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The objective of the present study was to investigate the frequency of oral leukoplakia and oral erythroplakia among young patients from three Brazilian reference centers in Oral and Maxillofacial Pathology. A retrospective study was carried out from 2011 to 2021 on 861 patients diagnosed with oral leukoplakia and oral erythroplakia. Demographic and clinicopathological data were evaluated. Fisher's exact test was used to evaluate the association among sex, age, anatomical location, and histopathological diagnosis. A total of 83 (9.64%) cases involved young patients (aged <40 years). Among these, biopsy records were included in 31 (37.34%) cases, all of which received a clinical diagnosis of oral leukoplakia. Seventeen (54.84%) patients were female, mostly in their fourth decade of life (n = 22/70.97%), and their mean age at diagnosis was 32.61(± 5.21) years. Among informed cases, seven (22.58%) patients were smokers. The lateral border of the tongue (n = 9/29.03%) was the most affected site. In 13 (41.94%) cases, oral leukoplakias showed a homogeneous appearance. The mean size of the lesions was 1.47 cm (0.2-3.0 cm) and the mean time of disease progression was 64.37 (± 65.90) months. The histopathological analysis showed that 11 cases (35.48%) exhibited some degree of epithelial dysplasia. Acanthosis and/or hyperkeratosis were observed in 20 cases (64.52%). No significant associations were observed between sex and anatomical location, age and anatomical location, nor between sex and histological diagnosis (p > 0.05). Oral leukoplakia and oral erythroplakia are uncommon diseases in young patients. In this population, oral leukoplakia shows a slight predilection for women aged between 30 and 39 years.
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Eritroplasia , Leucoplasia Oral , Humanos , Feminino , Leucoplasia Oral/patologia , Leucoplasia Oral/epidemiologia , Masculino , Estudos Retrospectivos , Brasil/epidemiologia , Adulto , Adulto Jovem , Eritroplasia/patologia , Eritroplasia/epidemiologia , Distribuição por Idade , Distribuição por Sexo , Adolescente , Biópsia , Fatores Etários , Fatores de Risco , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
OBJECTIVE: To assess the clinical scenarios in which nerve blocks are employed in the context of burning mouth syndrome (BMS). STUDY DESIGN: This scoping review followed the PRISMA-ScR. A protocol was generated on Open Science Framework. Electronic searches were performed in the following databases: PubMed, Scopus, EMBASE, Web of Science, LILACS, and Cochrane, in addition to the grey literature and citations from Grémeau-Richard et al. (2010). RESULTS: Nerve blocks were used for treatment purposes in all cases. The mandibular nerve and the stellate ganglion were both blocked in 50% studies, while the maxillary nerve and lingual nerve were blocked in 25% study each. The anesthetics used were lidocaine (50%) and bupivacaine (50%). Relief was generally reported after immediate block, and at a mean follow-up of 4.5 weeks, there was considerable improvement compared to the initial conditions when the mandibular and/or maxillary nerve were targeted. CONCLUSIONS: The use of nerve blocks has been employed in the treatment of patients with refractory BMS. Clinical studies with standardized methodology are necessary to validate and understand the potential role of mandibular and maxillary nerve block in this setting.
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PURPOSE: Oral alterations are frequently observed in patients undergoing palliative care and are linked to the direct or indirect effects of the primary medical condition, comorbidities and medical management, leading to oral pain, impacting oral intake, and affecting quality of life. This systematic review aims to assess the prevalence of oral disease in palliative care patients. METHODS: The protocol was registered at the PROSPERO database, and a systematic review of the literature was performed based on the PRISMA statement. A thorough evaluation of studies from five databases and gray literature was conducted. The risk of bias in each study was assessed using the Joanna Briggs Institute checklist for cross-sectional and case-control studies. A quantitative analysis was conducted on five studies using meta-analysis, and the degree of certainty in the evidence was determined using the GRADE tool. RESULTS: The sample consisted of 2,502 patients, with a slight male predominance (50.43%). The average age was 66.92 years. The prevalence of oral diseases among palliative care patients was as follows: caries 32% (95% CI, 0.11-0.56; I2 = 93%), and oral candidiasis 17% (95% CI,0.11-0.25; I2 = 74%). Gingivitis and stomatitis were also reported, but with less frequency. CONCLUSION: Dental intervention should take place as early as possible, ideally from the time of the patient's initial admission to palliative care, with regular monitoring of oral health. This approach can enhance the patient's comfort and quality of life and help prevent more severe complications in the future.
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Doenças da Boca , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Prevalência , Doenças da Boca/epidemiologia , Doenças da Boca/etiologia , Qualidade de Vida , Masculino , Feminino , IdosoRESUMO
OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.
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Cancer disclosure represents a complex healthcare dynamic. Physicians or caregivers may be prompted to withhold diagnosis information from patients. This study aims to comprehensively map and synthesize available evidence about diagnosis nondisclosure regarding head and neck cancer (HNC) patients. Following the Joanna Briggs Institute guidelines, a scoping review was conducted across major databases without period restriction, yielding 9238 publications. After screening and selection, a descriptive synthesis was conducted. Sixteen studies were included, primarily conducted in academic settings (75%) from Europe and Asia, with a total population of 662 patients predominantly diagnosed with brain, oral, pharyngeal, or laryngeal tumors. Remarkably, 22.51% of patients were unaware of their diagnosis. Although physicians were the main source of diagnostic information (35%), they reported to often use vague terms to convey malignancy. Additionally, 13.29% of patients were aware of their diagnosis from sources other than doctors or caregivers. Caregivers (55%) supported diagnosis concealment, and physicians tended to respect family wishes. A high diagnosis-to-death interval, education, and age significantly influenced diagnosis disclosure. HNC patients expressed a desire for personalized open communication. Multiple factors influenced the decision on diagnosis disclosure. Current evidence on this topic varies significantly, and there is limited research on the consequences of nondisclosure. These findings reflect the underestimation of the patients' outlook in the diagnosis process and highlight the need for further research, aiming to establish open communication and patient autonomy during the oncological journey.
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PURPOSE: This study describes a large, well-documented case series of salivary gland polymorphous adenocarcinomas (PAC) from a single Brazilian center. METHODS: Demographic data, clinical presentation, histopathological and immunohistochemical features from 26 cases of PAC were analyzed and discussed in detail. RESULTS: Most patients were females (n = 21), with a ratio of 1:4.2 (male: female) with a mean age of 58.8 years (ranging from 36 to 84 years). The most common clinical presentation was a fibrocollagenous, firm nodular lesion, with a mean size of 2.46 cm (ranging from 0.5 to 3 cm). Most lesions occurred on the palate (n = 16), followed by buccal mucosa (n = 3), upper lip (n = 3), buccal vestibule (n = 2) and alveolar ridge (n = 1). Histologically, various growth patterns were observed, including tubular, solid, cribriform, papillary, and cystic. Additionally, glomeruloid slit-like structures, mucous, and clear cells were noted. Surface papillary epithelial hyperplasia was observed in a few cases. Nine cases exhibited myxoid and collagenous areas, while two cases showed fusiform areas and another case demonstrated squamous differentiation. Clear cell predominance was noted in two cases, and peri- and intraneural invasion was seen in eight cases. Immunohistochemical analysis revealed positivity for S-100, p63 and CK7, and negativity for p40 in all cases. The Ki-67 proliferation index was markedly low in most cases, with a mean of 2.5%. CONCLUSION: We have provided a broad, detailed description of the clinical and microscopic features of PAC in a large, Brazilian cohort. These findings, in a resource-limited area, may be quite useful for establishing a proper diagnosis.
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Adenocarcinoma , Neoplasias das Glândulas Salivares , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Adulto , Idoso de 80 Anos ou mais , Adenocarcinoma/patologia , Neoplasias das Glândulas Salivares/patologia , Brasil , Biomarcadores Tumorais/análiseRESUMO
PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of salivary gland hypofunction and xerostomia in cancer patients. METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: Salivary gland hypofunction and xerostomia in cancer patients are managed by (i) stimulating saliva production of salivary glands with residual secretory capacity or (ii) artificial wetting of the oral and lip surfaces which can be achieved by pharmacological or non-pharmacological interventions. Pharmacological interventions encompass the use of sialagogues and sialolytics, while non-pharmacological interventions involve the use of moistening agents, mechanical, gustatory, or electrostimulation of the salivary glands. Additional treatment modalities may be incorporated in practice based on local availability and the clinician's experience. CONCLUSION: The information presented in this CPS offers clinicians convenient access to the dosages and regimens of different interventions for managing salivary gland hypofunction or xerostomia to facilitate clinical efficiency and conserve valuable time for clinicians.
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Neoplasias , Xerostomia , Humanos , Xerostomia/etiologia , Xerostomia/terapia , Neoplasias/complicações , Glândulas SalivaresRESUMO
OBJECTIVE: Histopathological grading of oral epithelial dysplasia (OED) is the current standard for stratifying cancer progression risk but is associated with subjectivity and variability. This problem is not commonly seen regarding the grading of epithelial dysplasia in other sites. This systematic review aims to compare grading systems for oral, anal, penile, and cervical epithelial dysplasia to determine their predictive accuracy for recurrence and malignant transformation (MT) outcomes. METHODS: The review protocol was registered in PROSPERO (CRD42023403035) and was reported according to the PRISMA checklist. A comprehensive search was performed in the main databases and gray literature. The risk of bias in individual studies was analyzed using the Joanna Briggs Institute checklist for each study design. RESULTS: Forty-six studies were deemed eligible and included in this systematic review, of which 45 were included in the quantitative analysis. Meta-analysis revealed that the binary system demonstrated a higher predictive ability for MT/recurrence of OED compared to multilevel systems. Higher predictive accuracy of MT was also observed for binary grading systems in anal intraepithelial neoplasia. CONCLUSIONS: No significant difference was found between the current grading systems of epithelial dysplasia in different body parts. However, binary grading systems have shown better clinical outcomes.
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OBJECTIVE: This study evaluated the influence of a single educational intervention on the perception and knowledge of strategies for communicating oral cancer diagnoses. METHODS: A educational intervention, 72 dentists and 41 dental undergraduates participated in the 'Maio Vermelho Project', a continuing education activity. Participants completed a 14-question online questionnaire concerning their experiences and perceptions of delivering difficult news. The educational intervention featured an interview illustrating the SPIKES protocol, broadcast on YouTube. RESULTS: Participants had a mean age of 40 years. A minority (21.2%) had encountered or experienced communicating an oral cancer diagnosis. Exposure to lectures on this topic during their education was uncommon (22.1%) but more prevalent among students. After the intervention, confidence in communicating a cancer diagnosis (29.2%) and addressing the patient's family (30.1%) in line with the SPIKES protocol increased. CONCLUSION: A training deficit persists in delivering cancer diagnoses, highlighting the need for educational interventions to empower students and professionals in this critical procedure. Integration of this topic into the dental undergraduate curriculum is imperative. CLINICAL RELEVANCE: Effectively communicating a cancer diagnosis poses challenges to healthcare professionals, impacting treatment outcomes. Implementing educational interventions ensures that professionals are well prepared to navigate this complex task, ultimately improving patient care.
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BACKGROUND: Neural tumors are difficult to distinguish based solely on cellularity and often require immunohistochemical staining to aid in identifying the cell lineage. This article investigates the potential of a Convolutional Neural Network for the histopathological classification of the three most prevalent benign neural tumor types: neurofibroma, perineurioma, and schwannoma. METHODS: A model was developed, trained, and evaluated for classification using the ResNet-50 architecture, with a database of 30 whole-slide images stained in hematoxylin and eosin (106, 782 patches were generated from and divided among the training, validation, and testing subsets, with strategies to avoid data leakage). RESULTS: The model achieved an accuracy of 70% (64% normalized), and showed satisfactory results for differentiating two of the three classes, reaching approximately 97% and 77% as true positives for neurofibroma and schwannoma classes, respectively, and only 7% for perineurioma class. The AUROC curves for neurofibroma and schwannoma classes was 0.83%, and 0.74% for perineurioma. However, the specificity rate for the perineurioma class was greater (83%) than in the other two classes (neurofibroma with 61%, and schwannoma with 60%). CONCLUSION: This investigation demonstrated significant potential for proficient performance with a limitation regarding the perineurioma class (the limited feature variability observed contributed to a lower performance).
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Estudos de Viabilidade , Neoplasias Bucais , Neoplasias de Bainha Neural , Redes Neurais de Computação , Neurilemoma , Neurofibroma , Humanos , Neurofibroma/patologia , Neurilemoma/patologia , Neoplasias de Bainha Neural/patologia , Neoplasias Bucais/patologia , Diagnóstico DiferencialRESUMO
BACKGROUND: Salivary gland cystadenoma (SGCA) is a rare benign tumor that predominantly occurs in the parotid gland. SGCAs affecting the minor salivary glands are uncommon and often resemble, clinically and histopathologically, other salivary gland lesions. METHODS: This study aimed to describe a series of four cases of SGCA affecting intraoral sites and performed a literature review of well-reported SGCA published in the English-language literature. RESULTS: SGCA cases included in this series were diagnosed in the buccal mucosa, lip, and hard palate of female patients aged between 19 and 78 years. All cases underwent excisional biopsy and were histologically characterized by a multicystic growth with variable degrees of capsule formation and were lined by several types of epithelium, including some cell types that are infrequently reported in SGCA. In some cases, a small collection of lymphocytes was observed adjacent to cystic formations. All SGCA were positive for periodic acid-Schiff, and immunohistochemical reactions were positive for CK7 and p63. The follow-up time ranged widely from 3 to 53 months, and to date, no recurrence has been observed. CONCLUSION: The literature review revealed a total of 33 published studies accounting for 55 SGCA cases.
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Cistadenoma , Neoplasias das Glândulas Salivares , Humanos , Feminino , Neoplasias das Glândulas Salivares/patologia , Adulto , Pessoa de Meia-Idade , Cistadenoma/patologia , Idoso , Adulto JovemRESUMO
OBJECTIVE: This study utilized bibliometric methodologies to explore the body of research presented at the World Workshop on Oral Medicine (WWOM) over the past 35 years. METHODS: A systematic tracking of articles across 8 editions of WWOM was conducted using databases such as Web of Science, Scopus, and PubMed. Comprehensive bibliographic analysis and data visualization were executed through Bibliometrix, Rstudio, and VOSviewer, facilitating an in-depth examination of citation metrics and collaborative networks. RESULTS: The investigation revealed that WWOM, held in 6 cities spanning four countries and addressing 33 distinct topics, demonstrated an annual citation growth rate of 8.29%, with an average of 49.31 citations per article. Notably, WWOM IV garnered the highest number of citations (1,342), reaching its peak in 2021 with 365 citations. Key contributors to the most-cited articles include Al-Hashimi, Dawes, and Syrjänen et al. Since its inception, the workshops have engaged 505 faculty members from 37 nations, with significant participation from the Americas and Europe, notably the United States and the United Kingdom, which also led in terms of publications. Network analysis delineated 6 country clusters, underscoring robust connections between the US and the UK. Co-authorship analysis revealed 18 clusters involving 267 authors. CONCLUSION: The influence of the WWOM on the field of oral medicine is clearly demonstrated by the outcomes of its publications, reflecting a collaborative effort to enhance comprehension and treatment modalities for patients with oral diseases. The study's findings provide insights into future research directions within the WWOM legacy.
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Bibliometria , Medicina Bucal , Humanos , Congressos como AssuntoRESUMO
BACKGROUND: The purpose of this systematic review (SR) is to gather evidence on the use of machine learning (ML) models in the diagnosis of intraosseous lesions in gnathic bones and to analyze the reliability, impact, and usefulness of such models. This SR was performed in accordance with the PRISMA 2022 guidelines and was registered in the PROSPERO database (CRD42022379298). METHODS: The acronym PICOS was used to structure the inquiry-focused review question "Is Artificial Intelligence reliable for the diagnosis of intraosseous lesions in gnathic bones?" The literature search was conducted in various electronic databases, including PubMed, Embase, Scopus, Cochrane Library, Web of Science, Lilacs, IEEE Xplore, and Gray Literature (Google Scholar and ProQuest). Risk of bias assessment was performed using PROBAST, and the results were synthesized by considering the task and sampling strategy of the dataset. RESULTS: Twenty-six studies were included (21 146 radiographic images). Ameloblastomas, odontogenic keratocysts, dentigerous cysts, and periapical cysts were the most frequently investigated lesions. According to TRIPOD, most studies were classified as type 2 (randomly divided). The F1 score was presented in only 13 studies, which provided the metrics for 20 trials, with a mean of 0.71 (±0.25). CONCLUSION: There is no conclusive evidence to support the usefulness of ML-based models in the detection, segmentation, and classification of intraosseous lesions in gnathic bones for routine clinical application. The lack of detail about data sampling, the lack of a comprehensive set of metrics for training and validation, and the absence of external testing limit experiments and hinder proper evaluation of model performance.
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Inteligência Artificial , Radiômica , Humanos , Ameloblastoma/diagnóstico por imagem , Ameloblastoma/patologia , Cisto Dentígero/diagnóstico por imagem , Doenças Maxilomandibulares/diagnóstico por imagem , Aprendizado de Máquina , Cistos Odontogênicos/diagnóstico por imagem , Cistos Odontogênicos/patologia , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To analyze the frequency of sequential oral squamous cell carcinomas (s-OSCC), preceded by oral potentially malignant disorders, and OSCC de novo (OSCC-dn) and explore differences in their clinicopathologic presentations. STUDY DESIGN: A structured electronic search strategy identified studies that analyzed frequency, clinical, biological, demographic, biomarkers, and prognostic features of s-OSCC and OSCC-dn according to PRISMA guidelines in PubMed, Scopus, Cochrane Library, and Google Scholar, up to January 31, 2023. Inclusion criteria were original English, Spanish, Portuguese, French, Italian, and German cross-sectional, cohort, and case-control studies. The quality of studies was assessed using the Agency for Research and Health Quality tool and the Newcastle-Ottawa Scale tool. RESULTS: The final selection included 40 studies. OSCC-dn and s-OSCC represent, respectively, 71% and 29% of cases of OSCC (P = .00), showing a higher percentage of T1 or of T1+T2 in s-OSCC (P < .0001). The association meta-analysis showed OSCC-dn with a significant association. The meta-analysis showed that s-OSCC was significantly associated with smaller tumor size, absence of distant metastases, relapses, male sex, and tumor sites different from tongue; and OSCC-dn was associated with more advanced tumor size, more regional and distant metastases, more advanced stages, and worse survival. CONCLUSIONS: S-OSCC was less frequent than expected. OSCC-dn seems to have specific clinical, biological, and prognostic features. Future perspectives on oral cancer prevention should address novel approaches and alternatives to screening, such as urgent referral of OSCC-dn.
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Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Prognóstico , Lesões Pré-Cancerosas/patologiaRESUMO
The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events.
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Burning mouth, also referred to as oral dysesthesia, is an underreported condition among cancer patients that may represent an early symptom of cancer or an adverse effect of treatment. This review sought to characterize this symptom in oncology care where burning symptoms may occur. A systematic review of the literature was performed based on the PRISMA statement, and the protocol was registered at PROSPERO database. A structured search was done using eight databases. The process of study selection was conducted in two distinct phases. The JBI Critical Appraisal Tools were utilized to evaluate the risk of bias in the studies included. Of the total number of studies assessed, sixteen met the eligibility criteria. Of these studies included, 7 were case reports, 7 cross-sectional studies, and 2 non-randomized clinical trials. Most studies presented low risk of bias (n = 9), while the remaining studies were evaluated and scored as moderate (n = 5) or high (n = 2) risk of bias. Burning mouth was reported as a first symptom of cancer in three studies, and as an adverse event of radiotherapy (n = 2), chemoradiotherapy (n = 2), and chemotherapy (n = 9). Burning mouth was a first symptom in 0.62% of oral squamous cell carcinoma (OSCC), and 3.3% of patients with pain as chief complaint. Oral dysesthesia prevalence was 13.6% in patients experiencing chemotherapy-induced oral adverse events. The symptom of burning mouth should be examined in oncology care, as it may be underreported and therefore undertreated. New therapies may be related to a higher risk of oral burning and studies assessing approach to management are needed. Current management borrows from the current management of burning mouth in the non-cancer setting.
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Síndrome da Ardência Bucal , Neoplasias , Humanos , Síndrome da Ardência Bucal/etiologia , Síndrome da Ardência Bucal/terapia , Neoplasias/terapia , Neoplasias/complicações , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagemRESUMO
Colonialism's enduring impact on Brazil has had significant implications for health and oncology outcomes. This historical essay delves into the profound changes brought about by the transatlantic slave trade from Africa to the Americas, particularly in terms of its influence on the economy, sociocultural habits, and health outcomes. This essay explores the enduring connections between the colonial period's operational dynamics in Brazil and the current epidemiological panorama of head and neck cancer (HNC). The examination provides original insights on the role of tobacco and alcohol production and consumption, alongside the investigation of structural racism, which contributes to disparities in access to diagnosis, treatment, and prognosis for patients with HNC. This article presents novel visions and an analysis of evidence-based strategies to disrupt the adverse impact of colonialism's legacy on the epidemiology of HNC in Brazil.