[Neurogenic bladder, neuromuscular bladder and intestinal bladder].
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BACKGROUND: Estrogen receptors (ERs) are known to mediate important physiologic responses as well as the growth of some tumors in response to estradiol stimulation. In a previous study the selective ER modulator raloxifene was shown to induce apoptosis in an ERbeta-positive bladder cancer cell line. However, the expression of ERbeta in human bladder cancer has not been thoroughly investigated. METHODS: ERalpha and ERbeta expression in 224 bladder tumor samples was evaluated using tissue microarray and immunohistochemistry. Levels of ERalpha and ERbeta protein and mRNA expression were determined in several bladder cancer cell lines using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. The effect of estradiol and antiestrogen treatments on RT4 bladder cancer cell growth was determined by cell proliferation assays. RESULTS: Analyses revealed that only 2 human bladder cancers weakly expressed ERalpha. In contrast, the expression of ERbeta was detected in 141 tumors (63%). ERbeta was expressed in 58% of WHO Grade 1 and 2 tumors, whereas 70% of Grade 3 tumors demonstrated expression (P = .085). Importantly, although only 53% and 55% of Ta and T1 tumors demonstrated ERbeta expression, 80% of T2, 81% of T3, and 75% of T4 tumors showed ERbeta expression. The differences in ERbeta expression between Ta/T1 and T2/T3/T4 tumors were found to be highly significant (P < .001). Metastatic transitional cell carcinomas had ERbeta expression (80%) comparable to that of muscle invasive bladder cancers. Western blot analysis detected ERbeta protein expression in each of the 5 bladder cancer cell lines tested, whereas no or very low levels of ERalpha were found. Quantitative RT-PCR revealed that higher levels of ERbeta than ERalpha mRNA were present in 5637, T-24, TSU-Pr1, and TCC-Sup bladder cancer cells, whereas ER-alpha mRNA levels were greater than ERbeta in RT4 cells. Treatment with 17beta-estradiol modestly increased RT4 cell growth, whereas the antiestrogens, 4-hydroxtamoxifen, raloxifene, or ICI 182,780 inhibited the growth of RT4 cells. CONCLUSIONS: ERbeta is the dominant receptor expressed in bladder cancer cell lines and in the majority of human bladder tumors. Moreover, the degree of ERbeta expression increases with increasing stage and grade of differentiation. Antiestrogens have an inhibitory effect on the growth of bladder cancer cells in vitro.
In a recent clinical study, we reported a selective uptake of hypericin in superficial bladder tumors. The results suggested that hypericin, a potent photosensitizer, could be used not only for diagnosis but also for photodynamic therapy (PDT) of superficial bladder tumors. In the present study, we investigated the biodistribution of hypericin in an orthotopic rat bladder tumor model by assessing the extent of hypericin penetration and the kinetics of accumulation into rat bladder tumors and normal bladder wall. Hypericin (8 or 30 microM) was instilled into the bladder via the catheter for 1, 2 or 4 hr. The fluorescence of hypericin in the bladder tumors and normal bladder was documented using fluorescence microscopy. In situ quantification of hypericin fluorescence in the tumor or normal bladder was performed using the laser-induced fluorescence technique. There was much more hypericin fluorescence in the tumor than in the normal bladder, with the tumor-to-normal-bladder ratio mounting to 12:1 after 4 hr of hypericin (30 microM) instillation. Moreover, hypericin was retained in the tumor for at least 1 hr before it was gradually lost from the tissue. Microscopically, the fluorescence of hypericin was restricted to the urothelial tumor and normal urothelium without fluorescence in the submucosa and the muscle layers. Subsequently no hypericin was detected in plasma, indicating that under these conditions systemic side effects should not be expected. Because the conditions used in this study were similar to those used in our previous clinical study, it is therefore likely that whole bladder wall PDT in the clinic under these conditions will produce selective urothelial tumor destruction without causing damage to the underlying muscle layers.
1. The effect of capsaicin on bladder motility in vivo (urethane anaesthesia) and in vitro, plasma extravasation (Evans blue leakage technique) and content of substance P-like immunoreactivity (SP-LI) of the urinary bladder was investigated in various mammalian species. 2. Systemic capsaicin desensitization (rat and hamster, 50 mg/kg s.c. 4 days before; guinea-pig 55 mg/kg s.c. 4-7 days before) increased bladder capacity in rats and guinea-pigs and reduced voiding efficiency in guinea-pigs. All other urodynamic parameters were unaffected in both rats, guinea-pigs and hamsters. 3. Reflex bladder voiding was abolished by spinal cord transection in anaesthetized rats and hamsters. On the other hand, hexamethonium-(20 mg/kg i.v.)sensitive voiding contractions were obtained in response to saline filling 45 min from cord transection in guinea-pigs, indicating a profound interspecies variation in the basic organization of micturition. 4. Exposure to capsaicin (1 microM) produced a contraction of the isolated bladder from rats, guinea-pigs (dome) and mice. Capsaicin produced only a slight contractile response in the guinea-pig bladder base. The motor response to capsaicin of the rat, guinea-pig and mouse bladder exhibited marked desensitization, suggesting a specific effect on sensory nerves. On the other hand, capsaicin (1 microM) produced a slight relaxation of the hamster isolated bladder but this effect was reproducible at 1-2 h intervals, suggesting an unspecific effect. Capsaicin (1-10 microM) did not affect motility of strips from the dome or the base of the rabbit bladder. 5. Intravenously administered capsaicin produced a marked plasma extravasation (Evans blue leakage) in the lower urinary tract of rats, mice and guinea pigs. In rats but not guinea-pigs the reaction in the bladder base was greater than in the dome. In hamsters intravenous capsaicin failed to induce any significant Evans blue leakage in the lower urinary tract. 6. SP-LI was detected in the lower urinary tract of rats, guinea-pigs, rabbits and mice but not hamsters. Bladder SP-LI was depleted by systemic capsaicin desensitization in rats, guinea-pigs and mice. Reverse phase HPLC indicated that all the immunoreactive material co-eluted with authentic substance P or its oxidized form. 7. These findings indicate that noticeable species-related differences exist with regard to the functions mediated by the capsaicin-sensitive neurons in the urinary bladder.
OBJECTIVES: To evaluate the effectiveness of combined local bladder hyperthermia and intravesical chemotherapy for the treatment of patients with high-grade (G3) superficial bladder cancer. METHODS: Patients with G3 bladder tumors (Stage Ta or T1) were treated with combined intravesical chemotherapy with mitomycin-C and local radiofrequency hyperthermia of the bladder wall. The patients were treated with either a prophylactic protocol (40 mg mitomycin-C) after complete transurethral resection of all tumors or with an ablative protocol (80 mg mitomycin-C) when visible tumor was seen on video-cystoscopy or bladder biopsies were positive for carcinoma in situ. RESULTS: Combined chemo-thermotherapy was administered to 52 patients with high-grade superficial bladder cancer (40 patients with Stage T1 tumor, 11 with Ta, and 3 with concomitant or isolated carcinoma in situ). At a median follow-up of 15.2 months (mean 23, range 6 to 90), no stage progression to T2 or disease-related mortality had occurred. The bladder preservation rate was 86.5%. The prophylactic protocol was administered to 24 patients. After a mean follow-up of 35.3 months, 15 patients (62.5%) were recurrence free. The bladder preservation rate was 95.8%. The ablative protocol was administered to 28 patients. Complete ablation of the tumor was accomplished in 21 patients (75%). After a mean follow-up of 20 months, 80.9% of these patients were recurrence free. The bladder preservation rate for the ablative group was 78.6%. CONCLUSIONS: Combined local bladder hyperthermia and intravesical chemotherapy has a beneficial prophylactic effect in patients with G3 superficial bladder cancer. Ablation of high-grade bladder tumors is feasible, achieving a complete response in about three quarters of the patients.
This is the first of 2 articles that summarize the findings of the International Consensus Panel on cytology and bladder tumor markers. The objectives of our panel were to reach a consensus on the areas where markers are needed, to define the attributes of an ideal tumor marker, and to identify which marker(s) would be suitable for diagnosis and/or surveillance of bladder cancer. Our panel consisted of urologists and researchers from Europe, Asia, and the United States who reviewed original articles, reviews, and book chapters on individual bladder tumor markers published in the English language mainly using the PubMed search engine. Panel members also met during 3 international meetings to write recommendations regarding bladder tumor markers. The panel found that the most practical use of noninvasive tests is to monitor bladder cancer recurrence, thereby reducing the number of surveillance cystoscopies performed each year. Markers also may be useful in the screening of high-risk individuals for early detection of bladder cancer. However, more prospective studies are needed to strengthen this argument. Case-control and cohort studies show that several markers have a higher sensitivity to detect bladder cancer. However, cytology is the superior marker in terms of specificity, although some markers in limited numbers of studies have shown specificity equivalent to that of cytology. Our panel believes that several bladder tumor markers are more accurate in detecting bladder cancer than prostate-specific antigen (PSA) is in detecting prostate cancer. However, bladder tumor markers are held to a higher standard than PSA. Therefore, use of bladder tumor markers in the management of patients with bladder cancer will require the willingness of both urologists and clinicians to accept them.
PURPOSE: Achievement of urinary continence in patients with the exstrophy-epispadias complex remains a challenge. We reviewed our experience with the modified Young-Dees-Leadbetter bladder neck repair in patients with bladder exstrophy who underwent primary bladder closure elsewhere. MATERIALS AND METHODS: We retrospectively reviewed exstrophy charts and database of 57 male and 11 female with classic bladder exstrophy who underwent bladder neck repair at our institute and successful primary bladder closure elsewhere during the last 2 decades. Osteotomy was performed at primary closure in 14 (20%) cases and 9 (13%) patients at bladder neck repair in 9 (13%) to aid in stabilizing the urethra and pelvic ring, and to help reapproximate the pelvic floor musculature facilitating urinary continence. RESULTS: Primary closure was done within 72 hours of life elsewhere in 41 (60%) patients, and between ages 72 hours and 5 years (most during the first month of life) in 27. Paraexstrophy skin flaps were used in 33 (48%) cases, and the most common complication was bladder outlet obstruction of the posterior urethra secondary to the skin flaps. Of the 68 patients 57 (83%) are continent and voiding per urethra without need for augmentation or clean intermittent catheterization, 9 (13%) required clean intermittent catheterization including 7 who underwent continent urinary diversion after failed bladder neck repair, and 2 are still incontinent due to a severe posterior urethral stricture. Urinary retention was the most common symptom after bladder neck repair which resolved following catheter dilation or prolonged suprapubic catheter drainage. CONCLUSIONS: Successful early primary closure of a good bladder template is the most important determinant of eventual bladder capacity and compliance.
PURPOSE: Functional bladder neck obstruction has been definitively diagnosed in the last few years due to detailed synchronous pressure flow, electromyography and video urodynamics. Clean intermittent self-catheterization and bladder neck incision are the modalities of treatment. To our knowledge the role of alpha-blockers is not yet defined in women. A new technique was developed to perform bladder neck incision using a pediatric resectoscope. MATERIALS AND METHODS: A total of 24 women with obstructive voiding symptoms or retention were evaluated with video pressure flow electromyography, and diagnosed with functional bladder neck obstruction due to high pressure and low flow on silent electromyography and bladder neck appearance on fluoroscopy. Patients were initially treated with clean intermittent self-catheterization and alpha-blockers. Catheterization was stopped when post-void residual was less than 50 ml. and only alpha-blocker therapy was continued. Bladder neck incision was performed in patients who had a poor response to or side effects of alpha-blocker therapy, or when therapy was discontinued due to economic reasons. Clean intermittent self-catheterization was continued in patients who had a poor response to alpha-blockers or refused to undergo bladder neck incision. Bladder neck incision was performed in the initial 2 cases with an adult resectoscope using a Collin's knife and subsequently a pediatric resectoscope (13F). Uroflow and post-void residual measurements were performed in all cases. RESULTS: Of the 24 patients 12 (50%) showed improvement in symptoms, peak flow and post-void residual (p <0.01) with alpha-blocker therapy only. Of the 12 patients who had a poor response to alpha-blockers 6 underwent bladder neck incision subsequently and 6 remained on clean intermittent self-catheterization. All 8 patients treated with bladder neck incision, including 2 who had a good response but discontinued alpha-blocker therapy, had sustained improvement in post-void residual and peak flow (p <0.01) after a mean followup of 3.8 +/- 2.4 years. Grade 1 stress incontinence in 2 adult resectoscope cases responded to conservative treatment. None of the pediatric resectoscope cases had stress incontinence. CONCLUSIONS: Clean intermittent self-catheterization and alpha-blockers are the initial treatment options for functional bladder neck obstruction. The alpha-blockers were successful in 50% of our patients. Bladder neck incision should be offered judiciously with minimal risk of curable stress incontinence. The pediatric resectoscope is useful to make a well controlled incision safely in the female urethra.
The glutathione S-transferase M1 (GSTM1) gene is polymorphic in humans, and the deficiency in enzyme activity of GSTM1 is caused by the inherited homozygous absence of the GSTM1 gene, or the "null" genotype (GSTM1, 0/0). The increased risk of bladder cancer has been shown to correspond with this gene defect. No reports, however, have been found in the literature regarding GSTM1 gene deficiency with superficial and invasive bladder cancer. In this study, we examined the association of the GSTM1-null genotype with superficial and invasive bladder cancer. Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the GSTM1 gene defect in Turkish patients with superficial bladder cancer (N = 61), invasive bladder cancer (N = 42), and control subjects (N = 202) who had no history of cancer. The GSTM1 null genotype was observed in 34.7% of the control subjects and in 54.3% of total bladder cancer patients (OR: 2.246; 95% CI: 1.384-3.645, P: 0.00094). In other words, the presence of the GSTM1-null genotype significantly increased the risk of bladder cancer development. Among invasive bladder cancers, the frequency of the GSTM1-null genotype was 64.3% (OR: 0.294, 95% CI: 0.147-0.590, P: 0.0003). This was also significantly higher than control subjects, indicating that patients carrying this genotype were at increased risk for developing invasive bladder cancer. This relationship was not statistically significant in the superficial bladder cancer group (OR: 0.585, 95% CI: 0.327-1.045, P: 0.06). Our results indicate that GSTM1 gene polymorphism should be considered as an important risk modifier in the development of bladder cancer and might be used as a predictive marker for invasive bladder cancer.
PURPOSE: The range of maximum bladder smooth muscle tension in the published literature varies between 1.3 and 59 N/cm (2) depending on the experimental setup. Based on own animal trials, we attempted to determine bladder wall tension during detrusor contraction in physiological and obstructed voiding and during detrusor instabilities in our patient collective. MATERIALS AND METHODS: In 24 patients (mean age 56 +/- 8.4 years), bladder wall tension as detrusor force per cross sectional area of bladder tissue [in N/cm (2)] was calculated following urodynamic evaluation and ultrasound determination of bladder wall thickness. The patients were divided into 3 groups with 8 patients per group as follows: group I: patients with bladder outlet obstruction in accordance with the Abrams-Griffiths nomogramme; group II: patients with detrusor instabilities; group III: patients with normal bladder emptying. RESULTS: Maximum bladder wall tension in group I was 9.8 +/- 3.9 N/cm (2). During bladder instabilities (group II), maximum bladder wall tension was 11.7 +/- 2.6 N/cm (2). Maximum bladder wall tension was 2.8 +/- 0.5 N/cm (2) in group III, which was significantly lower (p < 0.05, Mann-Whitney U-Test) than that of groups I and II. CONCLUSIONS: We conclude that bladder wall tension is distinctly lower in patients with normal voiding than in those with obstructed micturition or detrusor instabilities. Furthermore, our results suggest that the detrusor is not fully activated during normal voiding and is thus capable of compensating for to a greater stress situation with more effective contractions.
OBJECTIVE: Urinary retention and micturition disorders after overdistension are clinically well-known complications of subvesical obstruction. We attempted to evaluate whether bladder overdistension influences bladder response and whether overdistension supports detrusor decompensation. METHODS: Following lumbal laminectomy in 9 male foxhounds, the sacral anterior roots S2 and S3 were placed into a modified Brindley electrode for reproducible and controlled detrusor activation. The bladder was filled in stages of 50 ml from 0 to 700 ml, corresponding to an overdistension. At each volume, the bladder response during sacral anterior root stimulation was registered. After overdistension, the bladder was refilled stepwise from 0 to 300 ml and stimulated. RESULTS: In all dogs, the bladder response was influenced by the intravesical volume. The maximum pressure (mean 69.1 cm H(2)O) was observed at mean volume of 100 ml. During overdistension, a significant reduction in bladder response of more than 80% was seen. After overdistension, a significant reduction in intravesical pressure of 19.0% was observed. In 2 cases, reduction in bladder response was more than 50% after a single overdistension. CONCLUSIONS: We conclude that motoric bladder function is influenced during and after overdistension. A single bladder overdistension can support acute and long-lasting detrusor decompensation. In order to protect motoric bladder function, bladder overdistension must be prevented.
In urinary bladder and gall bladder of guinea-pig, the application of hyperosmotic 65.4 mM K solution induced a tonic contraction and increased the rate of oxygen consumption two or three times. The increased O2 consumption maintained steady level during 120 min. In isosmotic 154 mM K, Na-deficient solution, the tonic contraction gradually decreased and oxygen consumption also showed a transient increase followed by a small one. In the urinary bladder, the addition of pyruvic acid completely prevented the decline of the tonic contraction by iso-154K solution at 120 min, but this addition partially prevented it in the gall bladder. Hyperosmotic application of sucrose partially prevented it in the urinary bladder, but completely recovered it in the gall bladder. When NaCl was applied to iso-154K solution, the decrease of tonic contraction was prevented by half in both the muscles. The application of pyruvic acid and NaCl prevented the reduction of oxygen consumption by iso-154K solution in the urinary bladder, but in the gall bladder, this had little effect. There was a close correlation (r = 0.950) between the muscle tension and the rate of oxygen consumption in the urinary bladder at 120 min under various conditions. In the gall bladder, a correlation (r = 0.875) was also found between both when the results by hyperosmotic addition of NaCl and sucrose were omitted. In the urinary bladder, tension cost, a ratio of O2 consumption rate (mumol O2/g/min) to developed tension (kg force/cm2), was large (0.206) and similar to that of taenia coli; and that of gall bladder was small (0.130) and almost similar to that of vascular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
This is a quantitative study of the effect of a full and empty bladder on the position of the uterus, ovaries and bladder relative to the lumbar spine. Data are used to estimate the difference in radiation dose to these organs from performing a lumbar spine CT investigation or a lateral lumbar spine radiograph with a full bladder compared with an empty bladder. 12 women of child-bearing age underwent pelvic magnetic resonance scans with full and empty bladders. The positions of the uterus, ovaries and bladder were matched with the radiation dose distribution that would have occurred either side of the inferior boundary of the CT scan volume and the lateral lumbar spine radiograph. These radiation dose profiles were measured on phantoms using a combination of ionization chambers and thermoluminescent dosemeters. When the bladder was emptied, the mean position of the endometrial cavity fundal tip moved from 4.1 cm to 6.1 cm inferior to the centre of the L5/S1 disc space, and from 0.87 cm to 1.12 cm anterior to the centre of the L5/S1 disc space. This movement on micturation would have reduced the mean dose to the uterine internal fundal tip during a pelvic CT scan from 6.8 mGy to 3.9 mGy, which represents a mean reduction of 43% (range 12-67%). The mean dose from a lateral lumbar spine examination would have been reduced from 197 microGy to 126 microGy. The change in ovary position results in the mean ovary dose being reduced by 48% for the lumbar spine CT scan and by 43%) for a lateral lumbar spine radiograph. When the bladder was emptied, the average position of the bladder wall moved from 7.2 cm to 10.3 cm inferior to the L5/S1 disc space. This change in bladder position reduces the mean dose to the wall of a full bladder from 5.7 mGy for a CT scan and 114 microGy for a lumbar spine radiograph to 2.2 mGy and 42 microGy, respectively, for an empty bladder.
Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder afferent neurons. In adult female rats, NGF (2.5 microg/microl) was infused continuously into the intrathecal space at the L6-S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 microl/h). Bladder afferent neurons were labeled with axonal transport of Fast Blue injected into the bladder wall. After intrathecal injection of NGF, cystometrograms under an awake condition showed bladder overactivity revealed by time-dependent reductions in intercontraction intervals and voided volume. ELISA analyses showed significant increases in NGF levels in L6-S1 dorsal root ganglia of NGF-treated rats. In patch-clamp recordings, dissociated bladder afferent neurons exhibiting tetrodotoxin (TTX)-resistant action potentials from NGF-treated animals were larger in diameter and had significantly lower thresholds for spike activation compared with sham rats. In addition, the number of TTX-resistant action potentials during 600 ms depolarizing pulses was significantly increased time dependently after 1 or 2 weeks of NGF application. The density of slowly inactivating A-type K+ currents was decreased by 52% in bladder afferent neurons with TTX-resistant spikes after 2 week NGF treatment. These results indicate that increased NGF levels in bladder afferent pathways and NGF-induced reduction in A-type K+ current density could contribute to the emergence of bladder overactivity as well as somal hypertrophy and hyperexcitability of bladder afferent neurons.
The enzyme telomerase maintains a constant telomere length in immortalized cells, allowing unlimited cell proliferation. Almost all cancer cells express telomerase activity. However, little data is available regarding the role of telomerase activity in the detection of bladder cancer with a bladder wash specimen. We detected telomerase activity in a bladder wash specimen of bladder cancer and normal tissues, and compared them with final pathologic diagnosis. Twenty-three patients with transitional cell carcinoma (TCC) of the bladder were enrolled in our study. A bladder wash specimen was obtained before transurethral resection of the bladder (TURB) and normal and cancer tissues from the same patients during TURB. Telomerase activity was analyzed in each specimen a using telomeric repeat amplification protocol (TRAP) assay based on polymerase chain reaction (PCR) technique. Cytologic diagnosis was performed using Papanicolaou's stain with cytocentrifuged cytology preparation. We observed telomerase activity in 95.7% (22/23) of bath cancer tissues and bladder wash specimens; only one case did not express telomerase activity. Telomerase activity was undetected in all normal tissues except one, which was obtained from a patient with carcinoma in situ. A total of 69.6% (16/23) of wash specimens were positive in cytopathologic diagnosis. The accuracy of cytopathologic diagnosis in pathologic grade 2 or 3 was relatively high (83.3%, 15/18). However, in five cases of grade 1 TCC only 20% (1/5) of cytologic diagnosis was positive whereas the telomerase activity of wash specimens was detected in 80% (4/5). Our data demonstrates that not only the majority of human bladder cancer tissues, but also the bladder wash specimens obtained from patients with TCC, expressed telomerase activity. It indicates that telomerase activity may be a reliable marker in detecting bladder cancer especially in cases with a low grade that bladder wash cytology can miss.
PURPOSE: In this study, we have retrospectively compared patient backgrounds, prognosis and QOL (quality of life) in patients with invasive bladder cancer treated by radical cystectomy or by bladder preservation. PATIENTS AND METHODS: This study enrolled recent 30 cases from each institutions, totally 120 cases from four institutions. All patients were diagnosed with invasive bladder cancer in stage T 2 or T 3, N 0, M 0. The patients planned for preserving the bladder were treated with a combination of intra-arterial chemotherapy and radiation as an induction therapy. The questionnaire used to assess QOL was the EORTC QLQ-C 30 (Japanese-language edition). RESULTS: Radical cystectomy was selected as the initial treatment in 60 cases (the planned radical cystectomy group). Bladder preservation was planned but the presence of residual tumors after induction therapy underwent radical cystectomy in 18 cases (the preservation-radical cystectomy group). Bladder preservation was achieved in 42 cases (the preservation group). In a comparison of background factors, histologically grade 3 tumor and cases with histology other than transitional cell carcinoma, were significantly common in the planned radical cystectomy group. Because this study is not an randomized test, it is difficult to compare the outcomes between the patients treated by radical cystectomy or by bladder preservation. However, it is indicated that the candidates for bladder preservation therapy exist among the patients with T 2 or T 3, N 0, M 0 bladder cancer. Quality of life, as evaluated from global QL and from physical, cognitive, and emotional function, tended to be better in the patients with their bladder, although no difference was noted among the groups with regard to life role or social function. Symptoms such as sleep disturbance and diarrhea were common in the radical cystectomy groups, and financial impact, constipation, appetite loss, and dyspnea also tended to more frequently affect patients in these groups. CONCLUSION: Our results indicate that bladder preservation treatment using an induction therapy is one of option of the treatment for clinically T 2 or T 3, N 0, M 0 bladder cancer. We need a prospective randomized study with a long-term follow-up to elucidate true candidates for this treatment.