Novel method of image analysis that combines Radon and Fourier image transformations for the purpose of differentiating between malignant and benign colonic biopsies.

Colorectal cancer is the third most common type of cancer. It develops slowly as a polyp that can turn into a cancerous tumor. This study aimed to develop a decision-making algorithm of microscopic images using texture analysis that is orientation free, to be used for automated classification of normal and neoplastic (malignant or premalignant) colonic biopsies. Forty-nine colonic adenocarcinomas, 41 adenomas and a control group of adjacent normal colonic mucosa were included in the texture analysis. Radon transform followed by the Fast Fourier transform were applied to the images. Subsequently, the gray level co-occurrence matrix (GLCM) transform was applied allowing the extraction of four textural variables (homogeneity, contrast, correlation, and entropy). For classification and prediction of the diagnosis, a statistical multivariate regression model and a neural network (NNET) model were used and compared. The statistical model provided a sensitivity of 71.3% and a specificity of 50% (Area under the ROC curve: 0.67) for classifying the neoplastic and the normal images, respectively. The NNET model was superior to the statistical model and produced a sensitivity of 97.9% and specificity of 88% (Area under the ROC curve: 0.92). To our knowledge, this is the first study that used a combination of Radon, FFT, and GLCM transformations in order to overcome the tissue orientation problem in texture analysis of microscopic images of colonic biopsies. The NNET classifier trained by the extracted textural features proved to be superior to the statistical classifier, thus predicting colonic neoplasia with high accuracy. RESEARCH HIGHLIGHTS: We propose a novel decision-making algorithm of orientation invariant image texture analysis, fast and easily implemented for automated differentiation between benign and neoplastic epithelial tumors of the colon. This method can reduce the turnaround time allowing to prioritize the biopsies during their examination and diagnosis by the pathologist.

Complete digital pathology transition: A large multi-center experience.

INTRODUCTION: Transitioning from glass slide pathology to digital pathology for primary diagnostics requires an appropriate laboratory information system, an image management system, and slide scanners; it also reinforces the need for sophisticated pathology informatics including synoptic reporting. Previous reports have discussed the transition itself and relevant considerations for it, but not the selection criteria and considerations for the infrastructure. OBJECTIVE: To describe the process used to evaluate slide scanners, image management systems, and synoptic reporting systems for a large multisite institution. METHODS: Six network hospitals evaluated six slide scanners, three image management systems, and three synoptic reporting systems. Scanners were evaluated based on the quality of image, speed, ease of operation, and special capabilities (including z-stacking, fluorescence and others). Image management and synoptic reporting systems were evaluated for their ease of use and capacity. RESULTS: Among the scanners evaluated, the Leica GT450 produced the highest quality images, while the 3DHistech Pannoramic provided fluorescence and superior z-stacking. The newest generation of scanners, released relatively recently, performed better than slightly older scanners from major manufacturers Although the Olympus VS200 was not fully vetted due to not meeting all inclusion criteria, it is discussed herein due to its exceptional versatility. For Image Management Software, the authors believe that Sectra is, at the time of writing the best developed option, but this could change in the very near future as other systems improve their capabilities. All synoptic reporting systems performed impressively. CONCLUSIONS: Specifics regarding quality and abilities of different components will change rapidly with time, but large pathology practices considering such a transition should be aware of the issues discussed and evaluate the most current generation to arrive at appropriate conclusions.

Real-Life Utilization of Criteria Guidelines for Diagnosis of Cardiac Sarcoidosis (CS).

Despite the increasing recognition of cardiac involvement in systemic sarcoidosis, the diagnosis of cardiac sarcoidosis (CS) remains challenging. Our aim is to present a comprehensive, retrospective case series of CS patients, focusing on the current diagnostic guidelines and management of this life-threatening condition. In our case series, patient data were collected retrospectively, including hospital admission records and rheumatology and cardiology clinic visit notes, detailing demographic, clinical, laboratory, pathology, and imaging studies, as well as cardiac devices and prescribed medications. Cases were divided into definite and probable CS based on the 2014 Heart Rhythm Society guidelines as well as presumed CS based on imaging criteria and clinical findings. Overall, 19 CS patients were included, 17 of whom were diagnosed with probable or presumed CS based on cardiac magnetic resonance imaging (CMR) and/or cardiac positron emission tomography using 18F-Fluorodeoxyglucose (PET-FDG) without supporting endomyocardial biopsy (EMB). The majority of CS patients were male (53%), with a mean age of 52.9 ± 11.8, with CS being the initial manifestation of sarcoidosis in 63% of cases. Most patients presented with high-grade AVB (63%), followed by heart failure (42%) and ventricular tachyarrhythmia (VT) (26%). This case series highlights the significance of utilizing updated diagnostic criteria relying on CMR and PET-FDG given that cardiac involvement can be the initial manifestation of systemic sarcoidosis, requiring prompt diagnosis and treatment to prevent morbidity and mortality.

Fourier transformation based texture analysis for differentiating between hyperplastic polyps and sessile serrated adenomas.

Colorectal cancer (CRC) is the third most common type of cancer. One major pathway involved in the development of CRC is the serrated pathway. Colorectal polyps can be divided in benign, like small hyperplastic polyps and premalignant polyps, like the sessile serrated adenomas (SSA) that has a significant potential of malignant transformation. The morphological similarity between these types of polyp, not-infrequently raises diagnostic difficulties. This study aimed to morphologically differentiate between hyperplastic polyps (HP) and SSAs by using automated computerized texture analysis of Fourier transformed histological images. Thirty images of HP and 58 images of SSA were analyzed by computerized texture analysis. A fast Fourier transformation was applied to the images. The Fourier frequency plots were further transformed into gray level co-occurrence matrices and four textural variables were extracted: entropy, correlation, contrast, and homogeneity. Our study is the first to combine this type of analysis for automated classification of colonic neoplasia. The results were analyzed using statistical and neural network (NNET) classification models. The predictive values of these classifiers were compared. The statistical regression algorithm presented a sensitivity of 95% to detect the SSA and a specificity of 80% to detect the HP. The NNET analysis was superior to the statistical analysis displaying a classification accuracy of 100%. The results of this study have confirmed the hypothesis that Fourier based texture image analysis is helpful in differentiating between HP and SSA. RESEARCH HIGHLIGHTS: Colorectal polyps can be divided in benign, like hyperplastic polyps (HP) and premalignant, like the sessile serrated adenomas (SSA). There is a high morphologic similarity between these two types of polyp that not-infrequently raises diagnostic difficulties. The results of our morphometric analysis that were used to build a neural network based model of prediction of the polyp types, have a great clinical importance of identifying SSA polyps which have significant potential of malignant progression as compared to HP.

Short Training Significantly Improves Ganglion Cell Detection Using an Algorithm-Assisted Approach.

CONTEXT.­: Medical education in pathology relies on the accumulation of experience gained through inspection of numerous samples from each entity. Acquiring sufficient teaching material for rare diseases, such as Hirschsprung disease (HSCR), may be difficult, especially in smaller institutes. The current study makes use of a previously developed decision support system using a decision support algorithm meant to aid pathologists in the diagnosis of HSCR. OBJECTIVE.­: To assess the effect of a short training session on algorithm-assisted HSCR diagnosis. DESIGN.­: Five pathologists reviewed a data set of 568 image sets (1704 images in total) selected from 50 cases by the decision support algorithm and were tasked with scoring the images for the presence or absence of ganglion cells. The task was repeated a total of 3 times. Each pathologist had to complete a short educational presentation between the second and third iterations. RESULTS.­: The training resulted in a significantly increased rate of correct diagnoses (true positive/negative) and a decreased need for referrals for expert consultation. No statistically significant changes in the rate of false positives/negatives were detected. CONCLUSIONS.­: A very short (<10 minutes) training session can greatly improve the pathologist's performance in the algorithm-assisted diagnosis of HSCR. The same approach may be feasible in training for the diagnosis of other rare diseases.

Effects of COVID-19 Lockdowns on the Development of Educational, Social and Emotional Gaps among Children: A Retrospective Chart Review.

BACKGROUND: School closures due to the coronavirus disease 2019 (COVID-19) outbreak affected students physically, socially, and psychologically with an increase in the number of children and adolescent presenting with anxiety, depression, and drug abuse. OBJECTIVES: To examine the impact of COVID-19 and lockdown on the mental health of minors during the pandemic period and to characterize the type and number of referrals to a regional psychiatric outpatient clinic. METHODS: This study included 380 children evaluated in an outpatient child psychiatric clinic. They were divided into two groups: before the lockdowns (BLD) (n=248), from January 2019 to February 2020, and during the lockdowns (LD) (n=132), from March 2020 to April 2021. RESULTS: When comparing the LD to BLD, there was increase in suicide attempts (9.8% vs. 2.8%) and in the use of psychotherapy (81% vs. 56%). There was a decrease in the diagnoses of behavior disorders (29.5% vs. 44.8%) and ADHD (29.5% vs. 50%); as well as a decrease in stimulant usage (22.7% vs. 38%). There was a statistically non-significant increase in the number of children with depression, anxiety, and drug-use disorder. CONCLUSIONS: Many children developed educational, social, emotional, and behavioral gaps during LD, and they lost skills to deal with everyday problems due to social isolation. It is important to follow the long-term impact of the lockdowns and social isolation.

Deep learning-based image analysis predicts PD-L1 status from H&E-stained histopathology images in breast cancer.

Programmed death ligand-1 (PD-L1) has been recently adopted for breast cancer as a predictive biomarker for immunotherapies. The cost, time, and variability of PD-L1 quantification by immunohistochemistry (IHC) are a challenge. In contrast, hematoxylin and eosin (H&E) is a robust staining used routinely for cancer diagnosis. Here, we show that PD-L1 expression can be predicted from H&E-stained images by employing state-of-the-art deep learning techniques. With the help of two expert pathologists and a designed annotation software, we construct a dataset to assess the feasibility of PD-L1 prediction from H&E in breast cancer. In a cohort of 3,376 patients, our system predicts the PD-L1 status in a high area under the curve (AUC) of 0.91 - 0.93. Our system is validated on two external datasets, including an independent clinical trial cohort, showing consistent prediction performance. Furthermore, the proposed system predicts which cases are prone to pathologists miss-interpretation, showing it can serve as a decision support and quality assurance system in clinical practice.

Association between Nuclear Morphometry Parameters and Gleason Grade in Patients with Prostatic Cancer.

Objective: Gleason scoring system remains the pathological method of choice for prostate cancer (Pca) grading. However, this method of tumor tissue architectural structure grading is still affected by subjective assessment and might succumb to several disadvantages, mainly inter-observer variability. These limitations might be diminished by determining characteristic cellular heterogeneity parameters which might improve Gleason scoring homogeneity. One of the quantitative tools of tumor assessment is the morphometric characterization of tumor cell nuclei. We aimed to test the relationship between various morphometric measures and the Gleason score assigned to different prostate cancer samples. Materials and Methods: We reviewed 60 prostate biopsy samples performed at a tertiary uro-oncology center. Each slide was assigned a Gleason grade according to the International Society of Urological Pathology contemporary grading system by a single experienced uro-pathologist. Samples were assigned into groups from grades 3 to 5. Next, the samples were digitally scanned (×400 magnification) and sampled on a computer using Image-Pro-Plus software©. Manual segmentation of approximately 100 selected tumor cells per sample was performed, and a computerized measurement of 54 predetermined morphometric properties of each cell nuclei was recorded. These characteristics were used to compare the pathological group grades assigned to each specimen. Results: Initially, of the 54 morphometric parameters evaluated, 38 were predictive of Gleason grade (p < 0.05). On multivariate analysis, 7 independent parameters were found to be discriminative of different Pca grades: minimum radius shape, intensity­minimal gray level, intensity­maximal gray level, character­gray level (green), character­gray level (blue), chromatin color, fractal dimension, and chromatin texture. A formula to predict the presence of Gleason grade 3 vs. grades 4 or 5 was developed (97.2% sensitivity, 100% specificity). Discussion: The suggested morphometry method based on seven selected parameters is highly sensitive and specific in predicting Gleason score ≥ 4. Since discriminating Gleason score 3 from ≥4 is essential for proper treatment selection, this method might be beneficial in addition to standard pathological tissue analysis in reducing variability among pathologists.

The risk of PD-L1 expression misclassification in triple-negative breast cancer.

PURPOSE: Stratification of patients with triple-negative breast cancer (TNBC) for anti-PD-L1 therapy is based on PD-L1 expression in tumor biopsies. This study sought to evaluate the risk of PD-L1 misclassification. METHODS: We conducted a high-resolution analysis on ten surgical specimens of TNBC. First, we determined PD-L1 expression pattern distribution via manual segmentation and measurement of 6666 microscopic clusters of positive PD-L1 immunohistochemical staining. Then, based on these results, we generated a computer model to calculate the effect of the positive PD-L1 fraction, aggregate size, and distribution of PD-L1 positive cells on the diagnostic accuracy. RESULTS: Our computer-based model showed that larger aggregates of PD-L1 positive cells and smaller biopsy size were associated with higher fraction of false results (P < 0.001, P < 0.001, respectively). Additionally, our model showed a significant increase in error rate when the fraction of PD-L1 expression was close to the cut-off (error rate of 12.1%, 0.84%, and 0.65% for PD-L1 positivity of 0.5-1.5%, ≤ 0.5% ,and ≥ 1.5%, respectively, P < 0.0001). Interestingly, false positive results were significantly higher than false negative results (0.51-22.62%, with an average of 6.31% versus 0.11-11.36% with an average of 1.58% for false positive and false negative results, respectively, P < 0.05). Furthermore, heterogeneous tumors with different aggregate sizes in the same tumor, were associated with increased rate of false results in comparison to homogenous tumors (P < 0.001). CONCLUSION: Our model can be used to estimate the risk of PD-L1 misclassification in biopsies, with potential implications for treatment decisions.

Computerized morphometry analysis of epithelial fimbriae nuclear symmetry in BRCA carriers may identify patients at risk for developing ovarian cancer.

Serous ovarian tumors may originate in epithelial cells of the fallopian tubes. Computerized morphometry was able to find significant alterations in the fallopian tube epithelium of healthy BRCA carriers. The purpose of this study was to identify a subgroup of BRCA carriers that may be at risk of developing serous ovarian cancer by evaluation of the epithelial nuclear symmetry in the fallopian tubes. Four groups of patients were analyzed; healthy patients, ovarian cancer patients, BRCA carriers, and BRCA noncarriers. All fallopian tubes appeared normal by H&E examination. The ImageProPlus software was used to assess the nuclear symmetry of 65 fimbriae epithelium cells and an artificial neural network algorithm aided in detecting a subpopulation among fimbriae of healthy BRCA carriers at risk for ovarian cancer. Significant differences were found between healthy patients and ovarian cancer patients, and between BRCA carriers and noncarriers. The algorithm was able to accurately predict BRCA carriers with associated ovarian cancer based on fallopian tube nuclear symmetry characteristics. These results reinforce the hypothesis that fimbriae epithelial cells of BRCA carriers may undergo early-stage changes that could predict the risk of progression toward malignancy.

Differential Serum-intestinal Dynamics of Infliximab and Adalimumab in Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Therapeutic drug monitoring is used to guide anti-tumour necrosis factor [TNF] therapy. However, the associations between serum drug levels [SDL], TNF-bound, and free anti-TNF in the target tissue are incompletely defined. We aimed to assess the interactions between these parameters in inflammatory bowel disease [IBD] patients. METHODS: ENZYME-LINKED IMMUNOSORBENT: assays [ELISA assays] were used to detect free drug and TNF-drug complexes in intestinal tissues. Concurrent SDL, anti-drug antibodies [ADA], pharmacotherapy, clinical response, endoscopic appearance, and histological severity were determined. Comparisons between anti-TNFs and paired inflamed/non-inflamed tissue were performed. Variables were correlated and potential interactions detected using multivariate analysis. RESULTS: A total of 95 biopsies taken from 49 anti-TNF treated IBD patients [26 receiving infliximab and 23 adalimumab] were studied. Free drug levels were higher in inflamed compared with non-inflamed paired specimens. Tissue free-drug and TNF-drug complexes levels were higher in adalimumab-treated patients. In adalimumab-treated patients, SDL were correlated with free drug, but not TNF-drug complex levels, in both inflamed and non-inflamed segments. In infliximab-treated patients, higher SDL were associated with the presence of tissue free drug in both inflamed and non-inflamed segments, whereas TNF-drug complexes were mostly detected in non-inflamed but not in inflamed tissue. In the presence of ADA, neither free drug nor TNF-infliximab complexes were measured in the tissue. Tissue levels did not correlate well with clinical, endoscopic, or histological scores. CONCLUSIONS: SDL correlated with tissue free drug levels; however, different dynamics were observed for TNF-drug complex levels. Infliximab and adalimumab tissue drug dynamics differ. Better understanding of these interactions may allow future therapeutic optimisation.

Implementation of Comprehensive Genomic Profiling in Ovarian Cancer Patients: A Retrospective Analysis.

Comprehensive genomic profiling (CGP) allows for the detection of driver alterations at high resolution, but the limited number of approved targeted therapies and their high costs have contributed to its limited clinical utilization. We retrospectively compared data of 946 women with ovarian cancer (11.4% were referred to CGP, and 88.6% served as control) to examine whether CGP provides a prognosis benefit. Patient baseline parameters were similar between the groups. Cox regression analysis adjusted for age, disease stage at diagnosis, and recurrence status showed statistically significantly longer median overall survival (mOS) in the CGP group versus the control (73.4 versus 54.5 months, p < 0.001). Fifty-four patients (52.9%) had actionable mutations with potential treatments; twenty-six (48.2%) were treated with matched targeted therapy, showing a trend for longer mOS than the eighty-six women in the CGP group who were not given a suggested treatment (105.5 versus 63.6 months, p = 0.066). None of the genomic alterations predicted metastasis location. CCNE1 amplification and KRAS mutations were associated with shorter mOS. Patients with tumor mutation burden ≥4 mutations/megabase had longer mOS. High loss of heterozygosity was associated with longer mOS (99.0 versus 48.2 months, p = 0.004). CGP testing may provide both prognostic and predictive insights for treatment of patients with ovarian cancer. Prospective studies of larger cohorts are warranted.

Role of C-Reactive Protein in Discrimination between Transudative and Exudative Pleural Effusions.

BACKGROUND: There is still no wide agreement regarding the efficacy of the serum levels of C-reactive protein (CRPs), pleural fluid levels of CRP (CRPpf), and their ratio (CRPr) in the discrimination between transudative (Tr) and exudative (Ex) pleural effusions (PEs). Most of the previous studies were conducted on small cohorts, and the role of CRPs in the CRPpf gradient (CRPg) in this discrimination has not been previously reported. The present study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPg, and CRPr in the discrimination between TrPE and ExPE in a relatively large cohort of patients with PE. METHODS: The study population included 492 patients with PE, 210 of them with TrPE and 282 with ExPE. The levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. RESULTS: The mean levels of CRPs, CRPpf, CRPg, and CRPr of the TrPEs were 11.3 ± 5.7 mg/L, 4.6 ± 2.8 mg/L, 6.7 ± 3.9 mg/L, and 0.40 ± 0.14, respectively, and for the ExPEs, they were 140.5 ± 112.8 mg/L, 52.8 ± 53.2 mg/L, 87.2 ± 72.4 mg/L, and 0.37 ± 0.15, respectively. The levels of CRPs, CRPpf, and CRPg were significantly higher in the ExPEs than in the TrPEs (p < 0.0001). No significant difference was found between the two groups for the levels of CRPr (p = 0.15). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating TrPE from ExPE was for CRPs, 20.5 mg/L with area under the curve (AUC) = 97% and p < 0.0001; for CRPpf, 9.9 mg/L with AUC = 95% and p < 0.0001; and for CRPg, 13.6 mg/L with AUC = 96% and p < 0.0001. CONCLUSION: CRPs, CRPpf, and CRPg are strong markers for discrimination between TrPE and ExPE, while CRPr has no role in this discrimination.

ACKR2 limits skin fibrosis and hair loss through IFN-ß.

The resolution of inflammation facilitates proper wound healing and limits tissue repair short of exaggerated fibrotic scarring. The atypical chemokine receptor (ACKR)2/D6 scavenges inflammatory chemokines, while IFN-ß is a recently unveiled pro-resolving cytokine. Both effector molecules limit acute inflammatory episodes and promote their resolution in various organs. Here, we found fibrotic skin lesions from ACKR2-/- mice presented increased epidermal and dermal thickening, atrophy of the subcutaneous adipose tissue, augmented disorientation of collagen deposition, and enhanced deformation and loss of hair follicles compared to WT counterparts. In addition, affected skin sections from ACKR2-/- mice contained reduced levels of the pro-resolving mediators IFN-ß and IL-10, but increased levels of the pro-inflammatory chemokines CCL2 and 3, the pro-fibrotic cytokine TGF-ß, and the immune-stimulating cytokine IL-12. Notably, treatment with exogenous IFN-ß rescued, at least in part, all the pro-fibrotic outcomes and lesion size in ACKR2-/- mice and promoted expression of the pro-resolving enzyme 12/15-lipoxygenase (LO) in both ACKR2-/- and WT mice. Moreover, Ifnb-/- mice displayed enhanced pro-fibrotic indices upon exposure to bleomycin. These findings suggest ACKR2 is an important mediator in limiting inflammatory skin fibrosis and acts via IFN-ß production to promote the resolution of inflammation and minimize tissue scaring.

The Association Between Clearance of Human Papillomavirus After Conization for Cervical Cancer and Absence of Cancer.

OBJECTIVES: We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). MATERIALS METHODS: Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3-12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. RESULTS: The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV-negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006).In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. CONCLUSIONS: Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

Morphometric analysis of nuclear symmetry in urothelial carcinoma for predicting tumor recurrence.

Urothelial carcinoma is the ninth most common cancer in the world. Cytological analysis of the urine is used for screening, as well as for cases suspected for neoplasia of the urinary tract. However, the sensitivity of urine cytology examination is low. The golden standard for diagnosing bladder cancer relies upon cystoscopy followed by a biopsy, which is microscopically assessed by the pathologist. Treatment decisions are based on the histological grade and stage of the tumor. Posttreatment tumor recurrence is 50%. The purpose of this study is to predict recurrence of urothelial carcinoma using a novel morphometric method of nuclear symmetry analysis. This method may help tailor the appropriate treatment and may reduce the need of invasive surgical procedures in patients. Computerized morphometry was applied to develop multiple symmetry indices of the nuclei of the tumor cells as follows: each nucleus was physically divided along its digital axis in two segments that were separately analyzed for their shape, size, optical density, and texture. Subsequently, ratios were obtained by mathematically dividing between the morphometric values of the two nuclear segments where the denominator contained the largest value of the two. These ratios were named symmetry indices and were included as variables to predict the recurrence time of the tumors. The change in the symmetry indices (loss of symmetry) of the nuclear roundness, fractal dimension and margination were the only independent predictors of recurrence time. Computerized morphometry of nuclear symmetry indices may help to predict tumor recurrence in urothelial carcinomas.

Expression of Semaphorin 3A in Malignant and Normal Bladder Tissue: Immunohistochemistry Staining and Morphometric Evaluation.

INTRODUCTION: Our previous studies showed elevated levels of Semaphorin3a (Sema3A) in the urine of patients with urothelial cancer compared to healthy patients. The aim of this study was to analyze the extent of Sema3A expression in normal and malignant urothelial tissue using immune-staining microscopic and morphometric analysis. MATERIALS AND METHODS: Fifty-seven paraffin-embedded bladder samples were retrieved from our pathology archive and analyzed: 14 samples of normal urothelium, 21 samples containing low-grade urothelial carcinoma, 13 samples of patients with high-grade urothelial carcinoma, 7 samples containing muscle invasive urothelial carcinoma, and 2 samples with pure urothelial carcinoma in situ. All samples were immunostained with anti Sema3A antibodies. The area of tissue stained with Sema3A and its intensity were analyzed using computerized morphometry and compared between the samples' groups. RESULTS: In normal bladder tissue, very light Sema3A staining was demonstrated on the mucosal basal layer and completely disappeared on the apical layer. In low-grade tumor samples, cells in the basal layer of the mucosa were also lightly stained with Sema3A, but Seama3A expression intensified upon moving apically, reaching its highest level on apical cells exfoliating to the urine. In high grade urothelial tumors, Seama3A staining was intense in the entire thickness of the mucosa. In samples containing carcinoma in situ, staining intensity was high and homogenous in all the neoplastic cells. CONCLUSIONS: Sema3A may be serve as a potential non-invasive marker of urothelial cancer.

Computerized image analysis of blood vessels within mucosal defects for the prediction of delayed bleeding following colonic endoscopic mucosal resection: a pilot study.

BACKGROUND : Clinically significant post-endoscopic bleeding (CSPEB) is a common complication following colonic endoscopic mucosal resection (EMR). Current prediction tools are clinical and do not use the appearance of the post-EMR mucosal defect. We aimed to predict CSPEB by analyzing blood vessel morphology within the post-EMR mucosal defect. METHODS : 43 patients with CSPEB were matched to 43 non-bleeders for clinical variables associated with CSPEB. Computerized image analysis quantified the morphologic characteristics of the blood vessels in the defect. Variables were measured in relation to the mucosal defect area. Multivariate analysis and a neural network (NNET) were used as prediction models. RESULTS : The CSPEB group vessels had larger maximum diameter (113.07 vs. 69.03; P < 0.001), larger minimum radius (5.09 vs. 3.28; P = 0.002), larger perimeter value (337.82 vs. 193.86; P < 0.001), larger vessel length-of-outline (351.83 vs. 220.68; P = 0.002), and larger fractal dimension (1.11 vs. 1.10; P = 0.005) compared with non-bleeders. Discriminant analysis yielded 86 % sensitivity and 76.7 % specificity and an NNET classifier yielded 100 % sensitivity and 76.9 % specificity for identifying patients at risk. CONCLUSIONS : Blood vessel morphology in the post-EMR defect can be used to predict bleeding following colonic EMR.

Diagnostic Value of C-Reactive Protein in Discrimination between Uncomplicated and Complicated Parapneumonic Effusion.

OBJECTIVES: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort. METHODS: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. RESULTS: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group (p < 0.0001). No significant difference was found between the two groups for levels of CRPr (p = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and p < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and p < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and p < 0.0001. CONCLUSIONS: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.