5 years intravesical instillation with mitomycin-C and pirarubicin as a prophylactic treatment for superficial bladder cancer

PURPOSE: We studied prophylactic intravesical instillation of mitomycin C (MMC) and pirarubicin (THP) following transurethral resection of bladder tumor (TUR-Bt) for superficial bladder cancer. MATERIALS AND METHODS: Forty-six evaluable patients were administered intravesically 20 mg of MMC dissolved in 20 ml saline on day 1 and 20 mg of THP dissolved 20 ml 5% dextrose on day 2. The patients were followed up by cystscopy and urinary cytology. Intravesical instillations were performed once a month and continued for 5 years. RESULTS: The non-recurrence rates at 1, 3 and 5 years were 88.8%, 79.5% and 67.0%, respectively. No significant differences were observed between grade 1-2 and 3, male and female, and solitary and multiple tumors. Although the side effects were relatively mild, 6 patients were stopped intravesical instillation. CONCLUSIONS: Because non-recurrence rates of our report is not better than previous reports with shorter treatment periods, intravesical MMC and THP instillation for 5 years is not beneficial to the patients with superficial bladder cancer.     

Serum uptake of doxorubicin intravesically administered soon after transurethral resection of bladder carcinoma

To obtain the maximum prophylactic effect of intravesical chemotherapy on the bladder tumor recurrence treatment should be started early. Since 1983, we have been initiating prophylactic instillation of doxorubicin hydrochloride (DXR) on the first post-transurethral resection (TUR) day. This study was conducted to define serum uptake of DXR and systemic toxicity in the early post-TUR period. Fifteen TURs were carried out on 14 patients with superficial bladder carcinoma. DXR (30 mg) in normal saline (30 ml) was intravesically administered 1, 3, 5, 7 and 14 days after TUR, and every 4 weeks thereafter. DXR solution was kept in the bladder for 2 hours. The serum DXR concentration was measured 30 minutes and 2 hours after the instillation through 1 to 5 days after TUR. Intolerable vesical irritability was seen in 4 of 60 instillations. No systemic side effects, however, were observed. Three of 24 samples contained a detectable level (10 ng/ml) of DXR on the post-TUR day 1, 6 of 22 samples on the post-TUR day 3, and 6 of 14 samples on the post-TUR day 5. Overall, 15 of 60 samples contained more than 10 ng/ml DXR. The highest serum DXR level was 47 ng/ml at the post-TUR day 1. Frequency of detection and average levels of serum DXR in 30-minute and 2-hour samples were not significantly different. Average concentrations in patients with multiple or diffuse tumor and solitary tumor were also not significantly different. These results indicate that intravesical instillation starting within 24 hours after TUR does not produce significant serum uptake of DXR, and systemic toxicity can thereby be avoided.     

TUMOR LOCALIZATION AND SYSTEMIC ABSORPTION OF INTRAVESICAL INSTILLATION OF RADIO-IODINATED IODODEOXYURIDINE IN PATIENTS WITH BLADDER CANCER

PURPOSE: We evaluated tumor uptake and systemic distribution of intravesically instilled iododeoxyuridine (IUdR) in patients with superficial bladder cancer. MATERIALS AND METHODS: We performed 24 intravesical instillation studies in 11 patients with a mean age of 71 years. Radio-iodinated IUdR was administered through a Foley catheter. Gamma camera imaging was done after instillation and after 5 to 7 bladder irrigations. Tumor uptake was estimated by region of interest analysis. Bladder biopsy samples and surgical tumor specimens were tested for acid insoluble (deoxyribonucleic acid incorporated) radioactivity. Blood samples were obtained and analyzed for systemic absorption. RESULTS: Imaging was positive in all patients with bladder cancer. Average tumor uptake plus or minus standard deviation was 0.185+/-0.120% of the instilled dose. Preferential uptake of IUdR in the tumor was observed in all 6 patients undergoing tissue analysis. The tumor-to-normal bladder ratio ranged from 3.2 to 74,000 (median 202). Systemic absorption of IUdR was minimal. Blood sample analysis performed after intravesical instillation in all 11 cases revealed an average uptake of 3.2x10(-5)% instilled dose per ml. (range 0.69x10(-5) to 6.7x10(-5)) in the systemic circulation. Instillation within 24 hours after transurethral bladder tumor resection in 5 cases resulted in a higher but not dangerous average systemic uptake of 7.3x10(-4)% instilled dose per ml. (range 1.3x10(-5) to 2.6x10(-3)). Instillation 1 to 4 weeks after transurethral surgery in 8 cases resulted in no increased systemic absorption with an average blood level of 3.4+/-1.8x10(-5)% instilled dose per ml. There was no detectable distribution of radioactivity into other organs, including the thyroid. We noted no evidence of systemic toxicity in the study. CONCLUSIONS: Intravesical instillation of radio-iodinated IUdR achieves selective localization in the bladder tumor with minimal uptake by the normal bladder and minimal systemic absorption. The use of intravesical IUdR therapy for bladder cancer appears to be promising and requires further study.     

吡喃阿霉素膀胱内灌注预防浅表性膀胱癌术后复发

目的　评价吡喃阿霉素 (THP)膀胱内灌注预防浅表性膀胱癌术后复发的疗效和安全性。　方法　对 45例浅表性膀胱癌患者行经尿道膀胱肿瘤电切术 (TURBt)或膀胱部分切除术 ,术后定期应用THP(4 0mg/ 40ml)膀胱内灌注 ,每次药物在膀胱内保留 30min。　结果　 45例患者随访 9～ 12个月 ,无肿瘤复发 44例 (97.8% ) ,复发 1例。未见有全身性药物不良反应 ,仅 2例膀胱灌药后出现短时间轻度膀胱刺激症状。　结论　THP膀胱内灌注预防浅表性膀胱癌术后复发疗效满意 ,病人耐受性好 ,副作用小     

The fate of bacillus Calmette-Guerin after intravesical instillation

PURPOSE: Long-term activation of immunocompetent cells of the bladder wall as well as case reports of systemic infections some months or years after intravesical bacillus Calmette-Guerin (BCG) therapy imply that mycobacteria may persist in the body. Therefore. we investigated the fate of BCG in patients after uncomplicated intravesical instillation therapy. MATERIAL AND METHODS: A total of 49 patients were included in the study, from whom various numbers of specimens were used for mycobacterial culture and molecular biological detection techniques. In 23 patients who received a total of 128 instillations urine, sputum, venous blood and bladder biopsies were screened for BCG by acid-fast staining and culture at different times before and after instillation. From 16 of the 23 patients and from an additional 26 a total of 180 bladder biopsies obtained at intervals 3 to 30 months after instillation were screened for mycobacterial 16S ribosomal DNA by a nested polymerase chain reaction protocol. RESULTS: No viable BCG was found in venous blood or in 127 of 128 sputum specimens before and 2 hours after instillation. Two of 56 bladder biopsies were culture positive. In urine BCG was detected in 96.4% of the specimens after 2 hours and in 67.9% after 24 hours after instillation. The number of positive specimens decreased and it was 27.1% on day 7 immediately before the next instillation. In 14 of 44 bladder biopsies (31.8%) mycobacterial ribosomal DNA was found within 1 week after the sixth instillation. A positive polymerase chain reaction was evident up to 24 months in between 4.2% and 37.5% of the investigated biopsies. After 30 months no ribosomal DNA was evident in the 6 samples available for testing. CONCLUSIONS: Nontraumatic intravesical instillation of BCG is not accompanied by systemic mycobacterial spread. Local persistence during the instillation course is evident since viable BCG is commonly found in the urine. Long lasting and persistent BCG DNA in the bladder wall may account for long-term immuno-activation. However, the remaining BCG may be a possible source of late systemic infections.     

吡柔比星膀胱灌注预防浅表性膀胱癌术后复发

目的：评价吡柔比星（THP）膀胱内灌注预防浅表性膀胱癌术后复发的近期疗效。方法：对34例浅表性膀胱癌患者行经尿道膀胱肿瘤电切术（TURBt)或膀胱部分切除术，术后定期用THP（30mg/40ml）作膀胱内灌注，每周1次共8次，以后每月1次共1年。每次药物在膀胱内保留40min。结果：经10－12个月随访，无肿瘤复发32例，复发2例，复发率为5．9％；未见全身性药物不良反应，仅5例患者出现轻度膀胱刺激症状。结论：THP膀胱内灌注预防浅表性膀胱癌术后得发近期疗效满意，副作用轻，耐受性良好。     

Adjuvant intravesical treatment of superficial bladder cancer with a standardized mistletoe extract

PURPOSE: Adjuvant intravesical immunotherapy with bacillus Calmette-Guerin (BCG) for noninvasive superficial bladder cancer has been shown to decrease tumor recurrence significantly. However, serious local and systemic side effects of this treatment have promoted the use of other immunoactive substances, which to date have failed to show efficacy equal to that of BCG immunotherapy. MATERIALS AND METHODS: In the current phase I/II clinical trial an aqueous mistletoe extract standardized to mistletoe lectin was administered intravesically to 30 patients with superficial urothelial bladder carcinoma. About 4 weeks after transurethral resection each patient received 6 instillations at weekly intervals of 50 ml extract with mistletoe lectin concentrations between 10 and 5,000 ng/ml, which was retained in the bladder for 2 hours. Three patients per group received a dose, which was then doubled in the next group. Clinical followup consisted of examinations with cystoscopy, cytology and random biopsies. To detect cytokines and tumor necrosis factor-p75 receptor venous blood and urine samples were taken before instillation, and 2, 6 and 24 hours thereafter. RESULTS: The tolerability of intravesically administered mistletoe extract was good at all applied concentrations. None of the patients had local or systemic side effects according to WHO classification 1-4. Within the 12-month observation time study patients with pTa G2 and pT1 G2 tumors showed a recurrence rate of 33%, comparable to that in a local historical control group of patients with equal stage and grade who were treated with adjuvant BCG. Comparison of urine cytokine levels before instillation, and 2, 6 and 24 hours thereafter brought about no significant alterations in all measured cytokines. CONCLUSIONS: From these results it is concluded that standardized mistletoe extract could be a potential alternative adjuvant therapy for superficial bladder cancer. Nevertheless, the optimal intravesical treatment regimen has yet to be defined.     

A randomized study of pirarubicin (THP) versus adriamycin (ADM) for intravesical instillation therapy against superficial bladder cancer]

To determine the antitumor action by intravesical instillation prior to transurethral resection TUR, a randomized study on pirarubicin (THP) versus adriamycin (ADM) was performed for superficial, papillary and initially detected bladder cancers with participation of 21 Urological Clinics in 3 Tokai Prefectures. The instillation dose of 500 micrograms/ml was given 3 times per week for 3 weeks in both THP (n = 33) and ADM (n = 30) groups. The complete and partial response rates were 56.3% in THP group and 26.7% in ADM group. THP instillation was more effective against multiple tumors than a single tumor, stage Ta than T1 and grade G1 than G2 and G3. However, these findings were not statistically significant. Untoward effects were mainly bladder irritability and its frequency was 60.6% in the THP group and 23.3% in the ADM group. Contracted bladder was found in 2 of the 33 patients in the THP group and 2 of the 30 patients in the ADM group. The antitumor effect of a half dose of THP was equivalent to that of one dose of ADM, and the THP group showed a twofold higher frequency of side effects. Therefore, a clinical trial should be made comparing the effect of 500 micrograms/ml of THP and that of 1,000 micrograms/ml of ADM.     

吡柔比星术后即刻膀胱灌注联合常规灌注预防表浅性膀胱癌术后复发的对照研究

目的：比较吡柔比星两种膀胱内灌注方法预防表浅性膀胱癌术后复发的有效性及安全性。方法：将52例经尿道膀胱癌电切术后表浅性膀胱癌患者随机分为两组。每次吡柔比星灌注剂量30mg,治疗组术后24h内膀胱灌注1次,此后每周灌注1次,连续8周,再改为每月灌注1次,至术后1年。对照组术后2周开始灌注,此后每周灌注1次,连续8周,再改为每月灌注1次,至术后1年。结果：全部病例均获随访,时间为12～24个月,平均随访16．3个月。其中治疗组随访期内2例复发,复发率8％;对照组随访期内4例复发,复发率14％,两组复发率比较差异有统计学意义（P〈0．05）,不良反应主要为尿路刺激症状。结论：本研究显示,吡柔比星膀胱灌注预防表浅性膀胱癌术后复发的疗效满意,用药方便,患者耐受性好;术后即刻膀胱灌注联合常规灌注较常规灌注可以降低肿瘤复发率,值得推荐。     

Fundamental studies on intravesical instillation of cis-diamminedichloroplatinum for treatment of urinary bladder tumors. II. On the effects of intravesical instillation of cis-diamminedichloroplatinum in bladder cancer patients

This study was performed to determine whether intravesical Cis-Diamminedichloroplatinum (II) (DDP), one of the most effective agents in the treatments of advanced bladder cancer, is applicable for prophylaxis and/or definitive treatment of superficial bladder cancers. Six patients were instilled 10 mg/20 ml of DDP immediately after TUR-Bt, but no remarkable elevation of plasma platinum concentration was observed. In one patient planned to have total cystectomy, 20 mg/40 ml of DDP was instilled daily for 10 days. No remarkable changes in symptom and blood examination was found during the instillation periods. Transitional cell carcinoma of grade 2 was necrosed extensively, but minimum cellular injury was observed in normal mucosa. Tissue platinum concentration was 3.19 micrograms/g. wet in carcinoma and 0.28 microgram/g. wet in normal mucosa. Longterm prophylactic instillation of 20 mg/40 ml of DDP was performed in 16 patients starting immediately after TUR-Bt. As the side effects of DDP instillation, contracted bladder was observed in one patient and allergic reactions, such as flush of the skin and dyspnea, were observed in 4 cases. These allergic reactions were happened suddenly after 15 approximately 19 times of DDP instillation without any prelude. At present, intravesical instillation of DDP seems to cause minimal irritation of bladder and absorption through the bladder wall, but clinical trials of intravesical DDP should be taken under careful observation until the allergic reaction by intravesical DDP are clarified.     

Pharmacokinetics,efficacy, and safety of intravesical formulation of oxybutynin in patients with detrusor overactivity

OBJECTIVE: To determine the pharmacokinetics of oxybutynin and its main active metabolite, N-desethyloxybutynin, after multiple dosage (5 mg/30 ml three times daily) of intravesical oxybutynin formulation. Furthermore, to determine the efficacy and safety of intravesical oxybutynin in the symptomatic relief of urge incontinence or urgency in adult patients with detrusor hyperreflexia or instability. MATERIAL AND METHODS: Nine patients were randomly allocated to treatment with a special bladder instillation formulation of oxybutynin or placebo for two 14-day treatment periods in a double-blind, cross-over manner. The third, open study period was designed for pharmacokinetic purposes with all patients on the active drug. The pharmacokinetics was depicted by AUC0-24, Cmax, Cmin, and t(max), The efficacy was evaluated from the data collected from urinary voiding diaries and cystometries. The safety was measured by recording adverse events on questionnaires. Patients who were willing to continue with the intravesical oxybutynin treatment entered the 1-year extension part of the study. RESULTS: Oxybutynin was absorbed from the bladder with a geometric mean Cmax of 9.4 ng/ml and AUC0-24 of 92 ng x h/ml. For N-desethyloxybutynin, the geometric mean Cmax was 14.4 ng/ml and AUC0-24 186 ng x h/ml. Elimination of the drug was protracted, as there were detectable serum concentrations of both oxybutynin and N-desethyloxybutynin even 24 hours post-dose. The mean number of toilet visits/day decreased from the baseline value of 6.9 to 5.7 during oxybutynin treatment, whereas during the placebo period the value increased to 7.4 (p = 0.022). It remained at the same decreased level during the one-year follow-up period. CONCLUSIONS: Oxybutynin is readily absorbed from the bladder after intravesical administration. The serum concentrations of oxybutynin after single 5 mg intravesical doses are at least as high as those reported after oral drug intake, but the parent drug/metabolite ratio is much higher after intravesical administration. The elimination of oxybutynin as well as its metabolite is prolonged after intravesical administration compared with that reported after oral drug intake. The mean number of daily toilet visits decreased significantly in the oxybutynin group.     

Two cases of vesical nephrogenic adenoma

Case 1: A 52-year-old man receiving regular treatment for quadriplegia due to Friedreich disease visited our hospital with the chief complaint of macroscopic hematuria. He had undergone cystostomy 12 years ago due to neurogenic bladder. The computed tomography and cystoscopic examination revealed a bladder tumor with a few bladder stones. Transurethral resection of bladder tumor (TUR-Bt) was performed after bladder stone removal in May 2000. The pathological diagnosis showed nephrogenic adenoma. Case 2: A 54-year-old man had been treated with bladder tumor by TUR-Bt in Nov. 1995. The pathological diagnosis showed transitional cell carcinoma, G3, pT2 and intravesical instillation therapy using THP was performed. The bladder tumor had recurred twice and the instillation therapy had been exchanged to BCG since Nov. 1997. A small bladder tumor was observed in Jan. 2001, and from the biopsy specimen it was diagnosed as nephrogenic adenoma. Forty-six cases of urothelial nephrogenic adenoma including our cases have been reported in Japan. Chronic stimulation such as bladder stone and infection is thought to induce nephrogenic adenoma. BCG instillation therapy is believed to be an initiation factors for nephrogenic adenoma.     

Prospective randomized controlled trial of postoperative early intravesical chemotherapy with pirarubicin (THP) for solitary non-muscle invasive bladder cancer comparing single and two-time instillation

Purpose

Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC.

Methods

Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30 mg/50 mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1 day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266.

Results

Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71 months. The overall recurrence rate was 39 and 31%, respectively (p = 0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p = 0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p = 0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence.

Conclusions

Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.

     

米托蒽醌灌注预防膀胱癌术后复发的疗效观察(附98例报告)

目的　评价米托蒽醌 (MTZ)膀胱灌注预防浅表性膀胱癌术后复发的疗效和安全性。方法　对 98例浅表性膀胱癌患者行TURBT或膀胱部分切除术 ,术后 1周予MTZ 12mg 生理盐水 5 0ml膀胱内灌注 ,药物于膀胱内保留 2h ,每周 1次 ,连续 8周 ,以后每月 1次 ,连续 12个月。定期做血尿常规、肝肾功能及膀胱镜检查 ,并记录每次膀胱灌注后的全身及局部反应。　结果　 98例均未见全身性药物不良反应 ,随访 6～ 2 4个月 ,平均 13个月 ,复发 6例 ,复发率 6 .2 %。　结论　MTZ膀胱灌注防止膀胱癌术后复发疗效满意 ,安全性好     

Treatment of overactive bladder with modified intravesical oxybutynin chloride

Intravesical oxybutynin chloride has been reported to be effective for overactive bladder, although sometimes the efficacy does not last long enough. To improve this deficiency, we report the effects of intravesical oxybutynin chloride with hydroxypropylcellulose (modified intravesical oxybutynin). Modified intravesical oxybutynin (5 mg/10 mL, twice a day) was administered to six overactive bladder patients for more than 1 year (two men and four women; average age, 56.5 years) who did not respond to oral anticholinergic agents and electric stimulation. Cystometography (CMG) was performed before, 2 hours, and 1 week after the start of modified intravesical oxybutynin. In addition, plasma levels of oxybutynin and its active metabolite, N-desethyl-oxybutynin (DEOB), were measured by high-performance liquid chromatography before, 1, 2, and 4 hours after the initial treatment of modified intravesical oxybutynin. CMG studies revealed that two of the six patients did not demonstrate uninhibited contractions 1 week after the treatment and that cystocapacity of before, 2 hours, and 1 week after the initial modified intravesical oxybutynin was 141.8+/-15.3, 210.0+/-35.5, and 305.0+/-21.3 mL, respectively. Plasma levels of oxybutynin and DEOB before, 1, 2, and 4 hours after the first instillation of modified intravesical oxybutynin were oxybutynin; not detected, 8.8+/-2.5, 6.8+/-1.1, 3.0+/- 1.0 ng/ml, and DEOB; not detected, 4.2+/-1.3, 6.4+/-1.7, 5.1+/- 1.4 ng/ml, respectively. No side effects were observed in any of the patients. Modified intravesical oxybutynin is an effective and safe therapy option for overactive bladder patients who do not respond to other treatments such as oral anticholinergic agents and electric stimulation.     

A randomized study of prophylactic intravesical instillation of pirarubicin (THP) prior to transurethral resection of superficial bladder cancer

A prospective randomized study was conducted to evaluate the efficacy of prophylactic intravesical instillation of pirarubicin (THP) prior to transurethral resection (TUR) of superficial bladder cancer. A total of 63 patients were randomized into two groups, the THP group and the control group. In the THP group, 30 mg of THP dissolved in 50 ml saline was administered 4 times intravesically for 4 consecutive days before TUR. In the control group, no instillation was performed before TUR. The patients were followed by cystoscopy and urinary cytology every 3 months. The non-recurrence rates in the THP group and control group were 54.1% versus 37.6% at 1 year and 40.4% versus 26.8% at 2 years, respectively (P = 0.086). Time to recurrence for tumors larger than 1 cm was significantly longer in the THP group (P = 0.0137). Time to recurrence for single and grade 1+2 tumors tended to be longer in the THP group (P = 0.09, P = 0.079). No significant adverse effects were observed in any patient. Our findings suggest that intravesical THP instillation prior to TUR would be effective for patients with single, low grade lesions larger than 1 cm of superficial bladder cancer.     

吡柔比星(THP)膀胱灌注预防腺性膀胱炎术后复发的疗效观察

目的 评价吡柔比星(THP)膀胱灌注预防腺性膀胱炎术后复发的疗效。方法 对30例腺性膀胱炎患者行经尿道汽化电切术,术后定期应用THP(40mg/50ml)膀胱内灌注化疗。结果 30例患者随访5～20个月,平均14.5个月,3例复发(10％)。未见有全身性药物不良反应,仅2例血白细胞降至3000个/ml。结论THP膀胱灌注预防腺性膀胱炎术后复发疗效满意,病人耐受性好,副作用小。     

Bladder preservation by chemoradiotherapy in combination with radical TUR-Bt in muscle invasive bladder cancer

PURPOSE: To evaluate bladder preservation protocol by radical TUR-Bt and subsequent concurrent chemoradiotherapy in muscle invasive bladder cancer. PATIENTS AND METHODS: Twenty-six patients with muscle invasive bladder cancer (T2-T4NOM0) were treated with concurrent chemoradiotherapy after transurethral resection of the tumor as much as possible beyond muscle layers. Chemotherapy was consisted of systemic administration of methoterexete (30 mg/m2 day 1 and day 22) and intraarterial infusion of cisplatin (70 mg/m2, day 2 and day 23). The response was evaluated by TUR, urine cytology, CT and/or MRI 4 to 6 weeks after the treatment. RESULTS: Among 24 evaluable cases, pathological complete response was achieved in 13 cases (50%) and residual tumors were noted in 11 cases (pT1 in 9 and pT2 in 2). During follow-up period up to 69.8 months, invasive recurrence was observed in 2 cases, superficial recurrence was noted in 5 patients and distant metastasis without evidence of local recurrence was noted in 4 cases. Overall bladder preservation rate was 92%. CONCLUSIONS: The bladder preservation by radical TUR-Bt and chemoradiotherapy is a safe and effective treatment option for muscle invasive bladder cancer.     

浅表性膀胱肿瘤对化疗药物的敏感性研究

目的:探讨敏感化疗药物预防浅表性膀胱癌术后复发的作用。方法:对30例表浅性膀胱癌体外原代细胞培养,用表阿霉素、羟基喜树碱、吡柔比星、丝裂霉素和盐酸米托蒽醌进行MTT法药物敏感实验(敏感实验组),用最敏感药物行膀胱灌注;同期选择30例患者用吡柔比星灌注作为对照(对照组)。结果:敏感实验组17例对吡柔比星最敏感,6例对盐酸米托蒽醌最敏感,3例对丝裂霉素最敏感,1例对羟基喜树碱最敏感,1例对表阿霉素最敏感,2例对5种化疗药物都不敏感。28例患者分别选择最敏感药物灌注后随访2年,2例复发(7.1%)。对照组吡柔比星灌注后随访2年,有8例复发(26.7%)。两组比较差异有统计学意义(P<0.05)。结论:5种化疗药物对膀胱肿瘤的体外细胞毒作用不同,其中吡柔比星的抑制作用最强。根据药物敏感实验对浅表性膀胱肿瘤行灌注治疗,对预防肿瘤复发有较好效果。     

Decrease in intravesical saline volume during isovolumetric cystometry in the rat

This study was undertaken to examine the change in intravesical saline volume during isovolumetric cystometry in the urethane anesthetized female rat. The ureters were transected bilaterally and their distal ends were ligated. To prevent leakage of intravesical fluid, the proximal urethra was ligated after inserting a urethral catheter into the bladder. In 13 rats in which the bladder was filled with different volumes of saline between 0.3 and 2.0 ml and maintained under isovolumetric conditions for 3 hours, intravesical volume decreased (4–79%) when initial intravesical saline volume was equal to or greater than 0.6 ml (n = 9). In 9 rats in which intravesical volume decreased, mean final volume was 0.68 ± 0.09 ml. The percentage change in intravesical volume (y) significantly depended on initial volume (x) (y = −42x + 17, n = 13). In 7 rats in which the proximal urethra was ligated and the bladder was filled with different volumes of soybean oil between 0.25 and 2.0 ml, intravesical volume did not change. In 8 rats in which the bladder neck was ligated around a urethral catheter to block blood flow to the bladder and in which the bladder was filled with different volumes of saline (0.3–1.8 ml), intravesical volume decreased when initial volume was equal to or greater than 1.35 ml. These results demonstrate that intravesical saline is absorbed from the normal bladder wall when intravesical volume is greater than the volume (0.6 ml) necessary to evoke the micturition reflex in urethane anesthetized rats. Neurourol. Urodynam. 16:125–132, 1997. © 1997 Wiley-Liss, Inc.