Performance of Nomogram Prediction Combining MiRNAs in Cervical Mucus, HPV Genotype and Age for Cervical Cancer and its Precursor Lesions

Cervical cancer is the fourth most common cancer in women worldwide. Although cytology or HPV testing is available for screening, these techniques have their drawbacks and optimal screening methods are still being developed. Here, we sought to determine whether aberrant expression of miRNAs in cervical mucus could be an ancillary test for cervical neoplasms. The presence of miRNAs in 583 and 126 patients (validation and external cohorts) was determined by real-time RT-PCR. Performance of a combination with five miRNAs (miR-126-3p, -451a -144-3p, -20b-5p and -155-5p) was estimated by ROC curve analysis. Predicted probability (PP) was estimated by nomograms comprising -ΔCt values of the miRNAs, HPV genotype and age. A combination of five miRNAs showed a maximum AUC of 0.956 (95%CI: 0.933-0.980) for discriminating cancer. Low PP scores were associated with good prognosis over the 2-year observation period (p<0.05). Accuracy for identifying cancer and cervical intraepithelial neoplasia (CIN)3+ by nomogram was 0.983 and 0.966, respectively. PP was constant with different storage conditions of materials. We conclude that nomograms using miRNAs in mucus, HPV genotype and age could be useful as ancillary screening tests for cervical neoplasia.

P.051 Do clinical confounders to the neurological examination modify the diagnostic accuracy of CT-angiography for death by neurological criteria/brain death?

Background: CT-angiography is an ancillary test used to diagnose death by neurological criteria (DNC), notably in cases of unreliable neurological examinations due to clinical confounders. We studied whether clinical confounders to the neurological examination modified CT-angiography diagnostic accuracy. Methods: Systematic review and meta-analysis of studies including deeply comatose patients undergoing DNC ancillary testing. We estimated pooled sensitivities and specificities using a Bayesian hierarchical model, including data on CT-angiography (4-point, 7-point, 10-point scales, and no intracranial flow), and performing a subgroup analysis on clinical confounders to the reference neurological examination. Results: Of 40 studies included in the meta-analysis, 7 involve CT-angiography (n=586). There was no difference between subgroups (Table). The degree of uncertainty involving sensitivity estimates was high in both subgroups. Conclusions: Statistical uncertainty in diagnostic accuracy estimates preclude any conclusion regarding the impact of clinical confounders on CT-angiography diagnostic accuracy. Further research is required to validate CT-angiography as an accurate ancillary test for DNC. Table. Pooled sensitivities and specificities of CT-angiography for death by neurological criteria

Diagnostic Value of Galectin-3 in Distinguishing Invasive Encapsulated Carcinoma from Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features (NIFTP)

Background: non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), which is considered as low-risk cancer, should be distinguished from the malignant invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Improved discrimination of NIFTPs from invasive EFVPTCs using a molecular biomarker test could provide useful insights into pre- and post-surgical management of the indeterminate thyroid nodule. Galectin-3 (Gal-3), a β-galactosyl-binding molecule in the lectin group, is involved in different biological functions in well differentiated thyroid carcinomas. The aim of this study was to determine whether Gal-3 expression as a diagnostic marker could distinguish indolent NIFTP from invasive EFVPTC on tissue specimens from surgical thyroid nodules. Methods: immunohistochemical (IHC) analysis of cytoplasmic and nuclear Gal-3 expression was performed in formalin-fixed paraffin-embedded (FFPE) surgical tissues in four specific diagnostic subgroups- benign nodules, NIFTPs, EFVPTCs and lymphocytic/Hashimoto’s thyroiditis (LTs). Results: cytoplasmic Gal-3 expression (mean ± SD) was significantly increased in invasive EFVPTCs (4.80 ± 1.60) compared to NIFTPs (2.75 ± 1.58, p < 0.001) and benign neoplasms (2.09 ± 1.19, p < 0.001) with no significant difference between NIFTPs and benign lesions (p = 0.064). The presence of LT enhanced cytoplasmic Gal-3 expression (3.80 ± 1.32) compared to NIFTPs (p = 0.016) and benign nodules (p < 0.001). Nuclear Gal-3 expression in invasive EFVPTCs (1.84 ± 1.30) was significantly higher than in NIFTPs (1.00 ± 0.72, p = 0.001), but similar to benign nodules (1.44 ± 1.77, p = 0.215), thereby obviating its potential clinical application. Conclusions: our observations have indicated that increased cytoplasmic Gal-3 expression shows diagnostic potential in distinguishing NIFTP among encapsulated follicular variant nodules thereby serving as a possible ancillary test to H&E histopathological diagnostic criteria when LT interference is absent, to assist in the detection of the invasive EFVPTC among such nodules.

Complementary role of p57kip2 immunostaining in diagnosing hydatidiform mole subtypes

Objectives Gestational trophoblastic disease comprises of a spectrum of pregnancy-related tumours which includes complete (CHM) and partial hydatidiform moles (PHM). Accurate diagnosis and subclassification of HM subtypes are crucial as prognosis differs. Histopathological examination using haemotoxylin and eosin (H&E) staining remains the basis for diagnosing HM, with only 80% accuracy. p57kip2 is a cyclin-dependent kinase inhibitor (CDKI) protein and is strongly paternally imprinted, being expressed from maternal allele. Therefore, complete mole (CHM) with only paternal genome has nearly absent expression of p57kip2 compared to partial mole (PHM) having both paternal and maternal genomes. This study is aimed to determine usefulness of p57kip2 immunohistochemistry (IHC) analysis in the diagnosis of HM subtypes. Methods A total of 82 archived paraffin embedded HM tissues with subtypes classified based on H&E staining – 39 (47.5%) CHM, 41 (50.0%) PHM and two (2.43%) unclassified molar pregnancy were retrieved. All tissue samples were subjected for p57kip2 IHC analysis and HM subtypes were then reclassified. Results A total of 66 cases (80.5%) were re-classified as CHM, 14 cases (17.1%) as PHM and two cases (2.4%) were decidual and cystic tissues. Analysis using p57kip2 immunostaining showed a diagnostic discrepancy of 33.0% from routine H&E staining and helps to improve the characterisation of the HM subtypes specifically at early gestations which have less distinctive morphologies. Conclusions IHC using p57kip2 monoclonal antibody should be considered as a routine ancillary test to H&E in improving the diagnosis of HM subtypes particularly in developing countries with limited resources.

TOMOGRAFÍA DE COHERENCIA ÓPTICA COMO MARCADOR PARA LAS ENFERMEDADES NEURODEGENERATIVAS DE ALZHEIMER Y PARKINSON.

Background: Optical coherence tomography (OCT) is an ancillary test used in retinal pathology. The objective of the present dissertation is to review literature regarding (OCT) and its importance as a biomarker in neurodegenerative Alzheimer’s and Parkinson’s disease, through an analysis of medical journal articles published between 2015 and 2019. Methods: A retrospective systematic review without meta-analysis of literature was carried out using observational research design, allowing to summarize the results of multiple primary investigations. Ten studies published between 2015 and 2019 regarding the application of OCT and ANGIO OCT in adult patients older than 60 years of age with preclinical Alzheimer’s disease (AD) or Parkinson’s disease (PD) with retinal microvascular abnormalities, were selected. Results: Areas of increased thickness of ganglion cell-inner plexiform layer (GCIPL) and nerve fiber layer (NFL) adyacent to the macula suggest that dynamic changes can occur as a result of AD progression. Thinning of the retina is present during early stages of PD. This correlates with disease severity and may be related to degeneration of dopaminergic neurons in the substantia nigra. Conclusion: Optical Coherence Tomography is a potential biomarker for AD and PD, and if these pathologies are suspected early, and if these pathologies are suspected early, it could be requested as diagnostic support.

Frequency of Psychosomatic-Prone Myofascial Pain Syndrome in Patients with Incurable Cancer and its Association with the Armchair Sign: A Secondary Analysis of A Prospective, Multicenter, Observational Clinical Study

Background Few studies have reported psychosomatic-prone functional damage in cancer patients. Because psychosomatic diseases are pathological conditions, it is difficult to identify their degrees. The armchair sign is a test used to assess voluntary muscle relaxation. This study aimed to evaluate the frequency of psychosomatic-prone functional damage in cancer patients and its association with the armchair sign. Methods This was a secondary analysis of a prospective, multicenter, observational clinical study. We evaluated the frequency of psychosomatic-prone myofascial pain syndrome (MPS) in patients with incurable cancer who were at the start of palliative care and how it is associated with the armchair sign. Moreover, we assessed the usefulness of the armchair sign for the diagnosis of psychosomatic-prone MPS. Results A total of 101 patients were enrolled from March 2018 to December 2018, of whom 44 met MPS diagnostic criteria. Of these, 27 patients (61.3%) had psychosomatic-prone MPS. There was a significant association between the armchair sign and psychosomatic-prone MPS (p = 0.002). Sensitivity and specificity were 40.7% (95% confidence interval: 18.0–63.4) and 100.0%, respectively. The area under the curve score was 0.704 (95% confidence interval: 0.553–0.855). Conclusions MPS in patients with incurable cancer has a high frequency of psychosomatic pathology. The armchair sign may be useful as an ancillary test for the diagnosis of psychosomatic-prone MPS. Trial registration: UMIN000031338. Registered 16 February 2018.