Artigos e Materiais de Revistas Científicas - LIM/28

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.


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  • article 0 Citação(ões) na Scopus
    Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics
    (2024) MIRANDA, Lara Judith Cabral; DANILOVIC, Debora L. S.; VANDERLEI, Felipe Augusto Brasileiro; TAVARES, Marcos Roberto; NETO, Nicolau Lima; CAMARGO, Rosalinda Yossie Asato de; MARUI, Suemi
    Objective: Mutations in DICER1 are found in differentiated thyroid carcinoma (DTC) and in multinodular goiter (MNG) at a younger age with other tumors, which characterizes DICER1 syndrome. DICER1 is one driver to DTC; however, it is also found in benign nodules. We speculated that patients with mutations in DICER1 may present long-lasting MNG. Our aim was to investigate the frequency of DICER1 variants in patients with MNG. Subjects and methods: Patients who submitted to total thyroidectomy due to large MNG with symptoms were evaluated. DICER1 hotspots were sequenced from thyroid nodule samples. To confirm somatic mutation, DNA from peripheral blood was also analyzed. Results: Among 715 patients, 154 were evaluated with 56.2 +/- 12.3 years old (28-79) and the thyroid volume was 115.7 +/- 108 mL (16.2-730). We found 11% with six DICER1 variations in a homo or heterozygous state. Only rs12018992 was a somatic DICER1 variant. All remaining variants were synonymous and likely benign, according to the ClinVar database. The rs12018992 was previously described in an adolescent with DTC, measuring 13 mm. There were no significant differences according to gender, familial history of goiter, age, thyroid volume, TSH and TI -RADS classification between DICER1 carriers. Free T4 were lower in patients with DICER1 polymorphisms (13.77 +/- 1.8 vs. 15.44 +/- 2.4 pmol/L, p = 0.008), regardless of TSH levels. Conclusions: We conclude that germline DICER1 variants can be found in 11% of large goiters but no second -hit somatic mutation was found. DICER1 is one driver to thyroid lesion and a second -hit event seems unnecessary in the MNG development.
  • article 6 Citação(ões) na Scopus
    Comprehensive Glycoprofiling of Oral Tumors Associates N-Glycosylation With Lymph Node Metastasis and Patient Survival
    (2023) CARNIELLI, Carolina Moretto; MORAIS, Thayna Melo de Lima; PATRONI, Fabio Malta de Sa; RIBEIRO, Ana Carolina Prado; BRANDAO, Thais Bianca; SOBROZA, Evandro; MATOS, Leandro Luongo; KOWALSKI, Luiz Paulo; LEME, Adriana Franco Paes; KAWAHARA, Rebeca; THAYSEN-ANDERSEN, Morten
    While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), the heterogeneous and dynamic glycoproteome of tumor tissues from OSCC patients remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a cohort of resected primary tumor tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumor tissues displayed relatively uniform N-glycome profiles suggesting overall stable global N-glycosylation during disease progression, altered expression of six sialylated N-glycans was found to correlate with lymph node metastasis. Notably, glycoproteomics and advanced statistical analyses uncovered altered site -specific Nglycosylation revealing previously unknown associations with several clinicopathological features. Importantly, the glycomics and glycoproteomics data unveiled that comparatively high abundance of two core-fucosylated and sialylated N-glycans (Glycan 40a and Glycan 46a) and one N-glycopeptide from fibronectin were associated with low patient survival, while a relatively low abundance of N-glycopeptides from both afamin and CD59 were also associated with poor survival. This study provides insight into the complex OSCC tissue Nglycoproteome, thereby forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glycomarkers for OSCC.
  • article 0 Citação(ões) na Scopus
    Detection of serum biomarkers of HPV-16 driven oropharynx and oral cavity cancer in Brazil
    (2024) SICHERO, Laura; GONCALVES, Milena Giulia; BETTONI, Fabiana; COSER, Elisangela Monteiro; MOTA, Giana; NUNES, Rafaella A. L.; MERCANTE, Ana Maria da Cunha; NATALINO, Renato; UNO, Miyuki; ALVES, Maria Jose Ferreira; MATOS, Leandro Luongo; KOWALSKI, Luiz Paulo; KULCSAR, Marco Aurelio Vamondes; ALVARENGA, Gustavo Fernandes de; HOEFLER, Daniela; SCHROEDER, Lea; WATERBOER, Tim; TOMMASINO, Massimo; VILLA, Luisa Lina
    Background: HPV-16 driven oropharynx/oral cavity squamous cell carcinomas prevalence varies globally. We evaluated the presence of HPV-16 ctDNA and HPV-16 E6 antibodies in samples obtained from participants treated at the Instituto do Cancer do Estado de Sao Paulo, ICESP, and from whom tumoral HPV DNA, HPV-16 E6*I mRNA, and p16(INK4a) status was also accessed. Methods: HPV was genotyped by PCR-hybridization. All HPV DNA positive and similar to 10 % HPV DNA negative cases underwent p16(INK4a) immunohistochemistry and E6*I RNA testing using a multiplex bead based protocol. HPV-16 ctDNA and anti-E6 antibodies were assessed by ddPCR (digital droplet PCR) and multiplex serology, respectively. Results: The prevalence of HPV-16 in oropharynx carcinoma (OPC) cases was low (8.7 %) when considering solely HPV-16 DNA detection, and even lower (5.2 %) when taken into consideration the concomitant detection of HPV-16 E6*I RNA and/or p16(INK4) (HPV-16 attributable fraction - AF). None of the oral cavity cancer (OCC) cases were detected with HPV-16 DNA. HPV-16 ctDNA was more commonly detected than HPV-16 E6 antibodies (29.8 % versus 10.6 %). Both serum biomarkers attained 100 % sensitivity of detecting HPV-16 AF OPC, however the specificity of the HPV-16 anti-E6 biomarker was higher compared to ctDNA (93.2 % versus 75.0 %). Finally, when both HPV-16 ctDNA and anti-E6 biomarkers were considered together, the sensitivity and specificity for HPV-16 OPC detection was 100 % and about 70 %, respectively, independently of analyzing HPV-16 DNA positive or HPV-16 AF tumors. Conclusions: Our findings corroborate that serum biomarkers are highly sensitive and specific biomarkers for detection of HPV-associated OPC.
  • article 1 Citação(ões) na Scopus
    Congenital Midline Cervical Cleft and Thyroglossal Duct Fibrous Cord-Like, is There a Mixed Presentation?
    (2023) KRUSCHEWSKY, Leonardo de Souza; MATOS, Leandro Luongo de; ALONSO, Nivaldo; SEIDLER, Cariline da Silva; LISBOA, Sonyara Rauedys Oliveira; SILVA, Roberto Cintra Lomanto Santos; GOLDENBERG, Dov Charles; SILVA, Tatiana Valeria Novais
    Introduction:Congenital midline cervical cleft is a rare condition and is frequently misdiagnosed as thyroglossal duct cyst. Otherwise, the combination of congenital midline cervical cleft and thyroglossal duct fibrosis in the same patient is as rare as important to be registered with the intention to inform and offer specific managements details for the literature.Case Presentation:Eight-year-old boy with simultaneous congenital midline cervical cleft and a thyroglossal duct fibrosis. The anatomic, clinical, radiologic, and pathologic characteristics of the congenital midline cervical cleft are described as well as surgical technique for removal and repair with Z-plasty.Conclusion:Congenital midline cervical cleft is a rare condition and when diagnosed must be surgically treated as early as possible. Its differential diagnosis is a clinical challenge.
  • article 0 Citação(ões) na Scopus
    Malignant carotid body tumors: What we know, what we do, and what we need to achieve. A systematic review of the literature
    (2024) PIAZZA, Cesare; LANCINI, Davide; TOMASONI, Michele; ZAFEREO, Mark; POORTEN, Vincent Vander; HANNA, Ehab; MAKITIE, Antti A.; FERNANDEZ-ALVAREZ, Veronica; KOWALSKI, Luiz P.; CHIESA-ESTOMBA, Carlos; FERLITO, Alfio
    Malignant carotid body tumors (MCBT) are rare and diagnosed after detection of nodal or distant metastases. This systematic review (SR) focuses on MCBT initially approached by surgery. Preferred Reporting Items for SR and Meta-Analysis (MA) guided the articles search from 2000 to 2023 on PubMed, Scopus, and Web of Science. Among 3548 papers, 132 (337 patients) were considered for SR; of these, 20 (158 patients) for MA. Malignancy rate was 7.3%, succinate dehydrogenase (SDH) mutation 17%, age at diagnosis between 4th and 6th decades, with a higher prevalence of females. MCBTs were mostly Shamblin III, with nodal and distant metastasis in 79.7% and 44.7%, respectively. Malignancy should be suspected if CBT >4 cm, Shamblin III, painful or otherwise symptomatic, at the extremes of age, bilateral, with multifocal disease, and SDHx mutations. Levels II-III clearance should be performed to exclude nodal metastases and adjuvant treatments considered on a case-by-case basis.
  • article 0 Citação(ões) na Scopus
    Medical students' and residents' views on euthanasia
    (2023) DEDIVITIS, Rogerio Aparecido; MATOS, Leandro Luongo de; CASTRO, Mario Augusto Ferrari de; CASTRO, Andrea Anacleto Ferrari de; GIAXA, Renata Rocha; TEMPSKI, Patricia Zen
    BackgroundDoctors are increasingly faced with end-of-life decisions. Little is known about how medical students approach euthanasia. The objective of this study was to evaluate, among medical students and residents, the view on euthanasia and its variants; correlate such a view with empathy and religiosity/spiritualism; and with the stages of medical training in Brazil.MethodsThis is an exploratory cross-sectional study using an online questionnaire to be filled out on a voluntary basis among medical students and residents, consisting of: socio-demographic data, an empathy questionnaire and questions with elaborate clinical cases that typify situations of the variants of euthanasia.ResultsFrom 1550 invitations, 273 volunteer participants responded (17.6%). The percentages of strong agreement/agreement on the concepts were: passive euthanasia (72.9%); active euthanasia (22.3%), orthothanasia (90.1%), dysthanasia (18.7%), assisted suicide (33%) and sedation (82.8%). Passive euthanasia, active euthanasia, dysthanasia and assisted suicide showed greater refusal with increasing length of medical training. Religious belief and degree of empathy did not significantly influence the opinion about the concepts. Strong agreement/agreement were: passive euthanasia (72.9%); active euthanasia (22.3%), orthothanasia (90.1%), dysthanasia (18.7%), assisted suicide (33%) and sedation (82.8%).ConclusionsPassive euthanasia, active euthanasia, dysthanasia and assisted suicide showed greater refusal with increasing length of medical training. The external validation of our findings relies on the distinct legal, cultural, and religious frameworks found across various countries.
  • article 0 Citação(ões) na Scopus
    Sialendoscopy for treatment of major salivary glands diseases: a comprehensive analysis of published systematic reviews and meta-analyses
    (2023) -SILVA, Lucas Kallas; AZEVEDO, Maria Fernanda Dias; MATOS, Fatima Cristina Mendes de; PETRARROLHA, Silvia Picado; DEDIVITIS, Rogerio Aparecido; KULCSAR, Marco Aurelio Vamondes; MATOS, Leandro Luongo
    Objectives: Sialendoscopy is a minimally invasive procedure used to diagnose and treat obstructive salivary gland diseases. Previous studies in the topic have shown mixed results. The present study aimed to evaluate the efficacy and safety of sialendoscopy through previous systematic reviews for different outcomes of several diseases. We also aimed to assess studies' methodological quality and heterogeneity.Methods: We conducted a comprehensive systematic literature search of Pubmed, Embase, Lilacs and Cochrane Library. We included systematic reviews and meta-analyses that used sialendoscopy to treat both lithiasic and alithiasic salivary glands diseases. Data extraction included studies' characteristics and results. We assessed studies' methodological quality using the AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews 2) tool. Results: 13 studies were included in the review, being 9 in adult populations and 4 in pedi-atric populations. Sialendoscopy proved to be effective at the treatment of different lithiasic and other obstructive diseases, but with important heterogeneity. The technique was also considered highly safe in most studies. However, studies had a critically low quality of evidence. Conclusions: Most studies demonstrated high efficacy and safety of sialendoscopy, but with critically low quality of evidence. We still lack randomized studies in this field, and future systematic reviews on the topic should follow current guidelines to improve conduction and reporting. (c) 2023 Associacao Brasileira de Otorrinolaringologia e Cirurgia C ' ervico-Facial.
  • article
    Oral squamous cell carcinoma cancer stem cells have different drug sensitive to pharmacological NFκB and histone deacetylation inhibition
    (2023) SILVA, Luan Cesar; LEITE, Amanda Almeida; BORGATO, Gabriell Bonifacio; WAGNER, Vivian Petersen; MARTINS, Manoela Domingues; LOUREIRO, Felippe Jose Almeida; LOPES, Marcio Ajudarte; SANTOS-SILVA, Alan Roger; SPERANDIO, Marcelo; JUNIOR, Gilberto de Castro; KOWALSKI, Luiz Paulo; SQUARIZE, Cristiane H.; CASTILHO, Rogerio Moraes; VARGAS, Pablo Agustin
    Despite many progresses in the development of new systemic therapies for oral squamous cell carcinoma (OSCC), the five-year survival rate of OSCC is low. The traditional chemotherapies approach (cisplatin - CDDP) shows some limitations like drug toxicity, limited efficacy, and drug resistance. Promising studies suggested OSCC cancer stem cells (CSC) presented resistance to CDDP. We have previously studied many targets, and we extensively showed the efficacy of the NF kappa B signaling and the role of histones acetylation, on different malignant tumors, including adenoid cystic carcinoma and mucoepidermoid carcinoma, but until then the effects of the NFkB inhibitor and histone deacetylase (HDAC) inhibitor on the biology of OSCC were not evaluated. Here we assessed the pharmacological inhibitor of NF kappa B emetine and HDAC inhibitor SAHA on the behavior of CSC derived from OSCC. Our data suggested that CDDP administration resulted in reduced viability of bulk OSCC cells and increased CSC. A single and isolated shot of emetine and SAHA were able to disrupt CSC by inhibiting the NF kappa B pathway and increasing the histone acetylation levels, respectively. Further, the combined administration of emetine and SAHA presented the same CSC disruption as seen in emetine alone.
  • article 0 Citação(ões) na Scopus
    Cryoablation of Benign Thyroid Nodules: Preliminary Experience in 3 Cases
    (2023) FREITAS, Ricardo Miguel Costa de; VANDERLEI, Felipe Augusto Brasileiro; ROSENFELD, Matheus Gerhard; BORGES, Alessandra de Pinho Pimenta; KOWALSKI, Luiz Paulo; CHAMMAS, Maria Cristina
  • article 2 Citação(ões) na Scopus
    Management of Older Patients with Head and Neck Cancer: A Comprehensive Review
    (2023) MATOS, Leandro L.; SANABRIA, Alvaro; ROBBINS, K. Thomas; HALMOS, Gyorgy B.; STROJAN, Primoz; NG, Wai Tong; TAKES, Robert P.; ANGELOS, Peter; PIAZZA, Cesare; BREE, Remco de; RONEN, Ohad; GUNTINAS-LICHIUS, Orlando; EISBRUCH, Avraham; ZAFEREO, Mark; MAKITIE, Antti A.; SHAHA, Ashok R.; COCA-PELAZ, Andres; RINALDO, Alessandra; SABA, Nabil F.; COHEN, Oded; LOPEZ, Fernando; RODRIGO, Juan P.; SILVER, Carl E.; STRANDBERG, Timo E.; KOWALSKI, Luiz Paulo; FERLITO, Alfio
    The projected increase in life expectancy over the next few decades is expected to result in a rise in age-related diseases, including cancer. Head and neck cancer (HNC) is a worldwide health problem with high rates of morbidity and mortality. In this report, we have critically reviewed the literature reporting the management of older patients with HNC. Older adults are more prone to complications and toxicities secondary to HNC treatment, especially those patients who are frail or have comorbidities. Thus, this population should be screened prior to treatment for such predispositions to maximize medical management of comorbidities. Chronologic age itself is not a reason for choosing less intensive treatment for older HNC patients. Whenever possible, also older patients should be treated according to the best standard of care, as nonstandard approaches may result in increased treatment failure rates and mortality. The treatment plan is best established by a multidisciplinary tumor board with shared decision-making with patients and family. Treatment modifications should be considered for those patients who have severe comorbidities, evidence of frailty (low performance status), or low performance status or those who refuse the recommendations of the tumor board.
  • article 1 Citação(ões) na Scopus
    The use of deep learning state-of-the-art architectures for oral epithelial dysplasia grading: A comparative appraisal
    (2023) ARAUJO, Anna Luiza Damaceno; SILVA, Viviane Mariano da; MORAES, Matheus Cardoso; AMORIM, Henrique Alves de; FONSECA, Felipe Paiva; ST'ANA, Maria Sissa Pereira; MESQUITA, Ricardo Alves; MARIZ, Bruno Augusto Linhares Almeida; PONTES, Helder Antonio Rebelo; SOUZA, Lucas Lacerda de; SALDIVIA-SIRACUSA, Cristina; KHURRAM, Syed Ali; PEARSON, Alexander T.; MARTINS, Manoela Domingues; LOPES, Marcio Ajudarte; VARGAS, Pablo Agustin; KOWALSKI, Luiz Paulo; SANTOS-SILVA, Alan Roger
    Background: Dysplasia grading systems for oral epithelial dysplasia are a source of disagreement among pathologists. Therefore, machine learning approaches are being developed to mitigate this issue.Methods: This cross-sectional study included a cohort of 82 patients with oral potentially malignant disorders and correspondent 98 hematoxylin and eosin-stained whole slide images with biopsied-proven dysplasia. All whole-slide images were manually annotated based on the binary system for oral epithelial dysplasia. The annotated regions of interest were segmented and fragmented into small patches and non-randomly sampled into training/validation and test subsets. The training/validation data were color augmented, resulting in a total of 81,786 patches for training. The held-out independent test set enrolled a total of 4,486 patches. Seven state-of-the-art convolutional neural networks were trained, validated, and tested with the same dataset.Results: The models presented a high learning rate, yet very low generalization potential. At the model development, VGG16 performed the best, but with massive overfitting. In the test set, VGG16 presented the best accuracy, sensitivity, specificity, and area under the curve (62%, 62%, 66%, and 65%, respectively), associated with the higher loss among all Convolutional Neural Networks (CNNs) tested. EfficientB0 has comparable metrics and the lowest loss among all convolutional neural networks, being a great candidate for further studies.Conclusion: The models were not able to generalize enough to be applied in real-life datasets due to an overlapping of features between the two classes (i.e., high risk and low risk of malignization).
  • article 1 Citação(ões) na Scopus
    DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas
    (2023) CALANCA, Naiade; FRANCISCO, Ana Lucia Noronha; BIZINELLI, Daniela; KUASNE, Hellen; BARROS FILHO, Mateus Camargo; FLORES, Bianca Campos Troncarelli; PINTO, Clovis Antonio Lopes; RAINHO, Claudia Aparecida; SOARES, Milena Botelho Pereira; MARCHI, Fabio Albuquerque; KOWALSKI, Luiz Paulo; ROGATTO, Silvia Regina
    Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip). Reference-based computational deconvolution (MethylCIBERSORT) was applied to infer the immune cell composition of the bulk samples. The expression levels of genes encoding immune markers and differentially methylated lncRNAs were investigated using The Cancer Genome Atlas dataset. OSCC specimens presented distinct immune cell composition, including the enrichment of monocyte lineage cells, natural killer cells, cytotoxic T-lymphocytes, regulatory T-lymphocytes, and neutrophils. In contrast, B-lymphocytes, effector T-lymphocytes, and fibroblasts were diminished in tumor samples. The hypomethylation of three immune-associated lncRNAs (MEG3, MIR155HG, and WFDC21P) at individual CpG sites was confirmed by bisulfite-pyrosequencing. Also, the upregulation of a set of immune markers (FOXP3, GZMB, IL10, IL2RA, TGFB, IFNG, TDO2, IDO1, and HIF1A) was detected. The immune cell composition, immune markers alteration, and dysregulation of immune-associated lncRNAs reinforce the impact of the immune microenvironment in OSCC. These concurrent factors contribute to tumor heterogeneity, suggesting that epiimmunotherapy could be an efficient alternative to treat OSCC.
  • article 1 Citação(ões) na Scopus
    Overview of glottic laryngeal cancer treatment recommendation changes in the NCCN guidelines from 2011 to 2022
    (2023) ARBOLEDA, Lady Paola Aristizabal; NEVES, Aline Borburema; KOHLER, Hugo Fontan; VARTANIAN, Jose Guilherme; CANDELARIA, Leticia Miliano; BORGES, Matheus Ferraz; FERNANDES, Gisele Aparecida; CARVALHO, Genival Barbosa de; KOWALSKI, Luiz Paulo; BRENNAN, Paul; SANTOS-SILVA, Alan Roger; CURADO, Maria Paula
    BackgroundThe treatment of glottic cancer remains challenging, especially with regard to morbidity reduction and larynx preservation rates. The National Comprehensive Cancer Network (NCCN) has published guidelines to aid decision-making about this treatment according to the tumor site, clinical stage, and patient medical status. AimThe present review was conducted to identify changes in the NCCN guidelines for glottic cancer treatment made between 2011 and 2022 and to describe the published evidence concerning glottic cancer treatment and oncological outcomes in the same time period. Methods and ResultsClinical practice guidelines for head and neck cancer published from 2011 up to 2022 were obtained from the NCCN website (). Data on glottic cancer treatment recommendations were extracted, and descriptive analysis was performed. In addition, a review of literature registered in the PubMed database was performed to obtain data on glottic cancer management protocols and treatment outcomes from randomized controlled trials, systematic reviews, and meta-analyses published from 2011 to 2022. In total, 24 NCCN guidelines and updates and 68 relevant studies included in the PubMed database were identified. The main guideline changes made pertained to surgical and systemic therapies, the consideration of adverse features, and new options for the treatment of metastatic disease at initial presentation. Early-stage glottic cancer received the most research attention, with transoral endoscopic laser surgery and radiotherapy assessed and compared as the main treatment modalities. Reported associations between treatment types and survival rates for this stage of glottic cancer appear to be similar, but functional outcomes can be highly compromised. ConclusionNCCN panel members provide updated recommendations based on currently accepted treatment approaches for glottic cancer, constantly reviewing new surgical and non-surgical techniques. The guidelines support decision-making about glottic cancer treatment that should be individualized and prioritize patients' quality of life, functionality, and preferences.
  • article 0 Citação(ões) na Scopus
    Hematopoietic colony-stimulating factors in head and neck cancers: Recent advances and therapeutic challenges
    (2024) VIEIRA, Gustavo de Souza; KIMURA, Talita de Carvalho; SCARINI, Joao Figueira; LIMA-SOUZA, Reydson Alcides de; LAVAREZE, Luccas; EMERICK, Carolina; GONCALVES, Mayara Trevizol; DAMAS, Ingrid Iara; FIGUEIREDO-MACIEL, Tayna; SA, Raisa Sales de; AQUINO, Iara Goncalves; PAIVA, Joao Paulo Goncalves de; FERNANDES, Patricia Maria; GONCALVES, Moises Willian Aparecido; KOWALSKI, Luiz Paulo; ALTEMANI, Albina; FILLMORE, Gary Chris; MARIANO, Fernanda Viviane; EGAL, Erika Said Abu
    Colony-stimulating factors (CSFs) are key cytokines responsible for the production, maturation, and mobilization of the granulocytic and macrophage lineages from the bone marrow, which have been gaining attention for playing pro-and/or anti-tumorigenic roles in cancer. Head and neck cancers (HNCs) represent a group of heterogeneous neoplasms with high morbidity and mortality worldwide. Treatment for HNCs is still limited even with the advancements in cancer immunotherapy. Novel treatments for patients with recurrent and metastatic HNCs are urgently needed. This article provides an in-depth review of the role of hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3; also known as multi-CSF) in the HNCs tumor microenvironment. We have reviewed current results from clinical trials using CSFs as adjuvant therapy to treat HNCs patients, and also clinical findings reported to date on the therapeutic application of CSFs toxicities arising from chemoradiotherapy.
  • article 5 Citação(ões) na Scopus
    Deep learning applied to the histopathological diagnosis of ameloblastomas and ameloblastic carcinomas
    (2023) GIRALDO-ROLDAN, Daniela; RIBEIRO, Erin Crespo Cordeiro; ARAUJO, Anna Luiza Damaceno; PENAFORT, Paulo Victor Mendes; SILVA, Viviane Mariano da; CAMARA, Jeconias; PONTES, Helder Antonio Rebelo; MARTINS, Manoela Domingues; OLIVEIRA, Marcio Campos; SANTOS-SILVA, Alan Roger; LOPES, Marcio Ajudarte; KOWALSKI, Luiz Paulo; MORAES, Matheus Cardoso; VARGAS, Pablo Agustin
    Background: Odontogenic tumors (OT) are composed of heterogeneous lesions, which can be benign or malignant, with different behavior and histology. Within this classification, ameloblastoma and ameloblastic carcinoma (AC) represent a diagnostic challenge in daily histopathological practice due to their similar characteristics and the limitations that incisional biopsies represent. From these premises, we wanted to test the usefulness of models based on artificial intelligence (AI) in the field of oral and maxillofacial pathology for differential diagnosis. The main advantages of integrating Machine Learning (ML) with microscopic and radiographic imaging is the ability to significantly reduce intra-and inter observer variability and improve diagnostic objectivity and reproducibility.Methods: Thirty Digitized slides were collected from different diagnostic centers of oral pathology in Brazil. After performing manual annotation in the region of interest, the images were segmented and fragmented into small patches. In the supervised learning methodology for image classification, three models (ResNet50, DenseNet, and VGG16) were focus of investigation to provide the probability of an image being classified as class0 (i.e., ameloblastoma) or class1 (i.e., Ameloblastic carcinoma).Results: The training and validation metrics did not show convergence, characterizing overfitting. However, the test results were satisfactory, with an average for ResNet50 of 0.75, 0.71, 0.84, 0.65, and 0.77 for accuracy, precision, sensitivity, specificity, and F1-score, respectively.Conclusions: The models demonstrated a strong potential of learning, but lack of generalization ability. The models learn fast, reaching a training accuracy of 98%. The evaluation process showed instability in validation; however, acceptable performance in the testing process, which may be due to the small data set. This first investigation opens an opportunity for expanding collaboration to incorporate more complementary data; as well as, developing and evaluating new alternative models.
  • article 0 Citação(ões) na Scopus
    Comparing Mohs micrographic surgery and wide local excision in the management of head and neck dermatofibrosarcoma protuberans: a scoping review
    (2024) SANABRIA, Alvaro; PINILLOS, Pilar; CHIESA-ESTOMBA, Carlos; GUNTINAS-LICHIUS, Orlando; KOWALSKI, Luiz P.; MAEKITIE, Antti A.; RAO, Karthik N.; FERLITO, Alfio
    Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma with a propensity for recurrence. Its management, particularly in the head and neck (H&N) region, presents unique challenges. This study aimed to evaluate the effectiveness of Mohs micrographic surgery (MMS) compared to wide local excision (WLE) in treating H&N DFSP and its impact on recurrence rates and tissue preservation. A comprehensive search was conducted in PubMed/MEDLINE, yielding 29 relevant studies. We included studies comparing MMS and WLE in adult patients with H&N DFSP and reporting local recurrence outcomes. Data were analyzed using random effects analysis, with a meta-analysis performed for comparative studies. Analysis of studies demonstrated a lower recurrence for MMS. Comparative analysis of five studies involving 117 patients showed a significantly lower recurrence rate in the MMS group (2%) compared to the WLE group (19%). Margin status varied between studies, with some achieving negative margins at shorter distances. In the management of H&N DFSP, MMS has emerged as a superior surgical technique, consistently associated with reduced recurrence rates and the potential for tissue preservation. The adoption of MMS should be considered for its capacity to achieve negative margins with fewer processing steps, particularly in anatomically complex regions like the H&N.
  • article 1 Citação(ões) na Scopus
    Exploring the use of the GLIM criteria to diagnose malnutrition in cancer inpatients
    (2023) OZORIO, Gislaine Aparecida; RIBEIRO, Lia Mara Kauchi; SANTOS, Barbara Chaves; BRUZACA, Wannia Ferreira de Sousa; ROCHA, Gabriela Del Gallo Vieira da; MARCHI, Luani Maria da Fonseca; SANTOS, Fernando Magri; ALMEIDA, Maria Manuela Ferreira Alves de; KULCSAR, Marco Aurelio Vamondes; RIBEIRO, Ulysses; CORREIA, Maria Isabel Toulson Davisson; WAITZBERG, Dan Linetzky
    Objectives: The Global Leadership Initiative on Malnutrition (GLIM) criteria establish a diagnosis of malnutrition based on the presence of at least one phenotypic and one etiologic criterion. This study aimed to assess the concurrent and predictive validity of the GLIM criteria in hospitalized cancer patients.Methods: This is an observational retrospective study, including 885 cancer patients, ages >18 y, admitted to a medical oncology inpatient unit between 2019 and 2020. All patients at risk for malnutrition according to the Nutritional Risk Screening 2002 score were assessed by the subjective global assessment (SGA) and 14 different combinations of the GLIM criteria. The SGA was considered the gold standard for assessing the con-current validity of the GLIM combinations. For a subsample of patients with data available on inflammatory markers (n = 198), the serum albumin and C-reactive protein were included in the combinations as etiologic criteria. The predictive validity of the different combinations was tested using the occurrence of surgical complications as the clinical outcome. The sensitivity and specificity values were calculated to assess the con-current validity, univariate and multivariate logistic regression models were used to test predictive validity. Adequate concurrent and predictive validity were determined as sensitivity and specificity values >80% and odds ratio values >2.0, respectively.Results: The median age of the patients was 61.0 y (interquartile range = 51.0-70.0). Head and neck cancer was the prevailing diagnosis and 375 patients were at nutritional risk. According to the SGA, 173 (26.1%) patients were malnourished (SGA categories B or C) and the prevalence of malnutrition ranged from 3.9% to 30.0%, according to the GLIM combinations. None of the tested combinations reached adequate concurrent validity; however, the presence of malnutrition according to four combinations independently predicted surgical complications.Conclusions: The predictive validity of the GLIM was satisfactory in surgical cancer patients.
  • article 0 Citação(ões) na Scopus
    Expression data of FOS and JUN genes and FTIR spectra provide diagnosis of thyroid carcinoma
    (2024) QUEIROZ, Joao Paulo da Silva; PUPIN, Breno; BHATTACHARJEE, Tanmoy Tapobrata; UNO, Miyuki; CHAMMAS, Roger; KULCSAR, Marco Aurelio Vamondes; CANEVARI, Renata de Azevedo
    We explore the feasibility of using FOS and JUN gene expression and ATR-FTIR for diagnosis of thyroid cancer. For the study, 38 samples (6 non-neoplastic (NN), 10 papillary thyroid carcinoma (PTC), 7 follicular thyroid carcinoma (FTC), and 15 benign tumors (BT) were subjected to RNA extraction followed by quantitative real time PCR (qRT-PCR) and 30 samples (5 NN, 9 PTC, 5 FTC, and 11 BT) were used for Attenuated Total Reflectance - Fourier Transform Infrared (ATR-FTIR) followed by multivariate analysis. Of the above, 20 samples were used for both gene expression and ATR-FTIR studies. We found FOS and JUN expression in malignant tumor samples to be significantly lower than NN and benign. ATR-FIR after multivariate analysis could identify the difficult to diagnose FTC with 93 % efficiency. Overall, results suggest the diagnostic potential of molecular biology techniques combined with ATR-FTIR spectroscopy in differentiated thyroid carcinomas (PTC and FTC) and BT.
  • article 3 Citação(ões) na Scopus
    Review of Outcomes after Salvage Surgery for Recurrent Squamous Cell Carcinoma of the Head and Neck
    (2023) HARTL, Dana M.; GUERLAIN, Joanne; GORPHE, Philippe; KAPRE, Madan; GUPTA, Neeti Kapre; SABA, Nabil F.; ROBBINS, K. Thomas; RONEN, Ohad; RODRIGO, Juan P.; STROJAN, Primoz; MAEKITIE, Antti A.; KOWALSKI, Luiz P.; SHAH, Jatin P.; FERLITO, Alfio
    Simple Summary Local recurrences, isolated regional recurrences, and loco-regional recurrences are frequent after treatment for advanced stage head and neck squamous cell carcinoma. Salvage surgery may be possible in selected patients, taking into account the location and stage of the recurrent disease, patient age and comorbidities, tumor HPV status, and functional sequelae in relation to initial therapy. Results vary according to these parameters. Adjuvant treatments after salvage surgery are under investigation. The aim of this review is to present current knowledge concerning the incidence and management of recurrent head and neck squamous cell carcinoma and current data concerning survival and morbidity after salvage surgery.Abstract Surgery with adjuvant chemoradiotherapy or chemoradiotherapy is the mainstay in treatment for advanced stage head and neck squamous cell carcinoma; however, locoregional recurrences are frequent. Salvage surgery could be proposed in selected patients to improve local control, disease-free, and overall survival. Factors for improved disease-free and overall survival in patients treated with salvage surgery include age, tumor location, the initial T stage, HPV status, resection margins, and the time elapsing from the initial treatment. Clinical trials with adjuvant therapies have shown promise after salvage surgery in terms of tolerance and response, but clinical guidelines for using these adjuvant treatments are currently lacking. The aim of this review is to present current knowledge concerning the incidence and management of recurrent head and neck squamous cell carcinoma and current data concerning survival and morbidity after salvage surgery.
  • article 2 Citação(ões) na Scopus
    Impact of lymph node ratio and number of lymph node metastases on survival and recurrence in laryngeal squamous cell carcinoma
    (2023) MOLTENI, Gabriele; NOCINI, Riccardo; MATTIOLI, Francesco; NAKAYAMA, Meijin; DEDIVITIS, Rogerio A.; MANNELLI, Giuditta; CROSETTI, Erika; CHIESA-ESTOMBA, Carlos Miguel; SISTIAGA-SUAREZ, Jon A.; GIORDANO, Leone; GALLI, Andrea; LIONELLO, Marco; MERCANTE, Giuseppe; RALLI, Massimo; FERMI, Matteo; KLEIN-RODRIGUEZ, Alejandro; MAYO-YANEZ, Miguel; SERAFINI, Edoardo; PIROLA, Francesca; PADERNO, Alberto; CAMBRIA, Francesca; ORIDATE, Nobuhiko; SANO, Daisuke; BOSCOLO-RIZZO, Paolo; MARCUZZO, Alberto Vito; PARRINELLO, Giampiero; MARCHI, Filippo; SAIBENE, Alberto Maria; TUCCIARONE, Manuel; VISCASILLAS, Guillem; ZELENIK, Karol; RAMOS, Daniel Marin; PALACIOS-GARCIA, Jose; TIRELLI, Giancarlo; PELLINI, Raul; PALUDETTI, Gaetano; GALLI, Jacopo; ROSSI, Giorgia; VINCENTIIS, Marco De; CERNEA, Claudio Roberto; SPRIANO, Giuseppe; BUSSI, Mario; PERETTI, Giorgio; SUCCO, Giovanni; PIAZZA, Cesare; BERTOLIN, Andy; KOWALSKI, Luiz Paulo; PRESUTTI, Livio; SACCHETTO, Andrea
    IntroductionThe aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. Materials and methodsWe conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. Results2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. ConclusionOur data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.