Elismauro Francisco Mendonça

Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma

OBJECTIVE To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed. MATERIALS AND METHODS The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines. The level required for statistical significance was defined as p<0.05. RESULTS The data showed a predominance of M2 phenotype (high percentage of IL-10(+)TGF-β(+)) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-β was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGFβ and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months). CONCLUSION A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-β production, and consequently greater lymph node involvement and reduced patient survival time.

THE PREVENTION OF INDUCED ORAL MUCOSITIS WITH LOW-LEVEL LASER THERAPY IN BONE MARROW TRANSPLANTATION PATIENTS: A RANDOMIZED CLINICAL TRIAL

BACKGROUND DATA AND OBJECTIVE Patients who have received high doses of chemotherapy, either alone or in combination with total body irradiation often cite oral mucositis (OM) as the most debilitating side effect. The aim of this study was to investigate the clinical effects of low-level laser therapy (LLLT) on the prevention of conditioning-induced OM in hematopoietic stem cell transplantation (HSCT). METHODS We randomized 42 patients who underwent autologous or allogeneic HSCT. A low-level InGaAlP diode laser was used, emitting light at 660 nm, 40 mW, and 4 J/cm(2). An evaluation of OM was carried out using the World Health Organization scale. RESULTS AND CONCLUSION In the LLLT group, 57.1% of patients had an OM grade 0, 9.6% had grade 1, and 33.3% had grade 2, whereas in the control group, only 4.8% of patients were free of OM (grade 0). Our results indicate that the preventive use of LLLT in patients who have undergone HSCT is a powerful instrument in reducing OM incidence.

Occurrence of maxillary sinus abnormalities detected by cone beam CT in asymptomatic patients

BackgroundAlthough cone beam computed tomography (CBCT) images of the maxillofacial region allow the inspection of the entire volume of the maxillary sinus (MS), identifying anatomic variations and abnormalities in the image volume, this is frequently neglected by oral radiologists when interpreting images of areas at a distance from the dentoalveolar region, such as the full anatomical aspect of the MS. The aim of this study was to investigate maxillary sinus abnormalities in asymptomatic patients by using CBCT.Methods1113 CBCT were evaluated by two examiners and identification of abnormalities, the presence of periapical lesions and proximity to the lower sinus wall were recorded. Data were analyzed using descriptive statistics, chi-square tests and Kappa statistics.ResultsAbnormalities were diagnosed in 68.2% of cases (kappa = 0.83). There was a significant difference between genders (p < 0.001) and there was no difference in age groups. Mucosal thickening was the most prevalent abnormality (66%), followed by retention cysts (10.1%) and opacification (7.8%). No association was observed between the proximity of periapical lesions and the presence and type of inflammatory abnormalities (p = 0.124).ConclusionsAbnormalities in maxillary sinus emphasizes how important it is for the dentomaxillofacial radiologist to undertake an interpretation of the whole volume of CBCT images.

Differential infiltration of CD8+ and NK cells in lip and oral cavity squamous cell carcinoma.

BACKGROUND CD8+ and natural killer (NK) cells have been considered the most effective cells in the combat of cancer, contributing to better prognosis and longer survival. METHODS The aim of this study was to evaluate the population of CD8+ and NK cells, by immunohistochemistry, in samples of oral cavity squamous cell carcinoma (OCSCC) and lip squamous cell carcinoma (LSCC), leukoplakia, actinic cheilitis, and healthy oral mucosa (control). The relationship of CD8+ and NK cells with survival data, lymph node metastasis, tumor size, and proliferative index was also evaluated. RESULTS The number of peritumoral and intratumoral CD8+ and NK cells was significantly higher in LSCC, when compared with control, pre-malignant lesions, and OCSCC. A higher proportion of peritumoral CD8+ cells demonstrated correlation with a lower neoplastic proliferative index. Moreover, patients with OCSCC with a high density of peritumoral CD8+ cells showed a tendency towards a longer survival time. CONCLUSIONS The differential CD8+ and NK cells infiltration in oral SCC might reflect a distinctive tumor microenvironment with a favorable local cytotoxic immune response against neoplastic cells.

Involvement of CXCL12 and CXCR4 in Lymph Node Metastases and Development of Oral Squamous Cell Carcinomas

The chemokine stromal cell-derived factor (SDF-1/CXCL12) and its specific receptor, CXCR4, have been implicated in the regulation of tumor growth and organ-specific spread. The aim of this study was to determine the expression of CXCL12 and CXCR4 in samples obtained from primary squamous cell carcinoma (SCC) of the oral cavity (OCSCC) and of the lip (LSCC) and in metastatic and non-metastatic lymph node tissues. The relationship of CXCL12/CXCR4 with clinical and microscopic parameters was also evaluated. The analysis of mRNA expression revealed a higher expression of CXCR4 in oral SCC compared with healthy oral mucosa (p = 0.006). The density of CXCR4+ cells was higher in parenchyma of OCSCC with lymph node metastases than in LSCC. With regard to the stroma, OCSCC showed a greater CXCR4+ and CXCL12+ cell percentage in relation to LSCC. Furthermore, the density of CXCL12+ and CXCR4+ nodal cells was higher in metastatic than non-metastatic lymph nodes in the same patients. Considering clinical and microscopic parameters, we found a positive association between the percentages of CXCL12+ and CXCR4+ stromal cells and the tumor proliferation index. Our findings suggest that the CXCL12/CXCR4 system may play a role in tumor cell spread to lymph nodes and also in neoplastic development.

Distinctive clinical and microscopic features of squamous cell carcinoma of oral cavity and lip

OBJECTIVE This study was undertaken to gain insight into the distinctive features of squamous cell carcinoma of the lip (LSCC) and oral cavity (OCSCC). STUDY DESIGN A total of 37 cases of LSCC and 54 of OCSCC were compared regarding clinical and microscopic findings. RESULTS Predominance of head and neck TNM stages (HNTNM) T1-T2 in LSCC and T3-T4 in OCSCC was observed. A significant percentage (33.3%) of patients with OCSCC at HNTNM T1-T2 presented cervical lymph node metastasis and 18.75% died, whereas lymph node metastasis was absent and no patient died with LSCC at HNTNM T1-T2. LSCC demonstrated a higher number of cases with intense peritumoral inflammatory infiltrate compared with OCSCC. The analysis of the proliferative index demonstrated a significantly higher percentage of PCNA+ and Ki-67+ cells in OCSCC compared with LSCC. CONCLUSION Our results suggest that OCSCC and LSCC demonstrate distinct clinical and microscopic characteristics that reflect different biologic behavior and prognosis.

Differential Diagnosis of Apical Periodontitis and Nasopalatine Duct Cyst

INTRODUCTION An accurate differential diagnosis of apical periodontitis (AP) and nasopalatine duct cyst (NPDC) should be established to define the best treatment for endodontically treated maxillary anterior teeth with apical periodontitis. Three-dimensional cone beam computed tomography (CBCT) images help to plan treatment and to define an initial diagnostic hypothesis. However, endodontic treatment or retreatment may be unnecessarily prescribed when radiographs show a superimposition of the incisor foramen over the apex of maxillary central incisors, mimicking AP. Diseases of nonendodontic origin that affect the tooth apex, such as NPDC, should be included in the differential diagnosis. METHODS AND RESULTS Four clinical cases of patients with large periapical radiolucencies and similar radiographic features are described. AP is usually a consequence of endodontic infection; in cases of NPDC, however, spontaneous epithelial proliferation, in addition to bacterial infection and trauma, may also contribute to cyst formation. The frequency and recurrence rates of NPDC are low, and its behavior is less aggressive. Surgical enucleation of the periapical lesion is recommended after nonsurgical treatment does not heal AP. CONCLUSIONS The use of new diagnostic tools, such as CBCT imaging, may provide detailed high-resolution images of oral structures, which help to make an initial diagnostic hypothesis and to plan surgery. Histopathology is mandatory for the differential diagnosis.

Expression of bone resorption regulators (RANK, RANKL, and OPG) in odontogenic tumors.

OBJECTIVE To investigate the expression of bone resorption regulators (receptor activator of nuclear factor kappa B [RANK], RANK ligand [RANKL], and osteoprotegerin [OPG]) in calcifying cystic odontogenic tumor (CCOT), adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic tumor (CEOT), odontogenic myxoma (OM), and ameloblastic fibroma (AF). STUDY DESIGN The expression of these mediators was evaluated by means of immunohistochemistry. RESULTS All specimens demonstrated positive immunoreactivity to RANK, RANKL, and OPG. The quantification of these mediators in epithelium revealed a similar pattern of expression for RANKL and OPG in CCOT, AOT, CEOT, and AF. With regard to stromal/mesenchymal cells, the majority of AOT and CCOT cases showed a higher content of OPG than RANKL, whereas CEOT, OM, and especially AF had a tendency to present a greater content of RANKL than OPG. CONCLUSION Our data indicate that the CCOT, AOT, CEOT, OM, and AF cell constituents express key regulators of bone metabolism that might locally modulate tumor-associated bone resorption.

Effect of intraoral low-level laser therapy on quality of life of patients with head and neck cancer undergoing radiotherapy.

Low‐level laser therapy has been used to reduce complications of head and neck cancer treatment. The aim was to assess the impact of laser in the quality of life (QOL) of patients receiving radiotherapy.

Effect of low level laser therapy in the reduction of oral complications in patients with cancer of the head and neck submitted to radiotherapy.

The aim of this study was to assess the effect of low level laser therapy on reducing the occurrence and severity of oral complications in patients with head and neck cancer undergoing radiotherapy. Sixty head and neck cancer outpatients from a cancer hospital receiving radiotherapy were selected and randomly assigned into two groups. The laser group was irradiated with an InGaAlP laser and the control received sham laser. The assessment of complications (oral mucositis, pain) was carried out one week after starting radiotherapy, and at the fifteenth and thirtieth sessions of radiotherapy. All patients from both groups showed some degree of oral mucositis. Better outcomes were observed in the laser group when compared with the control in the follow-up sessions, indicating lower degrees of oral mucositis, pain and higher salivary flow (p < .05). These findings support the use of laser therapy as an adjuvant treatment for the control of oral complications.