Takashige Namima

Prospective Randomized Phase II Trial of a Single Early Intravesical Instillation of Pirarubicin (THP) in the Prevention of Bladder Recurrence After Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: The THP Monotherapy Study Group Trial

PURPOSE We evaluated the efficacy of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS From December 2005 to November 2008, 77 patients clinically diagnosed with UUT-UC from 11 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were preoperatively enrolled in this study. Patients were randomly assigned to receive or not receive a single instillation of THP (30 mg in 30 mL of saline) into the bladder within 48 hours after nephroureterectomy. Cystoscopy and urinary cytology were repeated every 3 months for 2 years or until the occurrence of first bladder recurrence. RESULTS Seventy-two patients were evaluable for efficacy analysis, 21 of whom had a subsequent bladder recurrence. Significantly fewer patients who received THP had a recurrence compared with the control group (16.9% at 1 year and 16.9% at 2 years in the THP group v 31.8% at 1 year and 42.2% at 2 years in the control group; log-rank P = .025). No remarkable adverse events were observed in the THP-treated group. Based on multivariate analysis, THP instillation (hazard rate [HR], 0.26; 95% CI, 0.07 to 0.91; P = .035) and open surgery (HR, 0.28; 95% CI, 0.09 to 0.84; P = .024) were independently predictive of a reduced incidence of bladder recurrence. CONCLUSION In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations.

Significance of simultaneous determination of serum human chorionic gonadotropin (hCG) and hCG-beta in testicular tumor patients.

Background : Simultaneous determinations of human chorionic gonadotropin hormone (hCG) and hCG‐β frequently produce discrepancies, that is when hCG or hCG‐β is normal, the other is elevated. Accordingly, we examined the significance of simultaneous determination of serum hCG and hCG‐β in testicular tumors.

Somatosensory evoked magnetic fields elicited by dorsal penile, posterior tibial and median nerve stimulation

The aim of this study is to localize the primary sensory cortex of urogenital organs in the human brain. Using a newly developed MRI-linked magnetoencephalography system, we measured somatosensory evoked magnetic fields (SEFs) for unilateral stimuli on the dorsal penile nerve (DPN), posterior tibial nerve (PTN) and median nerve (MN). In five healthy male subjects, SEFs were clearly observed. Peak latency of the first cortical components were 63.8 +/- 9.2 ms for DPN, 39.8 +/- 3.0 ms for PTN and 20.7 +/- 0.7 ms for MN stimuli. Peak amplitude of the first cortical components were 63.1 +/- 10.8 fT for DPN, 160.2 +/- 50.1 fT for PTN and 335.2 +/- 70.3 fT for MN stimuli. Isofield map for the peak latencies indicated a single dipolar pattern for DPN as well as for PTN and MN stimuli. Using a single current dipole model, all SEF sources were localized on the contralateral central sulcus to the stimuli, indicating the primary sensory cortex. The DPN sources were localized on the interhemispheric surfaces, corresponding to previous speculations by direct cerebral stimulation. This non-invasive SEF technique promises further brain functional mapping for the urogenital organs.

Acute eosinophilic pneumonia associated with intravesical bacillus Calmette-Guérin therapy of carcinoma in situ of the bladder

Abstract  A 71‐year‐old man with a history of rheumatoid arthritis was treated with intravesical bacillus Calmette‐Guérin (BCG) instillation of 80 mg once‐a‐week for carcinoma in situ. He developed low‐grade fever followed by dyspnea and severe hypoxemia. Radiological and laboratory studies revealed bilateral diffuse reticulonodular infiltrates and hypereosinophilia. A lymphocyte stimulation test for BCG was strongly positive. From these findings, a pulmonary hypersensitivity reaction to immunotherapy was suspected, and therefore, methylprednisolone (500 mg per day) was started. After that, the fever and dyspnea disappeared, the hypereosinophilia was normalised and chest radiography results were clear. The present case is the first reported case of eosinophilic pneumonia following intravesical BCG therapy.

Botulinum toxin A submucosal injection for refractory non-neurogenic overactive bladder: Early outcomes

The objective of the present study was to assess the short‐term effects of botulinum toxin A (BTX‐A) injection for refractory non‐neurogenic overactive bladder (OAB) in the setting of a prospective multicenter clinical trial. Refractory OAB was defined as persistent urgency urinary incontinence (UUI) ≥once a week despite taking anticholinergic agents, or the incapability to continue the agents because of the adverse effects. A total of 100 U of BTX‐A were reconstituted in 15 mL of normal saline and an aliquot of 0.5 mL was injected at 30 submucosal sites of the bladder wall. Nine men and eight women aged 67 ± 12 years were included. Subjective daytime frequency, urgency and UUI significantly decreased after treatment. On a 3‐day frequency‐volume chart, the daytime and night‐time frequency of UUI significantly decreased from 5.5 and 0.5 pre‐injection to 2.0 and 0.3 postinjection, respectively. Daytime urinary incontinence completely disappeared in six subjects. A urodynamic study showed the disappearance of detrusor overactivity in eight patients and a decrease in five patients. Maximum bladder capacity significantly increased from 179.9 to 267.3 mL. Difficulty on micturition or feeling of incomplete emptying was reported by 23.5% and 43.8% of patients at weeks 2 and 4, respectively. Postvoid residual urine increased to >100 mL in seven patients and >200 mL in one patient after injection; however, none of the patients required clean intermittent catheterization. These findings suggest promising efficacy of BTX‐A in Japanese OAB patients.

Effects and indications of sacral surface therapeutic electrical stimulation in refractory urinary incontinence

Objective: To describe the effects and indications of sacral surface therapeutic electrical stimulation (SS-TES) for refractory urinary incontinence. Design: Evaluation before and after therapy. Setting: On clinical site and at nursing home. Subjects: Seven neurogenic bladder, five unstable bladder and six nocturia cases were investigated. Twelve were outpatients and six were residents. Interventions: Surface electrodes were placed at the posterior sacral foramens of S2 and S4. Stimulation conditions were duration 0.3 ms, frequency 20 Hz and maximum intensity. The stimulation was continued for 15 min twice daily for over one month. Main outcome measures: Therapeutic effects were evaluated on the basis of voiding charts as subjective findings and urodynamic study as objective findings before and after therapy. Results: Subjective findings showed incontinence frequency significantly decreased from 2.39±1.4 times/day before therapy to 1.39±2.0 times/day after therapy (p≤0.01); 55.5% of patients were improved or greatly improved. Objective findings showed that maximum vesical capacity (MVC) significantly increased from 208.29±94.5 ml before therapy to 282.19±66.8 ml (p≤0.001). Uninhibited contraction significantly decreased from 40.4±31.4 cmH2O before therapy to 25.79±23.9 cmH2O (p≤0.01); 44% of patients were improved or greatly improved. This therapy was effective in particular for cases whose MVC was small before applying SS-TES. Conclusion: SS-TES was effective in some patients with refractory urinary incontinence.

Intravesical Seeding of Upper Urinary Tract Urothelial Carcinoma Cells During Nephroureterectomy: An Exploratory Analysis from the THPMG Trial

OBJECTIVE The Pirarubicin Monotherapy Study Group trial was a randomized Phase II study that evaluated the efficacy of intravesical instillation of pirarubicin in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma. This study conducted further analysis of the Pirarubicin Monotherapy Study Group cohort, focusing on intravesical seeding of cancer cells. METHODS Using the data from the Pirarubicin Monotherapy Study Group trial, bladder recurrence-free survival rates and factors associated with bladder recurrence in the control group were analyzed. RESULTS Of 36 patients in the control group, 14 with positive urine cytology had more frequent recurrence when compared with the 22 patients with negative cytology (P = 0.004). Based on the multivariate analysis in the control group, voided urine cytology was an independent predictive factor of bladder recurrence (hazard ratio, 5.54; 95% confidence interval 1.12-27.5; P = 0.036). Of 72 patients in the Pirarubicin Monotherapy Study Group trial, 31 had positive urine cytology. Among the 31 patients, 17 patients who received pirarubicin instillation had fewer recurrences when compared with 14 patients who received control treatment (P = 0.0001). On multivariate analysis, pirarubicin instillation was an independent predictor of better recurrence-free survival rates in the patients with positive urine cytology (hazard ratio, 0.02; 95% confidence interval, 0.00-0.53; P = 0.018). Of 21 patients with bladder recurrence, 17 had recurrent tumor around cystotomy or in the bladder neck compromised by the urethral catheter, supporting the notion that tumor cells seeded in the injured urothelium. CONCLUSIONS Intravesical instillation of pirarubicin immediately after nephroureterectomy significantly reduced the bladder recurrence rate in patients with positive voided urine cytology. The results suggest that intravesical seeding of upper urinary tract urothelial carcinoma occurs during nephroureterectomy.

Risk of Prostate Cancer in Older Japanese Asthmatics

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Spontaneous rupture of adrenal pheochromocytoma with capsular invasion

A 67‐year‐old Japanese man developed a sudden onset of severe right‐side upper abdominal pain, nausea and vomiting. On hospitalization, physical examination revealed sweating, tachycardia, hypertension and the appearance of peripheral vasoconstriction. An urgent computed tomography scan with contrast demonstrated a large hematoma in the right retroperitoneal space. A phentolamine test and an 131iodine metaiodobenzylguanidine scan suggested pheochromocytoma. An elective right adrenalectomy was successfully performed after pretreatment for sufficient volume replacement with continuous administration of α‐ and β‐adrenergic blocking agents. Pathological diagnosis was an adrenal pheochromocytoma 9.0 × 6.5 cm in diameter with evidence of capsular invasion, which could be associated with a tear in the capsule.

Botulinum toxin A injection for the treatment of neurogenic detrusor overactivity secondary to spinal cord injury: multi-institutional experience in Japan.

To examine the efficacy and safety of onabotulinumtoxinA (Botox) injection into the bladder wall for the treatment of neurogenic detrusor overactivity secondary to spinal cord injury in Japanese patients.