Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

STUDY QUESTION: Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER: Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY: Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S): Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.

Frontiers in pediatric testicular torsion: An integrated review of prevailing trends and management outcomes.

Testicular torsion remains the most frequent cause of testicular ischemia, especially in adolescents and young adults. Timely diagnosis and intervention are keys to saving the affected testicle. This review presents current trends in the diagnosis and treatment of torsion, potential pitfalls and consequent outcomes. Additionally, other salient issues surrounding testicular torsion are also discussed, including: pathogenesis of injury, legal ramifications, fertility outcomes, novel management techniques, and recent advances in diagnostic technology.

Impact and frequency of extra-genitourinary manifestations of prune belly syndrome.

INTRODUCTION: Prune belly syndrome (PBS) extra-genitourinary (extra-GU) manifestations are serious comorbidities beyond the genitourinary (GU) anomalies of this disease. We hypothesized an underestimation of the reported frequency and understated impact on quality of life (QOL) of extra-GU comorbidities in PBS survivors beyond the newborn period. To assess this, the frequencies of extra-GU manifestations of PBS in a contemporary cohort of living patients were compared to compiled frequencies from published literature. Second, the impact of extra-GU PBS manifestations on patient/family QOL was assessed via a non-validated open-ended survey. MATERIAL AND METHODS: From 2010 to 2013, PBS survivors were prospectively recruited locally or at three PBS Network National Conventions. The family/subject was asked to complete a detailed PBS questionnaire, non-validated QOL survey, and provide medical records for review. Clinical data were extracted from medical records for local patients. The frequencies of extra-GU manifestations were compared between the contemporary, living cohort and a published literature cohort derived from PubMed. RESULTS AND DISCUSSION: Seven of 706 published studies met criteria for frequencies tabulation of extra-GU PBS manifestations. This largest reported living PBS patient cohort (n = 65) was 99% male with mean age 10 years (1 month-45 years). The living PBS cohort had a statistically significantly higher incidence of gastrointestinal (63%), orthopedic (65%), and cardiopulmonary (49%) diagnoses compared to the compiled published cohort (n = 204). Eleven PBS males and 32 family members completed the QOL survey. Of these, 47% listed at least one non-GU problem (i.e. lung disease, skeletal problems, constipation) as negatively affecting their QOL; 42% listed at least one GU problem (i.e. self-catheterization, recurrent UTIs) as negatively affecting their QOL; 56% reported musculoskeletal surgery and 21% reported gastrointestinal surgery/medication as positively impacting their QOL. CONCLUSIONS: In this large contemporary series, surviving individuals with PBS had a significantly higher incidence of orthopedic, gastrointestinal, and cardiopulmonary diagnoses than previously reported in PBS publications. From the patient/family QOL perspective, non-GU PBS manifestations negatively impact their QOL and treatment of these non-GU conditions improves their lives. As urologic surgeons for these medically complex patients, it is extremely important to be aware of and prepare for the high incidence of non-GU PBS comorbidities directly impacting the medical and surgical treatment and QOL of PBS patients and their families.

Augmentation cystoplasty and risk of neoplasia: fact, fiction and controversy.

PURPOSE: We determined if ileal/colonic bladder augmentation performed in patients with congenital bladder abnormalities is an independent risk factor for bladder malignancy. MATERIALS AND METHODS: We reviewed a registry of patients with bladder dysfunction due to neurological abnormalities, exstrophy and posterior urethral valves. Individuals treated with augmentation cystoplasty were matched (1:1) to a control group treated with intermittent catheterization based on etiology of bladder dysfunction, gender and age (±2 years). RESULTS: We evaluated 153 patients with an ileal/colonic cystoplasty and a matched control population. There was no difference (p=0.54) in the incidence of bladder cancer in patients with augmentation cystoplasty (7 patients [4.6%]) vs controls (4 [2.6%]). In addition, there was no difference between the 2 groups regarding age at diagnosis (51 vs 49.5 years, p>0.7), stage (3.4 vs 3.8, p>0.5), mortality rate (5 of 7 [71%] vs 4 of 4 [100%], p>0.4) or median survival (18 vs 17 months, p>0.8). Irrespective of augmentation status patients with a history of renal transplant on chronic immunosuppression had a significantly higher incidence of bladder cancer (3 of 20 [15%]), compared to patients who were not immunosuppressed (8 of 286 [2.8%], p=0.03). CONCLUSIONS: In patients with congenital bladder dysfunction ileal/colonic bladder augmentation does not appear to increase the risk of bladder malignancy over the inherent cancer risk associated with the underlying congenital abnormality. In addition, immunosuppression irrespective of bladder treatment is an independent risk factor for malignancy in this patient population.