Comparison of mirabegron and vibegron for clinical efficacy and safety in female patients with overactive bladder: a multicenter prospective randomized crossover trial.

PURPOSE: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients. METHODS: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable. RESULTS: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron. CONCLUSION: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence.

Effect of imidafenacin on nocturia and sleep disorder in patients with overactive bladder.

OBJECTIVE: To evaluate the efficacy of imidafenacin on nocturia and sleep disorder in patients with overactive bladder (OAB). PATIENTS AND METHODS: A prospective multicenter study of imidafenacin 0.1 mg twice daily for patients with OAB and nocturia was conducted. At baseline and at week 4 and 8, patients were assessed using the overactive bladder symptom score (OABSS), frequency volume charts (FVC) and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Treatment with imidafenacin significantly improved OAB symptoms. Imidafenacin also improved PSQI, especially subjective sleep quality, sleep latency and daytime dysfunction. In FVC, the number of daytime voids and nighttime voids significantly decreased and average voided volume significantly increased after imidafenacin. Subanalysis of FVC based on the patients' age revealed that nocturnal polyuria was more often found in patients aged 75 years or over than in those aged under 75 years (79 vs. 55%, p < 0.05). Treatment with imidafenacin significantly reduced the nocturnal polyuria index only in patients aged 75 years or over. CONCLUSIONS: Imidafenacin can improve nocturia and sleep disorder in patients with OAB. The efficacy of imidafenacin on nocturia is attributable to an increase in bladder capacity and a decrease in nocturnal urine volume. We conclude that imidafenacin is an effective and safe drug for nocturia in patients with OAB.

[Bladder injury by penetration of artificial vessel graft].

Iatrogenic bladder injury by artificial vessel graft is extremely rare and only 3 cases have been reported. Herein, we report a case of bladder injury by penetration of artificial vessel graft. An 80-year-old male underwent a femoro-femoral crossover bypass surgery for arteriosclerosis obliterans in our hospital. Postoperatively he complained of urinary incontinence and was referred to the urology department. Ultrasonography for evaluating microscopic hematuria revealed a high echoic linear structure in the bladder and subsequent cystoscopy found an artificial vessel graft penetrating bladder wall. Vascular surgeons reconstructed femoro-femoral bypass and we removed the artificial vessel graft and repaired the injured bladder wall. This is the fourth case of bladder penetrating injury by artificial vessel graft and we summarize the reported cases.

Adrenalectomy for metastatic adrenal tumors.

The indications for adrenalectomy in cases of metastatic adrenal tumor remain controversial. To clarify indications and outcomes of adrenalectomy for adrenal metastasis, we performed a retrospective review of all 8 patients who underwent adrenalectomy for adrenal metastasis between 1990 and 2006 in Asahikawa Medical College Hospital. The Primary tumor was renal cell carcinoma in 2 cases, and eccrine poro carcinoma, rectal cancer, lung cancer, melanoma, bladder cancer and cancer of unknown origin in 1 case each. Open adrenalectomy was performed in all cases, including 1 case that was converted from laparoscopic adrenalectomy. Of the 4 patients with solitary adrenal metastasis, 3 were considered tumor-free after adrenalectomy, while the remaining patient was not due to unresectable primary tumor. Of the 3 patients with complete resection, one remained alive as of 88 months after adrenalectomy but was then lost to follow-up, and the other 2 patients remain alive 12 and 7 months after adrenalectomy. Of the 2 patients with other resectable metastasis who were tumor-free after removal of all metastases, one was alive 31 months postoperatively and the other died 23 months after operation. The remaining 2 cases with other unresectable metastasis died within 6 months after adrenalectomy. At least in cases of solitary adrenal metastasis, adrenalectomy can be effective if other valid methods are unavailable.

Case report of renal pelvic adenocarcinoma associated with a renal stone that produced carbohydrate antigen 125 and carbohydrate antigen 19-9.

A 68-year-old man underwent left side simple nephrectomy for symptomatic severe hydronephrosis with decreased function due to a renal stone. Because of severe adhesion around the kidney, the renal pelvic wall was torn during the operation. Pathological diagnosis was papillary adenocarcinoma of the renal pelvis with positive staining for carbohydrate antigen 125 (CA125) and carbohydrate antigen 19 9 (CA19-9). Retrospective analysis of preoperative blood sample showed a high level of CA125 and CA19-9. Four-cycle adjuvant chemotherapy with paclitaxel/carboplatin (TJ regimen) was performed. However, local recurrence developed 1 month after the termination of chemotherapy. Although papillary adenocarcinoma of the renal pelvis is extremely rare, the possibility of renal pelvic tumor should be kept in mind for patients who have a long-standing renal stone and hydronephrosis with irregularity at the renal pelvic wall. CA125 and CA19-9 can be useful markers for upper urinary tract tumor.

[A case report of urinary reconstruction by ileal neobladder performed 16 years after total cystectomy for bladder cancer].

We report a 59-year old male patient who successfully underwent urinary reconstruction by ileal neobladder that was performed 16 years after total cystectomy and ureterocutaneostomy for bladder cancer. He had been suffering from refractory contact dermatitis around the ureterocutaneostomy stoma and was referred to our hospital. In 2003, bilateral percutaneous nephrostomy was performed together with ureteral ligation at the most distal part. However recurrent pyelonephritis developed afterward because of nephrostomy catheter troubles and the patient's quality of life was markedly impaired. Then urinary reconstruction was planned in 2005. Because the urethra had not been resected and remained intact, ileal neobladder (Hautmann's method) was successfully created and he was free from nephrostomy catheter. Postoperatively there has been no recurrence of pyelonephritis. Long time insertion of nephrostomy catheter causes several complications, such as urinary tract infection and formation of urinary stones. To preserve renal function and improve quality of life, every chance for urinary reconstruction should be sought in those patients who suffer from upper urinary tract catheter troubles.

[A case of infected renal cyst suspected of originating from retrograde infection].

A 63-year-old man who had undergone Miles' operation for rectal cancer in another hospital was referred due to a high fever and renal failure. Abdominal computed tomographic (CT) scan revealed metastatic liver tumor, paraaortic lymph node swelling, bilateral hydronephrosis and a left simple renal cyst located at the lower pole. Bilateral ureteral stenting was undertaken for relieving ureteral obstruction. Serum creatinine and high fever improved immediately. However, at 11 days after the ureteral stenting the high fever recurred. CT scan and ultrasonography revealed persistent left hydronephrosis and a change of left simple renal cyst into infected cyst. After an exchange of left ureteral stent and percutaneous pus drainage from the left infected renal cyst, high fever declined immediately. A review of the literature suggests that this is the 100th case report of infected renal cyst in Japan. We discuss the clinical features, etiology, imaging study and treatment of infected renal cyst.

[Indication of repeat prostate biopsy for the diagnosis of prostate cancer].

There is no standard criterion for repeat prostate biopsy in cases with a negative initial biopsy. We retrospectively analyzed our experience of repeat prostate biopsy to establish its indication for the diagnosis of prostate cancer. From April 1997 to March 2005, 35 consecutive patients underwent repeat prostate biopsy at the department of Urology, Asahikawa Medical College Hospital because of clinically suspicious prostate cancer despite a negative initial biopsy. We compared patients' age, number of cores obtained during repeat biopsy, digital rectal examination findings, total prostate volume, the time from the first to the last biopsy, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity between cancer-positive and cancer-negative groups. Prostate cancer was detected in 17 of 35 patients (49%). Fifteen patients with prostate cancer were diagnosed by the first repeat biopsy and other 2 patients were diagnosed by the second repeat biopsy. A statistically significant difference was only noted in age and PSA density. Persistently elevated total PSA and a higher PSA density in cases with a negative initial biopsy might be a good indication of repeat prostate biopsy for the diagnosis of prostate cancer.

[Histological investigation of prostate cancer treated with hormonal agents].

The histological diagnosis of prostate cancer treated with hormonal agents is often difficult because of various morphological changes induced by androgen ablation. Immunostaining of cytokeratins may be useful to prevent the underdetection of cancer cells. We examined prostatic specimens with histological diagnosis of 11 pTO patients who had undergone neoadjuvant endocrine therapy followed by radical prostatectomy. Anti-cytokeratin antibody, AE1/AE3 was used to detect the prostatic epithelial cells. Anti-cytokeratin antibody, 34/3 E12 was used to detect the prostatic basal cells. The loss of basal cells indicates the acini to be cancer. The immunostaining with these antibodies revealed that 2 out of 11 cases had residual cancer and were not pTO. The immunostaining of cytokeratins was useful to detect the residual prostatic cancer after endocrine therapy.

[Case report of advanced renal cancer that showed different responses to the alteration of therapeutic cytokines].

We report a case of advanced renal cancer that showed different responses to the alteration of therapeutic cytokines. A 73-year-old man presented with asymptomatic macrohematuria, and was diagnosed as right renal cancer (11 x 9 x 9 cm in diameter) with metastases to abdominal and mediastinal lymph nodes (cT3bN2M1, stage IV). Transluminal embolization of the right renal artery was performed, and then he was treated by intramuscular administration of natural human interferon (IFN)-alpha (Sumiferon; 6 x 10(6) units) three times a week. Four months later, lymph node metastases enlarged, and human interleukin-2 therapy (intravenous administration; 1.4 x 10(6) units) was initiated instead of IFN-alpha. However, lymph node metastases further enlarged and multiple lung metastases newly appeared in 5 weeks after the alteration of the therapy. Then, the treatment was switched to intramuscular administration of another natural human IFN-alpha (OIF; 5 x 10(6) units) three times a week. In 3 months after OIF administration, all lung metastases disappeared. Lymph node metastases have shown no progression for 9 months after the switch to OIF. Different responses to the two types of IFN-alpha in this case may be caused by the difference in the composition of IFN-alpha subtypes. Alteration of therapeutic cytokines, especially a switch from one type to another IFN-alpha may be one of worth attempts even if other cytokines are not effective.

[Clinical significance of cystoscopy in transrectal prostate biopsy].

The clinical significance of cystoscopy in patients with benign prostatic hyperplasia or prostate cancer remains open to discussion. We have always performed cystoscopy with prostate biopsy and have discovered bladder cancer in some patients. The present study investigated the clinical significance of performing cystoscopy with prostate biopsy. Subjects were 458 patients who underwent cystoscopy and ultrasound-guided transrectal prostate biopsy from January 1998 to December 2004. Mean age of subjects was 71.3 years (range, 52-93 years). Prostate biopsy was performed modified Eskews systematic 5-region prostate biopsy (12 core). Some abnormalities were found in 43 of the 458 patients (9.3%). Among these 43 patients, bladder cancer was found in 11 patients (2.4%), and transurethral resection bladder tumor (TUR-Bt) was performed on all 11 patients. Pathological staging of bladder cancer was pT1 and G2 in all cases. Bladder stones were seen in 13 patients (2.8%), benign bladder tumor in 5 patients (1.1%), urethral polyp in 7 patients (1.5%), urethral stenosis in 6 patients (1.3%) and ureteral stones associated with ureterocele in 1 patient (0.2%). Appropriate examinations and treatments were performed for all cases. Cystoscopy may be needed at the time of prostate biopsy because: the above-mentioned abnormalities were first discovered on cystoscopy; and the frequency of bladder cancer was 2.4% for the total patient population, and endoscopic surgery was performed.

A case of metastatic renal cell carcinoma to the ovary.

A 52-year-old woman had a pathological fracture of the right femur. On histopathological examination bone metastasis from renal cell carcinoma was suspected. Abdominal computed tomography showed a heterogeneous mass (9.1 x 7.8 x 6.5 cm) in the left kidney and a cystic multilocular mass (12 x 10 cm) in the pelvis. Bone scintigraphy revealed an abnormal uptake in the left coracoid process, right third rib, and right distal femur and proximal tibia. Clinical diagnosis was left renal cancer with multiple bone metastases (cT2NOM1, stage IV) and a right ovarian tumor. We performed left radical nephrectomy and resection of right ovarian tumor by bilateral adnexectomy. On histopathological examination, the left kidney tumor was diagnosed as renal cell carcinoma (clear cell carcinoma with chromophobe component, G2 > G1). The ovarian tumor consisted of carcinoma of clear cell type (G2) that resembled components of left renal cell carcinoma, confirming the diagnosis of metastatic renal clear cell carcinoma to the ovary. Although she underwent immunotherapy with interferon, she died 10 months after nephrectomy. Metastasis to the ovary from renal clear cell carcinoma is very rare and only 18 cases have been reported in the literature. This rarity may be related to the difficulty of differential diagnosis between metastatic renal cell carcinoma to the ovary and primary ovarian clear cell carcinoma. Elaborate analysis of microscopic features and immunohistochemical profiles may help in the distinction of this metastatic lesion.

[A case of a ureteral inflammatory pseudotumor].

The patient was a 28-year-old woman. In February 2002, she visited another physician due to acute pyelonephritis. Based on CT findings, a lower ureteral stricture caused by a benign extraureteral tumor was diagnosed. The patient was being monitored by periodic exchange of ureteral stents. In February 2003, the patient visited our department seeking a second opinion. Retrograde pyelography showed an elliptical filling defect in the lower urinary tract. Ureteroscopy showed that the surface of the tumor was mostly smooth, regular and partially papillary. Biopsy was performed, and histological analysis revealed only nonspecific inflammation. In December 2003, based on a diagnosis of benign ureteral tumor, we performed partial resection of the right urinary tract and ureterocystoneostomy. As rapid intraoperative pathological analysis confirmed an inflammatory pseudotumor, total nephroureterectomy was avoided.

[A case of late recurrence of germ cell tumor].

A 19-year-old male was admitted to our hospital because of retroperitoneal tumor and metastases in the lung and liver. He underwent chemotherapy followed by retroperitoneal lymph node dissection and pathologic examination revealed mostly necrotic tissue with a small amount of teratomatous tissue. Two years later, a hyper echoic lesion was found in the left testis, and left high orchiectomy was performed. The resected specimen appeared to be a burned-out testicular tumor. Ten years later, CT scan detected lymph node swelling in the retroperitoneum, and excision of the tumor was performed. Pathologic examination revealed well-differentiated adenocarcinoma. Since no primary adenocarcinoma was found, this case was considered late relapse of a germ cell tumor.

[Postoperative hypoglycemia after resection of pheochromocytoma: a case report].

We report a case of severe hypoglycemia following resection of pheochromocytoma. A 39-year-old male was admitted to our hospital with a chief complaint of palpitation. Blood pressure and fasting blood glucose were within the normal range. Computed tomography and magnetic resonance imaging revealed a right adrenal tumor (7.5 x 5 x 7 cm) and 131I-MIBG scintigraphy showed marked tumor uptake of isotope. As plasma and urinary catecholamine levels were very high, a clinical diagnosis of pheochromocytoma was established. Doxazosin and propranolol were administered for 43 days prior to adrenalectomy. During intensive care monitoring 2 hours postoperatively, the patient became drowsy and began to sweat. Although blood pressure remained stable, severe hypoglycemia (38 mg/dl) and hyperinsulinism (63.67 microU/ml) were confirmed. Infusion of 50% glucose improved these symptoms and plasma glucose level and insulin secretion normalized within 15 days of surgery. We also reviewed 25 cases of hypoglycemia after resection of pheochromocytoma. We recommend close monitoring of blood glucose for at least 6 hours after adrenalectomy for pheochromocytoma.

Comparative study of novel endoluminal ultrasonography and conventional transurethral ultrasonography in staging of bladder cancer.

BACKGROUND: Recent advances in ultrasonic techniques have improved the image quality and diagnostic accuracy for staging of bladder cancer. The aim of this study was to assess the feasibility and usefulness of endoluminal ultrasonography (ELUS) in staging of bladder cancer, and to compare them with those of conventional transurethral ultrasonography (TUUS). METHODS: From 2000 to 2002, 19 patients with bladder cancer were evaluated by ELUS and TUUS before transurethral resection or biopsy. Clinical staging using ELUS, TUUS, computed tomography (CT) and magnetic resonance imaging (MRI) was compared with the results of pathological staging. RESULTS: In 16 of 19 patients, both ELUS and TUUS were able to diagnose tumor stage. In the remaining three patients, both methods were unable to evaluate stage of tumor. In two of these patients, this inability to evaluate tumor state was caused by a difficulty in depicting the tumor base in rectangular scanning. In the remaining patient, the inability to evaluate tumor stage was caused by a difficulty in recognizing the normal muscularis because of edema around the tumor base. Both diagnostic accuracies of ELUS and TUUS were 84%, which were superior to those of CT (44%) and MRI (82%). CONCLUSIONS: Endoluminal ultrasonography and TUUS were equally useful for staging diagnosis of bladder cancer. Because the ELUS probe is very small in diameter and can be manipulated under direct vision, it is superior to the TUUS in safety and in fine visualization. However, the main limitations of ELUS include an inability to evaluate the depth of invasion of large tumors and an inability to visualize the tumor base in the position of the bladder neck.

[Paravesical granuloma after inguinal herniorrhaphy].

Paravesical granuloma is a rare complication after inguinal herniorrhaphy. We report a case of this rare disease and review 27 previously reported cases. A 70-year-old male presented with hematopyuria. He had undergone right inguinal herniorrhaphy five years earlier. On presentation, the right inguinal area was wet with exudate. Cystoscopy revealed edematous mucosa on the right side of the bladder dome, but transurethral bladder biopsy demonstrated no malignancy. CT identified a 2-cm diameter mass with heterogeneous appearance on the right side of the bladder dome. Treatment with antibiotics proved ineffective and en bloc excision of the tumor with partial cystectomy was performed. Symptoms subsequently resolved completely. Histopathologically, the tumor represented inflammatory granuloma, and a mesh thought to be a remnant from the previous herniorrhaphy was found in the central portion of the tumor. Paravesical granuloma should be considered for patients with continuous hematopyuria and a history of inguinal herniorrhaphy.

Reversal of acquired cisplatin resistance by modulation of metallothionein in transplanted murine tumors.

BACKGROUND: The platinum-based chemotherapeutic agent cisplatin is involved in a broad spectrum of activities against human systemic malignancies. However, acquired resistance to cisplatin reduces its clinical efficacy. Elucidation of the molecular basis of cisplatin resistance is required to improve the effectiveness of cisplatin. In the present study, the mechanism of acquired resistance to cisplatin was studied in C3H mice inoculated with MBT-2 murine bladder tumor cells. METHODS: C3H mice were subcutaneously inoculated with 1.0 x 10(6) MBT-2 cells/mouse on day 0. The mice were given intraperitoneal injections of 10 micro mol/kg cisplatin and subcutaneous injections of 1000 micro mol/kg propargylglycine, an inhibitor of gamma-cystathionase, once a day for 10 consecutive days from day 11 to day 20. RESULTS: The metallothionein content of the tumors was increased to twice the control level by repeated administration of cisplatin. Co-administration of propargylglycine reduced metallothionein induction in the tumors and markedly enhanced the antitumor activity of cisplatin. In contrast, the glutathione content in the tumors did not change from the control level after cisplatin administration. The platinum accumulation in tumors treated with cisplatin alone was 1.7-fold greater than when propargylglycine was administered concomitantly. The platinum concentrations changed in accordance with the metallothionein contents. CONCLUSIONS: These observations suggest that metallothionein, but not glutathione or reduced platinum accumulation, might play a role in the acquired resistance to cisplatin of C3H mice inoculated with MBT-2. Moreover, reversal of this resistance might be possible by biochemical modulation of metallothionein.

[Ammonium acid urate stone due to laxative abuse: a case report].

We report a case of ammonium acid urate stone due to laxative abuse. A 27-year-old female complained of left flank pain. Computed tomography revealed bilateral ureter stones (right 16.5 x 9.0 mm; left 4 mm), while left ureter stone was radiolucent on the plain X ray film. Bilateral hydronephrosis was seen, but no therapy was performed for the right stone, because 99mTc-MAG3 scintigraphy revealed that right kidney had no function. The left stone was successfully removed by transurethral approach. The stone was revealed to be an ammonium acid urate by infrared spectrophotometry. She had been taking many laxatives (bisacodyl, sennoside, aloe extract) for 12 years to control her body weight. Ammonium acid urate stones are rarely seen in developed countries. We have reviewed 9 cases in Japan, describing ammonium acid urate stones due to laxative abuse. Among these patients, 24-hour urine volume and excretion in urinary sodium were decreased, and serum aldosterone was increased. The involvement of laxative abuse should be considered when ammonium acid urate is formed in a woman with a low body mass index.

[Tumor enucleation for pelvic schwannoma: a case report].

A 36-year-old man with a complaint of pollakisuria visited our hospital. A non-displaceable, palm-sized tumor was palpable in the lower abdomen. Laboratory data were normal except for slightly high serum S100 protein. Intravenous pyelography revealed hydronephrosis on the right side and deviation of the bladder to the left. Computed tomogaphy revealed a heterogenous tumor in the pelvis with a cystic lesion and calcification. The tumor was 16 x 12 x 11 cm in size and in contact with the sacrum. The tumor was extirpated following diagnosis as a benign schwannoma by needle biopsy. The pelvic cavity was occupied by the tumor rigidly adhered to the sacrum. Although serious complications, such as bleeding and nerve injury were apprehended, we incised the tumor capsule and enucleated the contents as much as possible. The histopathological diagnosis of the resected specimen was benign schwannoma, type Antoni A. In the last 10 years, 37 cases of pelvic schwannoma have been reported in the Japanese literature. In most of them, surgical extirpation was difficult to perform because of adhesion to the sacrum. If the tumor is confirmed benign from histopathologic findings preoperatively, tumor enucleation may become a therapeutic option.