Inter- and intraobserver agreement in whole-slide digital ThinPrep samples of low-grade squamous lesions of the cervix uteri with known high-risk HPV status: A multicentric international study.

BACKGROUND: High-risk human papilloma virus (HR HPV) testing and liquid-based cytology are used for primary cervical screening. Digital cytology, based on whole-slide scanned samples, is a promising technique for teaching and diagnostic purposes. The aim of our study was to evaluate the interobserver and intraobserver variation in low-grade squamous lesions, HR HPV status bias, and the use of whole-slide scanned digital cervical cytology slides. METHODS: Fifteen expert cytopathologists evaluated 71 digitalized ThinPrep slides (31 atypical squamous cells of undetermined significance [ASC-US], 21 negative for intraepithelial lesion or malignancy, and 19 low-grade squamous intraepithelial lesion cases). HR HPV data were accessible only in the second round. RESULTS: In interobserver analysis, Kendall's coefficient of concordance was 0.52 in the first round and 0.58 in the second round. Fleiss' kappa values were 0.29 in the first round and 0.31 in the second round. In the ASC-US category, Fleiss kappa increased from 0.19 to 0.22 in the second round and the increase was even higher expressed by Kendall's coefficient: from 0.42 to 0.52. In intraobserver analysis, personal scores were higher in the second round. CONCLUSIONS: The interobserver and intraobserver variability in low-grade squamous lesions was within fair agreement values in the present study, in line with previous works. The comparison of two rounds showed that expert cytopathologists are generally unbiased by the knowledge of HR HPV data, but that being informed of the HR HPV status leads to a better agreement. Stain quality and back discomfort were highlighted as factors affecting digital cytopathology use.

Estimating greenhouse gases emissions from horticultural peat soils using a DNDC modelling approach.

Peat soils represent an important global carbon (C) sink, but can also provide a highly fertile medium for growing horticultural crops. Sustainable crop production on peat soils involves a trade-off between ensuring food security and mitigating typically high greenhouse gas (GHG) emissions and rates of soil C loss. An alternative approach to resource intensive field-based monitoring of GHG fluxes for all potential management scenarios is to use a process-based model driven by existing field data to estimate emissions. The aim of this study was to evaluate the suitability of the Denitrification-Decomposition (DNDC) model for estimating emissions of CO2, N2O and CH4 from horticultural peat soils. The model was parameterised using climatic, soil, and crop management data from two intensively cultivated sites on soils of contrasting soil organic matter (SOM) contents (∼35% and ∼70% SOM content). Simulated emissions of CO2, N2O and CH4, and simulated soil physical and crop output values, were compared to actual GHG, soil and crop measurements. Model performance was assessed using baseline parameterisation (i.e. model defaults), then calibrated using pre-simulation and sensitivity analysis processes. Under baseline parameterisation conditions, DNDC proved poor at predicting GHG emissions and soil/crop variables. Calibration and validation improved DNDC performance in estimating the annual magnitude of emissions, but model refinement is still required for reproducing seasonal GHG patterns in particular. Key constraints on model functioning appear to be its ability to reliably model soil moisture and some aspects of C and nitrogen dynamics, as well as the quality of input data relating to water table dynamics. In conclusion, our results suggest that the DNDC (v. 9.5) model cannot accurately reproduce or be used to replace actual field measurements for estimation of GHG emission factors under different management scenarios for horticultural peat soils, but may be able to do so with further modification.

Advanced Ovarian Cancer Displays Functional Intratumor Heterogeneity That Correlates to Ex Vivo Drug Sensitivity.

INTRODUCTION: Epithelial ovarian cancer is recognized to be heterogeneous but is currently treated with a single treatment strategy. Successful patient stratification of emerging chemotherapy agents is dependent upon the availability of reliable biomarkers indicative of the entire tumor. AIM: The aim of this study was to evaluate intertumor and intratumor heterogeneity within a series of epithelial ovarian cancer using homologous recombination (HR) DNA repair status. METHODS: Primary cultures generated from ascites and solid tumor from multiple intra-abdominal sites were characterized by their morphology and expression of protein markers. Results were compared with Formalin fixed paraffin embedded tissue pathology.Homologous recombination function was determined by quantification of nuclear Rad51 foci. Growth inhibition (sulforhodamine B) assays were used to calculate the GI50 for cisplatin and rucaparib. RESULTS: Ascites with matched solid tumor were cultured from 25 patients.Concordance in functional HR status between ascites and solid tumor subcultures was seen in only 13 (52%) of 25 patients. Heterogeneity in HR status was seen even in patients with homogeneous histological subtype. Homologous recombination defective cultures were significantly more sensitive to cisplatin and rucaparib.Additionally, intertumor and intratumor heterogeneity was seen between the expression of epithelial and ovarian markers (EpCAM, cytokeratin, CA125, MOC-31, and vimentin). There was no relationship between heterogeneity of HR functional status and antigen expression. CONCLUSIONS: Intertumor and intratumor functional HR heterogeneity exists that cannot be detected using histological classification. This has implications for biomarker-directed treatment.

Ten-year outcomes of a one-stop colposcopy clinic: a unique service for low grade cytology.

OBJECTIVE: To determine patient acceptance of treatment, and treatment default rate, at a one-stop clinic, and to establish the concordance of punch and loop histology for high grade cervical intraepithelial neoplasia (CIN) by date of excisional treatment. STUDY DESIGN: Retrospective review of computerised data and clinic files of 2090 women with low grade cytology undergoing cervical punch biopsies between 2001 and 2011 at the colposcopy clinic, Northern Gynaecological Oncology Centre, Gateshead, UK. Punch biopsies were micro-wave processed and reported within 2h, and women were offered immediate loop biopsy if high grade CIN was confirmed. Data were collected regarding patients' choice for immediate or deferred treatment and default rate. Histological outcomes were compared between those undergoing immediate and deferred loop biopsies. RESULTS: Of the 360 women (17%) with high grade CIN on punch biopsy, 259 (72%) opted to have immediate loop treatment at the first visit. Of these women, 190 (73%) had high grade CIN on loop histology. Of 97 women (27%) who had deferred loop biopsy after a median of 28 days (range 7-112), 65 (67%) had high grade CIN on loop histology. The default rate at return for treatment appointments was 0% amongst all patients. CONCLUSION: This one-stop colposcopy clinic reduces defaulting from treatment. It has proven to be a sustainable service and the majority of women, when given the choice, opt for immediate loop treatment at their first visit.

The interobserver reproducibility of thyroid fine-needle aspiration using the UK Royal College of Pathologists' classification system.

The overall interobserver reproducibility of thyroid fine-needle aspiration (FNA) has not been comprehensively assessed. A blinded 6-rater interobserver reproducibility study was conducted of 200 thyroid FNA cases using the UK System, which is similar to The Bethesda System for Reporting Thyroid Cytology: Thy1, nondiagnostic; Thy2, nonneoplastic; Thy3a, atypia, probably benign; Thy3f, follicular lesion; Thy4, suspicious of malignancy; and Thy5, malignant. There was good interobserver agreement for the Thy1 (κ = 0.69) and Thy5 (κ = 0.61), moderate agreement for Thy2 (κ = 0.55) and Thy3f (κ = 0.51), and poor agreement for Thy3a (κ = 0.11) and Thy4 (κ = 0.17) categories. Combining categories implying surgical management (Thy3f, Thy4, and Thy5) achieved good agreement (κ = 0.72), as did combining categories implying medical management (Thy1, Thy2, and Thy3a; κ = 0.72). The UK thyroid FNA terminology is a reproducible and clinically relevant system for thyroid FNA reporting. This study demonstrates that international efforts to harmonize and refine thyroid cytology classification systems can improve consistency in the clinical management of thyroid nodules.

The post-LLETZ cervical smear: influence of time interval from LLETZ.

OBJECTIVE: To determine the effect of the time interval between large loop excision through the transformation zone (LLETZ) and the first subsequent cervical smear on the adequacy of the smear for cytologic interpretation and cytologic abnormality rates. STUDY DESIGN: A retrospective, case-note analysis of women attending a colposcopy clinic between May 1, 1999, and March 31, 2002, who had high grade histologic lesions on their LLETZ biopsy, irrespective of the referral indication. RESULTS: A total of 771 women were included in the study. Negative smears were reported in 639 (82.9%); 82 (10.6%) were abnormal and 50 (6.5%) unsatisfactory. The post-LLETZ smear was performed at a median interval of 105 days (range, 48-829). A univariate logistic regression analysis did not reveal any relationship between the rate of unsatisfactory or abnormal smears and the interval since having LLETZ (p = 0.935). CONCLUSION: These data do not support the traditionally held concept that performing the post-LLETZ smear before 6 months increases the rate of unsatisfactory or abnormal smears.