Prepubertal Patients Research Articles

Closed-loop driven by control-to-range algorithm outperforms threshold-low-glucose-suspend insulin delivery on glucose control albeit not on nocturnal hypoglycaemia in prepubertal patients with type 1 diabetes in a supervised hotel setting.

This randomized control trial investigated glucose control with closed-loop (CL) versus threshold-low-glucose-suspend (TLGS) insulin pump delivery in pre-pubertal children with type 1 diabetes in supervised hotel conditions. The patients [n = 24, age range: 7-12, HbA1c: 7.5 ± 0.5% (58 ± 5 mmol/mol)] and their parents were admitted twice at a 3-week interval. CL control to range or TLGS set at 3.9 mmoL/L were assessed for 48 hour in randomized order. Admissions included three meals and one snack, and physical exercise. Meal boluses followed individual insulin/carb ratios. While overnight (22:00-08:00) per cent continuous glucose monitoring (CGM) time below 3.9 mmol/L (primary outcome) was similar, time in ranges 3.9 to 10.0 and 3.9 to 7.8 mmoL/L and mean CGM were all significantly improved with CL (P < 0.001). These results were confirmed over the whole 48 hour. Disconnections between devices and limited accuracy of glucose sensors in the hypoglycaemic range appeared as limiting factors for optimal control. CL mode was well accepted while fear of hypoglycaemia was unchanged. CL did not minimize nocturnal hypoglycaemia exposure but improved time in target range compared to TLGS. Although safe and well-accepted, CL systems would benefit from more integrated devices.

Metabolomics changes in patients with PAPP-A2 deficiency in response to rhIGF1 treatment

ObjectiveMutations in the pregnancy-associated plasma protein A2 (PAPP-A2) gene have recently been shown to cause postnatal growth failure in two prepubertal patients from a non-consanguineous Spanish family due to the resulting decrease in IGF1 bioavailability. Although a specific pharmacological treatment of this entity is yet to be established, both children received progressive subcutaneous doses (40 to 120 μg/kg) of rhIGF1 twice daily for 2 years. The improvements in growth, hyperinsulinemia and bone mineral density have been previously reported. The objective of this study was to analyze the changes in metabolism associated with these responses to rhIGF1 treatment. DesignHerein we present a detailed characterization of the acute and long-term changes in the metabolic profiles of these two siblings with PAPP-A2 deficiency after the initial injections of rhIGF1 and after two years of treatment. ResultsBy using a GC-MS-based untargeted metabolomics approach, metabolic fingerprinting yielded the identification of 70 serum metabolites including amino acids (46%), organic acids (21%) carbohydrates (16%), fatty acids (14%), and purine bases (3%). Free fatty acids (FFAs) and amino acids showed the largest changes in the compared metabolic profiles, suggesting that rhIGF1 treatment has the greatest effects on lipid and protein metabolic pathways in the PAPP-A2 deficient subjects. ConclusionsThe administration of rhIGF1 resulted in changes related to crucial metabolic pathways, including lipid and protein metabolism, and this could be associated with the previously reported treatment-induced improvement in the mild basal hyperinsulinemia.

Fertility Preservation: Current and Future Perspectives for Oncologic Patients at Risk for Iatrogenic Premature Ovarian Insufficiency.

Progress in recent years in the efficacy of oncologic treatment and early diagnosis of cancer has determined an increase in life expectance in cancer patients. About 10% of all cancer cases affect women younger than 45 years; therefore nowadays approximately 5-6% of the population in childbearing age consists in cancer survivors. A crucial issue is the high risk of premature ovarian insufficiency due to possible gonadotoxic effects of oncologic treatments. Considering combined chemotherapy, radiation therapy, and bone marrow transplantation, this risk can reach 92-100%, depending on the age and ovarian reserve of the patient, as well as the schedule and type of therapy. International guidelines recommend addressing all the patients diagnosed with a neoplasia treatable with potentially gonadotoxic therapies to fertility preservation. Moreover, fertility preservation also seems to reserve fascinating implications for women who want to delay childbearing for social reasons or women affected with endometriosis, who could receive unexpected opportunities. At present, the most widespread techniques to preserve fertility in adult women are embryo or oocyte cryopreservation, depending on the presence of a partner or according to legislative issues, but these procedures require time for ovarian stimulation. In prepubertal patients or when there is no possibility of delaying chemotherapy, ovarian tissue cryopreservation and subsequent transplantation represent the main strategy.

Cryostorage of immature and mature human testis tissue to preserve spermatogonial stem cells (SSCs): a systematic review of current experiences toward clinical applications.

While the survival rate of children with cancer is increasing, preserving fertility for prepubertal boys is still a challenge. Although intracytoplasmic sperm injection (ICSI) using frozen sperms has revolutionized infertility treatment, it is not applicable for the patients who undergo chemotherapy before puberty since spermatogenesis has not begun. Therefore, preserving spermatogonial stem cells (SSCs) as an experimental option can be provided to prepubertal patients at a risk of damage or loss of their SSCs due to cancer treatments and developmental or genetic disorders. Using frozen SSCs in testicular tissue, successful SSC autotransplantation in mouse and nonhuman primates has shown a promising future for SSC-based cell therapy. Cryopreservation of testicular tissue containing SSCs is the first step to translate SSC-based cell therapy into clinical male infertility treatment, and in the investigation into SSCs, it is very important to evaluate their quantity and functionality during this process. This systematic review summarizes the published data on cryopreservation techniques in human testis tissue for potential utilization in future clinical applications.

Fertility preservation in pediatric and young adult female cancer patients.

As the 5-year survival rate increases up to 80% in pediatric cancer patients, the number of women patients with reduced gonadal function by chemotherapy and radiotherapy increases. The gonadal toxicity of pediatric patients varies highly according to the chemotherapeutic agent and the type of radiotherapy. Although American Society of Clinical Oncology published the guideline for fertility preservation, additional scientific and ethical concerns should be considered for clinical practice. In addition, only the experimental method can be applied for the prepubertal patients in contrast to the postpubertal patients. In this review, we will discuss some options for preserving fertility among women’s quality of life issues.

Development of Postmeiotic Cells In Vitro from Spermatogonial Cells of Prepubertal Cancer Patients.

Aggressive chemotherapy in childhood often results in testicular damage and consequently jeopardizes future fertility. The presence of spermatogonial cells (SPGCs) in the testes of prepubertal cancer patient boys (PCPBs) can be used to develop future strategies for male fertility preservation. In the present study, we examined the presence of SPGCs in testes of chemotherapy-treated PCPBs and their ability to develop spermatogenesis in vitro using a three-dimensional culture system. Seven testicular biopsies were obtained from chemotherapy-treated PCPBs and one from a patient with β-thalassemia major. Isolated testicular cells were cultured in a methylcellulose culture system (MCS)-containing StemPro enriched with growth factors for 5-15 weeks. The presence of premeiotic, meiotic, and postmeiotic cells was examined by immunofluorescence staining and/or reverse transcription-polymerase chain reaction (RT-PCR) analysis. We observed SPGCs in the examined testicular biopsies. Isolated testicular cells cultured in MCS developed into colonies and contained premeiotic, meiotic, and postmeiotic cells. Furthermore, we identified sperm-like cells that had developed from testicular cells of a PCPB. Our results demonstrate, for the first time, the presence of biologically active SPGCs in testicular biopsies of chemotherapy-treated PCPBs and their capacity to develop in vitro to different stages of spermatogenesis, including the generation of sperm-like cells. This study may open the way for new therapeutic strategies for fertility preservation of PCPBs and for azoospermic patients.

Deficiency in GnRH receptor trafficking due to a novel homozygous mutation causes idiopathic hypogonadotropic hypogonadism in three prepubertal siblings

Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by low levels of gonadotropins and delayed or absent sexual development. Most of the patients are diagnosed in late adolescence or early adulthood. Determining the diagnosis of IHH in prepubertal patients can be challenging. Making a timely, correct diagnosis has important clinical implications. Here we aimed to identify the genetic cause of IHH in three prepubertal siblings from a Chinese Han family and give appropriate treatment advice. Using whole exome sequencing (WES), we identified a novel homozygous GNRHR mutation (NM_000406; c.364C>T, p.L122F) in two prepubertal boys with cryptorchidism and micropenis. Sanger sequencing showed that their younger asymptomatic sister also had the homozygous GNRHR mutation. This mutation was inherited from the father and the mother. Immunofluorescence analysis showed that in permeabilized cells, expression of the mutant receptor on the cell membrane was significantly lower than that of wild-type. Calcium mobilization assays demonstrated that c.364C>T in the GNRHR gene is a complete loss-of-function mutation that caused IHH. These results may contribute to the genetic diagnosis of the three prepubertal siblings with IHH. According to this diagnosis, timely hormonal treatment can be given for the three prepubertal patients to induce pubertal development, especially for the asymptomatic female.

Thyroid Nodules in Pediatric Patients: Sonographic Characteristics and Likelihood of Cancer

Purpose To determine the relationship between demographic and sonographic characteristics of thyroid nodules and malignancy in a pediatric population. Materials and Methods All thyroid nodules in patients younger than 19 years that underwent ultrasound (US)-guided fine-needle aspiration biopsy between January 2004 and July 2017 were retrospectively identified. Age, sex, and background appearance of the thyroid gland were recorded for each patient, and sonographic characteristics and pathologic diagnosis were recorded for each nodule. Demographic and sonographic characteristics were assessed to determine which were associated with malignancy. Categorical and continuous variables and interobserver variability were assessed. Results A total of 404 nodules in 314 patients (82.8% female) (age range, 2-18 years; mean age, 14.9 years) were analyzed. A total of 77 nodules (19.1%) were malignant, the majority of which were papillary thyroid carcinoma (n = 68 [88.3%]). The likelihood of malignancy did not differ between boys and girls (27.8% vs 22.7%, P = .64), nor did it differ between prepubertal and pubertal patients (18.8% vs 19.1%, P > .99). The cancer rate in patients with a solitary nodule was higher than that in patients with multiple nodules (29.4% vs 14.2%, P = .003). Sonographic characteristics associated with malignant nodules included larger size, solid parenchyma, taller-than-wide shape, presence of speckled calcifications, lack of a smooth margin, and presence of abnormal lymph nodes. Interobserver variability for assessment of sonographic characteristics ranged from moderate to very strong. Conclusion In children with thyroid nodules, solitary nodules, larger nodule size, solid parenchyma, taller-than-wide shape, speckled calcifications, irregular margins, and abnormal lymph nodes raise concern for malignancy.

When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome?

When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome (KS)? In KS, germ cell loss is not observed in testicular tissue from fetuses in the second semester of pregnancy but present at a prepubertal age when the testicular architecture is still normal, while fibrosis is highly present at an adolescent age. Most KS patients are azoospermic at adult age because of a massive germ cell loss. However, the timing when this germ cell loss starts is not known. It is assumed that germ cell loss increases at puberty. Therefore, testicular sperm extraction (TESE) at an adolescent age has been suggested to increase the chances of sperm retrieval at onset of spermatogenesis. However, recent data indicate that testicular biopsies from peripubertal KS patients contain only a few germ cells. In this study, we give an update on fertility preservation in adolescent KS patients and evaluate whether fertility preservation would be beneficial at prepubertal age. The possibility of retrieving testicular spermatozoa by TESE was evaluated in adolescent and adult KS men. The presence of spermatogonia and the degree of fibrosis were also analysed in testicular biopsies from KS patients at different ages. The patients were divided into four age groups: foetal (n = 5), prepubertal (aged 4-7 years; n = 4), peripubertal (aged 12-16 years; n = 20) and adult (aged 18-41 years; n = 27) KS patients. In peripubertal and adult KS patients, retrieval of spermatozoa was attempted by semen analysis after masturbation, vibrostimulation, electroejaculation or by TESE. MAGE-A4 immunohistochemistry was performed to evaluate the presence of germ cells in testicular biopsies from foetal, prepubertal, peripubertal and adult KS patients. Tissue morphology was evaluated by haematoxylin-periodic acid Schiff (H/PAS) staining. Testicular spermatozoa were collected by TESE in 48.1% of the adult KS patients, while spermatozoa were recovered after TESE in only one peripubertal patient (5.0%). Germ cells were detectable in testicular biopsies from 21% of adult men for whom no spermatozoa could be retrieved by TESE and in 31.5% of peripubertal KS boys. Very small numbers of spermatogonia (0.03-0.06 spermatogonia/tubule) were detected in three out of four (75%) prepubertal patients. At a foetal age, the number of germ cells was similar for KS and control samples. Increased signs of fibrosis were not present at foetal and prepubertal ages, but peripubertal and adult KS patients showed high levels of fibrosis. N/A. Only four prepubertal biopsies were included in this study, but they all showed a very low germ cell number. A high variability in the number of spermatogonia per mm2 was observed in the limited (n = 5) number of foetal biopsies. However, testicular biopsies from prepubertal and foetal Klinefelter patients are difficult to obtain. Testicular tissue banking at a prepubertal age has been suggested as a potential method for fertility preservation in early diagnosed KS boys. However, our results show that a reduction in germ cell number has already taken place in childhood. Therefore, offering testicular tissue banking in young KS boys to prevent subsequent sterility might be a questionable strategy. However, this should be confirmed in a larger study population. This project was funded by the scientific Fund Willy Gepts from the UZ Brussel (D.V.S., J.D.S.), grants from the Vrije Universiteit Brussel (E.G.) and a Methusalem grant (K.S.). D.V.S is a post-doctoral fellow of the Fonds Wetenschappelijk Onderzoek (FWO; 12M2815N). No conflict of interest is declared.

Maxillary arch dimensions associated with acoustic parameters in prepubertal children.

To evaluate the association between maxillary arch dimensions and fundamental frequency and formants of voice in prepubertal subjects. Thirty-five consecutive prepubertal patients seeking orthodontic treatment were recruited (mean age = 11.41 ± 1.46 years; range, 8 to 13.7 years). Participants with a history of respiratory infection, laryngeal manipulation, dysphonia, congenital facial malformations, or history of orthodontic treatment were excluded. Dental measurements included maxillary arch length, perimeter, depth, and width. Voice parameters comprising fundamental frequency (f0_sustained), Habitual pitch (f0_count), Jitter, Shimmer, and different formant frequencies (F1, F2, F3, and F4) were measured using acoustic analysis prior to initiation of any orthodontic treatment. Pearson's correlation coefficients were used to measure the strength of associations between different dental and voice parameters. Multiple linear regressions were computed for the predictions of different dental measurements. Arch width and arch depth had moderate significant negative correlations with f0 ( r = -0.52; P = .001 and r = -0.39; P = .022, respectively) and with habitual frequency ( r = -0.51; P = .0014 and r = -0.34; P = .04, respectively). Arch depth and arch length were significantly correlated with formant F3 and formant F4, respectively. Predictors of arch depth included frequencies of F3 vowels, with a significant regression equation ( P-value < .001; R2 = 0.49). Similarly, fundamental frequency f0 and frequencies of formant F3 vowels were predictors of arch width, with a significant regression equation ( P-value < .001; R2 = 0.37). There is a significant association between arch dimensions, particularly arch length and depth, and voice parameters. The formant most predictive of arch depth and width is the third formant, along with fundamental frequency of voice.

Efficacy of Growth Hormone Treatment in Children with Type 1 Diabetes Mellitus and Growth Hormone Deficiency—An Analysis of KIGS Data

To analyze first-year treatment growth response and growth hormone (GH) dosage in prepubertal patients with the combination of type 1 diabetes mellitus (T1DM) and growth hormone deficiency (GHD). A total of 69 patients with T1DM and GHD treated with GH have been enrolled in KIGS (Pfizer International Growth Database). Of these, 24 prepubertal patients had developed T1DM before GHD and were included in this analysis. Of 30 570 patients with GHD without T1DM, 15 024 were prepubertal and served as controls. Values are expressed as mean ± SD. Patients with T1DM and GHD had similar characteristics compared with the GHD-alone group. Neither age (10.2 ± 3.13 vs 8.42 ± 3.46 years, P = .14), height SDS corrected for midparental height SDS at start of treatment (-1.62 ± 1.38 vs -1.61 ± 1.51, P = .80), nor GH dosage (0.24 ± 0.08 mg/kg/wk vs 0.20 ± 0.04 mg/kg/wk, P = .09) were different between those with and without T1DM. First-year catch-up growth was comparable between the 2 patient groups (first treatment year height velocity 7.54 ± 3.11 cm/year compared with 8.35 ± 2.54 cm/year in control patients, P = .38). Height SDS of children with T1DM and GHD improved from -2.62 ± 1.04 to -1.88 ± 1.11 over 1 year of GH treatment. Short-term response to GH therapy appeared similar in subjects with T1DM who then developed GHD and in those with GHD alone. Thus, T1DM does not appear to compromise GH response in children with GHD and should not exclude GH treatment in these children. GH treatment was safe in both subgroups of patients.

Cryopreservation of testicular tissue in pre-pubertal and adolescent boys at risk for infertility: A low risk procedure

Cryopreservation of testicular tissue (TT) has become an increasingly attractive option for fertility preservation (FP), particularly for pre-pubertal boys at risk for gonadotoxicity from cancer therapy. At our institution, all at-risk families undergo counseling regarding infertility risk and available FP strategies, including this vulnerable patient population. As the technology required to use the acquired tissue is, as yet, unproven, it is paramount to document minimal morbidity and complications from this procedure. Herein, we report these outcomes for all pre-pubertal patients who have undergone TT biopsies for FP. We retrospectively reviewed consecutive patients who underwent unilateral open TT biopsies between January 2014 and December 2016. Patient diagnosis, age, concomitant procedures, anesthetic type, complications, procedure times, planned therapy, and bleeding were evaluated. Of a total of 34 patients, mean age at biopsy was 6.9±4.4years. Diagnoses included: leukemia/lymphoma (n=12), solid tumors (n=15) and non-neoplastic disorders (hemophagocytic lymphohistiocytosis, aplastic anemia; n=7). Twenty-two patients (64.7%) were scheduled for stem cell transplantation. Eleven (32.4%) patients had not received any chemotherapy prior to TT biopsy, while all others had exposure preceding the biopsy. Biopsies were performed in conjunction with other procedures (central line placement, bone marrow biopsy, lumbar puncture, lymph node biopsy) in 29 cases (85.3%), with stand-alone procedures performed in the remainder (n=5). In stand-alone cases, mean anesthetic time was 22±8.7min. Overall, two (5.9%) patients had complications after biopsy: 1) ipsilateral epididymo-orchitis (resolved with antibiotics) and 2) ipsilateral torsedappendix testis (managed conservatively) (Table). In this series, pre-pubertal TT biopsy for cryopreservation was safely performed, and was most often coordinated concomitantly with other medically necessary procedures. The safety profile reported herein supports performing this procedure while technological advances fulfill the requirements to make it a viable option for future fertility.

Anthropometric and Biochemical Determinants of Estimated Glomerular Filtration Rate in a Large Cohort of Obese Children

We aimed to investigate which clinical and metabolic factors could influence the estimated glomerular filtration rate (eGFR) levels, evaluating a large population of obese children without suspect of primary kidney disease. Retrospective, cross-sectional study. Pediatric university department. We enrolled 2,957 obese children and adolescents consecutively attending our department between January 2000 and 2017. Inclusion criteria were body mass index (BMI)>95th percentile and eGFR > 90mL/min/1.73m2. Exclusion criteria were secondary forms of obesity, eGFR < 90mL/min/1.73m2, proteinuria/hematuria at urine dipstick, or consumption of any medication. Weight, waist circumference, height, waist to height ratio (W/Hr), BMI-standard deviation score (SDS), pubertal stage, systolic blood pressure (SBP) and diastolic blood pressure (DBP), duration of obesity, insulin, eGFR, and homeostasis model assessment (HOMA-IR) were obtained. A general linear model was performed for a multiple variable analysis. The population was divided in tertiles for BMI-SDS, W/Hr, SBP- and DBP-SDS, HOMA-IR, and duration of obesity. We compared eGFR levels among these tertiles. The eGFR levels significantly increased across both BMI-SDS and W/Hr tertiles. Conversely the eGFR levels significantly decreased across SBP-SDS, HOMA-IR, and duration of obesity tertiles. No significant differences in eGFR levels across DBP-SDS tertiles were detected. Pubertal patients presented significantly lower eGFR values compared with prepubertal patients. A general linear model for eGFR variance including as covariates W/Hr, HOMA-IR, duration of obesity, pubertal stage, BMI-SDS, and SBP-SDS (model R2 39.7%; model P<.00001) was performed. It confirmed a direct association of eGFR values with BMI-SDS and an indirect association with HOMA-IR, duration of obesity, pubertal stage, and SBP-SDS. We showed a positive correlation of eGFR with both BMI-SDS and a negative one with SBP-SDS, HOMA-IR, pubertal stage, and duration of obesity. The duration of obesity was the variable most significantly associated to eGFR levels.

Expansion of permanent first molars with rapid maxillary expansion appliance anchored on primary second molars.

BackgroundTo evaluate how the amount of expansion of the primary second molars, the patient’s age, and the skeletal maturation stage influence the amount of expansion at the level of the permanent first molars.Material and MethodsFifty-five patients aged between 6 and 11 years with a cervical vertebral maturation stage of CS1 or CS2 were retrospectively selected. The intermolar width was measured before and after expansion to evaluate the amount of expansion achieved at the level of the primary second molars and the permanent first molars. Stepwise multiple linear regression was used to evaluate how the amount of primary molars expansion, the patient’s age, and the cervical vertebral maturation stage predict the amount of permanent molar expansion.ResultsA significant regression equation was found, and for every 1 mm of primary molar expansion, 0.91 mm of permanent molar expansion can be expected. An age between 6 and 11 years and the CS1 or CS2 skeletal maturation stage were not significant predictors of permanent molar expansion.ConclusionsA rapid maxillary expansion appliance anchored on primary second molars is effective in expanding the permanent molars to correct a transverse maxillary deficiency in prepubertal patients, transferring the risks associated with the large forces used to the primary teeth. Key words:Maxillary expansion, transversal deficiency, primary molars.

Normal Growth in PKU Patients Under Low-Protein Diet in a Single-Center Cross-Sectional Study.

Dietary phenylalanine restriction in phenylketonuria (PKU) patients is usually mandatory in order to prevent cognitive impairment. The influence of a low-protein diet on growth has raised concerns in families and caregivers. This paper aims to investigate the growth in PKU patients treated with a low-protein diet including supplementation of amino acids and other nutrients according to standard protocols.We performed a single-center, cross-sectional study on growth in pediatric PKU patients (n=51) treated with low-protein diet over a 20-month period. Height of healthy siblings (n=44) and target height, calculated based on parents' height, served as controls.No statistically significant differences were found comparing mean height z-scores between patients and siblings (p=0.261). Patients <12years showed a reduction in mean height z-scores compared to the target height (p=0.020), whereas postpubertal patients ≥12years did not differ significantly in height z-scores compared to the target height (p=0.071). Healthy siblings' height did not differ from target height in neither age group (p=0.100/p=0.301).Our results suggest that PKU patients treated with low-protein diet can achieve normal growth with patients making up the leeway after puberty. While prepubertal patients were shorter than expected based on their target height, older patients were within their expected target height. This study indicates that current practice of low-protein diet in PKU patients allows normal growth.

Sexual precocity in a girl with early-onset Graves' disease.

.We describe the case of a girl diagnosed with Graves’ disease (GD) at 2 yr of age, who developed early puberty. Preoperative examination for craniosynostosis revealed thyrotoxicosis. While she was tall and her bone age was advanced at GD onset, her linear growth attenuated after commencement of anti-thyroid treatment. However, at approximately 6 yr of age, breast budding was recognized. Hormonal analysis revealed pubertal levels of LH response to a GnRH stimulation test and serum E2. Gonadal suppression therapy with GnRH agonist was initiated, and her adult stature slightly exceeded the genetic potential. Although accelerated growth and skeletal maturation are often reported to occur at GD onset in prepubertal patients, early puberty is unusual, and this is the first reported case of sexual precocity in a girl with GD.

Ovarian tissue cryopreservation and transplantation in patients with cancer.

Chemotherapy and radiotherapy improved survival rates of patients with cancer. However, they can cause ovarian failure and infertility in women of reproductive age. Infertility following cancer treatment is considered a major quality of life issue. Ovarian tissue cryopreservation and transplantation is an important option for fertility preservation in adult patients with cancer who need immediate chemotherapy or do not want to undergo ovarian stimulation. Ovarian tissue freezing is the only option for preserving the fertility of prepubertal patients with cancer. In a recent review, it was reported that frozen-thawed ovarian transplantation has lead to about 90 live births and the conception rate was about 30%. Endocrine function recovery was observed in 92.9% between 3.5 and 6.5 months after transplantation. Based on our review, ovarian tissue cryopreservation and transplantation may be carefully considered before cancer treatment in order to preserve fertility and endocrine function in young cancer survivors.

Controversies in the management of ovarian tumours in prepubertal children — A BAPS and UK CCLG Surgeons Cancer Group National Survey

BackgroundNo clear treatment and follow-up protocols have been established for prepubertal patients with ovarian tumours. The lack of adequate prospective data in the literature includes all aspects of their management. A significant number of children with ovarian masses present out of hours as a surgical emergency and are initially managed by paediatric surgeons without special interest in surgical oncology. Clear guidance on the management of such tumours is therefore fundamental. We hypothesised that – owing to the lack of clear guidelines – the current approach to prepubertal ovarian tumours amongst paediatric surgeons is highly heterogenous. MethodsAn eleven-item multiple choice questionnaire was distributed amongst all BAPS consultant paediatric surgeons in the UK and simultaneously to all paediatric surgical oncology members of the UK Children's Cancer and Leukaemia Group in order to survey the management of ovarian masses in children. We aimed to compare the management approaches in both groups. Results63 consultants participated in the survey; 49% with a special interest in surgical oncology, 48% with different subspecialty interests. The majority of participants (56%) performed 1–5 operations on ovarian tumours per year. Preoperative imaging of choice for the oncology surgeons was US and MRI (77.3%) versus 41.4% in the group of surgeons with different special interests. Surgeons with different special interests were more likely to request Ca125 as a preoperative tumour marker (62.1% vs 32.3%). 19.3% of oncology surgeons, and 27.6% of surgeons with other special interest stated they would never remove an ovarian tumour via the laparoscopic approach. Follow-up practise was highly variable amongst survey participants in both surgeon groups regarding frequency, duration and further investigations during follow-up. Almost 50% of participants follow their patients up according to personal practice protocols. ConclusionThis first national survey on the management of prepubertal ovarian tumours demonstrates great heterogeneity in the current approach amongst UK paediatric surgeons. Better evidence is needed to formulate clear guidance for the management of such tumours. We propose instigation of a multicentre registry for ovarian tumours to generate prospective data and clarify guidance for the future. Level of evidence statementThis is a level II evidence study. In itself it is a retrospective study, with the literature review including one large, high-quality prospective cohort study, and further prospective cohort studies of ordinary quality.

Fertility preservation in children and adolescents: current options and considerations.

The purpose of this review is to outline current pediatric fertility preservation options, and discuss ethical and financial considerations impacting this rapidly expanding field. With the improvement in treatment of pediatric malignancies and medical conditions that threaten fertility, survival rates are increasing. Therefore, minimizing long-term morbidities such as gonadal damage and infertility is of utmost importance. Impaired fertility not only has a significant negative impact on patient's quality of life; in women, gonadal damage puts patients at risk for premature menopause, and increased risk of cardiac, skeletal, and cognitive issues. Fortunately, fertility preservation options exist for both female and male prepubertal and pubertal patients, and discussion of such options with patients and their families prior to the initiation of therapy and/or before further deterioration of gonadal function is crucial. A multidisciplinary approach to fertility counseling, with attention to the patient's goals and cultural beliefs, is ideal. Although several national organizations support integrating a fertility consultation into routine care, fertility preservation is still underutilized. Continued research is needed to understand barriers for patients/families and reduce the number of missed opportunities for fertility preservation.

Future of Spermatogonial Stem Cell Culture: Application of Nanofiber Scaffolds.

Spermatogonial stem cells (SSCs) are unique in mammals because they can transmit genetic information from generation to generation and it is of significant importance. In testes, Sertoli cells, peritubular myoid cells, Leydig cells and other interstitial cells contribute to the spermatogonial stem cell "niche". So, creation of niche in an in vitro condition that mimics the in vivo environment is essential to maintain functional characteristic of SSCs. In this review, we describe the impact of nanofiber scaffolds on the culture of SSCs derived from human-to-mouse. Nanofiber Matrices mimic the architecture and size scale of the natural extracellular matrix (ECM). The scaffold provides more three-dimensional (3D), biomimicking and topographical signals to the cells and results in a more physiologically relevant cellular phenotype. Several investigators use different nanofiber scaffold-like carbon nanotubes (CNTs) scaffold, poly-L-lactic acid (PLLA) nanofiber scaffold, 3D soft agar culture system, human serum albumin (HSA)/tri calcium phosphate nanoparticles (TCPNPs) and electrospun polyamide nanofiber for proliferation and maintenance of self-renewal activity of the SSCs. Application of nanofiber scaffolds for in vitro culture of the SSCs may produce spermatogonial stem cells that can be used in regenerative medicine, tissue engineering, assisted reproductive technology and in the treatment of infertility in pre-pubertal cancer patients.