A Prospective Validation Study of the First 3D Digital Exoscope for Visualization of 5-ALA-Induced Fluorescence in High-Grade Gliomas.

BACKGROUND: We report on the first use of a digital 3-dimensional (3D) exoscope equipped with a 5-aminolevulinic acid (5-ALA) fluorescence visual system. METHODS: We conducted a prospective clinical trial to evaluate the utility and sensitivity/specificity of the Olympus Orbeye 3D digital exoscope when used to visualize 5-ALA-induced fluorescence in patients with high-grade glioma undergoing a clinically indicated craniotomy. At least 2 tissue samples were each obtained from regions of strong, weak. and no fluorescence and evaluated in a blinded manner by a neuropathologist. RESULTS: Twenty patients were enrolled. Intraoperative fluorescence was observed in 100% of subjects. One hundred twenty-one surgical specimens were collected for histopathological analysis; 40 with strong, 40 weak, and 41 with no visible fluorescence. Histopathology demonstrated 62.8% of samples (n = 76) contained abundant, 20.7% (n = 25) scarce, and 16.5% (n = 20) no tumor cells. Thirty-three of the 40 specimens (82.5%) in the strong fluorescence group correlated with abundant tumor cells and 7 (17.5%) with scarce. Twenty-nine of the 40 specimens (72.5%) in the weak fluorescence group correlated with abundant tumor cells, 7 (17.5%) with scarce, and 4 (10%) with none. Fourteen of the 41 (34.2%) specimens in the no fluorescence group had abundant tumor cells, 11 (26.8%) had scarce, and 16 (39%) had none. The sensitivity was 75% and specificity was 80%. The positive predictive value was 95% and negative predictive value was 39%. CONCLUSIONS: Visualization of 5-ALA-induced tumor fluorescence with use of the Orbeye 3D digital exoscope was feasible and associated with a high positive predictive value.

Optimization of the 2014 Gleason grade grouping in a Canadian cohort of patients with localized prostate cancer.

OBJECTIVES: To evaluate the five-tier Gleason grade group (GG) scoring of prostate cancers adopted by the International Society of Urology Pathology (ISUP) in 2014, and to propose modifications to optimize its performance. PATIENTS AND METHODS: Data were obtained from PROCURE, a prospective cohort of patients with localized prostate cancer undergoing radical prostatectomy in Québec, 2006-2013. Surgical specimens were evaluated by genitourinary pathologists using 2014 ISUP criteria. Treatment failure was defined as biochemical recurrence and/or initiation of secondary, non-adjuvant therapy. Analyses were conducted using Kaplan-Meier methods, log-rank tests, Cox proportional hazards models and Harrell's concordance indices. RESULTS: A total of 1 917 patients were included, with a median follow-up of 69 months. The 5-year treatment failure rates were 9.6%, 23.5%, 43.1%, 52.6% and 84.3% in GG1-5, respectively (P < 0.001 when comparing GG2 with GG3). Treatment failure rates for patients in GG2 and GG3 with tertiary Gleason 5 pattern were higher than patients in the same group without a tertiary pattern (P < 0.001), but were similar to rates for patients in GGs 3 or 4 without a tertiary pattern (P > 0.3). Primary Gleason pattern (4/5) predicted treatment failure in GG5 (5-year failure rates 82.3% vs 97.1%, respectively; P = 0.001). The five-tier GG system had greater accuracy as a prognostic indicator compared with the four-tier system (Harrell's concordance index 0.716 vs 0.676). When upgrading patients in GG2/3 with tertiary Gleason 5 pattern to patients in GG3/4, and separating patients in GG5 by primary Gleason pattern, the Harrell's concordance index increased to 0.730. CONCLUSION: The five-tier GG system increased accuracy for predicting treatment failure compared with the previous grading systems, but can be further improved.

Differentiation between low-grade and high-grade glioma using combined diffusion tensor imaging metrics.

OBJECTIVE: To ascertain whether diffusion tensor imaging (DTI) metrics including tensor shape measures such as planar and spherical isotropy coefficients (CP and CS) can be used to distinguish high-grade from low-grade gliomas. METHODS: Twenty-five patients with histologically proved brain gliomas (10 low-grade and 15 high-grade) were included in this study. Contrast-enhanced T1-weighted images, non-diffusion weighted b=0 (b0) images, fractional anisotropy (FA), apparent diffusion coefficient (ADC), CS and CP maps were co-registered and each lesion was divided into two regions of interest (ROI): enhancing and immediate peritumoral edema (edema adjacent to tumor). Univariate and multivariate logistic regression analyses were applied to determine the best classification model. RESULTS: There was a statistically significant difference in the multivariate logistic regression analysis. The best logistic regression model for classification combined three parameters (CS, FA and CP) from the immediate peritumoral part (p=0.02), resulting in 86% sensitivity, 80% specificity and area under the curve of 0.81. CONCLUSION: Our study revealed that combined DTI metrics can function in effect as a non-invasive measure to distinguish between low-grade and high-grade gliomas.

Initial experience with identifying high-grade prostate cancer using diffusion-weighted MR imaging (DWI) in patients with a Gleason score ≤ 3 + 3 = 6 upon schematic TRUS-guided biopsy: a radical prostatectomy correlated series.

INTRODUCTION: Diffusion-weighted magnetic resonance (MR) imaging (DWI) might be able to fulfill the need to accurately identify high-grade prostate carcinoma, in patients initially selected for active surveillance in the Prostate Specific Antigen (PSA) screening era based on transrectal ultrasound-guided biopsy Gleason score. We aimed to determine whether DWI is able to correctly identify those patients with a biopsy Gleason score of ≤ 3 + 3 = 6, but harboring Gleason 4 and/or 5 components in their radical prostatectomy (RP) specimen. MATERIALS AND METHODS: Whole-mount RP specimens were used to identify regions of interest corresponding with tumor on the DWI-derived apparent diffusion coefficient (ADC) maps in 23 patients with a Gleason ≤ 3 + 3 = 6 on biopsy. ADC values were correlated with RP Gleason grades. Statistical analysis was performed by calculating area under the receiver operating characteristic curve for identification of prostate cancer with Gleason 4 and/or 5 components using DWI, and Mann-Whitney U testing was performed to detect differences in median ADC values for tumors with presence of Gleason grade 4 and/or 5 versus a highest Gleason grade of ≤ 3 on RP. RESULTS: A diagnostic accuracy of median ADC values for identifying patients subject to transrectal ultrasound-guided biopsy undergrading with an area under the receiver operating characteristic curve of 0.88 was established using RP Gleason score as a reference. In patients harboring a Gleason 4 and/or 5 component, the median ADC was 0.86 × 10(-3) mm/s (standard deviation ± 0.21), whereas patients harboring no Gleason 4 and/or 5 component displayed a median ADC of 1.16 × 10(-3) mm/s (standard deviation ± 0.19) for the single tumor slice with the lowest median ADC (P < 0.002). CONCLUSIONS: DWI is able to predict the presence of high-grade tumor in patients with a Gleason ≤ 3 + 3 = 6 on biopsy, providing important information for treatment decisions.

In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study.

BACKGROUND: Dysplastic nevi are thought to be precursors of melanoma during a stepwise process. However, this concept is still controversial and precise correlation between clinical and histopathologic features is lacking. In vivo confocal microscopy represents a noninvasive imaging technique producing horizontal sections at nearly histopathologic resolution. OBJECTIVE: We sought to determine whether specific histologic features in dysplastic nevi have reliable correlates on confocal microscopy and to develop an in vivo microscopic grading system. METHODS: Sixty melanocytic lesions with equivocal dermatoscopic aspects, corresponding to 19 nondysplastic nevi, 27 dysplastic nevi, and 14 melanomas, were analyzed by confocal microscopy and histopathology, using the Duke grading criteria. RESULTS: All architectural and cytologic features of the Duke grading score had significant reflectance confocal microscopy correlates. Confocally, dysplastic nevi were characterized by a ringed pattern, in association with a meshwork pattern in a large proportion of cases, along with atypical junctional cells in the center of the lesion, and irregular junctional nests with short interconnections. A simplified algorithm was developed to distinguish dysplastic nevi from melanoma and nondysplastic nevi. The contemporary presence of cytologic atypia and of atypical junctional nests (irregular, with short interconnections, and/or with nonhomogeneous cellularity) was suggestive of histologic dysplasia, whereas a widespread pagetoid infiltration, widespread cytologic atypia at the junction, and nonedged papillae suggested melanoma diagnosis. LIMITATIONS: A small number of cases were evaluated because of the necessity to analyze numerous histopathologic and confocal features. CONCLUSION: The possibility to detect dysplastic nevi in vivo may lead to an appropriate management decision.

Computerized three-class classification of MRI-based prognostic markers for breast cancer.

The purpose of this study is to investigate whether computerized analysis using three-class Bayesian artificial neural network (BANN) feature selection and classification can characterize tumor grades (grade 1, grade 2 and grade 3) of breast lesions for prognostic classification on DCE-MRI. A database of 26 IDC grade 1 lesions, 86 IDC grade 2 lesions and 58 IDC grade 3 lesions was collected. The computer automatically segmented the lesions, and kinetic and morphological lesion features were automatically extracted. The discrimination tasks-grade 1 versus grade 3, grade 2 versus grade 3, and grade 1 versus grade 2 lesions-were investigated. Step-wise feature selection was conducted by three-class BANNs. Classification was performed with three-class BANNs using leave-one-lesion-out cross-validation to yield computer-estimated probabilities of being grade 3 lesion, grade 2 lesion and grade 1 lesion. Two-class ROC analysis was used to evaluate the performances. We achieved AUC values of 0.80 ± 0.05, 0.78 ± 0.05 and 0.62 ± 0.05 for grade 1 versus grade 3, grade 1 versus grade 2, and grade 2 versus grade 3, respectively. This study shows the potential for (1) applying three-class BANN feature selection and classification to CADx and (2) expanding the role of DCE-MRI CADx from diagnostic to prognostic classification in distinguishing tumor grades.

Role of endorectal magnetic resonance spectroscopic imaging in two different Gleason scores in prostate cancer.

OBJECTIVE: The major goal of the work was to record three-dimensional magnetic resonance spectroscopic imaging (MRSI) and to compare metabolite ratios between different Gleason scores (GS). MATERIALS AND METHODS: MRSI localized by endorectal coil-acquired point-resolved spectroscopy was performed in 14 men with prostate cancer of GS 6 (n = 7) and 7 (n = 7) using a 1.5-tesla MRI scanner. RESULTS: The ratio of (choline + creatine)/citrate was increased with an increase of GS, i.e. 0.590 ± 0.171 in the target lesion and 0.321 ± 0.157 in the contralateral region of patients with a GS of 6 as opposed to 1.082 ± 0.432 in the target lesion and 0.360 ± 0.243 in the contralateral region of patients with a GS of 7. CONCLUSION: Our pilot results demonstrated that MRSI was an additional biochemical tool which is complementary to the current imaging modalities for early diagnosis and therapeutic management of prostate cancer.