Can urine bound diagnostic tests replace cystoscopy in the management of bladder cancer?

PURPOSE: We compare the diagnostic value of NMP22 and BTA stat testing, and QUANTICYT computer assisted dual parameter image analysis to cytology and cystoscopy in patients who had symptoms suggestive of transitional cell cancer or were being followed after treatment for that disease. MATERIALS AND METHODS: We prospectively evaluated voided urine and/or barbotage specimens from 291 patients a mean of 65.2 years old. All voided urine samples were evaluated by quick staining and standard cytology, the BTA stat 1-step qualitative assay (which detects a bladder tumor associated antigen) and the NMP22 test (which detects a nuclear mitotic apparatus protein). In addition, barbotage specimens were evaluated by QUANTICYT computer assisted dual parameter image analysis. All patients underwent subsequent cystoscopy and biopsy evaluation of any suspicious lesion. Sensitivity, specificity, and the predictive value of positive and negative results were determined in correlation with endoscopic and histological findings. RESULTS: In 91 patients with histologically proved transitional cell carcinoma overall sensitivity was 48, 57, 58, 59 and 59% for the NMP22 test, the BTA stat test, rapid staining cytology of barbotage samples, rapid staining cytology of voided urine specimens and image analysis, respectively. For histological grades 1 to 3 underlying transitional cell carcinoma sensitivity was 17, 61 and 90% for urinary cytology, 48, 58 and 63% for the BTA stat test, and 52, 45 and 50% for the NMP22 test, respectively. Specificity was 100% for cytology, 93% for image analysis, 70% for the NMP22 test and 68% for the BTA stat test. CONCLUSIONS: Immunological markers are superior to cytological evaluation and image analysis for detecting low grade transitional cell carcinoma but they have low specificity and sensitivity in grade 3 transitional cell carcinoma. Urine bound diagnostic tools cannot replace cystoscopy.     

A bladder nephrogenic adenoma. A case report

OBJECTIVE: To report an additional case of nephrogenic adenoma of the bladder. METHODS/RESULTS: A case of nephrogenic adenoma of the urinary bladder in a 28-year-old female is described. Patient clinical history and diagnostic imaging findings are presented. CONCLUSIONS: Nephrogenic adenoma of the bladder is a rare benign tumor with specific histological features that has been associated with previous surgery, trauma, infections and lithiasis. Although it is currently not considered to be a premalignant lesion, its rate of recurrence is high (37%-49%). The treatment of choice is by transurethral resection and yearly cytological, ultrasound and cystoscopic follow-up evaluation to detect recurrence.     

Carcino-embryonic antigen activity in urine of patients with bladder carcinoma. Clinical evaluation of carcino-embryonic antigen. II

This paper deals with the study of CEA levels in urine from healthy control subjects, of patients with bladder carcinoma or previous bladder carcinoma, and other groups of patients. In 53% of the patients with bladder carcinoma and without urinary infection, urinary CEA was increased. There were no false positive results. It is concluded that urinary CEA is a valuable aid in the detection of malignant tumour growth in the bladder. The results are compared with several tumour parameters, e.g. tumour size, stage of disease and histological parameters. Evidence is presented that CEA in infected urine is not produced by bacteria and that, like soluble vaginal excretory products, this substance has antigenic groupings in common with CEA from bladder tumours.     

A simple and efficient urine sampling method for bacteriological examination in elderly women

AIM: to determine how collecting urine voided directly into a container compares with urine obtained by suprapubic aspiration. METHOD: urine samples were collected in a sterile recipient placed in the toilet or in the bed-pan during voiding, after the vulval region had been cleaned by water. These samples were compared with samples of the same urine obtained by suprapubic aspiration. The samples were examined for pyuria and bacteriuria. Applying the Kass criteria on the voided urine specimen and assessing the presence of leucocyturia, it was possible to differentiate urinary tract infection, asymptomatic bacteriuria and contamination. RESULTS: all 13 cases of infection found on suprapubic aspiration were also identified by this sampling technique. The technique produced four false-positive results. CONCLUSION: this simple sampling method may not only obviate the need for suprapubic aspiration but also for bladder catheterization in the diagnosis of urinary tract infection in many elderly women.     

Effectiveness of the massive campaign for immunization against Meningococcus (serogroup C) in the Autonomic Community of the Basque Province

A prospective study was conducted on 27 dogs with recurrent urinary tract infections (UTIs) and urolithiasis. Four sampling methods (i.e., urine obtained by cystocentesis, bladder mucosal swab, bladder mucosal biopsy, and urolith) were compared to identify UTI. Identical culture results were obtained from urine collected by cystocentesis and from the swab of bladder mucosa. In the presence of a positive urine culture, the same organism also was cultured from the bladder mucosal biopsy and urolith. However, in the presence of a negative urine culture, an organism was cultured from the bladder mucosal biopsy or the urolith in 18.5% of the cases. Therefore, when the culture from urine obtained by cystocentesis is negative, it is recommended that aerobic cultures of a bladder mucosal biopsy and a urolith be performed in cases of urolithiasis.     

The utilization of a paediatric emergency room in a general hospital in Kuwait

The objective of the study was to describe the ultrasonographic findings of urinary bladder urolithiasis and to determine the diagnostic value of the technique in feline lower urinary tract diseases (LUTD). Physical examination of the urinary system and routine clinicopathological analysis of the blood and urine were performed on 32 cats presented with clinical symptoms of LUTD. Cystosonography was done on all of the cats, while plain radiography was performed on 8 and double contrast cystography on 2 cats. Sonography of the bladder provided the following diagnoses: urolithiasis and chronic cystitis: 24 cases, chronic cystitis without urolithiasis: 4 cases, bladder neoplasm: 1 case, negative sonographic finding: 3 cases. Bladder calculi and/or plugs were diagnosed easily, up to a size of 2 mm, according to acoustic shadowing and/or reverberation and gravitation. When the bladder was empty, it was filled up with physiologic saline solution to visualise its contents more easily. Sonography proved to be a useful technique for diagnosing urinary bladder calculi and/or plugs even when they were radiolucent and for distinguishing among the different causes of LUTD. Although ultrasonography is a valuable diagnostic tool, radiography is still necessary to explore lower urinary tract diseases, especially when cystosonography provides negative results or urethral obstruction is suspected.     

Responses of natural killer cell activity to acute laboratory stressors in healthy men at different times of day

BACKGROUND: Five renal recipients with neurovesical dysfunction (NVD) were retrospectively reviewed focusing on anatomical and urodynamic abnormalities of the lower urinary tract and their management prior to kidney transplantation. METHODS: The underlying anomalies in these 5 patients were a posterior urethral valve (1 with an imperforate anus; n = 2), meningomyelocele (n = 2) and a congenital short urethra with an imperforate anus (n = 1). Their urinary tracts were evaluated prior to transplantation with voiding cystourethrography, urethrocystoscopy, cystometrography and electromyography of the external urethral sphincter to identify a possible focus of urinary tract infection, urine storage and voiding function. RESULTS: All 5 patients had NVD proven by urodynamic studies or by documentation of urinary retention in the absence of mechanical outlet obstruction. Bilateral high grade vesicoureteral reflux was noted in all patients, requiring ureteroneocystostomy. Clean intermittent catheterization (CIC) was ultimately employed for bladder emptying in all patients. Two patients with poor bladder compliance underwent augmentation cystoplasty before transplantation. The Mitrofanoff procedure was used in 2 patients with structural urethral abnormalities to access the bladder for catheterization. After eradication of possible sources of infection and establishment of a low-pressure urine storage system with bladder emptying by CIC, kidney transplantation was performed. Following kidney transplantation, all of the recipients were asymptomatic for urinary tract infections using CIC. Although 1 patient lost his graft due to chronic rejection, the other 4 other patients have good renal function. CONCLUSION: Kidney transplantation in patients with NVD can be performed provided that their urinary tract problems are properly resolved.     

Urinary incontinence and bacteriuria in women

We analyzed the urodynamic data and their relationship with significant bacteriuria in 103 consecutive female patients (mean age = 55.7 yrs) with urinary incontinence. Significant bacteriuria was observed in 25.2% of the cases. E. coli was the pathogen most frequently isolated (70.3%). Significant bacteriuria was demonstrated in 29.3% of the patients with urge-incontinence. The most frequent type of incontinence in patients with bacteriuria was no urodynamic reproduction of urinary incontinence (42.8%). Bladder instability was not associated with significant bacteriuria (27.2%). Significant bacteriuria was observed in 75% of the patients with lower urinary tract obstruction, 66.6% of the patients who voided by abdominal straining and 26.3% of those with postvoiding residual urine. These findings indicate that urine culture should be done in patients with no urodynamic reproduction of urinary incontinence. There was no statistically significant correlation between urge-incontinence/bladder instability and significant bacteriuria. Consequently, antibiotics should not be used routinely in female urinary incontinence.     

Three cases of the nephrogenic adenoma of the bladder

Nephrogenic adenoma is a rare, benign tumor of the urinary tract. The origin of this tumor is supposed to be a metaplastic transformation of urothelium in response to stimulation such as recurrent urinary tract infections or surgical trauma. We experienced three cases of nephrogenic adenoma originating in the bladder. The first patient was a 29-year-old man with right vesicoureteral reflux (VUR). When Teflon injection for VUR was performed, a papillary tumor was found on the right wall of the bladder. Transurethral resection of the bladder tumor (TUR-Bt) was performed. The second patient was a 72-year-old woman who was suffering from chronic cystitis. Although she was treated with antibiotics for one year, the symptoms were not improved. Cystoscopy showed multiple papillary tumors at the retrotrigonum of the bladder and TUR-Bt was performed. The third patient was a 75-year-old man who had a history of the left pelvic and bilateral ureteral tumors. Left radical nephroureterectomy and right radical ureterectomy with an ileal graft replacement was performed. Three years later, cystoscopy demonstrated a papillary tumor at the retrotrigonum, which was resected transurethrally. Our cases are the 20th to 22nd cases of the nephrogenic adenoma of the bladder reported in the Japanese literature.     

All-trans-retinoic acid in acute promyelocytic leukemia

We performed a retrospective analysis of all patients admitted to our institution with a diagnosis of infantile hypertrophic pyloric stenosis (IHPS) during a 10-year period from 1985-95 in order to assess the possible association between IHPS and urinary tract infections (UTIs). All 285 patients with IHPS had radiological or ultrasonographic confirmation of that diagnosis and underwent the Ramstedt procedure. Those who continued to be symptomatic were evaluated for UTI by urine analysis and culture. Positive cases were further evaluated for urinary system anomalies. The male:female ratio of IHPS was 3.4:1. Concomitant UTI was diagnosed in 8 patients by suprapubic aspiration or bladder catheterization. The prevalence of UTI in this series was 2.8%, 20-fold higher than the expected prevalence. Three of the 8 patients with UTI (37.5%) had urinary tract anomalies. These findings suggest an association between IHPS and UTI. We recommend that all IHPS patients be evaluated for UTI and positive cases undergo further evaluation for urinary anomalies.     

Six cases of upper urinary tract diseases including tumors and inflammatory lesions which suggest the significance of urine cytology in preoperative diagnosis

We present six cases of upper urinary tract diseases including tumors and inflammatory lesions in which the urine cytology rather than the radiological examinations was useful for their preoperative diagnoses. Three of the six cases had malignant diseases and the others had benign diseases. In all cases preoperative results of urine cytology were identical to histopathological findings of resected specimens; the cases with positive findings in urine cytology had ureter cancers and those with negative findings had benign diseases. Primary CIS of upper urinary tract was found in two of six cases, which is still uncommon in Japan. Since it is very difficult to make a preoperative diagnosis of primary CIS by radiological examinations, the present study showed that urine cytology is useful for its preoperative diagnosis. Recently endoscopic techniques for the diagnosis of upper urinary tract tumors are in clinical use. The ureteroscopic biopsy is recommended for the case in which the diagnosis using urine cytology is difficult.     

Purification and characterization of beta-N-acetylhexosaminidase from the phytopathogenic fungus Bipolaris sorokiniana

BACKGROUND: In an attempt to find a more sensitive and specific noninvasive assay for the detection of bladder carcinoma, the authors assayed exfoliated cells from patients' voided urine for the presence of telomerase, an enzyme that maintains a cell's chromosomal length and is thought to be active in the transformation of normal somatic cells into immortal human tumor cells. METHODS: The authors used a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay to determine the presence of telomerase activity in voided urine samples from patients with known but yet untreated bladder carcinoma (n = 104) and from patients with hematuria of benign causes (n = 47). For 88 of the patients with bladder carcinoma, cytology was determined independently of the telomerase results or the pathology findings. RESULTS: Of the 104 bladder carcinoma specimens, 88 (85%) tested positive for the presence of telomerase. Seventy-nine percent (23 of 29) of the Grade 1 tumors, 84% (32 of 38) of the Grade 2 tumors, and 87.5% (28 of 32) of the Grade 3 tumors were positive for telomerase activity. Five patients with carcinoma in situ (100%) were also positive. Telomerase activity was not found in 31 of 47 patients with bladder calculi, benign urethral stricture, benign prostatic hyperplasia, or inflammation. In the 16 patients (34%) who did have a false-positive result when tested for telomerase, all had either chronic or severe inflammation, including 1 patient with an inverted papilloma, 1 patient with cystitis cystica, and 1 patient with cystitis glandularis. However, for 35 normal, healthy volunteers whose voided urine samples were also assayed for the presence of telomerase activity, none was found. By comparison, only 51% (45 of 88) of the cytology samples from patients with bladder carcinoma yielded positive findings, whereas 49% (43 of 88) resulted in false-negative readings for tumors. Only 13% (3 of 23) of the Grade 1 tumors, 44% (14 of 32) of the Grade 2 tumors, and 82% (23 of 28) of the Grade 3 tumors were diagnosed by cytology. All five patients with carcinoma in situ were positive for cytology as well as for telomerase activity. When cytology was compared with the PCR-based telomerase assay in determining the presence of bladder carcinoma, the difference in the overall detection rates (85% for telomerase vs. 51% for cytology) was significant (P < 0.001). Furthermore, when telomerase activity was compared with cytology for low grade lesions (Grades 1 and 2), the difference in the detection rates (82% for telomerase vs. 31% for cytology) was also significant (P < 0.001). CONCLUSIONS: Urinary cytology yields poor results for low grade tumors. This study shows the possible application of the telomerase assay in detecting bladder carcinoma, in particular low grade tumors, in voided urine samples.     

Diagnosis of urinary tract infections in puerperium

Urinary tract infections (UTI) are the most frequent nosocomial infections of women during puerperium. Since, in these women, diagnostic accuracy is affected by lochial secretion, suprapubic urinary bladder puncture (SPB) is recommended. Between December 1989 and January 1993, we subjected 903 women to suprapubic urinary bladder puncture (SpBP) at the 4th or 5th day after delivery. A urine culture of SpBP was done in all cases. Semiquantitative leukocyte counts (n = 891) and nitrite test (n = 830) were done on mid-stream urine (MSU). Side by side with microbiological investigation for urinary tract pathogens via SpPB, MSU was performed in 246 cases immediately after SpPB had been carried out. Leukocyte counts were also estimated in SpBP urine samples. In 370 (41.1%) of 903 SpBP, one or more microorganisms were cultivated. Only 36 (4.0%) of 903 women showed UTI symptoms. Microorganisms were detectable via SpBP in only 26 (72.7%) of these 36 symptomatic patients. Vaginal-operative or secondary caesarean section are related to an increased UTI rate (p < 0.001). UTI were also significantly (p < 0.0001) more frequent in women subjected to catheterisation sub partu (54.5%) compared to no catheterism (24.4%). No significant differences between the number of leukocytes in MSU sediment and the SpBP findings were seen. Semiquantitative leukocyte counts in SpBP offered a significantly (p < 0.001) increased number of leukocytes in cases with microorganism detection in SpBP irrespective of MSU findings. These results justify the designation of uterine tract infection also in the absence of complaints as "infection" and not common "bacteriuria".(ABSTRACT TRUNCATED AT 250 WORDS)     

Urodynamic factors influence the duration of Escherichia coli bacteriuria in deliberately colonized cases

PURPOSE: We evaluated the influence of urodynamic factors on the establishment of bacteriuria, after deliberate intravesical inoculation with Escherichia coli. MATERIALS AND METHODS: Nine women and 7 men with recurrent symptomatic urinary tract infections underwent intravesical injection of E. coli 83972. This strain had documented ability to persist in the urinary tract and it lacks expressed virulence factors associated with urinary tract infection. RESULTS: Successful long-term colonization (5 months to 3 years) was achieved in 6 of 12 patients with neurogenic bladder disorder, including normal or high bladder capacity, normal or low detrusor pressure and residual urine. Short-term bacteriuria (13 days) occurred in 1 but long-term bacteriuria was not established in the 4 patients with normal lower urinary tract function. Occasionally urine samples from the colonized patients contained other bacterial strains, which cleared spontaneously except for a Klebsiella strain that became established in 2 and subsequently eliminated E. coli 83972. CONCLUSIONS: E. coli 83972 bacteriuria could only be established in a subset of patients with defective bladder voiding, suggesting that urodynamic defects permit a nonvirulent strain to establish in the urinary tract, but that additional host factors determine if bacteriuria will persist.     

Does p53 immunostaining improve diagnostic accuracy in urine cytology?

The frequent change of the transitional cell carcinoma of the urinary tract accounts for the fact that cytological abnormalities in urinary specimens are often not sufficient to enable a definitive diagnosis of malignancy. The purpose of this work was to evaluate the possible use of p53 protein in increasing the diagnostic accuracy of urinary cytology. The expression of p53 was investigated by immunocytochemistry in two groups of urinary specimens, one cytologically positive and the other cytologically negative for cancer. Immunostaining was carried out using a monoclonal antibody to p53. In the positive group, in which bladder cancer was confirmed by cystoscopy and biopsy (31 cases), positive reaction for p53 was found in 55% of the cases (17 cases). In the negative group (92 cases), presence of cancer was histologically ascertained in 64 cases and in this group 15 cases (23.4%) showed positive p53 staining. In the remaining 28 cases of this group, where TCC was not present, 7 cases showed p53 positivity in non-neoplastic urothelial cells. This result shows that, while immunocytochemical detection of p53 in urinary specimens may be used for prognostic evaluation of patients with bladder cancer, it does not contribute to the diagnostic accuracy in cases with morphologically inconclusive or negative cytology. The sensitivity and specificity of the method in detecting bladder carcinoma were 23.5 and 75%, respectively.     

Disseminated intravascular coagulation: pathophysiology and principles of management

OBJECTIVE: To analyze the survival and the main prognostic factors in patients with transitional cell carcinoma of the upper urinary tract. METHODS: From 1983 to 1996, we treated 50 patients with transitional cell carcinoma of the upper urinary tract. Treatment was basically conservative except in those cases whose tumor stage or grade required a radical approach. Grading and staging were performed according to the 1992 TNM classification. Eighteen patients had died at one year mean follow-up., At the time the study was completed (June, 1997), 32 patients were alive with a mean follow-up of 4.9 years. Disease-free survival, overall and specific survival were analyzed according to sex, age, association with bladder tumors, localization, type of treatment, tumor size, number, histological grade and stage. RESULTS: The male-to-female ratio was 5:1. Patient mean age was 65.7 years. Association with bladder tumors was observed in 50%. Treatment was conservative in 40% and radical in 60%. The five- and ten-year disease-free survival rates were 69%, overall survival 61% and specific survival 71%. The univariate analysis showed the following to be unfavorable prognostic factors for survival: renal vs ureteral tumors, radical vs conservative treatment, high grade and stage tumors. The association of carcinoma in situ with other tumors of the upper urinary tract was also found to be an unfavorable factor for disease-free survival. The multivariate analysis associated T4 and G3 tumors with poor prognosis. CONCLUSIONS: Transitional cell carcinoma of the upper urinary tract was associated with bladder tumors in 50% of the cases. Low grade stage tumors demonstrated a high survival rate, therefore conservative treatment should be the first approach. High grade/ stage tumors were found to be unfavorable prognostic factors for survival.     

The influence of bladder fullness on upper urinary tract dimensions and renal excretory function

Nearly full bladders (375 ml.) produced significantly greater dimensions of the renal calices, pelves and ureters on excretory urograms compared to nearly empty bladders. These dimensions were frequently to the point of being considered pathological dilatations. On planimetry the urographic areas of the pelviocaliceal systems decreased by 43 per cent on the right side and 38 per cent on the left side when the nearly full bladder was compared to the nearly empty bladder in 10 patients. Renal excretory function also was affected by nearly full bladders. Urea clearances after 1 hour were 24 per cent lower and creatinine clearances were 9 per cent lower when starting with a nearly full bladder as compared to starting with an empty bladder. The implications of these findings are of potential significance with respect to 1) interpretation of excretory urograms and 2) chronic urine holding in patients with recurrent urinary tract infections, impaired renal function and/or urolithiasis.     

Noninvasive detection of bladder cancer with the BTA stat test

PURPOSE: We assess the sensitivity and specificity of the noninvasive BTA stat urine test for detection of primary and recurrent bladder cancer with special reference to the size, grade and stage of the tumors, and examine the effect of intravesical bacillus Calmette-Guerin treatment on the results. MATERIALS AND METHODS: A total of 250 patients recruited from 3 medical centers provided voided urine samples for the BTA stat test and cytopathological study. Of these patients 162 were monitored following resection of bladder tumors and 88 were evaluated for the first time for hematuria or irritative voiding symptoms. Each patient underwent cystoscopy. Biopsies were obtained when a bladder tumor was seen or if carcinoma in situ was suspected. The sensitivity, specificity and accuracy of the BTA stat test were compared to standard voided urine cytology. RESULTS: No tumor was found in 122 patients, primary transitional cell carcinoma was found in 71 and cystoscopy revealed recurrent tumors in 57. Overall sensitivity of the BTA stat test was 82.8% and specificity was 68.9%. Sensitivity of urine cytology was 39.8% and specificity was 95.1%. The BTA stat test detected 90.1% of the primary and 73.7% of the recurrent tumors. All patients with carcinoma in situ, high grade tumors, muscle invasive cancer and tumors larger than 2 cm. were diagnosed by the BTA stat test. CONCLUSIONS: The BTA stat test can be used as a screening test for bladder cancer in patients with hematuria or irritative voiding symptoms and for surveillance of those who have not been treated with intravesical bacillus Calmette-Guerin.     

Nerve biopsy in children with severe Guillain-Barré syndrome and inexcitable motor nerves

PURPOSE: Urinary nuclear matrix protein (NMP22) was evaluated for detection of new and recurrent bladder tumors in patients with a history of transitional cell carcinoma. Our objective was to determine sensitivity and specificity of this marker for tumors of various stages and grades, as well as its use as an adjunct to or substitute for urinary cytology. MATERIALS AND METHODS: A total of 231 patients with a history of transitional cell carcinoma provided 288 voided urine samples before cystoscopic examination at 1 of 3 institutions (53 patients were reevaluated at least once). Urine samples were assayed for NMP22 using the NMP22 Test Kit. Select patients underwent biopsy with appropriate additional therapy. Voided urinary cytology was obtained in 200 cases. End points for determination of the absence and presence of tumor were negative cystoscopy and positive biopsy, respectively. A receiver operating characteristics curve was constructed to determine the optimal NMP22 threshold for detection of transitional cell carcinoma. For positive biopsies NMP22 values were also correlated with tumor stage and grade. Comparison to cytology was limited to patients with complete data. RESULTS: There were 208 negative cystoscopies (158 with cytology) and 66 positive cystoscopies with biopsy (42 with cytology). Of the cases 14 were eliminated from statistical analysis due to incomplete data. Receiver operating characteristics curve interpretation determined that 6.4 units per ml. was an optimal reference value for detection of transitional cell carcinoma in this patient group. Sensitivity and specificity for all pathological groupings was 68 and 80%, respectively. When compared to cytology the sensitivities of NMP22 and cytology were 67 versus 31 or 40% (depending on the definition of positive cytology). CONCLUSIONS: NMP22 values represented significant improvement over urinary cytology for detection of transitional cell carcinoma. The sensitivity of NMP22 for detection of transitional cell carcinoma in bladder cancer patients was as much as twice that of cytology when a reference value of 6.4 units per ml. was used. NMP22 analysis was less costly than cytology and operator independent. While NMP22 has previously been shown to be a strong predictor of recurrence after tumor resection, it is an effective and sensitive screening test for detecting tumors in patients with transitional cell carcinoma.