Mieke T. J. Bus

Volumetric In-Vivo Visualization of Upper Urinary Tract Tumors Using Optical Coherence Tomography: A Pilot Study

PURPOSE Knowledge of tumor stage and grade is paramount for treatment decision making in cases of upper urinary tract urothelial carcinoma but this condition cannot be accurately assessed by current techniques. Optical coherence tomography can hypothetically provide the urologist with real-time intraoperative information on tumor grade and stage. In this pilot study we report what are to our knowledge the first results of optical coherence tomography for grading and staging upper urinary tract urothelial carcinoma. MATERIALS AND METHODS Eight consecutive patients underwent ureterorenoscopy for suspicion or followup of upper urinary tract urothelial carcinoma. Optical coherence tomography data sets were intraoperatively obtained from the ureter and renal pelvis. All patients eventually underwent nephroureterectomy. Optical coherence tomography staging was done by visual inspection of lesions found on optical coherence tomography images. Optical coherence tomography grading was done by quantifying optical coherence tomography signal attenuation in mm(-1) on lesions and comparing results with the histopathological diagnosis. The Wilcoxon rank sum test was used for statistical analysis. RESULTS For 7 in vivo optical coherence tomography diagnoses staging was in accordance with histology. In patient 8 tumor thickness transcended optical coherence tomography imaging depth range and, therefore, invasiveness findings were inconclusive. For grading the median attenuation coefficient for grade 2 and 3 lesions was 1.97 (IQR 1.57-2.30) and 3.53 mm(-1) (IQR 2.74-3.94), respectively (p<0.001). Healthy urothelium was too thin to reliably determine the attenuation coefficient. CONCLUSIONS Optical coherence tomography is a promising, minimally invasive tool for real-time intraoperative optical diagnosis of tumors in the upper urinary tract. Our results warrant future research in a larger sample size to determine the accuracy of grading and staging by optical coherence tomography, and its possible implementation in the diagnostic algorithm for upper urinary tract urothelial carcinoma.

Prostate cancer diagnosis: the feasibility of needle-based optical coherence tomography

Abstract. The objective of this study is to demonstrate the feasibility of needle-based optical coherence tomography (OCT) and functional analysis of OCT data along the full pullback trajectory of the OCT measurement in the prostate, correlated with pathology. OCT images were recorded using a commercially available C7-XR™ OCT Intravascular Imaging System interfaced to a C7 Dragonfly™ intravascular 0.9-mm-diameter imaging probe. A computer program was constructed for automated image attenuation analysis. First, calibration of the OCT system for both the point spread function and the system roll-off was achieved by measurement of the OCT signal attenuation from an extremely weakly scattering medium (Intralipid® 0.0005 volume%). Second, the data were arranged in 31 radial wedges (pie slices) per circular segments consisting of 16 A-scans per wedge and 5 axial B-scans, resulting in an average A-scan per wedge. Third, the decay of the OCT signal is analyzed over 50 pixels (500  μm) in depth, starting from the first found maximum data point. Fourth, for visualization, the data were grouped with a corresponding color representing a specific μoct range according to their attenuation coefficient. Finally, the analyses were compared to histopathology. To ensure that each single use sterile imaging probe is comparable to the measurements of the other imaging probes, the probe-to-probe variations were analyzed by measuring attenuation coefficients of 0.03, 6.5, 11.4, 17, and 22.7 volume% Intralipid®. Experiments were repeated five times per probe for four probes. Inter- and intraprobe variation in the measured attenuation of Intralipid samples with scattering properties similar to that of the prostate was <8% of the mean values. Mean attenuation coefficients in the prostate were 3.8  mm−1 for parts of the tissue that were classified as benign (SD: 0.8  mm−1, minimum: 2.2  mm−1, maximum: 8.9  mm−1) and 4.1  mm−1 for parts of tissue that were classified as malignant (SD: 1.2  mm−1, minimum: 2.5  mm−1, maximum: 9.0  mm−1). In benign areas, the tissue looked homogeneous, whereas in malignant areas, small glandular structures were seen. However, not all areas in which a high attenuation coefficient became apparent corresponded to areas of prostate cancer. This paper describes the first in-tissue needle-based OCT imaging and three-dimensional optical attenuation analysis of prostate tissue that indicates a correlation with pathology. Fully automated attenuation coefficient analysis was performed at 1300 nm over the full pullback. Correlation with pathology was achieved by coregistration of three-dimensional (3-D) OCT attenuation maps with 3-D pathology of the prostate. This may contribute to the current challenge of prostate imaging and the rising interest in focal therapy for reduction of side effects occurring with current therapies.

Follow-up procedures for non-muscle-invasive bladder cancer: an update

Bladder carcinoma is the most common malignancy of the urinary tract. Approximately 75–85% of patients present with a disease that is confined to the mucosa (stage Ta, carcinoma in situ) or submucosa (stage T1). The stratification of patients to low-, intermediate- and high-risk groups represents the cornerstone for the indication of adjuvant and follow-up treatment. Owing to the high recurrence rate of bladder tumors, a surveillance protocol is recommended to all patients. Currently, the combination of cystoscopy, imaging and urinary cytology represent the follow-up. A systematic review of the recent English literature on follow-up procedures of non-muscle-invasive bladder cancer is performed. The authors review the existing follow-up procedures, with a focus on novel molecular-targeted approaches. At the present time, the additional use and utility of urine-based molecular markers in the follow-up of patients remains unclear and we have to rely on cystoscopic evaluation adapted to risk group classification.

Is photodynamic diagnosis ready for introduction in urological clinical practice

The aim of this review is to provide an up-to-date review of the available literature on photodynamic diagnosis (PDD) for nonmuscle-invasive bladder cancer, to present the technique in a comprehensive approach and, finally, to discuss the relevance of PDD in clinical practice in terms of indications, outcomes and its development trend. A literature search was conducted up to July 2012, using MEDLINE and EMBASE via Ovid databases to identify published studies on PDD for nonmuscle-invasive bladder cancer. Only English-language and human-based full manuscripts that reported on case series and studies with >40 participants, concerning clinical evidence of the technique, its efficacy and safety data were included. Evidence showed that PDD significantly improves detection of bladder cancer compared with standard white-light cystoscopy, having proven to be more effective for the diagnosis of carcinoma in situ. This condition seems to facilitate more complete resections, resulting in a lower residual tumor rate, which, in turn consecutively leads to higher recurrence-free survival rates. The literature search demonstrated that for mid- and long-term follow-up, PDD showed acceptable outcomes in terms of tumor detection, as well as lower residual tumor and lower recurrence rates compared with white-light cystoscopy. It has proven to be safe and well tolerated; the major limitations of PDD are its low specificity and elevated costs.

Urothelial carcinoma in both adnexa following perforation during transurethral resection of a non-muscle-invasive bladder tumor: a case report and literature review

In this article case report of urothelial carcinoma implantation in both adnexa is reported, following a perforation of the bladder wall during a transurethral resection of a bladder tumor. The 81-year-old female patient had an extensive history of multiple recurrent non-muscle-invasive urothelial carcinoma of the bladder. Intraperitoneal perforation was detected and managed conservatively. Fifteen months after the procedure, the patient presented at the gynecology department with a mass in the left adnex, which was suspicious for malignancy, for which she subsequently underwent hysterectomy in combination with bilateral resection of the adnexa. Pathology showed papillary urothelial carcinoma in both ovaries. A literature search was performed to present an up-to-date review of the available data on bladder perforations during transurethral resection of the bladder and tumor implantation, its management and oncological outcomes.

Optical Coherence Tomography in Bladder Cancer

The current diagnostic standard for grading and staging of non-muscle-invasive bladder cancer (NMIBC) is based on the histopathology obtained during transurethral resection of the bladder tumour (TURBT) or biopsies. Although considered reference standard, this technique has some limitations: First, no real-time intraoperative histological information is obtained on stage and grade. Real-time intraoperative histological information could be helpful when NMIBC is treated by electric coagulation or laser ablation. The urologist has to rely on his/her judgement of stage and grade since no tissue is harvested for histological confirmation. In addition, in many centres, patients with a history of low-grade, non-invasive NMIBC with small recurrent NMIBC are being followed up with regular cystoscopy, instead of having directly TURBT. Real-time histological confirmation during cystoscopy could be very helpful in these patients. Finally, carcinoma in situ (CIS) may appear as a red mucosal lesion, mimicking inflammation. Again, real-time histological information could help in discriminating between CIS and inflammation. CIS can easily be missed on cystoscopy due to its flat appearance. If urine cytology is suspicious for high-grade bladder cancer, random biopsies are taken from the bladder to confirm or exclude CIS. This method results in a high rate of unnecessary biopsies. Real-time histopathology can possibly guide the direction of biopsies and thus avoid taking unnecessary biopsies. These examples illustrate the need for a fast, effective minimally invasive tool for assessment of cancerous lesions in the bladder. Optical coherence tomography (OCT) is a technology that has the potential to provide real-time information on grade and stage of a bladder cancer lesion.

Beyond Endoscopy-Ultrasound, Optical Coherence Tomography and Confocal Laser Endomicroscopy

One of the main challenges in endoscopic diagnosis and treatment of upper urinary tract urothelial carcinoma is the complicated anatomy and the small size of the upper urinary tract, resulting in high demands on the armamentarium and expertise of the urologist. Difficulties to reach the complete collecting system could result in an incomplete visual inspection.

7 In vivo optisch coherente tomografie voor evaluatie van hogere urinewegurotheeltumoren – eerste resultaten van een pilotstudie

Tijdschrift voor Urologie mei 2013 nr. 3 Resultaten Zowel na behandeling met op TPCS2a gebaseerde fotodynamische therapie (PDT) alleen, als na behandeling met bleomycine of een van de controlechemotherapeutica alleen werd in alle 5 cellijnen een dosisafhankelijke inhibitie van celproliferatie gezien. Bij de combinatiebehandelingen werd enkel een significant (p < 0,001) synergistisch effect, dus een fotochemisch internalisatie-effect, geobserveerd voor PDT gecombineerd met bleomycine in de T24en de AY-27-cellijn.