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Treatment of patients with superficial bladder cancer by intravesical instillation of anticancer drugs plus oral chemotherapy following TUR-Bt: a randomized controlled trial.

We conducted a randomized controlled trial to compare local recurrence rate after transurethral resection of superficial bladder cancer treated by either intravesical instillation of an anticancer drug alone (method A) and the intravesical instillation plus oral chemotherapy (doxifluridine, 5'-DFUR, an intermediate metabolite of capecitabine) (method B). Results between groups showed no difference in recurrence-free survival curves in 196 patients subjected to primary analysis. However, patients subjected to secondary analysis (method B, over 3 months administration of 5'-DFUR) showed a significantly better prognosis than method A (p=0.0244, Wilcoxon). Regarding correlation between thymidine phosphorylase (TP, an enzyme to convert 5'-DFUR to 5-fluorouracil) level and prognosis, method A patients showed poorer prognosis in higher TP level cases than in lower TP levels. However, there was no significant difference in prognosis between those with higher and lower TP levels. In method B patients, there was no difference in prognosis between those with higher and lower TP levels. Method A patients tended to show a slightly better prognosis than those with lower TP levels, while method B patients tended to have a slightly better prognosis with higher TP levels, but no significant difference was observed. These findings suggested 5'-DFUR showed a mild efficacy in patients with higher TP levels and that patients with higher TP levels resulted in poorer prognosis.

Administration, Intravesical↗

Upper urinary tract transitional cell carcinoma in patients with bladder carcinoma and associated vesicoureteral reflux.

Of 269 patients with bladder neoplasms treated during a 20-year period 47 had associated vesicoureteral reflux. All 47 patients were followed for 3 years or more, or until death. Upper urinary tract transitional cell cancer developed in 3, each of whom had recurrent bladder cancer. Among the 222 patients who had vesical cancer without reflux transitional cell carcinoma of the ureter developed in only 1, 11 years after transurethral resection for a bladder tumor. The incidences of upper tract transitional cell cancer in patients with and without vesicoureteral reflux were 6.4 and 0.44 per cent, respectively, which support the suggested role of reflux in disseminating or seeding of cancer cells from the bladder into the upper urinary tract. Patients with bladder cancer and associated vesicoureteral reflux have an approximately 15-fold greater risk of upper tract cancer developing compared with those without reflux. We recommend vigilant scrutiny of patients with recurrent bladder cancer and associated vesicoureteral reflux for early detection of upper urinary tract transitional cell carcinoma.

Aged↗

[Polyps of the posterior urethra in children. Apropos of a case].

Posterior urethral polyp is a rare disease, predominantly affecting boys. The authors report the case of an 10-month-old boy admitted to hospital with acute urine retention. The diagnosis of polyp was established on cystourethrography, ultrasonography and endoscopy. The polyp was resected via a bladder incision after failure of transurethral resection. Posterior urethral polyp is a benign tumour whose clinical presentation is dominated by signs of lower urinary tract obstruction. Cystourethrography and ultrasonography confirm the diagnosis and assess the repercussions on kidneys and bladder. Endoscopy has a double role: diagnostic and therapeutic.

Cystoscopy↗

Ureteral stump transitional cell carcinoma in a patient with recurrent superficial bladder cancer: an argument for complete nephroureterectomy in selected patients.

A 62-year-old white man had diffuse transitional cell carcinoma of a right ureteral stump 2 1/2 years after initial transurethral resection of a bladder tumor and right radical nephrectomy for renal cell carcinoma. This case and review of the literature suggest an indication for complete ureterectomy in nephrectomy candidates with prior or concurrent transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗

Cognitive impairment after transurethral resection of the prostate (TURP).

PURPOSE: It has been suggested that cognitive impairment may occur following transurethral resection of the prostate (TURP) operations due to the effects of anaesthesia or hyponatraemia or both. The aim of the study was to investigate whether TURP was associated with long-term memory complaints or cognitive impairment. METHOD: Patients who had received a TURP or transurethral resection of a bladder tumour (TURT) in the previous 10 months were sent a questionnaire on memory problems and mood. Seventy-six TURP patients and 38 TURT patients returned the completed questionnaires. A sample of each patient group (30 TURP, 29 TURT) was assessed on standardized tests of cognitive abilities. RESULTS: There was no significant difference between the TURP and TURT patients on the Everyday Memory Questionnaire completed by themselves or by a family member (p > 0.05). On formal cognitive testing there were no significant differences between the groups, except on the overall grading of the Kendrick Assessment Scales of Cognitive Ageing, in which TURP patients performed at a significantly lower level than TURT patients. CONCLUSIONS: The results suggest that patients are no more likely to complain of memory problems following a TURP than with any other operative procedure. There was a slight difference in cognitive abilities but this did not indicate significant impairment of cognitive function.

Affect↗

Adjuvant intravesical mitoxantrone after transurethral resection of primary superficial transitional cell carcinoma of the bladder. A prospective randomised study.

A prospective randomised controlled clinical trial began in 1989 on 126 patients with superficial transitional cell carcinoma of the bladder (pTa-pT1, grades 1-3) to compare the efficacy of adjuvant topical mitoxantrone after transurethral resection versus no further treatment. 62 patients received no further treatment, 64 patients received weekly 20 mg mitoxantrone intravesically for 6 weeks after differentiated TUR of all visible tumours. The endpoint of the study was any progression of stage or grade or further recurrences. The median follow up was 29 months--the minimum follow up was 24 months. The percentage of recurrences (25.8 versus 23.4), the recurrence rate (1.2 versus 0.9), the overall disease free interval and the tumour progression rate showed no statistically significant differences (P > 0.05 Mantel-Cox test). Only the comparison of time to recurrence in tumours with recurrences showed a statistically significant difference, with a longer disease free interval for the TUR plus mitoxantrone group (P = 0.016 Mantel-Cox test).

Administration, Intravesical↗

Expression of cathepsins B, H, and L and their inhibitors as markers of transitional cell carcinoma of the bladder.

OBJECTIVES: It has been shown that the expression of the lysosomal proteolytic enzymes cathepsin B, H, and L (CB, CH, and CL, respectively) correlate with tumor progression in various neoplasms. However, no data are available in cell lysates and supernatants of differently differentiated human bladder cell lines or in noncancerous and cancerous bladder tissue. METHODS: Using spectrofluorometric assays, catalytic activities of CB, CH, CL, and their inhibitor (CIP) were measured both in differently differentiated human bladder cell lines (HCV29, normal; RT4, well differentiated; J82, poorly differentiated) and in noncancerous and cancerous tissue samples (n = 20) of transitional cell carcinoma obtained from transurethral resections of the bladder or cystectomies. Enzyme activities were related to the protein content in tissue samples or to the cell count in cell lines. RESULTS: In comparison to the intracellular activities of CB, CH, and CL in the poorly differentiated cell line J82, the intracellular activities in the normal cell line HCV29 were significantly greater (P <0.05), independent of stage or grade. In contrast, the portion of cathepsins released from cell line J82 into the supernatant revealed higher values than that from cell line HCV29. In cancerous bladder tissue, CB and CH were significantly greater than in the matched normal tissue (P <0.05). CL and CIP did not show any statistically significant differences. CONCLUSIONS: Increased cathepsin concentrations in the supernatant of the poorly differentiated J82 carcinoma cell culture, as well as in cancerous bladder tissue, are indicative of a proteolytic imbalance and potential indicators of bladder cancer.

Animals↗

'Will you be doing my operation doctor?' Patient attitudes to informed consent.

BACKGROUND: As part of the consent process, it is part of a doctor's duty of care to reveal any material risk. Depending upon the level of supervision, whether the operating surgeon is a trainee may be such a risk, but in our experience this is not routinely discussed with patients pre-operatively. We set out to discover patients' attitudes to being operated on by trainee urological surgeons. PATIENTS AND METHODS: A total of 101 completed questionnaires were received from patients (90 male, 11 female, mean age 72 years) undergoing transurethral resection of the prostate (TURP), transurethral resection of a bladder tumour (TURBT) or cystodiathermy on various aspects of their attitudes to being operated on by junior doctors as part of training. RESULTS: The response rate was 77%. Of the respondents, 94 patients (91%) thought that junior doctors should perform surgery as part of their training. Only 11 of 73 (15%) said they would be happy for a junior doctor, competent to perform the procedure, to operate unsupervised. Of 98 patients, 80 (82%) thought they should be told if the operation was going to be performed by a junior doctor, and 85 (87%) that they should be told their name and designation. CONCLUSIONS: For consent to be 'informed', the experience and identity of the surgeon should be made known to patients. Most patients are happy to be operated on by a junior doctor under consultant supervision, but would want to be told and know their name and status.

Aged↗

Nonsurgical management of benign prostatic hyperplasia in men with bladder calculi.

OBJECTIVES: To assess the outcome of men with bladder calculi who did not undergo transurethral resection of the prostate after endoscopic stone removal. Bladder calculi associated with benign prostatic hyperplasia (BPH) have historically been an absolute indication for transurethral resection of the prostate. METHODS: A retrospective analysis of the results of 23 men who underwent endoscopic removal of bladder calculi with subsequent medical management of BPH symptoms was performed. Inclusion criteria included men with bladder stones secondary to BPH, serum creatinine 1.6 mg/dL or less, no evidence of hydronephrosis, and no history of acute urinary retention or neurogenic bladder. The International Prostate Symptom Score and postvoid residual urine volume before and after treatment and the incidence of bladder stone recurrence and associated complications were recorded. All patients were treated with either an alpha-receptor blocker or alpha-receptor blocker and finasteride after bladder stone removal. RESULTS: The follow-up after endoscopic removal of the bladder calculi averaged 30.0 months (range 6 to 96). The International Prostate Symptom Score before and after treatment was 18.3 and 9.4 (P <0.01), respectively. The postvoid residual urine volume before and after treatment was 354 and 179 mL (P <0.01), respectively. Urinary tract infection, acute urinary retention, recurrent calculi, chronic renal insufficiency, or renal failure developed in 21.7% (n = 5), 17.4% (n = 4), 17.4% (n = 4), 4.3% (n = 1), and 0% (n = 0) of the 23 men, respectively. Overall, 18 (78%) did not have any complications. CONCLUSIONS: Many men with bladder stones can be successfully and safely treated with transurethral stone removal and medical management of BPH.

Adrenergic alpha-Antagonists↗

Stage T1, grade 3 transitional cell carcinoma of the bladder: an unfavorable tumor?

Transurethral resection only was performed in 172 patients with initial stage Ta, T1 transitional cell carcinoma of the bladder. Additional treatment during the course of disease was given to 9 patients with carcinoma in situ and to 8 patients with tumor progression. The mean followup was 106 months. The 10-year survival rates were 95 per cent for patients with stage Ta, grade 1 disease, 89 per cent for stage Ta, grade 2, 84 per cent for stage Ta, grade 3, 78 per cent for stage T1, grade 2 and 50 per cent for stage T1, grade 3. The percentage of first tumor recurrence at the same site increased with tumor grade (stage T1, grade 3 was 74 per cent). The recurrence rate in stage T1, grade 3 tumors (4.08) differed significantly from the other groups of superficial tumors. The tumor progression rate for stage T1, grade 3 tumors (32.5 per cent) was significantly higher as well. The characteristics of stage T1, grade 3 tumors with and without progression were different in regard to multiplicity, recurrence rate, mean interval to recurrence and type of tumor invasion. Of the 13 patients who died of progressive neoplastic disease 11 presented initially with stage T1, grade 3 tumors. When these results are considered it is obvious that a patient with a stage T1, grade 3 tumor deserves additional therapy, such as chemotherapy, immunotherapy or phototherapy.

Aged↗

The evaluation and follow-up of patients with Ta, Tcis, and T1 bladder cancer.

Endoscopic evaluation and transurethral resection are the most important steps in the management of patients with bladder cancer. While multifocality is primarily a prognostic factor with respect to tumor recurrence, tumor grade and depth of invasion are prognostic regarding progression in stage. Transurethral resection biopsies of the prostate should always been obtained in patients with high grade tumors. Follow-up of patients should be individualized: patients with risk for progression, but not necessarily for recurrence, should be followed more closely than patients with low-grade tumors and low risk for progression. In this setting cytology is especially helpful because most high-grade tumors will be detected by cytology. Intravesical therapy is indicated in patients with high-grade tumors, carcinoma in-situ and multiple low grade tumors. While there is a growing body of evidence that BCG is superior to intravesical chemotherapy, one also has to take into account the more frequent and more serious side effects of BCG when compared with mitomycin C or thiotepa.

Carcinoma in Situ↗

Comparison of the prophylactic usefulness of epirubicin and doxorubicin in the treatment of superficial bladder cancer by intravesical instillation: a multicenter randomized trial. Kobe University Urological Oncology Group.

A multicentric randomized trial was conducted for the purpose of investigating the prophylactic efficacy of intravesical epirubicin instillation following transurethral resection of superficial bladder cancer in comparison with the efficacy of doxorubicin. The patients were centrally randomized into 2 groups and received 19 intravesical instillations of epirubicin or doxorubicin at 30 mg/30 ml physiological saline twice a week for 4 weeks and then once monthly for 11 months. A total of 150 patients with Ta and T1 superficial bladder cancer were entered in the trial, and 114 were evaluable. The nonrecurrence rates determined for each group at 1 and 2 years by the Kaplan-Meier method were 92.8% and 88.6%, respectively, for the epirubicin group and 86.4% and 81.7%, respectively, for the doxorubicin group. The differences between the two groups were not statistically significant. The main side effects encountered in this study were symptoms of bladder irritation such as micturitional pain, pollakisuria, and hematuria. The respective frequencies of those symptoms were 10%, 15.0%, and 5.0% in the epirubicin group and 14.8%, 14.8%, and 0 in the doxorubicin group. These results suggest that epirubicin is a useful drug, comparable with doxorubicin, for intravesical instillation chemotherapy in the prophylactic treatment of superficial bladder cancer.

Administration, Intravesical↗

[A case of transitional cell carcinoma of the bladder in a juvenile patient].

A 15-year-old male was referred to our hospital with the chief complaint of gross hematuria. Cystoscopic examination revealed a papillary tumor on the posterior wall. Transurethral resection of the bladder tumor was performed. Histological examination of the excised tumor showed transitional cell carcinoma, grade 1, pTa. Recurrence has not been observed for about 2 years after the operation. We investigated 54 previously reported Japanese cases of bladder cancer before age twenty including the present case.

Adolescent↗

Carcinosarcoma of the urinary bladder.

A case of carcinosarcoma of the urinary bladder is reported. Transurethral resection was performed. Histologically the tumorous mass was composed of osteosarcoma, squamous cell carcinoma and transitional cell carcinoma. The histological findings, immunohistochemical features and clinical manifestations of bladder carcinosarcoma are discussed in relation to the literature.

Aged↗

Immunotargeting of urothelial cell carcinoma with intravesically administered Tc-99m labeled HMFG1 monoclonal antibody.

Ten patients with transitional cell carcinoma (TCC) of the bladder received 3-6 mCi of HMFG1 monoclonal antibody (MAb) intravesically. The antibody was labeled with Tc-99m using the 2-Iminothiolane method. All patients underwent transurethral resection of the bladder tumor within 12-20 h following intravesical administration of 99m-Tc-HMFG1. The presence of the radiolabeled MAb in the circulation was studied by measuring the radioactivity in the serum for a period up to 20 h. Three of 10 patients underwent immunoscintigraphy (SPECT) 2-3 h postadministration and cancerous areas could be easily localized. Biopsies were taken from the tumor sites as well as from normal bladder mucosa. Absolute uptake of the administered MAb expressed as percent administered dose/kg of tissue could be evaluated only in eight patients. Multiple specimen taken from various tumor sites in every patient gave a wide range of uptake values ranging from 0 to 9.29% adm. dose/kg, whereas normal tissue uptake values ranged from 0 to 1.63, respectively.

Administration, Intravesical↗

Prophylactic effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer. BLP Study Group.

A randomized controlled study was conducted in patients with superficial bladder cancer in order to investigate the safety of an orally administered (3 g/day) Lactobacillus preparation, biolactis powder (BLP), and its preventive effect on the recurrence after transurethral resection of the bladder tumor (TUR-Bt). Of 58 cases enrolled in the study 23 cases in the BLP group and 25 cases in the control group completed the study. There were no significant differences in the patient characteristics for the complete cases between the two groups. Comparison of the disease-free duration by the Kaplan-Meier method revealed that the 50% recurrence-free interval after TUR-Bt was prolonged by BLP treatment (350 days) to 1.8 times that in the control group (195 days). A significant difference between the groups was detected by the long-rank test (p = 0.03). No adverse side effect was observed. The results suggest that oral administration of BLP is useful for the prevention of the recurrence of superficial bladder cancer.

Administration, Oral↗

[Clinical statistics on inpatients and operations at the Department of Urology, the Center for Adult Diseases, Osaka, 1984-1988].

Statistical observation on inpatients and operations at our department between January 1984 and December 1988 revealed the following results: 1) The total number of inpatients was 1962 (male: 1658, female: 304). The most frequent diseases were bladder cancer (30.0%), benign prostatic hypertrophy (19.2%), prostatic cancer (10.6%) and renal cancer (6.7%). 2) The total number of operations was 1699. The most frequent operations were transurethral resection (TUR) of bladder tumor (22.8%), TUR prostate (20.7%), TUR biopsy (6.5%) and total cystectomy (5.4%).

Female↗

Intravesical gemcitabine in superficial bladder cancer: a phase II safety, efficacy and pharmacokinetic study.

BACKGROUND: We investigated the safety, efficacy and pharmacokinetics of the intravesical administration of 2000 mg gemcitabine once a week in the four weeks before transurethral resection of superficial bladder cancer (TUR), and in the four successive weeks. MATERIALS AND METHODS: Nine patients with superficial transitional cell bladder carcinoma were studied. Two thousand mg of gemcitabine dissolved in 50 ml of distilled water were administered intravesically. The dwell time was 60 min. The pharmacokinetics of gemcitabine and its metabolite, 2',2'-difluorodeoxyuridine (dFdU), were studied in plasma and urine before and after TUR. Cystoscopy was repeated 30 days after completion of the TUR treatment and subsequently at time intervals of one or two months. RESULTS: No systemic toxicity was noted, and only three patients displayed modest signs of local toxicity. One patient had recurrence 1 month after TUR, three between 3 and 6 months, and another three after 8, 11 and 18 months, respectively; two were recurrence-free after 21 and 22 months, respectively. The peak plasma concentrations of gemcitabine never exceeded 1000 ng/ml before TUR and 350 ng/ml after TUR, and declined rapidly. The plasma levels of dFdU were higher than those of gemcitabine, increased until 60 min and then declined little. Between 52% and 100% of the gemcitabine dose was present in voided urine. CONCLUSION: Intravesical gemcitabine, at the dose of 2000 mg, is well tolerated, is associated with minimal systemic absorption and has a moderate efficacy in the treatment of superficial bladder cancer.

Administration, Intravesical↗