Oral cancer detection and progression prediction using noninvasive cytology-based DNA ploidy approach.

Background: Despite the oral cavity being readily accessible, oral cancer (OC) remains a significant burden. The objective of this study is to develop a DNA ploidy-based cytology test for early detection of high-risk oral lesions.

Methods: This retrospective study was conducted using 569 oral brushing samples collected from 95 normal and 474 clinically abnormal mucosa with biopsy diagnosis of reactive, low-grade or high-grade precancer or cancers.

Delineating spatial cell-cell interactions in the solid tumour microenvironment through the lens of highly multiplexed imaging.

The growth and metastasis of solid tumours is known to be facilitated by the tumour microenvironment (TME), which is composed of a highly diverse collection of cell types that interact and communicate with one another extensively. Many of these interactions involve the immune cell population within the TME, referred to as the tumour immune microenvironment (TIME). These non-cell autonomous interactions exert substantial influence over cell behaviour and contribute to the reprogramming of immune and stromal cells into numerous pro-tumourigenic phenotypes.

Identification of a serum-based microRNA signature that detects recurrent oral squamous cell carcinoma before it is clinically evident.

Background: Survival rates for oral squamous cell carcinoma (OSCC) have remained poor for decades, a fact largely attributable to late-stage diagnoses and high recurrence rates. We report analysis of serum miRNA expression in samples from patients with high-risk oral lesions (HRL, including OSCC/carcinoma in situ lesions) and healthy non-cancer controls, with the aim of non-invasively detecting primary or recurrent disease before it is clinically evident.

Methods: Discovery, test, and validation sets were defined from a total of 468 serum samples (305 HRL and 163 control samples).

DNA Ploidy as a Potential Adjunct Prognostic Marker of Low-Risk Prostate Cancer Progression after Radical Prostatectomy.

Purpose: Post prostatectomy PSA kinetics and General Grade Groups (GGG) are the strongest prognostic markers of biochemical recurrence (BCR) and prostate cancer (PCa)-specific mortality after radical prostatectomy. Despite having low-risk PCa, some patients will experience BCR, for some, clinically significant BCR. There is a need for an objective prognostic marker at the time of prostatectomy to improve risk stratification within this population.

Polymorphisms in the Nonhomologous End-joining DNA Repair Pathway are Associated with HPV Integration in Cervical Dysplasia.

Unlabelled: Previous evidence indicates that human papillomavirus (HPV) integration status may be associated with cervical cancer development and progression. However, host genetic variation within genes that may play important roles in the viral integration process is understudied. The aim of this study was to examine the association between HPV16 and HPV18 viral integration status and SNPs in nonhomologous-end-joining (NHEJ) DNA repair pathway genes on cervical dysplasia.

Use of DNA image cytometry in conducting oral cancer screening in rural India.

Objectives: Oral cancer screening can assist in the early detection of oral potentially malignant lesions (OPMLs) and prevention of oral cancers. It can be challenging for clinicians to differentiate OPMLs from benign conditions. Adjunct screening tools such as fluorescence visualisation (FV) and DNA image cytometry (DNA-ICM) have shown success in identifying OPMLs in high-risk clinics.

Improvement in Work Productivity After Group Voice Therapy in Professional Voice Users.

Objective: A disordered voice may significantly impair the ability of workers to perform optimally on the job, especially those classified as professional voice users (PVU). Voice therapy is a common treatment option for voice disorders, but there are few studies demonstrating its effect on work productivity. The objective of this study was to evaluate the change in work productivity in PVU after group voice therapy.

Quantitative nuclear phenotype signatures predict nodal disease in oral squamous cell carcinoma.

Background: Early-stage oral squamous cell carcinoma (OSCC) patients have a one-in-four risk of regional metastasis (LN+), which is also the most significant prognostic factor for survival. As there are no validated biomarkers for predicting LN+ in early-stage OSCC, elective neck dissection often leads to over-treatment and under-treatment. We present a machine-learning-based model using the quantitative nuclear phenotype of cancer cells from the primary tumor to predict the risk of nodal disease.

Predicting Progression of Low-Grade Oral Dysplasia Using Brushing-Based DNA Ploidy and Chromatin Organization Analysis.

Most oral cancers arise from oral potentially malignant lesions, which show varying grades of dysplasia. Risk of progression increases with increasing grade of dysplasia; however, risk prediction among oral low-grade dysplasia (LGD), that is, mild and moderate dysplasia can be challenging as only 5%-15% transform. Moreover, grading of dysplasia is subjective and varies with the area of the lesion being biopsied.

Assessment of internal refractive index profile of stochastically inhomogeneous nuclear models via analysis of two-dimensional optical scattering patterns.

Significance: Optical scattering signals obtained from tissue constituents contain a wealth of structural information. Conventional intensity features, however, are mostly dictated by the overall morphology and mean refractive index of these constituents, making it very difficult to exclusively sense internal refractive index fluctuations.

Aim: We perform a systematic analysis to elucidate how changes in internal refractive index profile of cell nuclei can best be detected via optical scattering.

An improved algorithm using a Health Canada-approved DNA-image cytometry system for non-invasive screening of high-grade oral lesions.

Background: DNA-image cytometry (DNA-ICM) is able to detect gross alterations of cellular DNA-content representing aneuploidy, a biomarker of malignancy. A Health Canada-approved DNA-ICM system, ClearCyte in combination with a cytopathologist's review, has demonstrated high sensitivity (89%) and specificity (97%) in identifying high-grade oral lesions. The study objective was to create an improved automated algorithm (iClearcyte) and test its robustness in differentiating high grade from benign reactive oral lesions without a cytopathologist's input.

Multi-scale tissue architecture analysis of favorable-risk prostate cancer: Correlation with biochemical recurrence.

Purpose: Prostate cancer (PCa) with biopsy-based grade group (GG) 1 or 2 characteristics has a favorable outcome, yet some cases still progress after radical prostatectomy and present with biochemical recurrence (BCR). We hypothesized that the multi-scale tissue architecture (MSTA) analysis score would correlate with the aggressive PCa phenotype and could be used as a tool for risk assessment to improve the management of patients with favorable-risk PCa.

Materials And Methods: MSTA was evaluated in needle-biopsy samples from 115 patients with favorable-risk PCa, as defined by GG1 and GG2, a prostate-specific antigen (PSA) level of <10 ng/mL, a clinical stage of cT1c to cT2b, and general Gleason GG (GGG) and expert pathologist-assessed GG (EGG).

Factors Associated with Failure of Botulinum Toxin Injection in Adductor Spasmodic Dysphonia.

Objective: Electromyography (EMG) Guided botulinum toxin (BTX) injection is considered first-line treatment for adductor spasmodic dysphonia (SD). Failure rate can range between 6% and 29%. Study objective was to determine which factors were associated with failure.

Cervical cytology reproducibility and associated clinical and demographic factors.

Background: Although the Pap test has been the standard screening method for cervical precancer/cancer detection, it has been criticized for having a relatively low sensitivity and a low reproducibility between pathologists. There is limited knowledge about inter-rater agreement and what clinical and demographic factors are associated with disagreements between pathologists reading the same Pap smear.

Methods: This study aimed to assess inter- and intra- rater agreement of the Pap smear in 1619 cytologic slides with biopsy confirmation, using kappa statistics.

The role of DNA image cytometry in screening oral potentially malignant lesions using brushings: A systematic review.

It is believed that the majority of oral cancers develop from oral potentially malignant lesions (OPML). Though they can be easily detected during screening, risk stratification is difficult. During screening clinicians often find it difficult to distinguish OPMLs from benign lesions, and predicting OPML at risk of malignant transformation is particularly challenging.

Uveitis: Autoimmunity… and beyond.

Objective: Uveitis is the most common ophthalmological finding in the practice of rheumatology and clinical immunology. The condition is frequently idiopathic but about 60 causes of uveitis have been described. Our aim was to analyze the clinical patterns and etiologies of uveitis in a tertiary referral center.

Intravitreal Injections of Voriconazole for Endophthalmitis: A Case Series.

: endophthalmitis represents a therapeutic challenge, considering the inability of many antifungals to achieve adequate concentrations in the vitreous. Intravitreal injection (IVI) of antifungals (amphotericin b deoxycholate or voriconazole) is therefore recommended. Whereas amphotericin b IVI is well documented, clinical data on voriconazole IVI are limited.

Hyperspectral cell sociology reveals spatial tumor-immune cell interactions associated with lung cancer recurrence.

Background: The tumor microenvironment (TME) is a complex mixture of tumor epithelium, stroma and immune cells, and the immune component of the TME is highly prognostic for tumor progression and patient outcome. In lung cancer, anti-PD-1 therapy significantly improves patient survival through activation of T cell cytotoxicity against tumor cells. Direct contact between CD8+ T cells and target cells is necessary for CD8+ T cell activity, indicating that spatial organization of immune cells within the TME reflects a critical process in anti-tumor immunity.

Uveitis of Unknown Etiology: Clinical and Outcome features. A Retrospective Analysis of 355 Patients.

: Despite the huge advance in diagnostic technics, about one-third of uveitis is still considered of unknown etiology. In this study, we aimed to report their clinical features and to describe how a diagnosis has been finally reached for some patients.: We retrospectively reviewed all patients with uveitis referred to our tertiary center between 2002 and 2016.

Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer.

The incidence of HPV-positive oropharyngeal cancer (HPV+ OPC) is increasing, thus presenting new challenges for disease detection and management. Noninvasive methods involving brush biopsies of diseased tissues were recently reported as insufficient for tumor detection in HPV+ OPC patients, likely due to differences between the site of tumor initiation at the base of involuted crypts and the site of brush biopsy at the crypt surface. We hypothesized that histologically normal surface epithelial cells in the oropharynx contain changes in nuclear morphology that arise due to tumor proximity.

Using quantitative tissue phenotype to assess the margins of surgical samples from a pan-Canadian surgery study.

Background: The purpose of this study was to use quantitative tissue phenotype (QTP) to assess the surgical margins to examine if a fluorescence visualization-guided surgical approach produces a shift in the surgical field by sparing normal tissue while catching high-risk tissue.

Methods: Using our QTP to calculate the degree of nuclear chromatin abnormalities, Nuclear Phenotypic Score (NPS), we analyzed 1290 biopsy specimens taken from surgical samples of 248 patients enrolled in the Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer (COOLS) trial. Multiple margin specimens were collected from each surgical specimen according to the presence of fluorescence visualization alterations and the distance to the surgical margins.

Automatic labeling of molecular biomarkers of immunohistochemistry images using fully convolutional networks.

This paper addresses the problem of quantifying biomarkers in multi-stained tissues based on the color and spatial information of microscopy images of the tissue. A deep learning-based method that can automatically localize and quantify the regions expressing biomarker(s) in any selected area on a whole slide image is proposed. The deep learning network, which we refer to as Whole Image (WI)-Net, is a fully convolutional network whose input is the true RGB color image of a tissue and output is a map showing the locations of each biomarker.

Racial/ethnic differences in HPV 16/18 genotypes and integration status among women with a history of cytological abnormalities.

Objective: HPV genotype distribution varies by race/ethnicity, but is unclear whether there are racial/ethnic variations in HPV 16/18 integration in the host genome. We describe HPV16/18 infection and integration status in a racially/ethnically diverse sample of women with a recent abnormal Pap test.

Methods: Patients (n=640) represent a subset of women participating in a clinical trial.

Large-scale DNA organization is a prognostic marker of breast cancer survival.

Breast cancer is the leading cause of cancer-related deaths among women worldwide. We investigated whether changes in large-scale DNA organization (LDO) of tumor epithelial nuclei are an indicator of the aggressiveness of the tumor. We tested our algorithm on a set of 172 duplicates TMA cores samples coming from 95 breast cancer patients.

Quantification of large scale DNA organization for predicting prostate cancer recurrence.

This study investigates whether Genomic Organization at Large Scales (which we propose to call GOALS) as quantified via nuclear phenotype characteristics and cell sociology features (describing cell organization within tissue) collected from prostate tissue microarrays (TMAs) can separate biochemical failure from biochemical nonevidence of disease (BNED) after radical prostatectomy (RP). Of the 78 prostate cancer tissue cores collected from patients treated with RP, 16 who developed biochemical relapse (failure group) and 16 who were BNED patients (nonfailure group) were included in the analyses (36 cores from 32 patients). A section from this TMA was stained stoichiometrically for DNA using the Feulgen-Thionin methodology, and scanned with a Pannoramic MIDI scanner.