Anti-EGFR/BRAF-Tyrosine Kinase Inhibitors in Thyroid Carcinoma.

Alterations in significant genes located on chromosome 7 - including epidermal growth factor receptor (EGFR) and also v-Raf murine sarcoma viral oncogene homolog B (BRAF) as a mitogen-activated protein kinase (MAPK)  - combined or not with numerical imbalances of the whole chromosome (aneuploidy-polysomy) are crucial genetic events involved in the development and progression of malignancies. Identification of EGFR/BRAF-dependent specific somatic mutations and other mechanisms of deregulation (i.e., amplification) is critical for applying targeted therapeutic approaches [tyrosine kinase inhibitors (TKIs] or monoclonal antibodies (mAbs). Thyroid carcinoma is a specific pathological entity characterized by a variety of histological sub-types. Follicular thyroid carcinoma (FTC), papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC) represent its main sub-types. In the current review, we explore the role of EGFR/BRAF alterations in thyroid carcinoma in conjunction with the corresponding anti-EGFR/BRAF TKI-based novel therapeutic strategies for patients with specific genetic signatures.

The Landscape of Single Nucleotide Polymorphisms in Papillary Thyroid Carcinoma.

Thyroid carcinoma represents a leading malignancy among those derived from human endocrine systems. It comprises a variety of different histological subtypes, including mainly papillary carcinoma, follicular carcinoma, anaplastic carcinoma, and medullar carcinoma. A broad spectrum of genetic imbalances, comprising gross chromosomal (polysomy/aneuploidy) and specific gene (mutations, amplifications, deletions) alterations, has been reported. Interestingly, the role of isolated, specific gene polymorphisms, especially of the single nucleotide polymorphism (SNP) type, in thyroid carcinoma is under investigation. SNPs are the most common genetic variations in the genome. The current molecular review focuses on the impact of specific SNPs on the biological behavior of papillary thyroid carcinoma in their carriers.

P53 Suppressor Gene Tissue Microarray-based Protein Expression Analysis in Meningiomas.

BACKGROUND/AIM: Meningiomas represent the main intracranial primary central nervous system (CNS) tumour in adults worldwide. Oncogenes' over-activation combined with suppressor genes' silencing affect negatively the biological behavior of these neoplasms. This study aimed to explore the impact of p53 suppressor gene expression in meningiomas' clinic-pathological features based on a combination of sophisticated techniques. MATERIALS AND METHODS: Fifty (n=50) meningiomas were included in the study, comprising a broad spectrum of histopathological subtypes. An immunohistochemistry assay was applied on tissue microarray cores followed by digital image analysis. RESULTS: p53 protein over-expression (high staining intensity levels) was observed in 27/50 (54%) cases, whereas the rest (23/50-/46%) demonstrated moderate to low levels of the protein. p53 over-expression was statistically significantly correlated to the mitotic index of the examined cases (p-value=0.001). Interestingly, the atypical/anaplastic group of histotypes demonstrated the strongest p53 expression rates compared to the others (p-value=0.001). CONCLUSION: p53 overexpression is observed in a broad spectrum of meningiomas. High expression levels lead to an aggressive biological behavior of the malignancy (combined with increased mitotic rates), especially in atypical and anaplastic sub-types that also have a high recurrence rate.

ALK Protein Expression Patterns in Squamous Cell Carcinoma of the Oral Cavity.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by a broad spectrum of genomic imbalances, including gross chromosomal (polysomy/aneuploidy) ones as well as specific gene alterations. Aberrant expression of anaplastic lymphoma kinase (ALK) seems to be a useful molecular marker for discriminating patients based on genetic signatures in a variety of solid malignancies, such as lung carcinoma. Our aim was to analyze ALK protein expression patterns in a series of OSCCs. MATERIALS AND METHODS: Fifty (n=50) OSCC tissue sections were analyzed by implementing an ALK-based immunohistochemistry protocol. Digital image analysis was performed for measuring the corresponding protein expression levels. RESULTS: ALK overexpression was observed in 14/50 (28%) OSCC tissue sections, whereas the rest 36/50 (72%) demonstrated low expression levels. ALK expression was negatively associated with grade (p=0.027) and stage (p=0.0028) of the examined cases. CONCLUSION: Abnormal ALK expression in subsets of patients with OSCC seems to be related to an aggressive phenotype (advanced stage/progressive dedifferentiation). ALK protein overexpression may be used as a significant marker for applying targeted therapeutic regimens.

From delta to Omicron: S1-RBD/S2 mutation/deletion equilibrium in SARS-CoV-2 defined variants.

Coronavirus-related Severe Acute Respiratory Syndrome (SARS-CoV) in 2002/2003, Middle-East Respiratory Syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) affected negatively the national health systems' endurance worldwide. SARS-Cov-2 virus belongs to lineage b of beta-CoVs demonstrating a strong phylogenetic similarity with BatCoVRaTG13 type. Spike (S) glycoprotein projections -consisting of two subunits S1/S2- provide a unique crown-like formation (corona) on virion's surface. Concerning their functional role, S1 represents the main receptor-binding domain (RBD), whereas S2 is involved in the virus-cell membrane fusion mechanism. On Nov 26th 2021, WHO designated the new SARS-CoV-2 strain - named Omicron, from letter ''όµÎ¹κρον'' in the Greek alphabet - as a variant of concern (B.1.1529 variant). Potentially this new variant is associated with high transmissibility leading to elevated infectivity and probably increased re-infection rates. Its impact on morbidity/mortality remains under investigation. In the current paper, analyzing and comparing the alterations of SARS-CoV-2 S RNA sequences in the defined variants (Alpha to Omicron), we observed some interesting findings regarding the S1-RBD/S2 mutation/deletion equilibrium that maybe affect and modify its activity.

Impact of SARS-CoV-2 infection on oral carcinoma patients.

Coronavirus-related Severe Acute Respiratory Syndrome (SARS-CoV) in 2002/2003, Middle-East Respiratory Syndrome (MERS-Cov) in 2012/2013, and especially the current 2019/2020 Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) tested the national health systems' endurance worldwide. In order to fight this emergency situation, a variety of pharmaceutical companies focused on the design and development of efficient vaccines that are considered necessary for providing a level of normalization in totally affected human social-economical activity worldwide. COVID-19 led to an increased uncertainty in the field of oncological patients' management disrupting the normal conditions of therapeutic and monitoring procedures. In the current article, we explored the impact of SARS-CoV-2 infection on oral carcinoma patients. We observed COVD-19 pandemic negatively affects the normality regarding early diagnosis and optimal management (surgical operation, post-operational follow up/monitoring) in HNSCC/OSCC patients. Understanding the involvement of SARS-CoV-2 in the progression of malignancies is the first critical step for targeting the virus by efficient monoclonal antibodies and vaccines.

Mutational landscape in Uveal Melanoma.

Gross chromosomal and specific gene alterations are genetic aspects that are involved in rise, progression, and metastatic expansion of malignances. Concerning Uveal melanoma (UM), a variety of chromosome and gene functional and numerical imbalances in crucial molecular pathways such as cell cycle regulation, signaling transduction, apoptosis or angiogenesis have been identified and explained. UM is the most common primary ocular malignancy demonstrating increased rates, especially in middle-aged white (Caucasian) populations. Chronic exposure to ultraviolet rays/sunlight, race, gender (males), or some familial hereditary syndrome in sub-groups of patients are major factors correlated to increased risk for UM rise and progression. Specific genetic signatures at the level of chromosomal instability (CI) or at the gene mutations status characterize sub-groups of patients affecting the biological behaviour of the tumour leading to aggressive phenotypes (advanced stage-distant metastases, poor response, and survival rates). Sporadic or hereditary mediated mutations in genes including BAP1, EIF1AX, GNA11, GNAQ CHEK2, PALB2, SMARCE1, MBD4, MSH6 and MLH1. In the current molecular review, we present specific mutations -as a landscape- that are implicated in UM genetic substrate and create a variety of genetic signatures in the corresponding patients.

Variation of Marginal Mandibular Nerve in a Caucasian Male Cadaver: A Study Using the Anatomage Table.

Anatomage (Anatomage, Inc., San Jose, CA) is a modern method for studying anatomy. It is a state-of-the-art method used for the representation of the structure of the human body. In our study, we examined the seventh cranial nerve of a male Caucasian cadaver using an Anatomage Table in the Anatomy Department of the School of Medicine, National and Kapodistrian University, Athens, Greece. After exiting the skull from the stylomastoid foramen, the facial nerve divided into the temporofacial and cervicofacial main branches. The cervicofacial branch divided into its own branches, including the marginal mandibular nerve (MMN), which ran within the investing (superficial) layer of the deep cervical fascia. We found a variation of the course of the marginal mandibular branch of the facial nerve. In the area of the lower border of the mandible, where the MMN actually crossed the facial artery and vein, it appeared to run deeper than both of those vessels, rather than running superficially. This seemed to be a rare variation of the location of the MMN relative to the facial vessels, which suggested that extra care is essential in surgical approaches within this area.

Hypoglossal Nerve: Anatomy, Anatomical Variations Comorbidities and Clinical Significance.

We review the anatomical variations of the hypoglossal nerve and their surgical and clinical significance, and we report multiple diseases that affect function of the nerve leading to paresis, either unilateral or bilateral. The hypoglossal nerve is the 12th cranial nerve, and knowledge of the detailed anatomy and relationship with critical structures is of paramount importance in neurosurgery, head and neck surgery, and vascular surgery. Numerous studies have depicted conventional landmarks in the cervical part of the hypoglossal nerve, but their findings have not been consistent reliable. We analyze and review these critical landmarks used to identify and preserve the hypoglossal nerve during surgery and to minimize iatrogenic complications in head and neck, neurosurgical, and vascular procedures. We performed an online database search during January and February 2019 to pinpoint the diseases that affect function of the nerve. According to this literature review, apart from iatrogenic injury during surgery, the most frequently observed cause of paresis is pressure due to the presence of tumours and head injury. Furthermore, motor neuron degenerative conditions, such as amyotrophic lateral sclerosis, multiple sclerosis or tooth infection and presence of an aberrant vessel in the hypoglossal canal can affect the function of the nerve.

Uterus Transplantation as a Therapy Method in Mayer-Rokitansky-Küster-Hauser Syndrome.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is the most common cause of uterine aplasia (underdevelopment or absence) at a frequency estimated to be worldwide of 1/4500 births of new-born female infants. This is a literature review aiming to determine the sufficiency of the uterine transplantation (UTx) method as a therapeutic protocol for the MRKH syndrome. Online searches were carried out in PubMed, Embase, CINAHL and Google scholar databases, during January and February 2019. The search included a combination of the various terms (see key words) as well as a combination of these terms in Greek and English so as to identify and display articles that would be as close as possible to the subject of research. The online search yielded 95 articles. Eighty-five of these were considered as eligible and possible sources from the title and abstract presented but later were excluded, whereas 10 of them were selected to be included in the literature review. The literature review results showed that two therapeutic methods that are now successfully applied are the Vecchietti method and the Davydov method, which is the latest and less invasive technique but with equally if not improved immediate results. However, this treatment is not adequate to satisfy or provide a solution for the reproduction requirements of this patient group. The UTx proved sufficient. Although uterus transplant could be considered the ideal solution for the management of infertility and the satisfaction of the reproductive and sexual needs of women with MRKH syndrome, since the first successful pregnancy after uterine transplantation is a reality in the recent years, it is early days to be considered as a safe mode of management.

First experiences with patient safety initiatives in Greek rural primary care. Action research by the LINNEAUS collaboration on patient safety in primary care.

BACKGROUND: Accreditation of primary care organizations within Greece is still in its infancy. Our task in Greece was to attempt to introduce a patient safety initiative in a local area, focusing on developing minimum standards for accreditation, assess whether a pragmatic approach would engage physicians, and provide evidence of improvement. OBJECTIVE: To use monitoring of clinical performance as the basis for the launch of an accreditation system for primary care in Greece and to report on the process and lessons learnt. METHODS: An established set of clinical indicators for patient safety was introduced in five Greek primary health centres. A web-based platform, for reporting practitioners' scores on the selected indicators, was used to record the activity of the practitioners. RESULTS: There was considerable variation in the use of clinical indicators by individual GPs. Following the intervention, the reporting on the indicators had increased while the scores on indicators only increased slightly. However, GPs engaged with the process and recognized its relevance to improving patient safety. CONCLUSION: We successfully piloted a means of engaging with GPs to improve patient safety using established indicators even where there was limited infrastructure to support such initiatives.