Pleomorphic adenoma and carcinoma ex-pleomorphic adenoma tumorigenesis: A proteomic analysis.

OBJECTIVES: To conduct a comprehensive proteomic analysis of normal salivary gland tissue, pleomorphic adenoma (PA), and carcinoma ex-pleomorphic adenoma (CXPA), and validate the proteomic findings using immunohistochemistry. METHODS: Six normal salivary gland tissues, seven PA and seven CXPA samples underwent laser microdissection followed by liquid chromatography coupled to mass spectrometry. Protein identification and quantification were performed using MaxQuant software. Statistical analysis and functional enrichment were conducted using the Perseus platform and STRING tool, respectively. Immunohistochemistry was used for validation. RESULTS: Comparative proteomic analysis revealed 2680 proteins across the three tissue types, with 799 significantly altered between groups. Translocation protein SEC63 homolog, Annexin A6 and Biglycan were up-regulated in CXPA compared to PA. Decorin was markedly up-regulated in both PA and CXPA compared to normal salivary gland (log2 fold changes of 7.58 and 7.38, respectively). Validation confirmed elevated levels of Biglycan and Decorin in the extracellular matrix of CXPA compared to PA. CONCLUSIONS: Proteomic analysis identified differential protein expression patterns associated with malignant transformation of PA into CXPA. Findings indicate a crucial role for extracellular matrix proteins, specifically Biglycan and Decorin, in the tumorigenic progression of PA and CXPA.

Electrical Stimulation for Treatment of Dysphagia Post Head Neck Cancer: A Systematic Review and Meta-Analysis.

Introduction Dysphagia induced by radiotherapy in the head and neck region comprises a challenging scenario and sometimes difficult rehabilitation due to the severity of the adverse effects. Some resources such as electrical stimulation have emerged as an alternative to complement the therapeutic process, but there is still no consensus on its use. Objective The purpose of the present study was to evaluate, through a meta-analysis, the effect of electrical stimulation on the rehabilitation of dysphagia generated after head and neck cancer treatment. Data Synthesis Four randomized controlled trials with a total of 146 participants were included. The age of the participants was 58.37 ± 1.8 years old and there was a predominance of males. The time to start the intervention ranged from 50.96 ± 40.12 months after cancer treatment. The intervention showed great heterogeneity regarding the positioning of the electrodes, parameters, duration of the stimulus, number of sessions, and intensity. No difference was identified in the following aspects: oral transit time, hyoid elevation, penetration and/or aspiration after electrostimulation. The quality of the evidence ranged from very low to moderate and high risk of bias. Conclusion In this meta-analysis, we found weak evidence for small and moderate swallowing benefits in patients after radiotherapy for head and neck cancer in short-term clinical trials.

Electrical Stimulation for Treatment of Dysphagia Post Head Neck Cancer: A Systematic Review and Meta-Analysis

Abstract Introduction Dysphagia induced by radiotherapy in the head and neck region comprises a challenging scenario and sometimes difficult rehabilitation due to the severity of the adverse effects. Some resources such as electrical stimulation have emerged as an alternative to complement the therapeutic process, but there is still no consensus on its use. Objective The purpose of the present study was to evaluate, through a meta-analysis, the effect of electrical stimulation on the rehabilitation of dysphagia generated after head and neck cancer treatment. Data Synthesis Four randomized controlled trials with a total of 146 participants were included. The age of the participants was 58.37 ± 1.8 years old and there was a predominance of males. The time to start the intervention ranged from 50.96 ± 40.12 months after cancer treatment. The intervention showed great heterogeneity regarding the positioning of the electrodes, parameters, duration of the stimulus, number of sessions, and intensity. No difference was identified in the following aspects: oral transit time, hyoid elevation, penetration and/or aspiration after electrostimulation. The quality of the evidence ranged from very low to moderate and high risk of bias. Conclusion In this meta-analysis, we found weak evidence for small and moderate swallowing benefits in patients after radiotherapy for head and neck cancer in short-term clinical trials.

Ewing's sarcoma of the head and neck: A systematic review.

OBJECTIVE: The aim of the present study was to conduct a systematic review of head and neck Ewing sarcoma (ES) concerning patients' demographic and clinical features, histopathological findings, treatment, follow-up, and survival rate. MATERIALS AND METHODS: An electronic search was undertaken in four databases. Articles describing case reports or case series were included. Outcomes were evaluated by the Kaplan-Meier method along with Cox regression. RESULTS: The search yielded 186 studies describing 227 ES cases. The mean age was 22.7 years, and males were slightly more affected. Interestingly, more than half the cases were diagnosed up to 20 years. The respiratory tract was the most reported site, followed by the jawbones. Clinically, symptomatic swelling or nodules were described, with a mean duration of 4 months. Management involved multimodal treatment regimens. Local recurrence, lymph node and distant metastasis were observed in 10.7%, 12.6%, and 20.3% of cases, respectively. Statistical analysis revealed that older patients with distant metastasis had a lower overall survival rate (p < 0.05). CONCLUSION: This study provides an overall view of head and neck ES that can assist oral and maxillofacial pathologists with the diagnosis and extend the knowledge of surgeons and oncologists about this condition.

Acinic cell carcinoma of the oral and maxillofacial region: an international multicenter study.

The aim of this study was to describe the prevalence, clinicopathological, and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial region. AciCC cases were retrospectively retrieved from 11 pathology centers of three different countries. Medical records were examined to extract demographic, clinical, pathologic, and follow-up information. A total of 75 cases were included. Females (65.33%) with a mean age of 45.51 years were mostly affected. The lesions usually presented as an asymptomatic (64.28%) nodule (95.66%) in the parotid gland (70.68%). The association of two histopathological patterns was the most common finding (48.93%) and the tumors presented mainly conventional histopathological grades (86.11%). Surgical treatment was performed in the majority of the cases (59.19%). Local recurrence was observed in 20% of the informed cases, regional metastasis in 30.43%, and distant metastasis in 12.50%. The statistical analysis showed that the cases with a solid histopathological pattern (p=0.01), high-grade transformation (p=0.008), recurrence (p=0.007), and regional metastasis (p=0.03) were associated with poor survival. In conclusion, high histopathological transformation, presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region.

Epithelial salivary gland tumors in pediatric patients: An international collaborative study.

OBJECTIVE: Salivary gland tumors (SGT) are a diverse group of uncommon neoplasms that are rare in pediatric patients. This study aimed to characterize the clinicopathological profile of pediatric patients affected by SGT from a large case series derived from an international group of academic centers. STUDY DESIGN: A retrospective analysis of pediatric patients with SGT (0-19 years old) diagnosed between 2000 and 2021 from Brazil, South Africa, and the United Kingdom was performed. SPSS Statistics for Windows was used for a quantitative analysis of the data, with a descriptive analysis of the clinicopathological characteristics and the association between clinical variables and diagnoses. RESULTS: A total of 203 cases of epithelial SGT were included. Females were slightly more commonly (56.5%), with a mean age of 14.1 years. The palate was the most common site (43.5%), followed by the parotid gland (29%), lip (10%), and submandibular gland (7.5%). The predominant clinical presentation was a flesh-colored, smooth, and painless nodule. Pleomorphic adenoma (PA) was the most frequently diagnosed SGT (58.6%), followed by mucoepidermoid carcinoma (MEC) (26.6%). Surgery (90.8%) was the favored treatment option. CONCLUSIONS: Benign SGT in pediatric patients are more commonly benign than malignant tumors. Clinicians should keep PA and MEC in mind when assessing nodular lesions of possible salivary gland origin in pediatric patients.

Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma.

BACKGROUND: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model. METHODS: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n = 8); Immediate irradiation, PBMT since one week after tumor implantation (n = 6); and Late irradiation, PBMT after tumors reached 200 mm3 (n = 6). OSCC-PDX were daily irradiated (660 nm; 100 mW; 6 J/cm2 ; 0,2 J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis. RESULTS: No significant differences in the volumetric measurements (p = 0.89) and in the histopathological grade (p > 0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p = 0.9661); H3K9ac (p = 0.3794); and BMI1 (p = 0.5182), and the evaluation of the cell cycle phases (p > 0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups. CONCLUSION: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.

Acinic cell carcinoma of the oral and maxillofacial region: an international multicenter study

Abstract The aim of this study was to describe the prevalence, clinicopathological, and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial region. AciCC cases were retrospectively retrieved from 11 pathology centers of three different countries. Medical records were examined to extract demographic, clinical, pathologic, and follow-up information. A total of 75 cases were included. Females (65.33%) with a mean age of 45.51 years were mostly affected. The lesions usually presented as an asymptomatic (64.28%) nodule (95.66%) in the parotid gland (70.68%). The association of two histopathological patterns was the most common finding (48.93%) and the tumors presented mainly conventional histopathological grades (86.11%). Surgical treatment was performed in the majority of the cases (59.19%). Local recurrence was observed in 20% of the informed cases, regional metastasis in 30.43%, and distant metastasis in 12.50%. The statistical analysis showed that the cases with a solid histopathological pattern (p=0.01), high-grade transformation (p=0.008), recurrence (p=0.007), and regional metastasis (p=0.03) were associated with poor survival. In conclusion, high histopathological transformation, presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region.

Prognostic factors from squamous cell carcinoma of the hard palate, gingiva and upper alveolar ridge.

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.

MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study

Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutSαhigh and MutSβhigh based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively. Results: hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed. Conclusions: Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT.(AU)

Prognostic factors from squamous cell carcinoma of the hard palate, gingiva and upper alveolar ridge

Abstract: 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.

Mature T/NK-Cell lymphomas of the oral and maxillofacial region: A multi-institutional collaborative study.

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.

Oral and oropharyngeal lymphomas: A multi-institutional collaborative study.

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.

Cistos e tumores odontogênicos: estudo retrospectivo dos casos diagnosticados no período de 10 anos em um hospital no sul do Brasil / Odontogenic cysts and tumors: a retrospective study of the cases diagnosed in a period of 10 years in a southern Brazilian hospital

Introdução: as lesões odontogênicas (LOs) compreendem um grupo heterogêneo de patologias orais e maxilofaciais que apresentam características distintas. O objetivo do presente estudo foi identificar as características clínico--patológicas das LOs diagnosticadas em um hospital da região sul do Brasil. Materiais e métodos: foi realizado um estudo retrospectivo para levantamento dos casos com diagnóstico histopatológico de LOs no período entre 2007 e 2017. Os laudos dos pacientes foram avaliados para extração das características clínico-patológicas e dos diagnósticos histopatológicos de cada caso. Resultados: um total de 255 casos de LOs foram identificados. Destes casos, 197 (77%) cistos odontogênicos e 58 (23%) tumores odontogênicos foram coletados, sendo que somente um caso (0,39%) possuiu o diagnóstico de neoplasia odonto-gênica maligna. Os diagnósticos mais prevalentes foram cisto radicular (32,5%) e cisto dentígero (31,76%), seguidos de ceratocisto odontogênico (10,98%), odontoma (10%) e ameloblastoma (10%). A maioria dos casos acometeu mandíbula (53,7%), com uma discreta predileção pelo sexo feminino (51%). A média de idade foi de 34±20,53 anos. Discussão: os dados apresentados corroboram com a literatura no que se refere à raridade do diagnóstico de tumores odontogênicos. Conclusão: o presente estudo demonstrou as principais características clínico-pato-lógicas de LOs diagnosticadas em um hospital no sul do Brasil, contribuindo para um maior conhecimento do perfil destas lesões.

Introduction: odontogenic lesions (OLs) represent a heterogeneous group of oral and maxillofacial patho-logies presenting distinct characteristics. The present study aimed to identify the clinical and pathological characteristics of OLs diagnosed in a southern Brazilian hospital. Materials and methods: a retrospective study was performed to evaluate cases with histopathological diagnosis of OLs identified in the period between 2007 and 2017. The patient's medical records were evaluated in order to obtain the clinical and pathological charac-teristics and the histopathological diagnosis from each case. Results: a total of 255 cases of OLs were identified. From these, 197 (77%) odontogenic cysts and 58 (23%) odontogenic tumors were surveyed, with only one case (0,39%) of a malignant odontogenic neoplasm. The most prevalent diagnosis were radicular cyst (32.5%) and den-tigerous cyst (31.76%), followed by odontogenic keratocyst (10.98%), odontoma (10%) and ameloblastoma (10%). The majority of the cases affected the mandible (53.7%) with a slight preference by female individuals (51%). The mean age was 34±20.53 years old. Discussion: the presented data are in accordance with the literature regarding the rarity of the diagnosis of odontogenic tumors.Conclusion: the present study demonstrated the main clinical and pathological characteristics of OLs diagnosed in a southern Brazilian hospital, contrib-uting to a better understanding of these injuries profiles.

Salivary gland cancer in Southern Brazil: a prognostic study of 107 cases / Cáncer de glándula salival en el sur de Brasil: un estudio pronóstico de 107 casos

Background: Salivary gland cancers (SGC) represent an uncommon group of heterogeneous tumors. We per-formed a retrospective survey of SGC diagnosed in a reference center for treatment of malignant tumors from thesouth 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. Medicalrecords 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 mucoepidermoidcarcinoma (MEC) (n = 39) followed by adenoid cystic carcinoma (AdCC) (n = 29). Among AdCCs, 55.2% of caseswere classified as cribriform, 27.6% as tubular and 17.2% as solid. The tubular subtype had the highest percentageof cases with perineural invasion (p=0.01). Among MEC, 61.5% of cases were classified as low grade, 15.4% asintermediate grade and 19.9% as high grade. Low grade MEC had the lowest percentage of cases with perineuralinvasion (p=0.04). The 5-year survival for loco-regional control, disease-free survival (DFS) and disease-specificsurvival 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 diag-nosed with AdCC compared to MEC (p=0.02).Conclusions: The clinco-demographic and pathologic features identified as prognostic factors reveal the profile ofpatients at increased risk of recurrence and who would benefit from closer follow-up.(AU)

Immunoexpression of BDNF, TrkB, and p75NTR receptors in peripheral neural lesions of the head and neck.

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.

TrkB-Targeted Therapy for Mucoepidermoid Carcinoma.

The brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (TrkB) pathway was previously associated with key oncogenic outcomes in a number of adenocarcinomas. The aim of our study was to determine the role of this pathway in mucoepidermoid carcinoma (MEC). Three MEC cell lines (UM-HMC-2, H253 and H292) were exposed to Cisplatin, the TrkB inhibitor, ANA-12 and a combination of these drugs. Ultrastructural changes were assessed through transmission electron microscopy; scratch and Transwell assays were used to assess migration and invasion; and a clonogenic assay and spheroid-forming assay allowed assessment of survival and percentage of cancer stem cells (CSC). Changes in cell ultrastructure demonstrated Cisplatin cytotoxicity, while the effects of ANA-12 were less pronounced. Both drugs, used individually and in combination, delayed MEC cell migration, invasion and survival. ANA-12 significantly reduced the number of CSC, but the Cisplatin effect was greater, almost eliminating this cell population in all MEC cell lines. Interestingly, the spheroid forming capacity recovered, following the combination therapy, as compared to Cisplatin alone. Our studies allowed us to conclude that the TrkB inhibition, efficiently impaired MEC cell migration, invasion and survival in vitro, however, the decrease in CSC number, following the combined treatment of ANA-12 and Cisplatin, was less than that seen with Cisplatin alone; this represents a limiting factor.

Electrical stimulation in the treatment of radiotherapy-induced hyposalivation. / Estimulação elétrica no tratamento da hipossalivação induzida pela radioterapia.

PURPOSE: To analyze the effects of electrical stimulation on the salivary flow of head and neck cancer patients with radiotherapy-induced hyposalivation. RESEARCH STRATEGIES: Searches were made in the Medline (via Pubmed), Cochrane Library, Scopus and Lilacs databases. SELECTION CRITERIA: Selection included clinical trials that evaluated salivary flow objectively, published in the last 10 years in either Portuguese, English or Spanish. DATA ANALYSIS: The PEDro scale was used for the methodological evaluation of the studies. RESULTS: The search strategy resulted in 21 publications, 17 of which were excluded, hence there were 4 articles left. The included studies had a total of 212 participants, all of whom had an increase in salivary flow, both through the electroacupuncture method and direct application on the salivary glands. The score obtained through the PEDRo scale was low, evidencing questionable methodological quality and risk of bias. CONCLUSION: The included studies demonstrate the clinical potential of TENS to increase the salivary flow of head and neck cancer patients treated with RT.

OBJETIVO: Analisar os efeitos da eletroestimulação sobre o fluxo salivar de pacientes com hipossalivação induzida por radioterapia em região de cabeça e pescoço. ESTRATÉGIA DE PESQUISA: Utilizaram-se as bases de dados Medline (via Pubmed), Cochrane Library, Scopus e Lilacs. CRITÉRIOS DE SELEÇÃO: Foram selecionados os ensaios clínicos que avaliaram objetivamente o fluxo salivar, publicados nos últimos 10 anos em português, inglês ou espanhol. ANÁLISE DOS DADOS: Para avaliação metodológica dos estudos, foi utilizada a escala PEDro. RESULTADOS: A estratégia de busca resultou em 21 publicações, sendo que 17 foram excluídas, selecionando-se assim 4 artigos. Os estudos incluídos contaram com um total de 212 participantes, sendo que todos demonstraram aumento do fluxo salivar, tanto por meio do método de eletroacupuntura quanto pela estimulação aplicada diretamente sobre as glândulas salivares. A pontuação obtida por meio da escala PEDro foi baixa, evidenciando qualidade metodológica baixa e com consideráveis riscos de viés. CONCLUSÃO: os estudos incluídos demonstram o potencial clínico da TENS no aumento do fluxo salivar de pacientes com câncer de cabeça e pescoço tratados com RT.

Effects of transcutaneous electrical nerve stimulation on the salivary flow of patients with hyposalivation induced by radiotherapy in the head and neck region-A randomised clinical trial.

Hyposalivation is a frequent complication after treatment with radiotherapy. To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) on the hyposalivation assessed through stimulated salivary flow (SSF). In this clinical trial, 68 patients (with hyposalivation) were randomly assigned to control (n = 31) or TENS (n = 37) group. Participants in control group received habitual care, while those in TENS group received 8 sessions (20 minutes each) delivered twice a week for four weeks. The electrodes were attached over the skin covering the salivary glands. The electric pulse was adjusted at a frequency of 50 Hz, pulse width of 250 µs and as intense as tolerated. SSF was evaluated through sialometry. Self-perception of salivary flow (SPSF) and quality of life (QL) was evaluated prior to, during and at 1, 3 and 6 months after treatment. Although no changes were observed in the control group for SSF at any timepoints, TENS group showed a progressive increase in SSF from the third session until the end of the treatment. Significant improvements were also found in SPSF, especially when the SSF reached values ≥0.7 mL/minute. The most expressive results were evident at 6 months after treatment so that SSF, SPSF and QL remained significantly higher (F = 9.5, P = 0.0001; H = 143.77, P < 0.0001; χ2  = 9.162, P = 0.02, respectively). TENS was effective at improving hyposalivation. The benefits on SSF, SPSF and QL give base to a promising therapeutic strategy for patients with hyposalivation after radiotherapy treating head and neck cancer.