A Case of Solitary Kidney and Single-system Ectopic Ureter Draining Into the Vestibule in an Infant With Müllerian Duct Defect: Was the Bladder Missing?

We report a case of a solitary kidney and a single-system ectopic ureter draining into the vestibule in an infant with a Müllerian duct defect. Due to the absence of the upper vagina and uterus, an extremely underdeveloped bladder masqueraded as the vagina, and bladder agenesis was suspected preoperatively. Urinary continence was achieved using staged bladder surgery without augmentation or urinary diversion.

Prenatally Detected Intrascrotal Testicular Teratoma in an Infant.

Although teratomas are the most common tumors in the testes of prepubertal children, prenatally detected testicular teratomas are extremely rare. To date, only 6 cases of prenatally detected testicular teratomas have been reported in the English literature. An intra-abdominal mass and an ipsilateral undescended testis were confirmed after birth in all 6 cases. Preservation of testicular tissue was not performed in any case. Herein, we report the first case of prenatally diagnosed intrascrotal testicular teratoma in an infant who underwent testis sparing surgery.

Successful separation of male pygopagus with anal canal and urethral reconstruction: a case report.

BACKGROUND: Pygopagus is a type of conjoined twin binding at the buttocks. Some cases of pygopagus involve the fusion of the gastrointestinal tract, urinary tract, and spinal cord. Few cases of male pygopagus have been reported; however, the prognosis after separation is unclear. Herein, we report a case of male pygopagus in which successful separation was performed with the reconstruction of the anal canal. CASE PRESENTATION: Twins with male pygopagus were born at 35 weeks by cesarean section. They shared a common anus, penis, and scrotum with four testes. The infants had normal defecation and urination after birth. The separation surgery was scheduled when they were 5 months. Two distinct anesthesia teams and four surgical teams (neurosurgery, pediatric urology, plastic surgery, and pediatric surgery) were involved in the multidisciplinary approach. After separating the spinal cord, we found that the anal canal and sphincter muscle complex were fused near the anal aperture, and we separated them. The fused penis and testis were separated and reconstructed using the same incisional line as the other separation, and the reconstructions of the anal canals with the sphincter muscle complex were completed. Both patients had an uneventful postoperative course. At 2 years of age, they could walk and defecate independently. In addition, they voided spontaneously without urinary incontinence at the time of 3 years and 11 months. CONCLUSIONS: Separation of the spinal cord with anal canal and urethral reconstruction is important for male pygopagus patients as it allows them to preserve their independent function.

Bladder Cancer in a Long-term Survivor of the Prune Belly Syndrome.

Prune belly syndrome (PBS) is a rare but morbid complexity of congenital anomalies that consists of abdominal wall defect, bilateral cryptorchidism, and urinary tract dilation. With the recent advances in perinatal care, the life expectancy of patients with PBS has improved. Although renal and sexual outcomes are frequently discussed in the literature, little is known about urinary tract malignancies in adulthood. Herein, we present a case of advanced bladder cancer in a 38-year-old man with PBS. To the best of our knowledge, a malignant tumor arising in a nondefunctionalized or nonaugmented bladder in patients with PBS has not been reported previously.

Unilateral Fibrous Hyperplasia of the Labium Majus in Pre- and Early Pubertal Girls: A Report on 3 Cases.

BACKGROUND: In recent years, certain prepubertal cases of asymmetric enlargement of the labium majus came to be recognized as a physiological condition in response to hormonal stimulation. However, there exist only scattered case reports or a few case series on this entity, with different terminology. CASE: We present 3 cases of unilateral asymptomatic swelling of the labium majus in otherwise healthy pre- and early pubertal girls. Physical examination revealed painless, fluctuating, nontender bulging that was recognized for a few years on one side of the labium majus. Ultrasound and magnetic resonance imaging showed increased labial soft tissue without any masses. In all cases, surgical excision was performed for cosmetic request. Histopathological diagnosis was fibrous hyperplasia of the labium majus in all cases. Recurrence occurred in one of 3 cases a year after surgery. SUMMARY AND CONCLUSION: Due to the site- and age-specific non-neoplastic physiological condition, we recommend prepubertal unilateral fibrous hyperplasia of the labium majus (PUFHLM), as the terminology accurately reflects this entity. For the differential diagnosis of genital disorders in children, recognition of PUFHLM is important to avoid unnecessary biopsy or invasive procedures. Surgical excision for cosmetic reasons should not be considered because of the benign nature of this entity and a high recurrence rate in childhood and early adolescence.

[A CASE OF SPLENOGONADAL FUSION PRESENTING NON-PALPABLE TESTIS AND PROXIMAL HYPOSPADIAS].

A 9-month-old boy, having a history of cardiac surgery in neonatal period, was referred to our department for evaluation of genital anomalies. The antenatal course was uneventful, except for unknown gender. His family history was unremarkable. He was delivered at full term, and his birth weight was 3,510 g. Physical examination revealed proximal hypospadias and a non-palpable testis on the left side. Chromosome studies showed a normal male karyotype with positive SRY. At the age of 14 months, he underwent hypospadias repair. Three months later, left testicular exploration was performed along with orchidopexy of an ascending testis on the contralateral side. As nothing was found through an inguinal incision on the left side, laparoscopy was indicated. Laparoscopic observation revealed a small dark reddish mass cranially connected to the left hypoplastic testis that was located high in the left iliac fossa. The epididymis and vas deference looked abnormal, and detachment to the testis was apparent. Testicular vessels were undifferentiated from the mass. Therefore, the left testis was excised with the mass. Histopathological examination confirmed the testis and spleen tissue, and the diagnosis of splenogonadal fusion was made postoperatively.

Variation of Gonadal Dysgenesis and Tumor Risk in Patients With 45,X/46,XY Mosaicism.

OBJECTIVE: To describe the gonadal features of patients with 45,X/46,XY mosaicism, and to evaluate the prevalence of gonadal tumor in different phenotypes. MATERIALS AND METHODS: The medical records of consecutive patients with 45,X/46,XY karyotype or its variants who had undergone gonadal biopsy or gonadectomy at a single institute between 1996 and 2017 were retrospectively reviewed. RESULTS: Of 34 patients with 45,X/46,XY mosaicism, a unilateral dysgenetic testis and a contralateral streak gonad was detected in 20 patients (59%), bilateral streak gonads in 9 (26%), and bilateral dysgenetic testes in 5 (15%). A gonad composed of both streak and dysgenetic testicular portions was observed in 7 gonads of 6 patients. All streak gonads were removed, and bilateral gonadectomy was performed in 15 patients raised as girls. Pathologic examination revealed gonadal tumors in 6 of the 34 (18%) patients, including a gonadoblastoma in 7 gonads among 5 patients and an association of dysgerminoma with gonadoblastoma in 1 gonad. All 6 patients who developed gonadal tumor had female genitalia. Postoperative course was uneventful except 1 boy. A seminoma was developed in his soritaly scrotal testis at the age of 16 years. CONCLUSION: The prevalence of gonadal tumor in patients with 45,X/46,XY mosaicism may vary according to the phenotype, and high in patients with female phenotype. Considering the increased risk of gonadal tumors in such patients, early investigation and individual management, including prophylactic gonadectomy, are recommended. In male patients, a close follow-up of the preserved testes is mandatory until adulthood.

[LOCALIZED CYSTIC DISEASE OF THE KIDNEY IN A 6-YEAR-OLD GIRL].

Localized cystic disease of the kidney (LCDK) is a rare, non-hereditary, non-progressive benign cystic renal condition. It is found primarily in adults, and is rarely reported in children. To date, only 5 prepubertal cases of LCDK have been reported in the literature. In this report, we present a case of LCDK that was difficult to differentiate from malignant renal tumor in a 6-year-old girl. Nephron-sparing surgery could not be performed.A 6-year-old girl with no past medical history presented with gross hematuria and right-sided abdominal pain. An abdominal ultrasound at a local hospital showed multiple variable-sized cysts throughout the right kidney. She was referred to our hospital for further evaluation. Computed tomography demonstrated that the region between cysts was slightly enhanced in some part of the lower pole and was diagnosed III in the Bosniak classification. Nephrectomy was performed for possible cystic renal neoplasm. After surgery, a diagnosis of LCDK was made by histopathological examination.

[A CASE OF PARATESTICULAR FIBROUS HAMARTOMA OF INFANCY].

Fibrous hamartoma of infancy (FHI) is a rare, benign soft tissue tumor arising from subcutaneous tissue in children during the first two years of life. The tumor is commonly found in the axilla, shoulder and upper arm. Paratesticular FHI is extremely rare. To date, only a case of paratesticular FHI has been reported in Japan. We present a case of paratesticular FHI in an 11-month-old boy who eventually needed orchiectomy due to local recurrence one month after the excision of the tumor. Ten months postoperatively, there was no sign of recurrence.

[A CASE OF DEXTRANOMER-HYALURONIC ACID COPOLYMER (Deflux®) IMPLANTS CALCIFICATION MIMICKING DISTAL URETERAL CALCULI].

Since 2011, endoscopic correction of vesicoureteral reflux using dextranomer-hyaluronic acid copolymer (Deflux®) has been widely accepted in Japan due to its safety and minimally invasive nature. However, long-term complications are unknown. We present a case of Deflux® implants calcification mimicking distal ureteral calculi in a 12-year-old boy with a history of Deflux® injection performed at three years of age for primary VUR. We should be aware of this complication to avoid misdiagnosis and unnecessary invasive examination such as radiological imaging or endoscopy.

Aggressive Angiomyxoma of the Vulva Mimicking Clitoromegaly in a Young Child.

Aggressive angiomyxoma (AAM) is a rare soft tissue tumor of mesenchymal origin that chiefly involves the vulvar and perineal region. In 90% of cases, AAM presents in women of reproductive age with a peak incidence in the fourth decade of life. To date, AAM of the vulva in young children and infancy has never been reported. We present a case of AAM of the vulva that was initially interpreted as clitoromegaly in a 3-year-old girl.

A Case of Chromosomal Disorders of Sex Development with Transverse Testicular Ectopia Mimicking Mixed Gonadal Dysgenesis.

Transverse testicular ectopia (TTE) is a rare form of ectopic testis observed in boys with a normal 46, XY karyotype. TTE can be associated with persistent Müllerian duct syndrome or other genital anomalies such as hypospadias. However, TTE concomitant with both persistent Müllerian duct remnants and hypospadias has never been reported in the literature. A case of chromosomal disorders of sex development with TTE and persistent Müllerian duct remnants, which was initially presumed to represent mixed gonadal dysgenesis, is presented.

Mesenchymal stem cells protect against obstruction-induced renal fibrosis by decreasing STAT3 activation and STAT3-dependent MMP-9 production.

STAT3 is a transcription factor implicated in renal fibrotic injury, but the role of STAT3 in mesenchymal stem cell (MSC)-induced renoprotection during renal fibrosis remains unknown. We hypothesized that MSCs protect against obstruction-induced renal fibrosis by downregulating STAT3 activation and STAT3-induced matrix metalloproteinase-9 (MMP-9) expression. Male Sprague-Dawley rats underwent renal arterial injection of vehicle or MSCs (1 × 106/rat) immediately before sham operation or induction of unilateral ureteral obstruction (UUO). The kidneys were harvested after 4 wk and analyzed for collagen I and III gene expression, collagen deposition (Masson's trichrome), fibronectin, α-smooth muscle actin, active STAT3 (p-STAT3), MMP-9, and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) expression. In a separate arm, the STAT3 inhibitor S3I-201 (10 mg/kg) vs. vehicle was administered to rats intraperitoneally just after induction of UUO and daily for 14 days thereafter. The kidneys were harvested after 2 wk and analyzed for p-STAT3 and MMP-9 expression, and collagen and fibronectin deposition. Renal obstruction induced a significant increase in collagen, fibronectin, α-SMA, p-STAT3, MMP-9, and TIMP-1 expression while exogenously administered MSCs significantly reduced these indicators of obstruction-induced renal fibrosis. STAT3 inhibition with S3I-201 significantly reduced obstruction-induced MMP-9 expression and tubulointerstitial fibrosis. These results demonstrate that MSCs protect against obstruction-induced renal fibrosis, in part, by decreasing STAT3 activation and STAT3-dependent MMP-9 production.

Long-term Follow-up of Median Raphe Cysts and Parameatal Urethral Cysts in Male Children.

OBJECTIVE: To clarify the long-term outcome of median raphe cysts (MRCs) and parameatal urethral cysts (PUCs) in males, the clinical, anatomical, and histological findings of these cysts are described, along with treatment and follow-up. MATERIALS AND METHODS: Forty-six children diagnosed with PUCs and 23 children with MRCs at our institute during the past 14 years were retrospectively reviewed. The indications for surgery were symptoms or family preference. Telephone interviews of the parents or patients were conducted to ascertain the current condition of the cyst at a median age of 12.2 years. Fifty-nine children (85.5%) agreed to the telephone interview. RESULTS: Median age at first presentation was 41 months; 81% of children were asymptomatic. The main symptoms were voiding symptoms with PUCs and pain of the ruptured cyst in MRCs. A total of 41 (59%) children underwent complete excision at a median age of 58 months. No recurrences were encountered with surgery in all children. Of 28 children managed nonoperatively, 22 agreed to an interview. All children (95.5%), except for 1, remained free of symptoms. Six cysts showed spontaneous resolution at a median age of 24 months, and 15 improved or stabilized. No one was concerned about the genital appearance and opted for surgical intervention. CONCLUSION: Complete excision of the cyst is a durable procedure without recurrences in childhood. In the nonoperative management, several cysts may continue to be free of symptoms during childhood, and some cysts may resolve spontaneously during the first 2 years.

Utilizing an Umbilical Ligament for Complex Ureteroneocystostomy.

INTRODUCTION: To overcome the tension of anastomosis between ureter and bladder for complex ureteroneocystostomy in children, we describe a novel technique utilizing an ipsilateral umbilical ligament (occluded umbilical artery) to fix the bladder. TECHNICAL CONSIDERATIONS: From July 1991 to December 2013, 18 patients (13 girls, 5 boys) underwent our technique for complex ureteroneocystostomy. Median age at surgery was 61 months. The main indications for surgery were ectopic ureter in 9 patients, primary obstructive megaureter in 3, and persistent vesicoureteral reflux after surgery in 2. The ipsilateral umbilical ligament was ligated. A new hiatus was created craniolateral to the original hiatus. The submucosal tunnel was created trans-trigonally. The umbilical ligament was sutured to the whole bladder muscle at the hiatus. Ureteroneocystostomy was then performed. Mean duration of postoperative follow-up was 62.6 months. Seventeen patients underwent unilateral ureteroneocystostomy with our technique. One patient underwent bilateral ureteroneocystostomy with our technique on one side. Vesicoureteral reflux was not shown in 92.3% of patients and no signs of obstruction developed in any patients. No complications were encountered with our procedure. CONCLUSIONS: Utilizing an umbilical ligament for ureteroneocystostomy to fix the bladder is an excellent option when the distal ureter creates tension in uretero-bladder anastomosis. This method seems to be applicable in many cases of complex ureteroneocystostomy in children.

IL-18 induces profibrotic renal tubular cell injury via STAT3 activation.

IL-18 is an important mediator of obstruction-induced renal fibrosis and renal tubular epithelial cell (TEC) injury. IL-18's proinflammatory properties have been attributed, in part, to NF-κB activation and the stimulation of cytokine gene expression; however, STAT3 has increasingly been shown to mediate renal fibrotic injury. We therefore hypothesized that IL-18 mediates profibrotic TEC injury via STAT3 activation. Male C57BL6 wild-type mice and transgenic mice for human IL-18-binding protein were subjected to unilateral ureteral obstruction or sham operation. The kidneys were harvested 1 or 2 wk afterward and analyzed for active STAT3 (p-STAT3) expression (Western blotting, immunohistochemistry) and suppressor of cytokine signaling 3 (SOCS3) expression. In a separate arm, renal tubular cells (HK-2) were directly stimulated with IL-18 for 2 days with or without the STAT3 inhibitor S3I-201 (50 µM). Cell lysates were then analyzed for p-STAT3 and SOCS3 expression, profibrotic cellular changes (collagen and α-SMA expression), and tubular cell apoptosis. p-STAT3 and SOCS3 expression increased significantly in response to obstruction; however, a significant reduction in p-STAT3 and SOCS3 expression occurred following 1 wk, but not 2 wk, of obstruction in the presence of IL-18 neutralization. In vitro results similarly demonstrate increased p-STAT3, SOCS3, α-SMA, and collagen III expression, and increased collagen production and TEC apoptosis in response to IL-18 stimulation, but the response was significantly diminished in the presence of STAT3 inhibition. These results demonstrate that IL-18-induces profibrotic cellular changes and collagen production in TECs via STAT3 activation.

Renal IL-18 production is macrophage independent during obstructive injury.

BACKGROUND: Interleukin 18 (IL-18) is a pro-inflammatory cytokine that mediates fibrotic renal injury during obstruction. Macrophages are a well-known source of IL-18; however, renal tubular epithelial cells are also a potential source of this cytokine. We hypothesized that IL-18 is predominantly a renal tubular cell product and is produced during renal obstruction independent of macrophage infiltration. METHODS: To study this, male C57BL6 mice were subjected to unilateral ureteral obstruction (UUO) vs. sham operation in the presence or absence of macrophage depletion (liposomal clodronate (1 ml/100 g body weight i.v.)). The animals were sacrificed 1 week after surgery and renal cortical tissue harvested. Tissue levels of active IL-18 (ELISA), IL-18 receptor mRNA expression (real time PCR), and active caspase-1 expression (western blot) were measured. The cellular localization of IL-18 and IL-18R was assessed using dual labeling immunofluorescent staining (IFS). RESULTS: Immunohistochemical staining of renal tissue sections confirmed macrophage depletion by liposomal clodronate. IL-18 production, IL-18R expression, and active caspase 1 expression were elevated in response to renal obstruction and did not decline to a significant degree in the presence of macrophage depletion. Obstruction-induced IL-18 and IL-18R production localized predominantly to tubular epithelial cells (TEC) during obstruction despite macrophage depletion. CONCLUSION: These results demonstrate that renal tubular epithelial cells are the primary source of IL-18 production during obstructive injury, and that tubular cell production of IL-18 occurs independent of macrophage infiltration.

The role of the Janus kinase family/signal transducer and activator of transcription signaling pathway in fibrotic renal disease.

Over the past several years, a number of cytokines and growth factors including transforming growth factor ß1, tumor necrosis factor α, and angiotensin II have been shown to play a crucial role in renal fibrosis. The Janus kinase family (JAK) and signal transducers and activators of transcription (STATs) constitute one of the primary signaling pathways that regulate cytokine expression, and the JAK/STAT signaling pathway has increasingly been implicated in the pathophysiology of renal disease. This review examines the role of the JAK/STAT signaling pathway in fibrotic renal disease. The JAK/STAT signaling pathway is activated in a variety of renal diseases and has been implicated in the pathophysiology of renal fibrosis. Experimental evidence suggests that inhibition of the JAK/STAT signaling pathway, in particular JAK2 and STAT3, may suppress renal fibrosis and protect renal function. However, it is incompletely understood which cells activate the JAK/STAT signaling pathway and which JAK/STAT signaling pathway is activated in each renal disease. Research regarding JAK/STAT signaling and its contribution to renal disease is still ongoing in humans. Future studies are required to elucidate the potential role of JAK/STAT signaling inhibition as a therapeutic strategy in the attenuation of renal fibrosis.