[TREATMENT OUTCOMES OF BLADDER NECK CONTRACTURE AFTER TRANSURETHRAL PROSTATE SURGERY].

(Introduction) A known complication of the surgical treatment of benign prostatic hyperplasia (BPH) is bladder neck contracture (BNC). BNC is often treated using transurethral incision of the bladder neck (TUI-BN); however, there are few reports on the outcomes of TUI-BN. Therefore, we examined the outcomes of patients who underwent TUI-BN after transurethral prostate surgery. (Material and methods) We retrospectively examined 25 patients who underwent TUI-BN between February 2015 and January 2021 for the following: (1) patients' characteristics; (2) the time from transurethral prostate surgery to TUI-BN; (3) the trigger of BNC diagnosis; (4) surgical procedure of BNC repair/perioperative course; (5) micturition function immediately after TUI-BN; and (6) Postoperative outcomes. (Results) The median age of the patients was 77 years, and the surgical procedures for BPH were transurethral resection of the prostate (TURP) in four cases, transurethral resection in saline plasma vaporization of the prostate (TURisP) in nine cases, and transurethral enucleation with bipolar (TUEB) in 12 cases. The median time to onset of BNC symptoms was 364 days, and 18 patients (72%) were diagnosed within 2 years. The trigger of BNC diagnosis was urinary symptoms in 21 cases, of which 16 patients had exacerbation of urination. The median duration of the surgical procedure of BNC repair was 14 min, and the incisions most frequently used (in 44% of cases) were at the 4 o'clock and 8 o'clock positions. Transient stress urinary incontinence was observed as a complication in three cases. In the 4 o'clock and 8 o'clock incisions, the maximum urine flow rate improved significantly (11.1 mL/s perioperatively vs. 20.9 mL/s postoperatively; P=0.004). These symptoms improved in 16 of the 21 symptomatic cases, and the maximum urine flow rate improved significantly (P< 0.01). The median observation period after surgery was 170 days; eight postoperative patients were lost to follow up. There were two cases of recurrence. (Conclusions) BNC is likely to develop within 2 years after transurethral prostate surgery. In this study, the success rate of the initial TUI-BN was 92%, as reoperation was required in two cases; however, the overall prognosis was good.

[OUTCOMES OF CHRONIC UNILATERAL HEMATURIA TREATED USING DIGITAL FLEXIBLE URETEROSCOPE].

(Objectives) We examined the treatment outcomes in cases of chronic unilateral hematuria treated using flexible ureteroscope for observation and hemostasis. (Methods) The study included 14 patients (7 men and 7 women) with a median age of 56.5 years who underwent ureteroscopy using a digital flexible ureteroscope for chronic unilateral hematuria between March 2014 and August 2019. All the patients presented with macroscopic hematuria as a clinical symptom, but in one patient, the hematuria was accompanied by anemia and required a blood transfusion. In addition, bleeding occurred on the left side in 8 patients and on the right side in 3 patients; however, for the remaining 3 patients, the affected side could not be identified. Fourteen patients were examined on the basis of the ureteroscopic findings, number of bleeding sites, hemostatic intervention, treatment effect, and presence or absence of recurrences. (Results) The ureteroscopic findings showed a hemangioma in 7 patients and minute venous rupture in 3, but the remaining 4 patients showed no clear findings. The site of the findings was in the superior calyces in 8 cases, middle calyces in 4 cases, inferior calyces in 4 cases, and renal pelvic wall in 1 case. In addition, the findings were located at multiple sites in 6 cases, including all renal calyces in 2 cases. Ten patients with findings underwent hemostatic interventions (electrocoagulation and laser treatment). The median postoperative follow-up period was 32.4 months (range, 6.4-65.4 months). In all the cases, the hematuria disappeared after treatment. One of the 2 patients with findings in all renal calyces showed recurrence of macroscopic hematuria at 1 year and 6 months, which disappeared after conservative treatment. (Conclusions) In this study, observation using digital flexible ureteroscope was useful in the treatment of chronic unilateral hematuria, and the hemostatic interventions performed on the bleeding sites in the renal pelvis were effective.

[Case of brain infarction during cisplatin-based combined chemotherapy with bleomycin, etoposide and cisplatin for testicular cancer].

A 31-year-oldman presented with a 6-month history of right testicular enlargement. The patient underwent a right inguinal orchiectomy. Histopathological examination showed nonseminomatous germ cell tumor (choriocarcinoma>seminoma) which was confined to the tunica albuginea. The postoperative serum level of alpha-fetoprotein (AFP) and lactate dehydrogenase were normal. Serum level of human chorionic gonadotrophin(HCG), however, was 23,000 mIU/ml (normal, < 0.7 mIU/ml). A thoracic computed tomography (CT) at that time showed bilateral and multiple metastases to the lungs but the abdominal CT was normal. After the surgery, the patient was treated with conventional doses of cisplatin, etoposide, and bleomycin. On day 11 of the second chemotherapy course, the patient developed confusion and right sided weakness. Brain magnetic resonance imaging (MRI) showed an ischemic lesion in the left middle cerebral artery area. An echocardiogram showed normal left ventricular function and no valvular vegetations. Finally, the patient completed one additional course of chemotherapy with considerable measures to prevent side effects. A thoracic CT at the end of the third cycle showed no evidence of tumor. At 3 months followup after chemotherapy, he suffered from partial paralysis of right-sided upper and lower limbs but due to intensive rehabilitation he overcame the paralysis and is able to walk by himself. There was no evidence of tumor recurrence.

Chromophobe renal cell carcinoma with osteosarcoma-like differentiation.

Sarcomatoid differentiation in renal cell carcinoma is thought to be the result of the dedifferentiation of the parent tumor, and it can be found in the chromophobe renal cell carcinoma just as other subtypes. We report a case of chromophobe renal cell carcinoma, which showed osteosarcoma-like differentiation. This is the first known case ever to be clearly identified as such. The patient was a 74-year-old man, and the CT scan revealed a huge retroperitoneal mass, which protruded from the lower half of the kidney and directly invaded the colon. Intraabdominal dissemination and metastases to the liver and lungs were also found. The resected tumor histologically showed sarcoma-like spindle cell proliferation and partly produced massive osteoid, which simulated the osteosarcoma. In addition, a typical histology of chromophobe renal cell carcinoma was found in part of the tumor. Immunohistochemically, spindle cells were reactive for epithelial membrane antigen, cytokeratin, and vimentin. The cell nests that were labeled by epithelial membrane antigen and cytokeratin were also found in the osteosarcoma-like area. We think that these phenomena were the result of "dedifferentiation" and metaplasia of the chromophobe renal cell carcinoma.

Chemical bladder irritation provokes c-fos expression in the midbrain periaqueductal gray matter of the rat.

We investigated the topographical localization of c-fos expression in the midbrain periaqueductal gray matter (PAG) to detect nociception-induced neural activity in the PAG. In conscious female Wistar rats, c-fos expression was induced by continuous intravesical infusion of saline or 0.1% acetic acid. Number of c-fos protein (Fos)-positive cells was counted at each coronal section of the PAG as well as Barrington's nucleus. Fos-positive cells were also counted at L1 and L6 of the spinal cord, where most of the hypogastric and pelvic nerve afferent terminals project, respectively. Compared with saline infusion, acetic acid infusion provoked irritative bladder responses characterized by a marked increase in the frequency of bladder contractions, and induced a significant increase in the number of Fos-positive cells in both L1 and L6 of the spinal cord. Following acetic acid infusion, there was a significant increase in the number of Fos-positive cells in all coronal sections of the PAG compared with saline infusion, especially in the caudal part of the PAG. The increase in the number of Fos-positive cells was mainly observed in the ventrolateral and lateral parts of the caudal PAG, and in the dorsal part of the rostral PAG. However, there was no difference in the number of Fos-positive cells in Barrington's nucleus between saline and acetic acid infusion. In conclusion, nociception induced by chemical bladder irritation influences neural activity in the PAG. Implication of topographical difference in Fos expression in the PAG and its relevance to changes in bladder function remain to be elucidated.

Transient neonatal expression of NR2B/2D subunit mRNAs of the N-methyl-D-aspartate receptor in the parasympathetic preganglionic neurons in the rat spinal cord.

Physiological studies have shown that lower urinary tract function is regulated through glutamate receptors at the levels of spinal and supraspinal cord. Of the receptor family, N-methyl-D-aspartate (NMDA) receptors mediate activity-dependent changes of synaptic efficacy, underlying synaptic plasticity and synapse development. To know the ontogenic changes of NMDA receptor expression in the visceromotor system innervating pelvic organs, including the bladder, we employed double labeling technique of retrograde neuronal tracing and in situ hybridization for detecting NMDA subunit mRNAs in preganglionic neurons (PGNs) of the lumbosacral cord. Rats at postnatal day 7 (P7), 14 (P14), 21 (P21), and adult were used. In situ hybridization was conducted using 35S-labeled antisense oligonucleotides specific to mRNAs for NMDA receptor subunits. Hybridizing signals in PGNs were detected by a dark-field microscope equipped fluorescence detector. PGNs showed strong signals for NR1 subunit mRNA at each developmental stage examined. Moderate signals for the NR2B and NR2D subunit mRNAs were found in PGNs at P7. However, their expression levels decreased thereafter, reaching the minimal level in adults. No significant signals for NR2A and NR2C subunit mRNAs were detected at any stages. This temporal pattern of expression suggests a possible involvement of NMDA receptors in the development of micturitional neural circuit through activity-dependent mechanisms.

Ureteral stricture developing after partial nephrectomy with a microwave tissue coagulator: case report.

A 32-year-old man with a 1.7-cm tumor in the left kidney underwent laparoscopy-assisted partial nephrectomy. Although his postoperative course was uneventful, a 6-month postoperative CT scan showed hydronephrosis secondary to a severe stricture at the ureteropelvic junction. Heat injury to the urinary tract was strongly suspected. The use of microwave tissue coagulator for the tumor close to the renal sinus and excessive coagulation should be avoided to prevent heat-related complications.

[Management of pregnancy and delivery after augmentation cystoplasty].

We report 2 cases of women who became pregnant and experienced vaginal delivery after augmentation cystoplasty. CASE 1: A 23-year-old woman with spina bifida became pregnant 3 years after augmentation sigmoidocystoplasty which had been performed to treat intractable urinary tract infection and urinary incontinence. During pregnancy, she developed febrile urinary tract infection twice which required antibiotics together with tight adherence to clean intermittent catheterization. At 36 weeks of gestation, she was safely delivered of a healthy baby. No deterioration of urinary continence level and renal function was observed after the delivery. CASE 2: A 32-year-old woman became pregnant 23 years after augmentation ileocecocystoplasty which had been performed to reconstruct diverted urinary tract due to a congenital hour-glass bladder. At 19 weeks of gestation, she developed acute pyelonephritis and hydronephrosis at right kidney which required antibiotics and indwelling urethral catheter. At 21 weeks of gestation, a drip infusion of ritodrine hydrochloride was started and maintained until 34 weeks of gestation to inhibit premature uterine contraction. At 29 weeks of gestation, she developed acute pyelonephritis and progressive hydronephrosis at left kidney, for which percutaneous nephrostomy drainage was deemed to be mandatory. She was delivered of a healthy baby at 36 weeks of gestation. Ten days after the delivery, both nephrostomy tube and indwelling urethral catheter were removed and clean intermittent catheterization was resumed. Total renal function was maintained during and after the pregnancy, and no deterioration of urinary continence was observed after the delivery. Since urinary tract infection is extremely common during pregnancy after augmentation cystoplasty, prevention and prompt intervention for urinary tract infection should be mandatory. Significant upper tract obstruction, if developed, should be treated by an effective urinary drainage. Thus, urological as well as obstetrical appropriate management is mandatory for the safe accomplishment of pregnancy and delivery after augmentation cystoplasty.

[Ureteral and bladder metastases of renal cell carcinoma following synchronous renal cell carcinoma and bladder cancer; a case report].

A 73-year-old man presented with gross hematuria. Ultrasonography and computerized tomography showed small bladder tumors and a left renal mass protruding to renal pelvis. Transurethral resection of bladder tumor and ureteroscopic tumor biopsy were performed, and pathological examinations revealed transitional cell carcinoma in the bladder and renal cell carcinoma in the kidney. He underwent left radical nephrectomy. A 4-month postoperative cystoscopy revealed a solitaly non-papillary tumor in the bladder. Transurethral resection was performed and pathological diagnosis was metastasis from renal cell carcinoma. At that time, multiple metastases to ureteral stump and lung were found. He had undergone palliative treatment because of his poor general condition until he died 26 months postoperatively. Care should be taken for management of ureteral stump when diagnostic ureteroscopy was done for renal cell carcinoma invading the renal pelvis.

[Paclitaxel, ifosfamide, nedaplatin (TIN) for patients with metastatic urothelial cancer].

TIN (ifosfamide 1.5 g/m2 daily for 3 days, paclitaxel 175 mg/m2, and nedaplatin 70 mg/m2 on day 1) was administered to patients with metastatic urothelial cancer previously treated by platinum-based chemotherapy and repeated every 4 weeks. Four patients received maintenance therapy, which consisted of 5'-DFUR 800 mg/day orally for 12 weeks and 1 subsequent course of TIN. This therapy regimen was repeated for 2 years from initiation of TIN. Eleven of 12 patients (91.6%) demonstrated a major response (3 complete responses, 8 partial responses), with durations of response ranging from 3 to 20 months. Progression-free survival time was from 0 to 20 months (median 8 months). One-year progression-free survival rate was 45.8%. Overall survival time was from 2 to 20 months (median 10.5 months). One-year overall survival rate was 53.5%. Grade 3/4 hematologic toxicity involved neutropenia in 100% and thrombocytopenia in 33.3%. Febrile neutropenia was observed in 5 patients (41.6%). Grade 3 nonhematologic toxicity involved malaise in 15.3%. No patient discontinued this therapy because of complications. TIN is a potent, well-tolerated regimen for previously treated patients with urothelial cancer.

The long-term voiding function and sexual function after pelvic nerve-sparing radical surgery for rectal cancer.

BACKGROUND: The aim of the present study is to symptomatically analyze the extent to which pelvic nerve-sparing radical surgery for rectal cancer impacts on long-term voiding and male sexual function. METHODS: A self-administered questionnaire was mailed to 68 patients who underwent pelvic nerve-sparing radical surgery for invasive rectal cancer with 52 responses (28 men and 24 women; 27 complete and 25 incomplete preservation; response rate 76.5%). Each patient was asked to record if there had been any changes in lower urinary tract symptoms after surgery. Sexual function was also investigated in men. RESULTS: Of the 52 patients, 48 (92%) maintained voluntary voiding without catheterization in the long term. Clean intermittent self-catheterization was performed in only four patients with incomplete preservation because of persistent voiding dysfunction. Subjectively, approximately 60% of the patients remained unchanged in lower urinary tract symptoms after surgery. The satisfaction rate regarding the current voiding status was significantly higher in women than in men (83% versus 61%, P = 0.0294), but was not significantly different between those with complete (76%) and incomplete preservation (64%). Despite the acceptable urinary status, 88% of men had some deterioration in the erectile function, regardless of the types of surgical procedures. Overall, 64% of men were unsatisfied with the current sexual function. CONCLUSIONS: Pelvic nerve-sparing radical surgery for rectal cancer preserved the long-term voiding function in the majority of patients. In completely preserved patients and in women, symptomatic outcomes were more satisfactory. Postoperative erectile dysfunction was found to be a serious problem, even in complete nerve-sparing procedure.

Ras signal transduction in carcinogenesis and progression of bladder cancer: molecular target for treatment?

Ras oncogenes are considered to play a key role in the carcinogenesis and progression of human bladder cancer. The oncogenes code for the Ras p21 proteins, which localize in the internal part of the cell membrane and act as molecular switches to mediate downstream signaling from a variety of extracellular stimuli. Activation of Ras proteins induces the constitutive activation of downstream kinase cascades, which results in continuous mitogenic signaling and transformation of immortalized cells in human bladder cancer. Therefore inactivation of the activated Ras function might be effective for the development of a novel treatment strategy against human bladder cancer. Recently several ways to suppress Ras activities, including inhibitors of Ras signal transduction and a ras suppressor mutant, have been reported. Here we review the current concepts of the basic mechanisms of the intracellular Ras signaling pathway and ras activation in the carcinogenesis and progression of human bladder cancer and discuss clinical potentials of their therapeutic interventions.

Diameter of the external urethral sphincter as a predictor of detrusor-sphincter incoordination in children: comparative study of voiding cystourethrography.

PURPOSE: Voiding cystourethrography is a diagnostic procedure widely used to evaluate lower urinary tract abnormalities in children. In children with and without suspected voiding dysfunction we measured the internal diameter of the external urethral sphincter on voiding cystourethrography to evaluate its diagnostic accuracy as a predictor of detrusor-sphincter incoordination. MATERIALS AND METHODS: In part 1 of the study 59 boys and 37 girls with normal voiding function underwent voiding cystourethrography. In each child 1 to 6 voiding cystourethrograms (mean 2.1) were performed as a part of urological evaluation. Thus, a total of 200 voiding cystourethrograms were obtained. Underlying urological disease was primary vesicoureteral reflux in 57 cases, congenital hydronephrosis in 9, urinary tract infection in 6, ureteral anomalies in 11 and other in 13. To determine external urethral sphincter inner diameter on a given voiding cystourethrogram the sphincter was measured on consecutive images and the widest diameter was chosen. In part 2 of the study 43 children with suspected voiding dysfunction underwent voiding cystourethrography and external urethral sphincter electromyography. Electromyography results were comparatively analyzed with external urethral sphincter data. RESULTS: In part 1 an age dependent increase in external urethral sphincter inner diameter was noted in children with normal voiding function. External urethral sphincter inner diameter in mm. was determined by the formula, 0.166 x age in years + 4.31 in boys (p = 0.0001, r = 0.374) and 0.222 x age in years + 2.73 in girls (p <0.0001, r = 0.595). Overall the incidence of an external urethral sphincter inner diameter of less than 3 mm. was only 4% (8 of 200 patients). In part 2 external urethral sphincter electromyography documented detrusor-sphincter incoordination in 15 children (35%). When we defined an external urethral sphincter inner diameter of less than 3 mm. as a cutoff value for predicting detrusor-sphincter incoordination, the sensitivity, specificity, positive and negative predictive values were 93%, 89%, 82% and 96%, respectively. CONCLUSIONS: External urethral sphincter inner diameter has satisfactory sensitivity and specificity as a predictor of detrusor-sphincter incoordination in children. Thus, simple measurement of the inner diameter of the external urethral sphincter on voiding cystourethrography should be recommended in children with suspected voiding dysfunction before performing rather invasive urodynamic studies.

Creation of luminal tissue covered with urothelium by implantation of cultured urothelial cells into the peritoneal cavity.

PURPOSE: We established the culture condition of seeding urothelial cells onto a scaffold for implantation into the peritoneal cavity and evaluated the histology of implanted urothelial cells. MATERIALS AND METHODS: In part 1 of the study cultured porcine bladder urothelial cells were seeded onto 3 types of collagen gel made on microporous membrane, including collagen gel with or without cultured porcine bladder fibroblasts, or a feeder layer. The macroscopic and microscopic appearance of the gel with urothelial cells were examined in vitro. As an in vivo study, cultured porcine bladder urothelial cells were seeded onto a collagen gel/sponge matrix with or without cultured fibroblasts, or a feeder layer. Urothelial cell survival on each matrix was evaluated 28 days after implantation onto the omentum or mesentery of nude rats. In part 2 of the study rat urothelial cells were cultured and seeded onto fibrin gel/atelocollagen sponge matrix as an autologous implantation model. After 7 days of cultivation the matrix was folded with urothelial cells inside, implanted onto the mesentery and serially evaluated. RESULTS: Gel containing cultured fibroblasts was shrunken and basement membrane formation was observed on the gel with cultured fibroblasts or the feeder layer in vitro. Urothelial cells cultured with the feeder layer better survived on the collagen based matrix and formed a hollow-like lumen when implanted into the peritoneal cavity. The regenerated urothelium in an autologous implantation showed the same histological features as normal bladder urothelium. CONCLUSIONS: Selection of less degradable matrix and formation of basement membrane are critical for survival of implanted urothelial cells. The regenerated urothelium in an autologous implantation model seems to have the similar properties to the normal urothelium.

Expression of vascular endothelial growth factor and its receptors Flk-1 and Flt-1 during the regeneration of autotransplanted adrenal cortex in the adrenalectomized rat.

PURPOSE: Autotransplantation of the adrenal cortex may be a therapeutic alternative in the future. For successful adrenal transplantation revascularization is necessary. It is possible that vascular endothelial growth factor (VEGF), which is a potent angiogenic peptide, may have some roles in adrenal transplantation through 2 its receptors, kinase insert domain-containing region (Flk-1) and fms-like tyrosine kinase (Flt-1). Therefore, we studied sequential changes in expression of VEGF, Flk-1 and Flt-1 in regenerated adrenal. MATERIALS AND METHODS: Eight to 9-week-old male Wistar rats underwent bilateral adrenalectomy and immediate adrenal capsular autotransplantation. The expression of VEGF, Flk-1 and Flt-1 was analyzed by immunohistochemistry and reverse-transcriptase-polymerase chain reaction. RESULTS: Angiogenesis was observed in the remodeling of adrenal sinusoidal endothelium during adrenal regeneration. Reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that VEGF expression increased in grafted tissue with time after transplantation and its Flk-1 receptor, which localized to endothelial cells, increased transiently during the regeneration process. Immunostaining for Flt-1 receptor was identified in adrenocortical cells and its intensity gradually increased during adrenal regeneration. CONCLUSIONS: During adrenal gland regeneration VEGF and its receptors Flk-1 and Flt-1 are thought to be involved in neovascularization.

Medical management of recurrent aggressive angiomyxoma with gonadotropin-releasing hormone agonist.

Patients with aggressive angiomyxoma may experience local recurrences. We report a case of recurrent aggressive angiomyxoma medically treated successfully with a gonadotropin-releasing hormone agonist. A 34-year-old woman with a huge perineal tumor underwent an extensive resection of the abdominoperineal tumor combined with total pelvic exenteration. Histology showed aggressive angiomyxoma and the tumor cells were immunoreactive for estrogen and progesterone receptors. Although the patient had experienced no local recurrence for 12 months under adjuvant therapy with a gonadotropin-releasing hormone agonist, a recurrence occurred 3 months after the completion of adjuvant therapy. The patient underwent medical treatment with a gonadotropin-releasing hormone agonist and had a complete resolution of the recurrent tumor again. Hormonal treatment with a gonadotropin-releasing hormone agonist can be applied for small primary aggressive angiomyxomas in addition to adjuvant therapy for residual tumors.

Management of renal angiomyolipomas associated with tuberous sclerosis complex.

PURPOSE: Intensive management is generally recommended for angiomyolipomas associated with tuberous sclerosis complex (TSC), which are known to have a more aggressive nature than sporadic tumors. In this study we evaluated the management of these tumors. MATERIALS AND METHODS: The records of 6 men and 6 women with TSC and a mean age of 28.8 years) with angiomyolipomas treated from 1984 to 2000 were retrospectively analyzed. All patients had bilateral multiple tumors (mean size 6.6 cm). There were 10 lesions classified as small (less than 4 cm), 6 medium (4 to 10 cm) and 8 large lesions (10 cm or greater). Computerized tomography was repeated annually for followup observation and semiannually after embolization. RESULTS: Excluding from study 3 tumors treated prophylactically intervention was required in 20%, 50% and 100% of small, medium and large tumors, respectively. Among 14 tumors followed by observation, 8 grew and 4 required intervention. Uncontrollable hemorrhage did not develop in any patient. While some tumors showed remarkable growth in decade 3, growth did not exceed 1.5 cm per year. Embolization was performed in 11 tumors and tumors shrank in 10. Although 1 patient experienced renal atrophy, all patients but 1 are alive without renal failure with a mean followup of 60 months. CONCLUSIONS: Although asymptomatic angiomyolipomas associated with TSC grow gradually, severe hemorrhage is rare and most tumors can be managed conservatively with annual computerized tomography. Embolization is the first choice of intervention but should be reserved until symptoms develop.