Low anterolateral incision for single-port extraperitoneal robot-assisted pyeloplasty: description of technique and initial experience.

PURPOSE: This study aims to describe the surgical steps for the single-port low anterolateral extraperitoneal approach to pyeloplasty, report its feasibility, and share the initial outcomes of our experience. METHODS: We analyzed all consecutive patients who underwent single-port low anterolateral extraperitoneal pyeloplasty due to ureteropelvic junction obstruction (UPJO). The surgical steps included a pure single-port approach through a 3.5 cm low anterolateral incision two fingerbreadths above the superior pubic ramus. The ureter was localized and followed cranially, a dismembered pyeloplasty was performed, and a running ureteropelvic anastomosis was completed. No drains were placed. The urinary catheter was removed upon discharge, and the ureteral stent after 3-5 weeks. RESULTS: A total of eight cases (two adults and six children) were completed successfully, without complications or conversions. Median operative time, console time, and estimated blood loss were 208.5 min, 114.5 min, and 10.0 ml, respectively. All patients were discharged within 24 h, except for one that required urinary output observation due to retention. There were no major postoperative complications. The median pain score at discharge was 0/10. Only one patient was prescribed PRN opioids at discharge. The readmission rate was 0.0%. All patients were asymptomatic on their last follow-up with no definitive obstruction on imaging, and no requirement for additional procedures or stents. CONCLUSION: Single-port low anterolateral extraperitoneal pyeloplasty is a feasible alternative for surgical treatment of UPJO in adult and pediatric patients with improved recovery outcomes.

Kidney disease progression in pediatric and adult posterior urethral valves (PUV) patients.

BACKGROUND: Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. METHODS: We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20 ml/min/1.73 m2 after 1 year of age, no dialysis or kidney transplant history, and ≥ 2 yearly serum creatinine values after age 1 year. eGFRs were calculated using creatinine-based estimating formulas for children (CKID U25) or adults (CKD-EPI). The primary outcome was annualized change in eGFR, assessed with linear mixed effects models. We also examined the association of acute kidney injury (AKI), proteinuria, hypertension (HTN), and recurrent febrile urinary tract infections (UTIs) with eGFR decline. RESULTS: Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m2/year. Children (n = 35) and adults (n = 17) demonstrated progressive decline. Proteinuria and recurrent UTIs were significantly associated with faster progression; AKI and HTN were also associated but did not reach significance. CONCLUSION: PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies.

2021 update on the urinary tract dilation (UTD) classification system: clarifications, review of the literature, and practical suggestions.

In 2014, a multidisciplinary consensus on the classification of pre- and postnatal urinary tract dilation (UTD classification) was developed. Its goal was to provide a standardized system for evaluating and reporting urinary tract dilation both in the prenatal and postnatal periods. In this review, we summarize insights learned from the implementation of the UTD classification system since its inception, providing clarifications on common points of confusion. In addition, we review current literature in the clinical validation of the UTD classification system to provide credence for its use in managing fetuses and children with urinary tract dilation.

Mesenchymal stem cells protect against obstruction-induced renal fibrosis by decreasing STAT3 activation and STAT3-dependent MMP-9 production.

STAT3 is a transcription factor implicated in renal fibrotic injury, but the role of STAT3 in mesenchymal stem cell (MSC)-induced renoprotection during renal fibrosis remains unknown. We hypothesized that MSCs protect against obstruction-induced renal fibrosis by downregulating STAT3 activation and STAT3-induced matrix metalloproteinase-9 (MMP-9) expression. Male Sprague-Dawley rats underwent renal arterial injection of vehicle or MSCs (1 × 106/rat) immediately before sham operation or induction of unilateral ureteral obstruction (UUO). The kidneys were harvested after 4 wk and analyzed for collagen I and III gene expression, collagen deposition (Masson's trichrome), fibronectin, α-smooth muscle actin, active STAT3 (p-STAT3), MMP-9, and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) expression. In a separate arm, the STAT3 inhibitor S3I-201 (10 mg/kg) vs. vehicle was administered to rats intraperitoneally just after induction of UUO and daily for 14 days thereafter. The kidneys were harvested after 2 wk and analyzed for p-STAT3 and MMP-9 expression, and collagen and fibronectin deposition. Renal obstruction induced a significant increase in collagen, fibronectin, α-SMA, p-STAT3, MMP-9, and TIMP-1 expression while exogenously administered MSCs significantly reduced these indicators of obstruction-induced renal fibrosis. STAT3 inhibition with S3I-201 significantly reduced obstruction-induced MMP-9 expression and tubulointerstitial fibrosis. These results demonstrate that MSCs protect against obstruction-induced renal fibrosis, in part, by decreasing STAT3 activation and STAT3-dependent MMP-9 production.

Propranolol for Treatment of Genital Infantile Hemangioma.

PURPOSE: Genital infantile hemangiomas are vascular anomalies that often require complex management and interdisciplinary care. Propranolol was first used to treat patients with infantile hemangiomas in 2008 and has since gained acceptance as first-line therapy. MATERIALS AND METHODS: We review the presentation, course, management and outcomes of all cases of genital infantile hemangiomas managed by propranolol administration at a single institution from April 2010 to July 2014. RESULTS: During the study period 9 patients with genital infantile hemangiomas were referred to our hemangioma treatment clinic. Propranolol was initially administered under careful outpatient monitoring at a dose of 1 mg/kg daily in 8 patients. One patient, a 700 gm premature infant, was started on therapy in the inpatient setting at 0.5 mg/kg daily, given the history of prematurity. All patients underwent successful increase of dose to at least 2 mg/kg for the observation phase after tolerating the starting doses. One patient discontinued propranolol prematurely per parental request due to concern regarding peripheral vasoconstriction. Otherwise, no patient demonstrated significant hypotension, symptomatic bradycardia, hypoglycemia or other major side effect requiring treatment discontinuation. All patients who continued the treatment protocol had excellent response to therapy. CONCLUSIONS: Propranolol therapy for genital infantile hemangiomas was successfully initiated and the dosage increased in 9 young children without significant side effects and with marked improvement in all patients who continued on treatment. Propranolol is the only Food and Drug Administration approved therapy for treatment of patients with this vascular anomaly and should be considered first-line therapy for genital infantile hemangiomas.

Assessing health related benefit after reconstruction for urinary and fecal incontinence in children: a parental perspective.

PURPOSE: We sought to evaluate health related benefit in children undergoing surgical reconstruction for urinary and fecal incontinence from a parental perspective. MATERIALS AND METHODS: A health related benefit instrument was mailed to the parents or guardians of 300 consecutive patients who had undergone reconstruction for urinary and/or fecal incontinence at our institution between 1997 and 2011. We assessed parent reported health related benefit using the validated Glasgow Children's Benefit Inventory and satisfaction with 6 supplemental questions. One-sample t-tests as well as exploratory univariate and multivariate linear regressions were performed for statistical analysis. RESULTS: Response rate was 40.0% at a mean of 5.5 years (range 0.6 to 13.8) after reconstruction. Spina bifida was the most common primary diagnosis (48 patients, 56.5%). Mean total Glasgow Children's Benefit Inventory score and subscores for each domain were positive, indicating an improved health related benefit after reconstruction (all p <0.0001). Certain patients, possibly based on diagnosis and gender, may particularly benefit from reconstruction (p ≤0.04). Parents believed that the bladder augmentation and/or urinary continent catheterizable channel most changed the life of their child but that achievement of stool continence was most important to themselves. Only 17 families (16.2%) required more than 1 month to become comfortable with catheterizations, and 69 patients (68.8%) required less care or no assistance with daily activities after reconstruction. Only 2 parents (1.9%) would be unwilling to consent to the procedure again. CONCLUSIONS: We observed moderate parental satisfaction and parent reported improvement in health related quality of life for children undergoing surgical reconstruction for urinary and fecal incontinence.

Single-port robotic extraperitoneal pediatric pyeloplasty using low anterior access: Description of technique and initial experience.

INTRODUCTION: We aim to report our surgical technique, functional and radiological outcomes of single port (SP) extraperitoneal robotic pediatric pyeloplasty through a low anterior (3 cm) access using a da-Vinci single-port (SP) robotic surgical system in the pediatric population. MATERIAL AND METHODS: We present our initial series of 6 pediatric patients that underwent robotic SP extraperitoneal pyeloplasty between 2022 and 2023. Patient clinicopathologic variables and perioperative outcomes were collected prospectively. RESULTS: All cases of SP extraperitoneal pyeloplasty were completed without any intraoperative complications or conversion to an open, laparoscopic, or multi-port robotic pyeloplasty. Total operative times including cystoscopy ranged from 178 min to 240 min. All patients tolerated the surgery with minimal postsurgical pain and no narcotic requirement. No intraoperative or immediate postoperative complications were recorded in the cohort. There were no readmissions after discharge at a median follow-up of 12 months (6-18 months) in our series. CONCLUSIONS: Single port extraperitoneal pyeloplasty is a safe and feasible option for upper tract reconstruction in pediatric patients. All patients had complete resolution of symptoms and improvement of hydronephrosis on follow-up imaging.

IL-18 induces profibrotic renal tubular cell injury via STAT3 activation.

IL-18 is an important mediator of obstruction-induced renal fibrosis and renal tubular epithelial cell (TEC) injury. IL-18's proinflammatory properties have been attributed, in part, to NF-κB activation and the stimulation of cytokine gene expression; however, STAT3 has increasingly been shown to mediate renal fibrotic injury. We therefore hypothesized that IL-18 mediates profibrotic TEC injury via STAT3 activation. Male C57BL6 wild-type mice and transgenic mice for human IL-18-binding protein were subjected to unilateral ureteral obstruction or sham operation. The kidneys were harvested 1 or 2 wk afterward and analyzed for active STAT3 (p-STAT3) expression (Western blotting, immunohistochemistry) and suppressor of cytokine signaling 3 (SOCS3) expression. In a separate arm, renal tubular cells (HK-2) were directly stimulated with IL-18 for 2 days with or without the STAT3 inhibitor S3I-201 (50 µM). Cell lysates were then analyzed for p-STAT3 and SOCS3 expression, profibrotic cellular changes (collagen and α-SMA expression), and tubular cell apoptosis. p-STAT3 and SOCS3 expression increased significantly in response to obstruction; however, a significant reduction in p-STAT3 and SOCS3 expression occurred following 1 wk, but not 2 wk, of obstruction in the presence of IL-18 neutralization. In vitro results similarly demonstrate increased p-STAT3, SOCS3, α-SMA, and collagen III expression, and increased collagen production and TEC apoptosis in response to IL-18 stimulation, but the response was significantly diminished in the presence of STAT3 inhibition. These results demonstrate that IL-18-induces profibrotic cellular changes and collagen production in TECs via STAT3 activation.

IL-18 activation is dependent on Toll-like receptor 4 during renal obstruction.

PURPOSE: Interleukin 18 (IL-18) is a critical mediator of obstruction-induced renal injury. Although previous studies have demonstrated that IL-18 participates in a positive feedback loop via the IL-18 receptor (IL-18R) and localized renal IL-18 and IL-18R production to tubular epithelial cells (TEC), the mechanism of IL-18 activation during obstruction remains unclear. We hypothesized that IL-18 activation is dependent on Toll-like receptor 4 (TLR4) signaling during renal obstruction. MATERIALS AND METHODS: Male C57BL6 TLR4 knockout (TLR4KO) and wild-type (WT) mice were subjected to unilateral ureteral obstruction versus sham operation for 1 wk. The animals were sacrificed, and renal cortical tissue was harvested and analyzed for TLR4 expression (Western blot), active IL-18 production (enzyme-linked immunosorbent assay, real-time polymerase chain reaction), IL-18 receptor expression (real-time polymerase chain reaction), and TLR4/IL-18 versus IL-18R cellular localization (dual immunofluorescent staining). RESULTS: Renal TLR4 expression increased significantly in WT mice in response to obstruction, but remained at sham treatment levels in TLR4KO mice. IL-18 and IL-18R gene expression and active IL-18 production were similarly increased in WT mice in response to obstruction, but decreased significantly to sham treatment levels in the absence of TLR4. Dual immunofluorescent staining revealed co-localization of TLR4 and IL-18 to renal TEC during obstruction. CONCLUSION: IL-18 production and activation during renal obstruction is dependent on intact TLR4 signaling. Co-localization of IL-18 and TLR4 production to TEC during obstruction suggests that TEC are the primary site of IL-18 production and activation. Further characterization of the pathway may be necessary to develop targeted therapy in obstruction-induced renal injury.

Business and Practice Readiness of Early Career Urologists: an Unmet Need.

INTRODUCTION: Business education in surgical residency, defined as contract negotiation, investing, financial planning and information on practice types, is currently lacking, and it is unknown if early career urologists possess this business education. Thus, we investigated how young urologists perceive their business knowledge and which vehicles of education they most prefer. METHODS: A 12-question survey was distributed to all urology residents, fellows and recent graduates to assess their self-reported business preparedness. Questions were administered concerning financial planning, familiarity with business models, ancillary income opportunities, coding and billing, contract negotiation, and awareness/use of AUA (American Urological Association) resources. Data were stratified by training year and practice type. The respondents were also asked their most preferred format for business education. RESULTS: A response rate of 10% was obtained with 230 total responses, including 89 (38.7%) from practicing urologists and 141 (61.3%) from trainees. The majority (88.3%) of respondents were not comfortable planning the business side of their practice and 71% were not aware of the AUA resources. Only 8% of practicing urologists and trainees were extremely comfortable with contract negotiation and 70% were not comfortable with assessing their own financial value. A majority was interested in podcasts, websites and online education. CONCLUSIONS: The survey results demonstrate a significant unmet need among early career urologists regarding business education. This self-reported lack of business literacy presents a blind spot in urological training. The development of an accessible business curriculum along with practical resources may have a vital role in the promotion of wellness and financial success among early career urologists.

Use of 99mTc-sestamibi Single-photon Emission Computed Tomography / X-ray Computed Tomography in the Diagnosis of Hybrid Oncocytic / Chromophobe Tumor in a Pediatric Patient.

The differential diagnosis of solid renal neoplasms in adolescence includes aggressive malignancy and indolent oncocytic tumors, which are typically indistinguishable using conventional imaging. We report the use of 99mTc-sestamibi single-photon emission computed tomography / x-ray computed tomography (SPECT/CT) in characterizing enhancing renal neoplasms in a pediatric patient. Genetic testing suggested a hereditary syndrome associated with aggressive malignancy, whereas renal mass biopsy suggested an oncocytic tumor. 99mTc-sestamibi SPECT/CT indicated probable oncocytomas or hybrid oncocytic / chomophobe tumors. Enucleative resection was performed with final pathology demonstrating hybrid oncocytic / chomophobe tumors. This case highlights the potential utility of 99mTc-sestamibi SPECT/CT in characterizing indeterminate enhancing renal neoplasm in pediatric patients.

Do Routine Preoperative and Intraoperative Urine Cultures Benefit Pediatric Vesicoureteral Reflux Surgery?

Objective. To determine if routine preoperative and intraoperative urine cultures (UCx) are necessary in pediatric vesicoureteral (VUR) reflux surgery by identifying their association with each other, preoperative symptoms, and surgical outcomes. Materials and Methods. A retrospective review of patients undergoing ureteral reimplant(s) for primary VUR at a tertiary academic medical center between years 2000 and 2014 was done. Preoperative UCx were defined as those within 30 days before surgery. A positive culture was defined as >50,000 colony forming units of a single organism. Results. A total of 185 patients were identified and 87/185 (47.0%) met inclusion criteria. Of those, 39/87 (45%) completed a preoperative UCx. Only 3/39 (8%) preoperative cultures returned positive, and all of those patients were preoperatively symptomatic. No preoperatively asymptomatic patients had positive preoperative cultures. Intraoperative cultures were obtained in 21/87 (24.1%) patients; all were negative. No associations were found between preoperative culture results and intraoperative cultures or between culture result and postoperative complications. Conclusions. In asymptomatic patients, no associations were found between the completion of a preoperative or intraoperative UCx and surgical outcomes, suggesting that not all patients may require preoperative screening. Children presenting with symptoms of urinary tract infection (UTI) prior to ureteral reimplantation may benefit from preoperative UCx.

Predicting clinical end points: treatment nomograms in prostate cancer.

Due to the generally indolent nature of prostate cancer, patients must decide among a wide range of treatments, which will significantly affect both quality of life and survival. Thus, there is a need for instruments to aid patients and their physicians in decision analysis. Nomograms are instruments that predict outcomes for the individual patient. Using algorithms that incorporate multiple variables, nomograms calculate the predicted probability that a patient will reach a clinical end point of interest. Nomograms tend to outperform both expert clinicians and predictive instruments based on risk grouping. We outline principles for nomogram construction, including considerations for choice of clinical end points and appropriate predictive variables, and methods for model validation. Currently, nomograms are available to predict progression-free probability after several primary treatments for localized prostate cancer. There is need for additional models that predict other clinical end points, especially survival adjusted for quality of life.

Prognostic factors for survival in patients with hormone-refractory prostate cancer (HRPC) after initial androgen deprivation therapy (ADT).

Androgen deprivation therapy (ADT) is a standard mode of therapy for patients with metastatic prostate cancer. Controversy exists, however, as to the optimal timing of initiation of ADT, as well as whether this form of therapy imparts a survival benefit to patients with advanced disease. Side effects of ADT are not minimal and can seriously compromise a patient's quality of life. Additionally, ADT eventually results in hormone-refractory prostate cancer (HRPC). Despite new chemotherapeutic regimens and hormonal agents, overall survival in these patients remains universally low. Nonetheless, it is valuable to gauge a patient's prognosis to assist in decision making when considering treatment options. Contemporary series analyzing patients with HRPC have identified several factors prognostic of survival outcomes, such as lactate dehydrogenase (LDH), alkaline phosphatase (ALK), hemoglobin (Hgb), and serum prostate specific antigen (PSA) level. Nomograms have been developed that utilize these pretreatment clinical variables to predict clinical outcomes, including 1-year, 2-year, and median survival times in patients with HRPC. These instruments are capable of more accurately predicting survival outcomes than traditional tables of multivariate results or simple analysis of prognostic factors. We believe these nomograms will become indispensable tools for patient counseling and clinical trial design in patients with HRPC.

Refluxing ureteral reimplantation: a logical method for managing neonatal UVJ obstruction.

OBJECTIVE: An obstructed megaureter can be managed using a number of techniques, with the primary goal being to minimize the potential for further injury to the affected kidney. Classically, these obstructed ureters have been treated using cutaneous ureterostomy. However, this technique has certain limitations including the potential for stenosis. We describe our experience with the refluxing ureteral reimplantation as a novel, yet technically simple, method for temporary internal diversion of the obstructed megaureter. METHODS: Treatment consists of transecting the ureter proximal to the obstruction and performing an end-to-side anastomosis with the bladder in a freely refluxing fashion. Patients are placed on antibiotic suppression following surgery. Subsequent open definitive surgery is performed through the same incision site once the child is older than 1 year of age. RESULTS: Sixteen patients identified with severe hydroureteronephrosis were found to have an obstructed megaureter(s) involving 19 ureteral moieties. Patients underwent internal diversion at an average age of 5 months. All patients demonstrated improved drainage of the affected kidney(s) following surgery. Three patients developed a febrile urinary tract infection. Definitive surgical treatment was undertaken in 18 of 19 ureters, and consisted of ureteral reimplantation with tapering or plication (13), ureteral reimplantation without tapering (3), and nephrectomy (2). One patient with multiple other congenital anomalies is not a candidate for further genitourinary reconstruction. CONCLUSIONS: Refluxing ureteral reimplantation is a safe and easy method of temporary internal urinary diversion. Simple in principle, the concept of creating a refluxing ureteral reimplantation is no different from that of incising an obstructing ureterocele. This technique allows time for the child to mature, while preserving renal function and awaiting definitive repair.

Anterior urethral valve associated with posterior urethral valves: report of 2 cases and review of the literature.

Anterior urethral valve (AUV) associated with posterior urethral valves (PUVs) is an extremely rare congenital urologic anomaly resulting in lower urinary tract obstruction. We present our experience with 2 children with concomitant AUV and PUV as well as a literature review. The clinical presentation of concomitant AUV and PUV is variable. Successful endoscopic management can result in improvement in renal function, reversal of obstructive changes, and improvement or resolution of voiding dysfunction.

Testicular myeloid sarcoma: a rare manifestation of acute myeloid leukemia in an infant.

Myeloid sarcoma manifesting in the testis is rare and may occur concomitantly with bone marrow disease or as a separate entity. We describe our experience with a 6-month-old boy who presented with painless scrotal swelling and was found to have bilateral testicular masses on ultrasonography. The patient underwent unilateral radical inguinal orchiectomy. Surgical pathology revealed myeloid sarcoma of the testicle. He developed peripheral blood involvement 1 week postoperatively. Bone marrow biopsy showed acute myeloid leukemia. He is in remission after 2 cycles of induction chemotherapy, local radiation therapy, and allogeneic bone marrow transplantation.