[Treatment Outcome of Ureteral Reconstruction Surgery].

We retrospectively reviewed the surgical outcome of ureteral reconstruction that was performed in Asahikawa Medical University Hospital between 2005 and 2021. A total of 14 patients (3 males, 11 females; 15 ureters) were included in this analysis. The median age was 57 years old. The reason for ureteral reconstruction was ureteral injury or stenosis due to pelvic surgery in 9 patients, transurethral lithotripsy for ureteral stone in 3, ureteral invasion of sigmoid colon cancer in one and ovarian cancer in one. The site of ureteral reconstruction was proximal ureter in 2, middle in 3 and distal in 10. The surgical procedure was ureteroneocystostomy with Boari flap in 8 patients (57%), ureteroureterostomy in 4 (21%), transureteroureterostomy in one (7%), and transureteroureterostomy combined with Boari flap for bilateral ureteral stenosis in the remaining patient (7%). Postoperatively, vesicoureteral reflux, ileus and surgical site infection were observed in 3, 2 and 1 patient, respectively. No patient required nephrostomy or ureteral catheter, or any additional procedure after the surgery. There was no episode of febrile urinary tract infection after the surgery. The mean estimated glomerular filtration rate was, respectivery 75.8 and 78.5 ml/min/1.73 m2 before surgery and at 1-101 months (median of 18) after the surgery. In conclusion, satisfactory outcome was achieved after ureteral reconstruction surgery. We emphasize the importance of selecting the most appropriate procedure for ureteral reconstruction in each patient to prevent renal function deterioration and urinary tract infection.

[The Clinical Course of α1 Blocker Discontinuation in Patients with LUTS/BPH Receiving Combination Therapy of Dutasteride and α1 Blocker].

We retrospectively investigated the clinical course of α1 blocker discontinuation in patients who had lower urinary tract symptoms with benign prostate hypertrophy (LUTS/BPH) and received combination therapy ofdutasteride and α1 blocker. Among the patients with LUTS/BPH who had been receiving combination therapy, those who wished to reduce the number ofprescribed drugs and discontinue the use of α1 blocker because ofsymptom improvement were recruited in this study. Symptom scores including International Prostate Symptom Score (IPSS) and overactive bladder symptom score (OABSS), parameters ofuroflowmetry and prostate volume (PV) were evaluated at the time of α 1 blocker discontinuation. Twenty-two patients discontinued the use of α 1 blocker. The mean PV at the time of α 1 blocker discontinuation was 43.2 ml, and the mean duration ofcombination therapy was 39.4 months. In 11 (50%) patients, dutasteride monotherapy without α1 blocker was maintained for a mean follow-up of 10.5 months (9-12 months) after α1 blocker discontinuation (Non-resumption group). In the other 11 patients (50%), α1 blocker was resumed because ofthe patient's request to resume the use of α1 blocker (Resumption group). The mean length ofdutasteride monotherapy was 4. 5 months (1-8 months) in the resumption group. Compared with the non-resumption group, IPSS total score and storage sub-score ofIPSS at the time of α1 blocker discontinuation were significantly higher in the resumption group. Based on the ROC curve, IPSS total score <16, IPSS voiding/storage symptom score <7, OABSS <7 and PV 54 ml or more at the time of α1 blocker discontinuation were predictors ofnon-resumption of α1 blocker. These results suggest that if LUTS is controlled by a long-term combination therapy ofdutasteride and α1 blocker and still PV is large enough, α1 blocker can be discontinued.

[Initial Experiences of Dynamic Sentinel Lymph Node Biopsy (DSNB) in Patients with Penile Cancer].

We present 2 cases of penile cancer in which the inguinal lymph node was not palpable and inguinal lymph node dissection (ILND) could be safely avoided by conducting dynamic sentinel lymph node biopsy (DSNB). The first case was in a 54-year-old man complaining of penile tumor for at least 3 months. We performed partial penectomy and DSNB. The pathological diagnosis was squamous cell carcinoma (SCC), pT2-3. There was no cancer metastasis in sentinel nodes (0/2). There has been no recurrence for 6 years after operation. The second case was 65-year-old man suffering from penile tumor for at least 6 months. We performed partial penectomy and DSNB. The pathological diagnosis was SCC,pT2. There was no cancer metastasis in sentinel nodes (0/3). There has been no recurrence for 1 year after operation. ILND has been recommended for intermediate and high-risk penile cancer even in patients with non-palpable inguinal lymph nodes. However,the complication of ILND is very high. DSNB has the potential to avoid ILND if there is no cancer metastasis in sentinel nodes.

[Relationship between Early Complications after Radical Cystectomy and Psoas Muscle Mass].

Psoas muscle mass index (PMI) is related to sarcopenia. We examined whether PMI is associated with early complications after radical cystectomy. Seventy one male and 29 female patients who were 65 years old or older and who had undergone radical cystectomy at our hospital from April 2005 to March 2018 were retrospectively analyzed. Psoas muscle section area was measured manually on preoperative computed tomography (CT) scan and normalized by patient's height. Early postoperative complications of grade 3 or more occurred in 12 male (16.9%) and 5 female (17.2%) patients. PMI was lower in male patients who had early postoperative complications of grade 3 or more than in those without complications (5.61 vs 6.54 cm2 /m2, p=0. 08), although the difference was not statistically significant. There was suggested to be a relationship between early postoperative complications after radical cystectomy and preoperative PMI in elderly male patients.

[A Case of Adenocarcinoma of the Reconstructed Bladder 45 Years after Ileocystoplasty].

The patient was a 66-year-old man who had undergone ileocystoplasty and right nephrectomy at the age of 21 for the treatment of urinarytract tuberculosis. He had been receiving hemodialysis from the age of 58. Regular computed tomography (CT) examination at the age of 63 revealed a bladder mass, but the transurethral biopsyof the bladder mass did not reveal malignant findings. At the age of 66, his urine cytology indicated a suspicion of malignancy, and bladder tumor was detected by cystoscopy. The patient was referred to our hospital and we performed transurethral resection of the bladder tumor. Pathological diagnosis was papillaryadenocarcinoma. Because left lower ureteral cancer was also suspected byCT scan, we performed left nephroureterectomy and radical cystectomy. Pathological examination revealed adenocarcinoma of the reconstructed bladder. The patient remains free of disease for 1 year and 11 months after the operation. Forty-five cases of bladder cancer after enterocystoplasty have been reported in Japan. There are no guidelines for follow-up protocols after enterocystoplasty. A long-term follow-up is mandatory because of the possibilityof development of bladder malignancylong after the enterocystoplasty.

Urodynamic Efficacy and Safety of Mirabegron Add-on Treatment with Tamsulosin for Japanese Male Patients with Overactive Bladder.

OBJECTIVES: To investigate urodynamic efficacy and safety of mirabegron add-on treatment with tamsulosin for Japanese male patients with overactive bladder (OAB). METHODS: A prospective study was conducted in 26 consecutive male patients with OAB who had been taking tamsulosin. OAB was diagnosed by overactive bladder symptom score (OABSS). Before and 8 weeks after mirabegron add-on treatment with preceding tamsulosin, we assessed OABSS, International Prostate Symptom Score (IPSS), free uroflowmetry (UFM), filling cystometry and pressure-flow study (PFS). RESULTS: Mean age and prostate volume of the study patients were 75 ± 7 years and 32 ± 19 mL, respectively. Mirabegron significantly improved OABSS (from 8.5 ± 2.3 to 4.7 ± 2.5, P < 0.001). On free UFM, mirabegron significantly increased voided volume (from 135 ± 47 to 182 ± 102 mL, P = 0.01), maximum (from 10.7 ± 3.7 to 13.5 ± 6.4 mL/sec, P < 0.01) and average flow rate (from 5.5 ± 1.9 to 7.1 ± 3.3 mL/sec, P < 0.01), while postvoid residual urine volume did not change significantly (from 47 ± 38 to 63 ± 61 mL, P = 0.23). Before mirabegron, 24 patients (92%) had detrusor overactivity (DO). After mirabegron add-on, maximum cystometric capacity significantly increased from 170 ± 98 to 212 ± 95 mL (P = 0.01) and DO disappeared in six patients (25%). In the other 18 patients with persistent DO, amplitude of involuntary contraction decreased and bladder volume at first involuntary contraction increased with statistical significance. On PFS, detrusor pressure at maximum flow rate (from 79 ± 31 to 68 ± 19 cmH2 O, P = 0.10) or bladder contractility index (from 126 ± 39 to 120 ± 27, P = 0.45) did not change significantly. CONCLUSIONS: Mirabegron add-on treatment with tamsulosin has efficacy and safety because it improves storage symptom without impairment of bladder contractility during voiding in male patients with OAB.

Combination of GnRH Antagonist Degarelix and Antiandrogen Is Effective in PSA Reduction and Bone Management in Patients with Prostate Cancer.

OBJECTIVES: To investigate the efficacy of combination treatment of degarelix and antiandrogen in patients with prostate cancer. METHODS: We prospectively investigated the efficacy of combination treatment of degarelix and antiandrogen in 12 patients with treatment-naive prostate cancer. We surveyed PSA, LH, FSH and testosterone at day 3, 7, 14 and 28 during the initial month and thereafter once a month for 1 year. In cases with bone metastasis, we analyzed serum bone markers such as alkaline phosphatase(ALP), bone-type ALP and carboxyterminal telopeptide of type- I collagen once a month. Skeletal related events (SREs) were also monitored. RESULTS: PSA progression free survival was 65%. PSA was reduced from baseline by 80% at day 14 and by 93% at day 28. In all patients serum testosterone immediately reached castrate level at day 3 and was maintained for 1 year without breakthrough escape. Both LH and FSH were reduced to within normal range at day 3. In contrast, all bone markers temporarily increased at day 28, and thereafter decreased. Although 2 patients had suffered from SREs before treatment, there were no SREs after combination treatment. CONCLUSIONS: The present study showed that combination of degarelix and antiandrogen could lead to favorable PSA reduction and immediate castrate level at an earlier phase. However, further study is needed to compare the difference between degarelix monotherapy and these combinations.

[Successful Management by Immunoglobulin for Sunitinib-Induced Thrombocytopenia in a Patient with Advanced Metastatic Renal Cell Carcinoma].

An 81-year-old man was referred to our hospital because of a right renal tumor with vena cava thrombus and multiple lung metastases that were detected by computed tomography (CT) scan during evaluation of respiratory discomfort. We started medical treatment with sunitinib at a dose of 50 mg daily in a 2-week-on, 1-week-off schedule after confirming clear cell renal cell carcinoma by tumor biopsy. After 2-week sunitinib treatment, thrombocytopenia continued and platelet count decreased to 1.8×10(9)/l at day 11 after stopping sunitinib. We needed to administer a total of 60 units platelet transfusion because of persistent thrombocytopenia. Bone marrow aspiration did not reveal myelosuppression or carcinoma invasion to bone marrow. Under the clinical diagnosis of drug-induced thrombocytopenia secondary to sunitinib, we started immunoglobulin therapy at day 23 after stopping sunitinib. Platelet count returned to normal 10 days after starting immunoglobulin. The patient developed exacerbating lung metastasis and carcinomatous lymphangiosis during subsequent course and died of renal cell carcinoma 79 days after starting sunitinib. Thrombocytopenia after sunitinib therapy is often encountered but prolonged thrombocytopenia is rare after stopping sunitinib. This case suggests that immunoglobulin therapy is effective for drug-induced prolonged thrombocytopenia through immunological mechanism.

[A Case Report of Suspected Tuberculous Granuloma in the Kidney after BCG Perfusion Therapy for Urothelial Carcinoma of the Renal Pelvis].

A 66-year-old male patient was referred to our hospital for bilateral renal pelvic tumors. Ureteroscopic biopsy revealed urothelial carcinoma (UC) of low grade (G1) of the renal pelvis. Renal sparing treatment with systemic chemotherapy and percutaneous tumor resection was performed. However, during subsequent follow up, a recurrent tumor was found on the left ureter. After ureteroscopic laser ablation of the tumor, Bacillus Calmette-Guerin (BCG) perfusion therapy (once a week, total 6 weeks) was performed via a single J ureteral catheter with no adverse events. Later, another recurrent recurrence was found on the right ureter, and was managed by ureteroscopic laser ablation followed by BCG perfusion therapy via a single J ureteral catheter. However, the patient developed high fever with chill from the day after initial BCG perfusion therapy on the right side. Although we started antibiotics, high fever continued. Then antituberculous drugs were administered and his condition was improved. Computed tomographic scan revealed a right renal mass 57 mm in diameter, which was consistent with tuberculous granuloma. The tuberculous granuloma persisted despite the continuation of anti-tuberculous drugs. In exceptional cases of upper tract UC such as single kidney and bilateral tumor, BCG perfusion therapy has been used as adjunctive treatment to cure or prevent UC. However, dosages and administration methods of BCG perfusion therapy for upper tract UC still remain to be standardized. Serious adverse events after BCG perfusion therapy require prompt and proper management including the use of anti-tuberculous drugs.

Improvement of Overactive Bladder Symptoms and Bladder Ischemia with Dutasteride in Patients with Benign Prostatic Enlargement.

OBJECTIVES: To evaluate the correlation of clinical and urodynamic parameters with bladder vascular resistance before and after dutasteride treatment in patients with lower urinary tract symptoms associated with benign prostatic enlargement. METHODS: A prospective study was conducted in 30 consecutive patients with benign prostatic enlargement who had not been satisfied with alpha-adrenergic antagonist monotherapy. Before and 24 weeks after dutasteride add-on treatment, we assessed International Prostate Symptom Score (IPSS), prostate volume (PV), urodynamic study and contrast-enhanced color Doppler ultrasonography to measure bladder vascular resistive index (RI). RESULTS: Twenty-four weeks after dutasteride, PV significantly decreased from 68 ± 29 to 48 ± 28 mL (P < 0.001), and there was significant improvement of IPSS (from 18.8 ± 7.7 to 13.4 ± 7.2, P < 0.001). Urgency score of IPSS was also significantly improved from 2.3 ± 1.9 to 1.4 ± 1.4 (P < 0.01) after dutasteride. On pressure-flow study, bladder outlet obstruction index (BOOI) (from 58 ± 36 to 38 ± 27, P < 0.001) and detrusor pressure at Qmax (PdetQmax) (from 73 ± 34 to 54 ± 25 cmH2 O, P < 0.001) were significantly improved. RI significantly decreased after dutasteride (from 0.548 ± 0.069 to 0.486 ± 0.064, P < 0.001). In 20 patients with persistent urgency after dutasteride, RI was less improved than in another 10 patients without urgency (change of RI 0.045 ± 0.091 vs. 0.096 ± 0.042, P < 0.05). Post-treatment BOOI and PdetQmax in patients with persistent urgency was significantly higher than in those without urgency after dutasteride (BOOI: 46 ± 28 vs. 24 ± 20, P < 0.05, PdetQmax: 62 ± 26 vs. 40 ± 17 cmH2 O, P < 0.01). CONCLUSIONS: Reduction of obstruction and improvement of bladder ischemia might play an important role in a beneficial impact of dutasteride on overactive bladder symptoms.

[Perioperative complications of transurethral resection of bladder tumor in patients receiving antithrombotic therapy].

We examined perioperative complications of transurethral resection of bladder tumor (TURBT) in patients receiving antithrombotic therapy. We retrospectively studied 276 patients who underwent TURBT in our institute from January 2007 to March 2013. The study group consisted of 105 patients (38%) who were receiving antithrombotic agents, and the other 171 patients (62%) without antithrombotic agents were assigned to the control group. The period of discontinuation of antithrombotic agents complied with our institutional rule. The most frequently used agent was aspirin (69 patients : 66%), followed by warfarin (25 patients : 24%). Fourteen patients receiving warfarin (56%) needed heparin bridging therapy. There was no significant difference in average operative time (51 minutes versus 54 minutes), or average days to removal of urethral catheter (3.7 days versus 3.3 days) between the study and control groups. Hemorrhagic and ischemic complications were noted in 11 (10.5%) and 2 (1.9%) patients in the study group and 11 (6.4%) and none (0%) of the patients in the control group, respectively, with no significant difference between the 2 groups. However, prevalence of hemorrhagic complications in patients receiving heparin bridging therapy (21.4%) was significantly higher than that in the control group. Ischemic complications in the study group included chest pain suggestive of angina in one patient and acute myocardial infarction leading to death in another patient. We should pay attention to hemorrhagic complications in patients receiving heparin bridging therapy and keep in mind the possibility of lethal ischemic complications after discontinuation of antithrombotic agents.

Decreased urinary nerve growth factor reflects prostatic volume reduction and relief of outlet obstruction in patients with benign prostatic enlargement treated with dutasteride.

OBJECTIVES: To examine urinary nerve growth factor before and after dutasteride treatment, and to analyze correlations between clinical parameters and change of urinary nerve growth factor in patients with benign prostatic enlargement. METHODS: We prospectively studied 30 patients with benign prostatic enlargement who had not been satisfied with α-adrenergic antagonist monotherapy for more than 3 months. Before and 24 weeks after dutasteride add-on treatment, we assessed International Prostate Symptom Score, prostatic volume, filling cystometry and pressure-flow study. Urinary nerve growth factor was measured by enzyme-linked immunosorbent assay, and normalized to the urinary creatinine (nerve growth factor/creatinine) before and 24 weeks after dutasteride add-on treatment. RESULTS: In baseline characteristics before dutasteride, there was no significant correlation between urinary nerve growth factor/creatinine and any clinical parameters including age, International Prostate Symptom Score, prostatic volume, presence of detrusor overactivity, detrusor pressure at maximum flow rate, bladder outlet obstruction index or bladder contractility index. Dutasteride significantly reduced prostatic volume (from 68 ± 31 mL to 49 ± 28 mL) and improved International Prostate Symptom Score (from 17.2 ± 8.7 to 13.1 ± 6.8), storage (from 8.0 ± 4.3 to 6.0 ± 2.9) and voiding symptom subscore of International Prostate Symptom Score (from 9.3 ± 5.7 to 7.1 ± 4.5). In urodynamic study, detrusor pressure at maximum flow rate (from 77 ± 32 cmH2 O to 59 ± 24 cmH2 O) and bladder outlet obstruction index (from 62 ± 32 to 42 ± 27) were significantly decreased after dutasteride treatment. Urinary nerve growth factor/creatinine was significantly decreased after dutasteride from 2.61 ± 2.50 to 1.64 ± 1.68. The change of urinary nerve growth factor/creatinine significantly correlated only with the change of prostatic volume (r = 0.38) and bladder outlet obstruction index (r = 0.36). CONCLUSIONS: Urinary nerve growth factor decreases in association with reduction of prostatic volume and relief of bladder outlet obstruction. Urinary nerve growth factor might be useful as a biomarker to monitor the improvement of bladder outlet obstruction in patients with benign prostatic enlargement.

[Successful conservative management of blunt renal rupture in a girl].

An 11-year-old girl visited the emergency room of our hospital with complaints of pain, nausea and gross hematuria after abdominal injury due to a fall from a fence. Computed tomography (CT) showed ruptured right kidney, hematoma, urinoma, and slight liver damage in S7 area. According to the Classification of Renal Injury by the Japanese Association for the Surgery of Trauma, this case was Type IIIb, but according to the American Association for the Surgery of Trauma Organ Injury Severity Scale for the Kidney, it was Type V. Because her vital signs were stable after admission, conservative management was initiated. There was no progression of anemia, and blood transfusion was not required. Right ureteral stenting was performed on the 4th hospital day because of an increase in fluid accumulation around the right kidney. Percutaneous drainage was performed on the 9th hospital day because of a further increase in fluid accumulation around the right kidney. After percutaneous drainage, fluid accumulation around the kidney was improved, and the drainage tube was removed on the 20th hospital day. The patient was discharged on the 22nd day. Although the decreased blood flow in the ruptured portion of the right kidney was observed in a subsequent CT scan, renal scintigraphy showed a relatively well maintained function of the right kidney (split renal function; right 38% and left 62%). She had no increase in blood pressure one year after renal injury.

Effects of chronic treatment with cilostazol, a phosphodiesterase 3 inhibitor, on female rat bladder in a partial bladder outlet obstruction model.

OBJECTIVE: To investigate whether bladder dysfunction after bladder outlet obstruction (BOO) could be altered by treatment with cilostazol, a phosphodiesterase 3 inhibitor (PDE3i). METHODS: Twelve-week-old female Sprague-Dawley rats were divided into 5 groups: groups 1 and 2, sham-operated rats and groups 3-5, BOO rats. Group 1 and 3 rats were given normal diet, group 2 and 5 rats were given high-dose PDE3i diet, and group 4 rats were given low-dose PDE3i diet. PDE3i was given within diet from the day of surgery. Four weeks after BOO, the bladder was excised and dissected into 4 longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol, and potassium chloride (KCl) were determined for each group. RESULTS: BOO induced a significant increase in bladder weight in groups 3-5 compared with groups 1 and 2. PDE3i treatment did not affect bladder weight in sham or BOO rats. Contractile forces in response to EFS, carbachol, and KCl in group 3 were about 20%-40% of those in group 1. Contractile responses to EFS or KCl in PDE3i-treated BOO rats were not significantly different from those in group 3. Only high dose of PDE3i treatment in BOO rats caused a statistically significant increase in the response to carbachol compared with group 3. CONCLUSION: PDE3i has a small but significant protective effect on the contractile dysfunction induced by a 4-week BOO in rats, although the increase in bladder mass was not altered. PDE3i could be a useful protection against contractile dysfunction of the obstructed bladder.

Nocturia and sleep quality after transurethral resection of the prostate.

OBJECTIVES: To evaluate the clinical efficacy of transurethral resection of the prostate on nocturia and sleep disorders in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. METHODS: A prospective multicenter study including lower urinary tract symptoms suggestive of benign prostatic obstruction patients with nocturia (twice or more) undergoing transurethral resection of the prostate was carried out. All patients were assessed using the International Prostate Symptom Score and the Pittsburgh Sleep Quality Index at baseline, and 6 months after transurethral resection of the prostate. RESULTS: Overall, 49 patients were included in the study. A total of 20 of them (41%) had a sleep disorder defined as a score of 5.5 or more on the Pittsburgh Sleep Quality Index global score. The nocturia score significantly correlated with component 4 of the Pittsburgh Sleep Quality Index (habitual sleep efficiency). Nocturia significantly decreased after transurethral resection of the prostate from 3.0 ± 1.2 to 1.9 ± 0.8, whereas the global Pittsburgh Sleep Quality Index score did not. In 20 patients with a sleep disorder before transurethral resection of the prostate, subjective sleep quality (component 1) and habitual sleep efficiency (component 4) significantly decreased after transurethral resection of the prostate, but this was not the case for the global Pittsburgh Sleep Quality Index score. In 16 patients with a persistent sleep disorder after transurethral resection of the prostate, International Prostate Symptom Score, voiding and storage symptoms score were higher than those of patients without a sleep disorder, although the nocturia score improved equivalently in both groups. CONCLUSIONS: Transurethral resection of the prostate diminishes nocturnal urinary frequency and partly improves sleep quality in patients with nocturia and lower urinary tract symptoms suggestive of benign prostatic obstruction. A persistent sleep disorder after transurethral resection of the prostate is associated with persistent voiding and storage symptoms.

[A case of eosinophilic cystitis mimicking an invasive bladder cancer].

A 60-year-old woman was referred to our hospital because of gross hematuria, right lumbar pain and lower abdominal pain. Computed tomography (CT) scan revealed hydronephrosis of the right kidney, irregular bladder wall thickening at the right lateral and posterior portion and external iliac lymph node swelling of the right side. Laboratory data revealed disseminated intravascular coagulation syndrome (DIC) and eosinophilia. Because she developed a high fever that was caused by acute obstructive pyelonephritis of the right kidney, percutaneous nephrostomy was placed and the therapy for DIC was initiated. Pathological examination of transurethral resection of bladder tumor performed twice showed no malignancy but inflammatory infiltration of many eosinocytes, leading to the diagnosis of eosinophilic cystitis (EC). We considered the possibility of allergic reaction to the drugs she was taking as the etiology of EC and discontinued all drugs. Although eosinophilia was resolved afterward, she then developed brain infarction, followed by cerebral hemorrhage. She was transferred to a rehabilitation hospital for long-term care. CT scan that was performed 4 months after the initial presentation showed the resolution of hydronephrosis of the right kidney and external iliac lymph node swelling and the improvement of bladder wall thickness. Hydronephrosis of the right kidney has not recurred after removing the nephrostomy catheter. EC is a rare condition that could mimic an invasive bladder cancer. EC should be considered if bladder tumor is associated with eosinophilia. Therapeutic consideration for thromboembolic events should be made in patients with EC.

Urodynamic effects of dutasteride add-on therapy to alpha-adrenergic antagonist for patients with benign prostatic enlargement: prospective pressure-flow study.

AIMS: We prospectively investigated the effect of dutasteride on clinical and urodynamic parameters in patients with benign prostatic enlargement (BPE). MATERIALS AND METHODS: A prospective study was conducted in consecutive 52 patients with BPE who had not been satisfied with alpha-adrenergic antagonist monotherapy. Inclusion criteria were prostate volume (PV) ≥30 ml and the International Prostate Symptom Score (IPSS) ≥8 or QOL index ≥3 under administration of an alpha-adrenergic antagonist without anticholinergic agent. Before and 24 weeks after dutasteride (0.5 mg daily) add-on treatment with preceding alpha-adrenergic antagonist, we assessed IPSS, uroflowmetry (UFM), filling cystometry, and pressure-flow study (PFS). RESULTS: Dutasteride add-on treatment significantly improved IPSS (from 18.4 ± 7.5 to 13.8 ± 7.3) and maximum flow rate (from 11.4 ± 5.6 to 13.0 ± 6.8 ml/sec). Maximum cystometric capacity on filling cystometry did not change significantly by dutasteride add-on treatment (221 ± 97 and 240 ± 104 ml before and after dutasteride add-on, respectively). All of the 41 patients with detrusor overactivity (DO) before dutasteride add-on treatment showed apparent reduction in the amplitude of involuntary detrusor contraction after dutasteride add-on treatment, including seven in whom DO disappeared. Dutasteride significantly reduced PV from 66.4 ± 31.9 to 47.6 ± 26.1 ml. In PFS, detrusor pressure at maximum flow rate (PdetQmax) significantly decreased from 71.5 ± 30.1 to 59.1 ± 24.9 cmH2O after dutasteride add-on treatment. Bladder outlet obstruction index (BOOI) also decreased significantly from 55.2 ± 31.9 to 42.3 ± 27.9, and obstruction grade assessed by the Schäfer nomogram significantly improved. CONCLUSIONS: Dutasteride can improve lower urinary tract symptoms by improving storage bladder function and relieving obstruction.

Bladder function in 17ß-estradiol-induced nonbacterial prostatitis model in Wistar rat.

OBJECTIVES: To investigate bladder function in a model of nonbacterial prostatitis (NBP) induced in castrated rats by 17ß-estradiol injection. METHODS: Ten-month-old male Wistar rats were divided into two groups, sham and NBP (both N = 8). NBP was induced by castration followed by daily subcutaneous injection of 17ß-estradiol for 30 days. On the 31st day after surgery, we investigated (1) voiding behavior, (2) bladder blood flow (BBF), (3) prostate and bladder weight, and proinflammatory cytokines (TNF-α and CXCL1) levels and (4) bladder contractile responses to electrical field stimulation (EFS), carbachol and KCl. RESULTS: (1) Voiding behavior (average micturition volume, total urine volume and number of micturitions) and (2) BBF were not significantly different between the sham and NBP groups. (3) NBP led to a significant decrease in prostatic weight and increase in proinflammatory cytokine levels in the prostate, but NBP did not cause a significant change in bladder weight or proinflammatory cytokine levels in the bladder. (4) Bladder contractile forces in response to EFS, carbachol and KCl were not significantly affected by NBP. CONCLUSIONS: In this rat model, NBP did not cause a significant change in the level of proinflammatory cytokines in the bladder and affect bladder function.

Effect of intrathecal administration of E-series prostaglandin 1 receptor antagonist in a cyclophosphamide-induced cystitis rat model.

OBJECTIVES: To investigate the effect of intrathecal administration of E-series prostaglandin 1 antagonist in cyclophosphamide-induced murine cystitis. METHODS: Female Wistar rats were used for this experimental study. Intrathecal administration of E-series prostaglandin 1 antagonist (ONO-8711; 0.5, 5 and 50 µg) in sham controls and rats with cystitis induced by a single intraperitoneal injection of cyclophosphamide (300 mg/kg) was assessed by evaluating micturition pressure and intercontraction interval using a conscious-filling cystometry at 48 h after cyclophosphamide or saline injection. In both groups, prostaglandin E2 concentrations and the expression of E-series prostaglandin 1 receptor in the spinal cord were measured by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction, respectively. RESULTS: Rats with cyclophosphamide-induced cystitis showed a shorter intercontraction interval compared with controls, where the cumulative intrathecal administration of ONO-8711 did not significantly change micturition pressure or intercontraction interval compared with the baseline. In rats with cyclophosphamide-induced cystitis, each dose of ONO-8711 significantly increased the intercontraction interval compared with the baseline (46% increase at 50 µg intrathecally). Polymerase chain reaction revealed the expression of E-series prostaglandin 1 receptor in the spinal cord of both sham and cyclophosphamide-induced cystitis rats. In rats with cyclophosphamide-induced cystitis, PGE2 concentration in the dorsal horn of the L5-6 spinal cord was significantly higher than that in controls (3.55 ± 1.24 vs 0.99 ± 0.06 pg/mg tissue). CONCLUSIONS: In rats with cyclophosphamide-induced cystitis, urinary frequency seems to be caused by prostaglandin E2 acting on E-series prostaglandin 1 receptor at the level of the spinal cord. Blockade of the spinal E-series prostaglandin 1 receptor by ONO-8711 might have a therapeutic potential in the control of interstitial cystitis/bladder pain syndrome.

[Add-on effect of dutasteride in patients with benign prostatic hyperplasia treated with alpha blocker : its effect on overactive bladder].

We investigated the add-on effect of dutasteride (0.5 mg once a day) on lower urinary tract symptoms (LUTS), prostate volume (PV), and serum prostate specific antigen (PSA) and testosterone level in 72 patients with benign prostatic hyperplasia (BPH) who had been treated with alpha-blocker monotherapy. Inclusion criteria were men with BPH who had PV ≧30 ml and international prostate symptom score (IPSS) ≧8 or quality of life (QOL) index ≧3 under alpha-blocker monotherapy for more than 3 months. At the baseline, 12 and 24 weeks after dutasteride add-on, we assessed IPSS, overactive bladder symptom score (OABSS), PV, serum PSA and testosterone. Among 47 patients (65%) with OAB diagnosed by OABSS, responders were defined as those with urgency score of OABSS ＜2 or total score of OABSS ＜3. At the 24th week, dutasteride significantly improved IPSS (-4.2) and OABSS (-1.9) and reduced PV (-29%) compared with the baseline. Furthermore, dutasteride significantly decreased serum PSA (-45%) and increased testosterone (36%). Among OAB patients, dutasteride significantly improved urgency and urgency incontinence but not nocturia. Responders had lower OABSS, urgency incontinence score and serum testosterone at the baseline than non-responders. In conclusion, dutasteride add-on therapy is beneficial in patients with BPH who do not show enough improvement with alpha-blocker monotherapy.