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1.
Front Cell Dev Biol ; 12: 1337361, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38328551

RESUMO

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration. Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed. Results: Co-expression of CAF markers was frequent but not associated with HPV status. FAPhigh and PDGFRbhigh expression were associated with increased CD8 T-cell infiltration. Low expression of PDGFRb improved patient survival in female patients but not in male patients. We identified PDGFRblow periostinlow α-SMAlow status as an independent predictor of improved survival (hazard ratio 0.377, p = 0.006). Conclusion: These findings elucidate the co-expression of four established CAF markers in OPSCC and underscore their association with T-cell infiltration and patient survival. Future analyses of CAF subgroups in OPSCC may enable the development of individualized therapies.

2.
Eur Arch Otorhinolaryngol ; 281(2): 855-861, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38105362

RESUMO

PURPOSE: We hypothesized that using a 3D-exoscope (3Dex) in microlaryngoscopic phonosurgery is non-inferior to using a standard operating microscope (OM). To compare the above, we utilized a 3Dex and an OM for microlaryngoscopic vocal fold augmentation with autologous fat in patients with glottic insufficiency and compared the procedure itself and the long-term impact of vocal fold augmentation on subjective and objective voice parameters in both groups. METHODS: 36 patients with glottic insufficiency received microlaryngoscopic laryngeal augmentation with autologous fat. A 3Dex was utilized in 24 cases for visualization and compared to twelve cases in which an OM was used. Voice parameters were evaluated over a period of twelve months. RESULTS: Comparison of operation time and voice parameters between the 3Dex and OM groups did not reveal significant differences. Significant improvement of mean voice quality in all parameters excluding roughness was observed at 3 and 6 months followed then by a slight decrease of voice quality parameters between the 6 and 12 months interval in both groups. CONCLUSION: Our findings indicate no difference concerning operation time and outcome between the use of a 3Dex and an OM in phonosurgery. Our results highlight a significant voice improvement after vocal fold augmentation with autologous fat in glottic insufficiency mediated dysphonia. The smaller viewing system, better ergonomics for the primary surgeon and the assistant and a direct view for the entire surgical team make a 3Dex an interesting alternative for visualization in microlaryngoscopic phonosurgery.


Assuntos
Laringoplastia , Paralisia das Pregas Vocais , Voz , Humanos , Paralisia das Pregas Vocais/cirurgia , Resultado do Tratamento , Tecido Adiposo/transplante , Glote/cirurgia , Laringoplastia/métodos , Prega Vocal/cirurgia , Estudos Retrospectivos
3.
BMC Cancer ; 23(1): 1054, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919644

RESUMO

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is the only subgroup of head neck cancer that presents with an increased incidence. Gender-specific studies in other cancer entities have revealed differences in treatment response and prognosis. However, only limited data in OPSCC according to gender and human papillomavirus (HPV) status exist. Therefore, we aimed to investigate sex-specific differences in OPSCC and how these may be distributed in relation to HPV and other risk factors. METHODS: This retrospective, bicentric study included 1629 patients with OPSCC diagnosed between 1992 and 2020. We formed subgroups based on TNM status, American Joint Cancer Committee 8th edition (AJCC8), HPV status, treatment modality (surgery (± radio(chemo)therapy (RCT) vs. definitive RCT) and patient-related risk factors and investigated gender differences and their impact on patients survival via descriptive-,uni- and multivariate analysis. RESULTS: With the exception of alcohol abuse, no significant differences were found in risk factors between men and women. Females presented with better OS than males in the subgroup T1-2, N + , independent of risk factors (p = 0.008). Males demonstrated significant stratification through all AJCC8 stages (all p < 0.050). In contrast, women were lacking significance between stage II and III (p = 0.992). With regard to therapy (surgery (± R(C)T) - vs. definitive RCT) women treated with surgery had better OS than men in the whole cohort (p = 0.008). Similar results were detected in the HPV-negative OPSCC sub-cohort (p = 0.042) and in high-risk groups (AJCC8 stage III and IV with M0, p = 0.003). CONCLUSION: Sex-specific differences in OPSCC represent a health disparity, particularly according to staging and treatment, which need to be addressed in future studies.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estudos de Coortes , Neoplasias Orofaríngeas/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias de Cabeça e Pescoço/patologia , Prognóstico , Papillomavirus Humano , Papillomaviridae
4.
Open Res Eur ; 2: 73, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37645269

RESUMO

With the increasing electrical energy demands in aviation propulsion systems, the increase in the onboard generators' power density is inevitable. During the flight, forces coming from the gearbox or gyroscopic forces generated by flight manoeuvres like take-off and landing can act on the generators' bearings, which can lead to wear and fatigue in the bearings. Utilizing the radial force control concept in the electrical machine can relieve loads from the bearings that not only minimize the bearing losses but also increase bearing life. The objective of the MAGLEV project (Measurement and Analysis of Generator bearing Loads and Efficiency with Validation) is to study, demonstrate, and test a new class of high-speed generators with radial force control. In this paper, design steps of this type of generator and its test rig are presented and the measurement methodology used for radial force control is explained. The concept is developed in an electrical machine and is validated on a test rig by measuring required parameters like shaft displacement, vibrations and bearing temperature. Additionally, the friction moment of each generator's bearings is measured and validated in a separate test rig under comparable conditions to the bearing loads in the generator. Therefore, a novel approach to determine precisely the bearing friction in a radial load unit, rotatably supported by an additional needle bearing is used, which shows a good agreement with the calculated friction. Furthermore, new calculation methods for the operating behavior of cylindrical roller bearings with clearance are presented, which are utilized in the generator test rig.

5.
Cancers (Basel) ; 13(21)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34771428

RESUMO

The two pillars of therapy for oropharyngeal squamous cell carcinoma (OPSCC) are upfront surgery and primary chemoradiotherapy. Substantial regional preferences exist with regard to the selection of treatment. Despite new therapeutic approaches, patient survival remains poor, with an approximate overall survival (OS) rate of 50% at five years. This study was conducted to investigate a potential survival benefit depending on the treatment modality in OPSCC patients. We retrospectively collected data of 853 patients with histologically confirmed OPSCC from the Giessen and Maastricht cancer databases. To identify risk factors affecting survival, a Cox-proportional hazard model was applied to 442 patients with complete data sets. Based on this cohort a matched-pair analysis with 158 patients was performed to compare OS rates of patients treated either with upfront surgery or primary chemoradiation. For the collective cohort, patients treated with upfront surgery had significantly improved OS rates compared to patients treated with primary chemoradiation. In the matched-pair analysis adjusted for patients' T-, N- and HPV-status as well as risk profile, we observed that both treatment approaches offered equivalent OS rates. Our study emphasizes that treatment recommendations should be made whenever possible on the basis of side-effect profiles caused by the therapeutic approach used. To draw further conclusions, results of the ongoing "best of" (NCT2984410) study are eagerly awaited, investigating the functional outcome after treatment of OPSCC patients.

6.
Eur Arch Otorhinolaryngol ; 278(11): 4373-4381, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34226992

RESUMO

PURPOSE: To provide expert opinion and consensus on salvage carbon dioxide transoral laser microsurgery (CO2 TOLMS) for recurrent laryngeal squamous cell carcinoma (LSCC) after (chemo)radiotherapy [(C)RT]. METHODS: Expert members of the European Laryngological Society (ELS) Cancer and Dysplasia Committee were selected to create a dedicated panel on salvage CO2 TOLMS for LSCC. A series of statements regarding the critical aspects of decision-making were drafted, circulated, and modified or excluded in accordance with the Delphi process. RESULTS: The expert panel reached full consensus on 19 statements through a total of three sequential evaluation rounds. These statements were focused on different aspects of salvage CO2 TOLMS, with particular attention on preoperative diagnostic work-up, treatment indications, postoperative management, complications, functional outcomes, and follow-up. CONCLUSION: Management of recurrent LSCC after (C)RT is challenging and is based on the need to find a balance between oncologic and functional outcomes. Salvage CO2 TOLMS is a minimally invasive approach that can be applied to selected patients with strict and careful indications. Herein, a series of statements based on an ELS expert consensus aimed at guiding the main aspects of CO2 TOLMS for LSCC in the salvage setting is presented.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Terapia a Laser , Dióxido de Carbono , Consenso , Glote , Humanos , Neoplasias Laríngeas/cirurgia , Lasers , Microcirurgia , Terapia de Salvação , Resultado do Tratamento
7.
Eur Arch Otorhinolaryngol ; 278(6): 1723-1732, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33058010

RESUMO

PURPOSE OF REVIEW: To give an overview of the current knowledge regarding the diagnosis, treatment, and follow-up of laryngeal dysplasia (LD) and to highlight the contributions of recent literature. The diagnosis of LD largely relies on endoscopic procedures and on histopathology. Diagnostic efficiency of endoscopy may be improved using videolaryngostroboscopy (VLS) and bioendoscopic tools such as Narrow Band Imaging (NBI) or Storz Professional Image Enhancement System (SPIES). Current histological classifications are not powerful enough to clearly predict the risk to carcinoma evolution and technical issues such as sampling error, variation in epithelial thickness and inflammation hamper pathological examination. Almost all dysplasia grading systems are effective in different ways. The 2017 World Health Organization (WHO) system should prove to be an improvement as it is slightly more reproducible and easier for the non-specialist pathologist to apply. To optimize treatment decisions, surgeons should know how their pathologist grades samples and preferably audit their transformation rates locally. Whether carcinoma in situ should be used as part of such classification remains contentious and pathologists should agree with their clinicians whether they find this additional grade useful in treatment decisions. Recently, different studies have defined the possible utility of different biomarkers in risk classification. The main treatment modality for LD is represented by transoral laser microsurgery. Radiotherapy may be indicated in specific circumstances such as multiple recurrence or wide-field lesions. Medical treatment currently does not have a significant role in the management of LD. Follow-up for patients treated with LD is a fundamental part of their care and investigations may be supported by the same techniques used during diagnosis (VLS and NBI/SPIES).


Assuntos
Carcinoma in Situ , Doenças da Laringe , Neoplasias Laríngeas , Seguimentos , Humanos , Doenças da Laringe/diagnóstico , Doenças da Laringe/terapia , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/terapia , Imagem de Banda Estreita , Recidiva Local de Neoplasia
8.
Eur Arch Otorhinolaryngol ; 278(6): 1717-1722, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33051798

RESUMO

PURPOSE OF REVIEW: To give an overview of the current knowledge regarding the aetiology, epidemiology, and classification of laryngeal dysplasia (LD) and to highlight the contributions of recent literature. As most cases of dysplasia occur at the glottic level and data on diagnosis and management are almost exclusively from this location, laryngeal dysplasia in this position paper is taken to be synonymous with dysplasia of the vocal folds. LD has long been recognized as a precursor lesion to laryngeal squamous cell carcinoma (SCC). Tobacco and alcohol consumption are the two single most important etiological factors for the development of LD. There is currently insufficient evidence to support a role of reflux. Although varying levels of human papillomavirus have been identified in LD, its causal role is still uncertain, and there are data suggesting that it may be limited. Dysplasia has a varying presentation including leukoplakia, erythroleukoplakia, mucosal reddening or thickening with exophytic, "tumor-like" alterations. About 50% of leukoplakic lesions will contain some form of dysplasia. It has become clear that the traditionally accepted molecular pathways to cancer, involving accumulated mutations in a specific order, do not apply to LD. Although the molecular nature of the progression of LD to SCC is still unclear, it can be concluded that the risk of malignant transformation does rise with increasing grade of dysplasia, but not predictably so. Consequently, grading systems are inherently troubled by the weak correlation between the degree of the dysplasia and the risk of malignant transformation. The best data on LD grading and outcomes come from the Ljubljana group, forming the basis for the World Health Organization classification published in 2017.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Laringe , Lesões Pré-Cancerosas , Humanos , Hiperplasia , Neoplasias Laríngeas/etiologia , Leucoplasia , Lesões Pré-Cancerosas/etiologia
9.
Eur Arch Otorhinolaryngol ; 278(1): 1-7, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32506145

RESUMO

INTRODUCTION: The novel Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, may need intensive care unit (ICU) admission in up to 12% of all positive cases for massive interstitial pneumonia, with possible long-term endotracheal intubation for mechanical ventilation and subsequent tracheostomy. The most common airway-related complications of such ICU maneuvers are laryngotracheal granulomas, webs, stenosis, malacia and, less commonly, tracheal necrosis with tracheo-esophageal or tracheo-arterial fistulae. MATERIALS AND METHODS: This paper gathers the opinions of experts of the Laryngotracheal Stenosis Committee of the European Laryngological Society, with the aim of alerting the medical community about the possible rise in number of COVID-19-related laryngotracheal stenosis (LTS), and the aspiration of paving the way to a more rationale concentration of these cases within referral specialist airway centers. RESULTS: A range of prevention strategies, diagnostic work-up, and therapeutic approaches are reported and framed within the COVID-19 pandemic context. CONCLUSIONS: One of the most important roles of otolaryngologists when encountering airway-related signs and symptoms in patients with previous ICU hospitalization for COVID-19 is to maintain a high level of suspicion for LTS development, and share it with colleagues and other health care professionals. Such a condition requires specific expertise and should be comprehensively managed in tertiary referral centers.


Assuntos
Manuseio das Vias Aéreas/métodos , COVID-19/terapia , Intubação Intratraqueal/estatística & dados numéricos , Laringoestenose/epidemiologia , Respiração Artificial/efeitos adversos , Estenose Traqueal/epidemiologia , Traqueostomia/estatística & dados numéricos , COVID-19/diagnóstico , Constrição Patológica/etiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/efeitos adversos , Masculino , Otorrinolaringologistas , Otolaringologia , Pandemias , SARS-CoV-2 , Sociedades Médicas , Traqueostomia/efeitos adversos
10.
Acta Otolaryngol ; 140(12): 1032-1035, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32852240

RESUMO

BACKGROUND: Smell and taste disorders occur in COVID-19 with a high prevalence, but little is known about the duration of the symptoms. In particular, studies using validated olfactory tests are very rare to date. AIMS/OBJECTIVES: The aim of this study was to determine the olfactory function of COVID-19 recoveries by a detailed olfactory test. METHODS: 91 patients with PCR-confirmed, past COVID-19 disease were included. Olfactory history was taken using a questionnaire. Olfactory function was evaluated with the sniffin' sticks test, tasting function with taste sprays. RESULTS: 80 patients had experienced sudden olfactory loss during the course of disease and at the time of testing, 33 patients subjectively still had an impaired olfactory sense. Around 8 weeks had passed since the onset of symptoms. 45.1% of the tested individuals were still hyposmic according to the olfactory test while 53.8% showed an olfactory performance within the normal range. Patients' self-assessment correlated poorly with the measured olfactory performance. CONCLUSIONS AND SIGNIFICANCE: Half of the patients with an olfactory loss as a symptom of COVID-19 still have olfactory impairments after two months, although not all of these patients subjectively notice a restriction. Long-term measurements must confirm whether all affected patients will make full recovery.


Assuntos
COVID-19/complicações , Transtornos do Olfato/etiologia , SARS-CoV-2 , Limiar Sensorial/fisiologia , Olfato/fisiologia , Adulto , COVID-19/epidemiologia , COVID-19/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico , Pandemias
11.
Int J Mol Sci ; 21(15)2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32718057

RESUMO

Carcinogenesis of human papillomavirus (HPV)-related (+) oropharyngeal squamous cell carcinoma (OPSCC) differs from HPV-negative (-) OPSCC. HPV-related immune-escape-mechanism could be responsible for the development and progression of HPV+ tumors and an immunophenotype different from HPV- OPSCC is expected. The purpose of this study was to analyze the expression of programmed cell death protein 1 ligand 1 (PD-L1) and its prognostic relevance in relation to CD8+ tumor infiltrating lymphocytes (TILs) and the major histocompatibility complex (MHC) I expression in OPSCC. We quantified PD-L1 expression on tumor cells (TC) and macrophages and MHC I expression in association to CD8+ TILs by immunohistochemistry on tissue microarray derived from 171 HPV+/-OPSCC. HPV-status was determined by p16INK4a immunohistochemistry/HPV-DNA detection. Presence of CD8+ TILs, PD-L1 expression on TC, and a more frequent loss of MHC I in HPV+ compared to HPV- OPSCC was detected. A high amount of CD8+ TILs in the whole cohort and in HPV+ OPSCC and PD-L1 expression on TC in HPV- OPSCC was associated with favorable overall survival. There was a trend for an improved outcome according to PD-L1 expression (macrophages) in HPV+ OPSCC without reaching statistical significance. CD8+ TILs and PD-L1-expression have prognostic impact in OPSCC and might present useful biomarkers for predicting clinical outcome and personalized therapy concepts.


Assuntos
Antígeno B7-H1/imunologia , Biomarcadores Tumorais/imunologia , Linfócitos T CD8-Positivos , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias de Cabeça e Pescoço , Linfócitos do Interstício Tumoral , Proteínas de Neoplasias/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida
12.
Int J Mol Sci ; 22(1)2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33396515

RESUMO

Tumor growth and survival requires a particularly effective immunosuppressant tumor microenvironment (TME) to escape destruction by the immune system. While immunosuppressive checkpoint markers like programmed cell death 1 ligand (PD-L1) are already being targeted in clinical practice, lymphocyte-activation-protein 3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and V-domain Ig suppressor of T cell activation (VISTA) inhibitors are currently under investigation in clinical trials. Reliable findings on the expression status of those immune checkpoint inhibitors on tumor-infiltrating lymphocytes (TILs) in the TME of oropharyngeal squamous cell carcinoma (OPSCC) are lacking. This work aims to describe the expression of LAG-3, TIM-3, and VISTA expression in the TME of OPSCC. We created a tissue microarray of paraffin-embedded tumor tissue of 241 OPSCC. Expression of the immune checkpoint protein LAG-3, TIM-3, and VISTA in OPSCC was evaluated using immunohistochemistry and results were correlated with CD8+ T-cell inflammation and human papillomavirus (HPV)-status. 73 OPSCC stained positive for LAG-3 (31%; HPV+:44%; HPV-:26%, p = 0.006), 122 OPSCC stained positive for TIM-3 (51%; HPV+:70%; HPV-:44%, p < 0.001) and 168 OPSCC (70%; HPV+:75%; HPV-:68%, p = 0.313) for VISTA. CD8+ T-cells were significantly associated with LAG-3, TIM-3 and VISTA expression (p < 0.001, p < 0.001, p = 0.007). Immune checkpoint therapy targeting LAG-3, TIM-3, and/or VISTA could be a promising treatment strategy especially in HPV-related OPSCC. Future clinical trials investigating the efficacy of a checkpoint blockade in consideration of LAG-3, TIM-3, and VISTA expression are required.


Assuntos
Antígenos CD/metabolismo , Antígenos B7/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Orofaríngeas/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Neoplasias Orofaríngeas/imunologia , Neoplasias Orofaríngeas/metabolismo , Prognóstico , Taxa de Sobrevida , Proteína do Gene 3 de Ativação de Linfócitos
13.
Adv Otorhinolaryngol ; 83: 167-175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943472

RESUMO

Recent advances in minimal access surgery have shown promise in the treatment of limited hypopharyngeal lesions. In spite of their functionally excellent results in individual patients, it currently remains unlikely that these approaches will gain a more major universal impact on hypopharyngeal cancer care. In advanced stage hypopharyngeal cancer, the use of the traditional radical surgery, such as laryngo-pharyngectomy, is no longer accepted by many patients. In recent years, most would rather opt for less mutilating treatment, preferring a non-surgical option. Patients, families and medical practitioners frequently ignore or misunderstand the associated mortality and morbidity consequence of such an approach. Although synergy between chemotherapy and radiotherapy enhances the efficacy of the treatment, chemo-radiation as currently used achieves a tumour response in < 80%, with relapses of the tumour during the follow-up period, indicating that surgery is the only effective treatment option as salvage. Advances in molecular research have improved our understanding of oncogenesis, tumour spread and the mechanisms of metastases. Innovative strategies have become available that manipulating tumours or the host to favour conditions receptive for disease eradication. These advances have gone through pre-clinical testing and are currently being used in early clinical trials using approaches such as replacement of defective genes, suicide gene therapy, and immunologic gene therapy. Precision oncology may eventually be able to predict which patients are more likely to respond to specific cancer therapies based on increasingly accurate, high-resolution biomarkers based on molecular diagnostics of individual tumours. Currently concentrating cancer treatment at specialised head and neck cancer institutions is likely to contribute faster and more sustained results at improving patient outcomes for hypopharyngeal cancer care than any individual innovation in surgery, radiation oncology or systemic treatment. Preventative work should continue by governments with the elimination of the preventable risk factors (abusive use of alcohol, tobacco and betel nut chewing) may reduce the incidence of the disease.


Assuntos
Neoplasias Hipofaríngeas/terapia , Biomarcadores Tumorais , Proteína C-Reativa/análise , Terapia Combinada/tendências , Previsões , Humanos , Neoplasias Hipofaríngeas/diagnóstico , Prognóstico , Procedimentos Cirúrgicos Operatórios/tendências
14.
Adv Otorhinolaryngol ; 83: 27-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943503

RESUMO

Patients with hypopharyngeal cancers frequently present at advanced stage and in poor general health status. Their natural history is characterised by diffuse local primary disease, mucosal and submucosal spread, early cervical nodal metastasis, and a relatively high rate of distant spread. By the time of initial diagnosis, some 60% of all hypopharyngeal cancer patients will be with stage IV disease, some 5% will present with distant metastases, and almost 40% will have a significant reduction in performance status. Less than 20% are diagnosed with a localised early stage disease. A long-standing social habit of excess of alcohol and tobacco usage leads to cancerisation and accounts for the multiple, synchronous primary malignant lesions that occur in many hypopharyngeal cancer patients. The natural history of untreated head and neck squamous cell carcinoma has infrequently been documented in the medical literature. However, without understanding the natural history of hypopharyngeal cancer, patient counselling and clinical management are difficult. Less than 20% of untreated patients survive for > 12 months and only a small proportion of patients will survive for more than 2 years after initial diagnosis. The natural course of the disease in patients treated for cure or, at least, for the relief of symptoms, is certainly more favourable than that of those who are not suited for, or not willing to accept the adverse effects of treatment. However, treatment results are still considerably less encouraging than those that are being reported for other sub-sites of the head and neck region. Among all head and neck cancer sites, 5-year age-standardised relative survival is currently the poorest for cancer of the hypopharynx and the highest for larynx cancers, 25 and 59%, respectively. Among the head and neck cancers, only hypopharynx showed a low outcome (25% at 5 years), with survival figures ranging between ≤30 (North Ireland and Italy) and 8% (Bulgaria). Recent studies from the United States indicate that overall 5-year survival rates for hypopharyngeal cancer have improved significantly in recent years, with the average survival being ≥40%.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Neoplasias Hipofaríngeas/mortalidade , Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células Escamosas/terapia , Humanos , Neoplasias Hipofaríngeas/fisiopatologia , Neoplasias Hipofaríngeas/terapia , Taxa de Sobrevida
15.
Adv Otorhinolaryngol ; 83: 148-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943508

RESUMO

Hypopharyngeal cancer patients have a very poor prognosis and limited therapeutic options. Seventy to eighty per cent of all hypopharyngeal cancer patients will require palliative and/or end-of-life care for incurable end-stage disease during the course of their illness. The overall proportion of hypopharyngeal cancer patients not qualifying for initial curative treatment, or requiring palliation and supportive care over time is higher than for any other subsite of the head and neck. Surgery and radiotherapy usually have a very limited role in this setting, while systemic therapy will usually compete with supportive care as the best approach. Advances in medicine and oncological treatments for the management of patients with recurrent head and neck cancer have given physicians the opportunity to prolong life where possible. However, this increase in survival might not be clinically meaningful if patients do not simultaneously experience palliative benefits, such as a reduction in symptoms and an improvement in their overall quality of life (QoL). The optimal outcome of palliative treatment is the control of symptoms with minimal treatment toxicities while improving QoL. It remains unclear if current palliative treatment options are better at improving QoL than the best supportive care. An intervention that results in insufficient or unacceptable functional status to the extent that the patient cannot achieve treatment goals - even in the course of prolonging life - is questionable. When used for palliative care purposes, surgery, chemotherapy and radiotherapy commonly have limited effectiveness in improving QoL. Moreover, if these treatments are not congruent with a patient's end-of-life goals, they could constitute low-value care.


Assuntos
Neoplasias Hipofaríngeas/terapia , Cuidados Paliativos/métodos , Assistência Terminal/métodos , Humanos , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Hipofaríngeas/cirurgia , Imunoterapia , Prognóstico , Qualidade de Vida
16.
Adv Otorhinolaryngol ; 83: 47-53, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943512

RESUMO

Patients with hypopharyngeal cancer are difficult to treat because they typically present with advanced disease, poor general health status and severe nutritional problems. Currently, treatment options for previously untreated and newly diagnosed hypopharyngeal cancer patients include surgery of the primary tumour and lymph nodes metastasis, radiotherapy, systemic medical treatment, including traditional chemotherapy and immunotherapy. Currently, a multimodal treatment approach is preferred using surgery, radiotherapy and systemic therapy with curative intent and best supportive care in patients considered unfit for curative treatment or patients presenting with distant metastatic spread. More detailed topics regarding the choice of treatment include biological and immunological host factors and their use for defining individualised cancer care, integration of novel therapies, integration of patient autonomy into clinical reasoning and dealing with patients' trade-offs between oncological outcome and individual quality of life, local availability of diagnostic therapeutic procedures and volume-outcome relationships for head and neck cancer surgery, radiotherapy and specialised supportive care. They also include considerations regarding potential delay between diagnosis and treatment, and between different treatment modalities within the frame of multimodal therapy. To date only one randomised trial comparing surgical versus non-surgical approaches has been published. Most randomised trials dealing with hypopharyngeal cancer compare different chemo- and radiotherapy regimen, but do not compare with a surgical approach. On the other hand, most studies on the results of surgery are best considered to be of low-quality case series. At the same time, many of the chemotherapy and radiation oncology studies in head and neck cancer include patients with different primary sites, where hypopharyngeal cancer patients when included usually account for a minority of the study population. Therefore, choosing the best treatment for an individual patient with hypopharyngeal cancer relies on personal experience and local expertise of the multidisciplinary team involved in the therapeutic process.


Assuntos
Neoplasias Hipofaríngeas/terapia , Hipofaringe/cirurgia , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Humanos , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Hipofaríngeas/cirurgia , Imunoterapia
17.
Sci Rep ; 8(1): 8453, 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29855499

RESUMO

Walking along a beach one may notice debris being washed ashore from the vast oceans. Then, turning your head up at night you even might noticed a shooting star or a bright spot passing by. Chances are, that you witnessed space debris, endangering future space flight in lower earth orbit. If it was possible to turn cm-sized debris into shooting stars the problem might be averted. Unfortunately, these fragments counting in the 100 thousands are not controllable. To possibly regain control we demonstrate how to exert forces on a free falling debris object from a distance by ablating material with a high energy ns-laser-system. Thrust effects did scale as expected from simulations and led to speed gains above 0.3 m/s per laser pulse in an evacuated micro-gravity environment.

18.
Eur Arch Otorhinolaryngol ; 275(4): 847, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29488005
19.
Laryngoscope ; 128(5): 1075-1082, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28833184

RESUMO

OBJECTIVES/HYPOTHESIS: Consulting of patients with oropharyngeal carcinoma, classified as pT1pN1cM0 and pT2p/cN0cM0, about postoperative radiotherapy is a precarious task as data are lacking. The aim of this study was to evaluate the effects of postoperative radiotherapy for patients with intermediate-stage oropharyngeal carcinoma. STUDY DESIGN: Multicentric retrospective study. METHODS: This analysis was conducted at seven Austrian institutions and included data of patients treated between 2000 and 2012. A total of 81 patients with oropharyngeal squamous cell carcinoma were included, of whom 33 patients received postoperative radiotherapy. p16 status determined by immunohistochemistry was available in 68 patients. RESULTS: Median follow-up was 47.9 months. Postoperative radiotherapy showed no benefits in regard to overall survival (P = .701). In contrast, disease-free survival was significantly shortened in all patients without postoperative radiotherapy (P = .001). When dividing the cohort in dependence of p16, p16-positive patients did not benefit from postoperative radiotherapy regarding overall and disease-free survival (P = .934 and P = .102), whereas p16-negative patients showed improved disease-free survival after postoperative radiotherapy (P = .007). Multivariate analysis showed that outcome of postoperative radiotherapy is dependent on p16 status. CONCLUSIONS: In terms of disease-free survival, patients with p16-negative tumors may benefit from postoperative radiotherapy, whereas survival of p16-positive patients is good regardless of additional treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1075-1082, 2018.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Orofaríngeas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Carcinoma de Células Escamosas/cirurgia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Materials (Basel) ; 11(1)2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29286313

RESUMO

Ablating surfaces with a pulsed laser system in milling processes often leads to surface changes depending on the milling depth. Especially if a constant surface roughness and evenness is essential to the process, structural degradation may advance until the process fails. The process investigated is the generation of precise thrust by laser ablation. Here, it is essential to predict or rather control the evolution of the surfaces roughness. Laser ablative milling with a short pulse laser system in vacuum (≈1 Pa) were performed over depths of several 10 µm documenting the evolution of surface roughness and unevenness with a white light interference microscope. Power spectral density analysis of the generated surface data reveals a strong influence of the crystalline structure of the solid. Furthermore, it was possible to demonstrate that this effect could be suppressed for gold.

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