Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients / 亚洲男科学杂志(英文版)

Persistent Müllerian duct syndrome (PMDS) is a rare clinically and genetically overlapping disorder caused by mutations in the anti-Müllerian hormone (AMH) gene or the anti-Müllerian hormone receptor type 2 (AMHR2) gene. Affected individuals present uterus and tubes in normally virilized males and are discovered unexpectedly during other surgeries. Since it is rare and complex, a definitive clinical diagnosis can be missed, and there are no guidelines regarding how to deal with the uterus. In the present study, exome sequencing and Sanger verification were performed for causal variants in 12 PMDS patients. Preoperative diagnoses were made by positive exome sequencing in 8 patients. Of them, 7 patients evoked on the basis of ultrasound indicating bilateral testes on the same side of the body. Twelve different AMH variants (2 frameshift/nonsense, 1 deletion, 8 missense, and 1 in-frame) in 9 patients and 6 different AMHR2 variants (5 missense and 1 splicing) in 3 patients were identified. Seven variants were classified as "pathogenic" or "likely pathogenic", and 4 of them were novel. All but two patients with AMH defects showed low serum AMH concentrations, but all patients with AMHR2 defects showed elevated AMH levels. During surgery, an abnormal vas deferens was observed in half of the patients. Eight patients underwent orchidopexy with uterine preservation. Of them, 2 patients presented complications including irreducible cryptorchidism, and 3 patients developed Müllerian remnant cysts. Three patients underwent subtotal hysterectomy. Of them, one patient had complication of injury to the vas deferens, and one had hemorrhage after operation. This is the first report of PMDS involving a large Chinese population. The present study not only expands the variation spectrum but also provides clinical experience about the management of the uterus.

Advances in the diagnosis and hormone replacement treatment of 46, XY disorders of sex development / 中华男科学杂志

Disorders of sex development (DSD) is defined as a congenital condition or atypical development of the chromosomal, gonadal, or anatomic sex. The diagnosis, gender assignment, and treatment of DSD require the guidance from experienced multidisciplinary teams. So far there has been no consensus about it in China. Due to dysgenetic gonads, defects in sex steroid biosynthesis or action, or gonadectomy during the prepubertal years, those with DSD suffer from hypogonadism. The hormone replacement therapy of DSD aims at general physiological health and long-term prognosis as well as the avoidance of unnecessary genital and gonadal surgery. This review focuses on the advances in the studies of the diagnosis and hormone replacement therapy of 46,XY DSD.

Management of moderate to severe pediatric concealed penis in children by Devine's technique via incision between the penis and scrotum / 中华男科学杂志

<p><b>OBJECTIVE</b>To search for a simple and effective surgical approach to the management of moderate to severe pediatric concealed penis in children.</p><p><b>METHODS</b>We used Devine's technique via incision between the penis and scrotum in the treatment of 68 cases of moderate to severe pediatric concealed penis. The patients were aged 3 -13 (mean 6.5) years, 30 with moderate and 38 with severe pediatric concealed penis.</p><p><b>RESULTS</b>This strategy achieved good near- and long-term effects and satisfactory appearance of the penis, which was similar to that of circumcision. At 3 months after surgery, the penile length was 3 - 5.2 cm, averaging (2.35 +/- 0.35) cm.</p><p><b>CONCLUSION</b>Devine's technique via incision between the penis and scrotum is a simple and effective surgical option for moderate to severe pediatric concealed penis in children.</p>

Measurement of penile length in children and its significance / 中华男科学杂志

Nowadays, more and more parents are paying increasing attention to the penile length of their children. At present, the methods of measuring penile length mainly include manual measurement and ultrasonography. The former can be used to measure the flaccid, stretched and erected penile lengths, and its use for measuring the stretched penile length has been internationally accepted for its precise definition, unified description, and high repeatability. The latter, as a new method, is being gradually accepted for its imaging visualization and measurement accuracy. This article reviews different measurements of penile length in the mainstream literature of recent years, with an analysis of their advantages and disadvantages.

Testicular dysgenesis syndrome: an update / 中华男科学杂志

Researches on the testicular dysgenesis syndrome (TDS) have flourished in the recent decade, and a widely accepted view on its pathogenesis is that environmental endocrine disrupting chemicals (EDCs) act on Leydig cells and/or testicular Sertoli cells, resulting in abnormal development of the testis and leading to the symptoms of TDS. Molecular biological studies suggest a correlation of TDS etiology with insulin-like factor 3 (INSL-3), androgen receptor (AR), P27kip, WT-1 and Müllerian inhibiting substance (MIS). This review focuses on the progress in current researches on the etiology and mechanism of TDS.

Surgical approaches to the correction of congenital penile curvature / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate some currently used surgical approaches to the correction of congenital penile curvature.</p><p><b>METHODS</b>Seventy-six patients with congenital penile curvature underwent surgical correction, of whom 67 were accompanied with hypospadias, 5 with epispadias and 4 with normal urethral meatus. The methods for straightening the phallus included 5-week preoperative hCG treatment, complete degloving of penile skin, release of periurethral fibrous bands extending proximally to the meatus, plication of dorsal or ventral tunica albuginea, and embedding of dermis and tunica vaginalis grafts.</p><p><b>RESULTS</b>All the cases were followed up for 2 months to 2 years, and the mean follow-up time was 9.3 months. Satisfactory phallus straightening was achieved in 67 cases (88%), mild residual chordee remained in 6 (8%), which needed no reoperation for the time being unless warranted by follow-up, and relapse occurred in 3 (4%), which needed further operation.</p><p><b>CONCLUSION</b>Most cases of congenital penile curvature can be corrected sufficiently with the above methods.</p>

Treatment of advanced Wilms' tumor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To improve prognosis of the patients with advanced Wilms' tumor, the authors compared different therapeutic strategies including preoperative transcatheter arterial chemoembolization (TACE), conventional preoperative chemotherapy and initial surgery.</p><p><b>METHODS</b>Sixty-two patients aged from 5 months to 10 years (mean 3.2 years) were identified from medical records to have histologically confirmed advanced Wilms' tumor during the period from January 1993 to December 2002. The criteria for choice were huge tumor size with a volume more than 550 ml or the mass extending beyond the midline, involvement of vital structures, inferior vena cava invasion, distal metastasis or bilateral Wilms' tumor judged by imaging examination. All cases were divided into 3 groups according to the treatment received: 31 cases in group TACE received preoperative transcatheter arterial chemoembolization with Lipiodol-Epirubicin (EPI)-Vincristine emulsion. One week after TACE, systemic chemotherapy with Actinomycin D (ACTD) was administered and tumor resected at two weeks after TACE. 20 cases in group PC received conventional preoperative chemotherapy with VCR, ACTD plus EPI for 4-5 weeks, and 11 cases in group IS underwent initial surgery. Postoperative treatment for all patients was based on the postoperative staging and tumor histology.</p><p><b>RESULTS</b>In the patients treated with TACE, no drug-induced complications such as cardiotoxicity, nephrotoxicity, hepatic dysfunction or bone marrow suppression were observed except for mild fever due to tumor necrosis. The percentages of tumor size shrinkage were 32.4% and 20.3% in group TACE and group PC, respectively (P < 0.05). Complete surgical removal of the tumor was achieved in 27 patients (87.1%) in group TACE, significantly higher in comparison with 14 in group PC (70.0%, P < 0.05) and 2 in group IS (18.2%, P < 0.01). Event-free survival (EFS) at 2 years was 87.1% (27/ 31), 60.0% (12/20) and 18.2% (2/11), respectivrely. EFS at 4 years was 84.6% (11/13), 56.3% (9/16 ) and 18.2% (2/11) in groups TACE, PC and IS, respectively.</p><p><b>CONCLUSION</b>The present study has shown that both preoperative TACE and conventional preoperative chemotherapy can be applied to the patients with advanced Wilms' tumor who are not candidates for immediately surgical resection. The survival is significantly increased in the patients undergoing preoperativeTACE when compared with conventional preoperative chemotherapy and initial surgery.</p>

Tubularized incised plate urethroplasty for children's hypospadias / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate a new method of urethroplasty.</p><p><b>METHODS</b>A total of 212 patients with hypospadias aged from 4 months to 9 years (glans type, n = 8; penis type, n = 181, penoscrotal type, n = 23) underwent tubularized incised plate urethroplasty.</p><p><b>RESULTS</b>Followed up for 2 approximately 34 months, 188 cases obtained optimal functional and cosmetic results, 22 developed small fistulae and 16 were cured after a second operation 6 months later, 6 waited to be operated again, 2 cases of neourethra dehiscence were cured by second tubularized incised plate urethroplasty one year later.</p><p><b>CONCLUSION</b>With its simplicity, low complication rate and reliable creation of a normal-appearing glanular meatus, tubularized incised plate urethroplasty can particularly be applied to boys with proximal hypospadias absent of severe penile curvature.</p>

Overlapping coverage with bilateral shaft based vascularized dartos pedicle in Snodgrass hypospadias repair / 中华泌尿外科杂志

Objective To introduce a new technique for urethral coverage in Snodgrass hypospadias repair,and to evaluate its effectiveness and complications.Methods From April 2003 to February 2006, this new procedure was performed in 289 children with hypospadias aged 3 months to 12 years (mean age,2. 4 years).The native meatus of urethra was identified subcoronal in 78 cases,penile/shaft in 136,penoscrotal in 36 and scrotal in 16;and 23 cases had undergoneⅡstage operation and re-operation.The overlapping coverage with bilateral shaft based vascularized dartos pedicle was done in the new urethra by Snodgrass hy- pospadias repair in these children.Results All the cases were followed for 3 months to 2 years.Postoper- atively,urinary fistulas developed in 32 cases (11%).Of them,11 were cured spontaneously within 4 weeks. The incidence of actual urinary fistula was 7% (21/289).Of the 21 fistulas which were not cured,11 (5%) occurred in 214 cases of distal hypospadias;and 10 (13%) in 75 cases of proximal hypospadias,Ⅱstage and re-operation.No dehiscence and diverticulum was found.Combined with mucosal collar technique,the ventral skin of the penis was sewn on the midline.During the follow-up,excellent cosmetic results with normal-ap- pearing circumcised penis were achieved in most patients.Conclusions Bilateral shaft based vascularized dartos pedicle urethral coverage procedure is a reliable and effective method for preventing urethral cutaneous fistulas and dehiscence.This method can reconstruct a satisfactory cosmetic appearance of the penis.