Search Results (81)

Background: Burnout is increasingly being recognized as a contributory factor to the erosion of a positive psychological state. Studies have examined the relationship between burnout and various inflammatory markers such as IL-1, IL-6, and TNF-alpha. Burnout is also associated with increased systemic inflammation along a continuum of symptom severity. This protocol is for a scoping review looking at the link between burnout, inflammatory markers, and cardiovascular risks or diseases. Methods: This study will be based on the preferred reporting items for systematic reviews and meta-analyses guidelines/checklists and the report of the review will be based on the same guideline. The study seeks to address the following principal questions. (i) What are the relevant inflammatory biomarkers that mediate cardiovascular risk factors in burnout? (ii) How do inflammatory biomarkers mediate cardiovascular risk factors in burnout? The outputs obtained from the literature search will be deduplicated using the Rayyan software. Results: We would create table summaries of findings to inform a narrative synthesis of the evidence from the papers included. Conclusion: The review article would help to concisely synthesize the available evidence on the relationship between burnout, inflammatory markers, and cardiovascular diseases. Full article

The study aimed to compare 15 cases of mucoepidermoid carcinoma (MEC) and 15 cases of hyalinizing clear cell carcinoma (HCCC) using immunohistochemical staining and molecular analysis. Thirty samples were examined, and markers, including p63, CK5/6, SOX10, CK7, ATF1, and FISH probes specific to EWSR1 and MAML2, were used. Clear cell differentiation was observed in all MEC cases to some extent, with clear cell MEC showing the most prominent findings. Clear cell features were also present in conventional MEC, oncocytic MEC, and Warthin-like MEC, although to a lesser extent. The majority of cases were classified as low-grade MECs. MAML2 rearrangement was detected in all cases (except cases 11 and 14), while EWSR1 rearrangement was observed in a single case of clear cell MEC. These findings helped identify distinct subtypes within the mucoepidermoid carcinoma spectrum. The study emphasized the importance of utilizing immunohistochemical profiles, histopathological features, and molecular analysis for accurate diagnosis and classification of salivary gland neoplasms. HCCC was also discussed, and ATF1 was proposed as a marker to distinguish HCCC from morphologically similar neoplasms. The study concluded that a comprehensive approach combining immunohistochemistry, histopathology, and clinical correlation is essential for accurate diagnosis and classification, considering the variable expression of markers and potential overlap with other tumor types. Full article

Background: Understanding the distribution of HPV types in cervical cancer cases is crucial for evaluating the effectiveness of HPV screening and vaccination in reducing cervical cancer burden. This study aimed to assess genotype prevalence in the pre-vaccine era among 178 cervical cancer cases detected during a 20-year screening period in Northern Norway and compare the potential efficacy of HPV vaccines in preventing cervical cancer. Methods: A total of 181 formalin-fixed paraffin-embedded (FFPE) tissue samples from non-vaccinated women diagnosed with cervical cancer between 1995 and 2015 in Troms and Finnmark, Norway, were analyzed using a 45-type HPV DNA test. The results were compared to a 7-type HPV mRNA test targeting oncogenic types included in the nonavalent HPV vaccine. Results: Invalid HPV test results were observed in 1.7% (3/181) of the samples and were subsequently excluded from further analysis. Among the remaining cases, 92.7% (165/178) tested positive for HPV using any test combination. HPV DNA was detected in 159 cases (89.3%), while HPV mRNA was detected in 149 cases (83.7%). The most prevalent HPV types were 16 and 18, responsible for 70.8% of the cases, with the nonavalent vaccine types accounting for 86.6% of cases. HPV 35 was identified in eight cases (4.5%). Conclusion: The bivalent/quadrivalent HPV vaccines have the potential to prevent 76.4% (126/165) of HPV-positive cervical cancer cases, while the nonavalent vaccine could prevent 93.3% (154/165) of cases. Tailoring screening strategies to target HPV types with the highest oncogenic potential may improve cervical cancer detection and enable targeted interventions for high-risk individuals. The use of a 7-type HPV mRNA test holds promise as an advantageous approach. Full article

Foundation Medicine^® testing is a next-generation sequence (NGS)-based platform that allows clinicians to obtain the comprehensive genomic profiling (CGP) of several cancers. By using NGS approaches, relevant genomic alterations can be identified in a short timeframe, providing guidance to diagnostic and therapeutic decisions. This study reports the implementation of three commercially available Foundation Medicine^® tests in a Portuguese institution and explores the genomic alterations identified. Data obtained from 72 patients tested with Foundation Medicine^® between July 2017 and December 2020 were analysed retrospectively. A total of 290 gene alterations were identified, and TP53 was the gene most frequently altered. Among the 67 successfully profiled samples, 37.3% presented a potentially actionable variation. Breast carcinoma represented the most frequent tumour-carrying variation that can be targeted using currently approved drugs. A limited number of potentially actionable variants using approved drugs was found in this study; however, the genomic information provided by Foundation Medicine^® may help clinicians in directing cancer patients into clinical trials or to off-label treatments. Full article

Colorectal cancer is one of the most prevalent cancers nowadays. In the metastatic setting, diagnosis and treatment have relied on tumor tissue analysis. However, the different limitations of this approach have recently opened the door to the introduction of liquid biopsy in the clinical setting. Liquid biopsy provides real-time information about the tumor and its heterogeneity in a simple, non-invasive, and repeatable way. There are several analytes that can be sought: exosomes, circulating tumor cells, and circulating tumor DNA, showing promising results in the areas of early detection, minimal residual disease, prognosis, or response to treatment. Here, we review the clinical applications of liquid biopsy in advanced colorectal cancer patients, focusing on metastatic diagnosis, prognostic assessment, drug sensitivity, treatment response, and acquired resistance monitoring. Full article

The detection of driver oncogenic variants and the recent identification of tumor-agnostic genomic biomarkers has driven the use of comprehensive genomic profiling (CGP) for disease diagnosis, prognosis, and treatment selection. The Oncomine™ Comprehensive Assay Plus (OCA+) panel uses DNA and RNA to detect single nucleotide variants (SNVs), small insertions/deletions (Indels), and structural variants (SVs) across 501 genes. Moreover, microsatellite instability (MSI), tumor mutational burden (TMB), and homologous recombination deficiency (HRD) status are assessed in a single workflow. Herein, we present the analytical validation and clinical utilization of OCA+. By using commercial reference materials, we found good analytical sensitivity, specificity, and precision for all biomarkers analyzed. The limit of detection (LoD) was validated for SNVs and Indels at 4%, except for Indels located in homopolymeric regions, where the LoD was 10%. An additional set of 81 tumor samples, including cytology smears, were sequenced to assess the clinical utility of the OCA+ across different tumor types. Among the clinical cohort, OCA+ demonstrated 100% accuracy, sensitivity, and specificity for all biomarkers analyzed, except for MSI assessment of endometrial cancer cases, where 83% accuracy and 67% sensitivity were achieved, compared to PCR and IHC. The validation of accuracy and robustness of this assay supports the OCA+’s utility for solid tumor CGP. Full article

Osteosarcoma (OS) is a primary malignant bone tumour that usually occurs in children and adolescents. OS is a highly aggressive tumour type with a propensity for local invasion and systemic early metastasis to the lungs or other bones. According to the World Health Organization, there are different subtypes of OS, including conventional OS (osteoblastic, chondroblastic, fibroblastic), telangiectatic OS, low-grade OS, small-cell OS, parosteal OS, periosteal OS, and high-grade surface OS. In this mini review, we will discuss the background of OS and histopathological patterns and clinical behaviour of the disease. Understanding the subtypes of OS and their pathogenesis is crucial for developing more precise and effective therapies for OS patients. Full article

Adenoid cystic carcinoma (AdCC) is known to behave differently based on its location, histologic features, and molecular profile. Despite this understanding, efforts to use these molecular findings to develop personalized treatments have not yet been successful. The purpose of this retrospective study is to examine the molecular characteristics of AdCC with various histologic features in three different locations. A reference group of 20 classic cribriform AdCC cases from the parotid gland was included, along with 10 salivary AdCCs (Group 1), 10 sinonasal AdCCs with hyalinization (Group 2), and 10 solid mammary AdCCs with basaloid features (Group 3). Tissue samples were processed and tested using various molecular techniques, and the Wilcoxon signed-rank test was used to compare the different groups. Molecular data were obtained for both common and rare cases of sinonasal, salivary, and mammary AdCCs, revealing differences in molecular features depending on the tumor’s location. The molecular profile of the AdCCs in the experimental group varied depending on the site, with MYB gene rearrangements being common in all cases. We report the first MYB::KMT2C/D fusions in a subset of salivary AdCCs and sinonasal AdCCs but not in mammary adenoid cystic carcinoma with basaloid features. We conclude that co-occurring genetic alterations may vary among different sites and may have implications for the prognosis and treatment plan of AdCC. More research is needed to fully understand the mechanisms of KMT2C and KMT2D mutations in the development and progression of head and neck cancer, including their interactions with the NOTCH pathway. Full article

According to the ESMO and ASCO clinical guidelines, the main role of liquid biopsy in EGFR+ advanced NSCLC patients is represented by T790M detection after erlotinib/gefitinib/afatinib progression. However, the general international expert consensus regards osimertinib as the preferred upfront treatment in this setting; therefore, this role has been scaled back in recent years. As of today, liquid biopsy has no ASCO or ESMO recommendation following first-line osimertinib; in the same vein, no targeted therapy has received ASCO or ESMO recommendation following post upfront Osimertinib progression. However, this standard could change in the near future. Therefore, adopting a clinical point of view, this paper aims to provide a comprehensive review on the previous, the current and the possible future role of liquid biopsy in the framework of the diagnostic–therapeutic algorithm of EGFR+ advanced NSCLC. Full article

Background: A plethora of data supports HPV-based screening to be the preferred strategy for cervical cancer prevention. The shift to a more sensitive first-line test brings the need of effective triage up for discussion. Currently, most algorithms apply cytology as a triage of HPV-DNA positive women. This study compared the performance of a 7-type HPV-mRNA test to cytology. Methods: From 1 January 2019 until 31 December 2021, cervical samples from 58,029 women were examined at the University Hospital of North Norway. A total of 30.5% (17,684/58,029) fulfilled the criteria for HPV-DNA primary screening. All positive samples were triaged by cytology and followed-up according to national guidelines through 2022. Additionally, a 7-type HPV-mRNA test was applied. The study endpoint was a histologically confirmed high-grade lesion (CIN2+). Results: A total of 5.6% (990/17,684) had positive HPV-DNA test, 97.2% (962/990) with valid HPV-mRNA results. A total of 55.5% (534/962) had abnormal cytology (ASC-US+), and 35.1% (338/962) had a positive HPV-mRNA test. A total of 13.9% (134/962) had CIN2+. The sensitivity (CIN2+) of cytology versus the HPV-mRNA test was 76.1% (102/134) versus 73.1% (98/134), p = 0.67. The specificity was 47.8% (396/828) versus 71.0% (588/624), p < 0.001. PPV was 19.1% (102/534) and 29.0% (98/338), p < 0.001, respectively. The number of colposcopies per CIN2+ detected by cytology and HPV-mRNA test was 5.2 and 3.1. Conclusion: The 7-type HPV mRNA test was significantly more specific than cervical cytology in a triage of HPV-DNA positive women. Using this biomarker as the threshold for colposcopy may better balance the benefits and harms of screening. Full article

Genetic and drug sensitivity assays on primary cultures are not only of basic but also of translational interest and could eventually aid oncologists in the selection of treatments. However, cancer cells need to be identified and differentiated from the non-tumor cells always present in primary cultures. Also, successive passages can change the proportions of these two subpopulations. In this study, we propose fluorescence in situ hybridization (FISH) analysis on cell smears to determine the presence of tumor cells in primary cultures obtained from patients carrying translocations or copy number gains. FISH proved to be an easy, fast, economic, and reliable method of characterizing cell populations, which could be used repeatedly at different passages to monitor variations and to confirm the maintenance of translocations and copy number gains throughout the culture process. Full article

Somatic MET exon 14 skipping mutations (MET ex14) are targetable driver mutations for non-small cell lung cancer (NSCLC), responsive to MET inhibitors. Objective: This study seeks to further characterize the clinicopathologic features and mutational profile of MET ex14 variant NSCLC. Design: Retrospective review of all MET ex14 tested NSCLC. Testing for selected BRAF, EGFR, HER2, KRAS, and MET mutations was performed using a clinically validated NGS assay, followed by MiSeq sequencing. Variants were classified as significant (Tier1/2) or variants of uncertain significance (VUS) per 2017 AMP/ASCO/CAP Joint Consensus Guidelines. PD-L1 expression was assessed by immunohistochemistry. Results: Of 2296 NSCLCs tested between 2017-7/2019, MET ex14 variants were present in 44 (1.9%). A total of 32 of 44 variants were MET exon 14 skipping, while the other 12 mutations were significant missense (3) or VUS (9). Of nine VUS, five were adjacent to the canonical splice site and likely to impact splicing. Four cases had concomitant mutations. Of 35 cases with known clinical staging, stage 1–2 = 20 (57%), stage 3 = 3 (9%), and stage 4 = 12 (34%). Of 19 resected NSCLSs, histological types and growth pattern included 7 lepidic pattern-predominant. A high percentage of tumors with MET ex14 mutations are positive for PD-L1, and the percentage of cases with PD-L1 expression >50% trends higher in more advanced disease. Conclusions: Most MET variants identified in our cohort (73%) are MET ex14 skipping. The prevalence of MET ex14 variants is 1.9%, and a large percentage of tumors has lower clinical stage and less aggressive pathologic features. Full article

Lung cancer is one of the most common cancers and a leading cause of cancer-related mortality in Malaysia. This analysis aimed to evaluate the prevalence of actionable and common mutations, as well as co-mutations frequently occurring with EGFR variants in lung cancer. Mutational profiling of lung tumour samples was performed using next generation sequencing (NGS) panels at the Subang Jaya Medical Centre laboratory. A total of 469 lung tumour samples referred from several medical facilities in Malaysia were analysed and 84% were of the adenocarcinoma subtype. The three most frequent mutations found were EGFR (46.5%), TP53 (37.5%) and KRAS (14.3%). Actionable mutations with approved drug targets for lung cancer were detected in 63.5% of patient samples. Among patients with EGFR mutations, deletions in exon 19 were detected in 44.5% and p.L858R in 38.5% of samples. The most common co-mutations for samples with EGFR mutations were found in the TP53 gene (38.1%). A median turnaround time (TAT) of 3 working days was achievable with an automated NGS platform. NGS testing can provide valuable information on the mutational landscape and the prevalence of common or actionable mutations present in lung cancer patients. This real-world experience demonstrates the high percentage of actionable mutations detected and highlights the value of NGS testing in a clinical diagnostic setting. Full article