Predisposing factors for increased cortisol levels in oral cancer patients.

Cancer patients may have a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal secretion of cortisol. Increased cortisol levels have been associated with worse prognosis in patients with different types of tumors. Although anxiety and depression can trigger an abnormal cortisol secretion, little is known regarding the influence of these emotional disorders on HPA axis dysregulation in cancer patients when evaluating together with demographic, clinicopathological and biobehavioral variables. This cross-sectional study analyzed the pre-treatment plasma cortisol levels of 133 patients with oral squamous cell carcinoma (OSCC) and its association with demographic, clinicopathological, biobehavioral and psychological variables. Plasma cortisol levels were measured by electrochemiluminescence, and anxiety and depression symptoms were assessed using Beck Anxiety Inventory (BAI) and Depression (BDI), respectively. Demographic, clinicopathological and biobehavioral data were collected from patients' medical records. Results from multivariate analysis showed that the occurrence of cancer-induced pain was predictive for higher cortisol levels (OR = 5.388, p = 0.003). Men with OSCC were 4.5 times more likely to have higher plasma cortisol levels than women (OR = 4.472, p = 0.018). The effect of sex on cortisol concentrations was lost in the adjusted model for clinical staging (OR = 2.945, p = 0.116). The absence of chronic alcohol consumption history was a protective factor for highest hormone concentrations in oral cancer patients (OR = 0.104, p = 0.004). Anxiety symptoms measured by BAI as "hands trembling" (OR = 0.192, p = 0.016) and being "nervous" (OR = 0.207, p = 0.0004) were associated with lower cortisol levels. In contrast, the feeling of "fear of losing control" was a risk factor for highest hormone concentrations (OR = 6.508, p = 0.0004). The global score and specific symptoms of depression measured by the BDI were not predictive for plasma hormone levels (p > 0.05). Together, our results show that pain, alcohol consumption and feeling fear are independent factors for increased systemic cortisol levels in patients with oral cancer. Therefore, psychological intervention, as well as control of pain and alcohol consumption, should be considered to prevent the negative effects of cortisol secretion dysregulation in cancer patients.

Sex, pain, alcoholism and anxiety symptoms are predictive for systemic cortisol levels in oral cancer patients / Sexo, dor, etilismo e sintomas de ansiedade são preditivos para níveis sistêmicos de cortisol em paciente com câncer de boca

Pacientes com câncer podem apresentar uma desregulação do eixo hipotálamohipófise-adrenal (HPA) e secreção aumentada do hormônio cortisol. Níveis elevados de cortisol têm sido associados a pior prognóstico de diferentes tipos de câncer. Embora alterações psicológicas como ansiedade e depressão possam deflagrar uma secreção anormal de cortisol, pouco se sabe sobre a influência destas desordens emocionais na desregulação do eixo HPA em pacientes com câncer quando avaliadas em conjunto com variáveis demográficas, clinicopatológicas e biocomportamentais. Este estudo transversal avaliou os níveis plasmáticos de cortisol em 133 pacientes com carcinoma espinocelular (CEC) de boca e sua associação com variáveis demográficas, clínicopatológicas, biocomportamentais e psicológicas. Os níveis plasmáticos de cortisol foram mensurados por eletroquimioluminescência, e os níveis de ansiedade e depressão foram avaliados pelo Inventário de Ansiedade (BAI) e de Depressão (BDI) de Beck, respectivamente. Os dados demográficos, clinicopatológicos e biocomportamentais foram coletados dos prontuários dos pacientes. Os resultados da análise multivariada mostraram que homens com CEC de boca apresentaram 4,5 vezes mais chances de terem níveis elevados de cortisol plasmático do que as mulheres com a doença (OR=4,472; p=0,018). A presença de dor relacionada ao tumor primário também foi preditivo para maiores níveis de cortisol (OR=5,388; p=0,003). A ausência de histórico de consumo crônico de álcool foi um fator protetor para concentrações muito elevadas do hormônio nos pacientes com CEC de boca (OR=0,104; p= 0,004). Sintomas de ansiedade mensurados pelo BAI como "mãos trêmulas" (OR=0,192; p= 0,016) e estar "nervoso" (OR=0,207; p= 0,0004) foram associados a menores níveis de cortisol. Por outro lado, o sentimento de "medo de perder o controle" foi um fator de risco para níveis muito elevados de cortisol plasmático (OR=6,508; p= 0,0004). O score global e os sintomas específicos de depressão mensurados pelo BDI não foram preditivos para os níveis plasmáticos hormonais (p< 0,05). Juntos, os resultados mostram que sexo, dor, consumo de álcool e sintomas de ansiedade são variáveis independentes para os níveis sistêmicos de cortisol nos pacientes com câncer de boca. Portanto, intervenção psicológica, bem como o controle da dor e do alcoolismo devem ser considerados para a prevenção dos efeitos negativos da desregulação da secreção de cortisol nos pacientes diagnosticados com câncer de boca(AU)

Cancer patients may have a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal secretion of cortisol. Increased cortisol levels have been associated with worse prognosis in different types of cancer. Although anxiety and depression can trigger an abnormal cortisol secretion, little is known regarding the influence of these emotional disorders on HPA axis dysregulation in cancer patients when evaluating together with demographic, clinicopathological and biobehavioral variables. This crosssectional study analyzed the plasma cortisol levels of 133 patients with oral squamous cell carcinoma (OSCC) and its association with demographic, clinicopathological, biobehavioral and psychological variables. Plasma cortisol levels were measured by electrochemiluminescence, and anxiety and depression symptoms were assessed using Beck Anxiety Inventory (BAI) and Depression (BDI), respectively. Demographic, clinicopathological and biobehavioral data were collected from patients' medicalrecords. Results from multivariate analysis showed that men with OSCC were 4.5 times more likely to have higher plasma cortisol levels than women (OR = 4.472, p = 0.018). The presence of cancer-induced pain was predictive for higher cortisol levels (OR = 5.388, p = 0.003). The absence of chronic alcohol consumption history was a protective factor for highest hormonal concentrations in oral cancer patients (OR = 0.104, p = 0.004). Anxiety symptoms measured by BAI as "hands trembling" (OR = 0.192, p = 0.016) and being "nervous" (OR = 0.207, p = 0.0004) were associated with lower cortisol levels. In contrast, the feeling of "fear of losing control" was a risk factor for highest systemic levels cortisol (OR = 6.508, p = 0.0004). The global score and specific symptoms of depression measured by the BDI were not predictive for plasma hormone levels (p < 0.05). Together, our results show that sex, pain, alcohol consumption and anxiety symptoms are independent variables for systemic cortisol levels in patients with oral cancer. Therefore, psychological intervention, as well as control of pain and alcohol consumption, should be considered to prevent the negative effects of cortisol secretion dysregulation in patients with oral câncer(AU)

Fluorescence-guided surgical management of medication-related osteonecrosis of the jaws.

Medication-related osteonecrosis of the jaw (MRONJ) results in progressive destruction of the jawbones, and advanced cases demand surgical intervention. The total removal of necrotic bone is required to prevent recurrence and infection. However, determining the limits between necrotic and healthy bone is a challenge. The use of fluorescence to detect tissue alterations and determine necrosis extension is a promising method to avoid inadequate bone debridement. In the literature, there are several studies and reported cases that successfully use fluorescence-guided surgery (FGS) of MRONJ. The objective of this study was to present a critical review of the literature regarding the intraoperative use of optic fluorescence to differentiate healthy and necrotic bone in MRONJ. Studies that evaluated the intraoperative use of optic fluorescence to determine the surgical margins of MRONJ were searched in Pubmed/Medline and Scopus databases using the following terms: "medication-related osteonecrosis of the jaws" and "fluorescence". Eighteen papers describing the intraoperative use of FGS in ONJ management were selected, totalizing 218 patients. Of those 18 papers, only 5 were prospective studies, and the other 13 were isolated case reports, case series, and technical notes. The use of FGS to delimitate the resection margin of MRONJ is a promising method. There is no need for the application of exogenous fluorophore to perform FGS and the most often used light device was the VELScope® system. Further prospective studies with larger samples are still required to ascertain the fluorescence validity as a supporting method in MRONJ surgical treatment and to establish clinical protocols.

Benign symmetric lipomatosis in the tongue: an uncommon case.

Symmetric lipomatosis of the tongue (SLT) is rare and characterized by diffuse growth and unencapsulated lipomas. An 87-year-old man was referred for evaluation of tongue lesions. Intraoral findings showed soft yellowish nodules with a smooth shiny surface diffusely on the lateral border of the tongue, bilaterally. Our clinical diagnosis was multiple tongue lipomas and an incisional biopsy was done. Histopathological examination revealed unencapsulated lobules of mature adipocytes with slight variation in the size and shape, confirming the diagnosis of lipoma. The final diagnosis was SLT. On follow-up at 6 months, the tongue findings were unchanged and no new lesions were observed.

Can non-collagenous proteins be employed for the differential diagnosis among fibrous dysplasia, cemento-osseous dysplasia and cemento-ossifying fibroma?

Differential diagnosis among fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias is difficult, since there is considerable overlap of histologic features, but also extremely important, since they differ greatly in etiology, clinical behaviour, prognosis and terapeuthic approach. There is no data about the use of immunohistochemistry, a viable and accessible technique, for this purpose. The objective of this study was to investigate, comparatively, the immunohistochemical expression of major non-collagenous proteins (osteonectin [ON], osteopontin [OP], bone sialoprotein [BSP] and osteocalcin [OC]) of mineralized tissue extracellular matrix in 22 cases of fibrous dysplasias, 16 of cemento-ossifying fibromas and 16 of cemento-osseous dysplasias. ON maintained the same expression profile in all cases; the staining for OP was negative in fusiform cells producing cementoid globules and weak, as well as heterogeneous, in high mineralized matrixes; there was negativity for BSP in cementoid globules and in the fusiform cells that produce them, differently from the strong positive expression found in the majority of bone trabeculae and their peripheral cuboidal osteoblasts; and finally, the immuno-reactivity for OC was weak, except in cuboidal osteoblasts and osteocytes. We can conclude that the nature of mineralized structure and the cellular phenotype are much more responsible for variability in immunohistochemical profile than the type of lesion (fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias) which makes difficult, at least for a while, the use of these proteins with diagnosis purpose.

Delayed Diagnosis of Gorlin-Goltz Syndrome: The Importance of the Multidisciplinary Approach.

Gorlin-Goltz syndrome (GGS), also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant inherited disorder with high penetrance and variable expressivity. The classic triad originally described by Gorlin and Goltz in 1960 is composed of multiple nevoid basal cell carcinomas (NBCCs), odontogenic keratocysts (OKCs) in the jaws and bifid ribs. in 1977, this triad was modified by Rayner et al, and to GGS diagnosis, the OKCs had to appear in combination with calcification of the cerebellar falx or palmar and plantar pits. It may occur that although GGS syndrome is a well-known condition, only the specific symptom could be observed by different specialists. Therefore, the patient cannot be placed in an always complex clinical panel. The authors introduce an example in this report. In the present case, the patient had NBCCs, OKCs, and probably other signs of GGS since 1998, and has been treated for this conditions separated, without a diagnosis of a syndromic condition. A 54-year-old white woman was referred to the oral medicine service due to cyst located in the right mandibular body. She had history of skin cancer and undergone surgeries and radiotherapies for the lesions treatment, scars on the skin face due to the lesions removed, and a new ulcerated lesion on the back of was diagnosed. In addition, the patient presented frontal and parietal bossing leading to increased cranial circumference, hypertelorism, strabismus, broad base, and mandibular prognathism. To the image examination, skull radiography revealed calcification of the falx cerebri; on chest X-ray bifid rib was observed and spine radiography showed vertebral osteophytes. Panoramic radiograph showed a well-defined bilocular radiolucent image located in posterior and anterior mandibular region. The whole elements induced us to investigate the patient's past medical history, which revealed that since 1998 had the diagnosis of NBCC and OKC. A multidisciplinary approach becomes necessary for the diagnosis and follow-up of patients with GGS, considering the complexity of the clinical manifestations. Therefore, it is of primary importance for dental surgeons and dermatologists to know the signs and symptoms of GGS to perform early diagnosis and to avoid progression of the oral cysts or metastasis of the skin lesions.

Early life stress by maternal separation increases tumor onset and progression in a chemically induced oral cancer model / Estresse precoce de vida por separação maternal aumenta a incidência e progressão de tumor num modelo de câncer bucal quimicamente induzido em ratos

A ocorrência de eventos estressores nas fases iniciais de vida (estresse precoce de vida ­ EPV) pode afetar negativamente funções fisiológicas e psicológicas na fase adulta. Apesar de investigações pré-clínicas terem mostrado que o estresse crônico pode afetar a progressão do câncer, não há estudos que investigaram os efeitos do EPV na progressão do câncer bucal. No presente estudo, utilizamos um modelo animal de carcinogênese bucal induzida pelo carcinógeno 4- Nitroquinolona-1-Óxido (4NQO) para avaliar o impacto do EPV induzido por separação materna (SM) sobre a incidência e progressão do carcinoma espinocelular (CEC) de boca. As ninhadas submetidas ao protocolo de SM foram separadas de suas mães durante 3 horas por dia, do dia pós-natal 1 ao 21. Após os animais atingirem a idade adulta (90 dias), os grupos SM e controle foram tratados com 4NQO durante 120 dias. Análise histopatológica foi realizada para avaliar a incidência de CEC de boca e grau de malignidade do tumor entre os animais estressados e não estressados. Também foram avaliados o volume e espessura tumoral e o peso do baço e das glândulas adrenais. Os níveis níveis plasmáticos de norepinefrina foram analisados por ELISA e a expressão de RNAm para os genes relacionados à progressão do CEC de boca (IL-6, TNFalpha, VEGF, p53 e CDKN2A) foram analisados por PCR em tempo real. A SM no período pós-natal aumentou em aproximadamente 60% a ocorrência de CEC de boca na idade adulta. Os ratos submetidos à SM desenvolveram tumores mais espessos (p=0.02) e de maior volume (p=0.03) comparado ao grupo controle. Análise microscópica das características de malignidade dos CECs de boca mostraram pior padrão de invasão (p=0.004) e maior invasão perineural (p=0.04) nos tumores dos ratos estressados. O EPV no período neonatal diminuiu significativamente o peso do baço (p=0.003) e das glândulas adrenais (p=0.03) nos animais com câncer. Porém, não foi observada diferença nos níveis plasmáticos de norepinefrina. Os CECs dos ratos submetidos ao EPV apresentaram maior expressão de IL-6 (p=0.04) e menor expressão de p53 (p=0.02) em relação aos tumores dos ratos não estressados. Nossos achados fornecem a primeira evidência de que o EPV pode aumentar a incidência e progressão do câncer de boca quimicamente induzido, e sugerem que estes efeitos podem estar associados à uma desregulação da expressão de IL-6 e p53(AU)

Early life stress (ELS) may negatively affect the behavior and physiological functions in adulthood. Despite pre-clinical investigation have shown that chronic stress may affect cancer progression, there are no studies which have investigated ELS effects on oral cancer progression. In the present study, we used an oral carcinogenesis animal model induced by carcinogen 4- Nitroquinoline-1-oxide (4NQO) to assess the impact of ELS induced by maternal separation (MS) on the oral squamous cell carcinoma (OSCC) occurrence and progression. The litters underwent MS protocol were separated from their dam for 3 hours daily, during postnatal day 1-21. After animals reach adulthood (90 days), MS and control groups were treated with 4NQO during 120 days. Histopathological analysis was performed to evaluate the OSCC incidence and malignant degree between stressed and non-stressed rats. The volume and tumor thickness and the spleen and adrenal glands weight were also evaluated. Plasma norepinephrine levels were analyzed by ELISA and mRNA expression for OSCC progression-related genes (IL-6, TNF-alpha, VEGF, p53 and CDKN2A) were analyzed by real-time PCR. MS in neonatal period increased in almost 60% chemically induced OSCC occurrence in adulthood. Rats exposed to MS developed thicker (p=0.02) and larger tumors (p=0.03) compared to non-stressed rats. OSCCs from ELS rats showed worst pattern of invasion (p=0.004) and more perineural invasion (p=0.04) ELS also significantly reduced spleen (p=0.003) and adrenal glands (p=0.03) weight in cancer rats. ELS induced overexpression of IL6 (p=0.04) and attenuated p53 expression (p=0.04) in OSCCs. Our results provides the first evidences that ELS may increase oral cancer onset and progression, and suggest that this effect can be associated with altered expression of IL-6 and p53(AU)

Immediate Dental Implant Placement After Removal of Complex Odontoma.

The aim of the authors was to report a clinical case about immediate implant placement after the removal of complex odontoma. A 35-year-old female patient presented to private service complaining about absence of lower right first premolar. The computed tomographic showed radiopaque attenuation, surrounded by a narrow radiolucency in the area of dental absence, suggesting a mineralized lesion. The surgical removal of lesion was performed by intraoral access with general anesthesia and the implant of 3.75 × 10 mm (Neodent) was placed with the aid of a surgical guide, following the drill sequence established by the manufacturer. No complications were observed after 1 year with the prosthetic rehabilitation.

Photodynamic therapy in oral potentially malignant disorders-Critical literature review of existing protocols.

INTRODUCTION: Oral cancer is a serious public health issue. Apart from its high rate of prevalence, incidence and mortality, it can often result in more complex and expensive treatment when diagnosed late. Potentially malignant disorders (PMDs) can precede oral cancer, and are usually treated by surgical excision. However, in many cases patients are elderly and multiple interventions may be required. Photodynamic therapy (PDT) is a simple alternative, which has been successfully used in the treatment of oral PMDs. OBJECTIVE: Due to the lack of standardization regarding photosensitizers (PTSs), types of irradiation, and methods of application, the objective of this study was to analyze existing PDT protocols in an attempt to identify the one that demonstrates greater efficiency, reliability and feasibility in the treatment of oral PMDs for both researchers and clinicians. METHODS: Original clinical studies published only in English between 1993 and 2016 were searched in Pubmed/Medline database using the following keywords: photodynamic therapy; oral potentially malignant disorder; oral premalignant lesions. Review articles; experimental studies; case-reports; commentaries; and letters to the Editor were excluded from the selection. RESULTS AND CONCLUSION: Based on the 16 studies selected, the topical 5-ALA-20% PTS, associated to a LED light applied for 15min with a 7-day interval between sessions emerged as the most frequently used PDT protocol, with satisfactory results. Due to its low rate of side effects, this PDT protocol presents good potential for the treatment of oral PMDs. Further clinical studies are required to ascertain its long-term validity in preventing oral cancer.