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PubMed2000

A prospective pilot evaluation of urinary and immunohistochemical markers as predictors of clinical stage of urothelial carcinoma of the bladder.

OBJECTIVE: To determine, in patients newly diagnosed with bladder cancer, whether p53, epidermal growth factor receptor (EGFR), microvessel density (MVD), urinary bladder tumour antigen (BTA TRAKtrade mark, Bion Diagnostic Sciences, Redmond, WA) and cytology were predictive of clinical stage, evaluated as a function of the clinical stage obtained at transurethral resection of the bladder tumour with and without the addition of clinical grade, a known strong predictor of clinical stage. PATIENTS AND METHODS: Between December 1997 and September 1998, 22 men and seven women with a cystoscopic diagnosis of urothelial bladder carcinoma were prospectively enrolled in the study. Urine was collected for cytological and BTA TRAK evaluation before transurethral resection. Tumour grade and clinical stage were obtained from the transurethral resection specimen. MVD was evaluated by computerized calculations of 'optimal MVD' (OMVD) and 'area-weighted MVD' (AWMVD) while p53 and EGFR information was obtained by manual immunohistochemical techniques; 21 patients had sufficient tissue for all immunohistochemical assessments and comprised the study group. Univariate and multivariate comparisons were carried out to determine the contribution of each variable to the prediction of clinical stage. RESULTS: Although there was a trend, cytological analysis and p53 and MVD immunoreactivity did not significantly correlate with clinical stage, while tumour grade, BTA TRAK and EGFR immunoreactivity did. In a univariate analysis, tumour grade and BTA TRAK were related to clinical stage. In a multivariate analysis, grade was the single best predictor of clinical stage. This analysis also showed that the addition of BTA TRAK and MVD information to grade incrementally improved the predictive ability of grade. CONCLUSIONS: This pilot study suggests that BTA TRAK and MVD contribute incremental information to tumour grade in predicting the clinical stage of urothelial carcinomas of the bladder; grade remains the most important predictor. These results suggest that further work with BTA TRAK and MVD in more patients and on biopsy material obtained during clinic cystoscopy is warranted for the future development of less invasive methods of identifying patients with invasive bladder cancer.

Aged↗
PubMed2003

T2a transitional cell carcinoma of the bladder: long-term experience with intravesical immunoprophylaxis with bacillus Calmette-Guerin.

PURPOSE: In this prospective study we evaluate the effect of combined transurethral resection of early muscle invasive bladder cancer and immunotherapy with bacillus Calmette-Guerin (BCG) in patients unfit for radical cystectomy or refusing more aggressive therapies. MATERIALS AND METHODS: A total of 22 patients with a mean age 73.6 years were included in the study. Inclusion criteria were histologically proven muscle invasive transitional cell carcinoma of the bladder with a tumor-free second resection and negative staging examinations in patients unfit for radical cystectomy or refusing more aggressive therapies. All patients received 6 weekly instillations of 120 mg. BCG starting 14 to 21 days after the last transurethral resection of the tumor. Followup at 3 months included cystoscopy, urinary cytology, ultrasound of the abdomen and chest x-ray. Every 6 months computerized tomography of the abdomen and bone scans were performed. RESULTS: The overall 5-year survival rate was 69.1%, while the disease specific 5-year survival rate was 94%. One muscle invasive recurrence was noted at 69 months, which was again treated with the same regimen but ultimately led to radical cystectomy 21 months later. One patient died of progressive recurrence in the upper urinary tract. The 5-year recurrence-free survival rate was 46.5%. The only severe complication was BCG pneumonitis. CONCLUSIONS: The data show encouraging results for transurethral resection of bladder tumor with intravesical BCG therapy in select patients with T2a bladder cancer who are not candidates for radical cystectomy.

Administration, Intravesical↗
PubMed1999

An update of combined modality therapy for patients with muscle invading bladder cancer using selective bladder preservation or cystectomy.

PURPOSE: We update the results of tri-modality treatment for patients with muscle invading bladder tumors with selection for bladder preservation based on tumor response to induction therapy. MATERIAL AND METHODS: We reviewed the literature on modern tri-modality bladder preserving approaches using transurethral resection, radiation and concurrent chemotherapy followed by either bladder conservation with careful surveillance for complete responding patients or prompt cystectomy in those whose tumors persist after induction therapy. RESULTS: The published experiences from 3 centers and 2 prospective trials done by the Radiation Therapy Oncology Group were evaluated for 5-year overall survival of patients selected for bladder preservation or prompt cystectomy (49 to 63%) and for those with a conserved bladder (38 to 43%). The overall 5-year survival rates were comparable to other series of immediate cystectomy based approaches in patients of similar age and presenting with tumors of similar clinical stage. Of patients treated with the bladder preserving approach 20 to 30% cured of muscle invading cancer will subsequently have a new superficial tumor. The superficial tumors have responded well to intravesical drug therapy. Modern bladder preserving treatments usually result in a well functioning bladder without incontinence or significant hematuria. However, concurrent systemic chemotherapy and radiation have the potential for acute morbidity. Presently the ideal candidate for bladder preservation has primary clinical stage T2 tumor, no associated ureteral obstruction, visibly complete transurethral resection and complete response after induction chemoradiation based on endoscopic evaluation including re-biopsy and cytology. CONCLUSIONS: It is recommended that tri-modality treatment be administered by dedicated multimodality teams. In this country this approach to treatment is available at many of the institutions participating in the Radiation Therapy Oncology Group study. This treatment may be considered a reasonable alternative in patients who are deemed medically unfit for cystectomy and for those who are seeking an alternative to radical cystectomy.

Combined Modality Therapy↗
PubMed2001

Neo-adjuvant chemotherapy in invasive bladder cancer.

In patients with locally advanced muscle-invasive bladder cancer, neo-adjuvant chemotherapy was designed to treat micrometastatic disease present in up to 50% of patients at the time of diagnosis. Early chemotherapy has been combined with local therapy based on the reasoning that treatment of small volume disease would result in a better outcome. Another reason for giving neo-adjuvant chemotherapy is in an attempt to save the bladder. In selected patients, bladder preservation can be achieved with the use of chemotherapy plus radiotherapy, partial cystectomy, or transurethral resection of the bladder (TURB). Neo-adjuvant chemotherapy and bladder preservation remain controversial topics, as radical cystectomy is still considered to be the gold standard of treatment for muscle-invasive bladder cancer. The true success of bladder-preserving treatment by chemotherapy with or without RT will require validation in prospective randomized trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

The role of urinary cytology for detection of bladder cancer.

PURPOSE: The aim of the present study was to test the value of urinary cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: One thousand three hundred and eighty voided urine and bladder wash specimens of 495 patients were evaluated by urinary cytology. All patients then underwent transurethral resection of suspicious bladder areas if cystoscopy and/or preceding biopsy were positive. Statistical differences were analysed using the two-sided Fisher's exact test and Cochran's test (p<0.05). RESULTS: In 495 patients including 142 patients with bladder cancer urinary cytology revealed a sensitivity of 38.0% and a specificity of 98.3% with a positive and negative predictive value of 90.6 and 78.6, respectively. Sensitivity increased significantly with malignancy grade (p<0.05). In high grade tumours sensitivity improved from initial 52.2% up to 78.3% after the third sample. In sensitivity and specificity of voided urine and barbotage washing samples no significant difference was detected. CONCLUSIONS: Urinary cytology has its place as an additive diagnostic tool to cystoscopy. None of the currently available urinary markers can replace cystoscopy but are helpful for specific diagnostic problems.

Aged↗
PubMed1999

Predicting cancer progression in patients with stage T1 bladder carcinoma.

PURPOSE: A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach. PATIENTS AND METHODS: The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer. RESULTS: The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P =.037). The 5-year progression-free survival rate for patients with depth of invasion of >/= 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P =.009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression. CONCLUSION: The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.

Aged↗
PubMed2000

[Metastatic bladder tumor disseminated lymphogenously from gastric cancer: a case report].

A 59-year-old man was referred to our clinic with a complaint of frequent urination, voiding pain, and macroscopic hematuria. He had undergone total gastrectomy for mucinous adenocarcinoma, 21 months earlier. Pelvic computed tomography revealed a thick bladder wall all around. There were no other metastatic sites except for paraaortic lymph nodes. Transurethral resection of the bladder tumor was performed. The specimen showed signet ring cell carcinoma and revealed the same pathological findings as the primary gastric cancer. We diagnosed him with metastastic bladder tumor lymphogenously disseminated from gastric cancer. Such lymphogenous metastases from gastric cancer at the entire bladder wall without other apparent lesions have rarely been reported in the Japanese literature.

Adenocarcinoma, Mucinous↗
PubMed2002

[Urology].

We reviewed comparative clinical studies for prostate cancer and bladder cancer performed in Japan. A systematic search was done using PubMed and Icyushi WEB to find randomized clinical trials and the result was verified. Each manuscript was summarized according to the seven items of stage, entry period, exposure, endpoint, sample size, method of randomization and result. Forty reports were found as randomized clinical trials for prostate cancer, and sixty-two reports were identified for bladder cancer. Most exposures for advanced prostate cancer were hormonal therapy involving intravesical instillation after transurethral resection for superficial bladder cancer. At minimum, we have clarified that large scale randomized trials have been conducted in Japan for both prostate cancer and bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Intravesical 4'-epi-doxorubicin (epirubicin) versus bacillus Calmette-Guérin. A controlled prospective study on the prophylaxis of superficial bladder cancer.

BACKGROUND: The selection of the most appropriate antineoplastic agent and optimal treatment schedule for the prophylaxis of superficial bladder cancer against tumor recurrences is the subject of continual investigations. METHODS: A controlled prospective trial involving 161 patients evaluated and compared the efficacy of intravesical epirubicin and bacillus Calmette-Guérin (BCG) administration as prophylaxis against recurrences after complete transurethral resection of superficial bladder cancer. The treatment schedule, consisting of one 6- or 8-week course of instillations (50 mg epirubicin or 150 mg BCG per instillation) followed by single maintenance doses to the responders at follow-up examinations, was modified for those of the initial responders who were at high risk for recurrence and who received an additional separate 4-week course of treatment 6 months after the start of therapy. RESULTS: Sixty percent of the patients treated with epirubicin, 68% of the patients treated with BCG, and 41% of the control subjects, who underwent resection only, remained free of recurrences for a mean follow-up of 32.9 months. The only significant difference was found between patients treated with BCG and control subjects, in favor of the former. Conversely, recurrence rate per 100 patient-months and mean interval to recurrence showed both drugs to be superior to resection alone regarding several tumor characteristics. However, a significant benefit in favor of BCG when compared with epirubicin was shown in those patients who had Stage T1 and Grade 3 tumors at presentation. CONCLUSIONS: Intravesical epirubicin and BCG were superior to transurethral resection alone in the prophylaxis of superficial bladder cancer, but with respect to superficially invasive and high-grade tumors, BCG demonstrated a remarkable advantage.

Administration, Intravesical↗
PubMed1990

Intravesical bacillus Calmette-Guérin administration in the prophylaxis of superficial bladder cancer.

A total of 68 patients received prophylactic/adjuvant intravesical Pasteur strain bacillus Calmette-Guérin (BCG) instillations following transurethral resection for superficial bladder carcinoma. An induction phase consisting of 6 weekly instillations was followed by a maintenance phase consisting of 1 instillation given every 3 months. A second 6-week course of BCG was administered to initial failure followed again by a quarterly maintenance therapy. The response rate for patients treated with one 6-week course was 56%, while complete response was achieved in 72% when both treatment courses were considered. Follow-up period lasted at least 2 years after each course of BCG. These results suggest that additional courses of BCG increase the prophylactic efficacy of intracavitary BCG. Regarding the purified protein derivative (PPD) skin test and granulomatous response in the bladder, it has been shown in the present study that, although favourable results occurred more frequently among patients with either PPD conversion from negative to positive or vesical granuloma formation, neither of these indices should be considered reliable prognostic indicators.

BCG Vaccine↗
PubMed2001

Role of 5-aminolevulinic acid in the diagnosis and treatment of superficial bladder cancer: improvement in diagnostic sensitivity.

OBJECTIVES: To use 5-aminolevulinic acid (5-ALA) in diagnostic cystoscopy and during transurethral resection of the bladder (TURB) to treat transitional cell carcinoma. The efficacy of this new technique was compared with standard cystoscopy. METHODS: The 5-ALA, instilled in the bladder 2 hours before cystoscopy, makes the pathologic tissue fluorescent when illuminated with blue light (375 to 400 nm). This allows a better recognition of the neoplastic forms for both diagnostic and therapeutic purposes during TURB. This method has been used since May 1997 on 49 patients in whom bladder tumor was diagnosed either immediately or during postchemotherapy follow-up. RESULTS: One hundred seventy-nine biopsies were taken of fluorescent and nonfluorescent areas (3.5 per patient) to check the effectiveness of the new method compared with standard cystoscopy. A good correlation was found between 5-ALA cystoscopy and the histopathologic diagnosis, with a good sensitivity (87%). The 5-ALA cystoscopy allowed the diagnosis of a tumor in 24 patients with negative standard cystoscopic findings. Furthermore, 5-ALA cystoscopy detected 7 cases of carcinoma in situ. Neither local nor systemic (because of endovesical instillation) side effects were noted. CONCLUSIONS: We believe that 5-ALA could be routinely used in the diagnosis of superficial bladder tumors, as it was shown to improve the diagnostic sensitivity for carcinoma in situ and to reduce the risk of recurrence related to missed cancerous lesions or incomplete TURB.

Adult↗
PubMed1998

Local microwave hyperthermia and intravesical chemotherapy as bladder sparing treatment for select multifocal and unresectable superficial bladder tumors.

PURPOSE: The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neoadjuvant organ sparing clinical study. MATERIALS AND METHODS: A total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system, based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas. RESULTS: After treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved. CONCLUSIONS: Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.

Administration, Intravesical↗
PubMed1982

Unanticipated vesicoureteral reflux: a possible sequela of long-term thio-tepa instillations to the bladder.

Vesicoureteral reflux was studied by retrograde cystograms in 75 patients with recurrent transitional cell carcinoma of the bladder. Unilateral reflux was detected in 6 of the 14 patients (42.8 per cent) treated by transurethral resection of the bladder tumors. Five of these cases of reflux were anticipated and 1 was unanticipated. Among 61 patients treated by tumor resection and adjuvant instillations of thio-tepa reflux was found in 33 ureters of 25 patients (41.0 per cent). Of the 33 cases of reflux 15 were anticipated, while 18 were unanticipated. All the anticipated cases of reflux resulted from the direct effect of tumor resection on the ureteral orifice. The effect of thio-tepa on bladder mucosa and the ureteral orifices is suggested as a possible cause of the unanticipated cases of reflux.

Carcinoma, Transitional Cell↗
PubMed1991

Serum and urinary levels of beta human chorionic gonadotrophin in patients with transitional cell carcinoma.

Serum and early morning urine specimens were obtained from 62 patients. The levels of beta human chorionic gonadotrophin (BhCG) in both serum and urine were estimated simultaneously in all cases. At the time of estimation 43 patients had transitional cell carcinoma of the bladder, one had transitional cell carcinoma of the renal pelvis and three had carcinoma in situ (two of whom also had overt carcinoma). Raised serum and urinary levels were found in only three patients, all of whom had poorly differentiated or metastatic transitional cell carcinoma of the bladder. This observation is in accordance with previous studies. In one of these patients, who underwent transurethral resection of her bladder tumour, the urinary levels returned to within normal limits post resection. An additional three patients had elevations of serum BhCG. Two of these three patients had poorly differentiated transitional cell carcinoma present at the time of estimation and one had no sign of recurrence. Using immunoperoxidase staining a retrospective study was undertaken to stain all available sections belonging to patients studied to observe whether BhCG was being produced by the respective tumours. Twelve well differentiated, nine moderately well differentiated and seven poorly differentiated specimens were available. In no case was evidence of BhCG production demonstrated in these tumours despite its presence being demonstrable in positive controls. We confirm the production of BhCG associated with bladder tumours, a feature correlated with poorer differentiation. Studies employing larger patient numbers are necessary to clarify the role of this tumor marker in patients with well differentiated bladder tumours.

Carcinoma, Transitional Cell↗
PubMed2002

Prognostic significance of a combination of soluble Fas and soluble Fas ligand in the serum of patients with Ta bladder cancer.

Recurrence after transurethral resection is one of the major problems in the treatment of superficial bladder cancer. However, there are no potent prognostic markers for recurrence in superficial bladder cancer at present. As circulating soluble Fas (sFas) and soluble Fas ligand (sFasL) have been implicated in protection from Fas-mediated apoptosis against cancers and may interfere with immune surveillance against autologous cancers, sFas and sFasL in the serum of patients with Ta bladder cancer were evaluated as prognostic tumor markers for recurrence. The serum levels of sFas and sFasL were measured by an enzyme-linked immunosorbent assay. Patients with Ta bladder cancer with low serum levels of both sFas and sFasL had a significantly longer postoperative tumor-free interval than those with high serum level of either sFas or sFasL in the 3-year follow-up. There was no correlation between the serum levels of sFas and sFasL. The present study has demonstrated that elevated serum sFas or sFasL predicts early recurrence in patients with Ta bladder cancer. These findings suggest that the serum levels of sFas and sFasL can be used as a prognostic indicator for recurrence in patients with Ta bladder cancer, and that sFas and sFasL may independently inhibit Fas-mediated apoptosis.

Adult↗
PubMed2001

Differences in gene expression in muscle-invasive bladder cancer: a comparison of Italian and American patients.

OBJECTIVE: To seek differences in gene expression in the primary muscle-invasive bladder cancers of two cohorts of patients having different survival rates. An Italian group treated by transurethral resection of the bladder tumor (TURBT) and neo-adjuvant chemotherapy using methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) followed by TURBT, partial cystectomy or radical cystectomy (75% 3-year survival) was compared to an American cohort treated by radical cystectomy (51% 3-year survival). METHODS: Immunohistochemistry was used to examine the protein expression levels of three genes that act at the G1/S cell cycle checkpoint, p53, p21/waf-1/cip1 (a downstream effector gene in the p53 pathway) and Rb, plus a major inhibitor of apoptosis, Bcl-2. RESULTS: For the bladder cancers of the Italian patient cohort, there was a significantly higher rate of p53 immunopositivity (93 vs. 63%, p = 0.002) and a significantly lower rate of Rb loss (25 vs. 54%, p = 0.009). In bivariate analysis, 72% of Italian tumors were immunopositive for both p53 and p21 (p53+/p21+) vs. 49% for the American tumors. The subset of Italian patients with p53+/p21+ tumors were more frequently disease-free (stage pT0) following chemotherapy and were less likely to fail therapy than those with p53+/p21- tumors (p = 0.0357). Loss of Rb staining was associated with a decreased 5-year survival in the Italian, but not in the American patients. CONCLUSIONS: (1) Significant differences in the expression of the p53, p21 and Rb genes were found between the 2 groups of patients. (2) Italian patients with p53+/p21+ tumors had significantly lower recurrence rates after TURBT and chemotherapy than those having p53+/p21- tumors. (3) Absence of p21 immunopositivity in the Italian tumors may identify alterations in the p53 pathway that predict poor outcome.

Gene Expression Regulation, Neoplastic↗
PubMed1992

[Primary localized amiloidosis with recurrent relapse: a case report].

This is a case report of primary localized amyloidosis of the urinary bladder. The patient was a 73-year-old woman who had relapse of this disease three times. Primary localized amyloidosis of the urinary bladder is an especially rare disease and the prognosis is excellent in most cases. We performed transurethral resection of the bladder tumor (TUR-Bt) each time and we are following up this patient carefully. After the last TUR-Bt, she has had no recurrence for 7 months. Considering multifocal recurrence and excellent prognosis, we stress the importance of TUR-Bt for diagnosis and careful follow up.

Aged↗