Galectin-3 performance in histologic and cytologic assessment of thyroid nodules. A systematic review and meta-analysis

The literature on Galectin-3 (Gal-3) was systematically reviewed to achieve more robust information on its histologic reliability in identifying thyroid cancers and on the concordance between Gal-3 test in histologic and cytologic samples. A computer search of the PubMed and Scopus databases was conducted by combinations of the terms thyroid and Gal-3. Initially, 545 articles were found and, after their critical review, 52 original papers were finally included. They reported 8172 nodules with histologic evaluation of Gal-3, of which 358 with also preoperative FNAC Gal-3 assessment. At histology, Gal-3 sensitivity was 87% (95% confidence intervals [CI] from 86% to 88%), and specificity 87% (95% CI from 86% to 88%); in both cases, we found heterogeneity (I285% and 93%, respectively) and significant publication bias (p < 0.001). The pooled rate of positive Gal-3 at fine needle aspiration (FNAC) among cancers with histologically proven Gal-3 positivity was 94% (95% CI from 89% to 97%), with neither heterogeneity (I214.5%) nor bias (p = 0.086). These data show high reliability of Gal-3 for thyroid cancer at histology, while its sensitivity on FNAC samples is lower. The limits of cytologic preparations and interpretation of Gal-3 results have to be solved

Cancer rate of the indeterminate lesions at low or high risk according to italian system for reporting of thyroid FNA

Background: Italian consensus for the classification and reporting of thyroid cytology (ICCRTC) has been used in almost all Italian institutions since 2014. High reliability of ICCRTC in classifying low and high risk indeterminate nodules (Tir 3A and Tir 3B, respectively) was demonstrated. Here we reviewed our casuistry of thyroid indeterminate lesions to analyze the histologic outcome. Methods: All lesions undergone FNA and final histology at S. Andrea Hospital of Rome after a cytologic assessment of Tir 3A and Tir 3B, according to ICCRTC, were included in the study. Results: A number of 157 indeterminate FNA was found after the introduction of ICCRTC. Of these, 75 undergone surgery and were finally included for the study. At histology we found a 33.3% of cancers and a 67.7% of benign lesions. Out of the overall series, 25 were classified as Tir 3A and 50 as Tir 3B. Cancer rate observed in Tir 3A (1/25, 4%) was significantly (p = 0.0002) lower than that of Tir 3B (24/50, 48%). No significant difference was found in age and size between the two subcategories. Conclusions: We confirm in our series that Italian consensus for the classification and reporting of thyroid cytology allows to discriminate indeterminate lesions at low and high risk of malignancy

Detection rate of FNA cytology in medullary thyroid carcinoma. a meta-analysis

Background: The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. Research Design and Methods: A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. Results: Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. Conclusions: The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results. © 2014 John Wiley & Sons Ltd

The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma: a meta-analysis

Thyroid imaging reporting and data systems (TIRADS) are used to stratify the malignancy risk of thyroid nodule by ultrasound (US) examination. We conducted a meta-analysis to evaluate the pooled cancer prevalence and the relative prevalence of papillary, medullary, follicular thyroid cancer (PTC, MTC, and FTC) and other malignancies among nodules included in studies evaluating their performance. Four databases were searched until February 2020. Original articles with at least 1000 nodules, evaluating the performance of at least one TIRADS among AACE/ACE/AME, ACR-TIRADS, ATA, EU-TIRADS, or K-TIRADS, and reporting data on the histological diagnosis of malignant lesions were included. The number of malignant nodules, PTC, FTC, MTC and other malignancies in each study was extracted. For statistical pooling of data, a random-effects model was used. Nine studies were included, evaluating 19,494 thyroid nodules. The overall prevalence of malignancy was 34% (95%CI 21 to 49). Among 6162 histologically proven malignancies, the prevalence of PTC, FTC, MTC and other malignancies was 95%, 2%, 1%, and 1%, respectively. A high heterogeneity was found for all the outcomes. A limited number of studies generally conducted using a retrospective design was found, with possible selection bias. Acknowledging this limitation, TIRADSs should be regarded as accurate tools to diagnose PTC only. Proposed patterns and/or cut-offs should be revised and other strategies considered to improve their performance in the assessment of FTC, MTC and other malignancies

Predicting the Role of DNA Polymerase β Alone or with KRAS Mutations in Advanced NSCLC Patients Receiving Platinum-Based Chemotherapy

: Clinical data suggest that only a subgroup of non-small cell lung cancer (NSCLC) patients has long-term benefits after front-line platinum-based therapy. We prospectively investigate whether KRAS status and DNA polymerase β expression could help identify patients responding to platinum compounds. Prospectively enrolled, advanced NSCLC patients treated with a first-line regimen containing platinum were genotyped for KRAS and centrally evaluated for DNA polymerase β expression. Overall survival (OS), progression-free survival (PFS), and the objective response rate (ORR) were recorded. Patients with KRAS mutations had worse OS (hazard ratio (HR): 1.37, 95% confidence interval (95% CI): 0.70-2.27). Negative DNA polymerase β staining identified a subgroup with worse OS than patients expressing the protein (HR: 1.43, 95% CI: 0.57-3.57). The addition of KRAS to the analyses further worsened the prognosis of patients with negative DNA polymerase β staining (HR: 1.67, 95% CI: 0.52-5.56). DNA polymerase β did not influence PFS and ORR. KRAS may have a negative role in platinum-based therapy responses in NSCLC, but its impact is limited. DNA polymerase β, when not expressed, might indicate a group of patients with poor outcomes. KRAS mutations in tumors not expressing DNA polymerase β further worsens survival. Therefore, these two biomarkers together might well identify patients for whom alternatives to platinum-based chemotherapy should be used

Performance of Fatty Liver Index in Identifying Non-Alcoholic Fatty Liver Disease in Population Studies. A Meta-Analysis

Background. Fatty liver index (FLI) is a non-invasive tool used to stratify the risk of non-alcoholic fatty liver disease (NAFLD) in population studies; whether it can be used to exclude or diagnose this disorder is unclear. We conducted a meta-analysis to assess the prevalence of NAFLD in each FLI class and the performance of FLI in detecting NAFLD. Methods. Four databases were searched until January 2021 (CRD42021231367). Original articles included were those reporting the performance of FLI and adopting ultrasound, computed tomography, or magnetic resonance as a reference standard. The numbers of subjects with NAFLD in FLI classes <30, 30–60, and 60, and the numbers of subjects classified as true/false positive/negative when adopting 30 and 60 as cut-offs were extracted. A random-effects model was used for pooling data. Results. Ten studies were included, evaluating 27,221 subjects without secondary causes of fatty liver disease. The prevalence of NAFLD in the three FLI classes was 14%, 42%, and 67%. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for positive results, likelihood ratio for negative results, and diagnostic odds ratio were 81%, 65%, 53%, 84%, 2.3, 0.3, and 7.8 for the lower cut-off and 44%, 90%, 67%, 76%, 4.3, 0.6, and 7.3 for the higher cut-off, respectively. A similar performance was generally found in studies adopting ultrasound versus other imaging modalities. Conclusions. FLI showed an adequate performance in stratifying the risk of NAFLD. However, it showed only weak evidence of a discriminatory performance in excluding or diagnosing this disorder

Liquid and softgel levothyroxine use in clinical practice: state of the art

Levothyroxine is recognized as the treatment of choice for hypothyroidism. So far, the tablet levothyroxine has been the formulation almost exclusively used, even though an optimal daily dose of levothyroxine has been unsuccessfully sought and a consensus not achieved. Due to progressive use of a more individually tailored levothyroxine dose, increasing evidence has instead displayed that many gastrointestinal disorders, polypharmacy, and food interference may raise the daily levothyroxine requirement. In recent years, alternative levothyroxine formulations have become available and have rapidly gained attention because of their pharmacokinetic properties. This study aims to provide an overview regarding the use of softgel capsule and/or liquid levothyroxine solution while performing a review of published studies about such topic. A comprehensive computer literature search of the PubMed/MEDLINE, Scopus, and Google Scholar databases has been conducted to find published articles on this topic. The search algorithm was based on the combinations of the following terms: “oral solution” or “soft gel” or “liquid”, and “levothyroxine”. The computer search resulted in 75 articles; through a critical review of such titles and abstracts and a screening of their references lists, the review included 18 original articles relating to 800 patients treated with alternative formulations. Despite some limits, the results obtained using softgel and liquid levothyroxine were consistent with each other. In selected categories of levothyroxine-treated patients (pediatric, suffering from hypo-achlorhydria, polypharmacy, undergone bariatric surgery, fed through enteric tube) these new formulations have shown promising attributes in improving a treatment that needs to be individually tailored

Utility of the Ratio between Lactate Dehydrogenase (LDH) Activity and Total Nucleated Cell Counts in Effusions (LDH/TNCC Ratio) for the Diagnosis of Feline Infectious Peritonitis (FIP)

Background: We tested the hypothesis that the ratio between lactate dehydrogenase activity (LDH) and total nucleated cell counts (TNCC) in effusions may be useful to diagnose feline infectious peritonitis (FIP). Methods: LDH/TNCC ratio was retrospectively evaluated in 648 effusions grouped based on cytology and physicochemical analysis (step 1), on the probability of FIP estimated by additional tests on fluids (step 2) or on other biological samples (step 3, n = 471). Results of different steps were statistically compared. Receiver Operating Characteristic (ROC) curves were designed to assess whether the ratio identify the samples with FIP “probable/almost confirmed”. The cut-offs with the highest positive likelihood ratio (LR+) or Youden Index (YI) or with equal sensitivity and specificity were determined. Results: A high median LDH/TNCC ratio was found in FIP effusions (step1: 2.01) and with probable or almost confirmed FIP (step 2: 1.99; 2.20 respectively; step 3: 1.26; 2.30 respectively). The optimal cut-offs were 7.54 (LR+ 6.58), 0.62 (IY 0.67, sensitivity: 89.1%; specificity 77.7%), 0.72 (sensitivity and specificity: 79.2%) in step 2 and 2.27 (LR+ 10.39), 0.62 (IY 0.65, sensitivity: 82.1%; specificity 83.0%), 0.54 (sensitivity: 82.1%; specificity 81.9%) in step 3. Conclusions: a high LDH/TNCC ratio support a FIP diagnosis

BRAF-mutated carcinomas among thyroid nodules with prior indeterminate FNA report: A systematic review and meta-analysis

Background Several molecular analyses have been investigated for risk stratification of thyroid nodules, with a particular focus on the V600E mutation of the BRAF gene [BRAF(V600E)]. To date, there is no high-level evidence supporting or refuting a role for BRAF analysis in thyroid nodules with prior indeterminate cytology. To obtain more robust evidence, we reviewed and meta-analysed data from published articles. Research Design and Methods A comprehensive literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted using the terms ‘BRAF’, ‘thyroid’ and ‘indeterminate’. The search was updated until March 2015, and references of the retrieved articles were also screened. Only original articles reporting BRAF mutation testing within nodules with indeterminate FNA were eligible for inclusion. Results The literature search revealed 82 articles, of which 8 were eligible for the study. Five studies were prospective and three retrospective. The majority of authors analysed BRAF mutations in FNA samples which were classified by the British or Bethesda system. Of the initial series of studies, a pooled number of 1361 cases were achieved of which 43 were BRAF mutated. Overall, the BRAF mutation rate was 46% (95% CI: 1–108%), ranging from 0 to 229%. When we included only histological series, 978 thyroid nodules were found. Of these, 245 were cancers. Conclusions A very low rate of lesions with indeterminate cytology are BRAF mutated. Thus, the role of this biomarker to detect or exclude cancers in patients with such FNA reports is marginal and should be reconsidered in guideline