Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials

Objective: Interobserver agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. Study Design: Two adjacent serial histologic sections of oral lesions from 846 patients were independently scored by 2 different pathologists from a pool of 4. In instances where the original 2 pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. Results: Individual pathologist pair κ values ranged from 0.251 to 0.706 (fair-good) before the 3-stage review process. During the initial review phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. Conclusions: The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis

‘Cytology-on-a-chip’ based sensors for monitoring of potentially malignant oral lesions

Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. Objective To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. Materials and methods Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new ‘cytology-on-a-chip’ approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. Results Binary “low-risk”/“high-risk” models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity + specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. Conclusions This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum

Prevalence and risk factors for hepatitis B virus infections among visitors to an STD clinic.

OBJECTIVE: To determine the prevalence and risk factors for hepatitis B virus (HBV) infections among individuals attending an STD clinic in a low endemic region. STUDY DESIGN: A total of 1228 women and 1648 men attending the STD clinic at the University Hospital Rotterdam, Netherlands, were examined for HBV infection by determination of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core antigen (anti-HBc). Demographic characteristics, information on sexual behaviour, and intravenous drug use were recorded. RESULTS: The seroprevalence of HBsAg was 1.4% in women and 2.1% in men (0% in homosexual men). The seroprevalence of anti-HBc was 13% in women and 20% in men (36% in homosexual men). Native country, intravenous drug use, a history of STD, and the number of partners in the past half year (inversely) were independent risk factors for HBsAg positivity in women and heterosexual men. For anti-HBc independent associations were observed for native country, age, intravenous drug use, commercial sex, number of lifetime partners, homosexual contacts, orogenital contact (inverse), and a history of STD. CONCLUSION: The HBV prevalence in the STD clinic attendants was high, exceeding the national estimate, and indicates that the STD clinic population may be considered a high risk group. Our data confirmed an increased risk for HBV infections among established risk groups. Therefore, these risk groups should be routinely screened to identify HBV cases for counselling and contact tracing