Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients.

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.

Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for treatment of clear cell sarcoma of the kidney in children.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive malignant renal tumor. We describe our experience with neoadjuvant transcatheter arterial chemoembolization (TACE) and systematic chemotherapy for the treatment of advanced CCSK in children. METHODS: Between January 2010 and December 2016, seven patients (3 boys and 4 girls; median 2.2 years) with advanced CCSK received preoperative TACE of renal artery and systemic chemotherapy. The chemoembolic emulsion for TACE consisted of cisplatin, pirarubicin, vindesine, and iodized oil. Preoperative systemic chemotherapy with vindesine, ifosfamide, and etoposide was administered three weeks after TACE. Nephrectomy was performed three weeks after systemic chemotherapy. After surgery, patients received radiotherapy and postoperative chemotherapy. RESULTS: No cardiotoxicity, renal insufficiency, or hepatic dysfunction was found in any patients. Grade II-III marrow suppression developed in four patients. One patient with tumor progress during neoadjuvant therapy failed to successfully undergo surgery and died. Six patients underwent nephrectomy after neoadjuvant therapy. Median follow-up period was 49.5 months (range, 11-83 months). Five patients have recurrence-free survival. One patient is still in postoperative chemotherapy after nephrectomy, radiotherapy and thoracoscopic resection of lung metastases. CONCLUSIONS: Neoadjuvant TACE and systemic chemotherapy appeared to be feasible in the treatment of advanced CCSK in this pilot study. THE TYPE OF STUDY: A case series with no comparison group. LEVEL OF EVIDENCE: Level IV.

Neoadjuvant Intraarterial Chemotherapy for Treatment of Malignant Vaginal Tumors in Children: A Single-Center Experience.

Six patients (aged 3-36 mo) with vaginal tumors (rhabdomyosarcoma and endodermal sinus tumor [EST]; n = 3 each) received intraarterial chemotherapy (IAC) and intravenous chemotherapy. Patients underwent internal iliac artery infusion with cisplatin, pirarubicin, and vindesine. Intravenous chemotherapy with vindesine, ifosfamide, and etoposide was administered after 3 weeks. Vaginal tumors disappeared in all patients after 2 or 3 cycles of alternating therapy. Two patients underwent resection of pelvic metastases. Intravenous consolidation chemotherapy was applied. Four patients were disease-free at a median follow-up of 5.8 years. One patient had pelvic recurrence treated with "salvage" therapy with IAC and surgery and was disease-free for 2.5 years.

[Advances in the diagnosis and hormone replacement treatment of 46, XY disorders of sex development].

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].

OBJECTIVE: To search for a simple and effective surgical approach to the management of moderate to severe pediatric concealed penis in children. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A retrospective study of the preoperative treatment of advanced Wilms tumor in children with chemotherapy versus transcatheter arterial chemoembolization alone or combined with short-term systemic chemotherapy.

PURPOSE: To evaluate the therapeutic effect of preoperative transcatheter arterial chemoembolization (TACE) combined with short-term systematic chemotherapy in the treatment of advanced Wilms tumor. MATERIALS AND METHODS: This was a retrospective study on 66 patients with unilateral advanced Wilms tumor, age 5 months to 11 years (median, 2.9 years; 30 boys and 36 girls), treated at our institution between 1995 and 2007. Characteristics of the patient population were maximal tumor diameter > 10 cm, or involvement of periaortic lymph nodes, or inferior vena cava invasion, or distal metastasis, or tumor with anaplastic histology. Patients were divided into three groups. Twenty patients were treated with conventional preoperative chemotherapy (PC group) using vindesine, actinomycin D, and pirarubicin for 4 weeks; 21 patients were treated in the TACE group with preoperative renal arterial chemoembolization using Lipiodol-pirarubicin-vindesine emulsion; and 25 patients were treated with preoperative chemoembolization combined with short-term systematic chemotherapy (T+S) for 2 weeks. RESULTS: No drug-induced cardiotoxicity, nephrotoxicity, or hepatic dysfunction was observed. Complete surgical removal of the tumor was achieved in 12 (65.0%), 17 (80.9%), and 22 (88.0%) patients in the PC, TACE, and T+S groups, respectively (T+S group vs PC group, P = .030). The 2-year relapse-free survival rates were 65.0%, 80.9%, and 100.0% in the PC, TACE, and T+S groups, respectively (T+S vs PC, P = .001). CONCLUSIONS: From our experience, preoperative chemoembolization combined with short-term systematic chemotherapy is able to achieve higher rates of complete tumor resection and relapse-free survival in the treatment of advanced Wilms tumor.

[Testicular dysgenesis syndrome: an update].

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].

OBJECTIVE: To evaluate some currently used surgical approaches to the correction of congenital penile curvature. METHODS: 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. RESULTS: 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. CONCLUSION: Most cases of congenital penile curvature can be corrected sufficiently with the above methods.

[Treatment of advanced Wilms' tumor].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.