Priya N. Werahera

Three-Dimensional Reconstruction of Pulmonary Arteries in Plexiform Pulmonary Hypertension Using Cell-Specific Markers : Evidence for a Dynamic and Heterogeneous Process of Pulmonary Endothelial Cell Growth

The plexiform lesions of severe pulmonary hypertension (PH) are complex vascular structures composed primarily of endothelial cells. In this study, we use immunohistochemical markers to identify the various cell layers of pulmonary vessels and to identify different endothelial cell phenotypes in pulmonary arteries affected by severe PH. Our computerized three-dimensional reconstructions of nine vessels in five patients with severe PH demonstrate that plexiform (n = 14) and concentric-obliterative (n = 6) lesions occur distal to branch points of small pulmonary arteries. And, whereas plexiform lesions occur as solitary lesions, concentric-obliterative lesions appear to be only associated with, and proximal to, plexiform structures. The endothelial cells of plexiform lesions express intensely and uniformly the vascular endothelial growth factor (VEGF) receptor KDR and segregate phenotypically into cyclin-kinase inhibitor p27/kip1-negative cells in the central core of the plexiform lesion and p27/kip1-positive cells in peripheral areas adjacent to incipient blood vessel formation. Using immunohistochemistry and three-dimensional reconstruction techniques, we show that plexiform lesions are dynamic vascular structures characterized by at least two endothelial cell phenotypes. Plexiform arteriopathy is not merely an end stage or postthrombotic change--it may represent one stage in an ongoing, angiogenic endothelial cell growth process.

Clinical staging of prostate cancer : a computer-simulated study of transperineal prostate biopsy

To identify the precise location of prostate cancer within the gland and thus possibly permit more aggressive therapy of the lesion, while potentially sparing the noncancerous gland from ablative therapy.

Clinical-pathologic correlation between transperineal mapping biopsies of the prostate and three-dimensional reconstruction of prostatectomy specimens.

Extended transrectal ultrasound guided biopsies (TRUSB) of the prostate may not accurately convey true morphometric information and Gleason score (GS) of prostate cancer (PCa) and the clinical use of template‐guided (5‐mm grid) transperineal mapping biopsies (TPMBs) remains controversial.

COMPUTER MODELING OF PROSTATE BIOPSY: TUMOR SIZE AND LOCATION-NOT CLINICAL SIGNIFICANCE-DETERMINE CANCER DETECTION

PURPOSEnSampling error is an inherent problem of prostate biopsy, and the determination of clinical significance based on biopsy results is problematic. We quantify the dimensions of these problems by computer simulation.nnnMATERIALS AND METHODSnWe constructed 3-dimensional solid computer models of 59 autopsy prostates containing clinically undetected prostate cancer, and performed simulations of the standard prostate biopsy method.nnnRESULTSnBiopsy simulation detected 19 tumors from the 59 prostates, the majority of which were in the most accessible portion of the prostate, the posterior peripheral zone. Using 0.5 cc or greater tumor volume or less than 0.5 cc and Gleason sum 7 or greater as criteria of significance, the model detected 58% (11 of 19) significant tumors and 20% (8 of 40) insignificant tumors. With 0.25 cc or greater tumor volume or less than 0.25 cc and Gleason sum 7 or greater as criteria 15 of 29 significant (52%) and 4 of 30 insignificant (13%) tumors were detected. Among significant tumors defined by either volume criterion there was a statistical difference between detected and undetected tumors in terms of mean tumor volume and mean ratio of tumor volume-to-prostate volume. Among insignificant tumors defined by either criterion there was no such difference.nnnCONCLUSIONSnAs much as 20 to 40% of currently detected prostate cancer may be histologically insignificant, as 4 of 19 cancers were detected when 0.25 cc was used as volume determinant of clinical significance and 8 of 19 were detected when 0.5 cc volume was used. These tumors are detected randomly. On the other hand, perhaps only one-half to three-fourths of clinically significant prostate cancers are being detected, and then only because the volume and anatomic location make them hard to miss.

Morphological analysis and classification of latent prostate cancer using a 3-dimensional computer algorithm : Analysis of tumor volume, grade, tumor doubling time and life expectancy

PURPOSEnWe estimate the potential clinical significance of prostate cancers found at autopsy provided the individual had lived to the projected lifespan based on life expectancy tables.nnnMATERIALS AND METHODSnWe used 3-dimensional computer models of 59 autopsy prostates that contained clinically undetected carcinoma to determine tumor volumes. Using doubling times of 2, 3, 4 and 6 years, carcinoma volumes at autopsy were extrapolated through patient projected lifespans. The carcinomas were then classified as clinically insignificant or significant according to Mayo Clinic criteria.nnnRESULTSnIn 13 patients less than 60 years old, using doubling times of 2, 3, 4 and 6 years, clinically significant tumors were identified in 13 (100%), 10 (77%), 7 (54%) and 7 (54%), respectively. In 46 patients 60 years old or greater significant tumors were identified in 32 (70%), 22 (48%), 21 (46%) and 18 (39%), respectively. A statistical difference (p <0.0001) was found between the mean tumor volume (0.20 +/- 0.10 cc) of 43 organ confined carcinomas and the mean tumor volume (3.26 +/- 3.58 cc) of 16 extracapsular tumors. No capsule perforation was found in tumors with Gleason sums of 4 or less. However, capsule perforation was present in 8 of 31 tumors (25.8%) with Gleason sums of 5 or 6, and 8 of 11 tumors (72.7%) with Gleason scores of 7 or 8.nnnCONCLUSIONSnProstatic carcinomas that remain clinically insignificant throughout life are likely to have doubling times greater than 4 years. The subset of carcinomas that emerge as clinically significant are likely to have doubling times less than 3 years. Therefore, an accurate method to measure doubling time at diagnosis could, provide an objective indicator to guide clinical management.

Detection of abnormal E-cadherin expression by simulated prostate biopsy

PURPOSEnSampling error is an inherent problem of prostate biopsy. Consequently the determination of whether a given carcinoma is clinically significant based on biopsy results is problematic. We assess the dimensions of sampling error and, thereby, provide insight into the potential value of prognostic markers applied to needle biopsies.nnnMATERIALS AND METHODSnWe constructed 3-dimensional computer models of 21 prostatectomy specimens, including outlines of carcinomas, regions of abnormal E-cadherin expression and individual Gleason patterns. The 6 random systematic core biopsy technique and modifications were simulated using a computer algorithm.nnnRESULTSnIn 6 of 21 cases the area of abnormal E-cadherin expression and/or high grade carcinoma was not sampled on 6 random systematic core biopsy. The areas missed were either small or inconsistently under sampled regions of the prostate. Modifying the placement of biopsy needles improved the detection of these features. In addition, percent tumor in the needle appeared to be well correlated to percent tumor in the prostate (r = 0.891, r2 = 0.642).nnnCONCLUSIONSnTo avoid underestimating the aggressiveness of prostatic carcinoma at least 6 biopsies should be taken from each patient. A more extensive sampling is probably not warranted in all patients but it may prove useful in those in whom extent of disease is unclear or whose general health makes treatment decisions difficult. A reliable estimate of tumor volume in the prostatectomy specimen can be made based on relative amount of tumor in the biopsy specimen on an individual basis.

Laparoscopic Versus Percutaneous Cryoablation of Small Renal Mass: Systematic Review and Cumulative Analysis of Comparative Studies

&NA; The objective of this study was to compare the surgical, oncological, and functional outcomes of laparoscopic and percutaneous cryoablation for the treatment of small renal masses. A systematic review of the literature was performed through March 2016 using PubMed, Scopus, and Ovid databases. Article selection proceeded according to the search strategy on the basis of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses criteria. Only studies that compared laparoscopic and percutaneous kidney cryoablation were included in the meta‐analysis. Eleven retrospective comparative studies were identified and selected for the analysis, including 1725 cases: 804 (46.6%) percutaneous and 921 (53.4%) laparoscopic cryoablations. Percutaneous cryoablation was performed more frequently for posterior tumors (P < .001), whereas laparoscopy was more common for endophytic lesions (P = .01). The length of follow‐up was longer for laparoscopy (P < .001). Percutaneous cryoablation was associated with a significantly shorter hospital stay (P < .001). A lower likelihood of residual disease was recorded for laparoscopic (P = .003), whereas tumor recurrence rate favored percutaneous cryoablation (P = .02). The 2 procedures were similar for recurrence‐free survival (P = .08), and overall survival (P = .51). No significant difference was found in postoperative estimated glomerular filtration rate (P = .78). Laparoscopic and percutaneous kidney cryoablation offer similar favorable oncological outcomes with minimal effect on renal function. The percutaneous access can offer shorter hospital stay and faster recovery, which can be appealing in an era of cost restraint.

Diagnosis of prostatic Carcinoma on multiparametric magnetic resonance imaging using shearlet transform

This paper presents a method to diagnose prostate cancer on multiparametric magnetic resonance imaging (Mp-MRI) using the shearlet transform. The objective is classification of benign and malignant regions on transverse relaxation time weighted (T2W), dynamic contrast enhanced (DCE), and apparent diffusion coefficient (ADC) images. Compared with conventional wavelet filters, shearlet has inherent directional sensitivity, which makes it suitable for characterizing small contours of cancer cells. By applying a multi-scale decomposition, the shearlet transform captures visual information provided by edges detected at different orientations and multiple scales in each region of interest (ROI) of the images. ROIs are represented by histograms of shearlet coefficients (HSC) and then used as features in Support Vector Machines (SVM) to classify ROIs as benign or malignant. Experimental results show that our method can recognize carcinoma in T2W, DCE, and ADC with overall sensitivity of 92%, 100%, and 89%, respectively. Hence, application of shearlet transform may further increase utility of Mp-MRI for prostate cancer diagnosis.

Systematic diagnosis of prostate cancer using an optical biopsy needle adjunct with fluorescence spectroscopy

Transrectal ultrasound guided prostate biopsies often fail to diagnose prostate cancer with 90% of cores reported as benign. Thus, it is desirable to target prostate cancer lesions while reducing the sampling of benign tissue. The concentrations of natural fluorophores in prostate tissue fluctuate with disease states. Hence, fluorescence spectroscopy could be used to quantify these fluctuations to identify prostate cancer. An optical biopsy needle with a light sensitive optical probe at the tip of the inner needle was developed to take prostate biopsies after measuring tissue fluorescence with a laboratory fluorometer. The optical probe consists of eight 100 μm fibers for tissue excitation and a single 200 μm fiber to capture fluorescence spectra. Random biopsy cores were taken from 20 surgically excised prostates after measuring fluorescence spectra of tissue between 295-550nm for several excitations between 280-350nm. Each biopsy core was histopathologically classified and correlated with corresponding spectra. Prostate biopsies were grouped into benign or malignant based on the histological findings. Out of 187 biopsy cores, 109 were benign and 78 were malignant. Partial least square analysis of tissue spectra was performed to identify diagnostically significant principal components as potential classifiers. A linear support vector machine and leave-one-out cross validation method was employed for tissue classification. Study results show 86% sensitivity, 87% specificity, 90% negative predictive value, and 83% positive predictive value for benign versus malignant prostate tissue classification. This study demonstrates potential clinical applications of fluorescence spectroscopy guided optical biopsy needle for prostate cancer diagnosis with the consequent improvement of patient care.

The effect of digital rectal exam on the 4Kscore for aggressive prostate cancer

The 4Kscore is a new commercially available blood‐based diagnostic test which predicts risk for aggressive, clinically significant prostate cancer on prostate biopsy. The 4Kscore is currently restricted to patients who have not had a digital rectal exam (DRE) in the previous 96u2009h, owing to prior mixed data suggesting that prostate specific antigen (PSA) isoforms may increase by a statistically significant—if not necessarily clinically significant—amount shortly after DRE. Our primary objective was to determine if 4Kscore test results are affected by a preceding DRE.