncology procedures. RESULTS: Increased interest was found for all of the MIS procedures evaluated. Mean ARSV for robotic approach was higher for the search term 'prostatectomy" (44.8 vs. 13.5; p < 0.001) and 'partial nephrectomy" (27.1 vs.11.5; p = 0.02). No statistical difference was found for the search terms 'cystectomy" or 'nephrectomy". The analysis of mean (∆-ARSV) of MIS procedures measured between the first and last 12 months of the study period showed an increased interest with a more pronounced ∆-ARSV for robotic procedures. The top related searches for all surgical procedures were examined showing an increasing inquisitiveness with regards of type of urological cancers, treatment options, type of surgery and prognostic outcomes. CONCLUSIONS: People are increasingly searching the web for MIS urological procedures. A growing appeal for robotics is demonstrated, especially for prostatectomy and partial nephrectomy where the robotic approach is gaining traction, suggesting a shift in mind-set amongst people seeking urological healthcare information.

Discrepancies in the Recommended Management of Adrenal Incidentalomas by Various Guidelines.

PURPOSE: Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of Health consensus statement, there are still discrepancies in the most recent guidelines from organizations representing endocrinology, endocrine surgery, urology and radiology. We review recent guidelines across the specialties involved in diagnosing and treating adrenal incidentalomas, and discuss points of agreement as well as controversy among guidelines. MATERIALS AND METHODS: PubMed®, Scopus®, Embase™ and Web of Science™ databases were searched systematically in November 2019 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify the most recently updated committee produced clinical guidelines in each of the 4 specialties. Five articles met the inclusion criteria. RESULTS: There is little debate among the reviewed guidelines as to the initial evaluation of an adrenal incidentaloma. All patients with a newly discovered adrenal incidentaloma should receive an unenhanced computerized tomogram and hormone screen. The most significant points of divergence among the guidelines regard reimaging an initially benign appearing mass, repeat hormone testing and management of an adrenal incidentaloma that is not easily characterized as benign or malignant on computerized tomography. The guidelines range from actively recommending against any repeat imaging and hormone screening to recommending a repeat scan as early as in 3 to 6 months and annual hormonal screening for several years. CONCLUSIONS: After reviewing the guidelines and the evidence used to support them we posit that best practices lie at their convergence and have presented our management recommendations on how to navigate the guidelines when they are discrepant.