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.

In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections.

Bacterial biofilms play an important role in the pathogenesis of chronic upper respiratory tract infections. In addition to conventional antimicrobial therapy, N-acetyl-L-cysteine (NAC) and propolis are dietary supplements that are often recommended as supportive therapy for upper respiratory tract infections. However, no data on the beneficial effect of their combination against bacterial biofilms can be found in the scientific literature. Therefore, the aim of our study was to investigate the in vitro effect of N-acetyl-L-cysteine (NAC) and dry propolis extract in fixed combinations (NAC/dry propolis extract fixed combination) on biofilm formation by bacterial species isolated from patients with chronic rhinosinusitis, chronic otitis media, and chronic adenoiditis. The prospective study included 48 adults with chronic rhinosinusitis, 29 adults with chronic otitis media, and 33 children with chronic adenoiditis. Bacteria were isolated from tissue samples obtained intraoperatively and identified using the MALDI-TOF Vitek MS System. The antimicrobial activity, synergism, and antibiofilm effect of NAC/dry propolis extract fixed combination were studied in vitro. A total of 116 different strains were isolated from the tissue samples, with staphylococci being the most frequently isolated in all patients (57.8%). MICs of the NAC/dry propolis extract fixed combination ranged from 1.25/0.125 to 20/2 mg NAC/mg propolis. A synergistic effect (FICI ≤ 0.5) was observed in 51.7% of strains. The majority of isolates from patients with chronic otitis media were moderate biofilm producers and in chronic adenoiditis they were weak biofilm producers, while the same number of isolates in patients with chronic rhinosinusitis were weak and moderate biofilm producers. Subinhibitory concentrations of the NAC/propolis combination ranging from 0.625-0.156 mg/mL to 10-2.5 mg/mL of NAC combined with 0.062-0.016 mg/mL to 1-0.25 mg/mL of propolis inhibited biofilm formation in all bacterial strains. Suprainhibitory concentrations ranging from 2.5-10 mg/mL to 40-160 mg/mL of NAC in combination with 0.25-1 mg/mL to 4-16 mg/mL of propolis completely eradicated the biofilm. In conclusion, the fixed combination of NAC and dry propolis extract has a synergistic effect on all stages of biofilm formation and eradication of the formed biofilm in bacteria isolated from upper respiratory tract infections.

Effectiveness of the Treatment of Rhinogenic Headache Caused by Intranasal Contact.

OBJECTIVES: The aim of the study is to evaluate the effectiveness of the surgical and nonsurgical treatment of headache caused by contact points (CPs) between the nasal septum and inferior or middle turbinate. METHODS: The research was designed as a prospective clinical case-series study. The patients with CP headaches were offered to choose between 2 treatment options, surgery and medical treatment. Two groups of surgically treated patients (surgery groups 1 and 2, depending on whether there is a contact between nasal septum and inferior turbinate or middle turbinate) were evaluated and compared for headache intensity and frequency. Headache intensity was measured using a visual analog scale value from 0 to 10; the frequency of headache was expressed as the number of days during 1 month with a headache (before surgery, 1 month, and 6 months after surgery). A comparison was also made between surgically and nonsurgically treated patients. RESULTS: We found more intensive and frequent headache in patients who had CP between the nasal septum and the middle turbinate (P = .038 and P = .003, respectively). A significant reduction in headache intensity and frequency was found in both groups of surgically treated patients 6 months after surgery; however, this reduction was more significant in patients with mucosal contact between nasal septum and middle turbinate. The nonsurgical treatment made a significant reduction of headache intensity and frequency at 1-month follow-up (P = .012 and P = .031, respectively), but not at 6-month follow-up (P = .114 and P = .088, respectively). CONCLUSION: Surgery gave a statistically significant reduction in the intensity and frequency of headache, which was assessed 6 months after surgery. Surgery was found as superior to nonsurgical treatment in the therapy of CP headache.

The Expression of Hypoxia-Related Biomarkers: A Significance of HIF-1α C1772T Polymorphism as Predictor of Laryngeal Carcinoma Relapse.

INTRODUCTION: The association between the expression of HIF-1α in the laryngeal carcinoma and the prognosis of disease is quite well documented, but the significance of HIF-1α C1772T polymorphism and its relation to disease phenotype have to be clarified. The aim of this study was to investigate the influence of C1772T polymorphism on the clinical-pathological characteristics and disease-free survival after initial surgical treatment of patients with laryngeal carcinoma. MATERIALS AND METHODS: The prospective cohort study included 65 patients with laryngeal carcinoma. Two representative tumor tissue specimens were taken in each patient during surgery; 1 specimen was used to asses HIF-1α C1772T polymorphism and the other 1 to determine the immunohistochemical expression of HIF-1α, VEGF, as well as CD 34 proteins. The comparison of polymorphism frequency between study and control population was conducted by collecting a 5 mL of peripheral venous blood samples in each subject. RESULTS: Clinicopathological characteristics of laryngeal carcinoma didn't affect the expression of hypoxia-related biomarkers, such as HIF-1α, VEGF or MVD. The statistically significant association between HIF-1α and VEGF expression was found (P = .034), but not between HIF-1α expression and MVD value (P = .696). The expression of HIF-1α was significantly higher among CT heterozygotes (P = .029). We found a significantly more recurrence among CT heterozygotes compared with patients with CC homozygous alleles (57.10% and 24.30%, respectively; P = .007). Patients with C1772T polymorphic variants had significantly worse disease-free survival compared with patients without polymorphism (Log-rank test, P = .007). CONCLUSION: HIF-1α C1772T polymorphism was significantly associated with worse disease-free survival which nominates it as a predictor of laryngeal carcinoma relapse. The preoperative assessment of hypoxia-related biomarkers should be used in everyday practice in order to determine the treatment modalities for laryngeal carcinoma.

Immune Cell and Biochemical Biomarkers in Advanced Laryngeal Cancer.

Objective: The aim of this study was to evaluate cell and biochemical biomarkers and establish their prognostic value in patients with advanced laryngeal cancer. Material and Methods: A prospective study included 52 patients with advanced laryngeal carcinoma surgically treated at the tertiary referral center. Tumor tissue was immunohistochemically stained for T-cell markers (CD4 and CD8), and levels of cytokines (IL-6 and IL-8) and C-reactive protein were analyzed from blood samples. Results: Overall 3-year survival (OS) of patients included in the study was 69.2% and the disease specific survival (DSS) 72.5%. Higher expression of CD4+ and CD8+ were significant prognostic factors with positive impact on both OS and DSS in univariate analysis, but not in multivariate analysis. Levels of IL-8 were a significant predictor of 3-year OS and DSS survival in patients with advanced laryngeal cancer but not levels of IL-6 and CRP values. Conclusion: Though high expression of CD4 and CD8 were demonstrated in the tumor tissue, but their prognostic role was not established. Higher values of IL-8 proved to be significant negative predictor of DSS. This could further collaborate the inclusion of combination of biomarkers in assessment of favorable treatment choice in patients with advanced laryngeal carcinoma.

Otitis media with effusion as an initial manifestation of granulomatosis with polyangiitis.

Granulomatosis with polyangiitis is a systemic vasculitis of unknown etiology, characterized by necrotizing granulomas. It is an autoimmune disease affecting small- and medium-sized vessels of upper and lower respiratory tract, kidneys, and other organs. We described a case of a patient with otitis media with effusion as the first manifestations of granulomatosis with polyangiitis. A 54-year-old female presented as an urgent case with history of a severe otalgia, hearing loss, vertigo, and fever. The patient was treated with diagnosis of otitis media with effusion and acute rhinosinusitis, but without significant success. She developed an acute kidney dysfunction as a sign of glomerulonephritis with rapidly progressive renal failure. Diagnosis of granulomatosis with polyangiitis was confirmed after the histopathological analysis of kidney tissue, not by analysis of middle ear and paranasal sinus mucosa specimens. The patient was treated according to generally accepted protocol, and over time, there was an almost complete recovery.

Angiomyolipoma Originating From the Nasal Vestibule: A Case Report.

Angiomyolipoma is a benign, mesenchymal, hamartomatous lesion often described in the kidney and may be associated with tuberous sclerosis. Nasal angiomyolipoma is an extremely rare tumor with fewer than 20 cases reported in the literature. We report a case of angiomyolipoma arising in the right nasal vestibule in a 68-year-old male with mild, recurrent right-sided epistaxis, and nasal obstruction. With the exception of arterial hypertension, the patient did not have any comorbidities. Gross examination showed a well-circumscribed, lobulated mass. On the microscopic level, it was composed of mature smooth muscle cells, thick-walled blood vessels of varying sizes, and islands of mature adipose tissue. Angiomyolipoma should be considered as a differential diagnosis for unilateral nasal masses, especially those situated in the nasal vestibule.

Is otitis media with effusion associated with Samter's triad a new nosological entity? A preliminary report on inflammatory mediator production.

PURPOSE: Otitis media with effusion (OME) associated with Samter's triad (ST) is a difficult entity to treat. The aim of study was an investigation of the middle ear and nasal production of inflammatory mediators (IM) in patients with ST and analysing differences between them and controls. METHODS: Prospective case-control study. Nineteen patients with OME (five had allergic rhinitis, four had nasopharyngeal lymphoid hyperplasia, five had no evident sino-nasopharyngeal disease and five had confirmed ST) and 15 healthy participants were included. The concentrations of IM interleukin-1 beta (IL-1ß), interferon-alpha 2 (IFN-α2), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23 and IL-33 were measured in nasal and middle ear secretions. RESULTS: There was a difference that was close to a level of statistical significance only for IL-1ß levels in middle ear fluid (p = 0.052) between the ST subgroup and the other patients with OME. Also, we found a significant difference for IL-23 in nasal secretions between these subgroups (p = 0.040), whereas the difference in nasal fluid IL-33 was close to a level of statistical significance (p = 0.052). There was a significant difference in nasal concentrations of IL-1ß, IFN-α2, MCP-1, IL-8, IL-18 and IL-33 (p < 0.001, p = 0.005, p = 0.008, p = 0.011, p = 0.011 and p = 0.011, respectively) between the OME group and the healthy subjects. There were significant positive correlations between concentrations of IL-1ß, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-17A, IL-18 and IL-33 (p < 0.001, p < 0.001, p = 0.002, p = 0.028, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively) in nasal and middle ear secretions. CONCLUSION: This preliminary report showed some differences in IM production between the patients with OME associated with ST and those without it. Our results suggest a uniformity of the production of nasal and middle ear IM and supported the concept of a united airway respiratory disease.

Predictors of Complications Occurrence Associated With Emergency Surgical Tracheotomy.

OBJECTIVE: In emergency airway management, the occurrence of surgical tracheotomy complications is increased and may be fatal for the patient. However, the factors that play a role in complication occurrence and lead to lethal outcome are not known. The objective of this study was to determine predictors associated with the occurrence of complications and mortality after emergency surgical tracheostomy. STUDY DESIGN: Retrospective study with a systematic review of the literature. SETTING: Tertiary medical academic center. SUBJECTS AND METHODS: We included 402 adult patients who underwent emergency surgical tracheostomy under local anesthesia due to upper airway obstruction. Demographic, clinical, complication occurrence, and mortality data were collected. For statistical analysis, univariable and multivariable logistic regression methods were used. RESULTS: In multivariable analysis, significant positive predictors of complication occurrence were previously performed tracheotomy (odds ratio [OR] 3.67, 95% confidence interval [CI], 0.75-17.88), neck pathology (OR 2.05, 95% CI 1.1-1.77), and tracheotomy performed outside the operating room (OR 5.88, 95% CI, 1.58-20). General in-hospital mortality was 4%, but lethal outcome as a direct result of tracheotomy complications occurred in only 4 patients (1%) because of intraoperative and postoperative complications. CONCLUSION: The existence of neck pathology and situations in which tracheotomy was performed outside the operating room in uncontrolled conditions were significant prognostic factors for complication occurrence. Tracheotomy-related mortality was greater in patients with intraoperative and early postoperative complications. Clinicians should be aware of the increased risk in specific cases, to prepare, prevent, or manage unwanted outcomes in further treatment and care.

Management of Orbital Complications of Acute Rhinosinusitis in Pediatric Patients: A 15-Year Single-Center Experience.

BACKGROUND: The major clinical dilemma managing acute rhinosinusitis (ARS) in pediatric population is distinguishing uncomplicated rhinosinusitis from a complicated bacterial ARS and orbital complications, the latter requiring antimicrobials and surgical intervention. However, factors associated with severe orbital complications and the optimum management strategy remains controversial. The objectives of this study were to characterize the clinical outcomes of children with orbital complications of ARS and to identify risk factors associated with disease severity. METHODS: This retrospective cohort analysis evaluated the clinical outcomes of 61 children admitted for orbital complications between January 1, 2002 and December 31, 2017. Descriptive statistics were performed to examine the demographics and clinical findings. We compared groups using Mann-Whitney U test for continuous variables and χ for categorical variables. RESULTS: Although two-thirds of children had received prehospital antibiotics, half of the cohort presented with post-septal orbital complications. While 83% of isolates obtained from the same patients were susceptible to the prehospital antibiotics given, the majority of those who received prehospital antibiotics nevertheless required surgical intervention. We observed significant association between the age of presentation and disease severity. Children >5 years of age presented with more severe orbital complications despite prehospital antibiotics and were more likely to require surgical intervention (P < 0.001). CONCLUSIONS: In this study, stage II/III orbital complications at presentation and older age were the most important determinants of medical treatment failure. Early referral to eye, nose and throat (ENT) should be considered for children >5 years with ARS due to worse orbital complications despite prehospital antibiotics.

Laser transoral microsurgery in treatment of early laryngeal carcinoma.

PURPOSE: Laser transoral laryngeal microsurgery has become widely accepted treatment method because of its organ and function preservation and shorter period of hospitalization. The aim of this study was to examine the overall, disease-specific and disease-free survival in patients with early laryngeal carcinoma treated with laser depending on age, gender, common risk factors (tobacco and alcohol use), histopathological tumor grade, anterior commissure involvement, performed tracheotomy, positive surgical margins, T stage, type of endoscopic cordectomy, postoperative radiotherapy and laryngeal preservation. METHODS: Retrospective study included 234 patients with squamocellular carcinoma of the larynx treated with laser transoral laryngeal microsurgery. 5-year overall, disease-specific and disease-free survival and the prognostic impact of mentioned factors were evaluated using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: 5-year OS and DSS was 92.5% and 95.3%, respectively. OS was significantly lower for older patients and in patients with histologically poorly differentiated tumors, 3 and 5 years postoperatively (Log rank test; p = 0.031). DSS was significantly lower in patients with anterior commissure involvement, positive surgical margins and patients who underwent postoperative RT. DFS was significantly lower in patients with anterior commissure involvement, patients with T1b tumor stage and patients who underwent cordectomies type Vb and VI (Log rank, p < 0.05). Laryngeal preservation significantly influenced 5-year OS, DSS and DFS (Log rank, p ≤ 0.001). Multivariate Cox regression analysis showed that age, histological tumor grade and laryngeal preservation were significant negative prognostic factors for 5-year DSS and DFS. CONCLUSION: Transoral laryngeal microsurgery delivers excellent oncological results, even in selected patients with higher stages of early laryngeal cancer and anterior commissure involvement.

Characterization of the Variability of Epstein-Barr Virus Genes in Nasopharyngeal Biopsies: Potential Predictors for Carcinoma Progression.

Epstein-Barr virus (EBV) infection is a significant factor in the pathogenesis of nasopharyngeal carcinoma, especially in the undifferentiated carcinoma of nasopharyngeal type (UCNT, World Health Organization type III), which is the dominant histopathological type in high-risk areas. The major EBV oncogene is latent membrane protein 1 (LMP1). LMP1 gene shows variability with different tumorigenic and immunogenic potentials. EBV nuclear antigen 1 (EBNA1) regulates progression of EBV-related tumors; however, the influence of EBNA1 sequence variability on tumor pathogenesis is controversial. The aims of this study were to characterize polymorphisms of EBV genes in non-endemic nasopharyngeal carcinoma biopsies and to investigate potential sequence patterns that correlate with the clinical presentation of nasopharyngeal carcinoma. In total, 116 tumor biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT), collected from 2008 to 2014, were evaluated in this study. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. The presence of EBV DNA was significantly distributed between TNM stages. LMP1 variability showed six variants, with the detection of the first China1 and North Carolina variants in European nasopharyngeal carcinoma biopsies. Newly discovered variants Srb1 and Srb2 were UCNT-specific LMP1 polymorphisms. The B95-8 and North Carolina variants are possible predictors for favorable TNM stages. In contrast, deletions in LMP1 are possible risk factors for the most disfavorable TNM stage, independent of EBNA2 or EBNA1 variability. A newly discovered EBNA1 subvariant, P-thr-sv-5, could be a potential diagnostic marker, as it represented a UCNT-specific EBNA1 subvariant. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, type 1/Med/P-thr was identified as a possible risk factor for TNM stage IVB or progression to the N3 stage.

Recurrent malignant otitis externa with multiple cranial nerve involvement: A case report.

Introduction: Necrotizing otitis externa is a rare but conditionally fatal infection of external auditory canal with extension to deep soft tissue and bones, resulting in necrosis and osteomyelitis of the temporal bone and scull base. This condition is also known as malignant otitis due to an aggressive behavior and poor treatment response. Early diagnosis of malignant otitis is a difficult challenge. We present an illustrative case of necrotizing otitis externa and suggest some strategies to avoid diagnostic and treatment pitfalls. Case Outline: A 70-year-old patient presented with signs of malignant otitis externa, complicated by peripheral facial palsy. Adequate diagnostic and treatment procedures were performed with clinical signs of resolution. The recurrence of malignant infection had presented three months after previous infection with multiple cranial nerve neuropathies and signs of jugular vein and lateral sinus thrombosis. An aggressive antibiotic treatment and surgery were carried out, followed by substantial recovery of the patient and complete restoration of cranial nerves' functions. Conclusion: Necrotizing otitis externa is a serious condition with uncertain prognosis. The suspicion of malignant external otitis should be raised in cases of resistance to topical treatment, especially in patient with predisposing factors. Evidence-based guideline for necrotizing otitis externa still doesn't exist and treatment protocol should be adjusted to individual presentation of each patient.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Module, updated version: Preliminary psychometric data from Serbian laryngectomized patients.

BACKGROUND: We provided preliminary psychometric data for the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Head and Neck Module, updated version (QLQ-H&N43) from a group of Serbian laryngectomized patients. METHODS: The study included 170 subjects. The QLQ-H&N43 is a 43-item questionnaire, with 12 multi-item scales and 7 single-item symptom scales. All subjects also completed the Quality of Life Questionnaire-Core 30-questions (QLQ-C30). RESULTS: Good internal consistency (Cronbach's α of above 0.7) was found for 5 of the 7 scales. All QLQ-H&N43 scales correlated negatively as predicted with all QLQ-C30 functioning scales. The correlations with the QLQ-C30 symptoms supported discriminant validity, with only one exception: the head and neck social eating scale overlapped with the QLQ-C30 pain scale. For 14 of 19 QLQ-H&N43 scale scores, significant known-group differences were observed between those who differ in type of laryngectomy, adjuvant therapy, or 5-year survival. CONCLUSION: Preliminary evidence suggests that a great majority of the QLQ-H&N43 scales have acceptable internal consistency and promising construct validity, but more research studies are needed with other cancer groups to extend these findings. © 2015 Wiley Periodicals, Inc. Head Neck 38: E916-E924, 2016.

Tick on the tympanic membrane.

INTRODUCTION: Different foreign bodies can reach the lumen of the external auditory canal. Clinical presence of the foreign bodies depends on the nature of the foreign body, localization, morphological features, and the presence of pathological process. CASE REPORT: This study gives a report on a rare foreign body--a tick on the eardrum, which is a very rare localization in European countries. CONCLUSION: Identification, determination of the nature of the foreign body and the way of extracting it depend on the application of adequate diagnostic and therapeutic approaches.

Congenital cholesteatoma of the middle ear--uncommon clinical presentation.

INTRODUCTION: Congenital cholesteatoma of the middle ear is un uncommon and yet not well-defined disease. Only few cases of cholesteatoma in thefossa ovalis with unusual clinical presentation have been reported in medical literature. CASE REPORT: We reported a 16-year-old girl with congenital cholesteatoma in the fossa ovalis with minimal clinical presentation. A small mass was found occluding the fossa ovalis and mimicking otosclerotic process within tympanic cavity. The operation started as stapedotomy, and when the process was confirmed it converted to mastoidectomy via the retroauricular approach. CONCLUSION: The diagnosis of congenital cholesteatoma in children should always be considered, even if the clinical symptoms imitate other ear disorders, in our case otosclerosis.