Hematopoietic colony-stimulating factors in head and neck cancers: Recent advances and therapeutic challenges.

Colony-stimulating factors (CSFs) are key cytokines responsible for the production, maturation, and mobilization of the granulocytic and macrophage lineages from the bone marrow, which have been gaining attention for playing pro- and/or anti-tumorigenic roles in cancer. Head and neck cancers (HNCs) represent a group of heterogeneous neoplasms with high morbidity and mortality worldwide. Treatment for HNCs is still limited even with the advancements in cancer immunotherapy. Novel treatments for patients with recurrent and metastatic HNCs are urgently needed. This article provides an in-depth review of the role of hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3; also known as multi-CSF) in the HNCs tumor microenvironment. We have reviewed current results from clinical trials using CSFs as adjuvant therapy to treat HNCs patients, and also clinical findings reported to date on the therapeutic application of CSFs toxicities arising from chemoradiotherapy.

Head and neck squamous cell carcinoma: Exploring frontiers of combinatorial approaches with tyrosine kinase inhibitors and immune checkpoint therapy.

Squamous cell carcinomas (SCC) are the most common malignant tumors that arise in the head and neck. Despite advances in the management of affected patients, the mortality burden of these tumors is increasing every year. The discovery of a vast genetic landscape has revealed new opportunities for therapeutic intervention of head and neck SCC (HNSCC). Molecular alterations of tyrosine kinases are involved in the pathogenesis of cancer and may help keep cancer cells from growing. Currently, many drugs inhibit this enzyme family and are being studied by the pharmaceutical industry opening the room to expand the use and efficacy of this therapeutic modality alone or using combinatorial approaches including checkpoint inhibitors for treatment. In this paper, we explored the role of tyrosine kinases inhibitors of HNSCC, and clinical trials related to these molecules, expecting to provide references for HNSCC therapy.

Brazilian organic propolis for prevention and treatment of radiation-related oral acute toxicities in head and neck cancer patients: A double-blind randomized clinical trial.

Background: Oral mucositis (OM) is one of the most important acute toxicities from radiotherapy (RT) in head and neck cancer patients and can impair oncologic treatment. Dysphagia, dysgeusia, pain, and oral candidiasis are other common toxicities. Brazilian Organic Propolis (BOP) is a recently described propolis variant and BOP types 4 and 6 have shown important antioxidant, anti-inflammatory, and antifungal properties. Purpose: To investigate the use of BOP as a preventive and/or complementary therapeutic option for radiotherapy-induced oral mucositis, dysphagia, dysgeusia, pain, and oral candidiasis. Additionally, proinflammatory cytokines were assessed to investigate their anti-inflammatory role. Methods: Sixty patients were included in this randomized, double-blind, controlled clinical trial. Patients were randomized to receive either aqueous suspension of a BOP or placebo throughout RT. Also, all patients underwent low-level laser therapy as routine oral care. OM, dysphagia, and dysgeusia were assessed weekly according to WHO and NCI scales. Pain-related to OM was assessed according to a Visual Analog Scale and the presence or absence of oral candidiasis was checked by intraoral examination. Protein levels of TNF-α and IL-1ß from oral mucosa were assessed by ELISA. Results: Patients in the propolis group had a lower mean score of OM, dysphagia, dysgeusia, and most patients reported moderate pain. Fewer patients developed oral candidiasis in the propolis group, and the number of episodes was lower among patients that used BOP (p < 0.05). In addition, the BOP group presented significantly lower levels of IL-1ß since the beginning of treatment when compared with placebo patients (p < 0.05) and a lower level of TNF-α at the end of treatment (p < 0.001). Conclusion: Topic use of BOP reduced TNF-α and IL-1ß levels, oral candidiasis episodes, and seems to be a useful complementary option for the prevention and treatment of the main acute oral toxicities of RT. Clinical Trial Registration: http://www.ensaiosclinicos.gov.br/rg/RBR-9f8c78/, identifier RBR-9f8c78.

Tumor microenvironment in salivary gland carcinomas: An orchestrated state of chaos.

Salivary gland carcinomas (SGC) are rare tumors of heterogeneous morphology and many histological subtypes. Like other tumors, the SGC mass consists of a varied population of malignant cells and a diverse array of immune cells, cancer-associated fibroblasts, cytokines, chemokines, extracellular matrix proteins, and metalloproteinases, collectively known as the tumor microenvironment (TME). This chaotic network serves as an important physical mediator of cancer cell growth. In this review, we provided current insights into the TME of some of the most common SGC. Here, we highlighted the histological heterogeneity of these tumors, delineated the nature/intensity of inflammatory infiltrates, and the mechanisms involved in immunological escaping related to each SGC subtype.

Salivary gland cancer in the setting of tumor microenvironment: Translational routes for therapy.

Salivary gland carcinomas (SGC) are aggressive cancers that arise in minor and major salivary glands. Given the complexity and the multiple subtypes of this class of tumors, diagnosis and, treatment may be challenging for clinicians. Recently the tumor microenvironment, composed mainly of immune and stromal cells are been a target for treatment. Accumulating evidence indicates that cancer immunotherapies have made a significant impact on oncologic patients, however immunotherapeutic attempts in SGC have been shown limited improvement. Advances in the models that best translate aggressive SGC are needed for the development of clinical protocols grouping immunotherapies and other classes of drugs that will promote better responses in patients with advanced SGC stages. In this review, we introduced different experimental models for SGC with a focus on tumor microenvironment highlighting potential therapy applications for each model.

Oral manifestations of graft-versus-host disease in patients submitted to allogeneic hematopoietic stem cell transplantation: the experience of a Brazilian Cancer Center.

PURPOSE: Graft-versus-host disease (GVHD) is an important complication of allogeneic hematopoietic stem cell transplantation (AHCT) that affects several organs, including the mouth. OBJECTIVES: The aim of the present study was to describe the prevalence and clinical manifestations of oral GVHD, to determine the time interval from AHCT to the onset of oral GVHD manifestations, to identify predictive factors of oral GVHD, and to evaluate the survival rates of patients diagnosed with oral GVHD. METHODS: Medical records of 147 patients who underwent AHCT between January 2010 and January 2015 were reviewed for clinical features and the statistical establishment of risk factors. RESULTS: Of the 147 patients in the study, 99 (67.3%) developed GVHD. The skin was the most affected site (45.6%), followed by the gastrointestinal tract (27.9%) and oral cavity (17.7%). The mean post-AHCT oral GVHD development time was 229 days. Among patients with oral GVHD, pain was the main complaint (96.2%) followed by xerostomia (65.4%). The most common oral manifestations were ulcers (53.8%) followed by striae-associated ulcers (19.2%), mostly affecting the buccal mucosa and tongue. Seventy-three patients (48.6%) died within 20 months of receiving AHCT. Cox regression analysis indicated that patients who received myeloablative conditioning regimen had higher survival rate than those who underwent a reduced-intensity conditioning regimen (RR = 0.541; 95% CI, 0.334-0.878; p = 0.03). CONCLUSION: The mouth was the third most common GVHD-affected site. Pain, xerostomia, and ulcers with or without striae were the main clinical manifestations of GVHD observed in our study cohort. Reduced-intensity conditioning regimen showed significant relationship with mortality risk.

Langerhans cell histiocytosis in the oral and maxillofacial region: An update.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal proliferation and infiltration of histiocytic cells. METHODS: This review focused on the main aspects associated with LCH. RESULTS: LCH can involve single or multiple organs and systems, with bone and skin being the most commonly affected sites. Regarding skeletal manifestations, the jawbones are involved in about 20%-30% of all cases. Such lesions may present as unilocular or multilocular images mainly affecting the posterior mandible. Oral soft tissue lesions may also occur, with the gingiva and hard palate being the most frequently affected sites. CONCLUSION: The diagnosis and management of LCH are challenging, requiring a multidisciplinary approach, with dentists playing a central role since oral manifestations can be the first sign of the condition.

Non-ulcerated necrotizing sialometaplasia may mimic a salivary gland tumor.

Necrotizing sialometaplasia (NS) is a benign, self-limiting inflammatory entity that mainly affects the minor salivary glands located in the hard palate. Classically, NS is characterized as a nodule that evolves to a central ulcer. The most widely recognized triggering factor is an ischemic event. The diagnosis becomes a challenge in non-ulcerated NS cases which is essential to rule out the possibility of salivary gland tumors, especially the malignant ones. Here, we presented a case of a 32-year-old male patient with a 1-month complaint of a painful, slightly elevated erythematous area on the hard palate. Incisional biopsy was performed, and NS was diagnosed based on histopathological and immunohistochemical analyses. Clinicians should be aware of and consider NS as a differential diagnosis of minor salivary gland tumors, particularly when it presents as a non-ulcerated clinical aspect.

Evaluation of the quality of referral letters: experience of a Brazilian oral medicine service.

Optimizing the quality of referral letters could be the first step to a correct clinical approach for patients. Referral letters should be legible and contain the necessary information to avoid delaying the patient's diagnosis and treatment. However, to date, few studies have been conducted on how referrals are performed in Brazil. Knowledge regarding the quality of referral letters can provide information to better guide health care professionals. This study was aimed at analyzing all referrals received by a single oral medicine service in Brazil. Referral letters were classified into poor, regular, good, and excellent based on key items concerning the primary morphology of the lesion, location, diagnostic hypothesis, symptomatology, time of evolution, consistency, size, and limits. A total of 500 referral letters were evaluated, including 271 (54.2%) from a private service and 229 (45.8%) from a public service. Dentists and physicians had written 475 (95%) and 25 (5%) referral letters, respectively. Among the 500 referrals analyzed in this study, the number of regular, poor, good, and excellent referrals was 236 (47.2%), 203 (40.6%), 58 (11.6%), and one (0.6%), respectively, showing a lack of important clinical information in referrals.

Morphological patterns of circumpulpal dentin affected by radiation-related caries.

BACKGROUND: The aim of this work was to evaluate the microscopic characteristics through polarized light microscopy, scanning electron microscopy and the mineral content of circumpulpal dentin of irradiated (IT) and non-irradiated teeth (NIT), with deep caries that reached the root canal. MATERIAL AND METHODS: A total of 25 IT were analyzed macroscopically, and radiographed. 5 NIT were used as controls. Two 100-µm-thick sections, per specimen, were evaluated in a polarized light microscopy and a scanning electron microscope. Demographics and clinical data were collected. RESULTS: The results did not demonstrate distinct morphology of the IT compared with NIT. Mineral content values by weight percentage of Ca and P were also similar, corresponding to 66.65% and 33.21% in the IT and 66.60% and 33.29% in the NIT. The Ca/P ratio did not show statistical differences between groups being respectively 2.74 and 2.72, in the IT and NIT (p> 0.05). CONCLUSIONS: Radiotherapy does not change morphology and mineral content of circumpulpal dentin in IT. Key words:Root canal, radiation-related caries, polarization microscopy, scanning electron microscopy, radiotherapy, oral neoplasms, dentin.

Primary diffuse large B-cell lymphoma of the mandible.

Primary intraosseous non-Hodgkin lymphoma in the mandible is uncommon, representing about 0.6% of all extranodal lymphomas. We present the case of a 51-year-old male with a 4-month complaint of mandibular swelling and paresthesia, which had been previously submitted to an unsuccessful periodontal treatment. The intra-oral evaluation showed an extensive swelling with teeth mobility in the right mandible body. The panoramic radiography and computed tomography images showed an extensive osteolytic lesion. An incisional biopsy was performed and the histopathological and immunohistochemical analysis established the diagnosis of diffuse large B-cell lymphoma. The treatment included six cycles of chemotherapy with complete remission. The patient is under the seventh month of follow-up with no evidence of relapse. Although uncommon in the oral cavity, lymphoma should be considered in the differential diagnosis.

Primary diffuse large B-cell lymphoma of the mandible

Primary intraosseous non-Hodgkin lymphoma in the mandible is uncommon, representing about 0.6% of all extranodal lymphomas. We present the case of a 51-year-old male with a 4-month complaint of mandibular swelling and paresthesia, which had been previously submitted to an unsuccessful periodontal treatment. The intra-oral evaluation showed an extensive swelling with teeth mobility in the right mandible body. The panoramic radiography and computed tomography images showed an extensive osteolytic lesion. An incisional biopsy was performed and the histopathological and immunohistochemical analysis established the diagnosis of diffuse large B-cell lymphoma. The treatment included six cycles of chemotherapy with complete remission. The patient is under the seventh month of follow-up with no evidence of relapse. Although uncommon in the oral cavity, lymphoma should be considered in the differential diagnosis.

Melanotic Neuroectodermal Tumor of Infancy: a Clinicopathological Case Report.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that affects mainly children under 1 year of age. A 4-month-old boy was referred for evaluation of a lesion with 1 month of evolution. Intra-oral examination detected a firm upon palpation submucosal nodular mass, measuring 1.5 cm in diameter, affecting the anterior maxillary alveolar ridge and covered by a slightly blue mucosa with evident telangiectasia. The patient underwent an incisional biopsy and histological and immunohistochemical analyses revealed nests of AE1/AE3 positive epithelioid cells with abundant melanin pigmentation. Other cell types, resembling neuroblasts, were also present and positive for CD56, synaptophysin and enolase. The diagnosis of MNTI was established and the patient was referred for treatment. Conservative surgical resection was performed along with 3 adjacent teeth under general anesthesia. The patient is in follow-up for 1,5 year without recurrence. Conservative surgical management of MNTI may be an alternative to maxillectomy, contributing to the patient´s quality of life.

Unusual Intestinal Involvement by Paracoccidioidomycosis Diagnosed After Oral Manifestation.

Paracoccidioidomycosis is a common deep fungus infection in South America, particularly in Brazil. It is acquired through inhalation and primary involvement of lungs. Subsequently, dissemination may occur and oral mucosa is frequently affected and actually, in most of the cases the diagnosis is established because of the oral lesions. Thus, the role of the dentist is fundamental to correct diagnosis. However, the involvement of intestine is rarely reported. The current case describes a 36-year-old man who presented abdominal pain and intestinal constipation, being suspected and then confirmed as paracoccidioidomycosis after already be diagnosed with this disease by a dentist through oral manifestations.

Enucleaçäo ocular em crianças no Hospital Univeersitário Prof. Edgard santos / Ocular enucleation in children

Os autores estudaram 52 olhos enucleados em crianças de zero a doze anos, em um período de dez anos. Todos os olhos foram submetidos a estudo histopatológico. Nesta série, o retinoblastoma foi a principal causa isolada de enucleaçäo, sendo notada ainda uma queda na incidência de realizaçäo deste tipo de cirurgia com o avançar da faixa etária

Invasäo do nervo óptico por melanoma maligno da úvea / Optic nerve invasion by uveal malignant melanoma

Relato de um estudo clinico-patológico de um caso de invasäo do nervo óptico por melanoma maligno da úvea. Comentou-se as formas mais comuns de invasäo extra-ocular por melanomas da úvea ressaltando a raridade de invasäo extra-ocular destas neoplasias através do nervo óptico. Enfatizados a importância de seccionar o mais longo possível o nervo óptico ao realizarmos enucleaçöes

Fibrohistociotoma da conjuntiva / Fibrous histiocytoma of the conjunctiva

Descrevemos um caso de fibrohistiocitoma de conjuntiva em criança de dez ano cuja cura foi obtida através de excisäo cirúrgica total. Säo comentadas a raridade do caso, a natureza da neoplasia e a dificuldade no diagnóstico clínico.

Melanoma malígno após evisceraçäo / Malignant melanoma of the orbit after evisceration

Säo apresentados , clínica e histopatologicamente, três casos de melanoma malígno da órbita, que ocorreram após evisceraçäo do globo ocular. Os autores se pronunciam contra as evisceraçöes do globo ocular considerando que tais cirurgias dificultam extremamente o exame histopatológico além de possibilitarem sérias complicaçöes como a oftalmia simpática e a ocorrência de melanoma malígno na órbita, originando-se a partir de melanócitos da carapaça escleral remanescente na órbita, após tais cirurgias