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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Abnormal histology in testis from prepubertal boys with monorchidism.

BACKGROUND: Little is known about the histology of contralateral descended testes in boys with unilaterally absent testis. We investigated whether absence of one testis is associated with abnormal tissue architecture of the solitary contralaterally descended testis. DESIGN SETTING AND PATIENTS: For this retrospective study, we examined the results of biopsies of the contralateral descended testis in 43 boys with monorchidism. Data from 26 control testes from boys of matching ages were selected from results published in 1977 and 2009. During surgery, any nubbins were removed. In each case, the scrotal testis was biopsied, and the testis fixed by subdartos pouch or suture. RESULTS: Of the 43 affected boys, 23 had normal testicular histology in the contralateral descended testis, whereas 20 (46%) had abnormal histology. Eight of the abnormal biopsies matched the criteria for high infertility risk. Samples from three boys in this latter group revealed a Sertoli-cell-only phenotype. Immunohistochemical assays were positive for steroidogenic acute regulatory (STAR) protein in Leydig cells and spermatogonia. STAR expression was stronger in the monorchid group with normal testicular histology. CONCLUSIONS: Almost half of the patients with unilateral absent testis were at risk for subfertility or infertility. Our results emphasize the need for testicular biopsy of the solitary testis in boys with monorchidism to appropriately assess infertility risk.

CONTEXTE: Peux d'études ont analysé la structure des tissus testiculaires des testicules descendus controlatéraux chez les garçons avec des testicules unilatéraux absents. Nous avons investigué si l'absence congénitale d'un testicule est. associée à une histologie anormale des testicules descendus controlatéraux solitaires. CONCEPTION CONTEXTE ET PATIENTS: Cette étude rétrospective a examiné les résultats des biopsies des testicules descendus controlatéraux de 43 garçons monorchides. Les données de 26 testicules témoins ont été appariées surl'âge et sélectionnées à partir des données publiées en 1977 et 2009. Pendant l'opération, les nubins (reliquats) détectés ont été enlevés. Dans chaque cas, les testicules scrotaux ont fait l'objet d'une biopsie et d'une fixation par la technique de la valise ou par suture au subdartos. RÉSULTATS: Parmi 43 garçons, 23 avaient une histologie testiculaire normale dans les testicules descendus controlatéraux, tandis que 20 (46%) avaient une histologie anormale. Huit biopsies anormales correspondaient aux critères de risque élevé d'infertilité. Trois garçons de ce groupe avaient une histologie testiculaire montrant la présence de cellules Sertoli seules. L'analyse immunohistochimique de la protéine STAR a montré un signale dans les cellules de Leydig et dans les spermatogonies. L'expression STAR était plus forte dans le groupe des monorchides avec une histologie testiculaire normale. CONCLUSIONS: Près de la moitié des patients ayant des testicules congénitaux unilatéraux absents couraient un risque d'hypofertilité ou d'infertilité. Nos résultats soulignent la nécessité d'une biopsie testiculaire des testicules solitaires chez les garçons monorchides afin d'évaluer le risque d'infertilité de ces patients.

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 located in Y-chromosomal regions important for male fertility show altered transcript levels in cryptorchidism and respond to curative hormone treatment.

BACKGROUND: Undescended (cryptorchid) testes in patients with defective mini-puberty and low testosterone levels contain gonocytes that fail to differentiate normally, which impairs the development of Ad spermatogonia and ultimately leads to adult infertility. Treatment with the gonadotropin-releasing hormone agonist GnRHa increases luteinizing hormone and testosterone and rescues fertility in the majority of pathological cryptorchid testes. Several Y-chromosomal genes in the male-specific Y region (MSY) are essential for spermatogenesis, testis development and function, and are associated with azoospermia, infertility and cryptorchidism. In this study, we analyzed the expression of MSY genes in testes with Ad spermatogonia (low infertility risk patients) as compared to testes lacking Ad spermatogonia (high infertility risk) before and after curative GnRHa treatment, and in correlation to their location on the Y-chromosome. RESULTS: Twenty genes that are up- or down-regulated in the Ad- group are in the X-degenerate or the ampliconic region, respectively. GnRHa treatment increases mRNA levels of 14 genes in the ampliconic region and decreases mRNA levels of 10 genes in the X-degenerate region. CONCLUSION: Our findings implicate Y-chromosomal genes, including USP9Y, UTY, TXLNGY, RBMY1B, RBMY1E, RBMY1J and TSPY4, some of which are known to be important for spermatogenesis, in the curative hormonal treatment of cryptorchidism-induced infertility.

CONTEXTE: La non descente des testicules chez les garçons cryptorchides qui présentent une mini-puberté défectueuse et un taux réduit de testostérone (T) ont des gonocytes incapables de se différencier normalement en spermatogonie Ad. Cette dernière entraîne une infertilité. Le traitement avec l'agoniste du GnRH (GnRHa) augmente les taux de LH et T et permet de sauvegarder la fertilité chez la majorité des testicules cryptorchides pathologiques. Plusieurs gènes du chromosome Y localisés dans la région spécifique du mâle (MSY) sont essentiels pour la spermatogénèse, ainsi que pour le développement et la fonction testiculaires, et sont associés à l'azoospermie, l'infertilité et la cryptorchidie. Dans cette étude, nous avons analysé l'expression des gènes dans la région MSY des testicules avec et sans spermatogonies Ad, avant et après traitement par GnRHa. Les résultats sont corrélés avec la localisation des gènes dans le chromosome Y. RÉSULTATS: Dans le groupe Ad-, vingte gènes dont l'expression est. régulée à la hausse ou à la baisse sont respectivement localisés dans la région dégénérée du X ou dans la région ampliconique. Le traitement par GnRHa augmente les taux de mRNA de 14 gènes dans la région ampliconique et réduit l'expression de 10 gènes dans la région dégénérée du X. CONCLUSION: Nos résultats impliquent une participation des gènes du chromosome Y, compris USP9Y, UTY, TXLNGY, RBMY1B, RBMY1E, RBMY1J et TSPY4, dont certains sont importants pour la fertilité, dans le traitement curatif de l'infertilité due à la cryptorchidie.

Testicular expression of long non-coding RNAs is affected by curative GnRHa treatment of cryptorchidism.

BACKGROUND: Cryptorchidism is a frequent endocrinopathy in boys that has been associated with an increased risk of developing testicular cancer and infertility. The condition is curable by combined surgery and hormonal treatment during early pre-pubertal stages using gonadotropin releasing hormone agonist (GnRHa). However, whether the treatment also alters the expression of testicular long non-coding RNAs (lncRNAs) is unknown. To gain insight into the effect of GnRHa on testicular lncRNA levels, we re-analyzed an expression dataset generated from testicular biopsies obtained during orchidopexy for bilateral cryptorchidism. RESULTS: We identified EGFR-AS1, Linc-ROR, LINC00221, LINC00261, LINC00282, LINC00293, LINC00303, LINC00898, LINC00994, LINC01121, LINC01553, and MTOR-AS1 as potentially relevant for the stimulation of cell proliferation mediated by GnRHa based on their direct or indirect association with rapidly dividing cells in normal and pathological tissues. Surgery alone failed to alter the expression of these transcripts. CONCLUSION: Given that lncRNAs can cooperate with chromatin-modifying enzymes to promote epigenetic regulation of genes, GnRHa treatment may act as a surrogate for mini-puberty by triggering the differentiation of Ad spermatogonia via lncRNA-mediated epigenetic effects. Our work provides additional molecular evidence that infertility and azoospermia in cryptorchidism, resulting from defective mini-puberty cannot be cured with successful orchidopexy alone.

CONTEXTE: La cryptorchidie est. une endocrinopathie fréquente chez les garçons. Elle est. associée à un risque élevé de cancer des testicules et d'infertilité. La cryptorchidie peut être soignée par une thérapie incluant une intervention chirurgicale et un traitement hormonal par l'agoniste de l'hormone GnRH. Alors que l'effet de la thérapie sur l'expression des ARNm a été analysé, ses conséquences pour la transcription des longs ARNs non codants (ARNlnc) testiculaires restent inconnues. Afin de mieux comprendre les effets du GnRHa sur les concentrations cellulaires des ARNlnc dans le testicule, nous avons analysé des données d'expression d'ARN par séquençage (ARN-Seq) générées en utilisant des biopsies testiculaires obtenues dans le cadre d'une orchidopexie pour cryptorchidie bilatérale. RÉSULTATS: Nous avons identifié les ARNlnc EGFR-AS1, Linc-ROR, LINC00221, LINC00261, LINC00282, LINC00293, LINC00303, LINC00898, LINC00994, LINC01121, LINC01553, et MTOR-AS1 comme potentiellement pertinents pour la stimulation de la prolifération cellulaire induite par le GnRHa. Cette conclusion fait référence à leur association directe ou indirecte avec la croissance et division cellulaire mitotique rapide dans les tissus normaux et pathologiques. Nous constatons également que la chirurgie seule n'a pas d'effet détectable par ARN-Seq sur l'expression de ces ARNlnc. CONCLUSION: Étant donné que certains ARNlnc coopèrent avec des enzymes ayant un effet sur la structure chromatinienne et la régulation épigénétique des gènes, le traitement par GnRHa pourrait substituer la mini-puberté en déclenchant la différenciation des spermatogonies Ad par un mécanisme épigénétiques qui dépendrait des ARNlnc. Notre travail révèle des nouvelles pistes moléculaires soutenant l'hypothèse que l'infertilité et l'azoospermie associées avec la cryptorchidie sont la conséquence d'une anomalie de la mini-puberté. Cela explique pourquoi une thérapie efficace de cette pathologie ne nécessite pas seulement l'orchidopexie mais aussi un traitement hormonal.

Conservative treatment of caustic oesophageal injuries in children: 15 years of experience in a tertiary care paediatric centre.

INTRODUCTION: Endoscopic dilatation is good choice of conservative treatment for caustic digestive tract injuries in children. AIM: To set up a strategy of management of caustic digestive tract injury based on our experience and literature review. MATERIAL AND METHODS: We retrospectively analysed medical records of 34 paediatric patients who were admitted to the Centre of Paediatric Surgery of the Children's Hospital between 2000 and 2017. Age at presentation, gender, anatomic location, circumstances and distribution of injury, early and late complications, clinical signs, and the first aid were analysed. Upper gastrointestinal (GI) endoscopy was performed within 12-24 h after ingestion in all cases. The Zargar classification system was used to grade the severity of the injury. Fisher's exact test was used for statistical analysis, with p < 0.05 considered as the limit of statistical significance. RESULTS: The upper GI endoscopy revealed caustic injuries in 5 (15%) and 8 (23%) patients were classified as grade IIa and IIb, respectively. Oesophageal and ventricle caustic injuries in 3 (9%) and 2 (6%) patients were classified as grade IIIa and IIIb, respectively. Thirteen patients with grade IIa and IIIb injuries suffered permanent damage and required repeated dilatation. All patients underwent stricture treatment using late or early endoscopic dilatation of the oesophagus. An average of 15 dilatation procedures were required to achieve a satisfactory lumen. CONCLUSIONS: Our experience of 34 children revealed that endoscopic dilatation may be required as a primary treatment for oesophageal strictures.

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.

Management of Gonads in Adults with Androgen Insensitivity: An International Survey.

BACKGROUND: Complete and partial androgen insensitivity syndrome (CAIS, PAIS) are associated with an increased risk of gonadal germ cell cancer (GGCC). Recent guidelines recommend gonadectomy in women with CAIS in late adolescence. Nevertheless, many adult women prefer to retain their gonads. AIMS: This study aims to explore attitudes towards gonadectomy in AIS in centres around the world, estimate the proportion of adults with retained gonads and/or who developed GGCC, and explore reasons for declining gonadectomy. METHODS: A survey was performed among health care professionals who use the International DSD Registry (I-DSD). RESULTS: Data were provided from 22 centres in 16 countries on 166 women (CAIS) and 26 men (PAIS). In CAIS, gonadectomy was recommended in early adulthood in 67% of centres; 19/166 (11.4%) women refused gonadectomy. Among 142 women who had gonadectomy, evidence of germ cell neoplasm in situ (GCNIS), the precursor of GGCC, was reported in 2 (1.4%) out of 8 from whom pathology results were formally provided. Nine out of 26 men with PAIS (34.6%) had retained gonads; 11% of centres recommended routine gonadectomy in PAIS. CONCLUSION: Although development of GGCC seems rare, gonadectomy after puberty is broadly recommended in CAIS; in PAIS this is more variable. Overall, our data reflect the need for evidence-based guidelines regarding prophylactic gonadectomy in AIS.

PRDM Histone Methyltransferase mRNA Levels Increase in Response to Curative Hormone Treatment for Cryptorchidism-Dependent Male Infertility.

There is a correlation between cryptorchidism and an increased risk of testicular cancer and infertility. During orchidopexy, testicular biopsies are performed to confirm the presence of type A dark (Ad) spermatogonia, which are a marker for low infertility risk (LIR). The Ad spermatogonia are absent in high infertility risk (HIR) patients, who are treated with a gonadotropin-releasing hormone agonist (GnRHa) to significantly lower the risk of infertility. Despite its prevalence, little is known about the molecular events involved in cryptorchidism. Previously, we compared the transcriptomes of LIR versus HIR patients treated with and without hormones. Here, we interpreted data regarding members of the positive regulatory domain-containing (PRDM) family; some of which encoded histone methyltransferases that are important for reproduction. We found there were lower levels of PRDM1, PRDM6, PRDM9, PRDM13, and PRDM14 mRNA in the testes of HIR patients compared with LIR patients, and that PRDM7, PRDM9, PRDM12, and PRDM16 were significantly induced after GnRHa treatment. Furthermore, we observed PRDM9 protein staining in the cytoplasm of germ cells in the testes from LIR and HIR patients, indicating that the mRNA and protein levels corresponded. This result indicated that the curative hormonal therapy for cryptorchidism involved conserved chromatin modification enzymes.