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A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice.

PURPOSE: The commonly accepted diagnostic algorithm for hematuria includes excretory urography (IVP) and cystoscopy. Some have suggested that ultrasound of the upper urinary tract is adequate and that cystoscopy is not necessary in younger patients with microscopic hematuria. We ascertain whether a less intensive algorithm could be adopted while retaining diagnostic efficacy. MATERIALS AND METHODS: A total of 1,930 patients were enrolled prospectively in the study at a hematuria clinic between October 1994 and March 1997. Evaluation consisted of basic demographics, history and examination, routine blood tests, urinalysis and cytology. All patients underwent plain abdominal radiography, renal ultrasound, IVP and flexible cystoscopy. RESULTS: A total of 1,194 males and 736 females with a mean age of 58 years (range 17 to 96) were included in the study. Overall, 61% of patients had no basis found for hematuria, 12% had bladder cancer, 13% had urinary tract infection and 2% had stones. Kidney and upper tract tumors were noted in 14 patients (0.7%), including 4 who presented with microscopic hematuria. If only ultrasound or IVP had been performed 4 of these cases would have been missed. Of 982 patients presenting with microscopic hematuria 51 had cancer. Bladder cancer was found in 7 patients younger than 40 years. CONCLUSIONS: Our findings suggest that cystoscopy cannot be safely avoided even in younger patients with microscopic hematuria. Only a combination of ultrasound and IVP detected all upper tract tumors.

Adolescent↗

The dilemma of suspicious urine cytology in patients being followed for bladder cancer.

BACKGROUND AND AIMS: Urine cytology is gold standard for clinical tests used in the diagnosis and follow-up of bladder cancer. Cytology, however, exhibits variable sensitivity depending on tumour grade and interpretation of urine specimens is highly dependent on the skill of the examiner. Furthermore, a "suspicious" cytology report (class III) makes clinicians uncomfortable. In these cases, a more objective test, such as the BTA stat Test, may be useful in providing clarification. The aim of this study was to evaluate the dilemma of suspicious routine urine cytology and to determine whether the BTA stat Test provides diagnostic aid in this rare but controversial category. MATERIAL AND METHODS: 506 consecutive patients who were being followed for bladder cancer were included in the study. A voided urine sample was obtained prior to routine follow-up cystoscopy and split for culture and testing with the BTA stat Test. Clinical status of the disease was evaluated in patients with suspicious urine cytology, and the diagnostic aid of the BTA stat Test in these patients was determined. RESULTS: A total of 57 patients (11.3%) had urine cytology classified as suspicious. The BTA stat Test was positive in 29 (50.9%) and negative in 28 (49.1%) patients. Nineteen (33.3%) patients had recurrence at routine cystoscopy. Of the remaining 38 patients, 10 were further investigated due to a positive BTA stat Test. Two additional recurrences were detected bringing the total number of recurrences to 21 (36.8%), 48.3% (14/29) of the patients with positive and 25.0% (7/28) of the patients with negative BTA stat Test had recurrence (p = 0.069). Overall, 65.5% (19/29) of the patients with a positive BTA stat Test were found to have recurrence either at routine cystoscopy, at further investigations, or at the next cystoscopy compared to that of 35.7% (19/28) in those with negative testing (p = 0.024). The overall sensitivity of the BTA stat Test was 66.7%, and the specificity was 58.3%. CONCLUSIONS: At least a third of the patients under follow-up for bladder cancer with suspicious cytology had a recurrence, indicating that these patients are a risk group for recurrence. More importantly, a BTA stat Test result seems to provide some help in distinguishing those patients with very high risk for recurrence, for whom invasive further investigations should be conducted and a close follow-up policy maintained.

Aged↗

Diagnostic accuracy of urinary cytology, and deoxyribonucleic acid flow cytometry and cytology on bladder washings during followup for bladder tumors.

PURPOSE: We evaluated the diagnostic accuracy of cytology on urine and bladder washings, and deoxyribonucleic acid (DNA) flow cytometry on bladder washings compared to cystoscopy during followup for bladder tumors. MATERIALS AND METHODS: A cross-sectional analysis was performed on 166 patients with a history of bladder tumor for the initial visit when cytology and DNA flow cytometry results were available for urine and bladder washing samples. There were 114 bladder tumor events and 52 negative controls (normal cystoscopy). A prospective study was conducted among the 66 patients with no tumor detected by cystoscopy at the initial visit and for whom the 3 test results were available. The patients were followed from this visit until tumor recurrence or the end of the followup period. Cytological examination was considered positive only when interpreted as malignant. Suspicious examinations were considered negative for the purpose of our study. RESULTS: Sensitivity and specificity of urinary cytology were 59 and 85%, respectively. Sensitivity was increased to 66% using bladder washing cytology whereas specificity was moderately decreased to 83%. The sensitivity and specificity of DNA aneuploidy were 45 and 87%, respectively. Inclusion within the aneuploid category of hyperdiploid samples (defined as more than 7% of cells in the S + G2M phase) increased sensitivity to 77%, while specificity decreased to 42%. Kaplan-Meier analysis of tumor-free survival in patients initially free of bladder cancer at cystoscopy showed an inability of DNA flow cytometry to predict recurrence, whereas positive urine or bladder washing cytology predicted a shorter time to recurrence (log-rank test p <0.01). CONCLUSIONS: These results show that DNA flow cytometry and cytology on bladder washing samples add little information to that obtained from voided urine cytology.

Cross-Sectional Studies↗

Detection of bladder cancer using a point-of-care proteomic assay.

CONTEXT: A combination of methods is used for diagnosis of bladder cancer because no single procedure detects all malignancies. Urine tests are frequently part of an evaluation, but have either been nonspecific for cancer or required specialized analysis at a laboratory. OBJECTIVE: To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could enhance detection of malignancy in patients with risk factors or symptoms of bladder cancer. DESIGN, SETTING, AND PATIENTS: Twenty-three academic, private practice, and veterans' facilities in 10 states prospectively enrolled consecutive patients from September 2001 to May 2002. Participants included 1331 patients at elevated risk for bladder cancer due to factors such as history of smoking or symptoms including hematuria and dysuria. Patients at risk for malignancy of the urinary tract provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. MAIN OUTCOME MEASURES: The diagnosis of bladder cancer, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to cancer detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. RESULTS: Bladder cancer was diagnosed in 79 patients. The NMP22 assay was positive in 44 of 79 patients with cancer (sensitivity, 55.7%; 95% confidence interval [CI], 44.1%-66.7%), whereas cytology test results were positive in 12 of 76 patients (sensitivity, 15.8%; 95% CI, 7.6%-24.0%). The specificity of the NMP22 assay was 85.7% (95% CI, 83.8%-87.6%) compared with 99.2% (95% CI, 98.7%-99.7%) for cytology. The proteomic marker detected 4 cancers that were not visualized during initial endoscopy, including 3 that were muscle invasive and 1 carcinoma in situ. CONCLUSION: The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the accuracy of cystoscopy, with test results available during the patient visit.

Adult↗

Assessment of microsatellite instability in urine in the detection of transitional-cell carcinoma of the bladder.

Loss of heterozygosity (LOH) and alterations in microsatellite DNA markers have been reported in bladder-cancer tumors. We have studied, in a blinded fashion, using PCR-based microsatellite analysis, genetic alterations of cells exfoliated in urine of 59 Caucasian patients and control patients; 31 with initially confirmed bladder transitional-cell carcinoma (TCC), 17 with signs and symptoms suggestive of bladder cancer, 6 control patients who underwent renal transplantation, and 5 control patients with urolithiasis. Microsatellite analysis of cells exfoliated in the urine allowed the diagnosis of 83% (10/12) of patients with bladder TCC recurrence confirmed by cystoscopy, while 100% of patients followed up for transitional-cell carcinoma of the bladder for up to 12 months without evidence of tumor recurrence upon routine cystoscopy showed no microsatellite alterations. None of the patients without neoplasia (negative controls) had any microsatellite alterations, whereas all patients who underwent renal transplantation had additional new alleles corresponding to contamination with donor's renal and urothelial cells (positive controls). No control patients had any evidence of transitional-cell carcinoma by cystoscopy. Our results provide objective evidence that non-invasive molecular detection of bladder TCC by microsatellite analysis is reproducible with a sensitivity of 83% and a specificity of 100% in Caucasian patients. This non-invasive procedure represents a potential clinical tool for the detection and the screening of bladder TCC.

Adult↗

Neural network-based digitized cell image diagnosis of bladder wash cytology.

In this pilot study, we tested whether it is possible to apply neural network-based diagnostics on bladder washings to detect urothelial cell carcinoma of the bladder. Eighty-five bladder wash (BW) samples were chosen at random from our own database. Cystoscopy, histology, and follow-up data concerning tumor recurrence were available. Each slide was scanned by the neural network-based digitized cell image system. The neural network-based diagnosis (NNBD) was based on 128 digitized cell images provided by the system. The light microscopic diagnosis (LMD) was rendered by an experienced cytopathologist using the same terminology, i.e., negative, low-grade tumor, and high-grade tumor. Finally, an automatic QUANTICYT analysis was performed on the same material, with as classification low, intermediate, and high risk. The sensitivity for diagnosing a histologically confirmed tumor was for NNBD 92%, for LMD 50%, and for QUANTICYT 69%. For the three methods, receiver operating characteristic (ROC) curves were made for the thresholds low grade/intermediate risk and high grade/high risk. For the prediction of a positive cystoscopy, the highest area under the curve (AUC) was found for NNBD, being 0.71. The AUC for LMD was 0.58. QUANTICYT analysis had the highest AUC value (0.62) for predicting tumor recurrence after a negative cystoscopy, with a lower value for NNBD (0.50). These findings indicate that neural network-based diagnosis of bladder washing samples is highly promising.

Area Under Curve↗

Transrectal biopsy of the prostate and bacteraemia.

Bacteraemia and urinary tract infection are well-recognized complications of urological procedures. This paper compares, for the first time, the incidence of bacteraemia after cystoscopy and transrectal biopsy of the prostate with that following cystoscopy alone. The incidence of bacteraemia in those undergoing biopsy was 73 per cent; following cystoscopy alone the incidence was 13 per cent. In view of this high incidence we recommend prophylactic antibiotic cover of transrectal prostatic biopsy.

Biopsy↗

How painful are shockwave lithotripsy and endoscopic procedures performed at outpatient urology clinics?

Our aim was to investigate the subjective pain felt by patients during shockwave lithotripsy (SWL) and endoscopic procedures such as cystoscopy, retrograde ureteral stenting, retrograde pyelography (RGP), and ureteroscopic lithotripsy performed in an outpatient clinic, and to identify how severe pain during such procedures is. We estimated subjective pain in 984 patients after SWL (186), cystoscopy (489), retrograde ureteral stenting (127), RGP (97), and ureteroscopic lithotripsy (85) performed by a single expert in an outpatient clinic using a prospective questionnaire with a ten point visual analog scale between January 2001 and December 2003. There was no premedication in any procedure except ureteroscopic lithotripsy for which an intramuscular injection of analgesics (pethidine HCl 50 mg) was used. The pain scale score in SWL was 6.62+/-2.27, the highest among the procedures (P<0.05). Pain scores for endoscopies were 4.48+/-2.07 in retrograde ureteral stenting, 3.81+/-2.06 in ureteroscopic lithotripsy, 3.72+/-1.75 in RGP, and 3.08+/-1.95 in cystoscopy. In this study, we observed that patients feel most pain in SWL without anesthesia, and that pain during ureteroscopic lithotripsy under local anesthesia is not high, compared with other endoscopic procedures.

Adolescent↗

Cystoscopic and DMSA findings in relation to types of reflux demonstrated on percutaneous direct radionuclide cystography in children.

BACKGROUND: The new technique of percutaneous direct radionuclide cystography (PDRC) allows the accurate demonstration of vesicorenal reflux under physiological conditions during resting and micturition phases. Five types of reflux have been described, the clinical relevance of which is uncertain. OBJECTIVE: To determine whether a relationship exists between the type of reflux identified on PDRC and the appearance of the ureteric orifice at cystoscopy or the prevalence of renal abnormalities. MATERIALS AND METHODS: The reports of 281 PDRC examinations were reviewed and 76 children with reflux formed the population of this study. Studies of these children were reviewed to classify the reflux as types 1-5, and patient records were searched for cystoscopy and DMSA scan reports. RESULTS: Regardless of the type of reflux, the ureteric orifices were found to be open at cystoscopy in 60-66% of refluxing units. DMSA scan abnormalities were present in 68% of units with reflux at rest, 61% of units with reflux on micturition and 86% of units with reflux on both resting and micturition phases. In comparison with contralateral units that did not reflux, the presence of reflux had a significant association with openness of the ureteric orifice ( p<0.00001) and DMSA abnormality ( p<0.005). CONCLUSIONS: Reflux of any type is strongly associated with an open ureteric orifice. Units that reflux during both resting and micturition phases had a higher incidence of DMSA abnormality than those refluxing during one phase only, but this was not statistically significant.

Adolescent↗

Specific investigations in chronic urinary bilharziasis.

Seventy-two patients with histologically confirmed chronic urinary bilharziasis were studied for the reliability of some specific investigative tools in diagnosing this disease, namely urinalysis, serology, urography, and cystoscopy. Of the 72 patients 36 (50%) had hematuria and only 3 (4%) had ova of Schistosoma haematobium on urinalysis. Sixty-two patients (86%) had features of bilharziasis on intravenous urography (IVU). Of the remaining 10 patients with negative urography 6 underwent serology and all had positive results. Of the total patients 52 underwent serology and 49 had significant bilharzial antibody titer (94.2%). At cystoscopy all patients (100%) had features of bilharziasis. It is concluded that the most reliable diagnostic tools in chronic urinary bilharziasis are cystoscopy, serology, and to a lesser extent urography. Unlike early bilharziasis, chronic bilharziasis can be missed if total reliance is placed on urinalysis for screening a population at risk.

Adolescent↗

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↗

Should bladder biopsies be performed routinely after bacillus Calmette-Guérin treatment for high-risk superficial transitional cell cancer of the bladder?

OBJECTIVE: After endoscopic resection of high-grade superficial urothelial neoplasms (Ta, T1 or Tis), adjuvant bacillus Calmette-Guérin (BCG) therapy is performed routinely to avoid recurrence and/or progression. Vesical biopsies often are performed to assess the efficacy of treatment. The aim of our study was to evaluate the usefulness of these biopsies. MATERIALS AND METHODS: During this retrospective bi-centre study, 130 patients who had undergone vesical high-grade tumour resection were included. There were 40 Ta associated with Tis in three cases, 87 T1 associated with Tis in 13 cases, and three isolated Tis. After BCG treatment, the following parameters were studied: cytoscopic findings, urine cytology and the histologic results of systematised biopsies. RESULTS: Urine cytology was positive (high-grade) for 26 patients and negative (normal or low-grade) for 104 patients. For the 26 patients with positive cytology, vesical flexible cystoscopy findings were considered suspicious in 18 patients and normal in eight patients. As for the 104 patients who presented negative cytology, cystoscopic findings were considered negative in 76 patients and suspicious in 28 patients. In the present study, the sensitivity of cytology and cystoscopy in the detection of recurrence after BCG treatment was 56% and 87.5%, respectively; specificity was 56% and 81.6%, respectively. When the two examinations were combined, sensitivity was 100%, and specificity was 76%. CONCLUSIONS: After BCG therapy, the association of negative flexible cystoscopy findings and normal urine cytology made it possible to avoid routine biopsies. Patients could therefore avoid the morbidity of this procedure.

BCG Vaccine↗

Prediction of septicemia following endourological manipulation for stones in the upper urinary tract.

We investigated 117 patients undergoing percutaneous nephrolithotomy, percutaneous nephrostomy, ureterorenoscopy, the push-back or push-bang procedure for ureteral stones, Double-J* ureteral stenting plus extracorporeal shock wave lithotripsy (ESWL), ESWL alone or cystoscopy. Blood samples obtained before, during and 1 hour after the procedure were cultured and assayed for endotoxin and tumor necrosis factor. Also, culture was done of the urine preoperatively and postoperatively, and the stones when they could be retrieved. There was a temporal relationship among bacteremia, endotoxemia and elevation of tumor necrosis factor. An unexpected finding was peroperative endotoxemia in a significant number of patients with stones. Risk factors noted for postoperative bacteremia, endotoxemia and/or elevation of tumor necrosis factor included preoperative endotoxin level, type of procedure, presence of preoperative bacteriuria and pyuria. With respect to the procedure the risk was greatest after the push-back method and least after cystoscopy (push-back method greater than percutaneous nephrolithotomy/percutaneous nephrostomy greater than Double-J stenting plus ESWL greater than ureterorenoscopy greater than ESWL greater than cystoscopy). If the risk factors are measured preoperatively it may be possible to identify the risk of postoperative bacteremia/endotoxemia and, therefore, septic shock postoperatively. Our patients appear to be a good clinical model to investigate the problems related to septicemia.

Adolescent↗

Cocaine and lidocaine as topical urethral anesthetics.

To evaluate the efficacy of topical cocaine combined with lidocaine as a urethral anesthetic, a double-blind, randomized, prospective study was performed comparing lidocaine combined with cocaine or placebo in male outpatient cystoscopy. Evaluations were based on a scale of 1 to 10, with 1 representing no discomfort and 10 extreme discomfort as judged by the patient, and 1 representing the best tolerance and 10 extreme intolerance as judged by the physician. Patients who received lidocaine plus cocaine reported a mean score of 3.33 for over-all discomfort of cystoscopy. This was not significantly different than for lidocaine alone. This finding indicates a lack of a summation effect in combining topical anesthetics. Patients undergoing repeat examinations were no more comfortable than those undergoing initial cystoscopy but older patients tolerated the procedure significantly better than younger patients.

Anesthesia, Local↗

A new diagnostic algorithm for the evaluation of microscopic hematuria.

OBJECTIVES: To evaluate a new diagnostic algorithm for microscopic hematuria in which intravenous urography (IVU) is performed as a secondary radiographic study when microhematuria has persisted for 3 months after the initial workup with renal ultrasound (US) and cystoscopy was negative. METHODS: We evaluated 372 consecutive patients who presented with microhematuria and negative urine cultures and cytologic findings at our institution. All patients underwent renal US scanning and cystoscopy as their initial evaluation. All patients underwent re-evaluation 3 months after the initial workup. Patients with persistent microhematuria with no apparent etiology were then evaluated with IVU. RESULTS: The initial evaluation was negative in 212 of 372 patients. Eighty-one of these patients had persistence of their microhematuria at the 3-month follow-up without a definitive diagnosis. Seventy-five of these patients underwent IVU. Abnormalities were found in 11 of the 75 patients. Six patients had renal stones, two had ureteral stones, two had ureteral tumors, and one had a tumor of the renal pelvis. Forty of the 131 patients with resolution of their microhematuria underwent IVU at their request. All those studies were normal. CONCLUSIONS: The combination of cystoscopy and renal US along with urinalysis, urine culture, and cytology is a good initial evaluation in patients with microhematuria. Those patients with persistent microhematuria after 3 months without definite etiology of the bleeding may still benefit from IVU.

Adult↗

Routine bladder biopsy after bacille Calmette-Guérin treatment: is it necessary?

OBJECTIVES: To evaluate the need for routine biopsy at first follow-up after intravesical bacille Calmette-Guérin (BCG) therapy for superficial transitional cell cancer of the bladder (TCCB). We examined the potential role of voided urine cytology and cystoscopy as screening tools to determine which patients should undergo biopsy. METHODS: The records of 71 patients with TCCB who received a total of 95 courses of BCG were reviewed. The pathology findings before BCG and the cystoscopic, voided cytologic, and biopsy results after BCG were recorded. RESULTS: In 54 cases, the cystoscopic and/or cytologic findings were abnormal. In 19 (35%) of these 54 cases, TCCB was found on biopsy after BCG. In 41 cases, both cystoscopy and cytology were normal. In 1 of these 41 cases, a small superficial low-grade TCCB was found on biopsy. An abnormality on voided cytology or cystoscopy was more likely to occur after treatment for carcinoma in situ. CONCLUSIONS: Patients with papillary TCCB who have negative cystoscopic and negative urine cytologic results can safely be spared routine transurethral bladder biopsy with its associated cost and morbidity. However, patients with carcinoma in situ are very likely to have persistent abnormal cytologic or abnormal cystoscopic findings warranting investigation with biopsy and may benefit from routine scheduled biopsy.

Adjuvants, Immunologic↗

Qualitative and quantitative detection of urinary human complement factor H-related protein (BTA stat and BTA TRAK) and fragments of cytokeratins 8, 18 (UBC rapid and UBC IRMA) as markers for transitional cell carcinoma of the bladder.

OBJECTIVE: To evaluate the role of BTA stat, BTA TRAK, UBC Rapid, UBC IRMA and voided urinary cytology in the detection of bladder transitional cell carcinoma (TCC). METHODS: The study included 78 patients with TCC of the bladder (group A), 62 patients with a history of bladder TCC without tumor recurrence at the time of examination (B, control group), 20 patients with other malignancy of the urinary tract (C), 38 patients with non-malignant urinary tract diseases (D), 10 patients with urinary tract infection (E) and 10 healthy volunteers (F). Except in group F, voided urine was collected before cystoscopy or cystectomy. RESULTS: The specificity and sensitivity in bladder cancer detection were 87.1 and 74.4%, respectively with BTA stat, 79.3 and 48.7%, respectively with UBC Rapid, 100 and 33.3%, respectively with cytology, 72.6 and 75.6%, respectively with BTA TRAK, 64.5 and 70.5%, respectively with UBC IRMA. CONCLUSIONS: The BTA stat and BTATRAK tests are superior to UBC Rapid, UBC IRMA and urinary cytology in detection of bladder TCC. In daily practice however cytology remains the best adjunct to cystoscopy because of its high sensitivity in Tis and 100% specificity. Cystoscopy cannot be replaced by any of evaluated methods.

Adult↗

Transvaginal repair of bladder lacerations during LAVH.

Eight bladder lacerations occurred during laparoscopic-assisted vaginal hysterectomy (LAVH) at a university-affiliated private hospital. All were exposed vaginally. Six were repaired with a standard two-layer closure by the vaginal route. One patient had a combined vaginal and laparoscopic repair. Another had a partial ureteric avulsion that was repaired vaginally, and a double-J ureteric catheter was left in situ for 6 weeks. All patients underwent cystoscopy to confirm adequate closure and confirmation of ureteric patency. All repairs were successful. The planned procedure (LAVH) was completed without further complications and the hospital stay was not prolonged as a result of the injury. The patient with partial ureteric avulsion had a normal intravenous pyelogram, and the ureteric catheter was removed in the office by transurethral cystoscopy. We conclude that bladder injuries during LAVH can be readily identified intraoperatively. Excellent results can be achieved with transvaginal repair, and the planned procedure can be completed by the intended route. Cystoscopy to confirm ureteric patency is essential after all repairs.

Adult↗