Ronald O.P. Draga

In vivo bladder cancer diagnosis by high-volume Raman spectroscopy.

We studied the feasibility of Raman spectroscopy for the diagnosis of bladder cancer in vivo. Since the invasion stage is crucial for the treatment choice, a high-volume based Raman probe was used to investigate the potential of determining the invasiveness of bladder cancer. High quality spectra were obtained from suspicious and nonsuspicious bladder locations during the procedure of transurethral resection of bladder tumors (TURBT) with collection times of 1-5 s. Multivariate analysis was used to generate the classification models. The algorithm was able to distinguish bladder cancer from normal bladder locations with a sensitivity of 85% and a specificity of 79%. The Raman spectra of bladder cancer stages showed a gradual increase in the intensity of specific amino acid peaks and, most likely, an increase in the intensity of DNA peaks.

Percutaneous Nephrolithotomy: Factors Associated with Fever After the First Postoperative Day and Systemic Inflammatory Response Syndrome

OBJECTIVE Fever after the first postoperative day (POD1) after percutaneous nephrolithotomy (PCNL) is most likely caused by an infection that increases hospital stay and healthcare costs. The aim of this study was to find factors associated with fever after POD1 and systemic inflammatory response syndrome (SIRS). PATIENTS AND METHODS Ninety patients underwent 117 PCNLs. Patient characteristics, stone burden, and pre- and postoperative treatments were analyzed for association with fever (temperature >or=38 degrees C) and SIRS using univariate analysis. RESULTS In 35% of the patients with fever (temperature >or=38 degrees C), fever was present after POD1. Twelve patients developed signs of SIRS (11.2%). In univariate analysis, significant association was observed between fever after POD1 and previous ipsilateral PCNL (p = 0.022, odds ratio OR = 3.1), and between SIRS and paraplegia (p = 0.005, OR = 10.7) and caliceal stones (p = 0.03, OR = 4.8). CONCLUSIONS Previous ipsilateral PCNL increases the risk of fever after POD1. Paraplegic patients are at risk for developing SIRS after PCNL.

Photodynamic Diagnosis (5-Aminolevulinic Acid) of Transitional Cell Carcinoma After Bacillus Calmette-Guérin Immunotherapy and Mitomycin C Intravesical Therapy

BACKGROUND Photodynamic diagnosis (PDD) is a technique that enhances the detection of occult bladder tumors during cystoscopy using a fluorescent dye. OBJECTIVE To study the differential effects of bacillus Calmette-Guérin (BCG) and mitomycin C (MMC) intravesical therapy on the false-positive rate of PDD of bladder cancer. DESIGN, SETTING, AND PARTICIPANTS This study included 552 procedures and 1874 biopsies. INTERVENTION Tumors were resected and biopsies were taken from suspicious areas, under guidance of white-light endoscopy and 5-ALA (5-aminolevulinic acid)-induced fluorescence cystoscopy. MEASUREMENTS The influence of intravesical BCG immunotherapy and intravesical MMC chemotherapy on pyuria, inflammation, and PDD specificity was examined in univariate analyses. RESULTS AND LIMITATIONS BCG significantly results in inflammation (odds ratio [OR]: 1.53, p=0.002), leukocyturia (OR: 1.84, p=0.034), and false positives in PDD (OR: 1.49, p=0.001). However, a single BCG instillation within 3 mo before PDD is most likely not associated with increased false-positive rates (OR: 0.35, p=0.26). Leukocyturia normalizes within 6 wk after the last BCG instillation, but PDD specificity is reduced up to 3 mo. CONCLUSIONS BCG is an important predictor for false positives in PDD (5-ALA). More than one BCG instillation within 3 mo before fluorescence cystoscopy decreases the specificity of PDD.

Predictors of false positives in 5-aminolevulinic acid-induced photodynamic diagnosis of bladder carcinoma: identification of patient groups that may benefit most from highly specific optical diagnostics.

OBJECTIVES To identify patient groups associated with a high probability of false positives in photodynamic diagnosis (PDD) of bladder cancer for which the use of highly specific optical instruments could be beneficial. METHODS This study includes the data of 306 patients. Under white light and 5-aminolevulinic acid-induced fluorescence light guidance, tumor locations were recorded, cold-cup biopsies were taken and tumors resected. Age, gender, recent transurethral resection of bladder tumor (TURBT), previous intravesical therapy, and urinary tract infections were examined for association with the false-positive rates in fluorescence cystoscopy by performing a multivariate analysis. RESULTS Significant univariate associations were found between false positives and gender (P = .009, odds ratio [OR] = 0.51), previous intravesical therapy (P = .03, OR = 1.78), previous BCG instillations (P = .03, OR = 2.05), and TURBT in the past 90 days (P = .01, OR = 2.37). In the multivariate regression model, female gender (male; P = .005, OR = 0.41) and TURBT within 90 days before PDD (P = .01, OR = 2.38) are significant independent predictors of false-positive findings in PDD. CONCLUSIONS Recent TURBTs and female gender are significant independent predictors of false positives in fluorescence cystoscopy.

Bladder cancer diagnosis during cystoscopy using Raman spectroscopy

Raman spectroscopy is an optical technique that can be used to obtain specific molecular information of biological tissues. It has been used successfully to differentiate normal and pre-malignant tissue in many organs. The goal of this study is to determine the possibility to distinguish normal tissue from bladder cancer using this system. The endoscopic Raman system consists of a 6 Fr endoscopic probe connected to a 785nm diode laser and a spectral recording system. A total of 107 tissue samples were obtained from 54 patients with known bladder cancer during transurethral tumor resection. Immediately after surgical removal the samples were placed under the Raman probe and spectra were collected and stored for further analysis. The collected spectra were analyzed using multivariate statistical methods. In total 2949 Raman spectra were recorded ex vivo from cold cup biopsy samples with 2 seconds integration time. A multivariate algorithm allowed differentiation of normal and malignant tissue with a sensitivity and specificity of 78,5% and 78,9% respectively. The results show the possibility of discerning normal from malignant bladder tissue by means of Raman spectroscopy using a small fiber based system. Despite the low number of samples the results indicate that it might be possible to use this technique to grade identified bladder wall lesions during endoscopy.

Clinical superficial Raman probe aimed for epithelial tumor detection: Phantom model results

A novel clinical Raman probe for sampling superficial tissue to improve in vivo detection of epithelial malignancies is compared to a non-superficial probe regarding depth response function and signal-to-noise ratio. Depth response measurements were performed in a phantom tissue model consisting of a polyethylene terephthalate disc in an 20%-Intralipid(®) solution. Sampling ranges of 0-200 and 0-300 μm were obtained for the superficial and non-superficial probe, respectively. The mean signal-to-noise ratio of the superficial probe increased by a factor of 2 compared with the non-superficial probe. This newly developed superficial Raman probe is expected to improve epithelial cancer detection in vivo.

The quality of 5-aminolevulinic acid-induced photodynamic diagnosis and transurethral resection of bladder tumors: does the urologist play a role?.

Introduction: The aim of this study is to evaluate the quality of photodynamic diagnosis (PDD) and transurethral resection of bladder tumors (TURBT) among different urologists. Patients and Methods: The selected data consists of 194 patients, 268 5-aminolevulinic acid (5-ALA)-induced PDD procedures and 934 biopsies. Tumors were resected and biopsies were taken from suspicious areas under guidance of white light endoscopy and 5-ALA-induced fluorescence cystoscopy. The quality of PDD was determined by evaluating the mean number of tumors resected by 5 urologists and, thereafter, assessing the time to recurrence between groups. Results: Urologist 1 took 37% more biopsies (p < 0.001) and diagnosed 42% more tumors (p = 0.005) and 46% more false positives (p < 0.001) from bladders compared to urologists 2, 3, 4 and 5 together. The mean time to bladder cancer recurrence for all recurrences within 0–18 months was 11.0 months for operator 1 and 8.3 months for the other urologists (p = 0.01). Conclusions: The resecting urologist appears to be an important factor for the quality of standard and PDD-assisted TURBT. Learning curve programs may be required with experienced surgeons accompanying those with less experience.

The feasibility of real-time bladder mapping using a stereotactic navigational system

Stereotactic navigational devices have been implemented in neurosurgery, orthopedics and ear-nose-throat to improve surgical accuracy. However, the feasibility of navigating inside the bladder has not yet been investigated. Occasionally, transurethral resections of bladder tumors (TURBTs) are impeded by bleeding and cloudiness inside the bladder and, consequently, the bladder lesions are not found back easily. In addition, small bladder lesions are often concealed when viewed with the camera some distance away from the bladder wall due to low contrast differences. The aim of the study is to investigate the feasibility of real-time bladder mapping using the Medtronic Stealthstation system, without the use of pre-operative images. Seven patients scheduled for a TURBT were included in the study. During the TURBT procedure, the spatial coordinates of the bladder lesions were recorded two times independently, after filling the bladder with a fixed volume of 390 ml. The distance between the spatial coordinates of two consecutive measurements, in millimeters, was calculated. We found that bladder lesions can be found back using the navigational system with an accuracy of less than 12 mm. Real-time bladder navigation is feasible without the necessity of pre-operative images or calibration. If the coordinates are directly superimposed on the video image this could facilitate the retrieval of bladder lesions during TURBT. This system could reduce the stress for the surgeon and decrease the operating time.

Study of false positives in 5-ALA induced photodynamic diagnosis of bladder carcinoma

Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violetblue light. A disadvantage of PDD is the relatively low specificity. In this retrospective study we aimed to identify predictors for false positive findings in PDD. Factors such as gender, age, recent transurethral resection of bladder tumors (TURBT), previous intravesical therapy (IVT) and urinary tract infections (UTIs) were examined for association with the false positive rates in a multivariate analysis. Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Female gender and TURBT are independent predictors of false positives in PDD. However, previous intravesical therapy with Bacille Calmette-Guérin is also an important predictor of false positives. The false positive rate decreases during the first 9-12 weeks after the latest TURBT and the latest intravesical chemotherapy. Although shortly after IVT and TURBT false positives increase, PDD improves the diagnostic sensitivity and results in more adequate treatment strategies in a significant number of patients.

Noninvasive Transitional Cell Carcinoma is Associated with a High Occurrence of False Positives in Photodynamic Diagnosis

CIS = carcinoma in situ; N/A = not applicable. a There were 71 primary transurethral resections of bladder tumor, 9 cases with n case with previous T2 (7 cases had missing data). b There were 34 cases with no tumors and no fluorescence-positive lesions in th c Analyzed in R using the lmer statistical package (does allow for repeated meas d Analyzed in R using the lme statistical package (does not allow for repeated m * The pTa group is the reference group. ** p < 0.05. SFS is currently at Memorial Sloan-Kettering Cancer Center, New York, NY, USA.