The association between referral by specialists in oral diagnosis on survival rates of patients with oral cancer: A retrospective cohort study.

BACKGROUND: To assess the influence of diagnosis and referral provided by specialists in oral diagnosis on disease-free survival and overall survival of patients with oral cancer. METHODS: A cohort of 282 patients with oral cancer treated at a regional cancer hospital from 1998 to 2016 was analyzed retrospectively. The referral register of the patients was analyzed and assigned to two groups: (1) those referred by oral diagnosis specialists (n = 129), or (2) those referred by nonspecialized professionals (n = 153). The cancer treatment evolution was assessed from the patients' records, and the outcome was registered concerning cancer recurrence and death. Sociodemographic and clinicopathological variables were explored as predictors of disease-free survival and overall survival. RESULTS: Group 1 exhibited lower T stages and a reduced incidence of regional and distant metastases. Surgery was performed in 75.2% of cases in Group 1, while in Group 2, the rate was 60.8%. Advanced T stages and regional metastases reduced the feasibility of surgery. Higher TNM stages and tumor recurrence were associated with decreased disease-free survival, while surgical intervention was a protective factor. Higher TNM stage had a negative impact on the overall survival. CONCLUSION: Specialized oral diagnosis did not directly impact disease-free survival and overall survival and did not influence the indication of surgery in oral cancer; however, it was associated with the diagnosis of early tumors and better prognosis.

Effects of a mucoadhesive phytomedicine (Curcuma longa L. and Bidens pilosa L.) on radiotherapy-induced oral mucositis and quality of life of patients undergoing head and neck cancer treatment: randomized clinical trial.

PURPOSE: To assess the effect of a mucoadhesive herbal medicine containing curcuminoids and a glycerinated extract of Bidens pilosa L. (FITOPROT) in association with photobiomodulation (PBM) therapy and a Preventive Oral Care Program (POCP) compared to PBM and POCP in the treatment of radiotherapy (RT)-induced oral mucositis (ROM) and in the quality of life of these patients. METHODS: A double-blind clinical trial was performed with head and neck cancer patients undergoing RT or chemoradiotherapy. Participants were randomized into two groups: Group 1 (n=27): PBM and POCP; and Group 2 (n=25): PBM, POCP and FITOPROT. The PBM protocol was daily irradiation, 660 nm, 25mW, 0.25 J/point from the first until the last day of RT. The FITOPROT was used as mouthwash twice a day. ROM was evaluated based on the scales of the World Health Organization and National Cancer Institute. The quality of life was evaluated using the University of Washington Questionnaire, OHIP-14 and Patient-Reported Oral Mucositis Symptom Scale. The MMAS-8 questionnaire was used to evaluated the adherence to POCP and FITOPROT. Data were collected at baseline, 7th, 14th, 21st, and 30th RT sessions. RESULTS: No statistical differences were found between the groups for the ROM evaluation. Both groups experienced worsening of the quality of life during the RT. No statistically significant differences between groups were observed for any of the instruments evaluated. CONCLUSION: The results suggest that PBM associated with FITOPROT and POCP control the severity of ROM and stabilize the QoL of patients with head and neck cancer. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC-RBR-9vddmr; UTN code: U1111-1193-2066), registered in August 8th, 2017.

Orofacial Manifestations Assisting the Diagnosis of Cowden Syndrome in a Middle-Aged Patient: Case Report and Literature Overview.

Middle-aged and old adults (≥ 50 years) diagnosed with Cowden syndrome (CS) with orofacial manifestations are uncommon. We describe a case of CS in a 53-year-old female showing "narrow bird-like" face, macrocephaly, acral keratoses, oral candidiasis, burning in the mouth, and multiple asymptomatic papillomatous lesions with a cobblestone pattern distributed on the alveolar ridge, tongue, buccal mucosa, and commissure. The histopathological features of lesions of the oral mucosa were those of papillary fibroepithelial hyperplasia. Immunohistochemistry revealed strong positivity for PTEN and p53 in most epithelial cells, while the expression of Bcl-2, S-100, and Ki-67 was weak/negative. According to a review conducted in PubMed, Web of Science, Embase, and Scopus for the analysis of reports of CS individuals ≥ 50 years with orofacial manifestations, 56 cases have been described in literature. Predilection for women was observed, with a female:male ratio of 2.3:1. Thirty-five (62.5%) individuals developed some malignant neoplasms. Oral health providers should be aware of the orofacial aspects of CS, including multiple papillomatosis, which can be an important criterion for diagnosis. Since malignancies may occur in older adults with CS, the need for strict surveillance is necessary. The present case has been under follow-up for 7 years without evidence of other manifestations.

Angiogenesis pattern and H3.3 histone mutation in aggressive and non-aggressive central giant cell lesions.

OBJECTIVE: The aim of this study was to evaluate angiogenesis in central giant cell lesions (CGCL) and its association with biological behavior. In addition, investigation of the histone H3.3 mutation was performed. DESIGN: Thirty-eight cases of CGCL were classified as aggressive (n = 9) or nonaggressive (n = 29). Cases were submitted to immunohistochemistry to compare angiogenesis using Wilms' tumor protein 1 (WT1), platelet endothelial cell adhesion molecule (CD31) and endoglin (CD105) between groups. To verify the presence of genic mutation, histone H3.3 was investigated. RESULTS: WT1 was expressed in mononuclear and giant cells of all cases. CD31 and CD105 were expressed in CGCL microvessels, with a higher CD105 microvascular density than CD31. No statistically significant difference was observed between groups. None of the cases studied showed the histone mutation. CONCLUSIONS: There was no difference between aggressive and nonaggressive lesions regarding the angiogenic markers. The expression of WT1 and CD105 suggests that CGCL presents a tumoral vascular pattern with high neoangiogenic activity. The absence of histone mutation may indicate that CGCL is not a true giant cell tumor.

Central giant cell granuloma of the maxilla: Long-term follow-up of a patient treated with an adjuvant corticosteroid.

BACKGROUND: Central giant cell granuloma (CGCG) is one of the most intriguing lesions of the jaws and its nature has not yet been fully elucidated. Clinically, some CGCG behave more aggressively, while others have an indolent course. In cases of aggressive CGCG of the maxilla, effective personalized therapies are worth understanding. CASE REPORT: We report here a challenging case of aggressive CGCG in a 15-year-old girl which was misdiagnosed as an endodontic lesion. Radiographically, a large osteolytic lesion involving the hard palate from the central incisor to the second premolar, extending into the nasal cavity, with loss of the lamina dura and cortical resorption was observed. The lesion expanded aggressively after extensive curettage. With possible mutilation and defects due to a more radical approach to the lesion, treatment with systemic prednisone and intralesional triamcinolone hexacetonide associated with a calcitonin nasal spray was instituted. The decision in favor of this therapeutic strategy was made after careful immunohistochemical analysis of calcitonin and glucocorticoid receptors. The H-score for the staining of glucocorticoid and calcitonin receptors in multinucleated giant cells was 222 and 153.6, respectively. The lesion reduced in size, and no adverse effects associated with medications were observed. Another curettage was performed, and only fibrous connective tissue was found. The patient is in follow-up for 11 years without evidence of recurrence. CONCLUSION: Pharmacological agents hold clinical promise in cases of aggressive CGCG affecting the maxilla of pediatric patients. Investigating the expression of calcitonin and glucocorticoid receptors in order to plan treatment is very helpful in the decision to manage aggressive CGCG.

Pixel gray measurement for the diagnosis of dental ankylosis in cone beam computed tomography images.

OBJECTIVE: The aim of this study was to investigate dental ankylosis in unerupted or partially erupted teeth by using cone beam computed tomography (CBCT) to quantify pixel intensity. STUDY DESIGN: In total, 157 CBCT images from individuals with a total of 206 unerupted or partially erupted teeth with suspected ankylosis were evaluated. CBCT images were analyzed for the presence of ankylosis by 2 oral radiologists by quantifying mean pixel intensities (analysis 1) and variations in pixel intensities (analysis 2) in normal and ankylosed regions. The association between ankylosis and demographic and tooth-related factors was also examined. RESULTS: Ankylosis was diagnosed in 57 teeth (27.7%). The diagnosis was established with all 3 multiplanar reconstruction views in 22 of these teeth (38.6%). In analysis 1, a higher pixel intensity was observed in areas with ankylosis compared with normal periodontal ligament (PDL) density as a result of bone deposition in this region, which is characteristic of ankylosis (P < .001). In analysis 2, reductions in pixel intensity were greater in the PDL areas than in the ankylosed areas. Ankylosis was significantly associated with the anterior teeth, the maxillary arch, single-rooted teeth, and impacted teeth (P ≤ .026). CONCLUSIONS: Our results suggest that CBCT measurement of pixel intensity may be useful for the diagnosis of ankylosis.

Photobiomodulation reduces the impact of radiotherapy on oral health-related quality of life due to mucositis-related symptoms in head and neck cancer patients.

To assess the effectiveness of photobiomodulation therapy (PBMT) in the oral health-related quality of life (OHRQoL) of patients with head and neck cancer undergoing radiotherapy (RT), using the Oral Health Impact Profile-14 (OHIP-14) and the Patient-Reported Oral Mucositis (OM) Symptoms Scale (PROMS), and to correlate OM degree with the PROMS and OHIP-14 scores. Forty-eight patients undergoing RT for head and neck cancer were randomly assigned into two groups: PBMT group (n = 25)-daily PBMT associated with a preventive oral care program (POCP); and control group (n = 23)-receiving POCP exclusively. OHRQoL was assessed using the PROMS and OHIP-14 questionnaires. OM degrees were classified according to the World Health Organization and the National Cancer Institute scales. Assessments were performed at the 1st, 7th, 14th, 21st, and 30th RT sessions. PBMT was effective in preventing and treating severe OM. Both groups showed increased OHRQoL impacts throughout the RT sessions; however, higher impacts were observed in the control group, mainly at the final stage of treatment (21st and 30th RT sessions). Significant correlations were found between the severity of OM and PROMS scores in the total sample and the control group at all RT periods. PROMS and OM scores were positive correlated at 14th, 21st, and 30th RT sessions in the control group, suggesting that this instrument is useful in classifying OM. PBMT was effective in treating and preventing severe OM and OM-related symptoms, and with consequent positive impacts in OHRQoL in head and neck patients undergoing RT. The PROMS scale was helpful instrument for assessment of the severity of OM. Brazilian Clinical Trials database (ReBEC - RBR-5h4y4n), registered in Aug, 24th 2017.

A prospective study on oral adverse effects in head and neck cancer patients submitted to a preventive oral care protocol.

OBJECTIVE: To evaluate the occurrence and severity of oral complications, number of radiotherapy (RT) interruptions and quality of life (QoL) in a population of head and neck cancer patients receiving a preventive oral care program (POCP) and photobiomodulation therapy (PBMT). METHODS: Prospective cohort of 61 head and neck cancer patients undergoing radiochemotherapy were monitored and submitted to a POCP that included oral hygiene and plaque control, removal of infection foci, dental restorations, periodontal therapy, fluorotherapy, oral hydration, and denture removal at night, combined with daily PBMT. Outcomes included occurrence of adverse effects such as severity of oral mucositis (OM) and oral symptoms (pain, solid and fluid dysphagia, odynophagia, dysgeusia), quality of life impacts, and interruptions of radiotherapy (RT) due to symptoms. Disease-free and overall survival rates were evaluated. RESULTS: There was a significant improvement in oral health conditions between initial assessment and the two longitudinal assessments (p < 0.05), which indicates that the POCP was effective for plaque control and reduction of gingival inflammation. All participants were free of OM at the beginning of the RT regimen and only 45.9% after the 7th session, and few patients ranked the highest score of OM. For all symptoms related to OM, there was a progressive increase of severity until the 14th RT session, which remained stable until the completion of the RT regimen. The same effect was observed for the quality of life measures. Discontinued RT due to OM occurred in only three patients (5%), and the maximum duration was 10 days. The overall survival rate was 77% and disease-free survival was 73.8%. Lower survival time was observed for patients with no response to RT (p < 0.01). CONCLUSIONS: The findings of this study suggest a positive effect of an oral preventive care program for head and neck cancer patients submitted to RT. The PBMT associated with a rigorous POCP resulted in satisfactory control of oral adverse effects, reduction of quality of life impacts, and interruption of RT regimen due to severe OM.

Odontoma composto em adulto e sua complexidade de tratamento: relato de caso clínico / Compound odontoma in adult and its treatment complexity: clinical case report

Introdução: Odontoma é o tumor odontogênico mais frequente e é diagnosticado durante as primeiras décadas de vida, devido ao atraso na erupção de um dente ou por meio de exame radiográfico de rotina. As características radiográficas e microscópicas são úteis para sua classificação em complexo ou composto. Odontomas em pacientes adultos são incomuns e podem ser complexos de tratar. Objetivo: O objetivo deste trabalho foi relatar a complexidade de tratamento de um odontoma composto em paciente adulto. Material e Método: o presente artigo é do tipo relato de caso. Resultados: Paciente do sexo feminino, 32 anos, compareceu ao cirurgião-dentista para avaliação clínica de rotina. Durante o exame clínico foi observada a ausência do dente 43, exames radiográficos demonstraram lesão mista, bem delimitada, com estruturas semelhantes a dentículos, localizada na região anterior de mandíbula do lado direito, entre as raízes dos dentes 42 e 44, promovendo deslocamento do dente 43 para a base da mandíbula. Devido à localização da lesão e seus efeitos no dente 43, a paciente foi submetida à ressecção da lesão sob anestesia geral. Foi realizada osteotomia na tábua óssea vestibular da mandíbula, remoção de múltiplas estruturas semelhantes a dentes, instalação de placa de reconstrução mandibular sistema 2.4 com cinco parafusos do mesmo sistema e enxerto ósseo com biomaterial aloplástico. O dente 13 foi extraído. As radiografias de controle pós-operatório evidenciaram bom posicionamento do material. O controle pós-operatório indica que a paciente encontra-se bem e sem ausência de sinais de recidiva ou complicações cirúrgicas. Conclusão: O diagnóstico tardio de odontomas associado ao deslocamento dentário ocasionado pelo tumor podem tornar o seu tratamento mais complexo.

Introduction: The most common odontogenic tumor is Odontoma, and is diagnosed during the first decades of life, due to a delayed eruption of a tooth, or through routine radiographic examination. From the radiographic and microscopic characteristics is classified into complex or compound. Odontomas in adult patients are uncommon and can have a complex treatment. Aim: The aim of this study was to report the complexity of treating a compound odontoma in an adult patient. Material and Methods: the present research is a case report. Results: A 32-year-old female patient attended the dental surgeon for routine evaluation. During the clinical examination, the absence of tooth 43 was observed, image exams revealed a well-defined mixed lesion consisting of denticles, located in the anterior region of the right mandible, between the roots of the teeth 42 and 44, the lesion promoted displacement of tooth 43. Due to the location and its effects on tooth 43, the patient underwent resection of the lesion under general anesthesia. Surgery proceeded with buccal plate osteotomy, removal of multiple tooth-like structures, installation of mandibular reconstruction plates 2.4 with five screws and bone graft with alloplastic biomaterial. Tooth 13 was extracted. Postoperative control radiographs showed good positioning of the material. Postoperative control show that patient does not have recurrence signal or complications due to surgery. Conclusion: Late diagnosis of odontomas associated with tooth displacement caused by the tumor may make its treatment more complex.

Effect of photobiomodulation on the severity of oral mucositis and molecular changes in head and neck cancer patients undergoing radiotherapy: a study protocol for a cost-effectiveness randomized clinical trial.

BACKGROUND: Oral mucositis (OM) is the most frequent and debilitating acute side effect associated with head and neck cancer (HNC) treatment. When present, severe OM negatively impacts the quality of life of patients undergoing HNC treatment. Photobiomodulation is a well-consolidated and effective therapy for the treatment and prevention of severe OM, and is associated with a cost reduction of the cancer treatment. Although an increase in the quality of life and a reduction in the severity of OM are well described, there is no study on cost-effectiveness for this approach considering the quality of life as a primary outcome. In addition, little is known about the photobiomodulation effects on salivary inflammatory mediators. Thus, this study aimed to assess the cost-effectiveness of the photobiomodulation therapy for the prevention and control of severe OM and its influence on the salivary inflammatory mediators. METHODS/DESIGN: This randomized, double-blind clinical trial will include 50 HNC patients undergoing radiotherapy or chemoradiotherapy. The participants will be randomized into two groups: intervention group (photobiomodulation) and control group (preventive oral care protocol). OM (clinical assessment), saliva (assessment of collected samples) and quality of life (Oral Health Impact Profile-14 and Patient-Reported Oral Mucositis Symptoms questionnaires) will be assessed at the 1st, 7th, 14th, 21st and 30th radiotherapy sessions. Oxidative stress and inflammatory cytokine levels will be measured in the saliva samples of all participants. The costs are identified, measured and evaluated considering the radiotherapy time interval. The incremental cost-effectiveness ratio will be estimated. The study will be conducted according to the Brazilian public health system perspective. DISCUSSION: Photobiomodulation is an effective therapy that reduces the cost associated with OM treatment. However, little is known about its cost-effectiveness, mainly when quality of life is the effectiveness measure. Additionally, this therapy is not supported by the Brazilian public health system. Therefore, this study widens the knowledge about the safety of and strengthens evidence for the use of photobiomodulation therapy, providing information for public policy-makers and also for dental care professionals. This study is strongly encouraged due to its clinical relevance and the possibility of incorporating new technology into public health systems. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials-ReBEC, RBR-5h4y4n . Registered on 13 June 2017.

Expression of adhesion proteins (E-cadherin and ß-catenin) and cell proliferation (Ki-67) at the invasive tumor front in conventional oral squamous cell and basaloid squamous cell carcinomas.

OBJECTIVE: Investigate, on a comparative basis, the expression of the adhesion molecules E-cadherin (E-cad), ß-catenin (ß-cat) and the proliferation index (Ki-67) at the invasive tumor front (ITF) in squamous cell carcinoma (SCC) and basaloid squamous cell carcinoma (BSCC). MATERIAL AND METHODS: Thirty-five SCC and 16 BSCC cases were evaluated by immunohistochemistry. Clinicopathological and survival data were also evaluated and compared. RESULTS: There was a low expression of E-cad in the cytoplasmic membrane (p=0.50) as well as in the nucleus (p=0.31) for both SCC and BSCC. A high expression of E-cad was seen in the cytoplasm for the SCC group (80%) when compared to the BSCC group (25%) (p<0.01). The expression of ß-cat was low in the cytoplasmic membrane and high in the cytoplasm in both SCC and BSCC groups. Both types of carcinoma presented low expressions of ß-cat in the nucleus (p=0.03). The Ki-67 expression was low irrespective of tumor variant. The high expression of E-cad in the cytoplasm was associated with T3/T4 tumors (p=0.04) in the SCC group and there was no significant association of E-cad, ß-cat, Ki-67 with the other clinical variables. In terms of disease-free survival and overall survival, there were no significant differences between SCC and BSCC. CONCLUSION: The E-cad-ß-cat system was found to be dysregulated in both oral SCC and oral BSCC. The Ki-67 cell proliferation index was extremely low in the cases investigated and consequently had no prognostic value.

Characterization of dendritic cells in lip and oral cavity squamous cell carcinoma.

BACKGROUND: There may be differences in the antitumor immunity induced by dendritic cells (DCs) during the development of squamous cell carcinoma (SCC) located in the lip rather than in the oral cavity. The aim of this study was to evaluate the number of immature and mature DCs in SCC and potentially malignant disorders of the oral cavity and lip. METHODS: Immunohistochemistry was used to identify the number (cells/mm(2) ) of immature (CD1a(+) ) or mature (CD83(+) ) DCs in samples of oral cavity SCC (OCSCC) (n = 39), lip SCC (LSCC) (n = 23), leukoplakia (LK) (n = 21), actinic cheilitis (AC) (n = 13), and normal mucosa of the oral cavity (OC control, n = 12) and the lip (lip control, n = 11). RESULTS: The number of CD1a(+) cells tended to be higher in the OC control samples compared with the LK (P = 0.04) and OCSCC (P = 0.21). Unlike, this cell population was lower in the lip control than in AC or LSCC (P < 0.05). The number of CD83(+) cells was increased in the LSCC samples compared with the AC and lip control (P = 0.0001) and in OCSCC compared with both the LK (P = 0.001) and OC control (P = 0.0001) samples. LSCC showed an elevated number of CD1a(+) and CD83(+) cells compared with OCSCC (P = 0.03). The population of mature DCs was lower than the population of immature DCs in all of the tested groups (P < 0.05). CONCLUSION: There were a greater number of both mature and immature DC populations in the LSCC samples than in the OCSCC, which could contribute to establishing a more effective immune antitumor response for this neoplasm.

Glucocorticoids, calcitonin, and osteocalcin cannot differentiate between aggressive and nonaggressive central giant cell lesions of the jaws.

OBJECTIVE: To evaluate the expression of glucocorticoid receptor (GR), calcitonin receptor (CTR), and osteocalcin (OC) in aggressive and nonaggressive central giant cell lesions (CGCLs). The numbers of mitotic and multinucleated giant cells were also evaluated. STUDY DESIGN: Thirty-one cases of CGCL were submitted for immunohistochemistry. Mitotic figures and multinucleated giant cells were assessed through histochemical analyses. RESULTS: Positive staining for GR, CTR, and OC was observed in all cases studied. There were no differences between CGCL variants with regard to the expression of GR, CTR, or OC. The aggressive group showed a higher number of multinucleated giant cells compared with the nonaggressive group (P < .05). CONCLUSIONS: Nonaggressive and aggressive CGCLs cannot be distinguished by OC, CTR, or GR expression, although the number of multinucleated giant cells may help differentiate between CGCL types.