AUTOFLUORESCENCE GUIDED BIOPSY FOR THE EARLY DIAGNOSIS OF BLADDER CARCINOMA

Purpose

We validate the usefulness of laser-induced autofluorescence for the detection of bladder carcinoma.

Materials and Methods

We obtained and analyzed fluorescence spectra from 75 patients in whom bladder cancer was suspected. Tissue fluorescence was excited by a nitrogen laser using a quartz optical fiber placed in gentle contact with the area of interest. The laser-induced autofluorescence spectrum was recorded using an intensified optical multichannel analyzer system. Spectra were corrected for the spectral response of the optical system, and the ratios of laser-induced autofluorescence intensities (I) at 385 and 455 nm. (I₃₈₅/I₄₅₅) were determined. We had previously established this ratio as a diagnostic algorithm. We included only suspicious bladder lesions (erythematous, edematous, raised and so forth) that were difficult to diagnose by cystoscopy as well as areas from which random biopsies were obtained. The fluorescence ratio algorithm was applied to 130 bladder areas.

Results

Of the 130 biopsies obtained during routine cystoscopy 107 (82%) were nonmalignant by histological classification. In contrast, because laser-induced autofluorescence effectively guides biopsies towards malignant lesions, only 30 biopsies (72% fewer) would have been obtained from nonmalignant tissue if the fluorescence ratio that identifies 95% of malignant lesions (95th percentile) had been selected as the decision criterion during standard cystoscopy.

Conclusions

By guiding the surgeon to suspicious lesions that are most likely to be malignant, laser-induced autofluorescence substantially decreases the number of biopsies obtained from nonmalignant tissue during cystoscopy to diagnose bladder carcinoma.     

Laser Induced Autofluorescence Diagnosis of Bladder Tumors: Dependence on the Excitation Wavelength

Purpose

We assessed the ability of laser induced autofluorescence spectroscopy to distinguish neoplastic urothelial bladder lesions from normal or nonspecific inflammatory mucosa.

Materials and Methods

Three different pulsed laser excitation wavelengths were used successively: 308 nm. (xenium chloride excimer laser), 337 nm. (nitrogen laser) and 480 nm. (coumarin dye laser). The excitation light was delivered by a specially devised multifiber catheter connected to a 1 mm. core diameter silica monofiber introduced through the working channel of a standard cystoscope with saline irrigation. The captured fluorescence light was focused onto an optical multichannel analyzer detection system. Device performance was evaluated in 25 patients after obtaining consent and immediately before transurethral resection of a bladder tumor. Spectroscopic results were compared with histological findings.

Results

At 337 and 480 nm. excitation wavelengths the overall fluorescence intensity of bladder tumors was clearly decreased compared to normal urothelial mucosa regardless of tumor stage and grade. At the 308 nm. excitation wavelength the shape of the tumor spectra, including carcinoma in situ, was markedly different from that of normal or nonspecific inflammatory mucosa. No absolute intensity determinations were required in this situation, since a definite diagnosis could be established based on the fluorescence intensity ratio at 360 and 440 nm.

Conclusions

This spectroscopic study could be particularly useful to design a simplified autofluorescence imaging device for detection of occult urothelial neoplasms.     

Wide-field autofluorescence-guided TUR-B for the detection of bladder cancer: a pilot study

Purpose

The aim of this pilot study was to assess the feasibility and value of wide-field autofluorescence imaging (AFI) for the detection of bladder cancer during transurethral resection of the bladder (TUR-B).

Methods

For imaging, the D-Light/AF System (Karl Storz GmbH, Tuttlingen, Germany) and a customized band pass filter (≈ 480–780 nm) at the eyepiece of the endoscope were used. The excitation light wavelength was 440 nm. Representative spectral measurements of tissue autofluorescence (AF) were performed using a spectrometer attached behind the AF band pass filter in selected patients. During TUR-B, cystoscopy was performed in white light (WL) followed by wide-field AFI. Lesions were classified as suspicious or normal using either modality.

Results

Representative spectral measurements using excitation at a wavelength of 440 nm resulted in significantly lower fluorescence intensity of malignant versus non-malignant tissue. Overall, 56 lesions (30 cancerous and 26 non-malignant) in 25 patients were assessed and classified by wide-field AFI. Papillary tumors as well as flat lesions lacked the green fluorescence seen in normal urothelium, thus emerging as “brown-reddish” areas. When compared with histopathological findings, the pooled per-lesion sensitivity and specificity for AF were 96.7 and 53.8%, respectively. For WL these values were 86.7 and 69.2%, respectively.

Conclusion

Wide-field AFI imaging during TUR-B is simple and easy to use. Our preliminary data suggest that AFI has the potential to increase the detection rates of bladder tumors compared with WL without the need of intravesical instillation prior to the procedure.

     

Detection of Early Bladder Cancer by 5-Aminolevulinic Acid Induced Porphyrin Fluorescence

Purpose

We determined whether the sensitivity of detecting dysplasia or early bladder cancer can be improved by 5-aminolevulinic acid induced porphyrin fluorescence.

Materials and Methods

A 3 percent 5-aminolevulinic acid solution was instilled intravesically before cystoscopy in 104 patients. The 5-aminolevulinic acid induced porphyrin fluorescence was excited by violet light from a krypton ion laser (wavelength 406.7 nm.).

Results

The sensitivity of the fluorescence cystoscopy (96.9 percent) was significantly (p less than 0.0001) greater than that of white light cystoscopy (72.7 percent). There was no impact on specificity.

Conclusions

Due to the high sensitivity of the procedure fluorescence guided biopsies are recommended instead of random biopsies.     

Clinical recording of laser-induced fluorescence spectra for evaluation of tumour demarcation feasibility in selected clinical specialities

Laser-induced autofluorescence spectra from humans were recorded in vivo at three different clinics in a study aimed at investigating the capability of this method to discriminate between malignant tumours and normal surrounding tissues. For the recordings a mobile trolley with the necessary equipment was constructed for use in an examination room or in an operating theatre environment. Laser light was guided through a 600m optical fibre to the target tissue. The fluorescence from the excited tissue was collected with the same fibre and was fed to an optical multichannel analyser. Two excitation wavelengths were used (337 and 405 nm) in order to optimize the fluorescence signals in two interesting wavelength regions (380–500 and 550–700 nm). Oral and oropharyngeal tumours excited with 405 nm light contained detectable endogenous porphyrins and were in this way discriminated from the normal mucosa. Astrocytoma grade III–IV fluorescence different from that of normal brain tissue, while tumours in the bronchial tree were not detectable using the spectral shape of the pure tissue autofluorescence.     

The detection of oral pre- malignant lesions with an autofluorescence based imaging system (VELscope<Superscript>TM</Superscript>) – a single blinded clinical evaluation

Objective

The disease specific five-year survival rate especially for patients with advanced oral cancer has not improved significantly over the period of time. The most effective way of combating this dilemma is an early detection, diagnosis and eradication of early-stage lesions and their precursors. The use of VELscope^® using an autofluorescence as a diagnostic tool might be useful in early detection of oral malignant lesions.

Materials and methods

120 patients with suspicious oral premalignant lesions were examined with two examination methods. They were randomly divided into two groups. Group 1 was examined conventional with white-light and group 2 was examined additionally to the white-light-examination with an autofluorescence visualization device, VELscope^®. Biopsies were obtained from all suspicious areas identified in both examination groups (n?=?52). The diagnostic strategies were compared regarding sensitivity and specificity.

Results

Based upon the result, use of the VELscope^® leads to a higher sensitivity (22.0%), but regarding specificity the additional use of the VELscope^® is inferior (8.4%).

Conclusion

The VELscope device is a simple, non-invasive test of the oral mucosa, which can help the experienced clinician to find oral precursor malignant lesions.

     

Nonmalignant Breast Papillary Lesions at Core-Needle Biopsy: A Meta-analysis of Underestimation and Influencing Factors

Background

The clinical management of nonmalignant breast papillary lesions diagnosed at core-needle biopsy (CNB) is controversial. A meta-analysis was performed to evaluate pooled estimates of the underestimation of malignant papillary lesions (which were diagnosed as nonmalignant lesions at CNB) and to survey factors that affect that underestimation.

Methods

We searched for studies that provided data on CNB underestimates of malignant breast papillary lesions indexed in PUBMED. The pooled estimate for underestimation was calculated. The association between each variable and underestimation was investigated using either random- or fixed-effects logistic modeling.

Results

A total of 34 studies, which included 2,236 nonmalignant breast papillary lesions diagnosed at CNB and histologically examined after surgical excision, were included. Of these, 346 nonmalignant lesions at CNB were upgraded to malignant after surgical excision. The pooled estimate for the percentage of underestimation was 15.7 % [95 % confidence interval (CI): 12.8–18.5 %]. The factors associated with higher underestimation included atypical papillary lesions (P < 0.001), positive mammographic findings (P = 0.022), and article publication year before 2005 (P < 0.05).

Conclusions

It is recommended that atypical papillary lesions at CNB undergo surgical excision, and it is reasonable to follow patients with benign lesions with serial imaging. Lesion type, mammographic findings, and article publication year were significantly associated with underestimation.     

Argon Laser Induced Autofluorescence May Distinguish Between Normal and Tumor Human Urothelial Cells: A Microspectrofluorimetric Study

Purpose

To assess the ability of argon laser-induced autofluorescence spectroscopy (LIAFS) to discriminate normal from tumor human urothelial cells.

Materials and Methods

Emission spectra of single living cells excited at 488 nm. have been studied with a confocal microspectrofluorimeter.

Results

Cellular autofluorescence appeared as a broad band with a maximum in the same “green” spectral range, 550 to 560 nm., probably corresponding to oxidized flavoprotein emission. However, the maximum autofluorescence intensity of normal urothelial cells was much higher, 10 times (p less than 0.0001) that of any of the tumor cell types tested.

Conclusion

These results, suggesting a significantly reduced oxidized flavoprotein concentration in tumor urothelial cells, should prompt us to evaluate argon LIAFS as a potential tool to detect occult urothelial severe dysplasia and carcinoma in situ.     

Photodynamic Therapy on Rat Urinary Bladder with Intravesical Instillation of 5-Aminolevulinic Acid: Light Diffusion and Histological Changes

Purpose

Photodynamic therapy (PDT) has the potential to treat extensive premalignant lesions and microinvasive tumors in the bladder, but its use has been hampered by the risk of detrusor muscle damage and prolonged skin photosensitivity. We have shown that the rat urothelium can be sensitized by selectively using a 10 percent solution of 5-aminolevulinic acid (ALA) at pH 5.5 administered intravesically. This paper evaluates the photodynamic effects on sensitized bladders.

Materials and Methods

The bladders of Wistar rats were instilled with ALA solutions of different concentrations at pH 5.5 and subsequently treated with laser light at 630 nm. Bladders were harvested 1 to 7 days after PDT for histological assessment.

Results

Under optimum conditions (10 percent intralipid diffusion medium, light dose 50J) uniform urothelial necrosis was seen after 1 to 2 days; it healed in 7 days without damage to the underlying muscle layer although some increase in collagen was seen in the lamina propria. Overtreatment or poor light distribution resulted in muscle necrosis and scarring.

Conclusions

Selective urothelial necrosis is possible with PDT using intravesical ALA. There is now sufficient data for pilot clinical trials to start photodynamic therapy for management of superficial bladder cancer or carcinoma in situ.     

PHOTODYNAMIC THERAPY USING PORFIMER SODIUM AS AN ALTERNATIVE TO CYSTECTOMY IN PATIENTS WITH REFRACTORY TRANSITIONAL CELL CARCINOMA IN SITU OF THE BLADDER

Purpose

Photodynamic therapy combines a photosensitizer, such as porfimer sodium (Photofrin), with red laser light (630 nm.) to destroy cancer cells. Investigators have reported the effectiveness of photodynamic therapy in the treatment of patients with recurrent superficial bladder cancer. We assess the safety and efficacy of 1 or 2 photodynamic treatments using porfimer sodium and controlled uniform laser light (630 nm.) as an alternative to cystectomy in patients with refractory vesical carcinoma in situ of the bladder.

Materials and Methods

A total of 36 patients with carcinoma in situ were treated with whole bladder photodynamic therapy as an alternative to cystectomy. In all patients at least 1 course of bacillus Calmette-Guerin (BCG) had failed. Each patient received a single whole bladder photodynamic therapy treatment, consisting of 2 mg./kg. porfimer sodium intravenously followed 40 to 50 hours later by intravesical red light (630 nm.) at 15 J./cm.². Post-photodynamic therapy evaluations included weekly telephone contact to assess acute adverse reactions, and assessment of efficacy and bladder toxicity at 3 months and quarterly thereafter.

Results

At initial clinical evaluation at 3 months 58% of the patients had a complete response as indicated by negative cystoscopy, bladder biopsy and urine cytology but in 42% treatment failed. At a mean followup of 12 months (range 9 to 48) 10 of the 21 complete responders had recurrence for an overall durable response rate of 31%. Fourteen patients subsequently underwent cystectomy for persistent carcinoma in situ (12) and carcinoma in situ recurrence (2). Of the 36 patients 7 experienced bladder contracture.

Conclusions

The initial results are encouraging for a single whole bladder photodynamic treatment of patients in whom prior intravesical therapy for carcinoma in situ has failed. While followup is short, porfimer sodium photodynamic therapy appears potentially promising as an alternative to cystectomy in patients with refractory carcinoma in situ.     

Sodium fluorescein–guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study

Objective

In glioma surgery, the extent of resection (EOR) is one important predictor of progression-free survival. In 2006, fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) was shown to improve the EOR in malignant gliomas. However, the use of 5-ALA is complex and causes certain side effects. Sodium fluorescein (FL) is a fluorescent dye that is used for angiography in ophthalmic surgery. FL accumulates in areas of the disturbed blood-brain barrier and can be visualized under a 560-nm wavelength fluorescent light source (YELLOW 560 nm, Carl Zeiss Meditec, Oberkochen, Germany). Here, we present the first experiences with low-dose FL and YELLOW 560 nm in 35 patients with malignant brain tumors.

Patients and method

A total of 200 mg of FL (3–4 mg/kg bodyweight) was administered in 35 patients during craniotomy as an off-label use between May and August 2012. We retrospectively analyzed the histology, pre-treatment, clinical parameters pre- and postoperatively and occurrence of any adverse effects. The feasibility and efficacy (‘helpful,’ ‘not helpful’) of FL under YELLOW 560 nm (demarcation of the tumor margin) was assessed by the responsible neurosurgeon (n?=?5) for each surgical procedure.

Results

Twenty-six patients had gliomas (1 WHO grade I, 3 WHO grade II, 5 WHO grade III, 17 WHO grade IV), 5 patients had cerebral metastases, 2 had non-malignant astrogliosis and 2 had post-radiation necrosis. The fluorescence signal was detected in all patients immediately after the FL administration. FL application was classified as ‘helpful’ in 28 patients, implying improved visualization of the tumor margins. The intensity of the fluorescence signal seemed to be correlated to the histology and was strongly dependent on the pre-treatment status. We did not record any allergic reactions or any other adverse effects.

Conclusion

The use of FL for the resection of brain tumors is safe and feasible. Presumably, the visualization of the tumor margin depends on the histopathology and on the pre-treatment status. A randomized evaluation of FL under the YELLOW 560 nm filter is planned to prospectively analyze the extent of resection in patients with malignant brain tumors.     

Risk Factors for Bladder Tumors in Spinal Cord Injury Patients

Purpose

We evaluated risk factors for the development of bladder tumors in spinal cord injury patients.

Materials and Methods

A retrospective review was done of all bladder tumors at 1 institution with matched controls for 7 years.

Results

We identified 17 malignant and 2 benign tumors. Indwelling bladder catheters and a history of bladder stones were statistically significant risk factors. Four patients with negative biopsies underwent repeat biopsy due to suspicious cytology and cancer was found.

Conclusions

An indwelling urinary catheter and a history of bladder stones are statistically significant risk factors. Cytology and biopsy are complementary in the evaluation of urothelial malignancy in this population. A high index of suspicion and thorough evaluation are needed in spinal cord injury patients.     

Novel technique for identification of ureters using sodium fluorescein

Background

The unique property of sodium fluorescein has made it ideal for use in medical applications such as diagnostic ophthalmology and intravenous angiography. It is mainly excreted via the renal system and although extensively used in these diagnostic applications, it has not been widely used to aid in the visualization of the ureters. It is possible to visualize the urinary tract by shining a source of light and studying the fluorescence using a special filter. The goal of our study was to assess the real-time visualization of ureters using intravenous sodium fluorescein under the stimulus of a 530 nm wavelength light.

Materials and methods

Nine 250 gm Wister rats were given an intravenous dose of 0.01 ml of sodium fluorescein. A laparotomy was immediately performed following the administration of dye. Anesthesia was performed with an intraperitoneal dose of ketamine–xylazine. The retroperitoneum was exposed and observed under an alternating white xenon and a 530 nm excitation light with an objective to visualize the organs captured within the fluorescence of the compound (sodium fluorescein).

Results

Under xenon light, the location of the kidneys and urinary bladder were visualized, but not the ureters. The light was then changed to a 530 nm wavelength mode when the location and orientation of the ureters was visualized along with the peristaltic movements. Fluorescence visualization of the ureters was noted 5–10 min following kidney visualization. In addition, the vascular structures in close proximity to the ureters were also visualized. None of the rats underwent any retroperitoneal dissection, and in one case, partial mobilization of a kidney was undertaken. All rats were euthanized at the completion of the procedure.

Conclusion

Intravenous administration of sodium fluorescein enables fluorescence visualization of the ureters in a rat model, after activation with a 530 nm light transmitter.     

Accuracy of Residual Urine Measurement in Men: Comparison Between Real-Time Ultrasonography and Catheterization

Purpose

The practical value of ultrasonography as a rapid means to determine accurately residual urine volume was assessed.

Materials and Methods

Transverse and sagittal bladder diameters, as well as areas from longitudinal and transverse images, were measured with real-time ultrasonography in 324 men immediately after voiding. Calculated bladder volumes using measured diameters and areas for each of 11 formulas in the literature were compared to the corresponding measured total residual urine volumes.

Results

The lower limit of ultrasonographic visualization of urine in bladder was approximately 48 ml. No correlation existed between ultrasound calculated bladder volumes and measured residual urine for any of the 11 formulas.

Conclusions

Ultrasonography cannot rapidly measure bladder volumes accurately to date. Catheterization remains the most accurate method of assessing post-void residuals but in many cases it may not be the best approach to patient care.     

Enhanced Endoscopy in Bladder Cancer

Purpose of Review

Endoscopy coupled with targeted resections represents a cornerstone in the diagnosis, staging, and treatment of patients with bladder cancer. Direct visualization can be challenging and imprecise due to patient-, tumor-, and surgeon-specific factors. We will review contemporary endoscopic technologies and techniques used to improve our ability to safely identify and resect malignant lesions in patients with bladder cancer.

Recent Findings

Enhanced endoscopic imaging technology may improve detection rates for bladder cancer throughout the upper and lower urinary tract, which may lead to improvements in recurrence and progression rates for non-muscle invasive bladder cancer (NMIBC). New techniques including narrow-band imaging (NBI), photodynamic diagnosis (PDD), Storz Professional Image Enhancement System (SPIES), optical coherence tomography (OCT), and others have shown benefit and may further improve our ability to detect and stage bladder tumors.

Summary

Enhanced endoscopy technologies have already demonstrated value in improving the sensitivity of bladder cancer detection and early results suggest they may improve short- and long-term oncologic outcomes.

     

Fluorescence Cystoscopy with High-Resolution Optical Coherence Tomography Imaging as an Adjunct Reduces False-Positive Findings in the Diagnosis of Urothelial Carcinoma of the Bladder

Background

The advantage of photodynamic diagnosis in detecting urothelial cell carcinoma (UCC) of the bladder has been demonstrated clearly, but it comes at the price of a higher false-positive rate. Optical coherence tomography (OCT) is a noninvasive, real-time, microstructural imaging modality that uses near-infrared light for a point analysis of the bladder-wall microstructure.

Objective

To evaluate whether adding targeted OCT analysis of lesions that are suspicious at white-light (WL) and hexaminolevulinate (HAL) fluorescence cystoscopy improves diagnostic accuracy in the detection of UCC.

Design, setting, and participants

In this prospective single-center study with same-patient comparison, patients with suspected UCC first received an intravesical instillation of HAL. Cystoscopy was performed in WL, followed by blue-light inspection and OCT scanning.

Intervention

Suspicious lesions identified by WL or HAL were evaluated by OCT and were subsequently resected or biopsied.

Measurements

We measured changes in sensitivity and specificity in detecting UCC using WL, HAL, and targeted OCT.

Results and limitations

In 66 patients studied, 232 lesions were detected, were scanned by OCT, and were subsequently resected or biopsied. Additionally, 132 areas of normal-appearing urothelium were investigated by all three methods and biopsied. On a per-lesion basis, sensitivity and specificity were respectively 69.3% and 83.7% for WL, 97.5% and 78.6% for HAL, and 97.5% and 97.9% for HAL combined with OCT. Overall, UCC was diagnosed in 58 patients (87.9%), with a per-patient sensitivity of 89.7% for WL and 100% for both HAL alone and HAL with targeted OCT. Per-patient specificity for HAL alone and targeted HAL was 62.5% and 87.5%, respectively. The limitation of OCT results from poor visualization of flat lesions in WL, making scanning a time-consuming procedure.

Conclusions

Combining fluorescence cystoscopy with targeted OCT increases the specificity of fluorescence cystoscopy significantly, with no added morbidity, and reduces the need for unnecessary (false-positive) biopsies.     

TEMS: results of a specialist centre

Introduction

Transanal endoscopic microsurgery (TEMS) is becoming more widespread due to the increasing body of evidence to support its role. Previous published data has reported recurrence rates in excess of 10 % for benign polyps after TEMS.

Methods

Bradford Royal Infirmary is a tertiary referral centre for TEMS and early rectal cancer in the UK. Data for all TEMS operations were entered into a prospective database over a 7-year period. Demographic data, complications and recurrence rates were recorded. Both benign adenomas and malignant lesions were included.

Results

A total of 164 patients (65 % male), with a mean age of 68 years were included; 114 (70 %) of the lesions resected were benign adenomas, and 50 (30 %) were malignant lesions. Median polyp size was 4 (range 0.6–14.5) cm. Mean length of operation was 55 (range 10–120) min. There were no recurrences in any patients with a benign adenoma resected; two patients with malignant lesions developed recurrences. Three intra-operative complications were recorded, two rectal perforations (repaired primarily, one requiring defunctioning stoma), and a further patient suffered a blood loss of >300 ml requiring transfusion. Six patients developed strictures requiring dilation either endoscopically or under anaesthetic in the post-operative period.

Conclusions

We have demonstrated that TEMS procedures performed in a specialist centre provide low rates of both recurrence and complication. Within a specialist centre, TEMS surgery should be offered to all patients for rectal lesions, both benign and malignant, that are amenable to TEMS.     

PERCUTANEOUS ENDOSCOPIC CYSTOSTOMY FOR BLADDER LOCALIZATION AND EXACT PLACEMENT OF A SUPRAPUBIC TUBE

Purpose

We describe a new technique for exact positioning and placement of a suprapubic tube.

Materials and Methods

The bladder dome and its relative position on the lower abdomen are localized using a flexible cystoscope, light source and abdominal palpation.

Results

The technique has been successfully used in patients who require long-term urinary drainage.

Conclusions

Percutaneous endoscopic cystostomy is simple, effective and easily performed and it simplifies the placement of a suprapubic tube in the difficult to localize bladder.     

Urological Complications of Pancreatic Transplantation

Purpose

Pancreas transplantation is increasingly being used in the treatment of type I insulin-dependent diabetes mellitus. Because bladder drainage of the exocrine pancreatic secretion is the procedure of choice, urological complications are frequent. As the number of these procedures increases the urologist will have an extended role in the management of the postoperative complications, the majority of which are urological.

Materials and Methods

The literature from 1985 on the complications related to pancreas transplants was reviewed.

Results

Approximately 50 to 60% of bladder drained pancreas transplant recipients will have a urological complication postoperatively.

Conclusions

The increasing application of bladder drained pancreas transplantation in the treatment of type I insulin-dependent diabetes mellitus necessitates that the clinical urologist is familiar with the management of complications related to this procedure.     

THE MOLECULAR CHARACTERISTICS OF BLADDER CANCER IN YOUNG PATIENTS

Purpose

The molecular characteristics of bladder cancer in children and young adults remain largely undefined. We sought to identify common molecular changes in bladder tumors in young patients using standard immunohistochemical and interphase cytogenetic methods.

Materials and Methods

We retrospectively evaluated 73 bladder tumors removed from patients younger than 30 years for the p53 tumor suppressor gene product using immunohitochemical techniques and numerical aberrations of chromosomes 9, 17, X and Y.

Results

Regardless of stage, immunohistochemical evidence of p53 gene product over expression was found in the majority of tumors studied. Numerical abberations (mosomy) of chromosome 9 were rare. Aneuploidy of chromosome 17 was common, particularly in carcinoma in situ and invasive bladder cancer.

Conclusions

These data suggest that immunohistochemical evidence of p53 gene product over expression is common in bladder cancer in young patients. Further prospective analysis of lesions in this population may help to establish a comprehensive molecular progression model for urothelial neoplasms.