RESUMO
PURPOSE: Seroma/sialocele and haematoma formations following parotidectomy are common complications. Fibrin-sealant tissue glue (FSTG) applied to the surgical bed prior to closure has been used widely to reduce such complications at other surgical sites. We sought to evaluate a potential role in parotidectomy, examining outcomes before and after the use of FSTG was introduced in our department. METHODS: Outcomes were studied retrospectively for 1 year prior to the introduction of FSTG (group A, n = 31), and prospectively for 1 year subsequently (group B, n = 29). Primary outcome measures were seroma/sialocele and haematoma rates. Secondary outcome measures of interest included the use of a surgical drain and the duration of hospital stay. Chi-squared statistics and Mann-Whitney U tests were used to compare the outcomes between groups as appropriate. RESULTS: Seroma/sialocele rates were significantly lower in group B than in group A (n = 2 [6.9%] versus n = 8 [25.8%], p = 0.01) (Fig. 1), with an absolute risk reduction of 18.9%, a relative risk reduction of 26.7%, and a number needed to treat of 5.3. Haematoma rates were similar between groups (n = 0 [0%] versus n = 1 [3.2%], p = 0.36) (Fig. 2). In group A, a surgical drain was used in 24 cases (77.4%), while no cases in group B were drained.Fig. 1Seroma ratesFig. 2Haematoma rates CONCLUSION: The use of FSTG appears to significantly reduce the risk of post-parotidectomy seroma/sialocele formation and facilitates safe, drain-free daycase surgery. We hope this report will prompt other departments to consider using this technique and that our findings will help foster further appraisal in larger, prospective studies going forward.
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Adesivo Tecidual de Fibrina , Adesivos Teciduais , Adesivo Tecidual de Fibrina/uso terapêutico , Humanos , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos , Seroma/etiologia , Seroma/prevenção & controle , Adesivos Teciduais/uso terapêuticoRESUMO
OBJECTIVES: Surgical drainage is the traditional mainstay of treatment of paediatric deep neck space infection (DNSI), but recently non-operative management in selected cases has been advocated. We sought to identify any characteristics predictive of requirement for surgical intervention. DESIGN: Retrospective cohort study using receiver operating characteristics analyses. SETTING: Tertiary referral paediatric hospital. PARTICIPANTS: Children (≤16 years) with a radiologically confirmed diagnosis of retro- or parapharyngeal abscess over a ten-year period. MAIN OUTCOME MEASURES: Predictive value of clinical and radiological variables in determining the requirement for surgical intervention. Length of hospital stay (LoS) was also examined. RESULTS: Ninety-three children were studied, 15 (16.1%) of whom underwent immediate surgery, 42 (45.2%) of whom underwent delayed surgery following an initial period of conservative management, and 36 (38.7%) of whom were managed conservatively. Age, WCC and CRP were not predictive of the need for surgical drainage. Radiological abscess diameter, however, was predictive of requirement surgery (AUC = 0.85 [95% CI ± 0.09] P = 0.02), with a cut-off value of 2.5 cm determined assuming equal weight to sensitivity and specificity. All DNSIs were successfully treated with no adverse outcomes, and there was no significant difference in LoS between groups. In those managed surgically, outcome and LoS did not depend on yield of pus. CONCLUSIONS: Selected paediatric DNSIs can be successfully managed conservatively, with abscess diameter >2.5 cm a significant predictor of need for surgical intervention. Any benefit of surgery does not appear to depend on intra-operative yield of pus.
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Drenagem/métodos , Abscesso Retrofaríngeo/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Abscesso Retrofaríngeo/diagnóstico por imagem , Estudos RetrospectivosRESUMO
OBJECTIVES: Management of laryngopharyngeal reflux (LPR) typically comprises alginates and proton pump inhibitors (PPIs) alone or in combination, yet evidence to support any particular treatment regimen is lacking. We sought to evaluate the efficacy of Gaviscon® Advance alone versus co-prescription with a PPI in treating LPR. METHODS: One hundred consecutive LPR patients with a reflux symptom index (RSI) score > 10 attending our joint voice clinic (JVC) were studied prospectively. All were treated with Gaviscon® Advance four times daily. If patients had been started on a PPI prior to their JVC attendance, this was optimised to a twice-daily dosing regimen and continued. RSI scores were recorded at first attendance and 3 months post-treatment via postal questionnaire. Scores were analysed using t tests and Levene's test for equality of variances. RESULTS: Follow-up RSI scores were returned by 72 patients, 39 of whom were treated with Gaviscon® Advance only (group A) and 33 with Gaviscon® Advance + PPI (group B). Mean pre-treatment RSI scores were similar between groups [group A: 19.2, 95% confidence interval (CI) ± 2.4; group B: 21.3, 95% CI ± 3.2 (p = 0.65)]. No significant differences were observed with respect to 3-month post-treatment RSI scores [group A: 9.9, 95% CI ± 2.8; group B: 12.6, 95% CI ± 4.2 (p = 0.82)] and change in RSI scores [group A: 9.3, 95% CI ± 3.0; group B: 8.7, 95% CI ± 2.9 [p = 0.75]). CONCLUSIONS: Gaviscon® Advance alone is effective in treating symptoms of LPR, while co-prescription with a high-dose PPI offers no additional benefit.
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Alginatos/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Refluxo Laringofaríngeo/tratamento farmacológico , Ácido Silícico/administração & dosagem , Bicarbonato de Sódio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiácidos/administração & dosagem , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Humanos , Refluxo Laringofaríngeo/diagnóstico , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento , Voz/efeitos dos fármacosAssuntos
COVID-19/epidemiologia , Emergências , Neoplasias de Cabeça e Pescoço/epidemiologia , Acessibilidade aos Serviços de Saúde , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Reino Unido/epidemiologiaRESUMO
Transoral laser microsurgery (TLM) represents an important treatment for selected laryngeal cancers. Utilisation of TLM, however, is highly variable between United Kingdom (UK) centres, and published data relating to its use in the UK is scarce. We report outcomes from our tertiary referral centre, and highlight lessons learned. Patients undergoing primary TLM for laryngeal cancer with curative intent (2007-2011) were studied retrospectively. Survival analyses were evaluated using the Kaplan-Meier method and log-rank statistics used to examine the influence of several variables. Overall, 170 cases were included-153 glottic and 17 supraglottic. Median follow-up was 39 months (range 14-79 months). Respective 3-year local control (LC), overall survival (OS), disease-specific survival (DSS), and disease-free survival were 92, 92, 98, and 86 % for glottic carcinomas. Three-year LC and OS were both 88 % for supraglottic carcinomas. For glottic cases, a significant impact of pT stage on DSS was observed, and of age on OS. Median hospital stay was one and 19 days for glottic and supraglottic cases respectively, with respective 3-year laryngeal preservation rates of 97 and 94 %, and tracheostomy rates of 0 and 29 %. One patient in the glottic group and four in the supraglottic group failed to regain swallowing function post-operatively, remaining either PEG dependent or undergoing functional total laryngectomy. Our series confirms the oncological and functional efficacy of TLM, offering a unique large-scale UK perspective. Our experience indicates, however, that treatment of larger supraglottic tumours should be considered carefully, as functional outcomes may be compromised.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Laríngeas/cirurgia , Terapia a Laser , Microcirurgia/métodos , Recidiva Local de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Laringectomia , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Estudos Retrospectivos , Reino UnidoRESUMO
Bone-anchored hearing aids (BAHAs) are based on the principle of osseointegration, which is fundamental to implant stability and survival. Previous exposure to ionising radiation may compromise this, as evidenced in relation to dental and craniofacial implants. There is a dearth of data, however, regarding BAHA implant systems in patients with previously irradiated implant sites. We sought, therefore, to investigate implant stability and survival in such patients. Patients were identified retrospectively from our electronic BAHA database. Hospital records were reviewed for demographics; operative technique; complications; and details regarding previous irradiation. Implant stability was assessed by resonance frequency analysis (RFA), generating a numerical value-implant stability quotient (ISQ). Extrapolating from dental studies, successfully loaded implants typically have ISQs of ≥60. Readings were, therefore, interpreted with respect to this. Seven patients were identified for inclusion. Mean time between irradiation and implant insertion was 33 months (range 16-72 months), and mean time from implant insertion to RFA measurement was 41 months (range 3-96 months). Operatively, all patients underwent single-stage procedures under local anaesthesia. One patient suffered a Holger's grade 2 skin reaction, while two suffered significant skin flap failure, requiring revision procedures. The implant survival rate was 100 %. All ISQ values were >60, with a mean of 66.9 (95 % confidence interval 63.1-70.6). Our data support sufficient osseointegration of BAHA implant systems in post-irradiated patients, but highlight issues with wound healing. Contemporary soft tissue preservation operative techniques will likely overcome this, facilitating safe and efficacious BAHA insertion in this ever-increasing group of patients.
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Interface Osso-Implante , Auxiliares de Audição , Osseointegração/efeitos da radiação , Falha de Prótese/efeitos da radiação , Radioterapia/efeitos adversos , Interface Osso-Implante/fisiopatologia , Interface Osso-Implante/efeitos da radiação , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/reabilitação , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Cicatrização/efeitos da radiaçãoRESUMO
OBJECTIVES: The aim of this study was to measure the effect of endoscopic stapling of Zenker's diverticulum on the health status of patients. METHODS: We used the Glasgow Benefit Inventory (GBI) tool to ascertain patients' perceived experience. RESULTS: The study demonstrated a positive health impact following endoscopic stapling of the Zenker's diverticulum. The mean total GBI score was +18.9 (95% confidence interval, +/- 11.2). The impact of endoscopic stapling was positive for all three subsets of the GBI. The GBI scores were comparable to those obtained after other common otorhinolaryngological procedures such as tonsillectomy, rhinoplasty, and middle ear surgery. CONCLUSIONS: These data should improve our ability to counsel patients regarding important therapeutic decisions and expectations of surgical outcome.
Assuntos
Nível de Saúde , Grampeamento Cirúrgico/métodos , Divertículo de Zenker/cirurgia , Idoso , Idoso de 80 Anos ou mais , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos RetrospectivosRESUMO
Endoscopic stapling of Zenker's diverticulum (ZD) is now established practice in the UK and is routinely performed by the vast majority of otolaryngologists. Both The National Confidential Enquiry into Peri-Operative Deaths and the National Institute for Health and Clinical Excellence recommended that the procedure be undertaken at specialist centres and that each department should audit their respective outcomes. Despite the abundance of review articles, it remains unclear what variables a meaningful audit is required to collate and what gold standards every department in the UK undertaking surgery for ZD should aspire to achieve. The objective was to review the outcomes of endoscopic stapling of Zenker's diverticulum at this institution. In addition, a review of other UK departments was undertaken to formulate minimum clinical standards and recommendations of best practice. Review of patient case notes and a structured search of PubMed were used as materials. Fifteen retrospective case series were identified from the literature search which fulfilled the inclusion criteria. Fifty-one patients were identified from the present audit. When these were added to the review, a total of 585 patients were available for meta-analysis. 540 (92.3%) were successfully stapled. Forty-five (7.7%) procedures were abandoned intra-operatively. The most common reason was difficulty assessing the small pouch. The majority of patients (92%) had resumed oral intake by the second post-operative day. Most patients (87%) were discharged by the second post-operative day. Outcomes were good with over 90% reporting resolved or significantly improved symptoms. Minor complications included dental trauma, transient hoarseness and sore throat causing delayed resumption of oral intake. The overall perforation rate was 4.8%. One death was reported. In conclusion endoscopic stapling of pharyngeal pouch is a safe procedure that is associated with good outcomes and low complication rates. No death has been reported since 2000 in the UK. The data presented in this review represent current clinical standards reported over the past 15 years by UK departments and serve as a useful benchmark for any future audits undertaken.
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Endoscopia Gastrointestinal/métodos , Auditoria Médica/normas , Grampeamento Cirúrgico/métodos , Divertículo de Zenker/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Reino UnidoRESUMO
Autoimmune limbic encephalitis is an increasingly recognised cause of cognitive decline and confusion. The typical presentation is with subacute cognitive decline, behavioural disturbance and seizures. Magnetic resonance imaging may show characteristic changes in the medial temporal regions. The diagnosis is confirmed by identification of elevated voltage-gated potassium channel antibody (VGKC-Ab) titres. It is a highly treatable condition, often responding well to intravenous immunoglobulin or steroids. Recognition of autoimmune limbic encephalitis is sometimes delayed--usually because the diagnosis has not been considered--which can result in long-term neurological consequences.
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Doenças Autoimunes do Sistema Nervoso/diagnóstico , Encefalite Límbica/diagnóstico , Encefalite Límbica/imunologia , Autoanticorpos/análise , Transtornos Cognitivos/imunologia , Diagnóstico Diferencial , Progressão da Doença , Epilepsia Tônico-Clônica/imunologia , Evolução Fatal , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , PrognósticoRESUMO
Non-melanoma skin cancer (NMSC) is among the most common cancers worldwide, with an incidence that continues to rise. Although cutaneous squamous cell carcinoma (cSCC) constitutes only approximately 20% of such cases, it represents the most common cause of NMSC mortality, owing largely to the propensity for development of regional lymph node metastases (LNM), which, when present, carry a dismal prognosis. Whilst overall rates of LNM are low, there are a number of patient and tumour factors that likely confer considerably higher risks, which has led several investigators to propose more proactive elective management of regional nodal basins in selected high-risk cases. Current international guidelines, however, do not recommend any elective treatment or sampling of regional nodal basins in the absence of clinically apparent disease. The purpose of this review is to explore in detail the fundamental issues underlying this controversy, focusing specifically on cSCC of the head and neck (cSCCHN). In particular the rationale for more a proactive elective approach to regional nodal basins, including the evidence-base underlying identification of potentially high-risk factors for development of LNM is discussed, along with oncological outcomes for those patients that do go onto suffer LNM. We also provide contemporary perspectives and evidence for approaches to electively managing regional nodal basins, and offer insight into how these may develop both in the clinical and research arenas.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Cutâneas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Linfonodos , Metástase Linfática , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgiaRESUMO
BACKGROUND: A major objective in the management of human papillomavirus (HPV)-positive squamous cell carcinoma of the head and neck (SCCHN) is to reduce long-term functional ramifications while maintaining oncological outcomes. This study examined the metabolic profile of HPV-positive SCCHN and the potential role of anti-metabolic therapeutics to achieve radiosensitisation as a potential means to de-escalate radiation therapy. METHODS: Three established HPV-positive SCCHN cell lines were studied (UM-SCC-104, UPCI:SCC154, and VU-SCC-147), together with a typical TP53 mutant HPV-negative SCCHN cell line (UM-SCC-81B) for comparison. Metabolic profiling was performed using extracellular flux analysis during specifically designed mitochondrial and glycolytic stress tests. Sensitivity to ionising radiation (IR) was evaluated using clonogenic assays following no treatment, or treatment with: 25 mM 2-deoxy-D-glucose (glycolytic inhibitor) alone; 20 mM metformin (electron transport chain inhibitor) alone; or 25 mM 2-deoxy-D-glucose and 20 mM metformin combined. Expression levels of p53 and reporters of p53 function (MDM2, p53, Phospho-p53 [Ser15], TIGAR and p21 [CDKN1A]) were examined by western blotting. RESULTS: HPV-positive SCCHN cell lines exhibited a diverse metabolic phenotype, displaying robust mitochondrial and glycolytic reserve capacities. This metabolic profile, in turn, correlated with IR response following administration of anti-metabolic agents, in that both 2-deoxy-D-glucose and metformin were required to significantly potentiate the effects of IR in these cell lines. CONCLUSIONS: In contrast to our recently published data on HPV-negative SCCHN cells, which display relative glycolytic dependence, HPV-positive SCCHN cells can only be sensitised to IR using a complex anti-metabolic approach targeting both mitochondrial respiration and glycolysis, reflecting their metabolically diverse phenotype. Notionally, this may provide an attractive platform for treatment de-intensification in the clinical setting by facilitating IR dose reduction to minimise the impact of treatment on long-term function.
RESUMO
Patients with mutated TP53 have been identified as having comparatively poor outcomes compared to those retaining wild-type p53 in many cancers, including squamous cell carcinomas of the head and neck (SCCHN). We have examined the role of p53 in regulation of metabolism in SCCHN cells and find that loss of p53 function determines the Warburg effect in these cells. Moreover, this metabolic adaptation to loss of p53 function creates an Achilles' heel for tumour cells that can be exploited for potential therapeutic benefit. Specifically, cells lacking normal wild-type p53 function, whether through mutation or RNAi-mediated downregulation, display a lack of metabolic flexibility, becoming more dependent on glycolysis and losing the ability to increase energy production from oxidative phosphorylation. Thus, cells that have compromised p53 function can be sensitised to ionizing radiation by pre-treatment with a glycolytic inhibitor. These results demonstrate the deterministic role of p53 in regulating energy metabolism and provide proof of principle evidence for an opportunity for patient stratification based on p53 status that can be exploited therapeutically using current standard of care treatment with ionising radiation.
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Metabolismo Energético , Neoplasias de Cabeça e Pescoço/genética , Mutação , Proteína Supressora de Tumor p53/genética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/efeitos da radiação , Glicólise/efeitos dos fármacos , Glicólise/efeitos da radiação , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Fenótipo , Radioterapia , Espécies Reativas de Oxigênio/metabolismoRESUMO
INTRODUCTION: Data regarding regionally metastatic cutaneous squamous cell carcinoma of the head and neck (cSCCHN) is limited and derived almost exclusively from Australian and United States (US) institutions. We report the first United Kingdom perspective, with the aims of benchmarking survival outcomes and identifying clinically relevant prognosticators. MATERIALS AND METHODS: Ninety-one patients with regionally recurrent cSCCHN treated with curative intent over a ten-year period (2009-2018) were studied retrospectively. Time-to-event analyses were used to estimate oncological outcomes, and log-rank statistics and Cox proportional hazards models used to examine potential prognosticators. Receiver operating characteristics were also used to analyse the influence of nodal disease burden. RESULTS: Parotid involvement (with or without neck involvement) was most common (79.2%), and time to recurrence in those with parotid disease alone significantly shorter than for any other disease distribution (p = 0.034). Respective five-year overall, disease-specific, and disease-free survival estimates were 43.8%, 63.8%, and 36.2%. Extracapsular spread (ECS) portended reduced DFS and DSS (p = 0.012 and p = 0.005 respectively). Increasing nodal burden (≥4 involved nodes) also reduced DSS (p = 0.020), while parotid disease alone predicted more favourable DSS (p = 0.008). ECS and isolated parotid involvement remained significant on multi-variate analysis (p = 0.014 and p = 0.028 respectively). CONCLUSIONS: Oncological outcomes were unfavourable but broadly consistent with previous reports, notionally lending support to a more proactive approach in managing the clinically node negative neck/parotid in selected high-risk cases. Our data also support distinct parotid classification and consideration of involved lymph node number in future staging systems.
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Extensão Extranodal/patologia , Linfonodos/patologia , Esvaziamento Cervical , Recidiva Local de Neoplasia/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos , Radioterapia Adjuvante , Neoplasias Cutâneas/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pescoço , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Região Parotídea , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Reino UnidoRESUMO
INTRODUCTION: We describe the 5-year oncological and functional outcomes of transoral laser microsurgery, neck dissection (TLM + ND) and adjuvant radiotherapy (PORT) used to treat patients with oropharyngeal carcinoma. The effectiveness of external carotid artery (ECA) ligation in reducing post-operative bleeding, and fibrin glue following ND in reducing wound drainage and length of hospital stay is reported. MATERIALS AND METHODS: This retrospective case review of consecutive patients undergoing TLM between 2006 and 2017 used the Kaplan-Meier Estimator and Log-Rank Test for univariate, time-to-event analyses, and Cox-Proportionate Hazard modelling for multivariate analysis. RESULTS: 264 consecutive patients were included. Mean follow-up was 49.4 months. 219 (82.9%) patients received PORT. Five-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 74.9%, 73.7%, and 86.2%, respectively. Five-year locoregional control was 89.4%. 65.5% of cases were Human papillomavirus associated (HPV+), for whom OS, DFS and DSS was 85.6%, 84.7% and 92.7%, respectively, and demonstrated significantly higher OS (hazard ratio (HR) 0.28, CI 0.16-0.49, p < 0.0001), DFS (HR 0.28, CI 0.17-0.47, p < 0.0001) and DSS (HR 0.2, CI 0.09-0.44, <0.001). Post-operative oropharyngeal bleeding occurred in 23 patients (8.7%), of which 5 were major/severe, in patients without ECA ligation. Fibrin glue significantly reduced neck drain output (p < 0.001), and length of hospital stay (p < 0.001). One-year gastrostomy dependence rate was 2.3%. CONCLUSIONS: TLM + ND + PORT results in favourable 5-year survival and locoregional control rates, and low feeding tube dependency rates. ECA ligation and fibrin glue appear to reduce major post-operative haemorrhage, wound drainage and length of hospital stay.
Assuntos
Transtornos de Deglutição/epidemiologia , Terapia a Laser/métodos , Microcirurgia/métodos , Esvaziamento Cervical/métodos , Neoplasias Orofaríngeas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Radioterapia Adjuvante , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Artéria Carótida Externa/cirurgia , Deglutição , Transtornos de Deglutição/terapia , Intervalo Livre de Doença , Feminino , Adesivo Tecidual de Fibrina/uso terapêutico , Gastrostomia , Humanos , Tempo de Internação/estatística & dados numéricos , Ligadura , Masculino , Boca , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus , Complicações Pós-Operatórias/terapia , Hemorragia Pós-Operatória/prevenção & controle , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida , Adesivos Teciduais/uso terapêutico , Resultado do Tratamento , Técnicas de Fechamento de FerimentosRESUMO
Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD8+CD161+ T cell clusters were significantly lower in colonized than in non-colonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide-specific and total plasmablasts in blood. Moreover, increased responses of blood mucosal associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.
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Imunidade Adaptativa , Imunidade Inata , Imunidade nas Mucosas , Mucosa Nasal , Infecções Pneumocócicas , Streptococcus pneumoniae/imunologia , Adulto , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Feminino , Humanos , Masculino , Mucosa Nasal/imunologia , Mucosa Nasal/microbiologia , Mucosa Nasal/patologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/patologiaRESUMO
There is a pressing need to identify ways of sensitising squamous cell carcinomas of the head and neck (SCCHN) to the effects of current treatments, both from oncological and functional perspectives. Alteration to cellular metabolism is now widely considered a hallmark of the cancer phenotype; presents a potentially attractive therapeutic target in this regard; and as such has received renewed research interest in recent years. However, whilst metabolic disruption may occur to some degree in all tumours, there is undoubtedly heterogeneity and detailed study of individual tumour types is paramount if effective therapeutic strategies targeting metabolism are to be developed and effectively deployed. In this review we outline current understanding of altered tumour metabolism and how these adaptations promote tumorigenesis generally. We relate this specifically to SCCHN by focusing on several recent key studies specific to SCCHN, and by discussing the role TP53 mutation may play in this metabolic switch, given the fundamental role of this oncogenic event in SCCHN tumorigenesis. Finally, we also offer insight into the potential therapeutic implications this may have in the clinical setting and make recommendations for future study.
Assuntos
Genes p53 , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Mutação , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
BACKGROUND: Alternative splicing of the vascular endothelial growth factor (VEGF) gene results in a family of antiangiogenic isoforms (VEGFxxx b), not yet investigated in squamous cell carcinoma of the head and neck (SCCHN). We examined, therefore, the prognostic value of the relative expression of VEGF isoforms in SCCHN. METHODS: A tissue microarray comprising 187 SCCHNs was studied by immunohistochemistry with total VEGF (panVEGF) and VEGFxxx b-specific antibodies, and scored by 2 assessors for intensity and proportion. Scores were combined and expression ratios calculated. RESULTS: No meaningful significant differences were observed between panVEGF, VEGFxxx b, or expression ratio, and presence of lymphatic metastasis, or overall survival. This held true when tumor subsites were analyzed independently and when human papillomavirus (HPV) was accounted for in the oropharyngeal subgroup. CONCLUSION: Differential VEGF isoform expression is not a reliable prognostic biomarker for either the clinically node negative/pathologically node-positive neck or overall survival in pharyngeal and laryngeal SCCHNs.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Processamento Alternativo , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Isoformas de Proteínas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Análise Serial de TecidosRESUMO
BACKGROUND: The contemporary treatment of oropharyngeal squamous cell carcinoma (SCC) is an area of debate. We report outcomes of a minimally invasive approach involving transoral laser microsurgery (TLM). METHODS: A consecutive series of patients (n = 153) undergoing primary TLM for oropharyngeal SCC from 2006 to 2013 was studied. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry and high-risk HPV DNA in situ hybridization. Survival analyses were evaluated using Kaplan-Meier statistics. RESULTS: Tumor subsites included tonsil (n = 94; 61.5%), tongue base (n = 38; 24.8%), and soft palate (n = 21; 13.7%), with the majority being American Joint Committee on Cancer (AJCC) stage III/IVa (n = 124; 81.0%) and HPV-positive (n = 101; 66.0%). Three-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 84.5%, 91.7%, and 78.2%, respectively. HPV-positivity portended favorable oncologic outcomes. One-year gastrostomy tube (G-tube) dependency was 1.3%. CONCLUSION: To the best of our knowledge, this is the largest single-center TLM oropharyngeal SCC series to date. Our data suggest that TLM +/- postoperative radiotherapy (PORT) results in at least as good oncologic outcomes as chemoradiotherapy (CRT), while conferring swallowing function advantages. © 2016 Wiley Periodicals, Inc. Head Neck , 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38:1263-1270, 2016.