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).

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.

The "oldest and coldest" shipped living donor kidneys transplanted through kidney paired donation.

To date, thousands of living donor kidneys have been shipped through kidney paired donation (KPD). To expand on this growing segment of living donor transplantation, we evaluated the effect of advanced age donation ("oldest kidneys") and prolonged cold ischemia time ("coldest kidneys") on graft function and survival using the National Kidney Registry database from February 2008 to May 2018. Donors were stratified by age at time of donation (<65 or ≥65 years) and kidneys were stratified by cold ischemia time (<16 or ≥16 hours). We evaluated delayed graft function and death-censored graft failure (DCGF) for up to seven posttransplant years. Of the 2363 shipped living donor kidney transplants, 4.1% of donors were ≥65 years and 6.0% of transplanted kidneys had cold ischemia times ≥16 hours. Delayed graft function and DCGF occurred in 5.2% and 4.7% of cases. There were no significant associations between delayed graft function and donor age (P = .947) or cold ischemia (P = .532). Donor age and cold ischemia time were not predictive of delayed graft function (OR = 0.86,1.20; P = .8, .6) or DCGF (HR = 1.38,0.35, P = .5, .1). These findings may alleviate concerns surrounding the utilization of kidneys from older donors or those originating from distant transplant centers.

Which Patients with Negative Magnetic Resonance Imaging Can Safely Avoid Biopsy for Prostate Cancer?

PURPOSE: We sought to determine whether there is a subset of men who can avoid prostate biopsy based on multiparametric magnetic resonance imaging and clinical characteristics. MATERIALS AND METHODS: Of 1,149 consecutive men who underwent prostate biopsy from October 2011 to March 2017, 135 had prebiopsy negative multiparametric magnetic resonance imaging with PI-RADS™ (Prostate Imaging Reporting and Data System) score less than 3. The detection rate of clinically significant prostate cancer was evaluated according to prostate specific antigen density and prior biopsy history. Clinically significant prostate cancer was defined as Grade Group 2 or greater. Multivariable logistic regression analysis was performed to identify predictors of nonclinically significant prostate cancer on biopsy. RESULTS: The prostate cancer and clinically significant prostate cancer detection rates were 38% and 18%, respectively. Men with biopsy detected, clinically significant prostate cancer had a smaller prostate (p = 0.004), higher prostate specific antigen density (p = 0.02) and no history of prior negative biopsy (p = 0.01) compared to the nonclinically significant prostate cancer cohort. Prostate specific antigen density less than 0.15 ng/ml/cc (p <0.001) and prior negative biopsy (p = 0.005) were independent predictors of absent clinically significant prostate cancer on biopsy. The negative predictive value of multiparametric magnetic resonance imaging for biopsy detection of clinically significant prostate cancer improved with decreasing prostate specific antigen density, primarily in men with prior negative biopsy (p = 0.001) but not in biopsy naïve men. Of the men 32% had the combination of negative multiparametric magnetic resonance imaging, prostate specific antigen density less than 0.15 ng/ml/cc and negative prior biopsy, and none had clinically significant prostate cancer on repeat biopsy. The incidence of biopsy identified, clinically significant prostate cancer was 18%, 10% and 0% in men with negative multiparametric magnetic resonance imaging only, men with negative multiparametric magnetic resonance imaging and prostate specific antigen density less than 0.15 ng/ml/cc, and men with negative multiparametric magnetic resonance imaging, prostate specific antigen density less than 0.15 ng/ml/cc and negative prior biopsy, respectively. CONCLUSIONS: We propose that a subset of men with negative multiparametric magnetic resonance imaging, prostate specific antigen density less than 0.15 ng/ml/cc and prior negative biopsy may safely avoid rebiopsy. Conversely prostate biopsy should be considered in biopsy naïve men regardless of negative multiparametric magnetic resonance imaging, particularly those with prostate specific antigen density greater than 0.15 ng/ml/cc.

Management of extraretroperitoneal masses in germ cell tumor.

PURPOSE OF REVIEW: Management of extraretroperitoneal (ERP) germ cell tumor (GCT) is a complex clinical scenario faced by urologic oncologists. This article reviews the indications and approach to management of ERP GCT masses. RECENT FINDINGS: ERP GCT management starts with chemotherapy, and for any residual masses, a careful consideration of surgical intervention versus salvage chemotherapy. Decision-making regarding residual ERP masses hinges on tumor markers, and also the anatomical location. These factors should be contextualized by the patient's risk for teratoma or active GCT, which will impact outcome and thus weigh on decision-making conversations with patients who have advanced disease. Technical challenges of surgical management in the postchemotherapy setting also apply in ERP mass resection. The risks of surgical management in the lung and liver, in particular, add special considerations for morbidity. Surgical resection is often the only recourse for a patient who may have chemoresistant disease and may be an important step in achieving cure. SUMMARY: Surgical management of ERP GCT requires multidisciplinary input, and the urologic oncologist can help guide management with particular emphasis on the indication, timing, and approach to surgical resection.

The Role of Urodynamics in the Pre-transplant Evaluation of Renal Transplant.

PURPOSE OF REVIEW: The goal of this study is to delineate the role of advanced urologic evaluation with urodynamics prior to renal transplantation. We seek to report on its indications, possible findings, and subsequent treatment pathways. RECENT FINDINGS: This body of literature is largely comprised of retrospective, single-site studies. Patient selection for urodynamics can be determined based on patient history and voiding symptoms. Many of these renal transplant patients have urodynamic abnormalities such as decreased bladder capacity and compliance. Appropriate treatment of these abnormalities allows for average rates of graft survival. Urodynamic evaluation is not needed in every renal transplant recipient. However, in patients with oliguria or bladder dysfunction, urodynamics can often reveal significant pathology. The well-selected patient with lower urinary tract symptoms may also benefit from urodynamic evaluation. Treatment options are widely variable, from observation to reconstructive surgery, and should be based on the patient and urodynamic findings.

Lessons From Leprosy: Peripheral Neuropathies and Deformities in Chronic Demyelinating Diseases.

In light of the World Health Organization's push to accelerate progress toward a leprosy-free world by 2020, it is fitting to look back on the evolution of progress in treating lepromatous neuropathy and limb deformities. To date, no surgeon has had as great an impact on the understanding and treatment of this disease as Dr Paul Brand. Before Dr Brand's accomplishments, few surgeons participated in the management of the deformed leprous patient. By challenging conventional beliefs, Dr Brand revealed that many of the deformities associated with leprosy were in fact caused by nerve damage and subsequent limb anesthesia. His pioneering work centered on tendon transfers to provide hand and foot mobility to leprous patients, revolutionizing the surgical management of this patient population and restoring functionality to the lives of otherwise stigmatized and functionally handicapped individuals. In the process, he provided us with the surgical principles and techniques that we still apply today. Because of its predilection for the peripheral nervous system, leprosy also provides an excellent opportunity to investigate mechanisms of demyelination and chronic nerve degeneration in nonacute peripheral neuropathies. Processes underlying demyelination of infectious, traumatic, and genetic etiologies overlap and precede the onset of acute neuronal derangement. Glial pathology has been shown to be a common pathological element in leprosy, Charcot-Marie-Tooth type I, multiple sclerosis, and chronic nerve compression injury. The aim of this article is to provide an overview of lepromatous neuropathy with its subsequent deformities as it relates to the pathophysiology, surgical management, and potential therapeutic targets of other modern peripheral neuropathies.

Focal Therapy Eligibility Determined by Magnetic Resonance Imaging/Ultrasound Fusion Biopsy.

PURPOSE: We assessed focal therapy eligibility in men who underwent multiparametric magnetic resonance imaging and targeted biopsy with correlation to whole mount histology after radical prostatectomy. MATERIALS AND METHODS: Subjects were selected from among the 454 men in whom targeted biopsy proven prostate cancer was derived from regions of interest on multiparametric magnetic resonance imaging from 2010 to 2016. Focal therapy eligibility was limited to a maximum Gleason score of 4 + 3 in regions of interest with or without other foci of low risk prostate cancer (Gleason score 3 + 3 and less than 4 mm). Men who did not meet NCCN® intermediate risk criteria were classified as ineligible for focal therapy. Of the 454 men 64 underwent radical prostatectomy and biopsy findings were compared to final pathology findings. RESULTS: Of the 454 men with a biopsy proven region of interest 175 (38.5%) were eligible for focal therapy. Fusion biopsy, which combined targeted and template biopsy, had 80.0% sensitivity (12 of 15 cases), 73.5% specificity (36 of 49) and 75.0% accuracy (48 of 64) for focal therapy eligibility. Targeted cores alone yielded 73.3% sensitivity (11 of 15 cases), 47.9% specificity (23 of 48) and 54.7% accuracy (35 of 64). Gleason score and extension across the midline differed in 4 and 9, respectively, of the 13 cases that showed discordant biopsy and whole mount histology. CONCLUSIONS: Using intermediate risk eligibility criteria more than a third of men with a targeted biopsy proven lesion identified on multiparametric magnetic resonance imaging would have been eligible for focal therapy. Eligibility determined by fusion biopsy was concordant with whole mount histology in 75% of cases. Improved selection criteria are needed to reliably determine focal therapy eligibility.

Three-Piece Inflatable Penile Prosthesis Placement Following Pelvic Radiation: Technical Considerations and Contemporary Outcomes.

BACKGROUND: Pelvic radiation is a known risk factor for the development and progression of erectile dysfunction. When medical therapy fails, the 3-piece inflatable penile prosthesis (IPP) can offer patients a definitive treatment option. Because of radiation-induced vascular changes and tissue fibrosis, a careful surgical approach is necessary to avoid intraoperative complications and attain successful outcomes. Despite its widespread use in prostate cancer treatment, there are no contemporary studies examining the effects that pelvic radiation can have on 3-piece IPP placement and device survival. AIM: To present technical considerations and contemporary outcomes of placing a 3-piece IPP for refractory erectile dysfunction in patients with a history of pelvic radiation. METHODS: We retrospectively reviewed 78 patients who underwent placement of a 3-piece IPP (AMS 700; Boston Scientific, Marlborough, MA, USA) after being treated with pelvic radiotherapy from 2003 through 2016. All patients had been treated with external beam and/or brachytherapy for treatment of prostate malignancy. An infrapubic approach was used in all patients, with reservoir placement in the space of Retzius or in the lateral retroperitoneal space. Patient demographics, perioperative data, and postoperative outcomes including prosthetic infection and mechanical failure were examined and statistical analysis was performed. OUTCOMES: Rates of device infection, revision surgery, and reservoir complications. RESULTS: No intraoperative complications were observed. After a mean follow-up of 49.0 months (6.6-116.8), 2 patients developed an infection of their prosthesis that required explantation. These patients underwent successful IPP removal and immediate reimplantation. 11 patients (14.1%) required revision surgery (pump replacement, n = 4; pump relocation, n = 2; cylinder replacement, n = 4; reservoir replacement owing to leak, n = 1). No reservoir-related complications such as herniation or erosion into adjacent structures were observed. CLINICAL IMPLICATIONS: The 3-piece IPP can be placed safely in a broad range of patients treated with pelvic radiotherapy. STRENGTHS AND LIMITATIONS: This study describes contemporary long-term outcomes of the IPP in patients treated with pelvic radiation and includes patients with prior pelvic surgery and artificial urinary sphincter, which are commonly encountered in practice. It is limited by its single-center experience and lacks a comparison group of patients. Objective patient satisfaction data were not available for inclusion. CONCLUSIONS: The 3-piece IPP can be placed successfully in patients with a history of pelvic radiation without a significant increase in infectious complications, reservoir erosion, or mechanical failure compared with the global literature. Loh-Doyle J, Patil MB, Nakhoda Z, et al. Three-Piece Inflatable Penile Prosthesis Placement Following Pelvic Radiation: Technical Considerations and Contemporary Outcomes. J Sex Med 2018;15:1049-1054.

Contrast-Enhanced Transrectal Ultrasound in Focal Therapy for Prostate Cancer.

PURPOSE OF REVIEW: Contrast-enhanced transrectal ultrasound (CeTRUS) is an emerging imaging technique in prostate cancer (PCa) diagnosis and treatment. We review the utility and implications of CeTRUS in PCa focal therapy (FT). RECENT FINDINGS: CeTRUS utilizes intravenous injection of ultrasound-enhancing agents followed by high-resolution ultrasound to evaluate tissue microvasculature and differentiate between benign tissue and PCa, with the latter demonstrating increased enhancement. The potential utility of CeTRUS in FT for PCa extends to pre-, intra- and post-operative settings. CeTRUS may detect PCa, facilitate targeted biopsy and aid surgical planning prior to FT. During FT, the treated area can be visualized as a well-demarcated non-enhancing zone and continuous real-time assessment allows immediate re-treatment if necessary. Following FT, the changes on CeTRUS are immediate and consistent, thus facilitating repeat imaging for comparison during follow-up. Areas suspicious for recurrence may be detected and target-biopsied. Enhancement can be quantified using time-intensity curves allowing objective assessment and comparison. Based on encouraging early outcomes, CeTRUS may become an alternative imaging modality in prostate cancer FT. Further study with larger cohorts and longer follow-up are needed.

Targeted Biopsy to Detect Gleason Score Upgrading during Active Surveillance for Men with Low versus Intermediate Risk Prostate Cancer.

PURPOSE: We sought to determine the rate of upgrading to Gleason score 4 + 3 or greater using targeted biopsy for diagnosis and monitoring in men undergoing active surveillance of prostate cancer. MATERIALS AND METHODS: Study subjects comprised all 259 men, including 196 with Gleason score 3 + 3 and 63 with Gleason score 3 + 4, who were diagnosed by magnetic resonance imaging/ultrasound fusion guided biopsy from 2009 to 2015 and underwent subsequent fusion biopsy for as long as 4 years of active surveillance. The primary end point was the discovery of Gleason score 4 + 3 or greater prostate cancer. Followup biopsies included targeting of positive sites, which were tracked in an Artemis™ device. Kaplan-Meier curves were generated to determine upgrading rates, stratified by initial Gleason score and prostate specific antigen density. RESULTS: Based on a Cox proportional hazard model, men with Gleason score 3 + 4 were 4.65 times more likely to have upgrading than men with an initial Gleason score of 3 + 3 at 3 years (p <0.01). By the third surveillance year 63% of men with Gleason score 3 + 4 had been upgraded compared with 18.0% who started with Gleason score 3 + 3 (p <0.01). Of all 33 upgrades 32 (97%) occurred at a magnetic resonance imaging visible or a tracked site of tumor, rather than at a previously negative systematic site. Independent predictors of upgrading were Gleason score 3 + 4, prostate specific antigen density 0.15 ng/ml/cm3 or greater and a grade 5 lesion on magnetic resonance imaging. The incidence rate ratio of upgrading (Gleason score 3 + 4 vs 3 + 3) was 4.25 per year of patient followup (p <0.01). CONCLUSIONS: During active surveillance of prostate cancer, targeting of tracked tumor foci by magnetic resonance imaging/ultrasound fusion biopsy allows for heightened detection of Gleason score 4 + 3 or greater cancers. Baseline variables directly related to important upgrading that warrant increased vigilance include Gleason score 3 + 4, prostate specific antigen density 0.15 ng/ml/cm3 or greater and grade 5 lesions on magnetic resonance imaging.

Chronic nerve compression alters Schwann cell myelin architecture in a murine model.

INTRODUCTION: Myelinating Schwann cells compartmentalize their outermost layer to form actin-rich channels known as Cajal bands. Herein we investigate changes in Schwann cell architecture and cytoplasmic morphology in a novel mouse model of carpal tunnel syndrome. METHODS: Chronic nerve compression (CNC) injury was created in wild-type and slow-Wallerian degeneration (Wld(S) ) mice. Over 12 weeks, nerves were electrodiagnostically assessed, and Schwann cell morphology was thoroughly evaluated. RESULTS: A decline in nerve conduction velocity and increase in g-ratio is observed without early axonal damage. Schwann cells display shortened internodal lengths and severely disrupted Cajal bands. Quite surprisingly, the latter is reconstituted without improvements to nerve conduction velocity. CONCLUSIONS: Chronic entrapment injuries like carpal tunnel syndrome are primarily mediated by the Schwann cell response, where decreases in internodal length and myelin thickness disrupt the efficiency of impulse propagation. Restitution of Cajal bands is not sufficient for remyelination after CNC injury.

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.

Testicular Torsion From Bell-clapper Deformity.

A 12-year-old otherwise healthy boy presents to a local emergency room with sudden onset, sharp, continuous left testicular pain for 9 hours, associated with nausea and vomiting. Exam and ultrasound is consistent with testicular torsion. During scrotal exploration, a bell-clapper deformity of the left testicle is appreciated, with a normal gubernacular attachment of the right testicle. Bell-clapper deformity is a congenital failure of the posterior attachment of the gubernaculum to the testis, which increases testicular mobility within the tunica vaginalis and predisposes individuals to testicular torsion.