Pilot Study on the Molecular Pathogenesis of Pyeloureteral Junction Obstruction: Underdevelopment or Fibrosis?

Background and Objectives: Congenital ureteral stenosis is one of the leading causes of impaired urinary drainage and subsequent dilatation of the urinary collecting system, known as hydronephrosis or ureterohydronephrosis. The mechanism that leads to obstruction is not clearly known. Multiple studies in rat models have shown increased angiotensin II and TGFß levels in obstructed ureteral tissue. The aim of the study is to investigate the expression of fibrosis-related genes in obstructive and normal ureteral tissue. Material and Methods: It is a monocentric pilot study in which nineteen patients were selected prospectively. 17 patients underwent Hynes-Anderson pyeloplasty due to the PUJO; two patients underwent ureteroneocystostomy due to ureterovesical junction obstruction (UVJO); and six patients were chosen for the control group: five underwent nephrectomies due to the kidney tumor and one underwent upper pole heminephrectomy due to the duplex kidney with normal pyeloureteric junctions in all. Tissue RNA was chemically extracted after freezing the biopsy samples in liquid nitrogen, with cDNA synthesis performed immediately after nucleic acid isolation. qPCR was performed to evaluate the relative expression of Tgfb1, Mmp1, Timp1, Pai1, Ctgf, and Vegfa. Expression levels of the Gapdh and Gpi genes (geometric average) were used to calculate the relative expression of the investigated genes. Outliers were removed prior to calculating confidence intervals for the experimental groups, and a Wilcoxon rank-sum test was performed to determine the statistical significance of the differences. Results: Significant differences between healthy and stenotic tissue samples in Ctgf gene expression levels were observed, with the samples from afflicted tissue showing lower expression. No statistical difference in expression levels of Tgfb1, Timp1, Vegfa, Mmp1, and Pai1 was found. Conclusions: These findings suggest that tissue fibrosis, similar to other tissues and organs, is not the leading cause of stenosis, at least at the moment of surgery. Decreased CTGF expression is indicative of the developmental origin of obstruction.

Histopathology of Unilateral Cryptorchidism.

Defective mini-puberty inducing insufficient gonadotropin secretion is one of the most common causes of nonobstructive azoospermia in men suffering from congenital isolated unilateral or bilateral cryptorchidism. The aim of our study was to determine the risk for azoospermia by histologic criteria in a cohort of unilateral cryptorchid boys undergoing orchidopexy and bilateral testicular biopsy. We performed a retrospective analysis of data available in the library of the Cryptorchidism Research Institute, Liestal, Switzerland. Complete histological evaluations were available for 319 boys operated on for unilateral cryptorchidism with simultaneous biopsy of the contralateral descended testicle. The median age was 39 (5-192) months and 58 patients were <18 months of age. Forty-eight percent of undescended testis (UDT) and 21% of contralateral testis had no A dark (Ad) spermatogonia. Furthermore, in 11% of boys Ad spermatogonia were lacking in both testes. Positive correlation was found between the spermatogonia/tubule ratio of the UDT and contralateral testis (Spearman rank order correlation is 0.16, P = .003). The extent of alteration in the UDT correlated with the contralateral descended testis, indicating that unilateral cryptorchidism is a bilateral disease. Observed impaired transition from gonocytes into Ad spermatogonia indicates defective mini-puberty, providing one of explanations for azoospermia and infertility development in unilateral cryptorchid men.

Diuretic Enhanced Ultrasonography in the Diagnosis of Pyeloureteral Obstruction.

Background and Objectives: To determine the value of diuretic ultrasonography for the diagnosis of obstructive hydronephrosis. Materials and Methods: Diuretic enhanced ultrasonography was used routinely as a part of examination of patients with hydronephrosis in our Department. There were 72 patients (42 males, 30 females; aged 2 months to 17 years; median age 7.07 years) with a sonoscopic diagnosis of hydronephrosis included from January 2006 until October 2011. The anteroposterior diameter (AD) of renal pelvis was measured sonoscopically before and at sixty minutes after furosemide injection. A weight-adjusted dose of 1 mg/kg of furosemide was administered intravenously. Results: Patients were operated on if pyeloureteral obstruction was suspected because of low or deteriorating differential renal function, increasing hydronephrosis or symptoms thereof. Hydronephrosis was unilateral in 61 (84.7%) and bilateral in 11 (15.3%) patients. The median AD of pelvis before furosemide injection was 22 mm in operated and 17 mm in non-operated patients (p = 0.005). Sixty minutes after furosemide injection, the AD of pelvis in operated patients was 35.5 mm and 25.8 mm in non-operated-25.8 mm (p < 0.001). Logistic regression model demonstrated that significant factors for surgery were: AD 60 min after furosemide infection and ultrasonographic parenchymal sclerosis. Conclusion: Ultrasound measurement of the AD of renal pelvis 1 h after the injection of furosemide used as an additional investigation can help in predicting obstructive hydronephrosis.

Genes Involved in Long-Term Memory Are Expressed in Testis of Cryptorchid Boys and Respond to GnRHa Treatment.

It has been known for many years that boys with unilateral or bilateral undescended testis (cryptorchidism) tend to have a low IQ, and those who belong to the high infertility risk (HIR) group perform less well at school than low infertility risk (LIR) patients. However, the molecular biological processes underlying this phenomenon are not understood. In this study, we report the outcome of testicular RNA profiling for genes involved in long-term memory formation. We analyzed the histology and the transcriptome of testicular biopsies from bilateral HIR cryptorchid boys, comparing those who received GnRHa treatment for 6 months after the first surgery with those who did not receive GnRHa before the second surgery. We found that GnRHa treatment alters the testicular mRNA levels of neuronal genes that are involved in long-term memory and testosterone synthesis. These data highlight a possible molecular link between cryptorchidism, impaired mini-puberty, and diminished cognitive functions. Our results are consistent with the hypothesis that hypogonadotropic hypogonadism in cryptorchid boys with altered mini-puberty may affect neuronal genes important for memory and learning, which could help explaining the negative correlation between cryptorchidism and intellectual abilities.

Infantile hemangioma: Predicting proliferation by infrared thermography.

BACKGROUND AND OBJECTIVE: Infantile hemangiomas (IHs) are benign lesions found in infants. Predicting the cosmetic outcome of these lesions is very difficult. Therefore, in this prospective study, we assessed whether using an infrared thermometer (IRT) to measure the surface temperature of IHs would help to predict their proliferative potential. MATERIALS AND METHODS: Between January 2012 and March 2014, we prospectively investigated 103 children up to 6 months of age with a diagnosis of IH. None of them required immediate treatment. Two projection plain photographs of the IHs were obtained and the temperature of the IH surface was measured with the IRT at each visit. The IHs in these patients were divided into three groups: stable, slightly growing and growing IHs. We analyzed temperature differences between the groups, relative operating characteristic (ROC) curves, and possible application of this method to clinical practice. RESULTS: The median initial temperatures in the groups were 36.7°C for the stable group, 37°C for the slightly growing group, and 37.4°C for the growing group (P<0.01). The area under the ROC curve for the temperature values to predict growth was 0.929. Temperatures at or above 37.4°C showed a specificity of 95%, a sensitivity of 75%, a positive predictive value 81%, and a negative predictive value of 95%. CONCLUSIONS: IRT is a time and cost effective tool, and is easy to learn. The surface temperature of IH reflects its remaining growth potential and could be used in the outpatient setting for the evaluation and follow-up of IH.

Intravesical cidofovir to treat BK virus-associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation.

HC related to BK virus replication might be a severe complication following allogeneic HSCT. There are no clearly defined treatment guidelines in pediatric population. The data on the effectiveness of ICI to manage severe bleeding in children are very limited. We report our experience of intravesical cidofovir in four children, 6-15 yr of age, to manage grade III-IV BK virus-associated HC. Three of four children had high CSA serum level prior to developing cystitis. Intravesical instillations of cidofovir resulted only in temporal relief of bleeding. After immune suppression was withdrawn or tapered, intravesical instillations of formalin solution had to be undertaken to abort severe bleeding. We concluded that intravesical cidofovir alone did not appear to be sufficiently effective in case of severe HC, necessitating complimentary procedures to stop macrohematuria.

Cloacal reconstruction after a complex treatment of perineal haemangioma in a variant of PELVIS syndrome.

BACKGROUND: PELVIS is an acronym defining the association of perineal hemangioma, malformations of external genitalia, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus and skin tag. Eleven cases have been reported according to the Orphanet data. Acronyms of LUMBAR and SACRAL syndrome have been used and most probably represent a spectrum of the same entity. Very little is known about the success and timing of cloacal reconstruction after the treatment of hemangioma. We present a variant of PELVIS syndrome and discuss the possibilities and optimal timing of surgical reconstruction. CASE PRESENTATION: Female infant was born with persistent cloaca and multiple hemangiomas of genitals, perineal area and left thigh. Colostomy was performed after birth. In order to treat hemangioma and to make the reconstruction of cloaca possible, corticosteroid treatment orally and multiple laser treatments were performed alternating Nd:YAG laser and pulsed dye laser therapy. Cystoscopy confirmed hemangiomatosis in the mucosa of the common channel, bladder neck and septate vagina. Oral propranolol treatment was started at the age of 18 months and continued for 1 year. It induced rapid improvement of hemangiomas. Two more pulsed dye laser treatments were performed to remove residuals of hemangiomas from the perineum and genital area. Posterior sagital reconstruction by separation of the rectum, mobilization of urogenital sinus and vaginal reconstruction was performed with no major bleeding at the age of 4 years. Postoperatively, after a period of progressive rectal dilatation colostomy was closed. Girl is now 6 years old, dry day and night without residual urine and normal upper tracts. Rectal calibration is normal, fecal continence is still to be evaluated but constipation is easily manageable. CT of the spine and the perineum showed sacral dysplasia and spina bifida with lumbo-sacral lipoma and tethering of terminal filum without neurological deterioration at the moment but requiring close neurological monitoring. CONCLUSIONS: Large perineal hemangiomas are commonly associated with extracutaneous abnormalities. Successful reconstructive surgery is possible after significant reduction of hemangioma by complex treatment.

Incidence of High Infertility Risk among Unilateral Cryptorchid Boys.

BACKGROUND: Increasing evidence of progressive damage to germ cell development in boys with cryptorchidism suggests recommending surgery until one year of age. However, despite early and successful orchidopexy, cryptorchid boys with impaired mini-puberty will suffer from infertility. We reviewed changes in the timing of surgery during the past decade and the incidence of unilateral cryptorchid boys with defective mini-puberty. METHODS: Medical registries were reviewed for all patients who were operated on for cryptorchidism at the main pediatric urological center of the country. The ages of surgery in cases of unilateral cryptorchidism were compared between the years 2000-2001 and 2012-2013. A high risk of infertility was considered when no Ad spermatogonia were found. Two groups were compared: group I--operated on until the age of 1.5 years and group II--older than 1.5 years. RESULTS: The average age at operation decreased from 5.3 to 4.1 years. Forty-six biopsies in boys with unilateral cryptorchidism were made during orchidopexy on undescended testicles. Overall, 44% in group I and 50 % in group II (p > 0.05) had no Ad spermatogonia. CONCLUSIONS: The average age of operation for cryptorchidism has decreased, but remains far above the recommended age. The high prevalence of histologically proven risk of infertility underscores the necessity of more education regarding the importance of earlier surgery and the research on hormonal prevention of infertility.

Congenital hyperinsulinism.

Hyperinsulinism is the most common cause of hypoglycemia in infants. In many cases conservative treatment is not effective and surgical intervention is required. Differentiation between diffuse and focal forms and localization of focal lesions are the most important issues in preoperative management. We present a case of persistent infancy hyperinsulinism. Clinical presentation, conservative treatment modalities, diagnostic possibilities of focal and diffuse forms, and surgical treatment, which led to total recovery, are discussed.

Do MRI Results Represent Functional Outcomes Following Arthroscopic Repair of an Isolated Meniscus Tear in Young Patients?-A Prospective Comparative Cohort Study.

BACKGROUND: The use of postoperative MRI to assess the healing status of repaired menisci is a long-standing issue. This study evaluates and compares functional and MRI outcomes following an arthroscopic meniscus repair procedure with the aim of postoperative MRI diagnostic accuracy clarification in young patients. METHODS: A total of 35 patients under 18 years old who underwent isolated meniscus repair were included. The Pedi-IKDC score, Lysholm score, and Tegner activity index (TAS) were compared between the groups formed according to the Stroller and Crues three-grade classification of postoperative MRI-based evaluations. Grade 3 MRI views were classified as unhealed, grade 2 as partially healed, and grade 1 as fully healed within the repaired meniscus, whereas grade 3 cases were considered unsuccessful due to MRI evaluation. RESULTS: MRI assessment revealed 4 cases of grade 1 (11.4%), 14 cases of grade 2 (40.8%), and 17 cases of grade 3 (48.0%) lesions. Pedi-IKDC and TAS scores were significantly higher among MRI grade 2 patients than among MRI grade 3 patients (p < 0.05). Weak negative correlations between MRI grades and all functional scales were found (p < 0.05). ROC analysis showed that Pedi-IKDC and TAS scores could correctly classify 77% and 71% of MRI grade 3 patients, respectively. The optimal cut-off values to detect grade 3 patients were 88.74 for the Pedi-IKDC score and 4.5 for the TAS score. CONCLUSIONS: To conclude, established functional score cut-off values may help identify unhealed meniscus repair patients.

Epigenetics, cryptorchidism, and infertility.

BACKGROUND: Cryptorchid boys with defective mini-puberty and impaired differentiation of Ad spermatogonia (high infertility risk) have altered expression of several genes encoding histone methyltransferases compared to patients with intact differentiation of gonocytes into Ad spermatogonia (low infertility risk). RESULTS: High infertility risk cryptorchid boys display hypogonadotropic hypogonadism, which, together with the diminished expression of histone deacetylases and increased expression of HDAC8 decrotonylase, indicates altered histone marks and, thus, a perturbed histone code. Curative GnRHa treatment induces normalization of histone methyltransferase, chromatin remodeling, and histone deacetylase gene expression. As a result, histone changes induce differentiation of Ad spermatogonia from their precursors and, thus, fertility. In this short report, we describe key functions of histone lysine methyltransferases, chromatin remodeling proteins, and long-noncoding RNAs, and discuss their potential roles in processes leading to infertility. CONCLUSION: Our findings suggest that epigenetic mechanisms are critical to better understanding the root causes underlying male infertility related to cryptorchidism and its possible transgenerational transmission.

RéSUMé: CONTEXTE: Chez les garçons cryptorchides qui présentent une minipuberté défectueuse et une différenciation altérée des spermatogonies Ad (risque élevé d'infertilité), l'expression de plusieurs gènes codant pour les histone méthyltransférases est altérée par rapport aux garçons présentant une différenciation intacte des gonocytes en spermatogonie Ad (faible risque d'infertilité). RéSULTATS: Les garçons cryptorchides à risque élevé d'infertilité présentent un hypogonadisme hypogonadotrope, qui, avec la diminution de l'expression des histone désacétylases et l'augmentation de l'expression de la décrotonyase HDAC8, indiquent une altération des marques d'histones et, par conséquent, un code d'histones perturbé. Le traitement curatif par la GnRHa induit une normalisation de l'histone-méthyltransférase, du remodelage de la chromatine et l'expression du gène de l'histone-désacétylase. En conséquence, les changements d'histones induisent la différenciation des spermatogonies Ad à partir de leurs précurseurs, et donc la fertilité. Dans le court rapport qui suit, nous décrivons les fonctions clés des histones lysine méthyltransférases, des protéines de remodelage de la chromatine et des ARN longs non codants; leur rôles potentiels dans les processus menant à l'infertilité sont discutés. CONCLUSION: Nos résultats suggèrent que les mécanismes épigénétiques sont un élément critique pour une meilleure compréhension des causes sous-jacentes de l'infertilité masculine liée à la cryptorchidie et sa transmission transgénérationnelle.

The Significance of Selecting an Appropriate Patient-Reported Outcome Measure (PROM): A Cross-Cultural Adaptation of the Specific Paediatric International Documentation Committee Subjective (Pedi-IKDC) Knee Form.

INTRODUCTION: The selection of an appropriate PROM is a crucial aspect in assessing outcomes. Questionnaires that have not been designed or validated for a paediatric population are routinely used. Using a questionnaire requires translation, cultural adaptation, and testing the psychometric properties of the translated questionnaire. There is no applicable questionnaire in our country for children with knee-specific conditions in sports orthopaedics. Therefore, this study aims to translate, culturally adapt, and assess the psychometric properties of the Paediatric IKDC (Pedi-IKDC) questionnaire within the Lithuanian paediatric population. METHODS: The translation was conducted in accordance with international standards. Patients aged 11-17 years with various knee disorders participated in three surveys and completed the Pedi-IKDC, Lysholm, and PedsQL questionnaires. Interviews with patients following the translation process, in addition to floor and ceiling effects, were used to assess content validity. Cronbach alpha (α) statistics and the intraclass correlation coefficient (ICC) were applied to measure internal consistency and reproducibility, respectively. The standard error of measurement (SEM) and smallest detectable change (SDC) were calculated to assess reliability. Pearson correlations were calculated between Pedi-IKDC and Lysholm PedsQL scores to determine criteria validity. The effect size (ES) and standardised response mean (SRM) were calculated to assess the responsiveness to change. RESULTS: Cronbach's alpha (α) was 0.91 for the total score, 0.75 for symptoms, and 0.92 for the sport/function component. The ICC for overall scores was 0.98, with each question ranging from 0.87 to 0.98. The SEM was 2.97, and the SDC was 8.23. Lysholm and PedsQL physical functioning domain scores had moderate correlations (0.8 > r > 0.5), and the overall PedsQL score had a weak correlation (0.5 > r > 0.2) to the Pedi-IKDC score. The floor and ceiling effects were 3.3% and 1.6%, respectively. The SRM was 1.72 and the ES was 1.98. CONCLUSIONS: The Lithuanian Pedi-IKDC version is an appropriate evaluation instrument for assessing outcomes in children with knee disorders. All of the psychometric features produced acceptable results.

Gubernaculum and Epididymo-Testicular Descent: Review of the Literature.

Cryptorchidism is a common disorder in boys that has been widely studied both experimentally and clinically. The role of the gubernaculum, a mesenchymal tissue extending from the fetal testis and epididymis to the developing scrotum, is still unclear. Even the name is debated: 'gubernaculum epididymis' or 'gubernaculum testis'. This review does not aim to provide a global overview of competing theories on testicular descent, but focuses on the role of the gubernaculum in epididymo-testicular descent. We identified four major pitfalls of gubernaculum research: the role of the gubernaculum, of insulin-like peptide 3, anti-Müllerian hormone, and androgens. The major critical issues were that the gubernaculum plays a guiding role for the epididymis, descending prior to the testis and expanding the inguinal canal; insulin-like peptide 3 is not as important for the process of descent in humans as the rate of insulin-like peptide 3 mutations is low; anti-Müllerian hormone plays no significant role in epididymo-testicular descent; androgens and gonadotropins play a crucial role in epididymo-testicular descent. The role of the epididymis in the complex process of gubernaculum, epididymis, and testis migration is underestimated and should be included in future research.

A novel role for CFTR interaction with LH and FGF in azoospermia and epididymal maldevelopment caused by cryptorchidism.

Cryptorchidism occurs frequently in children with cystic fibrosis. Among boys with cryptorchidism and abrogated mini-puberty, the development of the epididymis and the vas deferens is frequently impaired. This finding suggests that a common cause underlies the abnormal development of Ad spermatogonia and the epididymis. The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette transporter protein that acts as a chloride channel. The CFTR gene has been associated with spermatogenesis and male fertility. In boys with cryptorchidism, prepubertal hypogonadotropic hypogonadism induces suboptimal expression of the ankyrin-like protein gene, ASZ1, the P-element induced wimpy testis-like gene, PIWIL, and CFTR. The abrogated expression of these gene leads to transposon reactivation, and ultimately, infertility. Curative gonadotropin-releasing hormone agonist (GnRHa) treatment stimulates the expression of CFTR and PIWIL3, which play important roles in the development of Ad spermatogonia and fertility. Furthermore, GnRHa stimulates the expression of the epididymal androgen-sensitive genes, CRISP1, WFDC8, SPINK13, and PAX2, which thereby promotes epididymal development. This review focuses on molecular evidence that favors a role for CFTR in cryptorchidism-induced infertility. Based on information available in the literature, we interpreted our RNA-Seq expression data obtained from samples before and after randomized GnRHa treatment in boys with bilateral cryptorchidism. We propose that, in boys with cryptorchidism, CFTR expression is controlled by luteinizing hormone and testosterone. Moreover, CFTR regulates the activities of genes that are important for fertility and Wolffian duct differentiation.

RéSUMé: La cryptorchidie survient fréquemment chez les enfants atteints de mucoviscidose et une altération du développement de l'épididyme et du canal déférent a été observée chez les garçons cryptorchides avec une mini-puberté abrogée. Cela suggère que le développement anormal des spermatogonies Ad et de l'épididyme ont une cause commune. CFTR est. une protéine de transport de cassette de liaison à l'ATP qui agit comme un canal chlorure. Plus précisément, le CFTR a été associé à la spermatogenèse et à la fertilité masculine. Chez les garçons cryptorchides, l'hypogonadisme hypogonadotrope prépubère induit une expression sous-optimale d'ASZ1, de quatre gènes PIWIL et de CFTR, entraînant la réactivation des transposons et l'infertilité. Le traitement curatif à la GnRHa stimule l'expression des gènes CFTR et PIWIL3 qui sont importants pour le développement des spermatogonies Ad et la fertilité subséquente. En outre. Le traitement à la GnRHa stimule les gènes épididymaires sensibles aux androgènes CRISP1, WFDC8, SPINK13, PAX2 favorisant le développement de l'épididyme. Cette revue se concentre sur les preuves moléculaires en faveur du rôle du CFTR dans l'infertilité causée par la cryptorchidie. Nous avons interprété les données d'expression de RNAseq obtenues avec des échantillons avant et après un traitement randomisé à la GnRHa chez des garçons cryptorchides bilatéraux dans le contexte des informations disponibles dans la littérature. Nous proposons que chez les garçons cryptorchides, le CFTR est. contrôlé par l'hormone lutéinisante (LH) et la testostérone et influence les activités des gènes qui sont importants pour la fertilité et la différenciation du canal de Wolff.

Early Bilateral Gonadoblastoma in a Patient with Mixed Gonadal Dysgenesis (Karyotype 45,X/46,XY): Case Report and Review of Literature.

Background: Mixed gonadal dysgenesis is a rare congenital and challenging condition, characterized mainly by 45,X/46,XY karyotype mosaicism, asymmetrical gonadal development and various internal and external genital anatomy. Because of frequent disorder of genital development and a higher risk of germ cell neoplasia, management of these patients is complex and requires multidisciplinary approach. Case: We present a 45,X/46,XY mixed gonadal dysgenesis patient diagnosed with gonadoblastoma in both gonads after bilateral gonadectomy at 1 year of age. Conclusions: Because of high risk for malignant transformation, gonadectomy of a streak-like gonad and biopsy with orchidopexy or gonadectomy of a dysgenetic testicle is recommended at an early age.

How the First Year of COVID-19 Affected Elective Pediatric Urology Patients: A Longitudinal Study Based on Waiting Lists and Surveys From 10 European Centers.

Introduction: COVID-19 impacted healthcare systems worldwide, and elective surgical activity was brought to a minimum. Although children were not primarily affected by the disease, pediatric urology was halted by clinical closedown and staff allocation. We aimed to document how these prioritizations affected waiting lists, and to investigate how European centers dealt with the challenge of these logistical and financial prioritizations. Materials and Methods: This was a 1-year prospective study, starting March 2020. Participants were surveyed at 3-month intervals about waiting lists for several common procedures as well as OR capacity and funding. Further, centers retrospectively reported on surgical and outpatient activity rates during 2019-2021. Waiting list tendencies were evaluated in relation to study baseline. Results: A marked decrease in surgical and outpatient activity was seen in the spring of 2020. Some included pediatric urology centers were able to increase their budget (15%) and staff working hours (20%) during part of the study period. Still, at the end of the study, the centers had increased the total number of patients on waiting lists with 11%, whereas the average days on waiting lists had accumulated with 73%, yielding a total of 6,102 accumulated waiting days in the study population. Centers with decreased resources had markedly negative effects on waiting lists. Conclusions: Correlations between COVID-19 derived burdening of healthcare systems and the availability of pediatric urology greatly depends on the prioritizations made at individual centers. Ongoing monitoring of these correlations is warranted to safely avoid unnecessary negative impact on the pediatric population.

Cloacal exstrophy: a case report and literature review.

Cloacal exstrophy is an extremely rare congenital malformation resulting in an exstrophy of the urinary, intestinal, and genital organs and associated with anomalies of other organ systems. We present a complicated case of cloacal exstrophy and the recent progress in the management of this probably most complicated anomaly in pediatric urology and surgery.

Molecular clues in the regulation of mini-puberty involve neuronal DNA binding transcription factor NHLH2.

Gonadotropin releasing hormone agonist (GnRHa) treatment following surgery to correct cryptorchidism restores mini-puberty via endocrinological and transcriptional effects and prevents adult infertility in most cases. Several genes are important for central hypogonadotropic hypogonadism in mammals, including many that are transcribed in both the brain and testis. However, the expression of these genes in prepubertal gonads has not been studied systematically, and little is known about the effect of hormone therapy on their testicular and neuronal expression levels. In this review, we interpret histological sections, data on hormone levels, and RNA profiling data from adult normal testes compared to pre-pubertal low infertility risk (LIR) and high infertility risk (HIR) patients randomly treated with surgery in combination with GnRHa or only surgery. We organize 31 target genes relevant for idiopathic hypogonadotropic hypogonadism and cryptorchidism into five classes depending on their expression levels in HIR versus LIR samples and their response to GnRHa treatment. Nescient-helix-loop-helix 2 (NHLH2) was the only gene showing a decreased mRNA level in HIR patients and an increase after GnRHa treatment. This phenomenon may reflect a broader effect of hormone treatment on gene expression in both testicular and central nervous system tissues, which could explain why the hypothalamus-pituitary-testicular axis is permanently restored by the administration of GnRHa.

RéSUMé: Le traitement par l'agoniste de l'hormone de libération des gonadotrophines (GnRHa) suite à une intervention chirurgicale pour cryptorchidie rétablit la mini-puberté par des effets endocrinologiques et transcriptionnels et prévient l'infertilité adulte dans la plupart des cas. Plusieurs gènes jouent un rôle important dans l'hypogonadisme hypogonadotrope central chez les mammifères, dont certains sont transcrits à la fois dans le cerveau et les testicules. Cependant, l'expression de ces gènes dans les gonades prépubères n'a pas été étudiée systématiquement et l'effet de l'hormonothérapie sur leurs niveaux d'expression testiculaire et neuronale n'est pas connu. Dans cette revue, nous interprétons des coupes histologiques, des données sur les taux d'hormones et des données de profilage d'ARN provenant de testicules normaux adultes et des patients prépubères à faible risque d'infertilité (LIR) et à haut risque d'infertilité (HIR) traités par chirurgie en association avec la GnRHa ou seulement la chirurgie dans le cadre d'une étude randomisée. Nous organisons 31 gènes cibles pertinents pour l'hypogonadisme hypogonadotrope idiopathique et la cryptorchidie en cinq classes en fonction de leurs niveaux d'expression dans les échantillons HIR et LIR et de leur réponse au traitement par GnRHa. Nescient-helix-loop-helix 2 (NHLH2) était l'unique gène dont le niveau d'ARNm diminue chez les patients HIR par rapport aux LIR et augmente suite au traitement par GnRHa. Ce phénomène pourrait être révélateur d'un effet généralisé du traitement hormonal sur l'expression des gènes dans les tissus testiculaires et du système nerveux central. Cela pourrait expliquer pourquoi l'axe hypothalamo-hypophyso-gonadique est définitivement rétablie par l'administration de la GnRHa.

Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis.

Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations. Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior-posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio. Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, ß2 microglobulin (ß2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the ß2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%. Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.

A crosscut survey on reproductive health in Lithuanian childhood cancer survivors.

OBJECTIVES: Sexual dysfunction was reported to compromise the quality of life in childhood cancer survivors. The aim of our study was to evaluate the reproductive health in long-term pediatric cancer survivors by conducting a crosscut survey. MATERIAL AND METHODS: Childhood cancer survivors over 18 years of age, who were in remission for more than 5 years, were invited to complete a gender-specific questionnaire surveying on their reproductive health. Demographic and treatment data were retrieved from their medical records. Treatment modalities were reviewed for its potential gonadotoxicity. RESULTS: 34 (17 males and 17 females, respectively) from 346 addressed survivors (9.8%) completed the questionnaire. Median age and follow-up after diagnosis was 27 (18-35) and 14 (3-25) years, respectively. Some respondents reported sexual concerns: 11.8% males experienced problems with penetration, two males (11.8%) who underwent semen analysis were found to be azoospermic. Similarly, 11.8% females reported delayed puberty, the average age of menarche was 14 (12-17) years, 29.4% females reported irregular menstrual cycles. Cyclophosphamide equivalent dose (CED) differed significantly between the patients treated for leukemia, lymphoma and solid tumors (3000 vs 4352 vs 6660 mg/m2, respectively, p = 0.014). CONCLUSIONS: Low prevalence of sexual dysfunction, fertility related disorders or delayed puberty in childhood cancer survivors was found. However, the results should be interpreted with caution taking into account a low response rate.