Add-on anticholinergic therapy for residual nocturia in patients with lower urinary tract symptoms receiving α1-blocker treatment: a multi-centre, prospective, randomised study.

PURPOSE: To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume. RESULTS AND LIMITATIONS: Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, -0.6 ± 0.9 in IM twice/day, and -0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged. CONCLUSIONS: A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.

[Analgesic effect of oral tramadol on transrectal ultrasound-guided needle biopsy of the prostate in a randomized double-blind study].

A total of 121 Japanese patients scheduled for prostate biopsy were randomly and double-blindly assigned to be given a single oral dose of 100 mg Tramadol mixed with 20 ml of sugar syrup or placebo, 30 minutes before the procedure. Pain severity was measured by verbal rating scale (VRS) and visual analog scales (VAS). We also analyzed cardio-respiratory parameters and complications. Of 121 patients, 117 replied validly to VRS and VAS ; and 91 of 117 patients replied to the cohort questionnaire for analysis of the late disorder, patient's impression, prolonged pain and past history of hemorrhoid treatment. Tramadol showed no significant effect on pain severity indicated by VRS and VAS, and no change in cardiorespiratory parameters. Furthermore, 70 patients without a history of hemorrhoid treatment, showed no significant analgesic benefits of Tramadol during the biopsy. In total, 3 patients had side effects of vomiting (CTCAE : grade 1)6), which subsided spontaneously. The oral administration of a single dose of 100 mg Tramadol 30 minutes before a transrectal needle biopsy of the prostate was safe, but was not effective to calm down the pain severity.

A successful conception by a shift from human menopausal gonadotropin therapy to therapy with recombinant human follicular-stimulating hormone for the treatment of male hypogonadotropic hypogonadism.

Stimulatory therapy with gonadotropins effectively induces spermatogenesis and increases the chances of successful reproduction. However, the optimal treatment modality and schedule, and required duration of treatment have not been determined. A 27-year-old man presented with erectile and ejaculatory disorder. Endocrinological examinations revealed isolated luteinizing hormone-releasing hormone (LHRH) deficiency of the hypothalamus, resulting in hypogonadotropic hypogonadism. No causative abnormality was detected in imaging studies. Having a diagnosis of adult-onset hypogonadotropic hypogonadism, the patient received pulsatile subcutaneous human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG). Hypogonadism did not improve with hCG/hMG combination therapy. He was successfully treated with the replacement therapy from hMG into recombinant human follicular-stimulating hormone (rhFSH) for induction of spermatogenesis, along with pregnancy in the female partner.

[Neuroendocrine differentiation in adenocarcinoma of the prostate during hormonal treatment : a case report].

A case of neuroendocrine (NE) differentiated prostate cancer is reported herein, which was progressed with NE differentiation during hormonal treatment in adenocarcinoma of the prostate. A 65-year-old man was admitted to our department with increased serum prostate specific antigen (PSA) (150 ng/ml). A prostate biopsy was performed and histological examinations indicated poorly differentiated adenocarcinoma with a Gleason score of 5 + 4 = 9. Further examinations showed metastases to systemic bones. The clinical stage was T3bN0M1b and hormonal therapy using leuprorelin was started. Eighteen months after hormonal therapy, the serum PSA level declined to 1.702 ng/ml. He subsequently experienced edema in his legs. Computed tomography (CT) demonstrated enlargement of the prostate and swelling of multiple pelvic lymph nodes. Immunohistochemical examination of a re-biopsy specimen revealed a neuroendocrine carcinoma. The neuron-specific enolase (NSE) level was 50.9 ng/ml. The treatment measure was changed from hormonal therapy to combination chemotherapy comprising cisplatin (CDDP) and irinotecan (CPT-11). Pelvic radiotherapy (50 Gy) was then performed. Two courses of the chemotherapy resulted in a great reduction of the tumor volume. However, he had liver metastases 3 months later. His condition worsened rapidly and he died at 8 months after definite diagnosis.

[Effect of prophylactic intravesical instillation of BCG for superficial bladder cancer].

Between January 1997 and February 2005, a total of 106 patients with superficial bladder cancer were treated with transurethral resection of bladder tumor followed by intravesical instillation of Tokyo 172 strain bacillus Calmette-Guerin (BCG) once a week for six weeks. The endpoints were tumor recurrence, tumor progression, and disease-specific survival. At a median follow-up of 27 months (range 2 to 105 months), 67 patients (63.2%) were recurrence-free and superficial recurrence including disease progressed with local invasion was noted in 39 patients (36.8%). The non-recurrence rate at one and three years were 75.9 and 54.6%. Twenty-four patients received an additional course of BCG instillation, and 14 (58.3%) showed no further recurrence. Thus, the overall success rate of 2 courses of BCG instillation was 76.4% (81 of 106 patients). Nine patients (8.5%) had progression and died of cancer. There was no significant differernce in recurrence rate among tumor characteristics. However, there was a significant differernce in survival rate between non-invasive and invasive tumor shape (p = 0.0189). Univariate analysis (Cox's proportional hazard model) demonstrated that tumor shape was associated with survival (p = 0.0486). Multivariate analysis demonstrated that gender and tumor shape were associated with survival (p = 0.0183, 0.025). Adverse effects included bladder irritability in 16 patients (15.1%), gross hematuria in 15 (14.2%), fever in 24 (22.6%), contracted bladder in 1 (0.9%) and interstitial pneumonitis in 1 (0.9%). Interstitial pneumonitis improved after pulse steroid therapy. BCG was found to be very useful for the treatment of superficial bladder cancer. Intravesical BCG instillation was effective for first recurrent superficial bladder cancer because of the low recurrence rate after a second instillation of BCG.

[A pheochromocytoma of urinary bladder treated with neoadjuvant chemotherapy].

A 69-year-old female presented with hypertension and a solid mass in the bladder on ultrasonography. Cystoscopy revealed a submucosal tumor in the right lateral wall of the bladder. A transurethral resection was performed. Histologically, pathologic examination revealed a malignant pheochromocytoma. She refused surgical therapy and radiation therapy. She had no treatment for two years. She suddenly complained of gross hematuria. T2-weighted magnetic resonance imaging showed a bladder tumor of high intensity and extra-bladder invasion. She was treated with chemotherapy (CVD) for 26 cycles. Since the tumor size was reduced, she was referred to our hospital for operative indication. Partial cystectomy was performed. Histologically, the tumor was a pheochromocytoma of the urinary bladder. Ten months after the operation, she has no clinical evidence of recurrence.

[Renal cell carcinoma in a horseshoe kidney: a case report].

A 59-year-old man visited another hospital with a chief complaint of malaise. Radiological examinations revealed a renal cell carcinoma associated with horseshoe kidney. He was referred to our hospital. The patient was successfully treated with open partial nephrectomy following isthmus division. Histological findings exhibited grade 2, pT1a, clear cell type, renal cell carcinoma. He is free of disease at twelve months after the operation.

Marked regression of liver metastasis by combined therapy of ultrasound-mediated NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse.

Nuclear factor-kappaB (NF kappaB) plays a pivotal role in cancer progression. In this study, we developed a decoy cis-element oligo-deoxyribonucleic acid against NF kappaB-binding site (NF kappaB-decoy), which effectively inhibits NF kappaB activity, and tested the effect of combined therapy comprising local transfection of NF kappaB-decoy into the liver and transportal injection of paclitaxel on cancer growth and metastasis using an orthotopic murine model of colon cancer liver metastasis. For NF kappaB-decoy transfection, we employed a novel approach using ultrasound exposure with an echocardiographic contrast agent, Optison. We examined the influence of NF kappaB-decoy transfer on susceptibility to paclitaxel in cancer cells and the mechanism involved using several in vitro analysis systems. We then studied the in vivo effect of combined NF kappaB-decoy transfer and paclitaxel in preventing cancer progression using a murine model of liver metastasis created by splenic injection of a human colon cancer cell line, HT29. In vitro experiments, including MTT-assay, fluorescence-activated cell sorter and cDNA array analysis, revealed that NF kappaB-decoy transfer significantly increased the susceptibility of cancer cells to paclitaxel, and that decreased expression of anti-apoptotic genes along with increased expression of genes relevant to the apoptosis-promotor may be involved. In vivo experiments showed that local transfection of NF kappaB-decoy into the liver followed by portal injection of paclitaxel effectively induced cancer cell apoptosis in the liver metastasis, and significantly prolonged animal survival compared to controls, without notable side effects. In conclusion, a combination of local NF kappaB-decoy transfer into the liver and transportal injection of paclitaxel may be a safe and effective new therapy for liver metastasis.

Basal cell carcinoma of the prostate: report of a case and review of the published reports.

Prostatic basal cell carcinoma (BCC), a distinctive variant of adenocarcinoma, is rare. We report a patient with pure basaloid BCC showing an extraprostatic extension and lymph node metastases. A 67-year-old man with urinary outlet obstruction was referred to our hospital. Digital rectal examination disclosed a stony hard prostate. Serum prostate-specific antigen and prostatic acid phosphatase were within the normal range. Transrectal needle biopsy of the prostate was followed by transurethral resection as symptomatic treatment. The lesion was diagnosed histopathologically as BCC. Despite antiandrogen therapy distant metastases developed, and the patient died 5 months postoperatively. We discuss the histological and immunohistochemical findings in this case.

[Prostatic stromal sarcoma: a case report].

Prostatic stromal sarcoma (PSS) is an unusual lesion that is reported only occasionally. Here we describe a case of prostatic stromal sarcoma in a 33-year-old man who had complained of perineal pain. The serum prostate-specific antigen (PSA) level was above the normal limit at 5.8 ng/ml, and abdominal computed tomography (CT) revealed a giant mass in the retrovesical region. Chest CT demonstrated lung metastases. Specimens obtained by transrectal needle biopsy of the prostate suggested a mesenchymal tumor, but a precise diagnosis required a larger specimen. Palliative transurethral resection (TUR-P) was performed because of obstruction of the urogenital tract, and the final diagnosis was made from this specimen. The tumor contained yellowish gelatinous materials, and the stromal element appeared histologically malignant, with increased cellularity, mitotic figures and pleomorphism. The histological diagnosis was PSS, and the patient received VIP (etoposide, ifosfamide, cisplatin) chemotherapy regimen. However, the pelvic mass continued to increase in size, and the patient's condition rapidly deteriorated and he died. Sarcoma of the prostate gland showing aggressive behavior is quite rare. The detailed histological and immunohistochemical findings in this case are reported, together with a review of the literature.

[Intravesical instillation with epirubicin as a prophylactic treatment for superficial bladder cancer--using two different schedules].

Intravesical chemotherapy is performed after transurethral resection of bladder tumor (TURBT) for superficial bladder cancer. We conducted a prospective randomized controlled study on the prophylactic effects of intravesical instillation of epirubicin (EPI) against recurrence to determine the effective administration schedule. Between April 1999 and March 2003, 54 patients with superficial bladder tumor (pTa or pT1, and G1 or G2 cancer) were assigned to two groups (25 in Group A, 29 in Group B) after TURBT. The schedule of instillation (intravesically 40 mg of EPI dissolved in 40 ml saline) was subsequently once every two weeks for 3 months (7 times) starting one week after TURBT (Group A, short period), and subsequently added every two weeks for 3 months starting 6 months after TURBT (Group B, long period). The patients were followed up by cystoscopy and urinary cytology. There was no significant difference in non-recurrence rates after either one year (A; 62.5%, B; 82.8%) or three years (A; 53.6%, B; 67.3%). A univariate analysis demonstrated that tumor grade and staging were significant predictors of high risk for recurrence. A multivariate analysis performed by using the Cox's proportional hazard model showed that the schedule of instillation was an independent prognostic factor for reccurence. In the present study, only 2 patients showed progression and one patient died of UC. There was no adverse event that forced discontinuation of the therapy. In conclusion, epirubicin instillation influenced the prevention of recurrence, but the benefit of long-term period was not confirmed.

[Port-site metastasis after retroperitoneoscopy-assisted nephroureterectomy and cystectomy for bladder cancer invading the ureter: a case report].

We report a case of port-site metastasis of bladder cancer after left retroperitoneoscopy-assisted nephroureterectomy and cystectomy. The patient was a 73-year-old man with a chief complaint of gross hematuria. The diagnosis was invasive bladder cancer with bone metastasis. He received two courses of chemotherapy (methotrexate, vinblastine, adriamycin, cisplatin), and this resulted in resolution of the bone metastases. Two months later, abdominal and pelvic computed tomography showed a bladder tumor invading the left lower ureter with hydronephrosis. Left retroperitoneoscopy-assisted nephroureterectomy and cystectomy were performed. The patient was unable to undergo systemic chemotherapy because of renal dysfunction. Four months later, a lateral abdominal wall tumor was found at a port-site, and needle biopsy confirmed this to be metastatic urothelial carcinoma. Clinicians need to be aware of port-site metastasis, particularly in patients with UC, and take steps to prevent it during laparoscopic procedures.

[Case of renal artery aneurysm treated by endovascular embolization].

A 60-year-old man was admitted to our department with a left renal artery aneurysm that was detected while performing an examination for dermatomyositis. A 3-dimensional image showed a saccular renal aneurysm whose diameter was 6 cm. He required operative intervention. Because of the location (near the renal hilum), selective transcatheter embolization using an interlocking detachable coil was performed for endovascular treatment. The postoperative course was uneventful. This method appears to be a good choice for the treatment of renal artery aneurysm, considering its safety and the likelihood of success.

[Skin reaction induced by subcutaneous injection of LH-RH analogue].

Luteinizing hormone-releasing hormone agonist (LH-RH analogue) therapy, is one of the most widely used hormonal therapies. Recently, subcutaneous injection of a new long acting 3-month LHRH analogue depot has been developed. We investigated the adverse events induced by injection of an LH-RH analogue in 82 patients (median age was 75 year old, 59-87) using our questionnaire. Forty-eight and 34 cases had been administered leuprorelin acetate (LSR) and goserelin acetate (ZLA). The presentation rate of skin reaction was 8.8% (3/34) in the ZLA group and 14.6% (7/48) in the LSR group. There was no significant difference in rate of skin reaction between the LSR and ZLA group (p = 0.5113). Eight patients had induration (6 in LSR 2 in ZLA). We also present a case of subcutaneous granuloma formation at the injection site after using the three-month type preparation of leuprorelin acetate. We should be aware of the risk of skin reactions at the injection site and monitor carefully when using an LH-RH analogue.

[Renal cell carcinoma with asynchronous contralateral adrenal metastasis and liver cirrhosis (four years after surgery): a case report].

We report a case of adrenal metastasis from renal cell carcinoma. A 52-year-old man was referred to our hospital for a left renal mass. A computed tomography revealed a left renal tumor. Liver cirrhosis and splenomegaly were observed. Blood tests revealed pancytopenia; platelet count was 2.5 x 10(4)/mm3. The patient was treated by partial splenic embolization (PSE) in an attempt to ensure a safe nephrectomy. After the embolization, his platelet count increased to 6.1 x 10(4)/mm3, and left nephrectomy was performed successfully. Histopathological finding was renal cell carcinoma (RCC). We concluded that PSE before surgery was useful for the patients with thrombocytopenia due to hypersplenism. Four years after surgery, computed tomography revealed the presence of a mass on the right adrenal gland. He was suspected of having a non-functioning adrenal tumor. Metastasis of the RCC was suspected and right adrenalectomy was performed by a laparoscopic procedure. Histologically, the mass was identified as a RCC metastasis. It is clinically rare for an RCC metastasis to the contralateral adrenal gland to occur.

[Ureteral-abdominal aortic fistula during the exchange of ureteral stenting: a case report].

We report a case of a patient with a fistula between the left ureter and abdominal aorta. The patient was a 44-year-old male who had undergone radiation therapy (intraoperative: 25 Gy, external beam: 50 Gy) and chemotherapy (CDDP: 250 mg) for retroperitoneal lymph node metastasis from seminoma. His postoperative course was complicated by stenosis of bilateral ureters, which were treated by indwelling double J-stents. Fifteen years after the operation, gross hematuria occurred from the left ureteral orifice when exchanging the left ureteral double J-stent. Computed tomographic scan demonstrated left ureteral-abdominal aortic fistula formation at the crossing point. Massive hemorrhage was suspected to have prompt fistula formation between the left ureter and the aorta. At exploration, there was a fistula of about 7 mm in diameter at the anterior surface of the aorta, and the stent was presumably inserted from it. The aortic fistula was successfully closed. In addition, the left ureter was ligated proximal to the fistula and percutaneous left nephrostomy were performed. His postoperative course was uneventful. We should be aware that uretero-arterial fistula can occur as a serious complication of ureteral catheter exchange after prolonged ureteral stenting and radiation therapy.

[Renal arteriovenous fistula: a case report].

Congenital arteriovenous fistula(AVF) of the kidney is a rare condition. We report a case of renal AVF with chief complaints of macroscopic hematuria, and treated with transcatheter arterial embolization (TAE) using coils. The patient was diagnosed as having left renal AVF by Color Doppler ultrasound. The signs and symptoms disappeared after embolization. The clinical course of a case is reported and the literature is reviewed. Color Doppler ultrasound is required to give a definite diagnosis of renal AVF.

[Urethral adenocarcinoma in a female: a case report].

A 67-year-old female was referred to our hospital with the chief complaint of genital bleeding. Physical examination revealed a thumb's-head-sized tumor at the external urethral meatus. Histopathological examination of the biopsy specimen suggested papillary carcinoma. She underwent partial urethrectomy with negative surgical margins. The final pathological diagnosis of the tumor was papillary adenocarcinoma, of Stage A according to Grabstald's classification. She is alive with no evidence of recurrence at 5 months after surgery.

[A case of prostatic cancer discovered from lung metastatic lesions].

We report a case in a 70-year-old patient indicated to have a metastatic lesion from a chest X-ray taken during a medical examination. His blood prostatic specific antigen level was very high at 100 ng/ml (normal, less than 4.0 ng/ml). Palpation of the prostate disclosed enlargement to hen's egg size with an irregular surface and indurations bilaterally. Transrectal sextant needle biopsy of the prostate was performed, revealing moderately differentiated adenocarcinoma. Computed tomography (CT) scan and bone scintigraphy showed intrapelvic lymphnode adenopathy and metastasis to the right pubic bone. Under a diagnosis of stage D2 prostate cancer, we initiated endocrine therapy (luteinizing hormone-releasing hormone analogue depot every 4 weeks and bicalutamide). Androgen blockage was very effective and after 6 months, the PSA level had decreased markedly to below 0.2 ng/ml. Sixteen months later, pulmonary metastasis completely disappeared. He is currently free from recurrence and progressing well.

[A case of transitional cell carcinoma of the bladder in a juvenile patient].

A 17-year-old male was referred to our hospital with the chief complaint of right back pain. Cystoscopic examination revealed a papillary tumor on the posterior wall following detection on screening ultrasound examination revealed a tumor in the bladder. Transurethral resection of the bladder tumor was performed. Histological examination of the excised tumor revealed transitional cell carcinoma, grade 1, pTa. No recurrence has been observed for about 1 year postoperatively.