Multipotent bone marrow cell-seeded polymeric composites drive long-term, definitive urinary bladder tissue regeneration.

To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies, including urinary diversion and bladder augmentation enterocystoplasty (BAE), utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist that need to be overcome in order to advance tissue-engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utility of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of an appropriate animal model for testing. In this study, we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold coseeded with autologous bone marrow-derived mesenchymal stem cells and CD34+ hematopoietic stem/progenitor cells support robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem-cell-seeded small-intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem-cell synergism promoted functional trilayer bladder tissue regeneration, including whole-graft neurovascularization, in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem-cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE.

Longitudinal Sociodemographic Analysis of Operative Circumcisions at Children's Hospitals.

OBJECTIVE: To characterize elective, post-neonatal operative circumcision at US children's hospitals, in the context of established sociodemographic disparities in access to neonatal circumcision. METHODS: A retrospective cohort study was performed of boys undergoing elective, operative circumcision at the 23 Pediatric Health Information System (PHIS) hospitals who contributed data from 2004-2018. Boys > = 36 months' and those with congenital anomalies of the penis were excluded. Bivariate statistics were used to compare the circumcision cohort to a referent cohort of boys undergoing other ambulatory surgery or having an observational hospital stay. RESULTS: The annual median number of operative circumcisions per hospital increased during the study (72 [IQR 54-162] to 136 [IQR 88-266], P = .003). Boys undergoing circumcision were mostly non-Hispanic White (46.7%) or non-Hispanic Black (30.9%), in the lowest income quartile (26.6%), from the Southern US (51.5%), and publicly-insured (60.5%). When compared to the reference cohort, boys undergoing circumcision were more likely to be non-Hispanic Black (30.9 vs 15.7%, P = .001) and publicly-insured (60.5 vs 45.9%, P = . 001). CONCLUSION: The number of post-neonatal operative circumcisions performed at US children's hospitals nearly doubled from 2004 to 2018. Study findings suggest an emerging healthcare disparity, with non-Hispanic Black boys of lower socioeconomic status undergoing more post-neonatal operative circumcisions that are more expensive and higher risk.

Safety and Efficacy of Robot-Assisted Laparoscopic Pyeloplasty Compared to Open Repair in Infants under 1 Year of Age.

PURPOSE: Robot-assisted laparoscopic pyeloplasty (RALP) use in children has increased, though many centers still favor open pyeloplasty (OP) in infants. This study aims to compare safety and efficacy of RALP and OP in infants. MATERIALS AND METHODS: A single-institution, retrospective cohort study of infants <1 year of age who underwent primary RALP or OP between January 2009 and June 2020 was performed. Primary outcomes were intraoperative and 30-day complications, postoperative radiographic improvement at last clinic visit, and operative failure leading to redo pyeloplasty. Multivariable logistic regression was performed for 30-day complications to adjust for demographic variation between groups. Survival analysis was performed to compare time to diagnosis of operative failure leading to redo pyeloplasty. RESULTS: Among 204 patients, 121 underwent OP and 83 underwent RALP (74.5% male). RALP patients were older (median 7.2 vs 2.9 months, p <0.001) and larger (median 8.2 vs 5.9 kg, p <0.001) than OP patients. Radiographic improvement was seen in 91.1% of RALP patients and 88.8% of OP patients at last visit. Median (interquartile range) followup in months was 24.4 (10.8-50.3) for the full cohort. In adjusted analysis, the odds of a 30-day complication (OR 0.40, 95% CI 0.08-2.00) was lower for RALP compared to OP, though not statistically significant. In survival analysis, there was no difference in time to diagnosis of operative failure and redo pyeloplasty between groups (p=0.65). CONCLUSIONS: RALP is a safe and effective alternative to OP for infants, with comparable intraoperative and 30-day complications, radiographic improvement at last followup, and risk of pyeloplasty failure.

Kidney, Ureteral, and Bladder Cancer: A Primer for the Internist.

Malignancies of the urinary tract (kidney, ureter, and bladder) are distinct clinical entities. Hematuria is a unifying common presenting symptom for these malignancies. Surgical management of localized disease continues to be the mainstay of treatment, and early detection is important in the prognosis of disease. Patients often require life-long follow-up and assessment for recurrence.

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.

Prostate Specific Antigen Nadir of 0.1 or Less Is a Predictor of Treatment Success in Men Undergoing Salvage Whole Prostate Gland Cryoablation.

PURPOSE: To assess factors that affect prostate biopsy results following salvage whole gland cryoablation. PATIENTS AND METHODS: One hundred seventy-four patients underwent prostate biopsy following salvage whole gland cryoablation of the prostate in the Cryo-OnLine Database registry. Wilcoxon rank-sum and χ2 tests and logistic regression analysis were used to assess predictors of positive biopsy. Prostate specific antigen (PSA) nadir was divided into a statistical tertile for comparisons between different nadir PSA cut points. RESULTS: Fifty-two of 174 (29.9%) of this highly select group of men who underwent biopsy had a posttreatment biopsy demonstrating malignant cancer. Men who had positive biopsy following salvage therapy had significantly higher median nadir PSA, shorter median time to prostate biopsy, and shorter median time to biochemical failure. Compared to the lowest tertile (PSA nadir defined as ≤0.1 ng/mL), PSA in the second tertile (0.11-0.8 ng/mL) and third tertile (>0.8 ng/mL) demonstrated increased odds ratio (OR) for positive biopsy, 4.34 (95% confidence interval [CI] 1.66, 11.4, p = 0.003) and 2.81 (95% CI 1.14, 7.00, p = 0.02), respectively, in adjusted models. In addition, men with a presalvage PSA >20 (OR 7.65; 95% CI 2.03, 28.9; p = 0.003) and Gleason score ≥8 (OR 2.26; 95% CI 0.93, 5.47; p = 0.07) had a higher OR of positive biopsy. CONCLUSIONS: Nadir PSA of 0.1 ng/mL or less following salvage cryotherapy is predictive of treatment success. Routine biopsy should be reserved for men with nadir PSA >0.1 ng/mL and patients with high risk features of prostate cancer before salvage cryoablation.

Gut microbiome and chronic prostatitis/chronic pelvic pain syndrome.

Analysis of the human microbiome continues to reveal new and previously unrealized associations between microbial dysbiosis and disease. Novel approaches to bacterial identification using culture-independent methods allow practitioners to discern the presence of alterations in the taxa and diversity of the microbiome and identify correlations with disease processes. While some of these diseases that have been extensively studied are well-defined in their etiology and treatment methods (colorectal cancer), others have provided much more significant challenges in both diagnosis and treatment. One such condition, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), has several etiological and potentiating contributions from infection, inflammation, central nervous system (CNS) changes, stress, and central sensitization-all factors that play important roles in the crosstalk between the human body and its microbiome. No singular cause of CP/CPPS has been identified and it is most likely a syndrome with multifactorial causes. This heterogeneity and ambiguity are sources of significant frustration for patients and providers alike. Despite multiple attempts, treatment of chronic prostatitis with monotherapy has seen limited success, which is thought to be due to its heterogeneous nature. Phenotypic approaches to both classify the disease and direct treatment for CP/CPPS have proven beneficial in these patients, but questions still remain regarding etiology. Newer microbiome research has found correlations between symptom scores and disease severity and the degree of dysbiosis in urine and gut (stool) microbiomes in these patients as compared to un-afflicted controls. These findings present potential new diagnostic and therapeutic targets in CP/CPPS patients.

Do Renin-Angiotensin Blockers Affect Renal Function and Cardiac Outcomes in Patients Undergoing Partial Nephrectomy?

PURPOSE: Currently no data exist to guide renal surgeons on the perioperative use of renin-angiotensin blockers despite potential cardiorenal benefits. We aimed to assess the impact of resuming renin-angiotensin blockers on postoperative renal function and adverse cardiac events following partial nephrectomy. MATERIALS AND METHODS: This is an observational analysis of patients who underwent robot-assisted laparoscopic partial nephrectomy from 2006 to 2014 at a single institution. The Wilcoxon rank sum and chi-square tests, and logistic regression were used to assess the risk of adverse renal and cardiac events stratified by history and pattern of renin-angiotensin blockade perioperatively. RESULTS: We identified 900 patients with a median followup of 16.3 months (IQR 1.4-39.1). There were no significant differences in severe renal dysfunction at last followup on univariate analysis or adverse cardiac events at 30 days on multivariate analysis in patients stratified by a history of renin-angiotensin blockade. Of the 338 patients 137 (41.9%) resumed renin-angiotensin blockade immediately after surgery, which did not result in any significant difference in the postoperative glomerular filtration rate (p >0.05). Resuming renin-angiotensin blockade at discharge home was associated with a decreased risk of heart failure within 30 days of surgery (0.3% vs 11.8% of cases) and stage IV/V chronic kidney disease at last followup (2.6% vs 25.5%, each p <0.001). CONCLUSIONS: Renin-angiotensin blockers appear safe to continue immediately after renal surgery. Discharge home with angiotensin converting enzyme inhibitors/angiotensin receptor blockers was associated with a decreased risk of heart failure and severe renal dysfunction. However, this risk may be overstated as a result of the small number of patients discharged without resuming the home medication.

The Impact of Documentation on Medicare and Medicaid Reimbursement of Subspecialty Urology in the Era of Health Care Reform.

INTRODUCTION: As health care reform is ongoing, reimbursement will continually be increasingly scrutinized and decreased despite growing numbers of patients with comorbid medical conditions. This study determined the impact of inpatient comorbidity documentation on hospital reimbursement in a female pelvic medicine and reconstructive surgery group. METHODS: Departmental financial records from 2011 to 2012 were reviewed. All admissions by 4 female pelvic medicine and reconstructive surgeons at a tertiary referral center were collected. All DRG (Diagnosis Related Group) codes of pathological conditions specific to males, stones and nonsubspecialty issues were excluded from analysis. Using CMS (Centers for Medicare and Medicaid Services) reimbursement rates the effects of documenting and coding comorbidities or complications were determined. Geographic multipliers were excluded. The study objective was to determine the impact of inpatient documentation on hospital reimbursement from a urological subspecialty group. RESULTS: Each of 4 surgeons admitted an average of 29 inpatients per year of whom 29% had a comorbidity or complication documented. Mean reimbursement was $3,486 greater for cases with versus without a coded comorbidity or complication. This resulted in an additional $31,374 of reimbursement annually per surgeon or $125,496 for the group. CONCLUSIONS: Documenting comorbidities and complications in urology patients appropriately results in a substantial increase in reimbursement. Care should be taken by urologists to accurately note comorbid medical conditions. This is especially crucial as health care reform continues and growing numbers of patients present with chronic disease while reimbursement is further scrutinized and decreased.

Implementation of a novel living-donor kidney transplant preoperative checklist within the electronic medical record: a pilot study.

BACKGROUND: Checklist utilization in surgery has contributed to improved patient safety and reduced numbers of preventable complications. A living-donor kidney transplant (LDKT) preoperative checklist embedded within electronic medical record (EMR) was developed to enhance patient safety and prevent "never" events including: unexpected donor-recipient blood (ABO) incompatibility, positive (XM) cross match, infectious disease transmission, or procurement of an anatomically inappropriate allograft. Review of the initial 2 years of checklist utilization was performed. FINDINGS: This safety instrument operates by facilitating critical review and referencing of source documentation to confirm ABO, XM, infectious risk, and organ anatomy compatibility. It was met with high compliance rates and no "never events" have occurred following its inception. The checklist is readily available in the EMR and is accessible by all members of the LDKT recipient healthcare team. CONCLUSIONS: Checklist utilization was associated with zero LDKT "never event" occurrences. Surgeons felt the checklist was easy to use.

The enigma of men with interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common and frequently misdiagnosed disorder in men. Hallmark symptoms are the presence of chronic discomfort attributed to the urinary bladder associated with bladder filling and relieved with bladder emptying, often associated with irritative voiding symptoms, in the absence of any other identifiable cause. It is often grouped with another common clinical entity, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Men with IC/BPS often suffer from a delay in diagnosis and subsequent treatment, often being categorized as having prostatitis, benign prostatic hyperplasia, or epididymitis before the correct diagnosis is reached. The etiology of IC/BPS is poorly understood, and its pathogenesis may involve multiple pathways leading to a common clinical entity. Diagnostic criteria continue to evolve over time as the understanding of IC/BPS improves, and a clinical diagnosis with properly performed history and physical exam is suitable for diagnosis after other processes such as infection, radiation, or pharmaceutical exposure are appropriately excluded. No set pathological findings, biomarkers, or phenotypic descriptions have been universally accepted as a result of conflicting studies. Guidelines for diagnostic and treatment options are limited by available data, and few studies incorporate substantial numbers of male patients. Reported outcomes for common therapies are mixed or have not yet been subjected to study in rigorous placebo-controlled clinical trials in men. Lessons learned from the treatment of CP/CPPS can be applied to IC/BPS, by favoring a phenotypically directed, multimodal approach rather than a stepwise algorithm as advocated by current practice guidelines.

Nanocarriers enhance Doxorubicin uptake in drug-resistant ovarian cancer cells.

Resistance to anthracyclines and other chemotherapeutics due to P-glycoprotein (pgp)-mediated export is a frequent problem in cancer treatment. Here, we report that iron oxide-titanium dioxide core-shell nanocomposites can serve as efficient carriers for doxorubicin to overcome this common mechanism of drug resistance in cancer cells. Doxorubicin nanocarriers (DNC) increased effective drug uptake in drug-resistant ovarian cells. Mechanistically, doxorubicin bound to the TiO(2) surface by a labile bond that was severed upon acidification within cell endosomes. Upon its release, doxorubicin traversed the intracellular milieu and entered the cell nucleus by a route that evaded pgp-mediated drug export. Confocal and X-ray fluorescence microscopy and flow cytometry were used to show the ability of DNCs to modulate transferrin uptake and distribution in cells. Increased transferrin uptake occurred through clathrin-mediated endocytosis, indicating that nanocomposites and DNCs may both interfere with removal of transferrin from cells. Together, our findings show that DNCs not only provide an alternative route of delivery of doxorubicin to pgp-overexpressing cancer cells but also may boost the uptake of transferrin-tagged therapeutic agents.

Preparation and in vivo evaluation of novel linkers for 211At labeling of proteins.

The syntheses, radiolabeling, antibody conjugation and in vivo evaluation of new linkers for (211)At labeling of monoclonal antibodies are described. Syntheses of the N-succinimidyl esters and labeling with (211)At to form succinimidyl 4-methoxymethyl-3-[(211)At]astatobenzoate (9) and succinimidyl 4-methylthiomethyl-3-[(211)At]astatobenzoate (11) from the corresponding bromo-aryl esters is reported. Previously reported succinimidyl N-{4-[(211)At]astatophenethyl}succinamate (SAPS) is employed as a standard of in vivo stability. Each agent is conjugated with Herceptin in parallel with their respective (125)I analogue, succinimidyl 4-methoxymethyl-3-[(125)I]iodobenzoate (10), succinimidyl 4-methylthiomethyl-3-[(125)I]iodobenzoate (12) and succinimidyl N-{4-[(125)I]iodophenethyl}succinamate (SIPS), respectively, for comparative assessment in LS-174T xenograft-bearing mice. With 9 and 11, inclusion of an electron pair donor in the ortho position does not appear to provide in vivo stability comparable to SAPS. Variables in radiolabeling chemistry of these three agents with (211)At are notable. Sequential elimination of acetic acid and oxidizing agent, N-chlorosuccinimide (NCS), from the (211)At radiolabeling protocol for forming SAPS improves yield, product purity and consistency. NCS appears to be critical for the radiolabeling of 6 with (211)At. Formation of 11, however, is found to require the absence of NCS. Elimination of acetic acid is found to have no effect on radiolabeling efficiency or yield for either of these reactions.