Impact of TLR9 and TLR7 gene polymorphisms on prognosis and survival of patients with oral squamous cell carcinoma.

Despite significant efforts in developing new diagnostic and therapeutic modalities, oral squamous cell carcinomas (OSCCs) still exhibit a high recurrence rate, a low five-year survival rate, and an increasing prevalence. Toll-like receptors (TLRs), which initiate and perpetuate immune mechanisms upon activation, have been linked to immune surveillance and the antitumor immune response. The aim of this study was to investigate the association between the polymorphisms of the TLR7 rs3853839 and TLR9 rs187084 genes and OSCC risk, clinicopathological features, and survival. Genotyping was assessed by real-time polymerase chain reaction (PCR) in 95 HPV-negative OSCC patients and 107 age- and sex-matched healthy controls. Patients with lymph node metastases had higher frequencies of the TLR9 rs187084 CC variant genotype compared to the major TT genotype (P = 0.020) and to T-allele carriers (combined TT + CT genotypes, P = 0.015). A higher prevalence of advanced stage III was observed in patients with the TLR9 rs187084 variant CC genotype compared to TT (P = 0.047) and to T-allele carriers (TT + CT, P = 0.037). Kaplan-Meier analysis revealed a lower overall survival rate in patients with the TLR9 rs187084 variant CC genotype compared to TT genotype (P = 0.010, log-rank test) and to T-allele carriers (TT + CT, P = 0.002), though it was not an independent predictor of overall survival. Both TLR9 rs187084 and TLR7 rs3853839 polymorphisms were associated with high alcohol consumption (P = 0.027 and P = 0.001, respectively). The investigated genetic variations were not associated with OSCC susceptibility. The variant CC genotype of the TLR9 rs187084 polymorphism might be a marker of poor survival and tumor progression in OSCC.

Prognostic impact of miR-34b/c DNA methylation, gene expression, and promoter polymorphism in HPV-negative oral squamous cell carcinomas.

Micro RNAs (miRNAs) have a key role in gene expression regulation in cancer. The aim of the current study is to evaluate the prognostic value of miR-34b/c promoter hypermethylation, gene expression, and polymorphism in HPV-negative oral squamous cell carcinomas (OSCC). MiR-34b/c promoter hypermethylation and pre-miR-34b/c polymorphism rs4938723 were evaluated in tumor tissues of 148 patients, and miR-34b expression in 123 HPV-negative OSCC. For risk assessment, the control group was comprised of 175 healthy individuals. MiR-34b/c promoter hypermethylation was determined by methylation-specific PCR. Gene expression, genotyping and HPV screening was assessed by Q-PCR. The data from our hospital cohort indicated that miR-34b/c DNA methylation was associated with nodal status (p = 0.048), and predicted the shorter overall survival of HPV-negative OSCC patients (p = 0.008). Down-regulated miR-34b/c expression was associated with smoking (p = 0.047), alcohol use (p = 0.009), stage (p = 0.025), recurrences (p = 0.000), and a poor survival (p = 0.00029). Median values of miR-34b expression were significantly lower in advanced stages III/IV as opposed to stage I/II, p = 0.006, and in nodal positive vs negative patients (p = 0.045). TCGA data also indicated that tumors with stage I-III expressed significantly higher levels of miR-34b, compared to tumors with stage IV (p = 0.035), Low miR-34b/c expression was associated with poor survival in smokers (p = 0.001) and patients with tongue carcinomas (p = 0.00003), and TCGA analysis confirmed these findings although miR-34b expression and miR-34b/c methylation were not associated with survival outcome in the whole TCGA cohort. A significant negative miR-34b/c expression-methylation correlation was observed in our hospital cohort (p = 0.017) and in TCGA cohort. Pre-miR-34b/c polymorphism was not associated with oral cancer risk. Our findings indicate that miR-34b/c hypermethylation and low miR-34b expression could promote the progression and predict the poor prognosis for HPV-negative OSCC, which suggests miR-34b/c as a promising biomarker and therapeutic target for OSCC in the future.

TMD in class III patients referred for orthognathic surgery: psychological and dentition-related aspects.

OBJECTIVE: To investigate temporomandibular disorders (TMD), psychosocial, and occlusal variables in class III orthognathic surgery patients with respect to the control subjects, and to compare psychosocial and occlusal features in class III patients with different Research Diagnostic Criteria for TMD (RDC/TMD) diagnoses. MATERIALS AND METHODS: The study enrolled 44 class III patients referred for orthognathic surgery and 44 individuals without a malocclusion. TMD, depression and somatization were assessed by RDC/TMD. Occlusal analysis included Helkimo's Occlusal Index items, overjet and overbite. RESULTS: In the controls, patients with class III deformities had higher prevalence of myogenic TMD, increased grade of chronic pain, and more occlusal deviations. Within the study group, TMD patients reported higher depression score (P < 0.01), myofascial pain was related to higher depression and somatization grades (P < 0.01, P < 0.05 respectively), and disc displacement showed relation with RCP-ICP slide interferences (P < 0.05). CONCLUSION: With respect to subjects without a malocclusion, TMD in class III dentofacial deformities is similar in prevalence, but differs in clinical appearance. Occlusal, but not psychosocial features deviate from those in the controls. While psychosocial variables accompanied TMD and myofascial pain, increased RCP-ICP slide was related to disc displacement in class III patients.

Clinical significance of vascular endothelial growth factor expression in patients with carcinoma of the mouth floor and tongue.

BACKGROUND/AIM: Although there are several types of malignant oral cancers, more than 90% of all diagnosed oral cancers are squamous cell carcinoma (OSCC). Angiogenesis is a cascade-like mechanism which is essential for tumor growth and metastasis. Therefore, vascular endothelial growth factor (VEGF) expression in OSCC and its effect on clinicopathological characteristics and prognosis is of major interest. So far researches have shown that increased expression of this gene, in other words enhanced sinthesis of this protein (VEGF), independently on other factors, increases a chance for local relapse, and distant metastasis. Consequently, patients with OSCC have poor disease-free survival, as well as poor overall survival. The aim of the study was to determine clinical significance of VEGF expression in patients with stage II and III OSCC. METHODS: This retrospective study analysed 40 patients who had been operated for OSCC of their tongue and the mouth floor. Of these patients, some had stage II and III OSCC with histological grade, G1-G3 and nuclear grade Ng1-Ng3. Two high quality tissue samples were obtained and immunohistochemical expression of VEGF was quantitatively determined by using high microscope amplification. The value of VEGF expression of 20% was rated as significant expression, whereas tumor cells reactivation less than 20% was considered very low or no expression at all. The patients were followed up for a 3-year period. RESULTS: The obtained results showed that 11 (17.5%) patients had VEGF expression less than 20% and 29 (82.5%) above 20%. A statistical significance was immanent with positive nodal status (p < 0.05) and disease stage (p < 0.05). No statistical correlation was found between the level of VEGF expression and histological and nuclear grade, tumor size, disease relapse or patients overall survival. CONCLUSION: Inspite the controversy about the prognostic relevance of VEGF our results as well as the results of previous studies, suggest that the expression of VEGF is not reliable as a clinical parameter for the prognosis and disease outcome but it is one of the important factors for the disease progression.

[Neuroendocrine tumor of the skin of head and neck].

BACKGROUND: Merkel cell carcinom is a rare neuroendrocine tumor of skin which manifests it self through aggressive growth and early regional metastasis. It develops mainly in older population. Locally, the tumor spreads intracutaneously. CASE REPORT: We showed two cases (females of 89 and 70 years old) hospitalized within the last two years. The first patient was treated surgically three times. After the surgery, the patient was treated with radio therapy, and died 3 years from the begining of the treatment. The second patient with this neuroendocrine tumor with the high malignacy potential and huge regional metastasis, was treated surgiclly, and died a month and a half after the operation. CONCLUSION: These two cases confirmed the aggressive and recidivant growth of this tumor with the difficut pathologic investigetion, and the extremlly bad prognosis inspite of the treatment.

[The use of magnetic resonance and MR angiography in the detection of cerebral infarction--a complication of pediatric bacterial meningitis].

BACKGROUND: Association of both cerebral infarction and acute bacterial meningitis is more common in younger patients than in the elderly. The rate of mortality and the frequency of sequela are very high inspite of the use of modern antibiotic therapy. In more than 30% of the cases of childhood bacterial meningitis, both arterial and venous infarctions can occur. The aim of this study was to present the role of the use of magnetic resonance (MRI), and MR angiography (MRA) in the detection of bacterial meningitis in children complicated with cerebral infarctions. METHOD: In the Centre for MR, the Clinical Centre of Serbia, 25 patients with the diagnosis of bacterial meningitis, of which 9 children with cerebral infarction whose clinical condition deteriorated acutely, despite the antibiotic therapy, underwent MRI and MR angiography examination on a 1T scanner. Examination included the conventional spin-echo techniques with T1-weighted saggital and coronal, and T2- weighted axial and coronal images. Coronal fluid attenuated inversion recovery (FLAIR) and the postcontrast T1-weighted images in three orthogonal planes were also used. The use MR angiography was accomplished by the three-dimensional time-of-flight (3D TOF) technique. RESULTS: The findings included: multiple hemorrhagic infarction in 4 patients, multiple infarctions in 3 patients, focal infarction in 1 patient and diffuse infarction (1 patient). Common sites of involvement were: the frontal lobes, temporal lobes and basal ganglia. The majority of infarctions were bilateral. In 3 of the patients empyema was found, and in 1 patient bitemporal abscess was detected. In 8 of the patients MR angiography confirmed inflammatory vasculitis. CONCLUSION: Infarction is the most common sequela of severe meningitis in children. Since the complication of cerebral infarction influences the prognosis of meningitis, repetitive MRI examinations are very significant for the evaluation of the time course of vascular involvement. The use of MRI, especially FLAIR imaging, confirmed its value in the detection and determination of the site and the extent of cerebral infarction. Non-invasive technique of examination, 3D TOF MR angiography clearly shoud show the presence of inflammatory vasculitis.

[FLAIR MR sequence in the diagnosis and follow-up of low-grade astrocytomas].

AIM: To evaluate the sensitivity of fluid-attenuated inversion recovery (FLAIR) sequence in the diagnosis and follow-up of the patients with low-grade astrocytomas compared with T2-weighted (T2W) sequence. METHODS: Twenty-four patients with biopsy-confirmed low-grade astrocytoma (age range, 15-66 years) underwent T1-weighted (T1W), T2W and FLAIR imaging with a superconducting unit 1.0 T. FLAIR images were qualitatively evaluated by comparison with T2W images by the three experienced neuroradiologists. To evaluate the diagnostic value of FLAIR, the neuroradiologists individually assessed the possibilities of the detection of lesions, as well as the possibilities of the differentiation of tumor from the surrounding edema on FLAIR vs. T2W images. Every examiner ranked FLAIR sequence vs. T2W in three degrees: worse, equal and better. RESULTS: The comparison of FLAIR with T2W spin-echo (SE) images with regard to the detection of the lesions showed that 82.8% of FLAIR studies were superior, 17.2% were of similar diagnostic value, and none was inferior to the T2W images. The comparison of images with regard to the differentiation of tumor boundaries vs. surrounding edema showed that 92.5% of FLAIR studies were superior, 7.5% were of similar diagnostic value, and none was inferior to the T2W images. CONCLUSION: Our results were similar to the previous studies' results concerning the advantages of FLAIR sequence in the diagnosis of low grade astrocytomas over T2W sequence. FLAIR was better at showing different tumor components, and at distinguishing CSF from the cystic component, and the postoperative cavity, compared with T2W images. Our conclusion was that FLAIR could be routinely used in the evaluation and follow-up of low-grade astrocytomas.

[Microvascular osteoseptocutaneous radial flap in reconstruction of mandible following war injury].

BACKGROUND: Vascularized osteoseptocutaneous radial flap is commonly used in the reconstruction of composite bony and soft tissue defects of the lower third of the face due to the outstanding quality of its cutaneous component. The aim was to evaluate the primary and overall success in the reconstruction of mandibular defects, following war injuries, with vascularized osteoseptocutaneous radial flap. METHODS: At the Department of Maxillofacial Surgery of the Military Medical Academy Belgrade, there were eight patients with this kind of defect following war injury, and the mandible was reconstructed with a vascularized osteoseptocutaneous radial flap. Bony compartment of the graft was harvested as up to 11 cm long segment of radial circumference. RESULTS: The localization and structure of the defect, features of a harvested compound graft, the procedure of the reestablishment of the mandibular continuity was presented as well as immediate and late complications during the consolidation period, and the primary successful reconstruction in 87.5% of the patients. CONCLUSION: The primary and overall success in the mandibular defects reconstruction with a vascularized osteoseptocutaneous radial flap was equal or even better than those presented in the literature on the reconstruction of the similar defects after tumor resections.

[Brown tumor of the maxilla in patient with secondary hyperparathyroidism]. / Smedi tumor gornje vilice kod bolesnika sa sekundarnim hiperparatireoidizmom.

Brown tumor or parathyroid osteopathy is a kind of bony lesion caused by hyperparathyroidism. It appears as an expansive osteolytic lesion mostly in mandible, ribs, pelvis and femur, but rarely in the upper jaw. Bone resorption is the result of osteoclastic activity due to an increased activity of parathyroid hormone. A 25-years-old male patient was operated on due to clinicaly and radiographicaly obvious maxillary tumor and increased values of parathyroid hormon (PTH-1 050 ng/l). The level of calcium in blood was normal (Ca 2.34 mEq/L). The patient was dialyzed for years because of the chronic renal failure. Histopathologic analysis confirmed brown tumor, that appeared as bony lesion of secondary hyperparathyroidism due to the chronic renal failure. The operation of the upper jaw had been performed before parathyroidectomy, due to an excessive growth of tumor followed by heavy epistaxes. The subsequent parathyroidectomy was followed by the regression of remaining bony lesions.