Role of a Preoperative Catheter Regimen in Achieving Early Primary Endoscopic Valve Ablation in Neonates with Posterior Urethral Valves.

PURPOSE: Primary valve ablation is preferred to vesicostomy in the initial management of posterior urethral valves. However, some neonates have a prohibitively small urethra. We describe our experience with a preoperative urethral catheter regimen to enhance the likelihood of neonatal valve ablation. MATERIALS AND METHODS: We performed a retrospective review of 126 neonates with posterior urethral valves treated between 2003 and 2019 with valve ablation prior to 10 weeks of age. The preoperative indwelling catheter either was gradually upsized to an 8Fr (progressive urethral dilation), was not upsized (nondilated) or was initially larger bore (8Fr only). The primary outcome was the ability to perform primary ablation by neonatal resectoscope. The secondary objective was to establish the parameters for considering progressive urethral dilation as well as its associated risks. RESULTS: Overall 97% could be ablated. The progressive urethral dilation group had the lowest mean weight (p <0.001). Only a larger catheter at the time of ablation was significantly associated with feasible ablation (p <0.001) and not urethral dilation, the infant's weight or his gestational age. Progressive urethral dilation was associated with a longer duration of catheterization as well as double the rate of febrile urinary tract infections (8.5%) over the nondilated group (3.6%). CONCLUSIONS: A much higher rate of primary ablation is feasible (97%) than previously reported (82%). More important than the infant's weight is whether a 6Fr to 8Fr catheter is in place at ablation. If an initial 6Fr to 8Fr catheter cannot be placed, urethral dilation to 8Fr should be performed before attempting ablation. This is both a technique and preoperative assessment that is useful for operative planning.

Surgical Scar Location Preference for Pediatric Kidney and Pelvic Surgery: A Crowdsourced Survey.

PURPOSE: The benefits of minimally invasive surgery in pediatric urology, such as reduced length of hospital stay and postoperative pain, are less predictable compared to findings in the adult literature. We evaluated the choices that adult patients make for themselves and their children regarding scar location. MATERIALS AND METHODS: We surveyed the preference for scar location/size based on surgery for bladder and kidney procedures with additional questions assessing the impact of a hidden incision, length of hospital stay and pain. The survey was posted to Amazon® Mechanical Turk®. RESULTS: We analyzed a total of 954 completed surveys. Surgical history was reported in 660 surveys (69%) with scar bother reported in 357 (54.2%). For pelvic surgery the initial choice was a Pfannenstiel incision for 434 respondents (45.5%), laparoscopy port incisions for 392 (41.1%) and no preference for incision location for 126 (13.2%). When incisions were illustrated relative to undergarments, 718 respondents (75.3%) chose Pfannenstiel. For kidney surgery 567 respondents (59.4%) initially chose the dorsal lumbotomy incision, 170 (17.8%) chose a flank incision, 105 (11.0%) chose laparoscopy ports and 110 (11.5%) had no preference. Respondents were told that minimally invasive surgery might result in less pain/length of hospital stay and were asked to restate the incision choice. For pelvic surgery 232 of 434 respondents (53.5%) who had chosen Pfannenstiel and 282 of 394 (71.6%) who had chosen laparoscopy remained consistent (p <0.001). For kidney surgery 96 respondents (56.5%) who chose a flank incision, 322 (56.8%) who chose dorsal lumbotomy and 68 (64.2%) who chose laparoscopy remained consistent (p = 0.349). Agreement between the incision choice by respondent as a child and for a child was 82% (κ = 0.69) for pelvic surgery and 84.6% (κ = 0.75) for kidney surgery. CONCLUSIONS: The smallest incision is not always the patient preferred incision, particularly in childhood when pain, length of hospital stay and blood loss may be equivocal among approaches. Discussion of surgical treatment options should include scar length, location and relationship to undergarments.

Functional supernumerary testis in a child with testicular torsion and review of polyorchidism.

Histologically confirmed polyorchidism is an uncommon condition. The majority of cases are asymptomatic and associated with inguinal hernia or cryptorchidism. There are few reported cases of pediatric supernumerary testis presenting with testicular torsion. We present a case of missed torsion with incidentally detected triorchidism as well as an overview of pediatric polyorchidism.

Preliminary experience with epsilon aminocaproic acid for treatment of intractable upper tract hematuria in children with hematological disorders.

PURPOSE: Gross, intractable hematuria is rare in children. Although the role of epsilon aminocaproic acid in the management of refractory hematuria is well established in the adult population, few data exist about its use in children for this indication. We present our initial experience with epsilon aminocaproic acid for the treatment of intractable hematuria after more conservative measures failed, and propose an algorithm for administration of epsilon aminocaproic acid in children. MATERIALS AND METHODS: We reviewed the charts of all patients treated with epsilon aminocaproic acid for intractable gross hematuria at our institution during a period of 36 months. All patients underwent hematological evaluation and any underlying bleeding dyscrasias were addressed. All patients also underwent renal and bladder ultrasound, retrograde pyelogram and ureteroscopy. Demographic information, medical and surgical histories, and epsilon aminocaproic acid dosing and outcomes were recorded. RESULTS: Three boys and 1 girl 11 to 17 years old were treated with epsilon aminocaproic acid. Three patients had sickle trait (1 with nutcracker phenomenon) and 1 had hemophilia A. Three patients required packed red blood cell transfusions to maintain hematocrit. Three renal angiograms were performed, all of which were nondiagnostic. Duration of hematuria ranged from 1 to 52 weeks before administration of epsilon aminocaproic acid. Endoscopic evaluation demonstrated hematuria localized to 1 ureteral orifice in all 4 patients. All patients received 100 mg/kg epsilon aminocaproic acid orally every 6 hours, which uniformly led to cessation of hematuria. CONCLUSIONS: Epsilon aminocaproic acid is useful for the management of gross refractory hematuria when more conservative measures fail. Because of its potential side effects, it should be used cautiously.

Same setting laparoscopic antegrade continence enema and antegrade bladder neck injection for constipation and urinary incontinence in the spina bifida population.

PURPOSE: Fecal impaction and urinary incontinence and are among the most important problems in patients with spina bifida. We report our preliminary results with a minimally invasive approach to these 2 problems, that is same setting laparoscopic antegrade continence enema and antegrade bladder neck injection. MATERIALS AND METHODS: We reviewed the charts of all patients who underwent same setting laparoscopic antegrade continence enema and antegrade bladder neck injection between January 1, 2006 and August 1, 2008. Demographic data, surgical indications, operative details and results were recorded. Surgical steps were uniform in all cases. Diagnostic laparoscopy was performed. Two additional 5 mm trocars were placed. The appendix was mobilized to reach skin in the right lower quadrant. The antegrade continence enema channel was matured. A small percutaneous cystotomy was then created via the suprapubic port site. The cystoscope was passed suprapubically and dextranomer/hyaluronic acid was injected in the bladder neck. A suprapubic tube was placed. RESULTS: We performed a total of 10 same setting laparoscopic antegrade continence enemas with antegrade bladder neck injection in 4 males and 6 females with a mean age of 9.4 years (range 6 to 13). All patients had a smooth walled bladder on cystogram, and good capacity, good compliance and low leak point pressure on urodynamics. There were no intraoperative complications and all patients were discharged home within 24 hours. At an average 18-month followup (range 12 to 27) all 10 patients were continent of stool and reported marked improvement in daily care. No patient experienced stool or gas leakage via antegrade bladder neck injection. Seven of 10 patients (70%) were continent of urine and no longer wore diapers. CONCLUSIONS: Same setting laparoscopic antegrade continence enema with antegrade bladder neck injection is a safe, efficacious, reasonably simple minimally invasive approach to severe constipation and urinary incontinence in patients with spina bifida.

Sutureless and scalpel-free circumcision--more rapid, less expensive and better?

PURPOSE: We previously reported our success with sutureless circumcision using 2-octyl cyanoacrylate in 267 patients. We have since modified our technique by making incisions with electrocautery. We report our results with this novel technique. We also performed a cost analysis. MATERIALS AND METHODS: We compiled data on all patients 6 months to 12 years old who underwent primary circumcision and circumcision revision in a 39-month period, as done by 3 surgeons. Study exclusion criteria were complexity beyond phimosis and Gomco clamp use. The technique included 1) a circumferential inner incision using electrocautery on cutting current, 2) a circumferential outer incision using electrocautery, 3) foreskin removal, 4) hemostasis with electrocautery, 5) skin edge approximation with 2-octyl cyanoacrylate or 6-zero suture and 6) antibiotic ointment application. We also determined the cost of all procedures based on anesthesia and operating room facility fees, and material costs. RESULTS: Between July 1, 2006 and October 1, 2009 we performed 493 primary circumcisions and 248 revisions using 2-octyl cyanoacrylate, and 152 primary circumcisions and 115 revisions using 6-zero sutures. Mean operative time for primary circumcision and revision using 2-octyl cyanoacrylate was 8 minutes (range 6 to 18), and for sutured primary circumcision and revision it was 27 minutes (range 18 to 48). At a mean 18-month followup (range 1 to 39) 3 patients treated with 2-octyl cyanoacrylate and 2 treated with sutures were rehospitalized for bleeding. When done with electrocautery, the cost of the 2-octyl cyanoacrylate technique was $743.55 less than the sutured technique as long as the 2-octyl cyanoacrylate procedures required less than 15 minutes and the sutured procedures required more than 15 minutes. CONCLUSIONS: Combined electrocautery and 2-octyl cyanoacrylate for circumcision is a safe, efficient, financially beneficial, cosmetically appealing alternative to traditional circumcision done with scalpel and sutures.

Magnetic resonance urography in pediatric urology.

PURPOSE OF REVIEW: Magnetic resonance urography (MRU) has evolved into an effective imaging tool for the evaluation of the urinary tract in children. The goal of this article is to describe current techniques and applications of MRU and to review recent advances. RECENT FINDINGS: MRU is most commonly applied to the evaluation of hydronephrosis and provides valuable insight into a wide range of obstructive uropathies. MRU was shown to be superior to renal scintigraphy for the diagnosis of pyelonephritis and renal scarring. The use of MRU for the assessment of urolithiasis, vesicoureteral reflux, renal trauma, and fetal urinary tract abnormalities is limited and technical refinements are required. Judicious use of gadolinium-based contrast agents in patients at risk for nephrogenic systemic fibrosis was recently shown to avoid new occurrences. Potential future applications include virtual endoscopy and MRU-guided procedures. SUMMARY: MRU has the potential to revolutionize imaging of the urinary tract in children. It integrates exquisite anatomical information with a variety of functional data and avoids ionizing radiation. MRU is increasingly employed as a problem solver when conventional imaging studies remain inconclusive and its growing application will likely improve availability and cost in the future.

Radiologic features of implants after endoscopic treatment of vesicoureteral reflux in children.

OBJECTIVE: Implants after endoscopic treatment of vesicoureteral reflux (VUR) in children will be more frequently detected on imaging studies and may lead to misinterpretation and unnecessary intervention. This article reviews the radiologic appearance of implants. CONCLUSION: Radiologic findings of implants depend on the imaging technique, bulking agent, and time after injection. A history of VUR or an antireflux procedure and the absence of hydronephrosis in cases of suspected urolithiasis are important clues to suggest implants.

Assessment of health literacy in adolescents with spina bifida and their caregivers: a multi-institutional study.

INTRODUCTION: and Objective: Health literacy is defined as the ability to obtain, integrate, and appraise health-related knowledge. It is known to correlate with disparities in clinical outcomes in adults with chronic disease. Patients with spina bifida represent a potentially vulnerable cohort as they often have multiple comorbidities. The authors aimed to characterize health literacy in adolescent patients with spina bifida and their caregivers. STUDY DESIGN: The Newest Vital Sign (NVS), a validated assessment of health literacy and numeracy, was administered to patients (aged ≥10 years) and caregivers in outpatient pediatric urology and multidisciplinary spina bifida clinics. Subjects not fluent in English or Spanish and those with cognitive delay were excluded. Survey responses and demographic information were analyzed and compared between the spina bifida and control groups. RESULTS: Three hundred eleven caregivers (caregivers for patients with spina bifida: 185, caregivers for the controls: 126) and 84 adolescents (those with spina bifida: 46, controls: 38) completed the NVS. Although there was no difference in health literacy between caregivers (p = 0.98), adolescents with spina bifida demonstrated lower NVS scores (spina bifida 1 [0-3] vs. control 2 [2-4]; p = 0.02) (Figure). Health literacy of patients with spina bifida and controls increased with age (p = 0.002). Adjusting for age and gender, the odds of having limited literacy were 5.5 times higher in patients with spina bifida than in the controls (p = 0.004). Inadequate caregiver health literacy was associated with a lower education level (p < 0.001). DISCUSSION: Spina bifida is among the most complex birth defects compatible with life and affects a multitude of systems. Although it is well established that limited health literacy in adults with chronic disease is associated with adverse outcomes, there are considerably fewer data in the pediatric population. The authors found that caregivers of patients with spina bifida exhibited health literacy and numeracy comparable with parents in the control group, despite lower education levels. In contrast, adolescents with spina bifida demonstrated poorer health literacy than the controls. Multidisciplinary care is necessary, given the medical complexity of spina bifida; therefore, impaired understanding of adults' own needs may pose a barrier to successful transition to their care and subsequent outcomes. CONCLUSIONS: The majority of surveyed caregivers for patients with spina bifida exhibited adequate health literacy, especially those with some college education; however inadequate health literacy was more likely among adolescents with spina bifida when compared with the controls. Screening for health literacy may be useful to assess readiness for transition to more independent self-care among patients with spina bifida.

Opioid utilization is minimal after outpatient pediatric urologic surgery.

INTRODUCTION: There are no guidelines for opioid use after pediatric urologic surgery, and it is unknown to what extent prescriptions written for these patients may be contributing to the opioid epidemic in the United States. We sought to characterize opioid utilization in a prospective fashion following outpatient pediatric urologic surgery at our institution. MATERIALS AND METHODS: After obtainingapproval from the Institutional Review Board, we prospectively recruited pediatric patients undergoing outpatient urologic surgery. All patients and families were counseled regarding appropriate use of over-the-counter pain medications as first-line agents, with opioids for breakthrough pain only. All patients received an opioid prescription (ORx), which we attempted to standardize to 10 doses. Parents were provided with a log for keeping track of pain medication administration. Postoperative surveys were sent at various time points after surgery to assess utilization of pain medications at home. We quantified unused opioids prescribed and evaluated factors potentially associated with opioid use. RESULTS: Two hundred and two patients were recruited. All patients were male, with a median age of 2.7 years (interquartile range (IQR) 5.5, range 0.5-17.9 years). One hundred and fifty-four children underwent penile surgery, 22 underwent scrotal surgery, and 27 underwent inguinal surgery. Nearly half of our study patients were black, 33.2% were white, 12.9% were Latino, and 4.0% were Asian. The median number of doses prescribed was 10 (IQR 0, range 4.0-20.8). Postoperative surveys were completed by 80.7% of study patients. The median number of opioid doses used was 0 (IQR 2), whereas the mean was 1.28 (standard deviation (SD) 1.98). None of the factors evaluated (including patient age, surgery type, perioperative pain management techniques, length of surgery, and insurance type) were associated with the amount of opioid used at home after surgery, as utilization was equally low across all groups. DISCUSSION AND CONCLUSIONS: Ensuring adequate postoperative pain control for children is critical, yet it is also important to minimize excess ORx. We found that the majority of pediatric patients used 0-2 doses of prescription pain medication after discharge following outpatient urologic surgery, representing a small percentage of the total prescribed amount. Low utilization was seen irrespective of patient age, procedure, and perioperative factors. These data can be used to guide perioperative patient and family counseling and to guide future efforts to standardize ORx following outpatient pediatric urologic surgery.

Appearance of dextranomer/hyaluronic Acid copolymer implants on computerized tomography after endoscopic treatment of vesicoureteral reflux in children.

PURPOSE: With the increasing popularity of endoscopic treatment for vesicoureteral reflux in children, dextranomer/hyaluronic acid copolymer implants are more frequently detected on computerized tomography, which may lead to misinterpretation and unnecessary intervention. The objective of this study was to characterize the long-term appearance of dextranomer/hyaluronic acid copolymer implants on computerized tomography. MATERIALS AND METHODS: We evaluated the hospital charts of 893 patients who had undergone dextranomer/hyaluronic acid copolymer injection for vesicoureteral reflux between July 2001 and November 2007 to identify those who underwent subsequent computerized tomography of the abdomen and pelvis. A total of 30 patients with ureterovesical junction stones served as the control group. Seven patients who proceeded to extravesical reimplantation after failed endoscopic treatment had dextranomer/hyaluronic acid copolymer implants explanted and microscopically evaluated. RESULTS: Of 893 patients who had undergone endoscopic treatment for vesicoureteral reflux 17 (1.9%) underwent subsequent computerized tomography. A total of 33 dextranomer/hyaluronic acid copolymer implants were detected on computerized tomography, and were classified as low density (21) or high density (12). Median density was 22 HU (range 15 to 27) for low density implants and 193 HU (126 to 367) for high density implants. Radiograph of the kidneys, ureters and bladder, and fluoroscopy did not visualize high density implants. Neither gender, age at endoscopic treatment, vesicoureteral reflux grade, hydrodistention grade, injection volume, success nor second injection was associated with a high density implant. Only elapsed time between surgery and computerized tomography was associated with increased implant density (p = 0.02). CONCLUSIONS: Dextranomer/hyaluronic acid copolymer implants may be encountered on computerized tomography as low or high density lesions. History of vesicoureteral reflux and absence of hydronephrosis as well as hematuria should provide reassurance and prevent inappropriate intervention for misdiagnosed ureteral stones.

Dynamic hydrodistention of the ureteral orifice: a novel grading system with high interobserver concordance and correlation with vesicoureteral reflux grade.

PURPOSE: We evaluated the usefulness and interobserver concordance of a novel grading system for dynamic ureteral hydrodistention. MATERIALS AND METHODS: Between May 1, 2002 and July 1, 2008 the hydrodistention grade in 697 ureters was prospectively assigned and recorded, including H0-no hydrodistention, H1-ureteral orifice open but tunnel not evident, H2-tunnel seen only and H3-extravesical ureter visualized. Specifically 489 refluxing ureters (vesicoureteral reflux group) were compared to 100 normal control ureters (normal control group). Additionally, the posttreatment hydrodistention grade in 56 ureters in which surgery for reflux failed was compared to that in 52 ureters with successful surgery. Hydrodistention grades assigned to an additional 77 ureters by 3 blinded observers were compared to assess the interobserver concordance of this system. RESULTS: Vesicoureteral reflux and hydrodistention grades correlated significantly (p <0.001). Ureters with a higher reflux grade also showed a higher hydrodistention grade. The normal control group (mean +/- SEM hydrodistention grade 0.62 +/- 0.07) showed a statistically lower hydrodistention grade than the reflux groups (overall mean hydrodistention grade 2.26 +/- 0.01). Mean posttreatment hydrodistention grade in the failed reflux surgery group was statistically higher than that in the mean successful reflux surgery group (2.03 +/- 0.09 vs 1.33 +/- 0.08). By defining the degree of hydrodistention as normal (H0-H1) and abnormal (H2-H3) the concordance between observers was 95% and 96%. CONCLUSIONS: The dynamic hydrodistention classification is a reliable method of evaluating the presence or absence of vesicoureteral reflux as it correlates significantly with radiographic reflux grade. It has high interobserver concordance.

The role of liver transplantation techniques in the surgical management of advanced renal urothelial carcinoma with or without inferior vena cava thrombus.

PURPOSE: Standard radical nephrectomy for large masses is significantly facilitated by liver transplantation techniques, which have been successfully employed over the last ten years at our institution. Large and locally-advanced urothelial carcinoma of the kidney with or without extension into the inferior vena cava is rare. The purpose of this study was to present the surgical management of large and locally-advanced urothelial tumors arising from the renal pelvis using liver transplantation techniques and to evaluate patient outcome. MATERIALS AND METHODS: Diagnostic work-up and surgical management of 4 patients with large and locally-advanced renal urothelial carcinoma were retrospectively reviewed. Two out of four patients with urothelial carcinoma presented with inferior vena cava thrombus. Mean tumor size was 11.6 cm. All patients underwent surgery, 2 patients with the presumed diagnosis of renal cell cancer. Liver transplantation techniques were an integral part in all radical nephrectomies. RESULTS: No intraoperative complications and postoperative mortality occurred. Mean operative time was 7.5 hours, estimated blood loss was 1.5 L, and an average of 4.8 units of blood was transfused intraoperatively. Three patients succumbed to cancer recurrence at a mean postoperative time of 6.3 months; 1 patient is still alive 24 months after surgery. CONCLUSIONS: Large and locally-advanced renal masses of urothelial origin can be successfully removed by a combination of radical nephrectomy with liver transplantation techniques. Since long-term outcome of such patients has been poor, accurate preoperative diagnosis is essential to consider neoadjuvant treatment and to plan nephroureterectomy.

Quantum dots: emerging applications in urologic oncology.

Quantum dots (QDs), nanometer-sized fluorescent probes with unique optical and electronic properties, offer a promising and powerful tool for cancer imaging and diagnostics. For the past few years, QDs were actively developed for biomolecular profiling of cancer biomarkers, in vivo tumor imaging, and even targeted drug delivery. These emerging applications are currently being improved and integrated into clinical practice. In this article, we describe the development of multifunctional QDs and their potential applications in oncology, with a particular emphasis on the diagnosis, prognosis, and treatment of urologic cancers.

Collagen-binding integrin alpha1beta1 regulates intestinal inflammation in experimental colitis.

Central to inflammatory responses are the integrin-mediated adhesive interactions of cells with their ECM-rich environment. We investigated the role of the collagen-binding integrin alpha(1)beta(1) in intestinal inflammation using the mouse model of colitis induced by dextran sodium sulfate (DSS). mAb's directed against murine alpha(1) were found to significantly attenuate inflammation and injury in DSS-treated wild-type mice; similar protection was seen in mice deficient for alpha(1)beta(1) integrin. Blockade or loss of alpha(1)beta(1) was also associated with decreased mucosal inflammatory cell infiltrate and cytokine production. Importantly, we demonstrated that development and alpha(1)-mediated inhibition of DSS-induced colitis occurred independently of lymphocytes (Rag-2(-/-) mice), and identified the monocyte as a key alpha(1)beta(1)-expressing cell type involved in the development of colitis in this model. In response to DSS, both alpha(1) deficiency and anti-alpha(1) mAb treatment significantly reduced monocyte accumulation and activation within the lamina propria. In summary, the data demonstrate that engagement of leukocyte-associated alpha(1)beta(1) receptors with ECM plays a pivotal role in mediating intestinal inflammation via promotion of monocyte movement and/or activation within the inflamed interstitium. Therapeutic strategies designed to disrupt such interactions may prove beneficial in treating intestinal inflammation.

HYAL1 hyaluronidase: a molecular determinant of bladder tumor growth and invasion.

Hyaluronic acid and HYAL1-type hyaluronidase show high accuracy in detecting bladder cancer and evaluating its grade, respectively. Hyaluronic acid promotes tumor progression; however, the functions of hyaluronidase in cancer are largely unknown. In this study, we stably transfected HT1376 bladder cancer cells with HYAL1-sense (HYAL1-S), HYAL1-antisense (HYAL1-AS), or vector cDNA constructs. Whereas HYAL1-S transfectants produced 3-fold more HYAL1 than vector transfectants, HYAL1-AS transfectants showed approximately 90% reduction in HYAL1 production. HYAL1-AS transfectants grew four times slower than vector and HYAL1-S transfectants and were blocked in the G2-M phase of the cell cycle. The expression of cdc25c and cyclin B1 and cdc2/p34-associated H1 histone kinase activity also decreased in HYAL1-AS transfectants. HYAL1-S transfectants were 30% to 44% more invasive, and HYAL1-AS transfectants were approximately 50% less invasive than the vector transfectants in vitro. In xenografts, there was a 4- to 5-fold delay in the generation of palpable HYAL1-AS tumors, and the weight of HYAL1-AS tumors was 9- to 17-fold less than vector and HYAL1-S tumors, respectively (P < 0.001). Whereas HYAL1-S and vector tumors infiltrated skeletal muscle and blood vessels, HYAL1-AS tumors resembled benign neoplasia. HYAL1-S and vector tumors expressed significantly higher amounts of HYAL1 (in tumor cells) and hyaluronic acid (in tumor-associated stroma) than HYAL1-AS tumors. Microvessel density in HYAL1-S tumors was 3.8- and 9.5-fold higher than that in vector and HYAL1-AS tumors, respectively. These results show that HYAL1 expression in bladder cancer cells regulates tumor growth and progression and therefore serves as a marker for high-grade bladder cancer.

HYAL1 hyaluronidase in prostate cancer: a tumor promoter and suppressor.

Hyaluronidases degrade hyaluronic acid, which promotes metastasis. HYAL1 type hyaluronidase is an independent prognostic indicator of prostate cancer progression and a biomarker for bladder cancer. However, it is controversial whether hyaluronidase (e.g., HYAL1) functions as a tumor promoter or as a suppressor. We stably transfected prostate cancer cells, DU145 and PC-3 ML, with HYAL1-sense (HYAL1-S), HYAL1-antisense (HYAL1-AS), or vector DNA. HYAL1-AS transfectants were not generated for PC-3 ML because it expresses little HYAL1. HYAL1-S transfectants produced < or = 42 milliunits (moderate overproducers) or > or = 80 milliunits hyaluronidase activity (high producers). HYAL1-AS transfectants produced <10% hyaluronidase activity when compared with vector transfectants (18-24 milliunits). Both blocking HYAL1 expression and high HYAL1 production resulted in a 4- to 5-fold decrease in prostate cancer cell proliferation. HYAL1-AS transfectants had a G2-M block due to decreased cyclin B1, cdc25c, and cdc2/p34 expression and cdc2/p34 kinase activity. High HYAL1 producers had a 3-fold increase in apoptotic activity and mitochondrial depolarization when compared with vector transfectants and expressed activated proapoptotic protein WOX1. Blocking HYAL1 expression inhibited tumor growth by 4- to 7-fold, whereas high HYAL1 producing transfectants either did not form tumors (DU145) or grew 3.5-fold slower (PC-3 ML). Whereas vector and moderate HYAL1 producers generated muscle and blood vessel infiltrating tumors, HYAL1-AS tumors were benign and contained smaller capillaries. Specimens of high HYAL1 producers were 99% free of tumor cells. This study shows that, depending on the concentration, HYAL1 functions as a tumor promoter and as a suppressor and provides a basis for anti-hyaluronidase and high-hyaluronidase treatments for cancer.

Benign Large-cell Calcifying Sertoli Tumor of the Testis in a 13-Year-Old Male Patient Treated With Partial Orchiectomy.

Large-cell calcifying Sertoli cell tumor (LCCSCT) of the testis is an exceptionally rare lesion, found sparsely in any medical literature. There is a correlation between this entity and Peutz-Jeghers syndrome and Carney complex (40% of tumors). The remaining 60% of tumors are sporadic. A 13-year-old male patient underwent a left partial orchiectomy. Intraoperative frozen section was used, and pathology revealed a benign LCCSCT with negative margins. To our knowledge, there is not a case in the literature of an LCCSCT being treated with partial orchiectomy in a pubertal male with a normal contralateral testis.