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Background: Gonadal damage is a consequence of therapy for pediatric malignancies. Prepubertal males have no semen or mature spermatozoa, posing a challenge for fertility preservation. Testicular tissue cryopreservation is a potential option but is still experimental. We report on a pilot protocol that offered testicular biopsy cryopreservation to families of prepubertal boys with newly diagnosed malignancy. The aims were to determine the acceptability and safety of this procedure.Methods: Parents of prepubertal boys with diagnoses at highest risk for treatment-related gonadal damage were offered the option of testicular cryopreservation. Half of the biopsy was frozen for the subject's potential future use and the remainder used for research. Data on negative intraoperative and/or 7 day post-operative sequelae of testicular biopsies were assessed. Two to four weeks later, parents were asked to complete a questionnaire on factors influencing their decision to have the biopsy or not.Results: Since January 2008, 24 boys have met the eligibility criteria but three required immediate treatment and were excluded. Sixteen of 21 families (76%) consented to testicular biopsy, indicating the prospective acceptability of this option to parents of boys aged 3 months to 14 years; 14 underwent the procedure without any negative intra- or post-operative sequelae. Although the time at diagnosis is stressful, families can give thoughtful consideration to this option. Factors such as religion, finance, ethics and the experimental nature of cryopreservation did not play a major role in decision-making.Conclusions: Parents of prepubertal boys with cancer are willing to pursue testicular tissue cryopreservation at diagnosis, and testicular biopsy caused no acute adverse effects. [ABSTRACT FROM AUTHOR]

Introduction: Testicular torsion is a surgical emergency that is managed with either septopexy-only or tunica vaginalis flap with septopexy if the testis is potentially viable or orchiectomy if not. Minimizing time from ischemia onset to surgery maximizes the likelihood of testicular preservation. While factors such as time from door to OR can be easily targeted, others such as inequalities in access to care are more difficult to address., Objective: We sought to determine whether patient transfer affects testicular outcomes intraoperatively and in the long-term. Secondary goals included investigating the impact of race and Child Opportunity Index (COI) on testicular torsion outcomes and defining the optimal time cutoff from symptom onset to presentation that predicts salvage., Methods: We reviewed our prospective testicular torsion database to identify boys who underwent operative intervention for testicular torsion between January 2015 and March 2022. The association of race and COI with testicular salvage, defined as septopexy-only, was evaluated with univariate and multivariate logistic regression controlling for time to presentation, while the association of transfer with salvage was evaluated with univariate and multivariate logistic regression controlling for age, time to presentation, and time to OR. To determine the optimal cutoff for time to presentation to predict testicular salvage, the Youden index was calculated., Results: Race and COI were not associated with testicular salvage on either univariate or multivariate logistic regression that controlled for time to presentation. Transfer status was not associated with salvage, while age, time from symptoms to presentation, and time from institutional arrival to OR were associated with salvage. The optimal time cutoff to predict salvage using the Youden index was 10.5 hours from symptom onset to presentation and 14.5 hours from symptom onset to detorsion., Discussion: Time to presentation was the strongest, modifiable risk factor associated with testicular salvage. As it may be difficult for children to accurately communicate their symptoms, diagnosis and prompt management of testicular torsion can be delayed. Improvement in outcomes can be achieved by placing greater efforts into patient, parental, and primary care provider education of the signs and symptoms of testicular torsion., Conclusions: Race, COI, and transfer status were not found to have a statistically significant effect on testicular salvage outcomes in patients presenting with testicular torsion. Despite the common premise of a 6-hour window until testicular loss, we found that intervention within the acute window of 14.5 hours from symptom onset is still associated with salvage., Competing Interests: Conflicts of interest None., (Published by Elsevier Ltd.)

Peutz-Jeghers syndrome (PJS) is a childhood-onset cancer predisposition syndrome that is associated with oral freckling and gastrointestinal polyposis. Male patients with PJS are at risk for large-cell calcifying Sertoli cell tumors in childhood. These tumors are estrogen-producing and can cause symptoms of precocious puberty, gynecomastia, and growth acceleration. Here we discuss our experience with spontaneous resolution or stabilization of breast enlargement without medical intervention in three patients with PJS and gynecomastia. These cases indicate that a watchful waiting approach can be considered in the management of gynecomastia in male children with PJS., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Purpose: Testosterone administration prior to hypospadias repair is common practice among pediatric urologists; however, its impact on surgical outcomes remains controversial. We hypothesize that testosterone administration prior to distal hypospadias repair with urethroplasty significantly decreases postoperative complications., Materials and Methods: We queried our hypospadias database for primary distal hypospadias repairs with urethroplasty from 2015 to 2021. Patients undergoing repair without urethroplasty were excluded. We collected information on patient age, procedure type, testosterone administration status, initial visit and intraoperative glans width, urethroplasty length, and postoperative complications. To determine the role of testosterone administration on incidence of complications, a logistic regression adjusting for initial visit glans width, urethroplasty length, and age was performed., Results: A total of 368 patients underwent distal hypospadias repair with urethroplasty. One hundred thirty-three patients received testosterone and 235 did not. Initial visit glans width was significantly larger in the no-testosterone vs testosterone group (14.5 mm vs 13.1 mm, P = .001). Testosterone patients had significantly larger glans width at the time of surgery (17.1 mm vs 14.6 mm [no-testosterone group], P = .001). On multivariable logistic regression analysis after controlling for age at surgery, preoperative glans width, testosterone status, and urethroplasty length, testosterone administration did show significant association with reduced odds of postoperative complications (OR 0.4, P = .039)., Conclusions: This retrospective review of patients shows that on multivariable analysis there is significant association between testosterone administration and decreased incidence of complications in patients undergoing distal hypospadias repair with urethroplasty. Future studies on testosterone administration should focus on specific cohorts of patients with hypospadias as benefits of testosterone may be more evident in some subgroups than others.

Introduction: Patients with Turner syndrome who harbor Y chromosome material are known to be at increased risk of developing germ cell neoplasms. The optimal timing to perform gonadectomy to reduce the risk of cancer development in these patients is not well defined. We present outcomes of Turner with a Y component (TSY) patients who underwent gonadectomy at our institution., Hypothesis/objective: We hypothesized that tumors could occur in a significant portion of TSY patients at any age and gonadectomy can be safely performed at diagnosis rather than deferred., Study Design: We performed an IRB-approved retrospective single center study in which we queried our institutions electronic health record to identify all patients with TSY who underwent gonadectomy at our institution from 2012 to 2021., Results: In our series of 18 consecutive TSY patients, a tumor was identified in 6 patients (33.3%): 4 (22.2%) with dysgerminoma (DG) [Fig. 1] and 2 (11.1%) with gonadoblastoma (GB)., Discussion: Our cohort of 18 consecutive TSY who underwent gonadectomy over a 9-year period is the largest published single site cohort to date. Additionally, our patient who was found to have GB at 40 days is to our knowledge the youngest TSY patient to be diagnosed with GB in the literature. This patient's remarkably early incidence of tumor occurrence illustrates the urgency of protective gonadectomy. Given the high incidence of tumor formation in this population and the minimal morbidity associated with gonadectomy, we do not recommend delaying gonadectomy in this population for any reason. Our study is vulnerable to selection bias and confounding innate to any retrospective study. There was variation with respect to the frequency and timing of pre-operative imaging as a strict preoperative imaging protocol with sequential studies was not in place at our institution. Additionally, we do not have a comparison cohort of patients who are being followed without operative intervention as all TSY patients at our institution have undergone gonadectomy., Conclusion: TSY patients cannot be safely observed for tumor formation based on clinical factors such as imaging or age. Gonadectomy is safe with a low complication rate and without tumor recurrence during three-year follow-up. We continue to recommend bilateral gonadectomy in this patient population at the time of diagnosis., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: Differences of sex development (DSD) are congenital conditions in which individuals are discordant in their chromosomal, phenotypic, and/or gonadal sex. Treatment of DSD can involve surgical intervention to external genitalia to make anatomy seem male-typical (i.e., male genitoplasty). Caregiver-perceived decisional regret regarding young boys with DSD was explored quantitatively and qualitatively., Method: Participants (N = 39) were caregivers of infants (N = 23) diagnosed with DSD (mean age = 8.9 months, standard deviation = 5.9 months) reared male participating in a longitudinal investigation of psychosocial outcomes. Qualitative data were collected at 6 to 12 months after baseline enrollment to evaluate caregiver decision-making corresponding to levels of regret concerning their child's treatment. All but one infant received genital surgery before caregiver reporting on their decisional regret. Quantitative exploratory analyses evaluated longitudinal predictors of decisional regret at 6 to 12 months., Results: When completing a write-in item inquiring about decision-making and potential regret, most caregivers (n = 16, 76%) reported that their child's genital surgery was their first medical decision. Two caregivers referenced gender assignment as a decision point. One-third of caregivers reported some level of decisional regret (33%), with 67% reporting no regret. No hypothesized predictors of decisional regret were statistically significant., Conclusion: Many caregivers of infants with DSD reared male view genital surgery as a first health care decision. Approximately one-third of caregivers reported some level of decisional regret. Further research is warranted to explore long-term decisional regret; it will be particularly important to investigate the decisional regret of patients with DSD., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Study Objective: Infants with genital development considered atypical for assigned female sex may undergo feminizing genitoplasty (clitoroplasty and/or vaginoplasty) in early life. We sought to identify factors associated with parent/caregiver decisions regarding genitoplasty for their children with genital virilization., Design: Longitudinal, observational study SETTING: Twelve pediatric centers in the United States with multidisciplinary differences/disorders of sex development clinics, 2015-2020 PARTICIPANTS: Children under 2 years old with genital appearance atypical for female sex of rearing and their parents/caregivers INTERVENTIONS/OUTCOME MEASURES: Data on the child's diagnosis and anatomic characteristics before surgery were extracted from the medical record. Parents/caregivers completed questionnaires on psychosocial distress, experience of uncertainty, cosmetic appearance of their child's genitalia, and demographic characteristics. Urologists rated cosmetic appearance. For 58 patients from the study cohort with genital virilization being raised as girls or gender-neutral, we compared these data across 3 groups based on the child's subsequent surgical intervention: (i) no surgery (n = 5), (ii) vaginoplasty without clitoroplasty (V-only) (n = 15), and (iii) vaginoplasty and clitoroplasty (V+C) (n = 38)., Results: Fathers' and urologists' ratings of genital appearance were more favorable in the no-surgery group than in the V-only and V+C groups. Clitorophallic length was greater in the V+C group compared with the V-only group, with substantial overlap between groups. Mothers' depressive and anxious symptoms were lower in the no-surgery group compared with the V-only and V+C groups., Conclusions: Surgical decisions were associated with fathers' and urologists' ratings of genital appearance, the child's anatomic characteristics, and mothers' depressive and anxious symptoms. Further research on surgical decision-making is needed to inform counseling practices., (Copyright © 2022. Published by Elsevier Inc.)

Introduction and Objective: Opioid stewardship is recognized as a critical clinical priority. We previously reported marked reductions in narcotic administration after implementation of an opioid reduction protocol for pediatric ambulatory urologic surgery. We hypothesize that a decrease in post-operative and discharge opioid administration will not increase short-term adverse events., Study Design: All pediatric patients undergoing open or robot-assisted laparoscopic pyeloplasty or ureteral reimplantation between 2015 and 2019 were included. Patients' demographics, opioid and NSAID administration, urology or pain-related emergency department (ED) visits, readmissions, and reoperations within 30 days of surgery, were aggregated., Results: 438 patients, with a median age of 3.5 years (IQR 1.5-8.3) at the time of surgery, met the inclusion criteria. Annual rates of inpatient opioid administration and prescriptions decreased significantly over the study period, while rates of intra-operative, inpatient, and prescribed NSAIDs significantly increased. There was no significant difference in the occurrence of ED visits, readmissions, or reoperations within 30 days of surgery between patients who received an opioid prescription and those who did not. Multivariate regression showed that patients who did not receive an opioid prescription at discharge were found to be at a lower risk for unplanned encounters including ED visits, readmissions, or reoperations (OR:0.5, 95%CI: 0.2-0.9, p = 0.04)., Discussion: The present study shows the decreasing trend in inpatient opioid administration and opioid prescription after discharge, when accompanied by an increase NSAID administration, does not result in a significant change in rates of unplanned encounters and complications, similar to results from previous studies on non-urological and ambulatory urological surgeries., Conclusions: Non-opioid pain control after major pediatric urologic reconstruction is safe and effective. We found that a reduction in opioid administration can be associated with a reduced risk of unplanned ED visits, readmissions, or reoperations. Further investigations are required to corroborate this finding., Competing Interests: Conflict of interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To report on our experience performing office-based pediatric urologic procedures. We hypothesize that office-based interventions are safe and effective for children, avoiding unnecessary risk and cost associated with general anesthesia., Methods: We retrospectively identified patients undergoing office-based interventions from 2014 to 2019, including lysis of penile or labial adhesions, division of skin bridges, meatotomy and excision of benign lesion. Success was defined as a completed attempt in the office. Failure includes any unsuccessful office attempts. Complications include 30-day ED visits/readmissions and recurrent skin bridge post division of skin bridge., Results: We identified 1326 interventions: 491 lyses of penile adhesions (37%), 320 division of skin bridges (24%), 128 lyses of labial adhesions (10%), 348 meatotomies (26%), and 39 excisions of benign lesions (3%) [Table 1]. There was a >95% success rate reported in every procedure with an overall complication rate of 0.6%. Excision of benign lesion had 100% success rate. ED visits within 30 days are rare (0.2%), and no patients required admission after their procedure [Table 2]. The rate of recurrence was highest following lysis of labial adhesions (13.3%). Of the 54 patients who underwent retreatment, very few required general anesthesia (n = 6)., Conclusion: Office-based urologic interventions in children are well tolerated with excellent safety and efficacy. Complications and recurrence are universally low. Ultimately, 99.5% of this cohort was managed under local anesthetics, thereby avoiding the risks of anesthesia use in the pediatric population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: This study identifies trajectories of parent depressive symptoms after having a child born with genital atypia due to a disorder/difference of sex development (DSD) or congenital adrenal hyperplasia (CAH) and across the first year postgenitoplasty (for parents who opted for surgery) or postbaseline (for parents who elected against surgery for their child). Hypotheses for four trajectory classes were guided by parent distress patterns previously identified among other medical conditions., Methods: Participants included 70 mothers and 50 fathers of 71 children diagnosed with a DSD or CAH with reported moderate to high genital atypia. Parents were recruited from 11 US DSD specialty clinics within 2 years of the child's birth and prior to genitoplasty. A growth mixture model (GMM) was conducted to identify classes of parent depressive symptoms over time., Results: The best fitting model was a five-class linear GMM with freely estimated intercept variance. The classes identified were termed "Resilient," "Recovery," "Chronic," "Escalating," and "Elevated Partial Recovery." Four classes have previously been identified for other pediatric illnesses; however, a fifth class was also identified. The majority of parents were classified in the "Resilient" class (67.6%)., Conclusions: This study provides new knowledge about the trajectories of depressive symptoms for parents of children with DSD. Future studies are needed to identify developmental, medical, or familial predictors of these trajectories., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Disorders/differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. While there remains controversy around the traditionally binary concept of sex, most patients with DSD are reared either male or female depending on their genetic sex, gonadal sex, genital phenotype and status of their internal genital tract. This study uses prospective data from 12 institutions across the United States that specialize in DSD care. We focused on patients raised female. Eligible patients had moderate to severe genital atypia (defined as Prader score >2), were ≤2 years of age at entry, and had no prior genitoplasty. The aim of this study is to describe early post operative complications for young patients undergoing modern approaches to feminizing genitoplasty. Of the 91 participants in the cohort, 57 (62%) were reared female. The majority had congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (n = 52), 1 had ovo-testicular syndrome, 2 had mixed gonadal dysgenesis and 2 had partial androgen insensitivity syndrome (PAIS). Of the 50 participants who received early genitoplasty, 43 (86%) had follow-up at 6-12 months post-surgery. Thirty-two participants (64%) received a clitoroplasty, 31 (62%) partial urogenital mobilization and 4 (8%) total urogenital sinus mobilization. Eighteen percent (9/50) experienced post-surgical complications with 7 (14%) being rated as Clavien-Dindo grade III. Both parents and surgeons reported improved satisfaction with genital appearance of participants following surgery compared to baseline. This information on post-operative complications associated with contemporary approaches to feminizing genitoplasty performed in young children will help guide families when making decisions about whether or not to proceed with surgery for female patients with moderate to severe genital atypia., (Published by Elsevier Ltd.)

Purpose: We evaluated demographic, financial and support predictors of distress for parents of young children with disorders of sex development including atypical genital development, and characterized early parental experiences. This work extends our previous findings to identify those parents at risk for distress., Materials and Methods: Participants included mothers (76) and fathers (63) of a child (78) diagnosed with disorders of sex development characterized by moderate to severe genital atypia. Parents completed a demographic questionnaire, measures of anxious and depressive symptoms, quality of life, illness uncertainty and posttraumatic stress symptoms, and rated their satisfaction with the appearance of their child's genitalia., Results: Depressive and posttraumatic stress symptoms of caregivers were comparable to standardized norms while levels of anxious symptoms were below norms. A subset of parents reported clinically elevated symptoms. Overall 26% of parents reported anxious symptoms, 24% reported depressive symptoms and 17% reported posttraumatic stress symptoms. Levels of illness uncertainty were lower than those of parents of children with other chronic illnesses. Differences by parent sex emerged, with mothers reporting greater distress. Lower income, increased medical care and travel expenses, and having no other children were related to increased psychosocial distress., Conclusions: Early psychosocial screening is recommended for parents of children with disorders of sex development. Clinicians should be aware that financial burden and lack of previous parenting experience are risk factors for distress.

Parents of children with disorders of sex development (DSD) report significant psychological distress, including posttraumatic stress symptoms (PTSS), with mothers consistently reporting higher rates of psychological distress than fathers. However, psychological factors contributing to PTSS in both parents are not well understood. The present study sought to fill this gap in knowledge by examining PTSS and illness uncertainty, a known predictor of psychological distress, in parents of children recently diagnosed with DSD. Participants were 52 mothers (M age  = 32.55 years, SD = 5.08) and 41 fathers (M age  = 35.53 years, SD = 6.78) of 53 infants (M age  = 9.09 months, SD = 6.19) with DSD and associated atypical genital development. Participants were recruited as part of a larger, multisite study assessing parents' psychosocial response to their child's diagnosis of DSD. Parents completed measures of illness uncertainty and PTSS. Mothers reported significantly greater levels of PTSS, but not illness uncertainty, than fathers, and were more likely than fathers to report clinical levels of PTSS (21.2% compared to 7.3%). Hierarchical regression revealed that parent sex, undiagnosed or unclassified DSD status, and illness uncertainty were each associated with PTSS. The overall model accounted for 23.5% of the variance associated with PTSS. Interventions targeting illness uncertainty may be beneficial for parents of children with newly diagnosed DSD.

Purpose: Upper pole nephrectomy has been the traditional surgical management of children with poorly functioning upper pole moieties in duplex renal collecting systems having ureteral ectopia and ureterocele. However, ablative surgery confers a risk of functional loss to the remnant moiety due to vasospasm or vascular injury. It was hypothesized that ipsilateral ureteroureterostomy (IUU) is a safe and feasible approach for the management of these patients and that residual function in the obstructed upper pole does not affect surgical outcomes., Materials and Methods: All patients with duplex systems who underwent IUU between 2010 and 2016 were retrospectively reviewed. Patients were sorted into two groups based on pre-operative imaging: those having <10% upper pole moiety function (UPMF) and those having ≥ 10% UPMF. Outcomes assessed were postoperative complications (Clavien-Dindo classification), need for secondary surgery, and radiological outcomes., Results: The study cohort comprised 53 children with ectopia or ureterocele affecting the upper pole in a duplex system, 21 with UPMF <10% (median function 0% and median age 1.49 years) and 32 with UPMF ≥ 10% (median function 15% and median age 0.91 years). Median follow-up was 27.4 months and 27.6 months. In both the groups, prenatal hydronephrosis was the most common presentation (57% and 56%, respectively; p = 0.18) followed by urinary tract infection. Mann-Whitney U test comparing the two groups revealed no significant differences in any of the outcomes assessed. No patient required secondary surgery., Conclusion: Ipsilateral ureteroureterostomy is a safe, definitive surgical intervention that preserves the renal architecture in children with duplex collecting systems regardless of upper pole function., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: Little is known about the phenotypes, diagnoses, and sex of rearing of infants with atypical genital development in the United States. As part of a multicenter study of these infants, we have provided a baseline report from US difference/disorder of sex development clinics describing the diagnoses, anatomic features, and sex of rearing. We also determined whether consensus guidelines are followed for sex designation in the United States., Methods: Eligible participants had moderate-to-severe genital atypia, were aged <3 years, and had not undergone previous genitoplasty. Karyotype, genetic diagnosis, difference/disorder of sex development etiology, family history, and sex of rearing were collected. Standardized examinations were performed., Results: Of 92 subjects, the karyotypes were 46,XX for 57%, 46,XY for 34%, and sex chromosome abnormality for 9%. The median age at the baseline evaluation was 8.8 months. Most 46,XX subjects (91%) had congenital adrenal hyperplasia (CAH) and most 46,XY subjects (65%) did not have a known diagnosis. Two individuals with CAH underwent a change in sex of rearing from male to female within 2 weeks of birth. The presence of a uterus and shorter phallic length were associated with female sex of rearing. The most common karyotype and diagnosis was 46,XX with CAH, followed by 46,XY with an unknown diagnosis. Phenotypically, atypical genitalia have been most commonly characterized by abnormal labioscrotal tissue, phallic length, and urethral meatus location., Conclusions: An increased phallic length was positively associated with rearing male. Among the US centers studied, sex designation followed the Consensus Statement recommendations. Further study is needed to determine whether this results in patient satisfaction.

Introduction: In testicular torsion, ischemia time from pain onset impacts testicular salvage. A tunica albuginea fasciotomy to relieve compartment pressure followed by a tunica vaginalis flap (TVF) may enhance salvage., Objective: To define the optimal window of ischemia time during which TVF may be most beneficial to avoid orchiectomy., Study Design: A retrospective cohort study of males presenting with testicular torsion at a single tertiary-care institution from January, 2003 to March, 2017. Ischemia time was defined as duration of pain from onset to surgery. Because TVF would be an option to orchiectomy, and it was found that ischemia time was longer in testicles that underwent orchiectomy, matching was performed. Cases of torsion treated with TVF were matched 1:1 with cases treated with orchiectomy on age at surgery, and ischemia time. Outcomes included postoperative viability, defined as palpable testicular tissue with normal consistency, and atrophy, defined as palpable decrease in size relative to contralateral testicle. Sensitivity analyses were performed restricting to the subgroups with postoperative ultrasound, >6 months' follow-up, and additionally matching for degrees of twist., Results: A total of 182 patients met eligibility criteria, of whom 49, 36, and 97 underwent orchiectomy, TVF, and septopexy alone, respectively. Median follow-up was 2.7 months; 26% of patients had postoperative ultrasound (61% of TVF group). In the orchiectomy, TVF, and septopexy groups, respectively, median ischemia times were 51, 11, and 8 h, postoperative viability rates were 0, 86, and 95%, and postoperative atrophy rates were 0, 68, and 24%. After matching, 32 patients with TVF were matched to 32 patients who underwent orchiectomy. In the TVF group, postoperative viability occurred in 95% (19/20) vs 67% (8/12) of patients with ischemia times ≤24 and >24 h, respectively. Atrophy occurred in 67% (12/18) vs 83% (10/12) of these same respective patients. Sensitivity analysis by ultrasound and longer follow-up found similar viability results, although atrophy rates were higher. Additional matching for degrees of twist showed lower viability and higher atrophy rates for increasing ischemia times., Discussion: Patients who presented with testicular torsion with ischemia times ≤24 h and who were being considered for orchiectomy may have benefitted most from TVF, albeit at high risk of atrophy. However, for ischemia times >24 h, TVF may still have preserved testicular viability in two-thirds of cases. A limitation was short follow-up., Conclusion: A TVF was a valid alternative to orchiectomy for torsed testicles, albeit with high testicular atrophy rates., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Re-operative penile reconstruction is challenging and requires tension-free skin closure. The repair popularized by Cecil and Culp in the 1940s, using the scrotum to provide a temporary vascularized bed for complex hypospadias repairs, fell out of favor due to temporal trends towards single-stage repairs and concern for utilizing hair-bearing skin on the penile shaft., Objective: It was hypothesized that a modified Cecil-Culp (CC) concept of penile scrotalization, leaving the penis attached to the scrotum for 1 year rather than 6 weeks as originally described, improves outcomes with this reconstruction for ventral skin deficiency or poor vascular support., Methods: Institutional Review Board-approved registries were reviewed to identify patients who underwent a CC repair during 1987-2016 at two institutions. Cecil-Culp technique was utilized in multi-stage hypospadias complication repairs or for insufficient ventral penile shaft skin coverage. Anatomic abnormality, number and type of prior surgeries, and complications before and after CC were recorded., Results: Thirty-nine patients underwent CC: 23 failed hypospadias repairs, three hypospadias after bladder exstrophy, 10 penile curvature following circumcision, and three with skin loss from trauma. Mean age at CC was 61.8 months (hypospadias), and 59.8 months (non-hypospadias). Hypospadias patients underwent a mean of 3.6 surgeries (range 1-9) prior to CC. Four of the 39 patients (10.3%) had perioperative complications after CC, including scrotal abscess, skin infections, and difficulty removing the urethral stent. Eight of 37 (21.6%) patients had longer-term complications related to their hypospadias repair, including fistulae, diverticula, dehiscence, and stricture. Mean time from CC placement to release was 345 and 473 days for hypospadias and non-hypospadias cases, respectively. There was no apparent scrotal skin transferred to the penile shaft at the final take-down. Mean follow-up was 22.3 months., Discussion: Embedding the penis into the scrotum for added vascularity and ventral skin coverage has been used effectively in cases of the most tenacious fistulas and for significant skin loss and trauma. Limitations of this study were its retrospective approach at two institutions over an extended period of time by multiple surgeons, so patient selection and procedure may have varied., Conclusions: Modification of CC repair by delaying 9-12 months before CC take-down enhanced the benefits of a robust vascular bed for wound healing, and helped to avoid transfer of hair-bearing scrotal skin to the penile shaft. The CC technique is an important tool for penile reconstructive surgery of complex hypospadias repairs with inadequate skin, and for traumatic injuries., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background/aims: Parents of children born with disorders of sex development (DSD) often experience anxiety, but risk factors, including parental perception of the severity of their child's DSD, have not been examined. We hypothesized that severity of illness (SOI) ratings would relate to parental anxiety, and would be higher for parents of children with a potentially life-threatening DSD (e.g., 21-hydroxylase deficiency)., Methods: Eighty-nine parents (Mage = 33.0, 56.2% mothers) of 51 children (Mage in months = 8.7) with a DSD including ambiguous genitalia were recruited from 12 specialized DSD clinics. Parents completed questionnaires prior to genitoplasty, 6 months post-genitoplasty, and 12 months post-genitoplasty (if completed). Data were analyzed with linear mixed modeling., Results: Parental anxiety decreased over time, χ2(1) = 10.14, p < 0.01. A positive relationship between SOI and anxiety was found, with SOI being a strong predictor of anxiety (b = 0.53, p < 0.01; χ2[1] = 5.33, p < 0.05). An SOI by time interaction indicated SOI had an increasing effect on anxiety over time, b = 0.06, p < 0.05; χ2(1) = 6.30, p < 0.05. There was no diagnosis by SOI interaction., Conclusion: Parental anxiety decreased over time, but those with higher SOI ratings reported greater initial anxiety followed by slower resolution over time. Underlying etiology of DSD had no effect on the relationship between SOI and anxiety., (© 2018 S. Karger AG, Basel.)

Purpose: We examined the psychological adjustment of parents of children born with moderate to severe genital atypia 12 months after their child underwent genitoplasty., Materials and Methods: Parents were recruited longitudinally from a multicenter collaboration of 10 pediatric hospitals with specialty care for children with disorders/differences of sex development and/or congenital adrenal hyperplasia. Parents completed measures of depressive and anxious symptoms, illness uncertainty, quality of life, posttraumatic stress and decisional regret., Results: Compared to levels of distress at baseline (before genitoplasty) and 6 months after genitoplasty, data from 25 mothers and 20 fathers indicated significant improvements in all psychological distress variables. However, a subset of parents continued endorsing clinically relevant distress. Some level of decisional regret was endorsed by 28% of parents, although the specific decision that caused regret was not specified., Conclusions: Overall the majority of parents were coping well 1 year after their child underwent genitoplasty. Level of decisional regret was related to having a bachelor's level of education, increased levels of illness uncertainty preoperatively and persistent illness uncertainty at 12 months after genitoplasty but was unrelated to postoperative complications., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The birth of a child with a disorder of sex development (DSD) and atypical genitalia can be traumatizing and isolating for families. Parents of children with DSD are at risk for increased levels of psychological distress, including depression, anxiety, illness uncertainty (IU), post-traumatic stress symptoms (PTSS), and impairments in quality of life (QOL). Our previous report indicated that although the majority of parents of children with atypical genitalia were coping well prior to the child's genitoplasty, approximately 25% of them reported experiencing some type of psychological distress., Objective: The current study sought to examine the trajectory of parental psychological distress prior to, and 6 months after their child underwent genitoplasty., Methods: Parents were recruited as part of an ongoing, prospective, multi-site study involving 10 pediatric hospitals with specialized care for children with atypical genitalia. Results from 49 parents (27 mothers, 22 fathers) of 28 children (17 female sex of rearing, 11 male sex of rearing) born with atypical genitalia (Prader rating of 3-5 in 46,XX DSD or by a Quigley rating of 3-6 in 46,XY DSD or 45,XO/46,XY) were included in the study., Results: There were no significant changes in level of depressive or anxious symptoms or quality of life between baseline and 6-month post-operative follow-up, although mothers continued to report significantly higher levels of depressive symptoms than fathers, and as a group, these parents reported lower QOL than published norms. The level of PTSS significantly decreased for all parents, suggesting that parents may have come through the acute stress phase associated with their child's diagnosis. Finally, while there were no significant changes in IU over the time period, the level of IU for parents of boys actually increased, while parents of girls reported no change (Figure)., Conclusion: Six months after their child has undergone genitoplasty, the majority of parents report minimal levels of psychological distress. However, a subset of these parents continue to experience significant distress related to their child's diagnosis. Specifically, parents of boys appear to be at increased risk for difficulties, which may be related to either the lack of clinical diagnosis for almost half of these children or the necessity of two-stage surgeries for the majority of them. We will continue collecting data on these families to better understand the trajectory of these adjustment variables., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Disorders of sex development (DSD) are a heterogeneous group of complex conditions that can affect chromosomal, gonadal, and/or phenotypical sex. In addition to impacts on internal and external genitalia,these conditions can affect fertility potentialto various degrees. In this review we discuss fertility issues including gonadalpreservation and reproductive outcomes based on specific DSD conditions., Methods and Materials: A systematic literature review was performed on Embase ™ , PubMed ® , and Google Scholar ™ for disordersof sex development and infertility. Original research articles and relevant reviews were examinedand a synopsis of these data was generated for a comprehensive review of fertility potential in disorders of sex development., Results: While patients with some DSDs may have functioning gonads with viable germ cells but an inability to achieve natural fertility secondary to incongruent internal or external genitalia, other patients may have phenotypically normal genitalia but infertility due to abnormal gonad development. Fertility rates in females with congenital adrenal hyperplasia (CAH) depend on phenotype and are inversely proportionalto the severity of the disease. Men with classic CAH have reduced fertility and due to the presence of testicular adrenal rest tumors and to suppression of the hypothalamic-pituitary-gonadal axis by high systemic levels of androgens. Infertility is seen in complete androgen insensitivity and subfertility is common in partial cases. Fertility is rare in pure or mixed gonadal dysgenesis, ovotesticular disorder, Klinefelter syndrome, and XX males., Conclusion: Fertility potential appears to be the highest in patientswith XX or XY CAH, especially non-classic forms. Advancements in assisted reproduction techniques has in rare cases produced offspring in some diagnoses thought to be universally infertile. Discussion of fertility issues with the patient and family is essential to the optimal treatment of each patient and an important part of the multi-disciplinary approach to evaluating and counseling these families., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: The symptomatic calyceal diverticulum is a rare event in the pediatric population. In adults, surgical options include ureteroscopy, percutaneous ablation, and laparoscopic decortication but there is a lack of experience in the literature with these techniques., Objective: We present our experience with both the ureteroscopic and laparoscopic approach to treating the pediatric calyceal diverticulum., Study Design: We performed a retrospective case series looking at patients who underwent treatment for calyceal diverticulum at our institution from January 2009 to May 2014. We reviewed patient demographics, indications for intervention, radiographic appearance, type of intervention, and perioperative outcomes. Ureteroscopic approach included dilation of infundibulum and ablation of diverticular cavity. Laparoscopic approach included ablation of the diverticulum with argon diathermy with or without surgical closure of the ostium., Results: There were 13 patients who underwent 15 procedures for symptomatic calyceal diverticulum (Table). Median age was 11 years. Indications for intervention were: pain and increasing size of diverticulum (8/15, 55%), hematuria (3/15, 20%), UTI (3/15, 20%), and calculi (1/15, 5%). 11/15 (73%) procedures were managed endoscopically and 4/15 (27%) were managed with laparoscopic decortication. Ureteral stent was left in all patients for a mean duration of 51 days (15-120 days). Follow up imaging at median of 2.1 years (0.5-4 years) revealed an initial success rate of 85% (11/13 patients). Two patients failed initial intervention (persistent pain/increasing size) necessitating successful secondary minimally invasive procedures. There were 2 (13%) complications: a perinephric hematoma post endoscopic ablation which resolved spontaneously and a deep venous thrombosis in a patient with a coagulation disorder in the laparoscopic group., Discussion: Limitations of our study include its retrospective design, lack of standardization of the treatment approach amongst the four treating surgeons, and the small number of patients requiring intervention for this relatively rare diagnosis. Our study is the largest to date in the pediatric population and is the first to report outcomes with ureteroscopic management of the calyceal diverticulum., Conclusions: We found that the pediatric calyceal diverticulum can be successfully treated in a minimally invasive manner. The endoscopic approach should be the first line option for patients with small, endophytic diverticula, particularly those located in the upper and mid pole. The laparoscopic approach is more invasive but should be considered for large diverticula that are exophytic with thin overlying parenchyma., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: Partial nephrectomy is increasingly used in children with bilateral Wilms' tumor (BWT) or contralateral recurrence. Nephron-sparing surgery seeks to achieve complete tumor removal while preserving functional renal parenchyma. Previous series have documented high rates of complications, recurrence, and mortality., Methods: Twelve patients (4 boys and 8 girls aged 9-42 months) with BWT or contralateral recurrence were treated at our institution with unilateral or bilateral partial nephrectomy. Preoperative imaging, operative notes, and pathology reports were reviewed. Outcomes analyzed included complications, recurrence, readmission rate, postoperative glomerular filtration rate (GFR), and survival., Results: All patients underwent successful nephron-sparing resection using standard techniques, with only 2 patients requiring unilateral nephrectomy. Median length of stay was 3 days. There were no major complications or urine leaks. Two patients were lost to follow-up. The remaining 10 were followed up for a median of 36 months (range, 3-79 months). There have been no recurrences or unplanned readmissions. Mean GFR is 107.7 (± 32.8) mL/min per 1.73 m(2), with no patient having a GFR below the lower limit of normal for age., Conclusion: Nephron-sparing resection is a safe and effective approach for children with BWT or contralateral recurrence and should be part of the multimodality therapeutic approach to this disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Human chorionic gonadotropin (HCG) has a stimulatory effect on testicular steroidogenesis and has been widely used for evaluating male Leydig cell function. However, considerable variability exists in the protocols for HCG stimulation tests. In the most commonly used protocols HCG is administered daily for several days. We examine the circulating androgen response after 1 and 3-dose HCG regimens., Materials and Methods: We evaluated 77 prepubertal boys diagnosed with hypospadias, cryptorchidism or micropenis. In 60 boys who underwent 1 dose of 100 IU/kg. or 5,000 IU/1.7 m.(2) HCG serum testosterone and dihydrotestosterone were sampled at 72 (28) and 96 (32) hours after injection, while in 17 who underwent 3 daily age adjusted doses hormone levels were determined on day 4. All blood specimens were obtained and injections were performed at 8:00 to 9:00 a.m. and all specimens were evaluated at the same endocrine reference laboratory., Results: Nonstimulated testosterone levels were prepubertal in all groups. In the 1-dose groups post-stimulation testosterone was elevated 22 to 29-fold from baseline after a weight based and 34 to 35-fold after a body surface area based dose. Testosterone increased 20-fold baseline in the multi-dose group. No significant differences were observed in 72 versus 96-hour hormone levels., Conclusions: Evaluating Leydig cell function by HCG stimulation is an important adjunct to the diagnosis of various urological conditions. A single weight or body surface area based HCG dose with androgen measurement after 3 or 4 days is a practical, reliable and cost saving change in testicular evaluation.

Purpose: Hypospadias is a common genitourinary anomaly affecting every 1/300 male newborns. The goals of hypospadiac surgery include a straight penis with a urethral meatus at the tip of the glans, a well vascularized neourethra of adequate caliber with a solid, straight urinary stream and achievement of sexual function when mature. Current theory advocates preservation of the urethral plate with chordee correction. Hypospadias repair without an adequate urethral plate to roll into a tube requires longitudinal incision of the plate or a transverse preputial island flap. We describe a technique of 1-stage urethroplasty using an inner preputial based dorsal inlay graft., Materials and Methods: After the penis is degloved and chordee corrected incisions are made bilaterally along the urethral plate from the native urethral meatus to the glans tip. The urethral plate is incised longitudinally. A graft harvested from the inner prepuce is defatted and sutured onto the incised urethral plate. The neourethra is rolled into a tube in Thiersch-Duplay fashion., Results: This technique was used in 32 patients. The original urethral meatus was coronal to penoscrotal and chordee release was performed concomitantly. At 21 months of followup no patient had a stricture, fistula or diverticulum at the inlay graft site., Conclusions: This technique successfully fulfills all traditional hypospadias repair criteria. We believe that the dorsal inlay graft after incision of the urethral plate is a rapid, easy and successful addition to the armamentarium of the "hypospadiologist."

Purpose: In patients suspected to have the vertebral, anal, tracheoesophageal, renal, radial, cardiac and limb abnormalities (VACTERL) association we studied the frequency of upper urinary tract anomalies, prevalence of these features, predictability of upper tract pathology and proper screening evaluation., Materials and Methods: From 1991 to 1998 we identified 55 patients with the VACTERL association. Upper urinary tract assessment, including initial renal ultrasound and voiding cystourethrography, and followup data were available for 29 boys and 15 girls. Patients were considered to have the VACTERL association when 3 or more organ systems were involved., Results: Average followup was 5.4 years. Upper urinary tract involvement was noted in 41 of the 44 patients (93.2%) and vesicoureteral reflux in 17 (25 renal units). Of the kidneys 21 were hydronephrotic without reflux or obstruction, 10 were solitary, 3 were multicystic dysplastic, 8 were obstructed and only 17 were normal. A total of 27 patients (61%) underwent at least 1 genitourinary procedure, primarily ureteroneocystotomy. All children were alive at the last followup., Conclusions: The VACTERL association involves multiple serious anomalies. However, these infants generally have a good outcome. Since the upper urinary system is the most common organ system involved, patients should receive prophylactic antibiotics until an initial urological assessment with renal ultrasound and voiding cystourethrography is performed. It is essential for physicians to know that most children with the VACTERL association have urological involvement that requires treatment and long-term management.

An infant born at 38 weeks' gestation with ambiguous genitalia had a prenatal 45X karyotype but an enlarged phallus on an ultrasound scan at 31 weeks' gestation. The newborn examination demonstrated penoscrotal hypospadias with chordee and two gonads palpable in the scrotum with a right hydrocele. Ultrasound showed a saccular structure containing debris behind the bladder. The postnatal karyotype was revealed to be 45X/46XY, with a pseudodicentric Y chromosome. Cystoscopy/genitography identified a uterus and a right fallopian tube, which were removed along with a dysgenetic right gonad. Biopsy of the descended left gonad revealed rare germ cells. The final diagnosis was 45X/46XY male pseudohermaphroditism with testicular dysgenesis. One should be aware of possible chromosomal mosaicism and combine the prenatal karyotype with the ultrasound genital findings to formulate an intersex differential diagnosis.

Purpose: Approximately 10 to 30% of prenatal cases of hydronephrosis result in the postnatal diagnosis of vesicoureteral reflux. Using a new generic prenatal-postnatal data sheet developed by the Society for Fetal Urology the characteristics, natural history and outcome of prenatal hydronephrosis confirmed postnatally to be vesicoureteral reflux were documented at 3 centers., Materials and Methods: We performed a retrospective multicenter review of Society for Fetal Urology data sheets completed for each patient in whom prenatal hydronephrosis was proved to be postnatal vesicoureteral reflux from 1993 to 1998., Results: In 56 male and 15 female patients with prenatal hydronephrosis a total of 116 refluxing renal units were confirmed postnatally. Of the 116 renal units 112 were hydronephrotic prenatally. During gestation increased hydronephrosis was noted with voiding in 4 cases. Of the 112 hydronephrotic renal units only 26 ureters in 15 patients were seen prenatally. The obstetrician considered the diagnosis of vesicoureteral reflux in only 24% of the cases. Postnatally 116 refluxing renal units were identified. Initial postnatal ultrasound was normal in 25% of the cases. Bilateral reflux was present in 36 male and 9 female patients. In 10 of the 19 uncircumcised patients (53%) urinary tract infection developed despite antibiotic prophylaxis. In 15 of the 74 renal units with grades III to V reflux the condition resolved at an average patient age of 0.9 and 2.1 years in boys and girls, respectively. A total of 27 refluxing renal units were reimplanted., Conclusions: The majority of prenatal reflux occurs in boys, and it is high grade and bilateral. The data sheets designed by the Society for Fetal Urology are useful data collection instruments. The presentation and natural history of vesicoureteral reflux are different in male and female individuals. In a significant number of renal units high grade reflux resolves spontaneously. Early circumcision may decrease the incidence of breakthrough urinary tract infection in this subpopulation. In addition, the effective management of prenatally detected reflux depends on multispecialty communication.

Purpose: Cryptorchidism is the most common congenital abnormality of the genitalia. However, its exact etiology remains to be defined. Homeobox (HOX) containing genes have a key role in the morphogenesis of segmental structures along the primary body axis, including the urogenital mesenchyma. In male mice with a targeted deletion of the HOXA10 gene cryptorchidism manifests in the absence of other major defects. Because to our knowledge this gene has never been examined for alterations in humans, we evaluated whether mutations of HOXA10 are associated with cryptorchidism in humans., Materials and Methods: Genomic deoxyribonucleic acid (DNA) was extracted from human blood or tissue samples from 16 noncryptorchid control subjects and 45 cryptorchid boys. To screen for mutations exons 1 and 2 of the HOXA10 gene were amplified individually by polymerase chain reaction using 6 overlapping oligonucleotide primer pairs. Single strand conformational polymorphism (SSCP) analysis of the amplified radiolabeled DNA fragments was performed. Variant band shifts were detected due to abnormal migration of the denatured DNA fragment compared to controls, suggesting an alteration in the DNA sequence. Sequence analysis of these variant bands was then done to define any mutations., Results: SSCP analysis revealed variants in 2 controls. Of the 45 samples from cryptorchid patients 30 had SSCP variants in exon 1. No variants were found in other regions of the gene. Sequence analysis revealed several DNA polymorphisms in exon 1 in controls and boys with cryptorchidism. Other nucleotide changes (point mutations) were noted only in exon 1 in the DNA of 5 cryptorchid patients, of whom 1 had a 24 nucleotide deletion., Conclusions: Our initial analysis of the HOXA10 gene in humans demonstrates that genetic alterations of this gene may be present in some boys with cryptorchidism. HOXA10 polymorphisms exist in normal control subjects as well as in cryptorchid patients. Further analysis of the function of the mutated protein will elucidate the role of this gene as a potential causative factor of testicular descent.

Purpose: The XX male syndrome presents with a spectrum of clinical appearances from phenotypic male individuals to true hermaphrodites. Previous reports established the sex determining region of the Y chromosome (SRY) gene as the testis determining factor. However, a subset of XX sex reversed male individuals exists without a translocation of SRY deoxyribonucleic acid (DNA) material to the X chromosome. In addition to clinical or endocrinological criteria, Y DNA probe studies, and radiological and surgical evaluation as indicated are necessary for an accurate diagnosis., Materials and Methods: We evaluated 5 XX sex reversed patients (2 true hermaphrodites and 3 male individuals) by physical examination, pedigree analysis, endocrinological testing, molecular analysis of Y DNA, radiological studies and surgery (exploration and/or biopsy)., Results: All patients were SRY gene negative. Two patients were siblings. Complete endocrinological testing was negative in all cases. Two patients had a normal male phenotype. Radiological findings confirmed by cystoscopy or laparoscopy revealed a utricle, vesicoureteral reflux, and cervix and uterus in various patients. Gonadal biopsy showed ovotestes or ovary and testis in the 2 true hermaphrodites. The 3 XX male individuals had normal immature testes on biopsy., Conclusions: Categories of XX sex reversal include classic XX male individuals with normal phenotypes, nonclassic XX male individuals with sexual ambiguity and XX true hermaphrodites. Simple translocation of the SRY gene to the X chromosome does not always account for testicular differentiation and a male phenotype. The masculinization of our patients in the absence of SRY suggests an alteration of 1 or more downstream Y, X or autosomal testis determining genes. We present another theory for male sex determination, including a downstream gene on the X chromosome in which expression is influenced by X inactivation. Y DNA genomic analysis, radiological studies and laparoscopic evaluation with gonadal biopsy as appropriate are recommended for complete assessment and treatment of these intersex patients.

Purpose: We evaluated 3 indexes used to assess patient co-morbidities to determine whether they could predict mortality among men with clinically localized prostate cancer., Materials and Methods: We measured the impact of co-morbidity classifications on all cause mortality using a parametric proportional hazards model based on a retrospective cohort analysis., Results: Each index tested is a highly significant predictor of mortality for patients dying of nonprostate cancer related causes after adjusting for age and Gleason score., Conclusions: Each co-morbidity index provides significant, independent predictive information concerning patient mortality beyond that provided by age, Gleason score and clinical stage alone.

Objective: To determine age-specific, all-cause mortality, disease-specific mortality, and life expectancy for men aged 65 to 75 years who are treated only with immediate or delayed hormonal therapy for newly diagnosed, clinically localized prostate cancer., Design: A population-based, retrospective cohort study., Setting: Patient records were abstracted from 37 acute care hospitals and two Veterans Affairs medical centers in Connecticut. Original pathology slides were sent to a referee pathologist who was blinded to case outcomes., Subjects: All men identified by the Connecticut Tumor Registry with clinically localized prostate cancer diagnosed in 1971 to 1976 who were aged 65 to 75 years at the time of diagnosis and were untreated or treated with immediate or delayed hormonal therapy., Main Outcome Measures: Parametric proportional hazards models incorporating tumor histologic findings, comorbidity, and age at the time of diagnosis to compare cohort survival with that of men in the general population., Results: After a mean follow-up of 15.5 years, the age-adjusted survival for men with Gleason score 2 to 4 tumors was not significantly different from that of the general population. Maximum estimated lost life expectancy for men with Gleason score 5 to 7 tumors was 4 to 5 years and for men with Gleason score 8 to 10 tumors was 6 to 8 years. Tumor histologic findings and patient comorbidities were powerful independent predictors of survival., Conclusions: Compared with the general population, men aged 65 to 75 years with conservatively treated low-grade prostate cancer incur no loss of life expectancy. Men with higher-grade tumors (Gleason scores 5 to 10) experience a progressively increasing loss of life expectancy. Case series reports of survival/mortality experienced by men with clinically localized prostate cancer that fail to control for age, tumor histologic features, and comorbidities risk significant bias.

Objective: To investigate the effects of pentoxifylline on cryopreserved human semen of spinal cord injured men, in efforts to enhance post-thaw motility., Design: Semen specimens were collected from: pregnancy-proven donors (n = 10), spinal cord injured (SCI) patients (n = 8), and infertility patients referred for white blood cell (WBC) screening of the semen (n = 18). Following at least 24 hours of freezing in 100% tes and tris-yolk buffer, 0.5-mL semen straws were thawed. Each sample was split into two equal aliquots, one of which was treated with 3.6 mM pentoxifylline. Following incubation, percent motility was recorded manually at 15 minutes, 1 hour, 2 hours, and 24 hours post-thaw. Percent original motility preserved (post-thaw motility/original motility X 100%) was calculated for each specimen., Results: Statistically significant differences (P < .05) were noted in the SCI and WBC patients when samples with and without pentoxifylline were compared at 15 minutes, 1 hour, and 2 hours. No significant difference was noted in the donor population at any time interval, and no difference was seen in any group at 24 hours post-treatment with pentoxifylline. The greatest differential between treatment and control groups was noted at 1 hour in all three populations., Conclusions: Pentoxifylline enhances post-thaw motility of cryopreserved sperm in male infertility patients from 15 minutes to 2 hours post-treatment. Pentoxifylline appears to be most useful at 1 hour post-treatment in the cryopreserved samples of SCI patients obtained by electroejaculation. It does not appear to have any significant effect on the post-thaw motility of pregnancy- proven donors. Pentoxifylline loses its in vitro efficacy prior to 24 hours post-thaw.

Microscopically extracted ductal sperm can be successfully cryopreserved using motility as the outcomes measure. The optimal regimen for cryopreservation of microscopically extracted ductal sperm awaits further determination. Pentoxifylline treatment improves initial post-thaw motility of cryopreserved microscopically extracted ductal sperm. The clinical efficacy of this practice awaits further determination. However, the best potential use for cryopreserved microscopically extracted ductal sperm may be IVF with subzonal or intracytoplasmic microinjection. If intracytoplasmic sperm injection becomes more widely available, then enhancement of motility with pentoxifylline may not be necessary. This approach allows for potential fertility insurance at the time of microsurgical bypass of obstruction, and it may preclude, the need for the andrologic surgeon to accurately time his sperm retrieval procedures with IVF. The latter potential advantage would significantly aid current logistical difficulties in the operating room.

Reactive oxygen species production has been demonstrated to impair sperm function. We have noted the potential for the cytokines IL-1 alpha, IL-1 beta, and TNF alpha to stimulate reactive oxygen species production by fertile donor sperm at levels that are consistent with the levels of IL-1 occurring in human seminal plasma. Reactive oxygen species-related sperm membrane peroxidation may be one mechanism by which cytokines can exert a detrimental effect on male fertility. This study suggests a new mechanism by which cell-mediated immunological male infertility may occur.

Objective: To design a protocol to evaluate individual variability in human semen cryoprotection by native seminal plasma., Design: Post-thaw motility from the frozen semen of pregnancy-proven donors (n = 10) and patients referred for infertility screening (n = 10) was examined in three equal aliquots (per original ejaculate) that comprised varying ratios of native seminal plasma to TES and Tris (TEST)-yolk buffer (Irvine Scientific, Irvine, CA) in a dose-titration curve format. All aliquots from the same ejaculate contained final vol/vol 6% glycerol, had equal sperm density, and had undergone centrifugation for 5 minutes at 600 x g before buffer:semen ratio adjustment and standard precooling protocol for submersion in liquid nitrogen. Post-thaw measurement of percent original motility preserved (post-thaw percent motility/original percent motility x 100) was used for standardization of results., Results: In 14 of 20 specimens (70%), the maximal yield of original motility was obtained in 50% seminal plasma, with an average post-thaw motile yield of 50%. In 6 of 20 specimens (30%), the best preservation of original motility was noted at 100% seminal plasma, with an average post-thaw motile yield of 58%. No specimen had a greatest percent motility preserved at 0% seminal plasma. Donor specimens have equal preference for either 50% or 100% seminal plasma, whereas patient specimens have a preference for 50% seminal plasma (P < 0.05)., Conclusions: Native seminal plasma has variable cryoprotectant qualities for which custom cryopreservation can compensate. A simple two-point dose-titration test of cryopreservation buffer:seminal plasma ratio (i.e., 50:50 versus 0:100) can determine the optimal mixture for cryopreservation of a given individual's semen.