Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors.

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings.

Surgical Resection of Nasal Chondroma via open Rhinoplasty Approach: A rare case Presentation and Review of Literature.

Chondromas are benign tumors composed of mature hyaline cartilage tissue with well-defined boundaries that are commonly localised in the extremities with very few cases described in the head and neck region. We present a case of 57-year-old patient who consulted a specialist for an examination due to a change in the tip of the nose that persisted for the past 2 years. The clinical exam revealed a firm, tumor-altered tip of the nasal pyramid, with hyperemia of the skin above the mass. Biopsy was taken under local anesthesia; the histopathology analysis indicated a mesenchymal tumor producing the chondroid matrix suggestive of nasal type chondroma. Computerized tomography showed an ovoid, moderately inhomogeneous, sharply limited formation measuring 21 × 18 × 24 mm present mediosagitally at the top of the nasal pyramid. After preoperative preparation, the surgery was performed by open rhinoplasty approach. Tumor was completely excised with reconstruction of nasal septum and alar cartilage. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03661-0.

Meta-signature guided investigation of miRNA candidates as potential biomarkers of oral cancer.

OBJECTIVES: This study aimed to experimentally validate dysregulated expression of miRNA candidates selected through updated meta-analysis of most commonly deregulated miRNAs in oral cancer and to explore their diagnostic and prognostic potential. MATERIALS AND METHODS: Five miRNAs (miR-31-3p, miR-135b-5p, miR-18a-5p, miR-30a-5p and miR-139-5p) from updated meta-signature were selected for validation by qRT-PCR method in 35 oral cancer clinical specimens and adjacent non-cancerous tissue. RESULTS: Updated meta-analysis has identified 13 most commonly deregulated miRNAs in oral cancer. Seven miRNAs were consistently up-regulated (miR-21-5p, miR-31-3p, miR-135b-5p, miR-31-5p, miR-424-5p, miR-18a-5p and miR-21-3p), while five were down-regulated (miR-139-5p, miR-30a-3p, miR-375-3p, miR-376c-3p and miR-30a-5p). Increased expression of miR-31-3p and miR-135b-5p, and decreased expression of miR-139-5p and miR-30a-5p were confirmed in oral cancer compared to adjacent non-cancerous tissue. A three miRNAs combination (miR-31-3p, miR-139-5p and miR-30a-5p) gave the most promising diagnostic potential for discriminating oral cancer from non-cancerous tissue (AUC: 0.780 [95% CI: 0.673-0.886], p < 0.0005, sensitivity 94.3%, specificity 51.4%). High expression of miR-135b-5p, miR-18a-5p and miR-30a-5p was associated with poor survival (p = 0.003, p = 0.048, p = 0.016 respectively). CONCLUSION: miR-31-3p, miR-139-5p and miR-30a-5p panel was confirmed as a potential diagnostic biomarker when distinguishing oral cancer from non-cancerous tissue. miR-135b-5p, miR-18a-5p and miR-30a-5p might serve as potential biomarkers of poor survival of oral cancer patients.

Clinicopathological Analysis of 907 Major and Minor Salivary Gland Tumors.

PURPOSE: The frequency and types of salivary gland tumors show significant geographical variations. The most common are primary epithelial tumors, with pleomorphic adenoma and mucoepidermoid carcinoma being the most frequent. This study aims to analyze the clinicopathological data of patients with major and minor salivary gland (MiSG) tumors. METHODS: The retrospective study included all patients with major and MiSG tumors diagnosed and treated between January 2000 and January 2019. Files of 907 patients were reviewed and investigated for clinicopathologic features of major and MiSG tumors in Serbia. RESULTS: The majority of tumors were of epithelial origin. Pleomorphic adenoma was the predominant type of tumor, with 35.1% among all tumors on all sites. Adenoid cystic carcinoma and mucoepider-moid carcinoma (with 7.1% and 2.7%, respectively) were the most common malignant ones. The most common localization was the parotid gland. Minor salivary gland tumors comprised 16.43% of all salivary gland tumors in our series, the most common localization being the oral cavity. The results of our study are mostly consistent with the results of other previously published studies. CONCLUSIONS: The most important finding, worth emphasizing, is that the most common malignant major and MiSG tumor in our population is adenoid cystic carcinoma, rather than mucoepidermoid carcinoma, in all investigated localizations. In addition, the nasal cavity is the most common localization among malignant MiSG tumors.

Micro-scale assessment of bone quality changes in adult cadaveric men with congestive hepatopathy.

Congestive hepatopathy (CH) is a chronic liver disease (CLD) caused by impaired hepatic venous blood outflow, most frequently resulting from congestive heart failure. Although it is known that heart failure and CLDs contribute to increased risk for age-related fractures, an assessment of CH-induced skeletal alterations has not been made to date. The aim of our study was to characterize changes in bone quality in adult male cadavers with pathohistologically confirmed CH compared with controls without liver disease. The anterior mid-transverse part of the fifth lumbar vertebral body was collected from 33 adult male cadavers (age range 43-89 years), divided into the CH group (n = 15) and the control group (n = 18). We evaluated trabecular and cortical micro-architecture and bone mineral content (using micro-computed tomography), bone mechanical competence (using Vickers micro-hardness tester), vertebral cellular indices (osteocyte lacunar network and bone marrow adiposity), and osteocytic sclerostin and connexin 43 expression levels (using immunohistochemistry staining and analysis). Deterioration in trabecular micro-architecture, reduced trabecular and cortical mineral content, and decreased Vickers microhardness were noted in the CH group (p < 0.05). Reduced total number of osteocytes and declined connexin 43 expression levels (p < 0.05) implied that harmed mechanotransduction throughout the osteocyte network might be present in CH. Moreover, elevated expression levels of sclerostin by osteocytes could indicate the role of sclerostin in mediating low bone formation in individuals with CH. Taken together, these micro-scale bone alterations suggest that vertebral strength could be compromised in men with CH, implying that vertebral fracture risk assessment and subsequent therapy may need to be considered in these patients. However, further research is required to confirm the clinical relevance of our findings.

The altered osteocytic expression of connexin 43 and sclerostin in human cadaveric donors with alcoholic liver cirrhosis: Potential treatment targets.

Previous studies suggested that osteocyte lacunar network disruption could play a role in the complex pathophysiology of bone changes in aging and disease. Considering that particular research interest is lacking, we aimed to assess alcoholic liver cirrhosis (ALC)-induced changes in osteocyte lacunar network and bone marrow adiposity. Immunohistochemistry was conducted to assess changes in the micro-morphology of osteocyte lacunar network and bone marrow adiposity, and expression of connexin 43 and sclerostin in vertebral and femoral samples collected from 40 cadaveric men (age range between 44 and 70 years) divided into ALC group (n = 20) and control group (n = 20). Furthermore, the assessment of the potential association between bone changes and the severity of the hepatic disorder (given by Knodell's pathohistologic scoring) was conducted. Our data revealed fewer connexin 43-positive osteocytes per vertebral and femoral bone area (p < 0.01), suggesting defective signal transduction among osteocytes in ALC individuals. Moreover, we found an ALC-induced increase in the number of adipocytes in the vertebral bone marrow (p = 0.038). Considering significant associations between the severity of liver tissue disturbances and impaired functionality of osteocyte lacunar network (Pearson's correlation analyses, p < 0.05), we may assume that timely treatment of the liver disease may delay bone impairment. ALC induced an increase in osteocytic sclerostin expression (p < 0.001), suggesting its role in mediating low bone formation among ALC individuals. Hence, medicaments targeting low bone formation may be beneficial to attenuate the bone changes among ALC patients. However, future clinical studies are required to verify the therapeutic utility of these findings.

Mechano-structural alteration in proximal femora of individuals with alcoholic liver disease: Implications for increased bone fragility.

Although increased hip fracture risk is noted in patients with alcoholic liver disease (ALD), their femoral microstructural and mechanical properties were not investigated previously. The present study aimed to analyze the associations between subregional deteriorations in femoral mechano-structural properties and clinical imaging findings to explain increased femoral fracture risk among ALD patients. This study analyzed proximal femora of 33 male cadaveric donors, divided into ALD (n = 13, 57 ± 13 years) and age-matched control group (n = 20, 54 ± 13 years). After pathohistological verification of ALD stage, DXA and HSA measurements of the proximal femora were performed, followed by micro-CT and Vickers microindentation of the superolateral neck, inferomedial neck, and intertrochanteric region. Bone mineral density and cross sectional area of the femoral neck were deteriorated in ALD donors, compared with healthy controls (p < 0.05). Significant ALD-induced degradation of trabecular and cortical microstructure and Vickers microhardness reduction were noted in the analyzed femoral regions (p < 0.05). Still, the most prominent ALD-induced mechano-structural deterioration was noted in intertrochanteric region. Additionally, more severe bone alterations were observed in individuals with an irreversible stage of ALD, alcoholic liver cirrhosis (ALC), than in those with an initial ALD stage, fatty liver disease. Observed osteodensitometric and mechano-structural changes illuminate the basis for increased femoral fracture risk in ALD patients. Additionally, our data suggest bone strength reduction that may result in increased susceptibility to intertrochanteric femoral fracture in men with ALD. Thus, femoral fracture risk assessment should be advised for all ALD patients, especially in those with ALC.

The severity of hepatic disorder is related to vertebral microstructure deterioration in cadaveric donors with liver cirrhosis.

Patients with liver cirrhosis (LC) commonly suffer from osteoporosis and vertebral fracture, but data about their vertebral micro-architectural changes are still limited. This study aimed to evaluate the potential differences in trabecular micro-architecture of lumbar vertebrae between male LC patients and healthy controls, in relation to etiology and pathohistological scoring of the liver disorder. After pathohistological examination of liver tissue, micro-computed tomography was performed on the vertebral samples included into: alcoholic liver cirrhosis group (ALC; n = 16; age: 59 ± 8 years), non-alcoholic liver cirrhosis group (non-ALC; n = 15; age: 69 ± 10 years) and control group (n = 16; age: 58 ± 6 years). Our data showed significant impairment of the trabecular microstructure in the lumbar vertebrae from LC donors, regardless of the alcoholic/non-alcoholic origin of liver disorder, as illustrated by lower BV/TV, Tb.Th, and Tb.N compared with controls (p < .05). Moreover, depredation in trabecular micro-architecture was inversely associated with pathohistological scores (p < .05), indicating that severity of liver disorder could be an important predictor of reduced vertebral strength in LC. We noticed significant micro-architectural deterioration in the trabecular compartment of the lumbar vertebrae of male individuals with alcoholic and non-alcoholic LC, which was associated with the severity of the liver disease. Thus, clinical assessment of fracture risk should be advised for all LC patients, regardless of the alcoholic origin of liver cirrhosis. Additionally, adequate and timely treatment of liver disorder may decelerate the progression of bone impairment in LC patients.

Severe hepatotoxicity induced by efavirenz in a treatment-naïve, low body mass index HIV-infected, female patient with no hepatitis and other virus co-infections.

Combined antiretroviral therapy (cART) consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI), such as efavirenz, is still the first-line treatment in resource-limited settings. However, efavirenz has shown strong prominence of disadvantages with variance in plasma concentration and central nervous side effects. Our study presents HIV infected, drug naïve, female patient with relatively low BMI, CYP2B6 516G>T (rs3745274) genotype with high efavirenz plasma concentration. In this case report, the patient was admitted at the hospital 6 months after cART initiation with drug-induced severe hepatotoxicity. Furthermore, pathophysiological findings proved confluent parenchymal necrosis after aspiration liver biopsy, with mild to moderate inflammation in portal tracts with focal interface hepatitis. All other possible causes were excluded. Thus, we conclude that efavirenz has a potential harmful effect in patients with low BMI, specific genotyping and interindividual pharmacokinetics affecting high plasma concentration.