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.

Bulky Recurrent Juvenile Nasopharyngeal Angiofibroma.

Juvenile nasopharyngeal angiofibroma is a rare and highly vascularized tumor that accounts for 0.05 to 0.5% of all head and neck neoplasms. The aim of this work was to present a case of a large recurrent juvenile nasopharyngeal angiofibroma coexisting with a facial lipoma in a 16-year-old boy. The patient was referred to our institution because of frequent unilateral epistaxis. Computed tomography revealed a hypervascular tumor with ethmoidal cell destruction and spread to the nasopharynx. Operative treatment of nasal cavity tumors was carried out using a transpalatal approach. After 6 months, the recurrence of the angiofibroma was verified radiologically. Primary as well as secondary surgical procedures were assisted with an endoscopic procedure. Accurate preoperative assessment and staging are essential for choosing a surgical procedure. The primary treatment is surgical excision. Early diagnosis, accurate staging, adequate treatment, and regular postoperative follow-up are essential in the treatment of these lesions.

Infratemporal Fossa Chondroblastoma.

INTRODUCTION: Chondroblastoma is a rare, benign mesenchymal tumor that can behave local aggressive. It most often occurs in the area of the epiphyses of long tubular bones, whereas the appearance in the region of the head and neck is rare, only few reports were published in literature. The incidence of chondroblastoma of the craniofacial region is about 6.4%. CLINICAL REPORT: A 46-year-old patient was hospitalized due to growth and pain in the area of the left half of the face, and a tumor of the left infratemporal fossa was diagnosed by computed tomography. The patient was operated with a preauricular surgical approach, parotidectomy, and complete tumor removal was performed. Pathohistological examination revealed chondroblastoma. CONCLUSIONS: Chondroblastoma of the craniofacial region is very rare pathohistological finding, characterized by slow and asymptomatic growth until it reaches the appropriate dimensions, the clinical symptomatology depends on the localization of the tumor. Computed tomography diagnostics provides important information about the location, size of the tumor, invasion of surrounding structures, and significantly contributes to the decision on the appropriate surgical approach. Diagnostic dilemma solving only final pathohistological verification.

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.

Chondroma of the Tongue.

INTRODUCTION: Chondromas are rare mesenchymal benign tumors that are most often encountered in pelvis and ribs, and rarely in head and neck region. They account for about 10% of all benign chondroid proliferations and the rarest occurrence of soft tissue chondromas is within oral cavity. CASE: A 10-year-old female patient was referred to our Clinic because of moderate speech impairment, swallowing disturbances and foreign body sensation in tongue. On clinical examination and MRI scans, hard, painless, clearly demarcated submucosal mass was observed on the left side of the tongue. Surgery was perfomed using intraoral incision approach, and the tumor was completly removed. Histopathological examination of the specimen was positive for chondroma. CONCLUSION: Chondromas benign tumors of mature hyaline cartillage localized in soft tissues of head and neck region. Growing slowly, and painlessly, they remain silent for some period, until reaching certain dimensions, and becoming symptomatous. Magnetic resonance imaging scan provides complete information about localization, size, growth of the tissue, and contributes significantly to the decision of appropriate surgical approach.

Risk factors for intraoperative bradycardia during ear, nose, throat and maxillofacial surgery.

Intraoperative bradycardia (IOB) is one of the most common cardiac arrhythmias observed in clinical anaesthetic practice. Controlled hypotension, as a strategy of lowering patient's blood pressure during anesthesia has been practiced for decades in head and neck surgery. The aim of our study was to determine the incidence and the risk factors for intraoperative bradycardia in maxillofacial, ear, nose and throat surgery, as well as to determine whether controlled hypotension affects the occurrence of IOB. The retrospective study included 2304 patients who underwent maxillofacial, ear, nose or throat surgery. We studied the influence of: sex, age, comorbidity, type of surgery, duration of anesthesia and controlled hypotension on the occurrence of IOB. IOB was registered in 473 patients (20.5%). Patients with controlled hypotension had IOB significantly more often than patients without controlled hypotension (33.9 vs 15.1%) (p = 0.000). The significant predictors of IOB were: age (OR = 1.158; 95% CI = 1.068-1.256; p = 0.000), sex (OR = 0.786; 95% CI = 0.623-0.993; p = 0.043), ischemic heart disease (OR = 2.016; 95% CI = 1.182-3.441; p = 0.010); ear surgery (OR = 1.593; 95% CI = 1.232-2.060; p = 0.000), anesthesia duration, (OR = 1.006; 95% CI = 1.004-1.007; p = 0.000) and controlled hypotension (OR = 2.204; 95% CI = 1.761-2.758; p = 0.000). IOB is common in maxillofacial, ear, nose and throat surgery, particularly in male, older age and patients with ishemic heart disease. The ear surgery, longer anesthesia duration and controlled hypotension raise the risk for occurrence of IOB.

Association between regional heterogeneity in the mid-facial bone micro-architecture and increased fragility along Le Fort lines.

BACKGROUND/AIM: Le Fort lines have traditionally been considered as zones of weakness in the mid-facial skeleton although the structural basis of increased bone fragility at these sites has not yet been investigated. Considering recent findings of occlusal loading-related regional heterogeneity in the mid-facial bone micro-architecture, the aim of this study was to explore whether such heterogeneity in cortical and cancellous bone micro-architecture may contribute to increased fragility at Le Fort fracture sites. MATERIALS AND METHODS: Twenty-five cortical and thirteen cancellous bone specimens were harvested from a dry skull and analyzed by micro-CT. Specimens were classified into Le Fort or Non-Le Fort groups based on their location in the mid-facial skeleton. RESULTS: Cortical bone along Le Fort lines showed tendencies toward lower thickness (1.5±0.63 vs 1.75±0.79; P=.39) and greater porosity (11.48±5.67 vs 10.28±5.28; P=.59). A significant difference was detected in the trabecular degree of anisotropy which was higher in cancellous bone from Le Fort fracture sites (2.14±0.69 vs 1.58±0.34; P=.02). CONCLUSIONS: Regional heterogeneity in cortical bone micro-architecture could not fully explain increased fragility of the mid-facial skeleton at the Le Fort lines. However, regional differences in trabecular bone anisotropy may contribute to increased bone fragility.

The MMP-2 and MMP-9 promoter polymorphisms and susceptibility to salivary gland cancer.

PURPOSE: Matrix metalloproteinases (MMPs) are a family of endopeptidases that may play an important role in the development of salivary gland cancer (SGC). MMP-2 and MMP-9, members of the gelatinase protein family, are capable of degrading type IV collagen of basement membranes, and their overexpression is often associated with tumor aggressiveness and poor prognosis. The aim of this study was to establish the role of single nucleotide polymorphisms (SNPs) in MMP-2 and MMP-9 genes as putative susceptibility factors for the development of SGC. METHODS: The MMP-2 -1306 C>T, MMP-2 -1575 G>A and MMP-9 -1562 C>T polymorphisms were analyzed in 93 SGC cases and 100 controls using PCR-RFLP. RESULTS: The T allele for the MMP-2-1306 C>T polymorphism exhibited its effect in heterozygous carriers, increasing the risk for SGC (odds ratio/OR 1.98, 95% CI 1.07-3.65, p=0.03). According to the dominant model, CT+TT genotypes had a 2-fold increased risk of developing SGCs (p=0.02).When the dominant model was applied for the MMP2 -1575 G>A, individuals with GA+AA genotypes exhibited a 1.77-fold increase in cancer risk, but with borderline significance (p=0.049). Heterozygous carriers of the variant T allele for the MMP-9 -1562 C>T polymorphism had roughly a 2-fold increase in susceptibility for SGC compared to wild type homozygotes (CC) (p=0.02). CONCLUSION: Our findings suggest MMP-2-1306 C>T and MMP-9-1562 C>T polymorphisms genotypes seem to influence the development of SGCs, whereas MMP-2 -1575 G>A seems to be of a minor importance.

Cytomegalovirus induces Interleukin-6 mediated inflammatory response in salivary gland cancer.

PURPOSE: The purpose of this study was to examine whether cytomegalovirus (CMV) is present in different histological types of salivary gland cancer (SGC) by detecting CMV immediate-early (IE) and early gene products, and to determine the presence of its association with the overexpression of interleukin (IL)-6. METHODS: Immunohistochemical analysis of 92 cases of different histological types of SGC was performed to determine the presence of IL-6 and CMV antigen and its intensity in tumor tissue. Twenty samples of normal salivary gland tissue obtained during autopsy served as healthy controls. RESULTS: CMV antigens were not found in healthy acinar tissue of salivary glands, but were expressed in epithelium of salivary gland ducts. Negative expression of CMV antigens was also found in salivary gland tissue surrounding tumors. On the other hand, CMV was detected in 65/92 SGC cases (70.6%). Higher expression of IL-6 was found in SGC (70.7%) than in normal tissue (20%). There was a high association of CMV antigen presence with the presence of IL-6, and with the IL-6 expression intensity. CONCLUSIONS: Positive expression of CMV antigens in a high percentage of SGC cells suggests that it might play an important role in carcinogenesis by increasing IL-6 production and leading to inhibition of apoptosis and tumor development.

Clinical outcomes and quality of life in patients with nasal polyposis after functional endoscopic sinus surgery.

The majority of studies have shown that the use of functional endoscopic sinus surgery (FESS) leads to symptomatic improvement in 73-98.4 % of patients with chronic rhinosinusitis and nasal polyposis (NP). The aim of the study is to evaluate clinical outcomes and quality of life (QoL) in patients with NP after FESS. The prospective study included 85 consecutive adult patients (≥18 years) with NP who were operated on using FESS after failure of the medicamentous treatment and in certain cases of surgical treatment. QoL was assessed by Short Form-36 Health Survey (SF-36) questionnaire, and the symptom intensity was presented using visual analogue scale (VAS). The objective finding was presented as endoscopic and computerized tomography (CT) score. The intensity of each symptom, the values of symptom scores (major, minor and total), the values of dimension scales and summary scales of the QoL, as well as the values of endoscopic score through three periods of time (pre-surgery, 6 and 12 months after the surgery) were analyzed. Following the FESS, mean intensity values of all individual symptoms and symptom scores were significantly lower and the values of all dimension scales and summary scales of QoL were significantly higher (p < 0.05). There was no statistically significant difference in symptom intensity and QoL after 6 and 12 months of surgical treatment (p > 0.05). Endoscopic score was on average significantly lower after 6 and 12 months of FESS (p < 0.05), but the mean score value after 12 months of operation was significantly higher in relation to that after 6 months of surgery (p < 0.05). Nevertheless, the recurrence of NP was observed in 28 patients (32.9 %) in the follow-up period. In conclusion, FESS in NP patients results in significant improvement of symptom intensity, QoL and endoscopic score. While the intensity of symptoms and QoL showed a tendency to maintain between 6 and 12 months after surgery, endoscopic score showed a tendency of exacerbation in the same period.

Late complication of the frontobasal trauma.

The injuries of the frontobasal region are always a great challenge to a surgeon, especially the management of bone defects of the frontal region. The authors present a patient with late, 33-year postaccident complication, which had been surgically treated, and whose frontal bone defect had been reconstructed with methyl methacrylate. Clinical examination and computed tomography confirmed signs of previous operation and presence of an infection and alloplastic material. Specific for this case was challenge to manage chronic infection and reestablish integrity of the skull in the frontal region. Out of a variety of autogenous or alloplastic materials, and considering the extent of bone defect and previous episodes of treatment aimed at aesthetic and functional results with good prognosis, we opted for reconstruction of the frontal region defect with combined titanium mesh impregnated with the hydroxyapatite cement.

Surgical management of cervical paragangliomas.

Carotid body tumors are rare, but represent the most common form of head and neck paraganglioma. We present 17 surgically treated patients. The present study reviews our experience in the diagnosis and treatment of these uncommon lesions. At surgery, 11 tumors were classified as Shamblin Class II and six as Class III. A cerebral angiogram was obtained in all cases before surgery. A cervical approach was the method of choice in 16 cases; in one case with mediastinal extension of the tumor we used a combined cervical and transsternal approach. Complete excision of the tumor was accomplished in all cases. Subadventitial tumor excision was performed in eight cases whereas internal carotid artery reconstruction was obtained in eight cases (three saphenous interposition vein grafts, two polytetrafluoroethylene (PTFE) 6 mm grafts, and end-to-end anastomosis in three cases). Resection of the left common carotid artery and reconstruction with a Dacron 8 mm graft was performed in the case with mediastinal tumor extension. Duplex scan along with angiography is effective in making the diagnosis. Excision is indicated for most tumors, and best results are achieved by an experienced vascular surgeon.

Analysis of reconstructive methods in surgical treatment of nasal skin defects.

Background/Aim: Surgeons often face with the problem when selecting a reconstructive method for nasal skin defects. The aim of this study was to determine functional and aesthetic character-istics of different reconstructive methods used for skin defects in different regions of the nose. Methods: The study involved 44 patients with basocellular carcinoma in nasal area. The nasal skin was divided into four subunits: the tip, the alar lobules, the side-walls and the dorsum. The average skin defect size was 10 mm in diameter. Local flaps and full thickness skin grafts were used in the study. We analyzed the functional and esthetic results of dif-ferent reconstructive methods used for nasal defects in different regions of the nose 12 months after the surgery. Results: The study shows that different reconstructive methods produce dif-ferent functional and esthetic results in the same nasal subunits and that the same reconstructive method produces different re-sults in different nasal subunits. Conclusions: Estimation the postoperative functional and esthetic characteristics of different reconstructive methods is one of the basic preconditions of suc-cessful reconstruction.

Giant destructive sinonasal polyposis.

INTRODUCTION: Authors report their clinical experience in managing a 46-year-old male patient with long lasting nose breathing difficulties caused by nasal obstruction due to a large bilateral tumor masses in both nasal cavities. CASE OUTLINE: Physical examination, laboratory and biochemistry analyses, as well as computed tomography showed an inhomogeneous soft-tissue tumor mass completely filling both nasal cavities, maxillary, ethmoidal, sphenoidal, and frontal sinuses on both sides, accompanied by destruction of bony walls of all sinuses. Preoperative histopathology analysis showed a polyp with squamous metaplasia.The gigantic polypoid mass was removed by bicoronal approach to the frontal and ethmoidal sinuses and by direct approach to the maxillary sinuses and nasal cavity. Definite histopathology analysis confirmed the initial diagnosis, but the presence of fungal hyphae in allergic mucus was also observed. CONCLUSION: Polypoid growth in the nose rarely grow to such gigantic dimensions that it causes destruction of all walls of paranasal sinuses. Considering so far published reports from the literature, the presented case is among the biggest nasal polyps reported until now.

Epithelial-myoepithelial carcinoma--review of clinicopathological and immunohistochemical features.

INTRODUCTION: Epithelial-myoepithelial carcinoma is a low-grade malignant salivary gland neoplasm with a biphasic cell population that encompasses around 1% of all salivary neoplasms. METHOD: We present different cases of epithelial-myoepithelial carcinoma, with special emphasis on histopathology, differential diagnosis, relevant prognostic factors and follow-up. RESULT: This study included 8 patients who were diagnosed with epithelial-myoepithelial carcinoma and treated surgically including a follow-up period of at least 19 months. CONCLUSION: Clinical and histopathological characteristics of these rare tumors are extremely valuable for accurate diagnosis and further therapy planning.

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.

Zygomatic bone metastasis as an initial presentation of hepatocellular carcinoma.

Hepatocellular carcinoma is the most common type of primary liver cancer. It metastasizes via blood or through lymphatic dissemination, most comonly to the lungs, abdominal lymph nodes, and bones. Metastases to the bones of the head and neck region, however, are extremely uncommon. A 70-year-old male was presented with a mass in the left zygomatic region. After the incisional biopsy, the histopathologic and immunohistochemical analysis confirmed a metastasis of hepatocellular carcinoma. An abdominal computerized tomography (CT) scan  revealed a large primary tumor in the right liver lobe. To the best of our knowledge, this is the second case of an isolated zygomatic metastasis as an initial presentation of hepatocellular carcinoma. We also reviewed the literature regarding clinical and histopathologic characteristics of hepatocellular carcinoma that produced metastases to the zygomatic bone and the maxilla.

[T lymphocyte function in laryngectomized patients].

AIM: Malignant tumors of the larynx account for 2.3% of all malignancies, while their frequency among tumors of the head and neck ranges between 12% and 20%. Research on the general immune competence in patients with malignant diseases has provided useful insight in the relationship between immune disorders on one side and the clinical course on the other. Unfortunately, only few complete studies have been published so far with this regard in patients with malignant tumors of the larynx, and therefore our study was essentially aimed at establishing of general immunocompetence, presence and levels of the possible immune disorders and their association with the malignant tumors. MATERIAL AND METHOD: The study included forty two patients with primary squamocellular laryngeal cancer. All the patients underwent surgery, out of whom fifteen were treated postoperatively with radiotherapy. We tested the immune competence prior to the operation and in the postoperative period nine months later. In the venous blood we examined T lymphocyte function, monocyte levels and mononuclear phagocyte function. RESULTS: Preoperative evaluation of the presence and levels of general immune competence in patients with laryngeal cancer, showed a distinct decrease in the proliferative response to the PHA mitogen in vitro, with a tendency to normalize in patients who do not develop a relapse of the disease or distant metastasis during the follow-up period. During the whole study period, the number of monocytes and mononuclear phagocyte activity was above the normal level. CONCLUSION: The patients with operable laryngeal carcinoma had considerable immune disorders at various levels, primarily at the level of T lymphocytes. Of all the disorders, reduced mitotic activity of T lymphocytes in response to mitogens showed the highest dependance on the presence of malignant tissue in the organism.

Temporalis fascia graft perforation and retraction after tympanoplasty for chronic tubotympanic otitis and attic retraction pockets: factors associated with recurrence.

OBJECTIVES: To correlate the recurrence of temporalis fascia graft perforation and retraction in adults and children after tympanoplasty for chronic tubotympanic otitis and deep attic retraction pockets with age, pathologic process, mucosal lesions, mucociliary transport time, chronic sinusitis, and lateral attic wall reconstruction. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: Two hundred seventy-four adult ears and 41 child ears were operated on for chronic tubotympanic otitis, 50 adult ears were operated on for traumatic tympanic membrane rupture, and 56 adult ears were operated on for attic retraction pockets. INTERVENTIONS: Underlay tympanoplasty with or without mastoidectomy and lateral attic wall reconstruction for attic retraction pockets. Mucociliary transport time was investigated using saccharin testing. MAIN OUTCOME MEASURES: Recurrent perforation, recurrent attic retraction, and temporalis fascia graft retraction were evaluated. RESULTS: Higher incidences of recurrent perforation were found in adults operated on for tubotympanic otitis vs traumatic tympanic membrane rupture (P = .02) and in children (P = .004), especially those 9 years and younger (P = .02). A risk factor in adults was chronic sinusitis (risk ratio, 35.0; 95% confidence interval, 32.1-38.2; P = .004). Temporalis fascia graft retraction correlated with slower mucociliary transport time in adults (P < .001). A lower incidence of recurrent attic retraction was associated with lateral attic wall reconstruction (P < .001). CONCLUSIONS: Recurrent temporalis fascia graft perforation after tympanoplasty for tubotympanic otitis may be related to age and coexisting chronic sinusitis. Temporalis fascia graft retraction correlates with slower mucociliary transport time in the eustachian tube. Lateral attic wall reconstruction minimizes recurrent attic retraction in adults.

[Surgical approach to parapharyngeal space tumors].

INTRODUCTION: Parapharyngeal space tumors are very rare comprising 0.5% of head and neck tumors. Tumors of this symptomatology as well as considerable surgical issue owing to inaccessibility. PATIENTS AND METHODS: Retrospective twenty-year study of patients with parapharyngeal space tumors included 69 patients. Data were obtained from medical records, and were pointed to diagnostic procedures, surgical approach and pathohistological findings. Symptoms and clinical signs were also investigated. RESULTS: Preoperative diagnostics is very important for precise tumor localization and relation to adjacent structures. Computerized tomography was the most common method used, and recently, magnetic resonance imaging and indication-based contrast angiography have been applied. All of 69 patients with parapharyngeal space tumors were treated surgically. The most often approach to this tumor was transcervical (62%), then transoral approach and combination transcervical transoral approach. Pathohistological examination verified that most of the tumors were benign (75%) and origin of these tumors was most frequently salivary (42%). CONCLUSION: For making a decision on surgical approach, diagnostic methods, other than thorough examination, such as computerized tomography (CT) and/or magnetic resonance imaging (MR), are necessary to be applied.