The diversity of hypospadias management in North America: a survey of pediatric urologists.

PURPOSE: To determine trends in hypospadias management, including surgical techniques and perioperative care, by pediatric urologists in North America. METHODS: An anonymous online survey was devised to assess approaches to hypospadias repair and management, including anesthetic considerations, catheter placement, choice of dressing, and postoperative antibiotic treatment. The survey was sent to all practicing members of the Societies for Pediatric Urology. RESULTS: The survey was completed by 133 (34.5%) respondents. Hypospadias repair was overwhelmingly recommended between ages 6-12 months (89.5%). A local or regional anesthetic block (caudal, penile, pudendal, spinal) is performed nearly universally (96.2%). The majority of surgeons perform distal repairs outpatient (70.7%), while fewer perform outpatient staged repairs (47.4%) or redo surgery (33.8%). Nearly all respondents preferred either VicrylTM/DexonTM (50.4%) or MaxonTM/PDSTM (48.1%) for urethroplasty. All but one respondent leaves a stent for midshaft to proximal repairs whereas stenting for glanular repairs was split with 53.4% leaving a stent. Most surgeons (60.9-70.9%) prescribe postoperative antibiotics regardless of severity and the majority (72.9%) prescribe narcotics for analgesia. CONCLUSIONS: Approaches to hypospadias repair are extremely varied such that there is a lack of consensus among pediatric urologists regarding most aspects of hypospadias management. Investigations comparing hypospadias practice patterns are necessary to develop a standard of care for this complex pediatric urologic entity.

The adolescent glans penis: Functional and aesthetic issues following childhood hypospadias repair.

INTRODUCTION: As children with childhood hypospadias repairs transition into adolescence, the function and appearance of the genitalia acquire greater importance. For some, the direction and shape of the urinary stream can be embarrassing if abnormal, and the appearance of the glans penis and meatus are a concern as they develop the capacity for self-awareness. OBJECTIVE: Herein, we address the surgical correction and outcomes of urine spraying with or without fistulae, and cosmesis over 12 years. We also analyze if any specific prior repairs were more related to their complaints i.e. cosmesis, spraying, and/or fistulae. STUDY DESIGN: We retrospectively reviewed hypospadias revisions by a single surgeon over 12 years. We included adolescents and young adults who complained of abnormal urinary stream and/or aesthetic complaints. Patients then evaluated the post op result as very good, good, acceptable, or unsatisfactory. RESULTS: Of 542 patients who underwent revisionary procedures, 90 (16.6%) presented with complaints of urinary spraying, and appearance of the glans penis and/or meatus (see figure). Of these, 19 (21.1%) presented with aesthetic complaints alone, 37 (41.1%) presented with aesthetic complaints and spraying, and 34 (37.7%) presented with aesthetic concerns, spraying, and were noted to have urethral fistula either during preoperative examination or during surgery. 3/90 patients (3.3%) developed wound infection and dehiscence (one had a tubularized incised plate repair, another a Thiersch-Duplay repair, and the primary repair of the third patient was unknown). CONCLUSIONS: Adolescents and young adults who underwent hypospadias repair during childhood can return with concerns regarding functional and aesthetic abnormalities of the glans penis. Glans sculpting and meatal contouring may be utilized to normalize the urinary stream and achieve a normal aesthetic appearance of the glans penis. Surgeons should follow these patients through adolescence and into adulthood, because complications from hypospadias repairs acquire greater significance later and young adults seek to normalize their phalluses.

Primary renal Ewing Sarcoma masquerading as Wilms in an adolescent female.

Primary renal Ewing's sarcoma (ES) of the kidney represents a rare oncologic entity belonging to the collection of small round cell tumors, which typically feature osseous presentations. Renal ES is an aggressive disease entity with high metastatic potential, either at time of presentation or following initial extirpative therapy. Herein, we report the case of a 14-year-old female who initially presented with intermittent gross painless hematuria and a large left renal mass identified on ultrasound and confirmed on follow up MRI. Following partial nephrectomy (PN), patient was diagnosed with primary renal ES and subsequently underwent completion nephrectomy and chemotherapy.

Advances in bladder substitution and creation of neobladders in children.

Cystectomy and urinary bladder substitution are rare in children but may be necessary in some cases of bladder exstrophy, in the setting of malignancy, or in other settings in which the bladder is severely dysfunctional. This article details advances in surgical techniques in creating continent urinary diversions in this specialized pediatric population.

Nerve Sparing Clitoroplasty is an Option for Adolescent and Adult Female Patients with Congenital Adrenal Hyperplasia and Clitoral Pain following Prior Clitoral Recession or Incomplete Reduction.

PURPOSE: In the past many female patients with congenital adrenal hyperplasia and atypical genitalia were surgically treated with clitoral recession or incomplete reduction of erectile bodies. We report the results of repeat clitoral surgery performed for clitoral pain or enlargement using a nerve sparing reduction clitoroplasty technique. MATERIALS AND METHODS: We identified 6 female patients with congenital adrenal hyperplasia who had undergone prior clitoral recession or incomplete reduction elsewhere. They then presented to our center with clitoral pain or enlargement, where they were treated with nerve sparing clitoroplasty between 2000 and 2010. We collected patient reported data relating to clitoral sensation and sexual function outcomes. RESULTS: Mean ± SD age at evaluation for repeat clitoral surgery was 21 ± 7 years and mean age at clitoroplasty was 22 ± 8 years. Median postoperative followup was 9 months (IQR 32-6). All patients showed improvement with resolution of clitoral pain or enlargement. CONCLUSIONS: Clitoral pain and enlargement upon arousal can be a major concern for women with clitoromegaly and congenital adrenal hyperplasia after clitoral recession is performed. Our series suggests that clitoral recession or incomplete reduction in childhood may be an inadequate initial solution in the congenital adrenal hyperplasia population due to the potential for future androgen elevation and the possibility of later symptom development. In addition we found that patients may be successfully treated with nerve sparing clitoroplasty, resulting in resolution of pain and ability to engage in sexual activity.

Age does not adversely affect sperm retrieval in men undergoing microdissection testicular sperm extraction.

OBJECTIVE: To evaluate the effect of male age on the outcome of microdissection testicular sperm extraction (micro-TESE) and assisted reproductive technology. DESIGN: Clinical retrospective study. SETTING: Center for reproductive medicine at a tertiary university hospital. PATIENT(S): One thousand sixty-seven men with nonobstructive azoospermia. INTERVENTION(S): Micro-TESE, with intracytoplasmic sperm injection when sperm found. MAIN OUTCOME MEASURE(S): Sperm retrieval and clinical pregnancy. RESULT(S): Sperm were successfully retrieved by micro-TESE in 605 men (56.6%) overall. Sperm retrieval rates (SRRs) were higher in men ≥50 years old than men <50, (73% in men ≥50, 56% in men <50). Of the 44 men ≥50 years old, men who had successful micro-TESE had larger mean testis volume (20.8 cc vs. 12.5 cc), a higher frequency of hypospermatogenesis (5.6% vs. 0%), and a lower frequency of Sertoli cells only (12.5% vs. 80%) on diagnostic biopsy. Clinical pregnancy rates were lower in partners of men ≥50 than in partners of men <50 (48% in men <50, 25% in men ≥50). Lower pregnancy rates may be at least partially explained by older female partners for men ≥50 compared to men <50 (mean age 38.0 vs. 36.2 years). Sperm were successfully retrieved across all age groups, and there was no upper male age limit above which sperm could not be retrieved. CONCLUSION(S): Overall, SRRs in men undergoing micro-TESE are not negatively affected by age. Despite successful sperm retrieval in older men with micro-TESE, couples have the best chance of clinical pregnancy with a female partner <35 years old. Some older men with azoospermia may have secondary azoospermia with hypospermatogenesis, explaining the high sperm retrieval rate.

Localization of sperm during microdissection testicular sperm extraction in men with nonobstructive azoospermia.

PURPOSE: We determined the location where sperm were identified during microdissection testicular sperm extraction and characterized the subset of patients for whom complete bilateral exploration was most beneficial. MATERIALS AND METHODS: A total of 900 men underwent a first attempt at microdissection testicular sperm extraction. Sperm extraction began with an initial wide incision in the larger testis. If no sperm were identified, the deeper tissue was extensively microdissected. A similar technique was used on the contralateral testis if no sperm were found on the initial side. RESULTS: In 474 men (52.6%) sperm were identified at the first microdissection testicular sperm extraction. Of these men 308 (65%) had sperm identified through the initial wide incision alone. In men with lower preoperative follicle-stimulating hormone, larger testicular volume, a varicocele history and hypospermatogenesis on preoperative or intraoperative diagnostic biopsy there was a greater chance of finding sperm in the initial wide incision alone (p <0.05). Only 40 of the 506 men (8%) who underwent bilateral testicular microdissection had sperm found on the contralateral side when no sperm were identified on the initial side. In men with Klinefelter syndrome and small testes the chance of sperm retrieval was higher on the contralateral side after negative unilateral microdissection (p <0.05). CONCLUSIONS: More than a third of the men with nonobstructive azoospermia required complete microdissection of the testes to identify sperm. Sperm were found on the contralateral side in up to 8% of the men in whom no sperm were identified in the initial testis.

A comparison of models for predicting sperm retrieval before microdissection testicular sperm extraction in men with nonobstructive azoospermia.

PURPOSE: We developed an artificial neural network and nomogram using readily available clinical features to model the chance of identifying sperm with microdissection testicular sperm extraction by readily available preoperative clinical parameters for men with nonobstructive azoospermia. MATERIALS AND METHODS: We reviewed the records of 1,026 men who underwent microdissection testicular sperm extraction. Patient age, follicle-stimulating hormone level, testicular volume, history of cryptorchidism, Klinefelter syndrome and presence of varicocele were included in the models. For the artificial neural network the data set was divided randomly into a training set (75%) and a test set (25%) with n1/n2 cross validation used to evaluate model accuracy, and then modeled with a neural computational system. In addition, a nomogram with calibration plots was developed to predict sperm retrieval with microdissection testicular sperm extraction. We compared these models to logistic regression. RESULTS: The ROC area for the neural computational system in the test set was 0.641. The neural network correctly predicted the outcome in 152 of the 256 test set patients (59.4%). The nomogram AUC was 0.59 and adequately calibrated. Multivariable logistic regression demonstrated patient age, history of Klinefelter syndrome and cryptorchidism to be significant predictors of sperm retrieval (p <0.05). However, follicle-stimulating hormone and testicular volume were not significant by internal validation. CONCLUSIONS: We modeled a combination of well described preoperative clinical parameters to predict sperm retrieval using a neural computational system and nomogram with acceptable predictive values. The generalizability of these findings requires external validation.

Overweight men with nonobstructive azoospermia have worse pregnancy outcomes after microdissection testicular sperm extraction.

OBJECTIVE: To evaluate the effect of obesity on the outcome of testicular sperm extraction (TESE) and assisted reproductive technology. DESIGN: Clinical retrospective study. SETTING: Center for reproductive medicine at a tertiary-care university hospital. PATIENT(S): Nine hundred seventy patients with nonobstructive azoospermia. INTERVENTION(S): Microdissection TESE followed by intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Sperm retrieval rate and clinical pregnancy rate. RESULT(S): Testicular sperm were successfully retrieved in 55% of men overall. Of those with sperm found, clinical pregnancy rate was 51% and live birth rate 40%. Sperm retrieval rates were similar in men with body mass index (BMI) <25 kg/m(2), 25-30 kg/m(2), and >30 kg/m(2) (59%, 57%, and 54%, respectively). Mean BMI of men who contributed to pregnancy (27.3 ± 4.9 kg/m(2)) was lower than for men whose sperm did not contribute to a pregnancy (28.2 ± 5.4 kg/m(2)). No man with BMI >43 kg/m(2) (n = 11) contributed to a successful pregnancy, even though sperm were found in men with BMI up to 57 kg/m(2). On multivariable logistic regression analysis, male BMI was the only predictor of successful pregnancy among the variables analyzed, including male age, female age, and female BMI. CONCLUSION(S): Overweight men have lower clinical pregnancy rate after microdissection TESE and ICSI compared with men with normal BMI. Men with BMI >43 kg/m(2) did not contribute to any pregnancies, despite successful sperm retrieval.

Preoperative radiographic parameters predict long-term renal impairment following partial nephrectomy.

PURPOSE: We analyzed radiographic parameters describing anatomic features of renal tumors to identify preoperative characteristics that could help predict long-term decline in renal function following partial nephrectomy. METHODS: We retrospectively reviewed the records of 194 consecutive patients who underwent partial nephrectomy from January 2006 to March 2009 and analyzed a cohort of 53 patients for whom complete clinical, radiographic, and operative information was available. Computed tomography images were reviewed by a single radiologist. Radiographic criteria for describing renal tumor size and location included diameter, volume, endophytic properties, proximity to collecting system, anterior/posterior location, location relative to polar lines, and R.E.N.A.L. nephrometry score. Postoperative estimated glomerular filtration rate was calculated using the MDRD study group equation with serum creatinine at last follow-up. RESULTS: The median preoperative and postoperative GFR values were 75 (IQR 65-97) and 66 (IQR 55-84) mL/min/1.73 m(2), respectively. At a median follow-up of 38 months, the median percentage decrease in GFR was 12%. On univariate analyses, tumor diameter (P = 0.002), tumor volume (P < 0.0001), nearness of tumor to collecting system (P = 0.017), and location relative to polar lines (P = 0.017) were associated with percentage decrease in GFR. Furthermore, higher R.E.N.A.L. nephrometry score was also associated with poorer renal functional outcomes following partial nephrectomy (P = 0.019). CONCLUSIONS: Anatomic features of renal tumors defined by preoperative radiographic characteristics correlate with the degree of renal functional decline after partial nephrectomy. Identification of these parameters may assist in patient counseling and clinical decision making following partial nephrectomy. Validation in larger prospective studies is necessary.

Laparoscopic and open partial nephrectomy: complication comparison using the Clavien system.

BACKGROUND AND OBJECTIVES: To compare postoperative complications in patients undergoing laparoscopic and open partial nephrectomy using a standardized complication-reporting system and a standardized tumor-scoring system. METHODS: We conducted a retrospective analysis of 189 consecutive patients with nephrometry scores available who underwent elective partial nephrectomy for renal masses. Demographic, perioperative, and complication data were recorded. By using the modified Clavien scale, we graded 30- and 90-day complication rates. RESULTS: 107 patients underwent laparoscopic partial nephrectomy and 82 underwent open partial nephrectomy (N=189). Open partial nephrectomy patients had higher nephrometry scores than laparoscopic patients had (7.1±2.4 vs. 5.6±1.8, P<.001). Surgical and hospitalization times were shorter, and estimated blood loss was lower in the laparoscopic group (P<.001). At 30 days, there were more overall complications in the open group, but more major complications in the laparoscopic group (P>.05). After multivariable logistic regression analysis, only higher body mass index and higher estimated blood loss were predictors of more overall complications. CONCLUSIONS: Laparoscopic partial nephrectomy has the advantages of decreased operative time, lower blood loss, and shorter hospital stay. The complication rate in the laparoscopic group is similar to that in the open group, despite favorable tumor characteristics in the laparoscopic group.

Role of optimizing testosterone before microdissection testicular sperm extraction in men with nonobstructive azoospermia.

PURPOSE: Although optimizing endogenous testosterone production before testicular sperm extraction is commonly practiced, whether improved preoperative testosterone levels enhance sperm retrieval remains unclear. We evaluated the influence of preoperative medical therapy in men with nonobstructive azoospermia before microdissection testicular sperm extraction. MATERIALS AND METHODS: A total of 1,054 men underwent microdissection testicular sperm extraction from 1999 to 2010. Patients with preoperative testosterone levels less than 300 ng/dl were treated with aromatase inhibitors, clomiphene citrate or human chorionic gonadotropin before microdissection testicular sperm extraction with the goal of optimizing testosterone levels. Patient demographics, preoperative testosterone levels, sperm retrieval rate and pregnancy outcomes were recorded and compared in men with different baseline testosterone levels. RESULTS: Of the 736 men who had preoperative hormonal data 388 (53%) had baseline testosterone levels greater than 300 ng/dl. The sperm retrieval rate in these men was 56%. In the remaining 348 men with pretreatment testosterone levels less than 300 ng/dl, the sperm retrieval rate was similar (52%, p = 0.29). In addition, the sperm retrieval, clinical pregnancy and live birth rates were similar between men who responded to hormonal therapy and those who did not. CONCLUSIONS: Men with nonobstructive azoospermia and hypogonadism often respond to hormonal therapy with an increase in testosterone levels, but neither baseline testosterone level nor response to hormonal therapy appears to affect overall sperm retrieval, clinical pregnancy or live birth rates.

Role of tissue digestion and extensive sperm search after microdissection testicular sperm extraction.

OBJECTIVE: To report the chance of sperm discovery in the laboratory when sperm were not identified in the operating room (OR). DESIGN: Clinical retrospective study. SETTING: Department of urology at a tertiary university hospital. PATIENT(S): A total of 1,054 men with nonobstructive azoospermia who underwent microdissection testicular sperm extraction. INTERVENTION(S): Preoperative and intraoperative parameters were analyzed relative to the chance of sperm identification using a tissue digestion protocol in the laboratory if no sperm were observed in the OR. MAIN OUTCOME MEASURE(S): Sperm retrieval, clinical pregnancy, and live birth rates. RESULT(S): Sperm were found in the OR in 52.5% of the 1,054 men. Of the 501 men for whom sperm were not identified by andrologists in the OR, sperm were found in the laboratory for an additional 35 (7%). On multivariable logistic regression analysis, the presence of germ cells intraoperatively was the only predictor of identifying sperm in the laboratory after tissue digestion. CONCLUSION(S): In men undergoing microdissection testicular sperm extraction, when sperm were not observed in the OR despite extensive mechanical processing, sperm were observed in the laboratory for 7% of the men. This information is valuable in counseling couples in the immediate postoperative period when no sperm were identified intraoperatively.

H2B- and H3-specific histone deacetylases are required for DNA methylation in Neurospora crassa.

Neurospora crassa utilizes DNA methylation to inhibit transcription of heterochromatin. DNA methylation is controlled by the histone methyltransferase DIM-5, which trimethylates histone H3 lysine 9, leading to recruitment of the DNA methyltransferase DIM-2. Previous work demonstrated that the histone deacetylase (HDAC) inhibitor trichostatin A caused a reduction in DNA methylation, suggesting involvement of histone deacetylation in DNA methylation. We therefore created mutants of each of the four classical N. crassa HDAC genes and tested their effect on histone acetylation levels and DNA methylation. Global increases in H3 and H4 acetylation levels were observed in both the hda-3 and the hda-4 mutants. Mutation of two of the genes, hda-1 and hda-3, caused partial loss of DNA methylation. The site-specific loss of DNA methylation in hda-1 correlated with loss of H3 lysine 9 trimethylation and increased H3 acetylation. In addition, an increase in H2B acetylation was observed by two-dimensional gel electrophoresis of histones of the hda-1 mutant. We found a similar increase in the Schizosaccharomyces pombe Clr3 mutant, suggesting that this HDAC has a previously unrecognized substrate and raising the possibility that the acetylation state of H2B may play a role in the regulation of DNA methylation and heterochromatin formation.