Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision).

Congenital adrenal hyperplasia is a category of disorders characterized by impaired adrenocortical steroidogenesis. The most frequent disorder of congenital adrenal hyperplasia is 21-hydroxylase deficiency, which is caused by pathogenic variants of CAY21A2 and is prevalent between 1 in 18,000 and 20,000 in Japan. The clinical guidelines for 21-hydroxylase deficiency in Japan have been revised twice since a diagnostic handbook in Japan was published in 1989. On behalf of the Japanese Society for Pediatric Endocrinology, the Japanese Society for Mass Screening, the Japanese Society for Urology, and the Japan Endocrine Society, the working committee updated the guidelines for the diagnosis and treatment of 21-hydroxylase deficiency published in 2014, based on recent evidence and knowledge related to this disorder. The recommendations in the updated guidelines can be applied in clinical practice considering the risks and benefits to each patient.

Validation of testicular workup for ischemia and suspected torsion score in patients with acute scrotum.

INTRODUCTION: The Testicular Workup for Ischemia and Suspected Torsion (TWIST) score was created to help physicians in the clinical evaluation of acute scrotum in which testicular torsion (TT) is suspected. There have been only a few reports on validation of the TWIST score since the original study was published. OBJECTIVES: To validate the TWIST score as a scoring system. PATIENTS AND METHODS: We reviewed the records of 106 patients with acute scrotum in our prospectively maintained database. The patients were divided into two groups by the final diagnosis: testicular torsion (group TT) or non-testicular torsion (group NTT). We retrospectively calculated the TWIST score of the patients. Patients were divided into low (0-2), intermediate (3-4), or high (5-7) risk groups according to the total score. RESULTS: Fifteen patients (14%) had TT. The median age at presentation was 13.3 years (range 1.6-16.2) in group TT and 10.4 years (range 0.25-18.9) in group NTT, respectively. The sensitivity of clinical and Color Doppler ultrasonography (CDUS) findings to diagnose TT was 100%, whereas the specificity was 93.4%. Positive predictive value (PPV) and negative predictive value (NPV) were 71.4% and 100%, respectively. According to the calculated TWIST score, 65, 23, and 18 patients belonged to low, intermediate, and high risk groups, respectively. TT was found in 1(1.3%), 3(13%), and 11 (61%) patients of low, intermediate, and high risk groups, respectively. The NPV of the TWIST score for the low risk group was 98.5%, whereas the PPV of the TWIST score for the high risk group was 61.1%. Among the four patients with TT in low risk and intermediate risk groups, three patients presented to our institutions within 6 h after the onset. The torsion was 180° in two of the three patients. CONCLUSION: The TWIST score can be useful for clinical diagnosis of testicular torsion, but is inferior to clinical findings along with CDUS. We should consider the possibility that a TWIST score could be underestimated when patients present with acute scrotum immediately after onset or the affected testis is mildly twisted.

Complete androgen insensitivity syndrome with accelerated onset of puberty due to a Sertoli cell tumor.

Complete androgen insensitivity syndrome (CAIS) is caused by mutations in the androgen receptor gene. Patients with this syndrome have a 46,XY karyotype, male gonads, and normal female external genitalia. While the pre-pubertal risk of developing gonadal tumors is low in these patients, it increases with age. Most gonadal tumors arise from germ cells; stromal cell tumors are uncommon. Herein, we report a CAIS patient with a feminizing Sertoli cell tumor. The patient presented at 8 yr of age with breast enlargement and growth acceleration, concomitant with elevated serum estradiol levels and suppressed serum gonadotropin levels; these findings were inconsistent with CAIS. The patient underwent gonadectomy at 10 yr of age, and histology demonstrated presence of a non-malignant Sertoli cell tumor in the right gonad. We conclude that this is the first reported case of CAIS with accelerated onset of puberty resulting from a Sertoli cell tumor.

The learning curve in proximal hypospadias repair.

INTRODUCTION: Although the learning curve in various surgical procedures is increasingly discussed, there have been only a few reports about the learning curve especially in proximal hypospadias repair. OBJECTIVES: To evaluate the learning curve in one-stage hypospadias repair for proximal hypospadias. MATERIALS AND METHODS: We retrospectively reviewed 73 cases of primary hypospadias repair by a single pediatric urologist using one-stage urethroplasty with a preputial skin graft between 2007 and 2018. The overall complication rate included fistula, glans dehiscence, and meatal stenosis. To analyze the impact of the surgeon's experience on the complication rate, we compared the complication rates among different groups of 20 consecutive cases each. In addition, we graphed the actual data of the operative time and cumulative complication rate to evaluate the learning curve. The cumulative complication rate was defined as the surgeon's complication rate (the number of complications accumulated at a time/number of cases at that time). RESULTS: The median age at surgery was 18 months (range: 7-87). The median follow-up was 40 months (range: 3-114). In total, 13 (18%) children had complications: 9 fistulae, 3 glans dehiscence, and 2 metal stenoses. The analysis of each 20 cases revealed that the complication rate declined over time as the surgeon became more experienced. It was mainly attributed to a decline of the fistula rate. The diagram of the operative time showed a reduction with the increasing surgical experience. Additionally, the diagram of the cumulative complication rate demonstrated a plateau after 50 cases. CONCLUSION: Our study showed the positive impact of surgeon experience on the outcome of one-stage repair for proximal hypospadias. In addition, the learning curve in proximal hypospadias repair stabilized after about 50 cases although the supervision of experienced surgeons is required during the early phase of learning curve.

Surgical correction of ectopic scrotum and penile torsion in a 5-year-old boy.

Ectopic scrotum is a rare condition, which is described as an anomalous position of one hemiscrotum along the inguinal canal. This anomaly is associated with other genitourinary anomalies. We report a 5-year-old boy with ectopic scrotum and penile torsion, who was successfully treated by simultaneous surgery.

Treatment guidelines for persistent cloaca, cloacal exstrophy, and Mayer-Rokitansky-Küster-Häuser syndrome for the appropriate transitional care of patients.

We developed treatment guidelines (TGs) for appropriate transitional care of the genitourinary system in patients with persistent cloaca (PC), cloacal exstrophy (CE), or Mayer-Rokitansky-Küster-Häuser syndrome (MRKH). These TGs are in accordance with the Medical Information Network Distribution Service (Minds), published in 2014 in Japan. Clinical questions (CQs) concerning treatment outcomes of the genitourinary system, pregnancy and delivery, and quality of life in adulthood were prepared as six themes for PC and CE and five themes for MRKH. We were able to publish statements on chronic renal dysfunction, hydrometrocolpos, and pregnancy, based on four CQs about PC, four about CE, and two about MRKH, respectively. However, due to the paucity of proper manuscripts, we were unable to make conclusions about the correct timing and method of vaginoplasty for patients with PC, CE, and MRKH or the usefulness of early bladder closure for patients with CE. These TGs may help clarify the current treatments for PC, CE, and MRKH in childhood, which have been carried out on an institutional basis. To improve clinical outcomes, systematic clinical trials revealing comprehensive clinical data of the urinary and reproductive systems, especially the length of the common channel in PC, are essential.

45,X mosaicism with Y chromosome presenting female phenotype.

Prophylactic gonadectomy is recommended in patients with 45,X mosaicism with the Y chromosome and presenting a female phenotype because of the risk of gonadoblastoma development. The characteristics of this disorder remain unclear because of its low incidence. We report 4 patients with 45,X mosaicism with the Y chromosome and presenting complete female external genitalia. We analyzed the characteristics and the macroscopic and histopathological findings of their gonads and performed hormonal assays of the 4 patients. All 4 patients were referred to us with short stature as the chief complaint. Chromosomal studies revealed 45,X/47,XYY in 1, and the others had a 45,X/46,XY karyotype. Three patients (6 gonads) underwent laparoscopic bilateral gonadectomy. The macroscopic appearance of gonads of 1 patient was similar to an ovary, whereas gonads of the rest appeared as streak gonads. The histopathological findings revealed bilateral gonadoblastoma in 1 patient, although the macroscopic findings did not show tumor characteristics. It is impossible to distinguish the histopathological findings of gonads according to their macroscopic appearance among patients with 45,X mosaicism with the Y chromosome and presenting a female phenotype.

Intrarenal reflux in primary vesicoureteral reflux.

OBJECTIVES: To elucidate the significance of intrarenal reflux. METHODS: We retrospectively analyzed 276 patients (age <5 years) with grade III to V vesicoureteral reflux. They were divided into two groups: 55 patients with intrarenal reflux and 221 patients without intrarenal reflux (control group). All patients received low-dose antibiotic prophylaxis. RESULTS: The most common initial presentation in both groups was febrile urinary tract infection. On dimercaptosuccinic acid scan, the rate of decreased differential renal function (<40%) was significantly higher in the intrarenal reflux group than in the control group (51% vs 33%, P < 0.05). Breakthrough urinary tract infections were observed in 26 patients (47%) in the intrarenal reflux group and 61 patients (28%) in the control group (P < 0.01). There was no statistically significant difference regarding spontaneous resolution of reflux, which occurred in nine patients (16%) in the intrarenal reflux group and 32 patients (14%) in the control group. Surgical treatment was selected more often in the intrarenal reflux group (P < 0.05) because of the high incidence of breakthrough urinary tract infection. CONCLUSIONS: The rate of spontaneous resolution of high-grade vesicoureteral reflux is similar between patients with and without intrarenal reflux. However, those with intrarenal reflux present are more likely to present a decreased differential renal function and breakthrough urinary tract infections. Consequently, surgical treatment is considered more frequently in cases with intrarenal reflux. Although high-grade vesicoureteral reflux with intrarenal reflux can be treated conservatively, physicians should take into account the higher risk of breakthrough urinary tract infections.

A case of 46, XY DSD presenting as a crossed ectopic gonad with a contralateral sliding inguinal hernia.

A three-month-old boy was referred to our facility for the treatment of a right impalpable testis, left inguinal hernia, and penoscrotal hypospadias with asymmetric external genitalia. The left gonad was palpated in the left scrotum. The chromosomal study revealed a normal male 46, XY karyotype. Operative findings showed that the right streak gonad, uterus, and fallopian tubes were in the wall of the left hernia sac, forming a sliding hernia. Laparoscopy confirmed that the right gonadal vessels had crossed to the left internal inguinal ring. Herniorrhaphy was done and the right streak gonad, uterus, and fallopian tubes were excised. An exploration of the left gonad revealed an ovotestis. The ovary was removed, and a left testicular biopsy was simultaneously performed. A one-stage hypospadias repair using Koyanagi procedure was also performed. The pathological findings showed an ovarian stroma in the right gonad and left ovary. Only Sertoli cells were detected in the biopsied specimen from the left testis.

[Case of mid-ureteral fibroepithelial polyps in a child].

A 11-year-old boy showed gross hematuria and left flank pain. Ultrasonography and CT revealed left hydroureteronephrosis, and he was referred to us for the further evaluation. MRI revealed left hydroureteronephrosis with filling defect at the distal end of the dilated ureter suggesting ureteral polyp. Open surgery was performed with the diagnosis of mid-ureteral obstruction. In the operative findings, multiple stalks of ureteral polyps arose from the entire ureteral wall over 5 cm in length at the site of ureteral obstruction. Mid-ureter with polyps was completely resected, and end-to-end anastomosis was performed. The pathological diagnosis was fibroepithelial polyp of the ureter.

Prepubertal testicular tumors: a 20-year experience with 40 cases.

Testicular tumors are rare in children. In addition, prepubertal testicular tumors (PTT) are fundamentally different from their postpubertal counterparts.We reviewed our 20-year experience with 40 cases to suggest an algorithm for the appropriate surgical approach for patients with PTT. All tumors ultrasonographically suspected of being benign were confirmed to be benign postoperatively. There was a significant difference between median preoperative a-fetoprotein (AFP) levels of infants with yolk sac tumor and teratoma. The majority of our cases were benign, with the most common histopathological subtype being teratoma, as recently reported. Testis-sparing surgery was carried out in five patients with teratoma and three patients with epidermoid cyst. Other than one patient with teratoma, none of the patients developed recurrence or testicular atrophy after testis-sparing surgery. When testis-sparing surgery is considered, our algorithm based on ultrasonographic findings and preoperative AFP levels might be helpful.

Objective patterning of uroflowmetry curves in children with daytime and nighttime wetting.

PURPOSE: Pediatric uroflowmetry curve interpretation is incompletely standardized. Thus, we propose new, objective patterning. MATERIALS AND METHODS: Uroflowmetry curves were obtained in 100 children presenting with daytime incontinence or enuresis. Each curve was compared with a standard curve generated from a published nomogram and a new patterning method was formulated. Staccato and interrupted patterns were defined using International Children's Continence Society criteria. The remaining curves were divided by the deviation of the maximal flow rate from the median nomogram value as certain patterns, including tower-greater than 130%, not abnormal-70% to 130% and plateau-less than 70%. The correlation between the presenting symptom and patterns or other uroflowmetry parameters was evaluated. Six pediatric urologists also patterned the same curves subjectively. RESULTS: All curves could be classified as 1 of the defined patterns using this method. Pattern distribution reflected the spectrum of presenting symptoms with more tower, interrupted and staccato patterns in children with daytime wetting than in those with monosymptomatic enuresis. Age adjusted voided volume was also smaller in the former group but post-void residual urine, and maximal and average flow rates did not correlate with presenting symptoms. Subjective patterning showed marked interobserver differences. When patterning applied by the current method was used as a reference, observer sensitivity for abnormal patterns inversely correlated with specificity. CONCLUSIONS: Subjective uroflowmetry patterning is liable to personal bias. The proposed method enables objective patterning that complies with International Children's Continence Society standardization and clinical presentation.

Risk factors for breakthrough infection in children with primary vesicoureteral reflux.

PURPOSE: Despite the widespread application of endoscopic therapy and the debate surrounding the use of prophylactic antibiotics to treat children with vesicoureteral reflux, many pediatric urologists still favor medical management. Breakthrough infection is one of the absolute indications for surgery. Data to predict breakthrough infection are warranted to manage cases of primary reflux. MATERIALS AND METHODS: We reviewed medical records of 72 girls and 138 boys (mean +/- SD age at diagnosis 2.66 +/- 3.23 years) with primary vesicoureteral reflux who were followed with antibiotic prophylaxis at Aichi Children's Health and Medical Center. We examined multiple factors by univariate/multivariate analysis to elucidate risk factors for breakthrough infection. RESULTS: Breakthrough infection developed in 59 children (28%). On univariate analysis higher reflux grade (p <0.05) and abnormal renal scan determined by (99m)technetium dimercapto-succinic acid (p <0.0001) were significantly associated with breakthrough infection. On multivariate analysis abnormal renal scan was an independent risk factor for breakthrough infection (OR 11.08, 95% CI 0.76-1.72, p <0.0001). CONCLUSIONS: Abnormal renal scan is an independent risk factor for breakthrough infection. Parents and physicians should remain aware that these patients are at high risk for breakthrough infection, which potentially could lead to renal damage.

A new technique of concealed penis repair.

PURPOSE: Phimosis associated with concealed penis is not amenable to ordinary circumcision. To our knowledge we describe a new technique to repair concealed penis. MATERIALS AND METHODS: From September 2003 to January 2008, 57 consecutive patients with concealed penis were treated using our technique. Median age at surgery was 33 months (range 7 months to 34 years). The technique consists of 3 steps. Step 1 is a ventral incision to slit the narrow ring of the prepuce and expose the glans. Step 2 is a circumferential skin incision made between 2 edges of the ventral diamond-shaped skin defect, followed by midline incision of the dorsal inner prepuce to make 2 skin flaps connected to the glans. Step 3 is skin coverage. Two skin flaps are brought down and sutured together on the ventral side of the penis. The suture line between the penile shaft skin and the flap eventually becomes elliptical. Medical records were reviewed for voiding function, scar formation, and replies from older patients and the parents of younger children about impressions of the surgical results. RESULTS: Median followup was 26 months. No patient had voiding problems. Lymphedema persisted due to suture line constriction in 2 patients who underwent incision of the constriction. All older patients and the parents of younger children were satisfied with the surgical results. CONCLUSIONS: Our new method is easy to design and perform to correct concealed penis. It provides a good cosmetic appearance and seems to be applicable in all cases with deficient penile shaft skin.

Renal scarring is associated with nonsecretion of blood type antigen in children with primary vesicoureteral reflux.

PURPOSE: Nonsecretor status of blood type antigen has been associated with higher risk of urinary tract infection (UTI) in women. However its implication in the modern management for pediatric UTI remains unclear. We evaluate the impact of secretor status on clinical course in children with primary vesicoureteral reflux (VUR). MATERIALS AND METHODS: From 1998 to 2002, 382 cases of primary VUR presented to our institute and were treated either surgically or nonoperatively in accordance with the American Urological Association guideline. Of these potential candidates 128 patients and their guardians volunteered to be entered into the study. Antiseptic swabs to collect saliva were sent to them. The secretor status was determined using the hemagglutination inhibition assay from the eluted saliva on the swabs and medical records of responders were evaluated retrospectively. RESULTS: Secretor status was not associated with gender, VUR grade, presentation, history of breakthrough UTI, laterality of VUR and conservative vs surgical treatment. However, nonsecretor status weakly correlated with decreased split renal function and significantly correlated with the presence of focal renal scarring (40.9% vs 21.7% for children with and without scarring, respectively) as determined by technetium dimercapto-succinic acid renal scan. CONCLUSIONS: These results demonstrate that secretor status represents unrecognized host disposition that affects the clinical course of primary VUR. Further study is needed to determine the significance of secretor status for clinical management and pathophysiology of VUR.