Masafumi Kita

To investigate the efficacy of combination treatment of degarelix and antiandrogen in patients with prostate cancer. 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. 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. 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.

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 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.

Using a videourodynamic study, we examined the efficacy of combination therapy with mirabegron for anticholinergic-resistant neurogenic bladder. We retrospectively studied 7 patients with neurogenic bladder (5 males and 2 females) who had detrusor overactivity (DO) or low compliance bladder (＜10 ml/cmH2O) despite taking anticholinergic medication. Bladder deformity was categorized from G0 to G3 by Ogawa's classification. Mean age of study patients was 51 years (25-76). Underlying diseases were spinal cord injury in 3 patients, spina bifida in 2, spinal cord infarction in 1, and post-radical hysterectomy in 1. Preceding anticholinergic medication was solifenacin 5 mg in 1 patient, solifenacin 10 mg in 5, and tolterodine 4 mg in 1. Before mirabegron, bladder deformity was G1 in 4 patients, G2 in 1 and G3 in 2, and vesicoureteral reflux (VUR) was detected in 3 patients. Five and 4 patients had detrusor overactivity and low compliance bladder, respectively. Videourodynamic study was reevaluated at a mean of 7 months (2- 12 months) after mirabegron. After mirabegron, urinary incontinence was improved in all patients. G3 bladder deformity was improved to G2 and G1 in one patient each, and VUR disappeared in all 3 patients. DO disappeared in 2 of the 5 patients, and bladder compliance was improved in all 4 patients with low compliance bladder. In conclusion, combination therapy of mirabegron is effective and beneficial for anticholinergic-resistant neurogenic bladder.

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.

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.

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.

Objective To investigate the relationship between chronic periodontal disease (CPD) and lower urinary tract symptoms (LUTS) in both sexes. Methods The interview sheet of the CPD self‐checklist and LUTS was distributed to 600 adult men and women (300 each) who visited the first dental examination at dental clinics. The International Prostate Symptom Score (IPSS) questionnaire/Quality Of Life (IPSS/QOL) and Overactive Bladder Symptom Score (OABSS) were used to assess LUTS. The relationship between the CPD score and LUTS or OAB was examined. Results The interview sheet was collected from 88 men (50.9 ± 16.6 years old) and 97 women (51.1 ± 15.5 years old). There was no statistically significant correlation between the CPD score and age, or between the CPD score and the presence of LUTS in either men or women. However, urgency and weak stream score of IPSS were significantly correlated with the severity of CPD in both sexes. Significant correlation between the severity of CPD and the presence of OAB was only noted in men but not in women. Conclusions The present study demonstrated for the first time that some storage and voiding symptoms were significantly associated with CPD in both sexes. Thus, although CPD and LUTS seem to have common pathophysiological factors, the interrelationship between CPD and LUTS is slightly different between men and women.

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.

Aims To evaluate bladder vascular resistance before and after transurethral resection of the prostate (TURP). Methods Thirty‐three patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction were prospectively studied. We analyzed correlations of bladder vascular resistance with various factors including age, vascular risk factors, symptom score, prostate volume (PV), and urodynamic parameters before and 3 months after TURP. Using contrast‐enhanced color Doppler ultrasonography for measuring bladder vascular resistance, resistive index (RI) of vesical arteries was calculated. Results Compared with healthy young male (n = 10) and age‐matched controls (n = 10), the study patients had a higher preoperative RI (0.403 ± 0.100, 0.436 ± 0.042, and 0.561 ± 0.089, respectively; P < 0.01). Preoperative RI was significantly higher in patients with PV ≥ 60 ml versus P < 0.01), and in patients with severe obstruction versus mild/moderate obstruction (0.615 ± 0.087 vs. 0.534 ± 0.078; P = 0.017). Overall RI decreased significantly after TURP (from 0.561 ± 0.089 to 0.450 ± 0.086; P < 0.001). In patients with persistent urgency after TURP, RI was less improved than in those without urgency after TURP (change of RI 0.068 ± 0.098 vs. 0.135 ± 0.090; P < 0.05). This study was limited by a small sample size. Conclusions Bladder vascular resistance in patients with LUTS was elevated in correlation with PV and severity of obstruction. Although bladder vascular resistance decreased significantly after TURP in overall patients, less reduction of vascular resistance was related to persistent urgency after TURP, implying that persistent urgency after TURP might be caused by persistent bladder ischemia. Neurourol. Urodynam. 31:659–663, 2012.