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Computed tomographic evaluation of carcinoma of the cervix.

To assess the accuracy of computed tomography (CT) in staging advanced carcinoma of the cervix, 18 staging evaluations were performed in 16 patients with locally advanced (FIGO Stage IB-IVA) cervical carcinoma. CT staging results were compared with the results of clinical staging and postoperative staging. CT was accurate in 12/18 (66%) cases, clinical staging was accurate in 10/18 (55%) cases, and clinical staging with cystoscopy was accurate in 14/18 (78%) cases. CT staging failed to detect microscopic pelvic sidewall involvement and bladder involvement when there was no contrast material in the bladder. In the detection of para-aortic lymph node involvement by tumor, there were 12 true-negative, 4 true-positive, 1 false-positive, and 1 false-negative study (sensitivity = 80%, specificity = 92%). It is concluded that CT is equal in accuracy to other clinical staging techniques and offers the advantage of visualizing the tumor, which allows for more accurate determination of radiation portals.

Carcinoma↗

Treating the human bladder with capsaicin: is it safe?

OBJECTIVES: Although human contact with capsaicin has occurred over thousands of years, some uncertainty surrounds its status as a possible carcinogen. This is the first report of bladder biopsies from patients who have been treated with capsaicin over a 5-year period. METHODS: Between 1991 and 1996, 20 patients (9 males, 11 females; mean age 52.5 years, range 40-70 years) with intractable detrusor hyperreflexia have had repeated instillations of intravesical capsaicin (1-2 mmol/l). The number of treatments per patient varied between 1 and 17 (total = 82; average 6/patient). The surveillance programme involved repeated flexible cystoscopy and bladder biopsies before and after capsaicin. Cryostat sections were stained with haematoxylin-eosin and examined by light microscopy. RESULTS: None of the bladder biopsies have shown metaplasia, dysplasia, flat carcinoma in situ, papillary or solid invasive cancer. CONCLUSIONS: No pre-malignant of malignant change has been found in biopsies of patients who had repeated capsaicin instillations for up to 5 years. However, as the morphological effects of chemical carcinogens may not be apparent for 10 years, further surveillance is being continued.

Adult↗

The Bard BTA test: its mode of action, sensitivity and specificity, compared to cytology of voided urine, in the diagnosis of superficial bladder cancer.

OBJECTIVES: Application of immunocytology directed against antigens of urothelial tumor cells or tumor-associated breakdown products intends to improve the sensitivity of the diagnosis of superficial transitional cell carcinoma (TCC) of the urinary bladder. In this study, the mode of action, sensitivity and specificity of the Bard(R) BTA test, detecting a tumor-associated release of a basement membrane complex, was addressed and compared with voided urine cytology (VUC). RESULTS: Contrary to grade, a significant (p = 0. 003) relationship between tumor stage and BTA test sensitivity was observed, being 23.8, 33.3 to 100% for Ta (n = 42), T1 (n = 6) to >/=T2 (n = 5), respectively. These data suggest an association between an increase of the BTA test sensitivity with an increase of basement membrane degradation or interruption. With regard to this mechanism, the BTA test may be of special importance for monitoring tumor progression or increase in tumor invasiveness. Detection of low-stage, low-grade tumors by noninvasive techniques remains a challenge. The sensitivity of the BTA test for the presence of TCC was 32.3%, while that of VUC was 17.7%, but in this study the difference was not statistically significant. Furthermore, the BTA test was not more effective in identifying the various tumor grades, stages or stage/grade groupings. However, dividing the patients in two groups of low risk (TaG1/TaG2) and high risk (TaG3 to >/=T2) leads to a significant (p = 0.008) increased sensitivity of the BTA test (27.3%) in detecting patients with low-risk tumors compared to VUC (3.0%). The specificity of the BTA test in patients with a history of TCC was 81.6%, while that of VUC was 98.9%. CONCLUSION: The sensitivity of the BTA test is at least equivalent to VUC and may be suited to monitor increase in stage in patients suffering from bladder carcinoma, but cannot replace cystoscopy in patients suspected for a bladder tumor.

Adult↗

T1 GIII bladder cancer. Management with transurethral resection only.

OBJECTIVE: Transurethral resection (TUR) is the elective procedure in the treatment of superficial bladder tumor. The association of intravesical chemotherapy has no influence on survival and cause specific survival. This study was carried out to determine the evolution of T1 GIII bladder carcinoma treated with TUR only. PATIENTS AND METHODS: We retrospectively reviewed the records of 42 consecutive patients with T1 GIII bladder carcinoma. Follow-up was available for 34 patients. No patient received either adjuvant or neoadjuvant therapy. All the patients were treated with TUR only and followed for a median of 40 months. They were followed by cystoscopy, urinary cytology and intravenous urography. RESULTS: Forty-seven percent of patients had a solitary tumor while 53% had multiple tumors. Tumor recurrence occurred in 50% with a disease-free interval until the first relapse of 9.6 months. Progression of the primary tumor was observed in 23.5% of patients. The overall survival rate was 73.6% and the cancer-specific survival estimate was 88.2% at mean 36 months of follow-up. CONCLUSIONS: T1 GIII bladder carcinoma may be treated initially with transurethral resection only with acceptable recurrence and progression rates. This would avoid costs and complications of the adjuvant/neoadjuvant therapies.

Adult↗

Diagnosis and management of eosinophilic cystitis: a pooled analysis of 135 cases.

OBJECTIVE: Eosinophilic cystitis is a rare disease. We reviewed the literature for clinical presentation, diagnosis and therapeutic options to establish recommendations for diagnostic and therapeutic management. METHODS: A pooled analysis was performed of 135 patients with eosinophilic cystitis presented in the literature. The evaluation included patient age, sex and race, presenting symptoms, diagnostic examinations, treatment and results, and complications. RESULTS: The mean age at diagnosis was 41.6 years (range 5 days to 87 years). An equal distribution existed between males (44%) and females (35%), but in children (21%) boys were more often affected (14%) than girls (7%). The most common presenting symptoms were frequency (67%), dysuria (62%), gross/microscopic hematuria (68%), suprapubic pain (49%) and urinary retention (10%). All patients had a cystoscopy and biopsy; a biopsy is mandatory to establish the diagnosis. Positive urine cultures were found in 26% of the patients. Periferal eosinophilia was present in 43%. An intravenous urography was performed in 66%, ultrasonography in 15%, cystography in 23% and a CT scan in 10%. The majority of patients was treated with combinations of corticosteroids, antihistaminics and antibiotics (45%), avoiding of the suspected antigen (17%), transurethral resection of the lesions (9%), partial cystectomy (4%) or total cystectomy (4%). The success rates for the different treatments were variable: transurethral resection combined with corticosteroids, antihistaminics or antibiotics seemed most successful, while total cystectomy is reserved for patients with unresponsive disease and hematuria. The most common complications were dilation of the upper urinary tract (27%) and eosinophilic gastroenteritis (4.5%); all other complications occurred in less than 3% of the patients. CONCLUSION: Eosinophilic cystitis is equally distributed among the sexes, but in children boys are affected more often than girls. The presenting symptoms are frequency, dysuria, hematuria, suprapubic pain and urinary retention. The treatment of choice is (radical) transurethral resection of the lesions in the bladder and a combination of corticosteroids and antihistaminics. Antibiotics are given when a urinary tract infection is present, or when dilation of the upper urinary tract exists. Most patients are cured but recurrence is a frequent finding.

Adolescent↗

The role of Borrelia burgdorferi in interstitial cystitis.

BACKGROUND/AIMS: Borrelia burgdorferi spirochete has been found both in bladder biopsies and the urine of patients with Lyme disease (LD) as well as in experimental animals. The urological symptoms in borreliosis resemble those of interstitial cystitis (IC): frequency, urgency and nocturia. The aim of this studies is to find the role of B. burgdorferi in interstitial cystitis. METHODS: We studied antibodies against B. burgdorferi from serum samples of 50 IC patients with two separate EIA tests. Patients with positive serology in both tests underwent cystoscopy and a bladder biopsy was taken. The presence of borrelia DNA was studied with borrelia-specific polymerase chain reaction (PCR), and with universal bacterial PCR. RESULTS: IgM class antibodies to B. burgdorferi were not found, but IgG antibodies were found in four samples (8%). This was higher than in the control material (2%). One patient's sample was strongly positive, whereas three samples were weakly positive. Bladder biopsies taken from the 4 patients were negative for borrelia DNA in both PCR tests. None of the seropositive patients had any symptoms consistent with LD. CONCLUSION: These results indicate that persistent infection of B. burgdorferi has no role in the etiology of IC. On the other hand a connection with a past borrelia infection and IC is not excluded.

Adult↗

Evaluation of the clinical value of urinary NMP22 as a marker in the screening and surveillance of transitional cell carcinoma of the urinary bladder.

PURPOSE: To prospectively evaluate the clinical role of urinary NMP22 as a marker for transitional cell carcinoma of the urinary bladder in screening and surveillance settings. PATIENTS AND METHODS: Single voided specimens were obtained from 211 consecutive patients who presented for flexible cystoscopy. Of these, 96 patients presented with haematuria or irritative symptoms (screening), the remaining 115 were patients with known transitional cell carcinoma on follow-up (surveillance). The urine sample was used for urine microscopy, cytology and for measuring NMP22 levels. RESULTS: Bladder tumours were found in 16 of 96 (16.6%) patients in the screening group and 17 of 115 (15.6%) patients on surveillance. The NMP22 levels were significantly lower in patients with lower stage (Ta vs. T1-3), low grade (G1, G2 vs. G3, CIS) and papillary morphology. The optimum threshold for NMP22 obtained from the ROC curve was 4.75 U/ml, providing a sensitivity, specificity, positive predictive value and negative predictive value of 42.4, 85, 38.5 and 88.6%, respectively. Sensitivity and specificity were better in patients being screened than in those on surveillance. In both groups, urinary NMP22 had similar diagnostic characteristics as urinary cytology. CONCLUSIONS: Urinary NMP22 levels are significantly higher in patients with bladder tumour than in those negative for tumours, and test predictability improves with increasing stage and grade. The overall sensitivity for urinary NMP22 is similar to, but not superior to urine cytology. Our study suggests that the clinical role of urinary NMP22 as a diagnostic marker can be at best supportive only.

Biomarkers, Tumor↗

Effect of intravesical instillations on the human complement factor H related protein (BTA stat) test.

OBJECTIVES: The BTA stat is a rapid, non-invasive, qualitative urine test that detects bladder tumor-associated antigen (human complement factor H related protein) in urine. The sensitivity of this test is superior to that of urine cytology in detecting primary and recurrent tumors of the urinary bladder. Intravesical instillations are widely used to avoid recurrences and even progression. The objective of this study was to evaluate the effect of intravesical treatments on the BTA stat Test. METHODS: 501 consecutive patients followed up for bladder cancer were studied, of which 490 were eligible for analysis. Three hundred and twenty-seven (66.7%) of the patients had no history of intravesical treatments, whereas the remaining 163 (33.3%) had received treatments: 66 (40.5%) at the time of evaluation. A voided urine sample was obtained prior to cystoscopy and split for culture and BTA stat testing. The overall sensitivity and specificity were calculated and compared to the patients with no, past and present instillations. RESULTS: The overall sensitivity for the BTA stat Test was 56.6%, and the specificity was 76.4%. The specificity of the BTA stat Test was 80.7, 70.7 and 65.3% in those with no, past or present intravesical instillation treatments, respectively. The difference in specificity between those with no and present instillations was significant (p = 0.023), whereas the notable difference between those with no and past instillations did not reach significance (p = 0.076), nor was the difference between patients with past and present instillations significant (p = 0.558). Present instillation of mitomycin C had the strongest adverse effect on the test as the specificity was only 25.0%, whereas past treatment did not interfere with testing. The adverse effect of BCG treatment on testing extended. CONCLUSION: The overall specificity of the test is decreased in patients receiving intravesical treatments, whereas past treatments did not interfere with testing in general. However, the adverse effect of BCG on testing seems to extend, and therefore it is suggested that the BTA stat Test should not be used in patients having received BCG, and in those with present instillation of any type.

Adjuvants, Immunologic↗

Frequency of positive biopsies after visual disappearance of superficial bladder cancer marker lesions.

INTRODUCTION AND OBJECTIVES: In phase II trials in superficial bladder cancer, marker lesions have been used to test the ablative activity of intravesical chemo- or immunotherapy. These studies provide important knowledge about drug activity and toxicity without exposing hundreds of patients in phase III trials to drugs which ultimately may not be successful in preventing tumour recurrence or progression. After treatment a deep biopsy was necessary at the site of the marker lesion even in the absence of any visual tumour. The question is if this biopsy, in the absence of any visual tumour, should be done. MATERIAL AND METHODS: The ablative effect of MMC, epirubicin, and quarter dose BCG instillations was evaluated in three different studies on a papillary marker lesion. Patients with multiple, primary or recurrent superficial bladder tumours were included. All visible Ta-T1 lesions were resected except for one marker lesion not exceeding 1 cm. TIS was excluded. In the last study, patients with T1 G3 tumours or multiple tumours >10 were also excluded. If the marker lesion disappeared completely, a deep biopsy was performed at the scar in order to prove histological disappearance of the tumour. RESULTS: 185 patients were evaluated. No visual tumours were seen in 110 patients and a TUR was performed in 101 of them. It revealed only 3 Ta lesions. In the 9 others no biopsy was performed but follow-up cystoscopy revealed no lesions. CONCLUSIONS: In the absence of any visual tumors, TUR and deep biopsy at the site of the scar of the marker lesion only rarely revealed (3 out of 110) the histological presence of a tumour. Therefore, this biopsy can be omitted in new marker lesion protocols in patient with Ta-T1, G1 G2 papillary superficial bladder tumours at intermediate risk for recurrence and low risk for progression.

Administration, Intravesical↗

Phase 1/2 study of synchronous methotrexate, cisplatin, vincristine (MOPq10) chemotherapy and radiation for patients with locally advanced bladder cancer.

PURPOSE: This phase 1/2 study was designed to test toxicity and effectiveness of combination chemotherapy and concurrent radiotherapy in the treatment of invasive bladder cancer. METHODS AND MATERIALS: 17 patients with localised muscle-invasive bladder cancer, clinical stages T2-3 N0, M0, were treated with a radiotherapy schedule of 55 Gy in 20 fractions over 4 weeks restricted to the bladder and 3 cycles of concurrent dose-intensive combination chemotherapy consisting of cisplatin 60 mg/m(2), vincristine 2 mg and methotrexate 60 mg/m(2) at 10-day intervals (MOPq10). RESULTS: The complete remission rate following MOPq10 chemotherapy and radiotherapy was 88% as assessed at first cystoscopy with 82% remaining disease-free at 1 year. Risk factor analysis shows those older than 63 years (median) and those with creatinine clearance equal or less than the mean did worse. Actuarial disease-free survival at 2 years was 68% and of the patients treated 4/17 experienced acute G3/4 toxicity. CONCLUSION: This combination regimen was feasible. Its high initial response rate justifies further exploration in a randomised phase 2/3 trial setting with bladder volume and quality of life assessment.

Aged↗

Urological treatment and clinical course of BK polyomavirus-associated hemorrhagic cystitis in children after bone marrow transplantation.

Hemorrhagic cystitis (HC) is a major complication of bone marrow transplantation (BMT). We describe the clinical course and urological management of BK polyomavirus-associated HC in children after bone marrow transplantation. From 8/88 to 11/95, a total of 117 consecutive pediatric patients received BMT. Nine patients (7. 7%) developed HC after transplantation. HC in all 9 patients was characterized by late onset (day +24 to +50 post-BMT), long duration (1-7 weeks) and the excretion of BK polyomavirus in the urine as confirmed by electron microscopy, DNA hybridization and PCR techniques. Six children developed mild HC (grade 1-2) and were treated successfully by hyperhydration. In 3 patients, severe HC (grade 3-4) over 6 weeks required surgical interventions. In these 3 patients, cystoscopy revealed circumscript papulous tumors as the source of hematuria. Severe and persistent hematuria required blood transfusions, insertion of large suprapubic catheters and permanent bladder irrigation because of recurrent blood clot retention. Attempts to stop the hematuria in 2 of these patients by coagulation and laser vaporization (Nd:YAG) failed to stop the bleeding. Differential diagnosis of hematuria after BMT includes urinary tract infection, cyclophosphamide-induced chemical cystitis and bleeding due to BMT-induced thrombocytopenia. With the increasing number of BMTs in children, urologists may be confronted with BK polyomavirus-associated HC and must consider this in the differential diagnosis of hematuria after BMT.

Adolescent↗

Recurrence and progression of T1G3 transitional cell carcinoma of the bladder treated with intravesical bacillus Calmette-Guérin.

OBJECTIVE: To examine the incidence of recurrence and progression in patients with stage T1, grade-3 carcinoma of the bladder treated with endovesical bacillus Calmette-Guérin (BCG) after complete transurethral resection. MATERIAL AND METHODS: From May 1995 to June 2002, 937 patients with superficial bladder cancer underwent transurethral resection. 46 patients (4.9%) had T1G3 tumors. All patients received endovesical BCG therapy 2-3 weeks after transurethral resection, given in 6 sessions as weekly instillations of 120 ml Pasteur strain BCG in 50 ml saline. Success was defined by normal cytology and cystoscopy, and normal bladder biopsies. Recurrent tumors were resected and a second or third cycle of therapy was given according to pathological status. Progressive tumors were managed by radical cystectomy, radiotherapy and/or chemotherapy depending on the nature of the tumor or clinical status of the patient. RESULTS: During follow-up 60.7% of the patients (28 of 46) remained tumor free after only 1 BCG cycle and 73.9% (34 of 46) after the third BCG cycle, and the bladder was preserved in all. Muscle-invasive progression was noted in 10 (21.7%) patients at the end of the BCG cycles. Radical cystectomy was done in 10 patients. The tumor-free survival rate of all patients including those who underwent cystectomy is 84.8% (39 of 46) with a median follow-up of 61 (range 39-118) months. CONCLUSION: Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective treatment for bladder preservation in stage pT1, grade-3 carcinoma of the bladder. pT1G3 tumors with early high-grade recurrence after failed immunotherapy should be regarded as candidates for early radical cystectomy.

Adjuvants, Immunologic↗

Leiomyoma of the urinary bladder.

We report a case of urinary retention in a women caused by a leiomyoma of the bladder. The intramural form often causes obstruction, as it is usually located near the bladder base. Treatment is surgical, and the prognosis is excellent. Therefore, cystoscopy is recommended in women with urinary retention.

Cystoscopy↗

Nephrogenic adenoma of the bladder in children.

Nephrogenic adenoma is reported in 3 young girls, whose bladders had all previously been operated on. Nephrogenic adenoma is most likely a metaplastic reaction of the bladder epithelium to irritative stimuli. Malignant degeneration has not been proven. Treatment consists of transurethral resection with fulguration of the tumor base. A follow-up as for other bladder tumors--cystoscopy at regular intervals--is recommended.

Adenoma↗

Incidence and diagnostic aspects of the bladder disorders in diabetics.

Bladder disorders are important among the various complications of diabetes, both because of their frequency and the severe involvements they can cause to the urinary tract and ultimately to the renal function. Because they are often mild, especially in the first stage, bladder disorders call for early detection and for a judicious assessment as possible by careful investigation. The incidence of bladder disorders was studied in 50 diabetics by performing cystoscopy, micturition cystourethrography and cystometry. The results emphasize the importance of these investigations, particularly the cystometric one, in recognizing such bladder troubles before severe complications occur.

Adult↗

Diagnostic contribution of bladder washing and multiple biopsies in bladder cancers.

The superior diagnostic contribution of bladder washing as compared to routine urinary cytology was demonstrated in a prospective study. Random mucosal biopsies of normal-looking mucosa taken at the time of treatment or of the first control cystoscopy revealed the presence of multiple cancerous or precancerous lesions in a variety of patients. The heterogeneity of bladder cancer had to be recognized for adequate follow-up and treatment.

Biopsy↗

One-shot intravesical instillation of the mucous adhesive anticancer agent hydroxypropylcellulose-doxorubicin for the treatment of superficial bladder carcinoma is sufficient to determine antitumor effects.

A 20 mg/20 ml dose of the membrane adhesive anticancer preparation, hydroxypropylcellulose-doxorubicin (HPC-doxorubicin), was instilled into urinary bladders through a catheter for the treatment of superficial bladder carcinomas (Ta-T1). After 14-30 days, the effects of the drug on tumors was examined by cystoscopy, and the residual tumor tissue where reduction in size was observed was resected by transurethral resection (TUR). Therapeutic effects were as follows: a complete response (CR) was found in 6 cases (37.5%), a reduction in size of more than 50% (partial response = PR) in 4 cases (25%), and a less than 25% reduction (no change = NC) in 6 cases (37.5%). In no case was progression of the disease noted. In CR cases, cold cup punch biopsy revealed no tumor cells remaining at the site where the tumor was present before the instillation. Side effects such as bladder irritation were found in 4 cases, but they were only temporary in nature. The one-dose HPC-doxorubicin approach developed by ourselves allowed detection of antitumor effects between 14 and 30 days after the instillation and therefore determination of sensitivities at an earlier stage than with instillation of the conventional water-soluble type of doxorubicin hydrochloride.

Administration, Intravesical↗