RESUMO
In vivo reflectance confocal microscopy (RCM) is poorly investigated in oral pathology due to the peculiar anatomical and topographical oral mucosa features. A dedicated handheld confocal microscope with an intra-oral probe was developed for oral mucosa imaging. The main objective was to describe the healthy oral mucosa and the cytoarchitectural findings detectable in different oral disorders by means of the newly designed handheld confocal microscope. Secondary aim was to identify the main RCM criteria that differentiate oral lesions in order to provide algorithm for a rapid non-invasive evaluation. This observational retrospective study included all consecutive patients with oral disorders and volunteers with healthy oral mucosa who underwent RCM examination in our outpatient clinic from September 2018 to December 2021. Three different investigators examined together the RCM images to detect the key features and secondary criteria for each type of oral lesion collected. The study population included 110 patients affected by oral lesions and seven volunteers with healthy oral mucosae. A total of 15 oral disorders were imaged and divided in three main groups: white, red and pigmented lesions. Key features and secondary criteria were identified for every single type of oral disease. RCM permits a cytoarchitectural evaluation of the oral mucosae affected by inflammatory, dysplastic and neoplastic diseases, thus orienting the clinicians towards non-invasive diagnosis and enhancing the diagnostic management. The "tree diagrams" proposed allow a schematic and simplified view of confocal features for each type of oral disease, thus drastically reducing the diagnostic timing.
Assuntos
Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Microscopia Intravital , Mucosa Bucal , Microscopia Confocal/métodos , Dermoscopia/métodosRESUMO
PURPOSE: The purpose of this study was to analyse the oncologic results of open partial horizontal laryngectomy (OPHL) and to assess the prognostic factors that could affect the survival of patients affected by T2, T3 and T4a laryngeal cancer. Using this data, we aim to identify clinical criteria to select patients amenable to conservative surgery, and to facilitate a more targeted approach in the management of advanced laryngeal cancer. METHODS: A retrospective study was performed in patients who underwent OPHL type II for laryngeal squamous cell carcinoma from January 2005 to December 2018. We analysed a total of 170 patients; 21(12.36%) cases were staged as pT2, 116 (68.23%) as pT3 and 33 (19.41%) as pT4a. RESULTS: Five-year overall survival (OS) was 80.9%, 79.3%, 70.4% for T2, T3 and T4 respectively. Disease-specific survival (DSS) was 90.4%, 85.3% and 77.4%. Posterior tumour extension, perineural invasion and N status showed to considerably influence survival in both uni- and multivariate analyses. CONCLUSION: The oncological outcomes from our study show that OPHL for advanced laryngeal cancer can guarantee a high percentage of success. Accurate patient selection is of utmost importance to differentiate advanced disease amenable to conservative surgery, and treatment options should consider selected criteria based on tumour and patient features.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Neoplasias de Cabeça e Pescoço/patologia , Hospitais , Humanos , Neoplasias Laríngeas/patologia , Laringectomia/métodos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Cutaneous squamous cell carcinoma of the head and neck district are generally treated with surgery. Surgery is the standard treatment in early stages and local advanced tumors, followed by adjuvant therapy, radiation or concurrent chemoradiation therapy. Local recurrence treatment depends on previous therapies, though radical surgery is often the first choice at the expense of anatomy preservation. We present the case of a patient with cutaneous squamous cell carcinoma of the nasal dorsum which relapsed after surgery and radiation therapy. The patient refused radical surgery and electrochemotherapy under general anesthesia was administered. After 6 months from treatment, the patient showed a complete clinical response. Electrochemotherapy could be considered as an alternative to surgery in small lesion when other approaches are refused.
Assuntos
Eletroquimioterapia/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Nasais/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso de 80 Anos ou mais , Bleomicina/administração & dosagem , Feminino , Humanos , Neoplasias Nasais/radioterapia , Neoplasias Nasais/cirurgia , Radioterapia Adjuvante , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgiaRESUMO
PURPOSE: The objective of the current systematic review with meta-analysis was to report the pooled survival outcomes of supracricoid partial laryngectomy in the setting of radiorecurrent laryngeal cancer to investigate if and when an organ-sparing surgical treatment is adequate. METHODS: The search included all original papers from 1990 to December 2017. The search terms included the following: cricohyoepiglottopexy; cricohyoidopexy; cricohyopexy; horizontal laryngectomy; and partial, subtotal, supracricoid, and supraglottic laryngectomy. Inclusion criteria were as follows: (1) data clearly distinguish results of partial laryngeal procedures; (2) clear description of tumor stage and selection criteria; (3) clear description or derivability of local control and survival rates. RESULTS: Eleven out of 270 papers were analyzed, and a total of 251 cases were included. Two-year LC, 3-year DFS, and 5-year OS were 92, 80, and 79%, respectively. Heterogenicity evaluated with the I2 parameter was 14, 0, 0%, respectively. The larynx preservation rate was 85.2%, the decannulation rate was 92.1%, and swallowing recovery was 96.5% (PEG dependence and the aspiration pneumonia rate were 3.5 and 6.4%, respectively). CONCLUSIONS: SCPL is oncologically sound, guaranteeing a high percentage of success. The homogeneity of data should encourage the use of SCPL as salvage treatment for recurrent LSCC.
Assuntos
Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Laringectomia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Cartilagem Cricoide/patologia , Cartilagem Cricoide/cirurgia , Humanos , Neoplasias Laríngeas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Terapia de Salvação , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Head and neck squamous cell carcinoma is typically characterized by a high incidence of local recurrences. It has been extensively shown that mucosa from head and neck squamous cell carcinoma patients carries both genetic and gene expression alterations, which are mostly attributable to major etiologic agents of head and neck squamous cell carcinoma. We previously identified a signature of microRNAs (miRNAs) whose high expression in tumors is predictive of recurrence. Here, we investigated whether the deregulation of miRNA expression in the tumor-surrounding mucosa is correlated to disease recurrence. Specifically, comparing the miRNA expression in matched tumoral, peritumoral, and normal tissues collected from head and neck squamous cell carcinoma patients, we identified 35 miRNAs that are deregulated in both tumoral and peritumoral tissues as compared with normal matched samples. Four of these composed a miRNA signature that predicts head and neck squamous cell carcinoma local recurrence independently from prognostic clinical variables. The predictive power of the miRNA signature increased when using the expression levels derived from both the peritumoral and the tumoral tissues. The expression signal of the miRNAs composing the predictive signature correlated with the transcriptional levels of genes mostly associated with proliferation. Our results show that expression of miRNAs in tumor-surrounding mucosa may strongly contribute to the identification of head and neck squamous cell carcinoma patients at high risk of local recurrence.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , TranscriptomaAssuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Neurilemoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias do Sistema Nervoso Periférico/cirurgia , Adulto , Imagem de Difusão por Ressonância Magnética , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Neurilemoma/diagnóstico por imagem , Neoplasias do Sistema Nervoso Periférico/diagnóstico por imagemRESUMO
BACKGROUND: Human papilloma virus (HPV) related cancers of the oropharynx are rapidly increasing in incidence and may soon represent the majority of all head and neck cancers. Improved monitoring and surveillance methods are thus an urgent need in public health. MAIN TEXT: The goal is to highlight the current potential and limitations of liquid biopsy through a meta analytic study on ctHPVDNA and TTMV-HPVDNA. It was performed a Literature search on articles published until December 2023 using three different databases: MEDLINE, Embase, and Cochrane Library. Studies that evaluated post-treatment ctHPVDNA and TTMV-HPVDNA in patients with HPV + OPSCC, studies reporting complete data on the diagnostic accuracy in recurrence, or in which the number of true positives, false positives, true negatives, and false negatives was extractable, and methods of detection of viral DNA clearly defined. The meta-analysis was conducted following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) reporting guidelines. The aim of this meta-analysis was to evaluate the sensitivity, specificity, and accuracy of ctHPVDNA and TTMV by ddPCR to define its efficacy in clinical setting for the follow up of HPV-OPSCC. CONCLUSION: The 12 studies included in the meta-analysis provided a total of 1311 patients for the analysis (398 valuated with ctHPVDNA and 913 with TTMV-HPVDNA). Pooled sensitivity and specificity were 86% (95% CI: 78%-91%) and 96% (95% CI: 91%-99%), respectively; negative and positive likelihood ratios were 0.072 (95% CI: 0.057-0.093) and 24.7 (95% CI: 6.5-93.2), respectively; pooled DOR was 371.66 (95% CI: 179.1-918). The area under the curve (AUC) was 0.81 (95% CI, 0.67-0.91). Liquid biopsy for the identification of cell free DNA might identify earlier recurrence in HPV + OPSCC patients. At the present time, liquid biopsy protocol needs to be standardized and liquid biopsy cannot yet be used in clinical setting. In the future, a multidimensional integrated approach which links multiple clinical, radiological, and laboratory data will contribute to obtain the best follow-up strategies for the follow-up of HPV-OPSCC.
Assuntos
DNA Viral , Neoplasias Orofaríngeas , Humanos , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/diagnóstico , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Papillomaviridae/genética , Biópsia Líquida/métodosRESUMO
BACKGROUND: First aim was to compare ddPCR assays of ctHPVDNA with p16 IHC and qualitative HPV PCR. Second aim was to carry out longitudinal blood sampling to test for association of ctHPVDNA with histological confirmed recurrence. Third aim was to perform a multidimensional assessment which included: (1) clinical features; (2) ctHPVDNA; (3) MRI-based tumor size measurements of primary tumor (PT) and cervical lymph node metastases (CLNM). METHODS: Plasma samples were collected before treatment and during follow-up, and ddPCR assay comprising E6 of HPV16 and HPV 33 and HPV 35 was used. RESULTS: Present study was conducted at diagnosis in 117 patients and revealed a ctHPVDNA sensitivity of 100% (95% CI 95.5-100) and a specificity of 94.4 (95% CI 81.3-99.3), positive predictive value (PPV) of 94.4 (95% CI 81.3-99.3), and negative predictive value (NPP) of 100% (95% CI 89.7-100). During follow-up ctHPVDNA had a sensitivity of 100% (95% CI 72.1-100)% and specificity of 98.4% (95% CI 91.7-100)%, PPV% of 90.9% (95% CI 62.3-98.4) and NPV% of 100% (95% CI 94.3-100) for ability to detect recurrence. Correlation between both the CLNM volume and the sum of PT and CLNM volume was observed. CONCLUSIONS: ctHPVDNA was superior to p16 in identification of HPV-OPSCC at diagnosis. Introduction of ctHPVDNA, beyond diagnostic setting, represents a great opportunity to improve follow-up protocol of OPSCC patients.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Feminino , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/sangue , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , DNA Viral/sangue , DNA Tumoral Circulante/sangue , Sensibilidade e Especificidade , Adulto , Recidiva Local de Neoplasia/virologia , Metástase Linfática , Reação em Cadeia da Polimerase , Valor Preditivo dos TestesRESUMO
Locoregional recurrences represent a frequently unexpected problem in head and neck squamous cell carcinoma (HNSCC). Relapse often (10-30%) occurs in patients with histologically negative resection margins (RMs), probably due to residual tumor cells or hidden pre-cancerous lesions in normal mucosa, both missed by histopathological examination. Therefore, definition of a 'clean' or tumor-negative RM is controversial, demanding for novel approaches to be accurately explored. Here, we evaluated next generation sequencing (NGS) and digital PCR (dPCR) as tools to profile TP53 mutational status and circulating microRNA expression aiming at scoring the locoregional risk of recurrence by means of molecular analyses. Serial monitoring of these biomarkers allowed identifying patients at high risk, laying the ground for accurate tracking of disease evolution and potential intensification of post-operative treatments. Additionally, our pipeline demonstrated its applicability into the clinical routine, being cost-effective and feasible in terms of patient sampling, holding promise to accurately (re)-stage RMs in the era of precision medicine.
RESUMO
The first aim was to define the oncologic outcomes of open partial laryngectomy (OPL) in naïve pT3 laryngeal cancer. The second aim was to analyze the outcomes after OPL versus total laryngectomy (TL). A literature search was conducted in three databases (MEDLINE, EMBASE, and Cochrane Library) until January 2022. In 805 patients treated with OPL, 5-year OS, DSS, DFS and LFS were 80.5% (95% CI 70.6-87.6), 83.4% (95% CI 75.7-89), 77.4% (95% CI 66.3-85.7) and 77.9% (95% CI 68.7-85), respectively. Three articles compared TL versus OLP: 5-year OS, DSS and DFS risk difference were 0.100 (95% CI -0.092 to 0.291), 0.067 (95% CI -0.085 to 0.220) and 0.018 (95% CI -0.164 to 0.201) respectively. OPL for selected pT3 laryngeal cancer is able to guarantee a high percentage of oncological success. Accurate patient selection is of utmost importance to differentiate advanced disease amenable to conservative surgery.
Assuntos
Neoplasias Laríngeas , Humanos , Gerenciamento de Dados , Neoplasias Laríngeas/cirurgia , Laringectomia , Seleção de Pacientes , Estudos RetrospectivosRESUMO
The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However, these data are from small cohorts and available tests for detection of ctHPVDNA are not fully validated. The aim is to evaluate sensitivity, specificity, and accuracy of ctHPVDNA by ddPCR to define its efficacy in the clinical setting for the diagnosis of HPV + OPSCC. A comprehensive search of three different databases: MEDLINE, Embase, and Cochrane Library databases. A total of 998 patients were evaluated from the 13 studies. OPSSC p16+ were 729, while controls p16- were 269. The meta-analytic study estimated the diagnostic performance of ctHPVDNA as follows: pooled sensitivity and specificity of 0.90 (95% CI: 0.82-0.94) and 0.94 (95% CI: 0.85-0.98), respectively; positive and negative likelihood ratios of 12.6 (95% CI: 4.9-32.1) and 0.05 (95% CI: 0.02-0.13), respectively. ddPCR for ctHPVDNA has good accuracy, sensitivity, and specificity for diagnosis of HPV + OPSCC. ctHPVDNA kinetic represents a great reliable opportunity to improve diagnostic and therapeutic management of cancer patients and could open new perspectives for understanding tumor biology.
Assuntos
DNA Tumoral Circulante , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/diagnóstico , Papillomaviridae/genética , Neoplasias Orofaríngeas/patologia , Papillomavirus Humano , DNA Viral/análiseRESUMO
BACKGROUND AND AIM: Free flaps or pedicle flaps are the mainstay of cancer surgery in the head and neck area. However, their long-term sequelae are still poorly understood. Among these, the development of a secondary primary tumor on a flap is a rare and uncertain reported event. Methods: A computer-aided systematic literature search was performed by using the PubMed, EMBASE and Cochrane Library databases. A systematic review of the literature, following the PRISMA checklist, was carried out with the aim of analyzing all the citations reporting this second primary, with attention to risk factors, behavior, etiological causes. Results: Overall, 27 cases of second primary squamous cell carcinoma arising on a pedicle or free flap were identified. In addition, other three cases were discussed. Conclusions: Persistent exposure to oral stimuli such saliva, oral microbiome, smoke or a colonization by the adjacent mucosa were considered as a possible cause of second primary carcinoma. Although rare, a new neoplasm onset should know and considered as a new concept in the follow-up of patients undergoing reconstruction with free or pedicle flaps.
Assuntos
Carcinoma de Células Escamosas , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Segunda Neoplasia Primária , Procedimentos de Cirurgia Plástica , Humanos , Retalhos de Tecido Biológico/patologia , Retalhos de Tecido Biológico/cirurgia , Pescoço/patologia , Pescoço/cirurgia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/cirurgia , Segunda Neoplasia Primária/patologia , Recidiva , Neoplasias de Cabeça e Pescoço/cirurgiaRESUMO
OBJECTIVES/HYPOTHESIS: The aim of this study was to assess the value of cell-free human papillomavirus-DNA (cfHPV-DNA) as a diagnostic test for the post-treatment surveillance of patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) through a systematic review and meta-analysis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A literature search was conducted in three databases (MEDLINE, Embase, and Scopus) in January 2021. The population included patients with HPV-positive HNSCC. The intervention was the use of the repeated liquid biopsy with circulating HPV-DNA detection during follow-up. The outcome was to establish the value of cfHPV-DNA as a diagnostic test for the post-treatment surveillance of patients with HPV-positive HNSCC. RESULTS: Ten studies included in the meta-analysis provided a total of 457 patients with HPV-positive HNSCC. The meta-analytic study estimated the diagnostic performance of cfHPV-DNA as follows: pooled sensitivity and specificity of 0.65 (95% confidence interval [CI]: 0.40-0.84) and 0.99 (99% CI: 0.96-0.99), respectively; positive and negative likelihood ratios of 62.5 (99% CI: 22.9-170.2) and 0.05 (99% CI: 0.013-0.24), respectively; and pooled diagnostic odds ratio of 371.66 (99% CI: 60.4-2286.7). CONCLUSION: Currently, the follow-up protocol for HNSCC patients includes routine clinical evaluation and radiological imaging. Biomarkers to monitor this disease are not established. Considering its high specificity, cfHPV-DNA represents a potential confirmatory test in the case of positive positron emission tomography and computed tomography. In the near future, cfHPV-DNA could be used as a biomarker for monitoring the treatment response during the clinical trials of de-escalation therapy or immunotherapy. Larger sample sizes and the homologation of study protocols and methodology are needed to better establish its utility in the clinical practice. Laryngoscope, 132:560-568, 2022.
Assuntos
Carcinoma de Células Escamosas/virologia , Ácidos Nucleicos Livres/genética , DNA Viral/genética , Neoplasias de Cabeça e Pescoço/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Biópsia Líquida , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Surgical treatment of hypopharyngeal cancer is indicated in advanced stages and recurrent/persistent disease after conservative regimens. As of today, no criterion standard treatment is applicable to all cases. Comparing functional results, complication rates and feasibility of different techniques proposed (free flaps, gastric pull-up, etc), and poor outcome in disease-free survival and in overall survival are more related to the tumor stage rather than the reconstruction technique. The authors discuss reconstructive surgery performed in 52 patients using a pectoralis major myocutaneous flap, according to a technique proposed by Spriano et al in 2001, after total circular partial/total hypopharyngectomy and total laryngectomy from January 1993 to 2008. Primary surgical treatment was performed in 38 patients. Surgery after radiotherapy/chemotherapy failure was performed in 8 patients. Surgery after chemotherapy was performed in 6 patients. Postoperative radiation treatment was administered in 35 patients. Two patients did not receive complementary radiotherapy: 1 patient died perioperatively and 1 had previous radiation treatment in 2002 for oropharyngeal cancer. Follow-up period ranged from a minimum of 7 months to a maximum of 15 years. Overall survival was 19.6%. To date, disease-free survival is 9 (17.3%) of 52 patients. Long-term follow-up shows that late complications are low or absent. For this reason, we consider this procedure to be time-sparing and safe, especially in this category of patients commonly affected by malnutrition and other long-term diseases.
Assuntos
Neoplasias Hipofaríngeas/cirurgia , Músculos Peitorais/transplante , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/terapia , Laringectomia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Faringectomia , Complicações Pós-Operatórias , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Literature data suggests that age, gender and body mass index (BMI) could be associated with difference in immune responses to vaccines. The first goal of the study was to analyze the antibody titre seven days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCWs). The second goal was to analyze how antibody titre changes in correlation with age, gender, BMI and hypertension. METHODS: An immunogenicity evaluation was carried out among HCWs vaccinated at the Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy. All HCWs were asked to be vaccinated by the Italian national vaccine campaign at the beginning of 2021. 260 vaccinated HCWs were enrolled in the study. All eligible participants were assigned to receive the priming dose in two weeks' time and the booster dose exactly 21 days thereafter. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Quantitative measurements of IgG antibodies against S1/S2 antigens of SARS-CoV-2 were performed with a commercial chemiluminescent immunoassay. Presence of SARS-Cov-2 in nasopharyngeal swab was determined by commercial RT-PCR testing. FINDINGS: 248 HWCs were analyzed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7) was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with p<0.0001. Multivariate linear regression analysis of AU/mL by age, gender and BMI multivariate was performed by the inclusion of covariates. This analysis demonstrated that age (p<0.0001) and gender (p = 0.038) are statistically associated with differences in antibody response after vaccination, whereas BMI and hypertension have no statistically significant association (p = 0.078 and p = 0.52 respectively). INTERPRETATION: 99.5% of HCW developed a humoral immune response and female and young participants seem to have an increased capacity to mount humoral immune responses. BMI and hypertension seem not associated with difference in immune response to the vaccine. FUNDING: None.
RESUMO
BACKGROUND: The first goal of the study was to analyse the antibody titre 21 days after the first dose of the BNT162b2 vaccine in a group of 252 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and body mass index (BMI). METHODS: Participants had a nasopharyngeal swab for SARS-CoV-2 and were assessed for the presence of SARS-CoV-2 antibodies at baseline and 21 days after the BNT162b2 priming dose. RESULTS: First dose of BNT162b2 activated immune responses in 98% of the participants. Five HWC had no increase in antibody titre 21 days after the first dose. Antibody titre was greater in young (<38 years) vs. older participants (<38 vs. 47-56 p = 0.002; <38 vs. >56 p = 0.001). Higher antibody levels were detected in underweight vs. pre-obesity group (p = 0.026) and in normal-weight vs. pre-obesity group (p = 0.007). This association was confirmed after adjusting for age (p = 0.0001) and gender (p = 0.00001). CONCLUSIONS: Our study demonstrates that a single dose of BNT162b2 activates the immune response, and being young and normal-weight correlate positively with this response. Larger specifically designed clinical trials are needed to validate these results.
RESUMO
PURPOSE: Mutation of TP53 gene is a hallmark of head and neck squamous cell carcinoma (HNSCC) not yet exploited therapeutically. TP53 mutation frequently leads to the synthesis of mutant p53 proteins with gain-of-function activity, associated with radioresistance and high incidence of local recurrences in HNSCC. EXPERIMENTAL DESIGN: Mutant p53-associated functions were investigated through gene set enrichment analysis in the Cancer Genome Atlas cohort of HNSCC and in a panel of 22 HNSCC cell lines. Mutant p53-dependent transcripts were analyzed in HNSCC cell line Cal27, carrying mutant p53H193L; FaDu, carrying p53R248L; and Detroit 562, carrying p53R175H. Drugs impinging on mutant p53-MYC-dependent signature were identified interrogating Connectivity Map (https://clue.io) derived from the Library of Integrated Network-based Cellular Signatures (LINCS) database (http://lincs.hms.harvard.edu/) and analyzed in HNSCC cell lines and patient-derived xenografts (PDX) models. RESULTS: We identified a signature of transcripts directly controlled by gain-of-function mutant p53 protein and prognostic in HNSCC, which is highly enriched of MYC targets. Specifically, both in PDX and cell lines of HNSCC treated with the PI3Kα-selective inhibitor BYL719 (alpelisib) the downregulation of mutant p53/MYC-dependent signature correlates with response to this compound. Mechanistically, mutant p53 favors the binding of MYC to its target promoters and enhances MYC protein stability. Treatment with BYL719 disrupts the interaction of MYC, mutant p53, and YAP proteins with MYC target promoters. Of note, depletion of MYC, mutant p53, or YAP potentiates the effectiveness of BYL719 treatment. CONCLUSIONS: Collectively, the blocking of this transcriptional network is an important determinant for the response to BYL719 in HNSCC.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Mutação com Ganho de Função , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Proteína Supressora de Tumor p53/genética , Animais , Apoptose , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
This is a retrospective study to evaluate the outcomes and complications of combined treatment, surgery with or without adjunctive intraoperative radiotherapy, of locally advanced temporal bone squamous cell carcinoma. A series of 17 patients with locally advanced squamous cell carcinoma of the temporal bone were treated between September 2002 and February 2007. Eleven patients had primary tumors, and 6 patients had recurrences. According to the University of Pittsburgh staging system, 5 patients were stage II (T2 N0), 6 patients were stage III (5, T3 N0 and 1, T1 N1), and 6 patients were stage IV (5, T3 N2b and 1, T4 N0). All patients underwent lateral temporal bone resection and pedicle flap reconstruction. Eight patients received intraoperative and postoperative radiotherapies, 4 patients underwent postoperative radiation alone, whereas 5 patients did not receive any adjunctive treatment. Median follow-up was 29.5 months. No major complications were observed. No patients were found to have residual gross tumor. Disease-free survival was 73.3%, and overall survival was 75.6%. Radical external auditory canal and/or middle ear canal resection is of utmost importance to obtain a good surgical outcome. Postoperative radiotherapy is necessary to obtain good local control; no major adverse effects were observed in the intraoperative radiotherapy patients. The incidence of major complication is minimal after pedicle flap reconstruction.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Meato Acústico Externo/cirurgia , Neoplasias da Orelha/cirurgia , Orelha Média/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Audiometria de Tons Puros , Intervalo Livre de Doença , Meato Acústico Externo/efeitos da radiação , Neoplasias da Orelha/radioterapia , Orelha Média/efeitos da radiação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Músculos Peitorais/transplante , Radioterapia Adjuvante , Radioterapia de Alta Energia , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Transplante de Pele , Neoplasias Cranianas/radioterapia , Neoplasias Cranianas/cirurgia , Retalhos Cirúrgicos , Taxa de Sobrevida , Osso Temporal/efeitos da radiação , Osso Temporal/cirurgia , Músculo Temporal/transplante , Resultado do TratamentoRESUMO
Head and neck squamous cell carcinomas (HNSCCs) are tumors with propensity mostly for locoregional spread. Most frequent sites of metastasis from cancer of the oral cavity include lung, bone, liver, adrenal, heart, and kidney. The advent of newer surgical techniques and an improved understanding of head and neck cancer have further improved control of cancer above the clavicles. Furthermore, the overall survival rate in patients with advanced head and neck cancer has not improved significantly. This has been partly because of the emergence of second primary cancers and the development of distant metastasis defined as cancer deposits below the clavicles. Authors reported a case of a 60 years-old man affected by squamous cell carcinoma of the oral cavity treated with surgery and adjuvant radiochemotherapy that developed a metastatic lesion to the left talus 10 months after primary treatment. In conclusion, bone is a rare metastatic site for HNSCC, much rarer in case of sites distal to the knee. Owing to paucity of the literature on this, no definite predisposing factor is identifiable. Because of the rarity of these lesions, bone scintigraphy remains not indicated in case of HNSCC, but attention has to be paid to eventual symptoms, also if frequently sensitive for advanced lesions.
Assuntos
Neoplasias Ósseas/secundário , Carcinoma de Células Escamosas/secundário , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Tálus/patologia , Amputação Cirúrgica , Neoplasias Ósseas/terapia , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante , Evolução Fatal , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/terapia , Esvaziamento Cervical , Estadiamento de Neoplasias , Radioterapia AdjuvanteRESUMO
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer worldwide. They are typically characterized by a high incidence of local recurrence, which is the most common cause of death in HNSCC patients. TP53 is the most frequently mutated gene in HNSCC and patients carrying TP53 mutations are associated with a higher probability to develop local recurrence. MiRNAs, which are among the mediators of the oncogenic activity of mt-p53 protein, emerge as an appealing tool for screening, diagnosis and prognosis of cancer. We previously identified a signature of 12 miRNAs whose aberrant expression associated with TP53 mutations and was prognostic for HNSCC. Among them miR-96-5p emerges as an oncogenic miRNAs with prognostic significance in HNSCC. METHODS: To evaluate the oncogenic role of miR-96-5p in a tumoral context, we performed colony formation, cell migration and cell viability assays in two HNSCC cell lines transfected for miR-96-5p mimic or inhibitor and treated with or without radio/chemo-therapy. In addition, to identify genes positively and negatively correlated to miR-96-5p expression in HNSCC, we analyzed the correlation between gene expression and miR-96-5p level in the subset of TCGA HNSCC tumors carrying missense TP53 mutations by Spearman and Pearson correlation. To finally identify targets of miR-96-5p, we used in silico analysis and the luciferase reporter assay to confirm PTEN as direct target. RESULTS: Our data showed that overexpression of miR-96-5p led to increased cell migration and radio-resistance, chemotherapy resistance in HNSCC cells. In agreement with these results, among the most statistically significant pathways in which miR-96-5p is involved, are focal Adhesion, extracellular matrix organization and PI3K-Akt-mTOR-signaling pathway. As a direct target of miR-96-5p, we identified PTEN, the main negative regulator of PI3K-Akt signalling pathway activation. CONCLUSIONS: These results highlight a new mechanism of chemo/radio-resistance insurgence in HNSCC cells and support the possibility that miR-96-5p expression could be used as a novel promising biomarker to predict radiotherapy response and local recurrence development in HNSCC patients. In addition, the identification of pathways in which miR-96-5p is involved could contribute to develop new therapeutic strategies to overcome radio-resistance.