Regulation of bladder dynamic elasticity: a novel method to increase bladder capacity and reduce pressure using pulsatile external compressive exercises in a porcine model.

PURPOSE: Dynamic elasticity is a biomechanical property of the bladder in which muscle compliance can be acutely adjusted through passive stretches and reversed with active contractions. The aim of this study was to determine if manipulating dynamic elasticity using external compression could be used as a novel method to acutely increase bladder capacity and reduce bladder pressure in a porcine model. METHODS: Ex vivo experiment: bladders underwent continuous or pulsatile compression after establishing a reference pressure at bladder capacity. Bladders were then filled back to the reference pressure to determine if capacity could be acutely increased. In-vivo experiments: bladders underwent five cycles of pulsatile external compression with ultrasound confirmation. Pre and post-compression pressures were measured, and pressure was measured again 10 min post-compression. RESULTS: Ex vivo experiment: pulsatile compression demonstrated increased bladder capacity by 16% (p = 0.01). Continuous compression demonstrated increased capacity by 9% (p < 0.03). Comparison of pulsatile to continuous compression showed that the pulsatile method was superior (p = 0.03). In-vivo experiments: pulsatile external compression reduced bladder pressure by 19% (p < 0.00001) with a return to baseline 10 min post-compression. CONCLUSIONS: These results suggest that regulation of bladder dynamic elasticity achieved with external compression can acutely decrease bladder pressure and increase bladder capacity. Pulsatile compression was found to be more effective as compared to continuous compression. These results highlight the clinical potential for use of non-invasive pulsatile compression as a therapeutic technique to increase bladder capacity, decrease bladder pressure, and reduce the symptoms of urinary urgency.

A preliminary study of bilateral color mapping of pig bladder vasculature demonstrates potential for acute hemi-ischemic events.

BACKGROUND: Chronic ischemia is a known risk factor for the development of lower urinary tract symptoms (LUTS) and bladder hypocontractility. Less is known, however, about the impact of acute ischemia. Classic teaching suggests that collateral circulation is robust in the bladder and, therefore, loss of a single source of blood flow should have no deleterious effect. This study aims to provide visual evidence that segmental vascular supply is critical for maintaining adequate perfusion to the bladder. METHODS: Ex vivo pig bladders were cannulated bilaterally in the superior vesical arteries and perfused using contrasting red and green dye. Images were collected at each step of the perfusion dyeing process and these images were analyzed using a custom program to calculate the average hue of each side. Statistical analysis was performed using Student's t-test. RESULTS: The two halves being perfused by separate arteries showed a statistically significant difference when compared (P<0.05) on both the outer wall (n=9) and in the mucosal layer (n=4). On the outside wall, the average normalized hue of the green halves was 27.5°±14.3°, while the average normalized hue of the red halves was -58.7°±3.1°. In the mucosa, the average normalized hue of the green halves was 34.5°±17.4°, while the average normalized hue of the red halves was -51.5°±3.5°. CONCLUSIONS: This study identified a novel color mapping method to study pig bladder vascular supply. The results demonstrated a lack of collateral blood flow, highlighting the possibly of acute hemi-ischemic event. However, further research in the effect of acute ischemia on bladder function is necessary.

Simplified PADUA Renal (SPARE) Nephrometry Scoring System: External Validation, Interobserver Variability, and Comparison with RENAL and PADUA in a Single-center Robotic Partial Nephrectomy Series.

BACKGROUND: The RENAL (radius [R], exophytic/endophytic [E], nearness to collecting system/sinus [N], anterior/posterior [A], and location relative to polar lines [L]) and the PADUA (preoperative aspects and dimensions used for an anatomical classification) scores help in quantifying tumor complexity. However, nephrometry scoring systems have low interobserver variability. To simplify and improve score reproducibility, a new Simplified PADUA Renal (SPARE) scoring system was introduced. OBJECTIVE: To externally validate the SPARE nephrometry scoring system and to determine its interobserver variability. DESIGN, SETTING, AND PARTICIPANTS: A total of 202 patients were included in the analysis. We performed a retrospective analysis of robot-assisted partial nephrectomy (RAPN) cases for a single renal mass performed at a single academic institution during the period 2008-2018. For each renal mass, PADUA, RENAL, and SPARE nephrometry scores were calculated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three urology residents (URs), two urology attendings (UAs), two radiology residents (RRs), and one radiology attending (RA) retrospectively reviewed computed tomography scans blinded to clinical outcomes. The accuracy of the SPARE nephrometry score in the prediction of any complication (Clavien grade ≥1) was compared with other scoring systems in a univariable and a multivariate fashion. The area under the curve (AUC) and kappa statistics were used to assess interobserver variability of the SPARE score. RESULTS AND LIMITATIONS: The SPARE score was not inferior to the PADUA and RENAL scores (AUC 0.61, 0.59, and 0.57, respectively, p = 0.43). Patients with intermediate to high SPARE scores had longer operative time (158 vs 135 min, p = 0.10) and a higher rate of complications (28% vs 14%, p = 0.012). Univariable analysis predicting overall complications showed that RRs performed slightly better than URs and UAs using the SPARE score. Interobserver agreement was 84% between an RA and an RR (kappa 0.42), 85% between an RA and a UA (kappa 0.39), and 85% between an RA and a UR (kappa 0.45). CONCLUSIONS: These findings confirm that the SPARE nephrometry scoring system is a reproducible and easy tool offering overall fair interobserver agreement regardless of years of training or type of practice, while maintaining the predictive capabilities of more established nephrometry scores. PATIENT SUMMARY: In this study, a novel and simple classification system was assessed using a sample of cases from our institution to define surgical complexity renal masses detected on radiological imaging. Our findings suggest that this tool can be useful in clinical practice to facilitate the characterization of renal masses and predict the complications of surgical treatment.

Phases of decompensation during acute ischemia demonstrated in an ex vivo porcine bladder model.

BACKGROUND: The aim of this project was to develop an ex-vivo porcine bladder model to test the effects of increasing durations of acute ischemia on detrusor function. METHODS: Porcine bladders were perfused through bilateral vesical arteries at physiologic flow (4 mL/min) and filled through a urethral catheter. Intravesical pressures were continuously recorded using standard urodynamics equipment. Bladder contractions, with simulated voiding, were induced by arterial infusion of KCl at 250 mL. Total, passive, and active pressures were recorded for each contraction and data were normalized to the control fill. Bladders underwent the following perfusion protocol by adjusting the arterial flow rates: Equilibration (4 mL/min), control (4 mL/min), partial ischemia (2 mL/min), global ischemia (0 mL/min) and reperfusion (4 mL/min). Perfusion periods were held for 15 min for one group and 30 min for another group of bladders. RESULTS: Porcine bladders (N=19) including 8 (15 min group) and 11 (30 min group) were used. With 15 min ischemia, passive pressure increased 39% (P=0.03) and the active pressure decreased 23% (P=0.002). Total pressure remained constant, identifying a compensated phase. Values returned to baseline with reperfusion. With 30 min ischemia, passive pressure remained unchanged. However, there was a decrease in total pressure 34% (P<0.001) and active pressure 61% (P<0.001), which incompletely recovered to baseline values, identifying a decompensated phase with incomplete recovery upon reperfusion. CONCLUSION: In the porcine bladder, 15 min ischemia resulted in a compensated phase and 30 min ischemia resulted in a decompensated phase of detrusor function. This study provides mechanistic insight into the natural history of ischemia-mediated voiding dysfunction.

Focal therapy for prostate cancer: recent advances and future directions.

Prostate cancer is the most frequently diagnosed cancer in men after skin cancer. Owing to the rising popularity of prostate-specific antigen screening, large numbers of patients are receiving a diagnosis of prostate cancer and undergoing whole-gland treatment. Some patients with a diagnosis of low-risk, localized disease may not benefit from whole-gland treatment, however, given its known morbidity. In response to advances in prostate imaging and evidence suggesting that the prognosis in prostate cancer is related to the index lesion, many patients have begun to opt for focal therapy, which targets a lesion rather than the entire prostate. This "middle ground" of therapy, between active surveillance and whole-gland treatment, is appealing to patients because the risk for side effects is believed to be lower with focal therapy than with whole-gland treatment. This review discusses the oncologic rationale for focal therapy in localized prostate cancer, examines the major therapy modalities, and addresses future directions.

Outcomes and predictors of benign histology in patients undergoing robotic partial or radical nephrectomy for renal masses: a multicenter study.

INTRODUCTION: Theaim of this study was to assess preoperative factors associated with benign histology in patients undergoing surgical removal of a renal mass and to analyze outcomes of robotic partial nephrectomy (PN) and radical nephrectomy (RN) for these masses. MATERIAL AND METHODS: Overall, 2,944 cases (543 benign and 2,401 malignant) who underwent robotic PN and RN between 2003-2018 at 10 institutions worldwide were included. The assessment of the predictors of benign histology was made at the final surgical pathology report. Descriptive statistics, Mann-Whitney U, Pearson's χ2, and logistic regression analysis were used. RESULTS: Patients in the benign group were mostly female (61 vs. 33%; p <0.001), with lower body mass index (BMI) (26.0 vs. 27.1 kg/m2; p <0.001). The benign group presented smaller tumor size (2.8 vs. 3.5 cm; p <0.001), R.E.N.A.L. score (6.0 vs. 7.0; p <0.001). There was a lower rate of hilar (11 vs.18%; p = 0.001), cT≥3 (1 vs. 4.5%; p <0.001) tumors in the benign group. There was a statistically significant higher rate of PN in the benign group (97 vs. 86%; p <0.001) as well as a statistically significant lower 30-day re-admission rate (2 vs. 5%; p = 0.081). Multivariable analysis showed male gender (OR: 0.52; p <0.001), BMI (OR: 0.95; p <0.001), and cT3a (OR: 0.22; p = 0.005) to be inversely associated to benign histology. CONCLUSIONS: In 18% of cases, a benign histologic type was found. Only 3% of these tumors were treated with RN. Female gender, lower BMI, and higher T staging showed to be independent predictors of benign histology.

Bladder volume correction factors measured with 3D ultrasound and BladderScan.

INTRODUCTION: The aim of this study was to investigate conventional 3D ultrasound and portable BladderScan volume measurements and implement correction factors to ensure accurate volume metrics. MATERIALS AND METHODS: Healthy participants without urinary urgency were recruited for a prospective hydration study in which three consecutive voids were analyzed for two separate visits. Just before and after voiding, 3D ultrasound and BladderScan volumes were measured. Estimated voided volumes were calculated as the volume immediately prior to void minus any post void residual and were compared to actual voided volumes measured using a graduated container. Percent errors were calculated, and an algebraic method was implemented to create correction factors for 3D ultrasound and BladderScan. RESULTS: Sixteen individuals completed the study, and six voids were recorded for each participant. A total of 96 volume measurements ranging from 0 mL to 1050 mL with an average of 394 +/- 26 mL were analyzed. Both 3D ultrasound and BladderScan significantly underestimated voided volumes with averages of 296 +/- 22 and 362 +/- 27, respectively. Average percent error for the 3D ultrasound group was 30.1% (pre-correction) and 20.7% (post-correction) (p < 0.01) and 22.4% (pre-correction) and 21.8% (post-correction) for the BladderScan group (p = 0.20). The voided volume correction factors for 3D ultrasound and BladderScan were 1.30 and 1.06, respectively. CONCLUSION: BladderScan and 3D ultrasound typically underestimate voided volumes. Correction factors enabled more accurate measurements of voided volumes for both 3D ultrasound and BladderScan. Accurate volume measurements will be valuable for the development of non-invasive urodynamics techniques.

An external compress-release protocol induces dynamic elasticity in the porcine bladder: A novel technique for the treatment of overactive bladder?

INTRODUCTION: Dynamic elasticity is an acutely regulated bladder material property through which filling and passive emptying produce strain softening, and active voiding restores baseline pressure. The aim of this study was to test the hypothesis that strain softening produced by filling-passive emptying is equivalent to that produced by compression-release in a porcine bladder model. METHODS/MATERIALS: Latex balloons and ex vivo perfused pig bladders were used for a series of alternating fill-passive emptying ("Fill") and external compress-release ("Press") protocols. For the Fill protocol balloons/bladders were (1) filled to defined volumes (prestrain softening), (2) filled to capacity to strain soften (reference), and (3) passively emptied to the original volume (poststrain softening). For the Press protocol, balloons/bladders were (1) filled to defined volumes (prestrain softening), (2) externally compressed to reference pressure and then released for five cycles (poststrain softening). After each protocol, bladders were voided with high-KCl buffer to induce "active" voiding. RESULTS: In both balloons and porcine bladder, both the Fill and Press protocols produced significant strain softening (P < 0.05) and poststrain softening pressures were not different for Fill and Press protocols (P > 0.05), indicating a similar degree of strain softening with both methods. CONCLUSIONS: Repeated external compression can induce bladder strain softening similar to filling and passive emptying. This technique may represent a means to acutely regulate bladder compliance and potentially be used as a mechanical treatment for urinary urgency.

Trifecta Outcomes in Multifocal Tumors: A Comparison Between Robotic and Open Partial Nephrectomy.

OBJECTIVES: To report a comparative analysis of outcomes in patients who underwent multiple excisions for unilateral synchronous multifocal renal tumors using both open and robotic approaches. METHODS: We retrospectively reviewed 110 patients who underwent robotic and open partial nephrectomy and had multiple tumor excisions in an ipsilateral kidney. "Trifecta" was defined as negative surgical margins, no urologic complications, and a glomerular filtration rate (GFR) preservation of ≥90% at last follow-up. Inverse probability of treatment weighting (IPTW) was applied to equilibrate treatment groups, minimize selection bias, and optimize inference on the basis of each patient's clinicodemographic characteristics. RESULTS: Sixty-eight robotic and 42 open patient approaches had sufficient data for IPTW. After weighting, there were no statistical differences in baseline characteristics between the two groups. On adjusted analyses, robotic partial nephrectomy achieved equivalent rates of trifecta to open surgery (16.3% vs 16.5%, p = 0.99), which persisted on subgroup analyses of patients with two (20.1% vs 23.7%, p = 0.82) or more than two tumors (6.8% vs 7.4%, p = 0.95). There were no differences between robotic and open cohorts for negative margin rates, absence of complications, or GFR ≥90%. The robotic cohort had a shorter mean length of stay (3.4 vs 4.9 days, p < 0.001). CONCLUSIONS: Surgical resection remains the mainstay for patients with unilateral, synchronous, and multifocal renal tumors. Our analysis found that both open and robotic approaches to partial nephrectomy are equally likely to achieve the "trifecta" outcome in an equilibrated high-risk group of patients. The robotic approach for these complex patients may be safe and feasible for a carefully selected group of patients.

Robot-assisted ureteral reconstruction - current status and future directions.

Robotic surgery in the treatment in certain urological diseases has become a mainstay. With the increasing use of the robotic platform, some surgeries which were historically performed open have transitioned to a minimally invasive technique. Recently, the robotic approach has become more utilized for ureteral reconstruction. In this article, the authors review the surgical techniques for a number of major ureteral reconstuctive surgeries and briefly discuss the outcomes reported in the literature.

Testicular seminoma: oncologic rationale and role of surgery in treatment.

Seminomas account for approximately 50% of all cases of testicular cancer. Testicular cancer is a highly curable disease that can be broadly classified as either seminomatous or nonseminomatous; the management and treatment of the 2 forms vary widely. Although surgery plays a large role in the management of nonseminoma, its role in the management of seminoma is much more limited. Most clinicians in the United States choose orchiectomy followed by surveillance for patients with stage I seminomatous disease, and chemotherapy or radiation-followed by surgery for the management of residual masses-for patients with disease that is stage II and higher. Recently, clinicians have proposed a larger role for surgery in stage II seminoma to avoid the long-term toxic effects of chemotherapy and radiation therapy. In this review, we discuss the oncologic rationale for the treatment of seminoma, the role of surgery, and the use of minimally invasive operative techniques for retroperitoneal lymph node dissection.

Defining Field Cancerization of the Skin Using Noninvasive Optical Coherence Tomography Imaging to Detect and Monitor Actinic Keratosis in Ingenol Mebutate 0.015%- Treated Patients.

OBJECTIVE: The objective of this study was to assess the ability of optical coherence tomography to detect clinical and subclinical actinic keratoses confirmed by histopathology. The efficacy of ingenol mebutate treatment of actinic keratosis was also evaluated using optical coherence tomography, and correlation of treatment efficacy with severity of local skin reactions was determined. DESIGN: Single-arm, open-label, split-face study. SETTING: Hospital outpatient clinic. PARTICIPANTS: Male subjects (N=30) with seven actinic keratoses. MEASUREMENTS: A suspected actinic keratosis and the normal-appearing, perilesional skin were imaged, biopsied for histopathologic analysis, and the results compared with the clinical and a blinded optical coherence tomography diagnosis. Treatment with ingenol mebutate gel 0.015% was randomly administered to three clinically suspected actinic keratoses and the perilesional skin; three additional, suspected actinic keratoses lesions and perilesional areas were left untreated. Clinical and optical coherence tomography images were obtained for all lesions. Severity of local skin reactions was recorded to evaluate the relationship between local skin reaction and treatment effect. RESULTS: Optical coherence tomography analysis had a 100-percent (28/28) correlation with the clinical diagnosis of actinic keratosis and detected 16 of 22 (73%) histopathologically confirmed subclinical lesions from perilesional skin sites. By optical coherence tomography assessment, the clearance rate for clinically observed lesions was 76 percent for ingenol mebutate-treated areas versus 11 percent for untreated areas; the clearance rate for treated subclinical lesions was 88 percent versus 43 percent for untreated areas. Clearance rates did not vary with the severity of the local response. CONCLUSION: Optical coherence tomography is effective at detecting clinical and subclinical actinic keratoses and monitoring their response to treatment.

Differentiation of Basal Cell Carcinoma Subtypes in Multi-Beam Swept Source Optical Coherence Tomography (MSS-OCT).

BACKGROUND: Optical coherence tomography (OCT) is a technique that enables real-time in-vivo examination of tissue. This technology provides the clinician with the potential to use a non-invasive tool in the identification and diagnosis of many skin lesions. However, the diagnostic features of basal cell carcinoma have not yet been described with comparison to their histopathology.
OBJECTIVES: To identify and describe key features of basal cell carcinoma (BCC) and its subtypes as they present in multi-beam Swept Source - OCT (MSS-OCT), and to correlate those against conventional histopathology.
METHODS: A total of 40 lesions were assessed by MSS-OCT prior to biopsy. 60-slice OCT images of the lesions were obtained and correlated with histology sections taken in the same plane. OCT scans were assessed retrospectively by a panel to determine the OCT criteria for BCC and its subtypes.
RESULTS: The following diagnostic criteria were identified: hyporeflective ovoid structures (40/40), dark halo boundaries (38/40), epidermal thinning (28/40), and collagen compression (14/40). Lesional tissue also showed a destruction of layers when compared to the surrounding normal tissue. In addition to the shared criteria, other subtypes showed distinct diagnostic criteria.
CONCLUSION: With its higher sensitivity, using MSS-OCT allowed for non-invasive, accurate identification of the key diagnostic features of BCC and its subtypes with high correlation to the histopathologic features found with biopsy.

J Drugs Dermatol. 2016;15(5):545-550.

Comparison of Renal Cell Carcinoma Surveillance Guidelines: Competing Trade-Offs.

PURPOSE: We estimated the differences in intensity, cost, radiation exposure and cancer control of published surveillance guidelines screening for secondary renal cell carcinoma in patients treated with partial nephrectomy. MATERIALS AND METHODS: We developed a Monte Carlo simulation model to contrast the existing guidelines in terms of cost, radiation exposure and cancer control. Model inputs were extrapolated from the existing literature. Surveillance guidelines were analyzed from the AUA, CUA, EAU and NCCN®. Risk stratification among patients treated with partial nephrectomy was based on tumor characteristics. RESULTS: Expected costs during the 5 years after partial nephrectomy were $587 (CUA), $1,076 (AUA), $1,705 (EAU) and $1,768 (NCCN) for low risk patients, and $903 (CUA), $2,525 (EAU) and $3,904 (AUA and NCCN) for high risk patients. Radiation exposure ranged from 31.41 mSv (CUA) to 104.34 mSv (NCCN) for low risk patients and 46.88 mSv (CUA) to 231.61 mSv (AUA and NCCN) for high risk patients. The EAU and CUA guidelines led to the diagnosis of the highest percentage of low risk patients (more than 95%) while all guidelines diagnosed more than 92% of high risk patients with recurrence. CONCLUSIONS: Renal cell carcinoma surveillance guidelines differ greatly in terms of intensity, cost and radiation exposure. It is important for clinicians to adopt standardized surveillance strategies that limit unnecessary cost and radiation exposure without compromising cancer control.

Robotic Anterior Pelvic Exenteration for Bladder Cancer in Patient With Previous Kidney-Pancreas Transplantation.

INTRODUCTION: To demonstrate the feasibility of robotic anterior pelvic exenteration with intracoporeal ileal conduit for bladder cancer in a patient with previous kidney-pancreas transplantation. TECHNICAL CONSIDERATIONS: Technical considerations included avoiding injury to transplant graft, minimizing devascularization of transplant ureter, intracorporeal mobilization of bowel with pancreas graft, and positioning of ileal conduit. Surgical approach required multidisciplinary approach for surgical planning and medical management. CONCLUSION: The patient's preoperative serum creatinine was 1.22 ng/mL and was unchanged at 1.21 ng/mL 1 month following surgery. Total robotic console time was 4 hours and 21 minutes and estimated blood loss is 30 cc. There were no intraoperative complications. Final pathology demonstrated pT1N0 high-grade multifocal micropappilary urothelial cell carcinoma with carcinoma in situ, and all surgical margins were negative. Robotic anterior pelvic exenteration with intracorporeal urinary diversion for bladder cancer in patient with previous kidney-pancreas transplantation is a challenging but a feasible surgical technique that requires a multidisciplinary team and a low threshold to convert to open surgery.