Koichi Kambe

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.

Clinical Application of Extracorporeal Shock Wave Lithotripsy using Microexplosions

Extracorporeal stone disintegration using a chemical explosive (10 mg. lead azide) as an energy source of underwater shock waves was performed in 105 patients 11 to 72 years old who had stones in the upper urinary tract. We used a prototype disintegrator in this series. The over-all rate free of stones 3 months after treatment was 82 per cent. Shock wave therapy was performed alone in 77 patients (73 per cent), while the remainder required combined treatment with percutaneous and/or transurethral lithotripsy. The most common complications were colic pain (30 per cent) and fever (23 per cent). In 4 patients other complications, that is bacteremia, gastrointestinal bleeding, ureteral injury and subcapsular renal hematoma, were observed but they were treated conservatively with no serious adverse effects. Our study demonstrates the safe use of this method for clinical treatment.

Extracorporeal Stone Disintegration Using Chemical Explosive Pellets as an Energy Source of Underwater Shock Waves

Extracorporeal renal stone disintegration using a chemical explosive pellet (lead azide 10 mg.) as an energy source of underwater shock waves has been successfully performed in animals. The shock wave was observed by holographic interferometry. Shock wave generation was performed by a reflector whose configuration was part of a pseudoellipsoid. The explosions were conducted 10 to 100 times for each animal and the stone (extracted human renal calculus or model calculus of activated alumina) placed in the renal pelvis was disintegrated satisfactorily. Negative findings in explorative laparotomy and histological examination, except for minor bleeding in several tubular lumina of the kidney, indicated that the method was clinically applicable.

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.

Mechanism of Fragmentation of Urinary Stones by Underwater Shock Wave

The focusing of an underwater shock wave, generated by an underwater microexplosion, has been studied by several methods, such as holography, pressure measurement and pressure print. It has been shown that the shock wave could be focused within the range of a few millimeters and with an amplitude of 1 kbar. The acoustic impedances of various kinds of urinary stones were measured by the original graphical method using holographic interferrometry. The process of breaking a stone by a focused underwater shock wave was observed with high-speed cinematography. It was supposed that the main mechanism of breaking the stone is the tensile stress at the solid-water acoustic interface.

Renal tissue damage induced by focused shock waves

Biological evidence of renal arterial wall damage induced by the microjet due to shock wave‐cavitation bubble interaction was demonstrated in living dog kidneys. We also intended to clarify the mechanism of renal tissue damage and the effects of different conditions of shock wave exposure (peak pressure of focused area, number of shots, exposure rate) on the renal tissue damage in comparison to stone disintegration.Disruption of arterial wall was the most remarkable histological change in the focused area of the kidneys. This lesion appeared as if the wall had been punctured by a needle. Large hematoma formation in the renal parenchym, and interstitial hemorrhage seemed to be the results of the arterial lesion. This arterial disorder also led to ischemic necrosis of the tubules surrounding the hematoma. Micro‐angiographic examination of extracted kidneys also proved such arterial puncture lesions and ischemic lesions.The number of shots required for model stone disintegration was not inversely proportiona...

Anti-miss-shot control device for selective stone disintegration in extracorporeal shock wave lithotripsy

A new device to prevent erroneously focused shock waves to the renal parenchyma during extracorporeal shock wave lithotripsy (ESWL) has been developed; an anti-miss-shot control device (AMCD) and experiments have been conducted to evaluate its effectiveness. For shock wave generation and stone localization, piezoceramic elements (PSE) and ultrasound localization, respectively were used. After stone localization, probing ultrasounds (PU) were emmitted from the PSE towards the focal region and the reflected sound levels (RSL) were monitored by the PSE which also functioned as a microphone. A direct hit by the PU to the stone or a miss was judged from the RSL, i.e. a high RSL indicates a direct hit and a low RSL indicates a miss. Shock waves were generated only when the RSL exceeded the level which indicated a direct hit. The experimental results showed that the injury to the renal parenchyma was decreased by using the AMCD. Clinical application of the AMCD is expected to increase the safety of ESWL.

Intermittent irrigation system for dissolution of renal calculi monitored by computer.

An intermittent irrigation system was tested in vitro and in a clinical case. In vitro experiments showed that the intermittent irrigation was more efficient to dissolve calculi compared to the continuous irrigation. The pelvic irrigation was performed clinically by a cystoscopically passed angiographic catheter. The system could be operated in constant low pressure without supervision. The result shows that this system will be safe and valuable for pelvic irrigation.

Acoustic cavitation bubbles in the kidney induced by focused shock waves in extracorporeal shock wave lithotripsy (ESWL)

On an ultrasonic imaging system a hyperechoic region was observed in a focal area of fucused shock waves in the dog kidney. This study was performed to learn whether cavitation bubbles are responsible for this hyperechoic region.The ultrasonic images in water of varying temperatures were not markedly different. In the flowing stream of distilled water, the stream was demonstrated as a hyperechoic region only with a mixture of air bubbles. Streams of 5%–50% glucose solutions were also demonstrated as a hyperechoic region. However, such concentration changes in living tissue, as well as thermal changes, are hardly thought to be induced.The holographic interferometry showed that the cavitation bubbles remained for more than 500 msec. in the focal area in water. This finding indicate that the bubble can remain for longer period than previously supposed.These results support the contentions that cavitation bubbles are responsible for the hyperechoic region in the kidney in situ.

On-Line Adjustment of Sampling Interval by Fuzzy Controller.

制御結果に応じてOn lineで測定間隔を調節するファジィ制御系を構成した.制御対象の出力が目標値に維持されている時には測定・制御動作の間隔を延ばし, 対象の特性が急変している時には頻繁に計測と制御を行なうものであり, 主に医用への応用を目的として開発した.この方法によれば測定回数を通常のデジタル制御系に比べ減少することが可能である.実際の制御対象に対する有効性を確認するために, 生体血圧の昇圧制御に対して適用し, 動物実験を行なった.その結果, 制御対象の出力に応じて測定間隔が適切に調節され, 十分な制御性能が得られることが確認された.