Trends in the Rates of Pediatric Pyeloplasty for Ureteropelvic Junction Obstruction over 19 Years: A PHIS Database Study

Background. Over the past 20 years, the management of ureteropelvic junction obstruction (UPJ) has shifted. While many urologists note a decrease in the number of pyeloplasties performed over time, the nature of the change in practice has yet to be defined. In the current study, we utilize a national, multi-institutional database of children’s hospitals to evaluate trends in patients undergoing pyeloplasty as well as the rate of surgical reconstruction over the past 20 years. Material/Methods. We queried the Pediatric Health Information System (PHIS) database for all children undergoing primary pyeloplasty between 1992 and 2011. Clinical variables, including age at time of surgery, gender, length of stay (LOS), and geographic region, were determined. Age-adjusted rate of repair was also calculated per 100,000 PHIS inpatients. Results. 6,013 patients were included in the study, of which 71.6% were male and 64.2% were under the age of 24 months at time of surgery. Over the study period, the median age at time of surgery increased from 2–4 months to 12–14 months (P<0.01). LOS decreased from a median of 5 days to 2 days (P<0.001). The rate of surgery increased by 10.6 pyeloplasties per 100,000 PHIS inpatients from 1992 to 2011 (P<0.01). The highest rate of pyeloplasty was in the northeast. The increase in pyeloplasties performed from 1992 to 1999 was specific to children aged greater than 24 months, while rates stayed the same in infants younger than 2 years during the same time period. In contrast, from 1999 to 2011, the rate of pyeloplasty decreased in patients less than 2 years of age, while the rate remained constant in patients over age 2. Conclusion. The rate of pyeloplasty increased in PHIS hospitals from 1992 to 2011. Trends are due to an increase in surgery in infants younger than 2 years from 1992 to 1999, followed by a progressive surgical rate decline, characterized by a shift towards patients older than 2 years of age

Proceedings of the Working Group Session on Fertility Preservation for Individuals with Gender and Sex Diversity

Children and adolescents with gender and sex diversity include (1) gender-nonconforming and transgender individuals for whom gender identity or expression are incongruent with birth-assigned sex (heretofore, transgender) and (2) individuals who have differences in sex development (DSD). Although these are largely disparate groups, there is overlap in the medical expertise necessary to care for individuals with both gender and sex diversity. In addition, both groups face potential infertility or sterility as a result of desired medical and surgical therapies. The Ann and Robert H. Lurie Children's Hospital of Chicago (Lurie Children's) gender and sex development program (GSDP) provides specialized multidisciplinary care for both transgender and DSD patients. In response to patient concerns that recommended medical treatments have the potential to affect fertility, the Lurie Children's GSDP team partnered with experts from the Oncofertility Consortium at Northwestern University to expand fertility preservation options to gender and sex diverse youth. This article summarizes the results of a meeting of experts across this field at the annual Oncofertility Consortium conference with thoughts on next steps toward a unified protocol for this patient group.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140296/1/trgh.2016.0008.pd

Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors : a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium

Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.Peer reviewe

A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement

Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future

Can the external masculinization score predict the success of genetic testing in 46,XY DSD?

Genetic testing is judiciously applied to individuals with Disorders of Sex Development (DSD) and so it is necessary to identify those most likely to benefit from such testing. We hypothesized that the external masculinization score (EMS) is inversely associated with the likelihood of finding a pathogenic genetic variant. Patients with 46,XY DSD from a single institution evaluated from 1994-2014 were included. Results of advanced cytogenetic and gene sequencing tests were recorded. An EMS score (range 0-12) was assigned to each patient according to the team's initial external genitalia physical examination. During 1994-2011, 44 (40%) patients with 46,XY DSD were evaluated and underwent genetic testing beyond initial karyotype; 23% (10/44) had a genetic diagnosis made by gene sequencing or array. The median EMS score of those with an identified pathogenic variant was significantly different from those in whom no confirmed genetic cause was identified [median 3 (95% CI, 2-6) versus 6 (95% CI, 5-7), respectively (p = 0.02)], but limited to diagnoses of complete or partial androgen insensitivity (8/10) or 5-reductase deficiency (2/10). In the modern cohort (2012-2014), the difference in median EMS in whom a genetic cause was or was not identified approached significance (p = 0.05, median 3 (95% CI, 0-7) versus 7 (95% CI, 6-9), respectively). When all patients from 1994-2014 are pooled, the EMS is significantly different amongst those with compared to those without a genetic cause (median EMS 3 vs. 6, p &lt; 0.02). We conclude that an EMS of 3 or less may indicate a higher likelihood of identifying a genetic cause of 46,XY DSD and justify genetic screening, especially when androgen insensitivity is suspected

Differential DNA Methylation Regions in Adult Human Sperm following Adolescent Chemotherapy: Potential for Epigenetic Inheritance

The potential that adolescent chemotherapy can impact the epigenetic programming of the germ line to influence later life adult fertility and promote epigenetic inheritance was investigated. Previous studies have demonstrated a number of environmental exposures such as abnormal nutrition and toxicants can promote sperm epigenetic changes that impact offspring. Adult males approximately ten years after pubertal exposure to chemotherapy were compared to adult males with no previous exposure. Sperm were collected to examine differential DNA methylation regions (DMRs) between the exposed and control populations. Gene associations and correlations to genetic mutations (copy number variation) were also investigated. A signature of statistically significant DMRs was identified in the chemotherapy exposed male sperm. The DMRs, termed epimutations, were found in CpG desert regions of primarily 1 kilobase size. Observations indicate adolescent chemotherapy exposure can promote epigenetic alterations that persist in later life. This is the first observation in humans that an early life chemical exposure can permanently reprogram the spermatogenic stem cell epigenome. The germline (i.e., sperm) epimutations identified suggest chemotherapy has the potential to promote epigenetic inheritance to the next generation

Examination of generational impacts of adolescent chemotherapy Ifosfamide and potential for epigenetic transgenerational inheritance

The current study was designed to use a rodent model to determine if exposure to the chemotherapy drug ifosfamide during puberty can induce altered phenotypes and disease in the grand-offspring of exposed individuals through epigenetic transgenerational inheritance. Pathologies such as delayed pubertal onset, kidney disease, and multiple pathologies were observed to be significantly more frequent in the F1 generation offspring of ifosfamide lineage females. The F2 generation grand-offspring ifosfamide lineage males had transgenerational pathology phenotypes of early pubertal onset and reduced testis pathology. Reduced levels of anxiety were observed in both males and females in the transgenerational F2 generation grand-offspring. Differential DNA methylated regions (DMRs) in chemotherapy lineage sperm in the F1 and F2 generations were identified. Therefore, chemotherapy exposure impacts pathology susceptibility in subsequent generations. Observations highlight the importance that prior to chemotherapy, individuals need to consider cryopreservation of germ cells as a precautionary measure if they have children.[Display omitted]•Chemotherapy-induced sperm DNA methylation facilitates epigenetic inheritance•Chemotherapy promotes epigenetic transgenerational inheritance of pathology•Pubertal exposure to chemotherapy impacts later life sperm epigenetics and genetics•Cancer chemotherapy treatment needs to consider later life and generational impactsDevelopmental genetics; Epigenetics; Omic

The human sperm chemotherapy-associated DMR associated gene classifications (i.e. functional categories).

<p>The number of DMR associated genes for specific classification categories are presented.</p