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This review outlines the historical perspective, status, and future challenges of oral medicine (stomatology) in Brazil based on the records of the Brazilian Society of Stomatology and Oral Pathology (SOBEP) and the Brazilian Federal Dental Council as well as expert evidence input from academic leaders from 3 different generations of Brazilian oral medicine specialists. The beginning of oral medicine in Brazil dates to 1969, followed by the organization of SOBEP in 1974; however, official recognition as an independent specialty was achieved more recently within the Brazilian Federal Dental Council in 1992. After a 50-year maturation period of oral medicine in Brazil in terms of specialty crystallization across dentistry, medicine, and research, it is now time to follow the historical trends of the specialty internationally and establish a standard curriculum at a post-graduate level that will lead to uniformity of training for oral medicine in Brazil., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The aim of the present study was to integrate the available data published in the literature on oral and maxillofacial neuroendocrine carcinomas concerning the demographic, clinical and histopathological features of this condition. An electronic search with no publication date restriction was undertaken in April 2021 in four databases. Eligibility criteria included reports published in English having enough data to confirm a definite diagnosis, always showing a neuroendocrine marker. Cases originating in the oropharynx, including base of the tongue and tonsils, were excluded. Outcomes were evaluated by the Kaplan-Meier method along with Cox regression. Twenty-five articles (29 cases) from nine different countries were detected. Mean patient age was 56.3 (± 17.5) years, with a slight male predilection. Symptomatology was present in 72.2% of informed cases. Regarding clinical presentation, a non-ulcerated nodule located in the gingiva with a mean size of 3.4 (± 2.0) cm was most frequently reported. Concomitant metastasis was identified in seven individuals. Histopathologically, most neoplasms were of the small cell type, and immunohistochemistry for both epithelial and neuroendocrine differentiation was used in 65.5% cases. Radical surgery was the treatment of choice in almost all cases, with or without adjuvant therapy. Mean follow-up was 20.5 (± 21.2) months, and only four patients developed recurrences. Eleven (44.0%) individuals died due to the disease. Ulcerated lesions were a prognostic factor. This study provides knowledge that can assist surgeons, oncologists, and oral and maxillofacial pathologists with the diagnosis and management of neuroendocrine carcinomas. Our findings demonstrated that the long-term prognosis of this lesion continues to be poor., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Experimental studies are controversial regarding the effects of radiotherapy for head and neck cancer (HNC) on the dental pulp. Therefore, a systematic review of clinical studies is necessary to investigate whether alterations in pulp status occur., Objectives: To evaluate the evidence on radiotherapy for HNC and pulp status., Methods: A systematic search of articles published until November 2021 was performed in the MEDLINE/PubMed, Cochrane Library, Web of Science (All Databases), Scopus, EMBASE, and Open Grey databases. The eligibility criteria were based on the PICOS strategy, as follows: (P) vital teeth of adult patients with intraoral and/or oropharyngeal cancer; (I) radiotherapy; (C) control group or values of the same tooth before radiotherapy (basal values); (O) pulpal status after radiotherapy; and (S) clinical studies. The Cochrane Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the quality of the included studies. Meta-analyses were performed using fixed and random effects. The overall quality of evidence was assessed through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool., Results: Six studies were included for qualitative analysis. Five were classified as serious risk of bias and one as moderate risk of bias. Four studies reported altered pulp responses to cold thermal tests after radiotherapy initiation. Meta-analyses were performed using three included studies. From these, all were included in the meta-analysis for pulp response values to cold sensitivity test immediately after radiotherapy initiation (risk ratio: 0.00 [CI: 0.00, 0.02], p < .00001; I 2  = 0%); and two in the meta-analysis for pulp response values to cold sensitivity test after 4-5 months of radiotherapy (risk ratio: 0.01 [CI: 0.00. 0.06], p < .00001; I 2  = 0%). Two reported progressively higher readings to pulp response in the electrical test after radiotherapy initiation (mean difference: -11.46 [-13.09, -9.84], p < .00001; I 2  = 68%). Two studies demonstrated a pulp oxygen saturation (SpO 2 ) decrease at the end of radiotherapy; and an increase after 4-6 months of radiotherapy beginning. And other demonstrated normal dental pulp SpO 2 4-6 years after treatment. GRADE analysis presented a moderate certainty of evidence., Discussion: This review verified that radiotherapy for HNC causes significant alterations on the dental pulp responses, but does not seem to induce pulp necrosis. Significant limitations regarding controlling for confounding factors, classification of interventions, and measurement of outcomes were verified, evidencing the need for well-designed studies., Conclusions: This systematic review demonstrated that radiotherapy for HNC induced significant changes in the pulp response with moderate quality of evidence. Such altered responses cannot determine pulp status accurately., (© 2022 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Oral potentially malignant disorders (OPMD) represent a group of lesions with increased risk for malignant transformation. The management of such injuries is based on surgical treatment or detailed follow-up throughout the patient's lifetime. This systematic review and meta-analysis investigated and critically evaluated the use of autofluorescence and fluorescent probes as potential techniques for the early detection of OPMD. A comprehensive search was performed on Pubmed, Scopus, Web of Science and LIVIVO databases. The gray literature was also consulted and included Google Scholar, Proquest and Open gray databases. 2715 articles were retrieved, and after the different stages of critical evaluation, were reduced to 25 articles that fully met the inclusion criteria. VELscope® was the most used equipment for autofluorescence, while aminolevulinic acid (5-ALA) was the main representative of the probes. The meta-analysis performed included 10 articles that used VELscope® as a method to detect oral disorders. A 95% confidence interval (CI) with a p value significance <0.05 was considered as a criterion for the statistical analysis. The combined sensitivity was 74% (CI95 60-76%, p = 0.0001) and the specificity was 57% (CI95 52-60%, p = 0.0000). The inclusion of these adjunct methods in clinical practice is very promising, since they are able to help both the clinician and the specialist in the early detection of potentially malignant oral disorders, favoring a better prognosis. However, it is still necessary to carry out further studies, with the aim of establishing a protocol for use and qualification of results., (Copyright © 2022. Published by Elsevier B.V.)

Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS) is the most frequent non-Hodgkin lymphoma subtype. This aggressive neoplasm may variably express the CD30 protein, which may be used as a therapeutic target for this tumor. However, CD30 expression in DLBCL NOS arising from the oral cavity and the oropharynx has not been investigated. Therefore, this study aims to determine the frequency of CD30 expression and its prognostic significance for patients affected by oral/oropharyngeal DLBCL NOS. Fifty cases were retrieved from pathology files and submitted to immunohistochemistry against CD30. Reactivity was accessed by two oral pathologists using two cut-off values (> 0% and > 20% of tumor cells) to determine positivity in each case. Clinical data were obtained from the patients' medical files to investigate the prognostic potential of the protein. Seven high-grade B cell lymphomas and two EBV-positive DLBCL NOS were identified. We found one CD30-positive case in each of these two groups of lymphomas. Among the remaining 41 DLBCL NOS, other four cases (three in the oral cavity and one in the oropharynx) were positive for CD30, but only two expressed the protein in > 20% of tumor cells, both in the oral cavity. Survival analysis demonstrated that CD30-positive cases had a higher five-year overall survival rate (75%) than CD30-negative cases (32.3%), although a statistically significant result was not achieved (p = 0.19). Only a minor subset of oral and oropharyngeal DLBCL NOS express CD30 and these patients seems to have a higher survival rate., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aimed to assess the genotoxicity and cytotoxicity of Sealer Plus BC (SBC), AH Plus (AHP) and MTA Fillapex (MTF)., Methods: Human periodontal ligament dental stem cells (hPDLSCs) from third molars were isolated and cultured in a clonogenic medium. Cells were maintained in an incubator, and cell growth was monitored daily. hPDLSCs were characterised under flow cytometry and stem cell surface markers. The tested groups were a control group, SBC, AHP and MTF. Each sealer was prepared according to the manufacturer's instructions and placed in a clonogenic medium to produce a conditioned media. Conditioned media were then diluted to 10% to be placed in contact with culture cells in cell viability assay afterwards. The cells were harvested and plated into 96 wells culture plates. Genotoxicity was assessed by evaluation of micronucleus formation and cytotoxicity by MTT-based assay. All experiments were performed in triplicate. Data normality was verified by the Kolmogorov-Smirnov test. Statistical analysis for genotoxicity was performed with Kruskal-Wallis and Dunn's tests and two-way ANOVA for cytotoxicity, both with a significance level of 5%., Results: Cells expressed typical levels of mesenchymal stem cell surface markers. No differences in the number of micronuclei were observed among all groups (P>0.05). In all periods analysed (24, 48, and 72 h), the sealers presented statistically different results for cell viability (P<0.05), with SBC presenting the lowest cytotoxicity, followed by the control group, MTF, and AHP., Conclusion: All sealers presented low genotoxicity, and Sealer Plus BC presented the lowest cytotoxicity.

The purpose of this study was to evaluate the clinicodemographic characteristics and treatment protocol as prognostic factors in patients with oral squamous cell carcinoma (OSCC) of the hard palate, upper gingiva, and alveolar ridge (HPUGAR). This retrospective cohort study collected data of patients treated in two head and neck surgery departments in southern Brazil between 1999 and 2021. Information on clinicodemographic data, habits, site, size, clinical aspect, clinical staging, cervical metastasis, treatment, and survival was collected. Associations between independent variables and outcomes were assessed using Pearson's chi-square test and binary regression. Kaplan-Meier test was employed to compare the survival between the neck approaches. Forty-one patients were included; most were male (61%), with a mean age of 68.8 (± 13.9) years. The consumption of tobacco (p = 0.003) and alcohol (p = 0.02) was significantly higher in male than in female patients. The main clinical features observed in the study sample were lesions larger than 2 cm (48.7%), no cervical (90.2%), or distant metastasis (90.2%). Surgery alone was the main treatment approach (48.8%). The watch-and-wait strategy was adopted in 34 cases (83.0%), while elective neck dissection was applied in five (12.2%). Only two patients with cN0 disease (4.9%) presented with cervical metastasis at follow-up. Eight patients (12.2%) died of the disease. Clinicodemographic variables, habits, surgical margins, and histological subtype were not significantly associated with cervical metastasis or survival. Cervical metastasis (p = 0.004) was associated with poor survival. No difference was detected in survival between different neck approaches (p = 0.28). Cervical metastasis and local recurrence are negative prognostic factors for HPUGAR OSCC.

Objectives: Oral mucositis (OM) is an acute toxicity related to cancer treatment. This systematic review aimed to identify potential risk factors associated with the development of OM in pediatric cancer patients., Methods: A search was performed in four electronic databases to identify studies that analyzed risk factors for OM in pediatric cancer patients., Results: Nineteen articles were included. The incidence of OM ranged from 20% to 80.4%. Chemotherapeutic agents were potential risk factors for OM in eight (42%) studies. Hematological, hepatic, and renal parameters were also considered in eight (42%) studies, while specific individual factors were reported in five (26.3%) studies. Baseline disease, oral microbiota, genetic profile, and biomarkers were reported in four (21.5%) studies each. Meta-analysis showed that groups submitted to high-risk chemotherapy for OM had a 2.79-fold increased risk of OM., Conclusions: Identifying risk factors for OM is essential in order to allow individualized and early prevention treatment., (© 2021 Wiley Periodicals LLC.)

The aim of this study was to evaluate the impact of photobiomodulation therapy (PBMT) on histomorphological aspects of submandibular gland (SMG) submitted to salivary gland duct obstruction in hypothyroid rats. Fifty-six male Wistar rats (250 to 300 g) were divided into 4 groups (n = 14): euthyroid (EU), EU + PBMT, hypothyroid (HYPO), and HYPO + PBMT. Duct obstruction of the left submandibular gland (LSMG) was performed in all animals by a ligature procedure. For the induction of hypothyroidism, total thyroidectomy was performed. PBMT groups received irradiation with AlGaInP diode laser (808 nm, 0.04 W, 0.04cm 2 spot size, 60 s, 2.4 J per point, 60 J/cm 2 , 1 W/cm 2 ). Irradiation was performed immediately, 24 h, and 48 h after the obstruction of the salivary gland duct, in one point, extra oral and perpendicular to the gland. Animals were sacrificed after 24 h and 72 h after duct ligature. Our results indicated that salivary duct obstruction and hypothyroidism caused negative modifications on the salivary glands' histomorphology, especially acinar atrophy, after 24 h and 72 h. HYPO + PBMT showed a significant reduction of the inflammatory infiltrate, congested blood vessels, and acinar atrophy in the SMG submandibular salivary gland in 72 h compared to 24 h (p < 0.05). In conclusion, obstruction of the salivary gland excretory duct and hypothyroidism causes severe sialoadenitis with expressive atrophy of the glandular parenchyma. However, PBMT was able to modulate the inflammatory process and delaying acinar atrophy. This study provided insights to better understand the role of the PBMT on the altered salivary gland by duct ligation and associate hypothyroidism., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objective: This living systematic review aims to integrate the morphological and tissue-based molecular characterization of oral lesions occurring in individuals infected by COVID-19 (OLICs)., Materials and Design: This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Web of Science, Scopus, Ovid, Embase, and LILACS were searched to identify reports on OLICs with morphological and/or tissue-based molecular data., Results: Four studies reporting five cases were included. Three patients were male, and the mean age of the individuals was 47.6 years. The most reported anatomical location was the palate (n = 4), whereas ulcers were the most frequent clinical presentation (n = 3). Histopathologically, all cases revealed cell vacuolization and exocytosis in the epithelial layer. In the mesenchymal layer, inflammatory cell infiltrate and thrombi/microvascular thrombosis were observed in three cases. Immunohistochemical reactions were performed in two cases. Both cases were negative for HHV-1, HHV-2, and CMV. One case revealed positivity for SARS-CoV-2 spike protein. No other molecular tests were found for the characterization of OLIC., Conclusions: The pathological characteristics of OLICs are still unspecific. However, with the ongoing COVID-19 pandemic and well-documented new cases, whether OLICs are due to coinfections or has a primary origin can be determined., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To systematically integrate the available data published in the literature on oral pigmented lesions (OPL) associated with syndromes, summarizing the clinical and demographic features of the individuals., Materials and Methods: An electronic search was undertaken in six databases. Eligibility criteria were articles in English, Spanish, and Portuguese describing case reports or case series of OPL associated with syndromes. Data were aggregated and statistically evaluated., Results: About 108 articles reporting 149 cases of individuals with syndromes were identified. Among the affected individuals, nine syndromes were reported. The mean age at diagnosis was 35.93 years (0.41 to 83 years), with a predilection for white (n = 85/85.86%) female (n = 102/68.46%) individuals. As regards the number of lesions, 109 (73.15%) were multiple and 40 (26.85%) were single. Lip represented the anatomical location more affected (122 cases/38.01%), followed by the buccal mucosa (100 cases/31.15%). Brownish lesions accounted for 82 (69.49%) cases. The mean time of evolution was 10.52 years (0.16 to 56 years). OPL preceding diagnosis of the syndrome was observed in 111 (74.50%) cases., Conclusions: Although these syndromes are uncommon, dentists should be able to recognize their manifestations, since oral manifestations can represent an important aspect in early diagnosis., (© 2021 Wiley Periodicals LLC.)

Purpose: This study aimed to evaluate the effects and mechanisms of action of royal jelly (RJ) and propolis compared to photobiomodulation therapy (PBMT) in an animal model of 5-fluorouracil-related oral mucositis (OM)., Methods: Seventy-two male Wistar rats were randomly allocated to four groups (n = 18 each): control (no treatment), PBMT (intraoral laser, 6 J/cm 2 ), RJ, and propolis. On days 0 and 2, the animals received an injection of 5-fluorouracil (5-FU). The buccal mucosa was scratched (days 3 and 4) and the treatments were initiated on day 5. Six animals of each group were euthanized on days 8, 10, and 14. Phytochemical analysis (thin-layer chromatography, TLC) and clinical, histopathological, and immunohistochemical analysis of pS6, pAKT, and NF-κB were performed, and oxidative stress markers were also investigated., Results: TLC revealed the presence of large amounts of sucrose (Rf 0.34) in RJ and of flavonoids in propolis. Lower clinical OM scores were observed on day 8, and improved morphological data were observed on day 10 in the PBMT, RJ, and propolis groups (p < 0.05). On day 8, immunoexpression of pS6, pAKT, and NF-κB was increased compared to control. On day 14, reduced glutathione (GSH) antioxidant levels were increased in the propolis group compared to control (p < 0.05)., Conclusions: Our results showed that RJ and propolis, as well as PBMT, are effective in the treatment of OM. Considering that some patients who develop OM do not have access to PBMT, the present study demonstrated that topical application of RJ and propolis may be an important alternative for the treatment of OM., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We present a challenging case of HIV-related lymphangioma-like Kaposi sarcoma (LLKS) affecting the oral cavity. A 54-year-old Brazilian male patient was referred to our center complaining of bleeding lesions affecting the oral cavity for 2 months. Interestingly, these oral lesions were the first clinical manifestation of HIV infection. Clinically, multiple erythematous nodular and patch lesions were observed. An incisional biopsy was performed, revealing numerous microscopic angled and irregular vascular channels lined with flattened endothelial cells. More cellularized and solid areas consisting of more fusiform cells with little pleomorphism and with slit-like vascular channels were noted. Based on immunoreactivity for CD31, CD34, D2-40, and HHV-8, the final diagnosis was oral LLKS. Highly active antiretroviral therapy (HAART) was initiated with dolutegravir, tenofovir, and lamivudine. During follow-up, the patient showed KS metastases to other sites and a chemotherapeutic protocol was initiated. Regression of the oral lesion was clearly noted by the clinicians 1 year after the KS diagnosis. Dentists should be able to recognize systemic diseases that affect the oral cavity such as KS in order to make an early diagnosis of its oral manifestations and to implement effective therapeutic measures to ensure a better prognosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aluminum (Al) is one of the most abundant elements on Earth, and its high extraction rate and industrial use make human exposure very common. As Al may be a human toxicant, it is important to investigate the effects of Al exposure, mainly at low doses and for prolonged periods, by simulating human exposure. This work aimed to study the effects of low-dose exposure to chloride aluminum (AlCl 3 ) on the oxidative biochemistry, proteomic profile, and morphology of the major salivary glands. Wistar male rats were exposed to 8.3 mg/kg/day of AlCl 3 via intragastric gavage for 60 days. Then, the parotid and submandibular glands were subjected to biochemical assays, proteomic evaluation, and histological analysis. Al caused oxidative imbalance in both salivary glands. Dysregulation of protein expression, mainly of those related to cytoarchitecture, energy metabolism and glandular function, was detected in both salivary glands. Al also promoted histological alterations, such as acinar atrophy and an increase in parenchymal tissue. Prolonged exposure to Al, even at low doses, was able to modulate molecular alterations associated with morphological impairments in the salivary glands of rats. From this perspective, prolonged Al exposure may be a risk to exposed populations and their oral health.

Introduction: Postoperative management of patients undergoing tonsillectomy is challenging. Photobiomodulation therapy (PBMT) has emerged as a new tool providing therapeutic benefits. However, the contribution of PBMT to the postoperative outcomes of tonsillectomy is still undefined. This systematic review and meta-analysis evaluated the published literature addressing the effects of PBMT on post-tonsillectomy. Methods: Searches in Scopus, PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and grey literature were carried out for the identification of randomised controlled trials reported up to August/2021. The risk of bias with the Cochrane Collaboration tool and meta-analysis was performed. Outcomes were assessed with the Kaplan-Meier method and the log-rank test. Results: A total of 1183 articles were retrieved, of which only two were included for qualitative and quantitative analysis. The wavelengths were 685 nm and 980 nm with energy density set at 4 J/cm 2 . The mandibular angle and the surgical wound were the sites of laser irradiation. Individuals who had not undergone PBMT after tonsillectomy were more likely to report pain and odynophagia in the first 24 hours after surgery than individuals who had undergone PBMT after tonsillectomy ( P <0.001). Children who received PBMT after tonsillectomy were equally affected by pain and odynophagia in the first seven days after surgery compared to children who had not undergone PBMT after tonsillectomy ( P >0.05). However, both studies found a significant association of PBMT with reduced analgesic consumption. Conclusion: Although PBMT seems promising for the management of individuals undergoing tonsillectomy, a limited number of studies are available in the literature., (Copyright © 2022 J Lasers Med Sci.)

The aim of the present study was to analyze the relationship of OM with possible risk factors such as oral health condition, immunological status and IL-1β profile in patients submitted to hematopoietic stem cell transplantation (HSCT). Fifty-four individuals submitted to HSCT were included. All patients received previous dental treatment and photobiomodulation (PBM) as the institutional OM preventive protocol. OM scores, immune status, and IL-1β levels were determined during the conditioning period and at D+3 and D+8 after HSC infusion. IL-1β gene polymorphism was also analyzed during conditioning. Possible associations of OM with risk factors were analyzed using conditional Fisher's exact test. OM was observed in 34 patients (62.9%) classified as Grade 1 (13 patients/24.1%), Grade 2 (14 patients/25.9%), Grade 3 (3 patients/5.5%), and Grade 4 (4 patients/7.4%). Allogeneic HSCT individuals exhibited a higher OM grade than autologous subjects. Moreover, an association was observed between severe OM and severe gingivitis (p = 0.01), neutropenia (p = 0.03), and leukopenia (p = 0.04). A significant association between OM and lower IL-1β levels was detected at three time points, i.e., conditioning (p = 0.048), D+3 (p = 0.01), and D+8 (p = 0.005). The results showed that IL-1β gene polymorphism was not associated with OM. Our study provided important insights into the scope of OM risk factors in the setting of HSCT. Patients submitted to HSCT with severe gingivitis prior to chemotherapy and with severe neutropenia and leukopenia exhibited a higher OM grade. Further investigation will be necessary to better understand the exact role of IL-1β in the context of OM pathobiology and to validate cytokine analysis in larger cohorts.

Objective: The aim of the present study was to carry out a systematic review of available data regarding case reports and case series of oral and maxillofacial benign fibrous histiocytoma (BFH)., Study Design: A search strategy was performed using the PubMed, Web of Science, Scopus, and EMBASE electronic databases., Results: Male individuals (56.89%) were more affected, with a mean age of 34.55 ± 20 years. The buccal mucosa (20.33%) represented the most common site, with the clinical presentation of a painless (86.95%) nodule (98.03%). The clinical hypothesis of a fibroma was reported in most cases (31.57%). Radiographic presentation of intraosseous lesions showed multilocular radiolucent images (55.55%). Regarding the histopathologic features, the biphasic population of fibroblastic and histiocytic cells was seen in 21 cases (39.62%), and a spindle-shaped fibroblastic cell population organized into a storiform pattern was observed in 25 cases (47.16%). CD68 (n = 26) and vimentin (n = 25) showed immunoreactivity in all BFH cases in which they were used. All cases were treated with a surgical resection, and 8.10% recurred., Conclusions: The current systematic review demonstrated that BFH represents a rare lesion that mainly affects the buccal mucosa of male individuals, and the treatment is mainly surgical with a good prognosis., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Lymphatic malformations are characterized by the overgrowth of lymphatic vessels during development. Activation of PI3K/AKT and MAPK/ERK signaling pathways occur in isolated lymphatic malformation and in those associated with syndromes such as CLOVES and Klippel-Trenaunay. We aimed to assess the activation of these pathways in sporadic oral lymphatic malformations., Study Design: A convenience sample of 14 formalin-fixed paraffin-embedded samples of oral lymphatic malformations underwent immunohistochemical reactions for the phosphorylated forms of AKT1 (pAKT-Ser473) and ERK1/2 (pERK1/2-Thr202/Tyr204), which are markers of PI3K/AKT and MAPK/ERK pathways activation, respectively., Results: Positive staining for pAKT1 and pERK1/2 was observed in the endothelial cells in all samples of oral lymphatic malformations evaluated., Conclusions: Our results suggest that activation of PI3K/AKT and MAPK/ERK signaling pathways participates in the pathogenesis of oral lymphatic malformations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study tested the hypothesis that head and neck radiotherapy (HNRT) impacts the immunoexpression of type I collagen, bone sialoprotein (BSP) and bone morphogenetic protein 4 (BMP4), thereby leading to micromorphological changes in the dentin-pulp complex (DPC), and promoting the onset and progression of radiation caries (RC). Twenty-two demineralized sections of carious teeth (a group of 11 irradiated teeth and a control group of 11 non-irradiated teeth) extracted from 19 head and neck cancer patients were analyzed by conventional optical microscopy and immunohistochemistry to investigate the micromorphology (cellular layer hierarchy, blood vessels, odontoblasts, fibroblasts, extracellular matrix, calcification, necrosis, reactionary dentin formation, and chronic inflammation), and the patterns of staining/immunolocalization of type I collagen, BSP and BMP4 in the dental pulp of irradiated and control samples. No significant differences attributable to the direct impact of radiotherapy were detected in DPC micromorphology between the groups. In addition, the patterns of immunohistochemical staining and immunolocalization of the proteins studied did not differ between the irradiated and the control samples for type I collagen, BSP or BMP4. This study rejected the hypothesis that HNRT directly damages dentition by changing the organic components and the microstructure of the DPC, ultimately leading to RC.

Skin wounds represent a burden in healthcare. Our aim was to investigate for the first time the effects of defocused high-power diode laser (DHPL) on skin healing in an animal experimental model and compare it with gold standard low-level laser therapy. Male Wistar rats were divided into 5 groups: Negative control; Sham; 0.1 W laser (L0.1 W); DHPL Dual 1 W (DHPLD1 W); and DHPL Dual 2 W (DHPLD2 W). Rats were euthanized on days 3, 5, 10, 14 and 21. Clinical, morphological, PicroSirus, oxidative stress (MDA, SOD and GSH) and cytokines (IL-1β, IL-10 and TNF-α) analyses were performed. A faster clinical repair was observed in all laser groups at D10 and D14. DHPLD1 W exhibited lower inflammation and better reepithelization compared to other groups at D10. DHPL protocols modulated oxidative stress by decreasing MDA and increasing SOD and GSH. Collagen maturation was triggered by all protocols tested and L0.1 W modulated cytokines release (IL-1β and TNF-α) at D3. In conclusion, DHPL, especially DHPL1 W protocol, accelerated skin healing by triggering reepithelization and collagen maturation and modulating inflammation and oxidative stress., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Considering the lack of studies determining the real TPTD efficacy in individuals who develop MRONJ, our objective was to combine the available data on MRONJ cases treated with TPTD. The findings demonstrated that TPTD in combination with another therapy, especially antibiotic therapy, can be considered an effective protocol for MRONJ., Purpose: To integrate the data published on the effect of teriparatide (TPTD) therapy on cases of medication-related osteonecrosis of the jaws (MRONJ) into a comprehensive analysis of clinical features., Methods: An electronic search was undertaken in six databases. Descriptive analyses of clinicodemographic data of MRONJ were carried out. Poisson regression was also run to evaluate predictors of total resolution of MRONJ treated with TPTD., Results: Twenty-six publications comprising 111 cases were included. Most reported cases affected female individuals (82.0%) with a mean age of 76.54 years. Osteoporosis (76.5%) represented the main reason for using antiresorptive drugs, with bisphosphonates (98.1%) as the most frequently reported. Comorbidities were commonly present. The most related trigger factor of MRONJ was dental extraction (61.7%). Mandible (75.8%) was the most commonly affected site, with a mean evolution time of 5 months. MRONJ stage 2 (61.3%) was the most prevalent. Regarding TPTD treatment, in 45.1% cases, TPTD was used alone, with the total resolution being observed in 59.5% of the individuals. Associated therapy (54.9%) included surgery, antibiotic therapy, and laser therapy. Mean follow-up was 8.7 months. Poisson regression demonstrated that individuals with MRONJ stage 1 were 1.21 times more likely to present total resolution of osteonecrosis than individuals with MRONJ stage 3 (CI = 1.02-1.43; p < 0.023). Individuals who had undergone treatment with TPTD in association with another therapeutic modality were 1.21 times more likely to present total resolution of osteonecrosis than those who had undergone treatment with TPTD alone (CI = 1.40-1.39; p < 0.010)., Conclusion: TPTD in combination with another therapy, especially antibiotic therapy, should be considered an effective therapeutic modality for MRONJ., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Purpose: To investigate the incidence and risk factors for oral mucositis (OM) in patients with childhood cancer undergoing chemotherapy., Methods: Eight hundred and twenty-nine cycles of chemotherapy were evaluated in 112 patients with childhood cancer undergoing chemotherapy. Chemotherapy protocol, hematological, hepatic, and renal function parameters were collected and compared to presence and severity of OM, as graded by the World Health Organization (WHO) scale. Patients received counseling on oral hygiene and those who presented with OM (grade ≥1) received photobiomodulation therapy (PBMT)., Results: Age ranged from 0 to 17 years (mean/SD, 8.58 ± 5.05) and fifty-one patients (45.54%) were females. The most common baseline diseases were leukemia (51%) followed by sarcomas (23%) and lymphomas (18%). Eight hundred and twenty-nine cycles of chemotherapy were evaluated, and OM was diagnosed in 527 cycles (63.57%). Higher incidence and severity of OM was observed in protocols using high-dose methotrexate (MTX-HD), MTX-HD cyclophosphamide/doxorubicin combination, and MTX-HD combined with cyclophosphamide (p <0.001). Patients with severe OM had lower levels of leukocytes (p = 0.003), hemoglobin (p = 0.005), platelets (p = 0.034), and higher levels of total bilirubin (p = 0.027), alanine aminotransferase (ALT) (p = 0.001), and creatinine (p = 0.007)., Conclusion: The study contributes to the elucidation of the risk factors for OM in pediatric cancer patients. Chemotherapy protocols using MTX-HD, MTX-HD associated with doxorubicin and cyclophosphamide, and MTX-HD and cyclophosphamide a have higher incidence of severe grades of OM. Other toxicities such as hematological, hepatic, and renal also developed in patients with OM., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To compare the efficacy of intraoral and extraoral photobiomodulation (PBM) protocols for the prevention of oral mucositis (OM) in hematopoietic stem cell transplantation (HSCT) patients. A total of 60 patients was randomized into intraoral PBM (IOPBM) and extraoral PBM (EOPBM) groups. Both PBM protocols were well tolerated and no side effects were observed. EOPBM session times were one fourth of IOPBM durations. Of 60 patients, 35 (58.3%) developed ulcerated OM between day +3 and day +12. No intergroup difference was observed in OM healing times (p = 0.424). The lateral border of the tongue was the most common site affected in both groups. However, the incidence of mucositis on buccal mucosa was significantly reduced in the EOPBM group (p = 0.021). Young patients (OR.5.35, 95%CI 0.94-30.4, p = 0.058) and those who had received myeloablative conditioning (OR.55.1, 95%CI 2.69-1129.3, p = 0.009) were more likely to develop ulcerated OM, whereas autologous HSCT recipients (OR 0.079, 95% CI 0.009-0.67, p = 0.021) had a lower probability of developing ulcerated OM independent of PBM protocol. EOPBM protocol was as effective as IOPBM in the management of OM in HSCT patients, with the advantage of shorter treatment sessions. Trial registration number: RBR-7nww56. Date of trial registration submission: 30th September 2019., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Skin ulcers, wounds, or burns represent a burden for health care worldwide. Our aim was to explore the effects of mucoadhesive formulation with Curcuma longa L. extract mucoadhesive formulation containing curcumin (MFC) on skin healing in Wistar rats. Fifty-four rats were randomly allocated into 3 groups: control, vehicle, and MFC. A full-thickness circular wound was induced on the back of each animal. Two daily applications of the products were performed according to the experimental group. On days 3, 10, and 21, 6 animals in each group were euthanized. Clinical analysis was based on wound area. Histologic analysis was performed in hematoxylin and eosin-stained sections, with re-epithelization and inflammation being assessed by means of semiquantitative scores. To analyze the Akt/mTOR pathway, immunohistochemistry for phospho Akt (pAkt) and phospho ribosomal protein S6 were investigated. In addition, nuclear factor kappa-light-chain-enhancer of activated B cells immunolabeling was performed. Clinical analysis revealed wounds with a smaller area on days 3 and 10 in curcumin-treated animals. Histologically, MFC had a significant impact on inflammatory events on days 3 and 10 and promoted faster re-epithelization, which was evidenced on day 10. MFC-treated wounds exhibited pAkt upregulation on day 10 and both pAkt and phospho ribosomal protein S6 downregulation on day 21. Nuclear factor kappa-light-chain-enhancer of activated B cells expression varied through the evaluation periods; however, no significant difference was observed between groups. Collectively, our results indicate that MFC is efficient in accelerating cutaneous wound repair through modulation of the inflammatory process and stimulus of re-epithelization by an Akt/mTOR-dependent mechanism., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Cutaneous basal cell carcinoma recurrence is associated with inadequate surgical margins. The frequency of and the factors associated with compromised or inadequate surgical margins in head and neck basal cell carcinoma varies., Objective: The purpose of this study was to evaluate the clinical and pathological factors associated with inadequate surgical margins in head and neck basal cell carcinoma., Methods: We developed a cross-sectional study comprising all patients who had undergone resection of head and neck basal cell carcinoma from January 2017 to December 2019. Data on age, sex, head and neck topography, histopathological findings, and staging were retrieved and compared. Each tumor was considered an individual case. Compromised and close margins were termed "inadequate" or "incomplete". Variables that were significantly associated with the presence of incomplete margins were further assessed by logistic regression., Results: In total, 605 tumors from 389 patients were included. Overall, sixteen cases (2.6%) were classified as compromised, 52 (8.5%) as close, and 537 (88.7%) as free margins. Presence of scleroderma (p=0.005), higher Clark level (p<0.001), aggressive variants (p<0.001), invasion beyond the adipose tissue (p<0.001), higher T stage (p<0.001), perineural invasion (p=0.002), primary site (p=0.04), multifocality (p=0.01), and tumor diameter (p=0.02) showed association with inadequate margins. After Logist regression, multifocality, Clark level and depth of invasion were found to be independent risk factors for inadequate margins., Conclusion: Gross clinical examination may be sufficient for determining low prevalence of inadequate surgical margins when treating head and neck basal cell carcinoma in highly experienced oncologic centers. Multifocality, Clark level and depth of invasion were found to be independent risk factors for incomplete margins., (Copyright © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Objectives: DNA methyltransferases (DNMTs) and the histone modification H3K9ac are epigenetic markers. This study aimed to describe the immunohistochemical expression of DNMT1, DNMT3A, DNMT3B, and H3K9ac in the dental follicle (DF), ameloblastoma (AME), and ameloblastic carcinoma (AC), correlating these expressions with the recurrence and aggressive behavior in ameloblastoma. Study Design: Immunohistochemical reactions were performed in 10 human DFs, 38 ameloblastomas, and 6 AC samples. Another 59 ameloblastomas assembled in a tissue microarray were used to compare the immunoexpression with the clinical, radiographic, and histopathological characteristics and the presence of BRAFv600e mutation. Each slide was digitized as a high-resolution image and quantified by Aperio ScanScope Nuclear V9 software. All statistical analyzes were performed using GraphPad Prism statistical software. Results: DNMT3B expression was higher in ameloblastomas than in the DFs, while the AC overexpressed all proteins. The ameloblastomas with BRAFv600e mutation, vestibular/lingual, or vestibular/palatine bone cortical disruption and maxilla involvement showed DNMT1 overexpression, while recurrent cases had high DNMT3B levels. Conclusions: DNA methylation and histone modification might play a role in the development, clinical aggressiveness, and recurrence rates of ameloblastoma, such as the progression to AC. Further investigation about gene methylations in ameloblastomas is needed to better understand its relationship with aggressiveness and recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Amaral-Silva, Morais, Wagner, Martins, Fregnani, Soares, Rocha, Pontes, Santos-Silva and Vargas.)

The role of digital pathology in remote reporting has seen an increase during the COVID-19 pandemic. Recently, recommendations had been made regarding the urgent need of reorganizing head and neck cancer diagnostic services to provide a safe work environment for the staff. A total of 162 glass slides from 109 patients over a period of 5 weeks were included in this validation and were assessed by all pathologists in both analyses (digital and conventional) to allow intraobserver comparison. The intraobserver agreement between the digital method (DM) and conventional method (CM) was considered almost perfect (κ ranged from 0.85 to 0.98, with 95% CI, ranging from 0.81 to 1). The most significant and frequent disagreements within trainees encompassed epithelial dysplasia grading and differentiation among severe dysplasia (carcinoma in situ) and oral squamous cell carcinoma. The most frequent pitfall from DM was lag in screen mirroring. The lack of details of inflammatory cells and the need for a higher magnification to assess dysplasia were pointed in one case each. The COVID-19 crisis has accelerated and consolidated the use of online meeting tools, which would be a valuable resource even in the post-pandemic scenario. Adaptation in laboratory workflow, the advent of digital pathology and remote reporting can mitigate the impact of similar future disruptions to the oral and maxillofacial pathology laboratory workflow avoiding delays in diagnosis and report, to facilitate timely management of head and neck cancer patients. Graphical abstract., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim of the present systematic review was to analyze the available data regarding acinic cell carcinoma of the oral and maxillofacial region., Methods: A search strategy was performed using PubMed, Web of Science, Scopus, and Embase electronic databases., Results: Available data revealed a slight female preference (54.73%) and a mean age at diagnosis of 47.51 ± 19.85 years. The parotid glands (67.72%) were most frequently affected, and most cases were asymptomatic (69.54%). A microcystic histopathological pattern was reported in 21.56% of the cases, and the Periodic acid-Schiff was the staining method most frequently used, after the hematoxylin and eosin staining, in the tumors analyzed. The lesions were mainly treated by surgical removal (72.32%). Recurrence was reported in 81 cases (27.83%) and metastasis in 100 (42.91%). Statistical data analysis revealed that tumors located in major salivary glands and exhibiting high-grade histology were associated with local recurrence (P = .01). In addition, the patients older than 57 years, lesions with bone involvement, the high-grade tumors and the cases with a history of recurrence and metastasis were associated with a lower overall survival (P < .05)., Conclusion: By assembling all eligible cases in the literature, the present systematic review determined the most common clinicopathological profile of acinic cell carcinoma and the most relevant prognostic factors in a distinctly representative sample. The survey demonstrated the importance of considering the histopathological grading in order to better define the treatment for each case., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate systematically the evidence about the failure rates of endodontically treated teeth (ETT) restored with intraradicular metal posts (MPs) or fiber posts (FPs)., Data: The review protocol was registered on PROSPERO (CRD42020189792). Eligibility criteria included randomized clinical trials (RCT) and prospective clinical trials (PCT) that compared the failures between FP and MP restorations for ETT. Meta-analyses were conducted for failure rates using fixed- and random-effects models. Subgroup and funnel plot analyses were performed., Sources: Four electronic databases (MEDLINE/PubMed, Web of Science, Scopus, and Cochrane Library), manual, and grey literature were screened by two researchers independently for articles published until November 2020 without language or time restrictions. For the analysis of the risk of bias, the Cochrane collaboration tool and ROBINS-I were used. The certainty of the evidence was evaluated using GRADE., Study Selection: Ten studies were included. A total of 704 participants with a mean age of 42.7 years with a total of 844 ETT were restored using 453 FPs and 391 MPs. The FPs presented similar failures to that with MPs (P=0.39; risk ratio [RR]:0.82; 95% confidence interval [CI]: 0.52 to 1.29). Subgroup analysis showed no significant differences between the FPs and MPs for the anterior region (P=0.60; RR:0.88; [CI]: 0.54 to 1.42), posterior region (P=0.52; RR:1.18; [CI]: 0.71 to 1.98), root fracture (P=0.44; RR:0.78; [CI]: 0.41 to 1.49), and debonding (P=0.56; RR:1.27; [CI]: 0.57 to 2.80). Additionally, FP showed similar failures compared with those of cast (P=0.36; RR:0.63; [CI]: 0.23 to 1.72) and prefabricated MPs (P=0.68; RR:0.90; [CI]: 0.54 to 1.50). The RCT and PCT studies revealed a low risk of bias for most of the domains. However, the certainty of evidence was considered low., Conclusion: No evidence of difference was observed for failure rates between FPs, and MPs, independent of region and different MPs used in ETT. However, further well-conducted clinical studies with high-quality evidence are encouraged., Clinical Significance: Our results indicate that both retainer posts can be considered an adequate alternative in restoring ETT. Therefore, the choice of post (fiber or metal) could be based on dentist preference or individual characteristics of the patient as the failure rates for different posts are similar., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Methylmercury (MeHg) is one of the main global pollutants. The vulnerability of fetus and newborn to MeHg-induced changes is extensively reported, making relevant investigation possible for alternative sample matrix for human biological monitoring for at this stage of life. This study aimed to characterize tissue change effects of environmental-experimental MeHg on salivary glands of offspring rats after pre- and postnatal exposure. For this, pregnant Wistar rats were orally exposed to MeHg (40 μg/kg BW/day) or only vehicle (control group), from the gestational period to the end of the lactation period. Salivary glands (SG) were collected from the offspring to analyze possible Hg levels and main findings by histopathological evaluations and CK19 and α-SMA immunostaining. The results indicated that Hg levels in SG of intoxicated offspring were associated with histologic abnormalities, such as acinar atrophy and an increase in the intercellular matrix among the acini, as well as damages in the architecture of epithelium and myoepithelial cells, evidenced by a decrease in immunostaining area. Thus, this is the first study to show in the literature the toxicopathologic findings on SG of offspring after pre- and postnatal exposure to MeHg. Moreover, it presents the SG as an attractive target to futures studies, mainly in children exposed to environmentally relevant doses.

This randomized placebo-controlled trial evaluates the impact of photobiomodulation (PBMT) on the salivary flow and biochemistry of patients with chronic kidney disease (CKD) on hemodialysis. Forty-four patients on hemodialysis self-responded two questionnaires for oral health and salivary gland function perception. The subjects were evaluated for function of salivary glands and randomly allocated to two groups: PBMT group (three irradiations at 808 nm, 100 mW, 142 J/cm 2 , and 4 J per site); and placebo group. Patients were submitted to non-stimulated and stimulated sialometry and after the treatment at baseline and 14 days. Salivary volume and biochemical of the saliva were analyzed. At baseline, most subjects had self-perception of poor oral health (52.6%) and salivary dysfunction (63.1%). Clinical exam revealed that 47.3% of subjects presented dry mucosa. PBMT promoted increase of the non-stimulated (p = 0.027) and stimulated saliva (p = 0.014) and decrease of urea levels in both non-stimulated (p = 0.0001) and stimulated saliva (p = 0.0001). No alteration was detected in total proteins and calcium analysis. Patients with kidney disease can present alteration in flow, concentrations, and composition of saliva, affecting oral health, but our findings suggest that PBMT is effective to improve hyposalivation and urea levels in saliva of patients with CKD., (© 2021. Springer-Verlag London Ltd., part of Springer Nature.)

Introduction: Regional metastases of cutaneous head and neck squamous cell carcinoma occur in approximately 5 % of cases, being the most important prognostic factor in survival, currently with no distinction between parotid and neck metastasis., Objective: The purpose of this study was to evaluate the prognostic features among patients with head and neck cutaneous squamous cell carcinoma exhibiting regional metastasis., Methods: A retrospective analysis of patients with cutaneous squamous cell carcinoma who underwent parotidectomy and/or neck dissection from 2011 to 2018 at a single institution tertiary center was performed. Patient demographics, clinical, surgical and pathological information, adjuvant treatments, and outcome at last follow-up were collected. Outcomes included disease recurrence and death due to the disease. Prognostic value of clinic pathological features associated with disease-specific survival was obtained., Results: Thirty-eight cases of head and neck cutaneous squamous cell carcinoma with parotid and/or neck metastasis were identified. Overall, 18 (47.3 %) patients showed parotid metastasis alone, 12 (31.5 %) exhibited neck metastasis alone and 8 (21.0 %) had both. A primary tumor in the parotid zone (Hazard Ratio ‒ HR = 5.53; p = 0.02) was associated with improved disease-specific survival. Poorer disease-specific survival was observed in patients with higher primary tumor diameter (HR = 1.54; p = 0.002), higher depth of invasion (HR = 2.89; p = 0.02), invasion beyond the subcutaneous fat (HR = 5.05; p = 0.002), neck metastasis at first presentation (HR = 8.74; p < 0.001), number of positive lymph nodes (HR = 1.25; p = 0.004), and higher TNM stages (HR = 7.13; p = 0.009). Patients presenting with isolated parotid metastasis during all follow-ups had better disease-specific survival than those with neck metastasis or both (HR = 3.12; p = 0.02)., Conclusion: Head and neck cutaneous squamous cell carcinoma with parotid lymph node metastasis demonstrated better outcomes than cases with neck metastasis., (Copyright © 2019 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Although uncommon, mature small B-cell lymphomas may arise in the oral/maxillofacial area and oral pathologists must be aware of the key characteristics of these neoplasms to perform an accurate diagnosis. In this manuscript, we attempted to integrate the currently available data on the clinicopathological features of follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT-L), and chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) affecting these anatomical regions., Methods: An updated descriptive literature review was carried out and a detailed electronic search was done in multiple databases to gather all cases affecting the oral/maxillofacial region and palatine tonsils., Results: We observed that MALT-L was the most frequently reported subtype, followed by FL, MCL, and CLL/SLL. The palate was affected in a high proportion of cases and the most usual clinical presentation was an asymptomatic swelling. MALT-L and CLL/SLL neoplastic cells were strongly associated with small salivary glands. FL showed no gender preference, while MCL and CLL/SLL were more prevalent in males and MALT-L in females. Overall, cases were more common in elderly individuals. Patients' treatment and outcome varied, with MCL being the most aggressive neoplasm with a dismal prognosis in comparison to FL and MALT-L., Conclusion: Despite the poor documentation in many of the cases available, especially regarding the microscopic and molecular features of tumors, this review demonstrated that the oral mature small B-cell lymphomas investigated share similar clinical presentation, but carry different prognostic significance, demanding an accurate diagnosis., (© 2021 The Authors. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.)

Background: Lymphomas in the oral and oropharyngeal regions are relatively uncommon, and their diagnosis is challenging and complex due to the myriad histopathological subtypes. Herein, we report a large series of oral and oropharyngeal lymphomas and compare our data with the currently available literature., Methods: All cases diagnosed as lymphomas affecting the oral and oropharyngeal regions were retrospectively retrieved from seven Brazilian institutions. Clinicodemographic data and histopathological features were evaluated and described, while a comprehensive literature review was undertaken in order to compare our findings., Results: A total of 304 cases of oral and oropharyngeal lymphomas were obtained, mostly affecting individuals aged 60-69 years (n = 68) with a mean age at diagnosis of 54.2 ± 20.1 years. Males and females were equally affected. Mature B-cell neoplasms (87.2%) were the most common group, followed by mature T- and NK-cell neoplasms (11.2%) and precursor lymphoid neoplasms (1.6%). The most frequent subtypes in each group were diffuse large B-cell lymphomas, not otherwise specified (n = 99), extranodal NK/T-cell lymphomas, nasal type (n = 12), and B-lymphoblastic leukaemia/lymphomas, not otherwise specified (n = 4). The most commonly involved sites were the palate (26.3%), mandible (13%), and maxilla (10.5%)., Conclusion: Diffuse large B-cell lymphoma, not otherwise specified, remains the most common subtype of lymphomas in the oral and oropharyngeal region. Older patients are the most affected, with no gender predilection and the palate and jaw are usually affected., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mucositis is one of the more frequent and costly adverse events following cancer treatment. To evaluate and report the direct economic outcomes associated with the management of mucositis across several cancer treatments we conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE/PubMed, and Embase were searched electronically and a total of 37 relevant studies were included. The costs attributable to mucositis in the hematopoietic stem cell transplantation setting ranged from 1124,47 US dollars (USD) to 299 214,14 USD per patient. The radiotherapy/chemoradiotherapy/radiotherapy plus molecular targeted therapy accounted for mucositis costs that ranged from 51,23 USD to 33 560,58 USD per patient. Costs for mucositis in the chemotherapy setting ranged from 4,18 USD to 31 963,64 USD per patient. When the cancer treatment was not specified, costs of mucositis ranged from 565,85 USD to as high as 20 279, 12 USD per patient. Mucositis costs from multimodal therapy ranged from 12,42 USD to 5670,46 USD per patient. The molecular targeted therapy setting included only one study and depending on the healthcare providers' perspective of each country evaluated, mucositis' costs ranged from 45,78 USD to 3484,91 USD per patient. Mucositis is associated with increased resource use, consultations, hospitalizations and extended hospitalizations, leading to a substantial incremental cost that exacerbates the economic burden on the patient, health plan and health system across several cancer treatments and diagnosis. More studies with a prospective evaluation of the economic costs associated with mucositis management are needed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The diagnosis of oral and maxillofacial mature T/NK-cell neoplasms is challenging because of their rarity, morphological heterogeneity and complex immunophenotype with scarce available data describing their clinical and microscopic aspects. Therefore, in this study, we investigated a series of mature T/NK-cell neoplasms affecting this anatomical region and provided an updated literature review., Methods: Cases diagnosed as mature T/NK-cell lymphomas affecting the oral and maxillofacial region were retrospectively retrieved from six pathology files and their diagnoses were confirmed using haematoxylin and eosin-stained slides, immunohistochemical reactions and in situ hybridization for Epstein-Barr virus (EBV) detection. Patients' clinical data were collected from their pathology forms., Results: A total of 22 cases were included in this study. Eleven (50%) consisted of extranodal NK/T-cell lymphomas, nasal type; eight (36.4%) were peripheral T-cell lymphomas, NOS; two (9.1%) were adult T-cell leukaemia/lymphomas, and one (4.5%) was an ALK-positive anaplastic large cell lymphoma. Overall, males predominated, with a mean age of 55.7 years. The palate was the most affected site (50%), and tumours usually presented as destructive and painful ulcers. EBV was present in all cases of extranodal NK/T-cell lymphoma nasal type but was absent in the other subtypes., Conclusion: Among mature T/NK-cell lymphomas of the oral and maxillofacial region, extranodal NK/T-cell lymphoma, nasal type and peripheral T-cell lymphoma, NOS predominated. Older men were the most affected patients, and this heterogeneous group of neoplasms has a very aggressive clinical behaviour., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This paper intends to describe the demand for referrals to the stomatology service requested by the medical teams for inpatients in a reference hospital in the south of Brazil. This research is a retrospective cross-sectional descriptive study focusing on data collection and assessment of information about referrals to the stomatology unit carried out from January 2008 to December 2018. All information was obtained from the hospital management software database, then transferred and analyzed individually for descriptive statistics. A total of 4433 cases were referred to the stomatology team, with an average of 403 cases by year. Hematology/hemato-oncology (37.3%) was the specialty asking for the majority of the referrals, followed by Oncology (20.4%) and Pneumology (8.2%). The mean patients' profile was males (55.5%), receiving a diagnosis of oral mucositis (43.5%), and with the first and second decades of life being the most prevalent ones (34.9%), with a mean age of 34.8±22.3 years. The most common treatment performed by the stomatology team was the photobiomodulation therapy (44.8%). This retrospective study demonstrated the important profile of the stomatological care in hospitalized patients from a specific hospital, especially referred by the hematology/hemato-oncology team. These results evidenced the importance of the stomatology specialty in the hospital environment.

The aim of this study was to identify tumor parenchyma cells exhibiting immunohistochemical profile of stem cells by evaluating the immunoreactivity of OCT4 and CD44 in a number of cases of salivary gland neoplasms. The sample consisted of 20 pleomorphic adenomas, 20 mucoepidermoid carcinomas, and 20 adenoid cystic carcinomas located in major and minor salivary glands. The expression of OCT4 and CD44 was evaluated by the percentage of positive cells and the intensity of expression. All studied cases showed positive expression of OCT4 and CD44 and higher values than the control groups. For OCT4, luminal and non-luminal cells were immunostained in the case of pleomorphic adenomas and adenoid cystic carcinomas. Moreover, the immunoreactivity of CD44 was particularly evident in the non-luminal cells of these lesions. In mucoepidermoid carcinomas, there was immunoreactivity for both markers in squamous and intermediate cells and absence of staining in mucous cells. For both markers, a significantly higher immunostaining was verified in neoplasms located in the major salivary glands compared with lesions in minor salivary glands (p<0.001). In the total sample and in minor salivary glands, malignant neoplasms exhibited higher immunoreactivity for OCT4 than pleomorphic adenoma. A significant moderate positive correlation (r = 0.444 and p ≤ 0.001) was found between OCT4 and CD44 immunoexpression in the total sample. The high expression of OCT4 and CD44 may indicate that these proteins play an important role in identifying tumor stem cells.

Timely diagnosis and treatment of oral and oropharyngeal cancers are central for the patient's survival. Our objective was to document the impact of the COVID-19 pandemic on the rate of hospitalizations due to these cancers in Brazil's National Health System (SUS). The number of hospitalizations by these cancers during the first periods of the pandemic-and between the same period of 2016 to 2019-was retrieved from the SUS Hospital Information System. We compared hospitalization rates between pre- and pandemic periods, by State. The hospitalization rate for oral and oropharyngeal cancer during the pandemic was lower than that of the same period of previous years. The decline between 2019 and 2020 was of 49.3%, reaching 60% in the North. The reduction in hospitalization during an extended period suggests that oral and oropharyngeal cancer care will be postponed, with potentially detrimental impact on survival., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Salivary gland cancers (SGC) represent an uncommon group of heterogeneous tumors. We performed a retrospective survey of SGC diagnosed in a reference center for treatment of malignant tumors from the south of Brazil aiming to determine the prognostic value of demographic, clinic and pathologic features., Material and Methods: Cases diagnosed as SGC between 2006 and 2016 were retrospectively collected. Medical records were examined to extract demographic, clinic, pathologic and follow-up information., Results: One-hundred and seven cases of SGC were identified. The most common SGC were mucoepidermoid carcinoma (MEC) (n = 39) followed by adenoid cystic carcinoma (AdCC) (n = 29). Among AdCCs, 55.2% of cases were classified as cribriform, 27.6% as tubular and 17.2% as solid. The tubular subtype had the highest percentage of cases with perineural invasion (p=0.01). Among MEC, 61.5% of cases were classified as low grade, 15.4% as intermediate grade and 19.9% as high grade. Low grade MEC had the lowest percentage of cases with perineural invasion (p=0.04). The 5-year survival for loco-regional control, disease-free survival (DFS) and disease-specific survival were 75%, 70% and 84%, respectively. The following features were associated with poor DFS: advanced age (p=0.03), rural residency (p=0.01), being a smoker or former smoker (p=0.01), pain (p=0.03), nodal metastasis (p<0.001), need for chemotherapy (p=0.02), neck dissection (p=0.04), perineural invasion (p=0.01), and being diagnosed with AdCC compared to MEC (p=0.02)., Conclusions: The clinco-demographic and pathologic features identified as prognostic factors reveal the profile of patients at increased risk of recurrence and who would benefit from closer follow-up.

Background: Brain-derived neurotrophic factor (BDNF) and neurotrophin receptors have been recognized as fundamental regulators of normal brain development, homeostasis, and plasticity. They have also been studied in the behavior of central nervous system tumors. Here, we studied the pattern of BDNF, TrkB and p75NTR immunoexpression in peripheral benign and malignant neural lesions in head and neck., Methods: This cross-sectional analytical study included 79 cases of head and neck neural lesions. Nineteen cases of traumatic neuromas (TN), 20 cases of granular cell tumors (GCT), 16 cases of neurofibromas (NF), 20 cases of schwannomas (SC), and 4 malignant peripheral nerve sheath tumor (MPNST) were submitted to immunohistochemistry with BDNF, TrkB, and p75NTR antibodies. A semi-quantitative analysis was performed., Results: The analysis of BDNF demonstrated a high percentage of positive cells in TN, GCT and SC with a decrease in cases of NF and MPNST. TrkB presented a lower significant immunoexpression in GCT in relation to the TN, NF, SC, and MPNST (P < .0001); and TN showed less percentage of positive cell compared to SC (P = .0017). Regarding p75NTR, the percentage of positive cell was significantly reduced in MPNST compared GCT (P = .009), NF (P = .0138) and SC (P = .0069). Also, a decrease in TN compared to GCT (P = .007) was observed., Conclusions: Our results showed the immunoreactivity of BDNF, TrkB, and p75NTR in head and neck peripheral neural lesions. Reduction of BDNF and p75NTR in MPNST might suggest down-regulation during the acquisition of malignant phenotype., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: This systematic review aimed to address whether the alveolar socket repair after a tooth extraction is impacted by an osteoporotic phenotype and propose methodological observations., Design: A search strategy in MEDLINE/PubMed, EMBASE, Web of Science, and Scopus databases was performed. Quality assessment was carried out through the SYRCLE Risk of Bias tool., Results: Out of the 1147 potentially relevant records, 25 met the inclusion criteria. Most of the studies were performed in rats, and ovariectomy (OVX) was the most frequent osteoporosis induction method. Histomorphometry, micro-computed tomography (microCT), and immunohistochemistry were the main bone repair evaluation methods. Most of the included studies (88 %) presented negative impacts of osteoporosis on the alveolar socket repair. Only three studies (12 %) showed no statistical differences among groups. Overall, most of the quality assessment categories presented a high percentage of unclear risk of bias due to insufficient information in the studies., Conclusions: The results indicated that an osteoporotic phenotype seems to impair alveolar socket repair after tooth extraction. However, there is still a lack of information and standardization. Therefore, further studies should consider the proposed methodological aspects regarding animal characteristics, OVX associated with a low calcium diet, waiting 8 weeks to osteoporosis induction, maxillary molars as the best option for tooth extraction, confirming and reporting OVX and osteoporosis success, and an appropriate method of repair analysis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Salivary gland tumors are a diverse group of uncommon neoplasms that are rare in pediatric patients. The aim of this study was to evaluate the clinicopathological profile and survival outcomes of pediatric patients affected by salivary gland tumors., Materials and Methods: An extensive search was carried out using the MEDLINE/PubMed, EMBASE, Scopus databases, and grey literature. The risk of bias was available in all papers included., Results: A total of 2,830 articles were initially retrieved with 54 remaining for data extraction, resulting in 2,937 cases. This comprised forty-five case series' and nine cohort studies. These tumors were slightly more prevalent in females (57.4%). The patients' age ranged from 0.3 to 19 years old, with a mean age of 13.3 years. Parotid was the most affected site (81.9%), and 99.2% of cases clinically exhibited a swelling. Presence of pain/tenderness was reported in 13.5% of the cases, with an average duration of 12.6 months for the appearance of symptoms. Most of the reported cases were malignant tumors (75.4%), with mucoepidermoid carcinoma the most common tumor of all tumors (44.8%), followed by pleomorphic adenoma (24.1%). Surgery alone was the leading treatment choice in 74.9% cases, and the 5-year overall survival rate of patients was 93.1%. Patients with symptoms (P = .001), local recurrence (P < .001), metastasis (P < .001), and those not undergoing surgery or surgery combined with radiotherapy (P < .001) showed lower survival rates., Conclusion: The pediatric patients present a high frequency of malignant salivary neoplasms and a high overall survival rate., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Odontogenic lesions (OL) are an important group of oral and maxillofacial diseases represented by odontogenic cysts, benign, and malignant tumors. The brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) signaling pathway has multiple biological actions and has been identified as an important pathway in the proliferation, invasion, and survival of different epithelial tumors. Its role in the development of OL, however, has so far been unexplored. Our aim was to evaluate the BDNF/TrkB/Akt/p-RPS6 signaling pathway in OL of epithelial origin. This cross-sectional study comprised 3 cases of tooth germs, 25 cases of odontogenic keratocyst (OK), 29 cases of ameloblastoma (Am), and 6 cases of ameloblastic carcinoma. Immunohistochemical staining for BDNF, TrkB, p-Akt, and p-RPS6 was performed. OLs were evaluated according to the pattern of immunohistochemical expression in epithelial cells and by semiquantitative scores that considered the intensity of staining and percentage of positive cells. BDNF stromal expression was also assessed. No significant differences were observed with respect to the percentage of positive cases for all markers. Regarding the immunoreactive scores, BDNF and p-RPS6 expressions were similar in the odontogenic epithelium of all OL. However, TrkB and p-Akt were overexpressed in OK compared with ameloblastic carcinoma. In Am, epithelial BDNF was significantly higher compared with stromal expression. In conclusion, BDNF seems to participate in the development of cystic, benign, and malignant odontogenic epithelium to similar degrees. The acquisition of the invasive or malignant phenotype in odontogenic neoplasms is not associated with alterations in the BDNF/TrkB/Akt/RPS6 axis, which could be implicated in the differentiation process., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)