Akihiro Nakane

The modified Koyanagi repair for severe proximal hypospadias

Objective To report the method and results of a modified one‐stage Koyanagi repair (urethroplasty with a parameatal‐based and fully extended circumferential foreskin flap) to preserve the vascularity to the peripheral portion of the neourethra, in the repair of severe hypospadias.

Scrotal dartos flap for the prevention of the urethrocutaneous fistula on hypospadias urethroplasty.

Abstract  Background:  Urethrocutaneous fistula is a common complication of urethroplasty for severe hypospadias, even when a microsurgical technique is applied.

Long-term physical, hormonal, and sexual outcome of males with disorders of sex development

PURPOSE We investigated the long-term physical, hormonal, and sexual outcomes of males with disorders of sex development (DSD) and discussed the necessity of long-term follow-up for these patients after surgery. PATIENTS AND METHOD Twelve DSD patients (average age, 21.0 +/- 3.6 years old) who had been designated as male in childhood (3 ovotesticular DSD, four 45,XO/46,XY mixed gonadal dysgenesis, four 46,XX testicular DSD, and one 46,XY DSD; androgen insensitivity syndrome) were enrolled. For these patients, height, penile length, and testicular volume were evaluated in adulthood. Serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone were also measured during follow-up. In addition, sexual function and romantic relationships were evaluated. RESULTS Development of the penis and testes was poor. According to the hormonal study, these patients were diagnosed with hypergonadotropic hypogonadism or normogonadism; 90% patients had experienced penile erection and masturbation at the time of participation, and 70% and 40% patients had experienced ejaculation and sexual intercourse with female partners, respectively. No patients preferred to avoid sexual contact with women. CONCLUSION Although DSD males had an undeveloped penis and testis and had hypergonadotropic hypogonadism or normogonadism, most had male sexual potential and male sex identity as long as testicular tissues were preserved.

Activation of NF-κB Associated With Germ Cell Apoptosis in Testes of Experimentally Induced Cryptorchid Rat Model

OBJECTIVES To evaluate the behavior of NF-kappaB in the cryptorchid testes, we investigated the testes of an experimentally induced cryptorchid rat model. Cryptorchid testes exhibit degenerative changes in the germinal epithelium with germ cell apoptosis, which results in future infertility. However, the mechanisms of apoptosis in the germ cells are multifactorial and have not been completely elucidated. NF-kappaB is a transcription factor considered to play an important role in the apoptosis of various cells. METHODS The cryptorchid rat model was generated by the administration of an antiandrogenic agent during the fetal period. The unilateral cryptorchid testes and contralateral descended testes were removed at 7-10 weeks after birth, and histopathologic examination and Western blot analysis were performed. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining, and the expression of NF-kappaB and IkappaB proteins was investigated using immunohistochemistry. RESULTS In the present model, spermatogenesis was arrested at the spermatid differentiation stage, and elongated spermatids or spermatozoa were not detected. Apoptosis was noted predominantly in the primary spermatocytes, and Sertoli cells and Leydig cells did not undergo apoptosis. On immunohistochemistry, NF-kappaB signals were increased and focused on the nucleus of the germ cells in the cryptorchid testes, consistent with TUNEL-positive cells. On Western blot analysis, the NF-kappaB and IkappaB proteins were detected more intensely in the cryptorchid testes. CONCLUSIONS The activation of NF-kappaB was associated with germ cell apoptosis in experimentally induced cryptorchid testes, suggesting that NF-kappaB has certain roles in germ cell apoptosis. The results of the present study may guide toward new therapeutic possibilities for the impairment of spermatogenesis in patients with cryptorchidism.

Tubularized incised‐plate urethroplasty for secondary hypospadias surgery

Abstract Purpose: Reoperation for failed hypospadias has been considered to be seriously bothersome because abundant penile skin does not tend to remain for urethroplasty or for penile shaft skin coverage. In this study, the tubularization of incised urethral plate was employed for those who had no excessive penile skin after failure of hypospadias repair.

Dullard/Ctdnep1 Modulates WNT Signalling Activity for the Formation of Primordial Germ Cells in the Mouse Embryo

Dullard/Ctdnep1 is a member of the serine/threonine phosphatase family of the C-terminal domain of eukaryotic RNA polymerase II. Embryos lacking Dullard activity fail to form primordial germ cells (PGCs). In the mouse, the formation of PGCs is influenced by BMP4 and WNT3 activity. Although Dullard is reputed to negatively regulate BMP receptor function, in this study we found mutations in Dullard had no detectable effect on BMP4 and p-Smad activity. Furthermore Dullard mutations did not influence the dosage-dependent inductive effect of Bmp4 in PGC formation. However, Dullard may function as a positive regulator of WNT signalling. Combined loss of one copy each of Dullard and Wnt3 had a synergistic effect on the reduction of PGC numbers in the compound heterozygous embryo. In addition, loss of Dullard function was accompanied by down-regulation of WNT/β-catenin signalling activity and a reduction in the level of Dishevelled 2 (Dvl2). Therefore, Dullard may play a role in the fine-tuning of WNT signalling activity by modulating the expression of ligands/antagonists and the availability of Dvl2 protein during specification of the germ cell lineage.

Extravesical robot-assisted laparoscopic ureteral reimplantation for vesicoureteral reflux: initial experience in Japan with the ureteral advancement technique.

To report our initial experience with robot‐assisted laparoscopic extravesical ureteral reimplantation using the ureteral advancement technique.

Optimal Cutoff Value of Contralateral Testicular Size for Prediction of Absent Testis in Japanese Boys With Nonpalpable Testis

OBJECTIVES To investigate the accuracy of contralateral testicular hypertrophy in Japanese boys with a nonpalpable testis and to determine the optimal cutoff value of the contralateral testicular size to predict the absence of the testis. METHODS From December 2003 to November 2009, we evaluated 55 boys <60 months old (mean age 19.4) with a unilateral nonpalpable testis and compared their findings with those of a control group. The control group included 20 age-matched boys with 40 testes. The nonpalpable status of the testes was diagnosed by physical examination, and the contralateral testis was measured with calipers before surgery. A sensitivity and specificity analysis were performed using computer software. RESULTS At surgery, the testis was found in 22 of the 55 boys and was absent in 33. Of the 33 boys with an absent testis, 4 had a blind-ending vessel and 29 had an atrophic cord and testicular nubbin in the canal or scrotum. The mean contralateral testicular length and volume in the boys with an absent testis was 22.4 mm and 2.20 cm(3) compared with 16.6 mm and 1.10 cm(3) in the boys with the testis present and 16.6 mm and 1.18 cm(3) in the controls, respectively (P < .01). The predictive accuracy, sensitivity, and specificity for an absent testis was 87.3%, 81.8%, and 95.5% for the length and 85.5%, 84.8%, and 86.4% for the volume, respectively, at the optimal cutoff value of 21 mm in length and 1.6 cm(3) in volume. CONCLUSIONS Our data have shown that contralateral testicular hypertrophy strongly indicates an absent testis in Japanese boys. The optimal cutoff for contralateral testicular hypertrophy with calipers was 21 mm and 1.6 cm(3). This result has provided valuable information for preoperative counseling and treatment planning.

Neo-modified Koyanagi technique for the single-stage repair of proximal hypospadias

PURPOSE To retrospectively analyze the results of a modification of the Koyanagi hypospadias repair developed to reduce complications. MATERIALS AND METHODS Twelve boys underwent a modified Koyanagi repair over the past 3 years. The technique included the preservation of a wide vascular pedicle for each parameatal flap. The distal urethral plate was left intact and attached on each lateral side to the medial side of each distal Koyanagi pedicle flap. RESULTS One boy (8%) developed a urethral fistula. There was no instance of meatal stenosis, sacculation or urethral stricture. CONCLUSIONS Modifying the Koyanagi repair by preserving a wide vascular pedicle for the distal skin flaps and utilizing the distal urethral plate as the base for the distal neourethra has lowered the incidence of complications. This technique is a suitable alternative to a two-stage approach for the correction of proximal hypospadias.

Novel technique for correcting penile curvature with severe hypospadias; Ventral lengthening with tunica vaginalis flap patching

Abstract  The adequate correction of penile curvature is essential for successful hypospadias surgery. We describe a novel technique to correct severe penile curvature with a tunica vaginalis flap on the penile ventrum. We applied a tunica vaginalis flap to lengthen the ventral aspect of the tunica albuginea in two boys with significant curvature and proximal hypospadias. Tunica vaginalis flap patching to the ventral aspect of the penis is safe and technically feasible. If penile curvature is severe or the penis is small in hypospadiac patients, lengthening the ventral aspect using a tunica vaginalis flap is likely to expand instead of dorsal plication or ventral graft.