Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area.

Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.

Prevalence of malocclusions in a young Brazilian population.

Malocclusions are generally treated in adolescents and adults, but they are established at an early age. The purpose of this study was to determine the prevalence of malocclusions in a young Brazilian population. The sample included 926 children, 8 to 12 years old, attending 5 public schools in the state of Goias, Brazil The type of occlusion was visually determined during the oral exam and statistical analysis, Chi-square test, was performed to correlate the prevalence of malocclusion with gender and with age. 819 patients out of the 926 patients had some type of malocclusion. From those, 513 patients had a class I malocclusion, 201 patients were classified as class II malocclusion, and 105 patients were class III malocclusion. Vertically, 62 patients showed a deep bite and 61 patients had an open bite. Transversely, 40 patients presented a bilateral posterior crossbite, 54 patients had a posterior crossbite on the left side, and 39 patients had a posterior crossbite on the right side. No significant correlation between gender and malocclusions was found and the number of patients with malocclusions between boys and girls were similar. Considering the three spatial planes, there is a high prevalence of malocclusions among the young Brazilian population. Therefore, the dental community must improve health policies and treat malocclusions earlier.

Radiation treatment of glottic squamous cell carcinoma, stage I and II: analysis of factors affecting prognosis.

PURPOSE: At least in some European Countries, there is still considerable controversy regarding the choice between surgery and radiotherapy for the treatment of patients with early laryngeal-glottic carcinoma. METHODS AND MATERIALS: Two hundred and forty-six patients with laryngeal-glottic neoplasms, Stage I-II, were treated with radical radiotherapy. Before radiotherapy the patients were evaluated to determine the surgical procedure of choice. Either 66-68.4 Gy (33-38 fractions) or 63-65 Gy (28-29 fractions) of radiation therapy (RT) were administered. The overall disease free survival was determined for each subgroup of patients. Univariate and multivariate analyses were performed to determine significant prognostic variables. RESULTS: Five- and 10-year overall survival rates were 83 and 72%, respectively. At a median follow-up of 6 years 204 patients are alive and disease free. No patient developed distant metastases. One patient died of a large local recurrence, 38 patients died of causes unrelated to their tumor, and 3 patients were lost to follow-up. The multivariate analysis confirmed that performance status (PS), macroscopic presentation of the lesion, and persistence of dysphonia after radiotherapy are significant prognostic factors. CONCLUSIONS: According to the multivariate analysis, the patients with PS > 80 and with exophytic lesions are eligible for radical RT. The surgical procedure proposed for each patient was not found to be an independent prognostic factor.

Submandibular approach and use of the harmonic instrument in lateral oral cavity and oropharyngeal oncologic surgery.

The approach to the surgical treatment of lateral oral cavity and oro-pharyngeal cancer has undergone many changes over the years, passing from a demolitive approach involving segmental resectioning of the mandible to a conservative approach with temporary mandibulotomy. The complications resulting from these two different approaches invited further review of the various indications related to them. The present report considers, through a retrospective analysis, whether the sub-mandibular approach, which envisages the use of the harmonic instrument, is an oncologically correct alternative and whether it actually reduces the number of early and late complications. From 2003 to 2009, 259 patients underwent surgery for lateral oral cavity and oro-pharyngeal cancer. A sub-mandibular approach was used in 163 patients, and a conservative trans-mandibular approach in 12. The results showed that the number of late complications and T recurrences was significantly lower in those patients in whom the sub-mandibular approach was carried out. There was no difference in the microscopic examination of the resection margins. The use of the harmonic instrument made it possible to perform "en bloc" (T+N) operations working in narrow spaces with less intra-operative bleeding, which contributed to adequate oncological radicality.