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1.
Am J Respir Crit Care Med ; 210(1): 63-76, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38626355

RESUMEN

Rationale: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia, and primary immunodeficiency disorders), but most cases remain idiopathic. Objectives: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. Methods: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived cells, cell cultures, and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. Measurements and Main Results: We identified biallelic pathogenic variants in WAP four-disulfide core domain 2 (WFDC2) in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and, thus, secretion of mature WFDC2. Conclusions: WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis.


Asunto(s)
Bronquiectasia , Pólipos Nasales , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Bronquiectasia/genética , Bronquiectasia/fisiopatología , Pólipos Nasales/genética , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP
2.
Eur J Neurol ; 29(4): 1165-1173, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34862828

RESUMEN

BACKGROUND AND PURPOSE: Idiopathic inflammatory myopathy (IIM) can present with dysphagia as a leading or only symptom. In such cases, diagnostic evaluation may be difficult, especially if serological and electromyographical findings are unsuspicious. In this observational study we propose and evaluate a diagnostic algorithm to identify IIM as a cause of unexplained dysphagia. METHODS: Over a period of 4 years, patients with unexplained dysphagia were offered diagnostic evaluation according to a specific algorithm: The pattern of dysphagia was characterized by instrumental assessment (swallowing endoscopy, videofluoroscopy, high-resolution manometry). Patients with an IIM-compatible dysphagia pattern were subjected to further IIM-focused diagnostic procedures, including whole-body muscle magnetic resonance imaging, electromyography, creatine kinase blood level, IIM antibody panel and, as a final diagnostic step, muscle biopsy. Muscle biopsies were taken from affected muscles. In cases where no other muscles showed abnormalities, the cricopharyngeal muscle was targeted. RESULTS: Seventy-two patients presented with IIM-compatible dysphagia as a leading or only symptom. As a result of the specific diagnostic approach, 19 of these patients were diagnosed with IIM according to the European League Against Rheumatism (EULAR) criteria. Eighteen patients received immunomodulatory therapy as a result of the diagnosis. Of 10 patients with follow-up swallowing examination, dysphagia improved in three patients after therapy, while it remained at least stable in six patients. CONCLUSIONS: Idiopathic inflammatory myopathy constitutes a potentially treatable etiology in patients with unexplained dysphagia. The diagnostic algorithm presented in this study helps to identify patients with an IIM-compatible dysphagia pattern and to assign those patients for further IIM-focused diagnostic and therapeutic procedures.


Asunto(s)
Trastornos de Deglución , Miositis , Algoritmos , Deglución , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Humanos , Imagen por Resonancia Magnética , Miositis/diagnóstico , Miositis/diagnóstico por imagen , Estudios Retrospectivos
3.
Artículo en Inglés | MEDLINE | ID: mdl-34464957

RESUMEN

BACKGROUND: European health-care systems are faced with a backlog of surgical procedures following the suspension of routine surgery during the COVID-19 crisis. Routine rhinology surgery under general anaesthetic (GA) is now faced with significant challenges which include limited theatre capacity, the negative ramifications of surgical prioritization, reduced patient throughput in secondary care, and additional personal protective equipment requirements. Delayed surgery in rhinology, particularly with regards to chronic rhinosinusitis, has previously been shown to have poorer surgical outcomes, a detrimental effect on quality of life and long-term negative health socio-economic effects. Awake rhinology surgery under local anaesthetic (LA) provides an ideal alternative to GA. It provides a means of operating on patients in a setting alternative to currently oversubscribed main theatres, by utilizing satellite facilities, while ensuring identical surgical outcomes for patients who may otherwise have been forced to wait a long time for their procedure. It also confers additional benefits in terms of shorter recovery time and hospital stay for patients. OBJECTIVES: We have developed a set of recommendations that are intended to help support clinicians and managers to better adopt LA rhinology protocols and minimize the risk to the patient and health-care professionals involved. METHODOLOGY: International roundtable forums were conducted and supplemented by individual interviews. The international board consisted of 12 rhinologists experienced in awake rhinology surgery. Feedback was analysed and shared to develop a consensus of best practice. RECOMMENDATIONS: Local and national guidelines need to be adhered to with specific focus on patient and clinician safety. When performing awake rhinology procedures in the COVID-19 recovery process, consider implementing specific safety measures and workflow practices to safeguard patients and staff and minimize the risk of infection. CONCLUSION: Awake surgery potentially provides quicker access to routine rhinology surgery in the post-COVID-19 recovery phase, ensuring patients are treated in a timely matter, thereby avoiding higher downstream costs, and improving outcomes.


Asunto(s)
COVID-19 , Procedimientos Quirúrgicos Otorrinolaringológicos , Europa (Continente) , Humanos , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Pandemias/prevención & control , Rinitis/cirugía , Sinusitis/cirugía , Vigilia
4.
Eur Arch Otorhinolaryngol ; 278(4): 1247-1255, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32897443

RESUMEN

PURPOSE: SARS-CoV-2 is detected on the mucosa of the upper airways to a high degree. In the course of the COVID-19 pandemic, otorhinolaryngologists (ORL) are assumed to be at high risk due to close contact with the mucosa of the upper airways. No data are yet available providing evidence that ORLs have an increased risk of infection. METHODS: German ORLs were invited via e-mail through the German Society of ORL, Head and Neck Surgery and the German ENT Association to participate in a web-based survey about infection with SARS-CoV-2 and development of COVID-19. Data of infections and concomitant parameters in German ORLs were collected and compared to the total number of infections in Germany. RESULTS: Out of 6383 German ORLs, 970 (15%) participated. 54 ORLs reported testing positive for SARS-CoV-2. Compared to the total population of Germany, ORLs have a relative risk of 3.67 (95% CI 2.82; 4.79) of contracting SARS-CoV-2. Domestic quarantine was conducted in 96.3% of cases. Two individuals were admitted to hospital without intensive care. No casualties were reported. In 31 cases, the source of infection was not identifiable whereas 23 had a clear medical aetiology: infected patients: n = 5, 9.26%; medical staff: n = 13, 14.1%. 9.26% (n = 5) of the identified cases were related to contact to infected family members (n = 3), closer neighbourhood (n = 1) or general public (n = 1). There was no identified increased risk of infection due to performing surgery. CONCLUSION: German ORLs have an almost 3.7-fold risk of contracting SARS-CoV-2 compared to the population baseline level. Appropriate protection appears to be necessary for this occupational group.


Asunto(s)
COVID-19 , Internet , Salud Laboral , Otolaringología , Médicos , SARS-CoV-2 , Alemania/epidemiología , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Transmisión de Enfermedad Infecciosa de Profesional a Paciente , Pandemias , Equipo de Protección Personal
5.
HNO ; 69(8): 658-665, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34086058

RESUMEN

PURPOSE: The SARS-CoV­2 pandemic has affected the health and practice of otorhinolaryngologists (ORLs) for over 1 year. Follow-up data of a national survey with German ORLs were evaluated regarding differences between the two waves of the pandemic. METHODS: As in the initial survey, German ORLs were addressed via e­mail through the German Society of ORL, Head and Neck Surgery and the German ENT Association. All ORLs afflicted with SARS-CoV­2 were invited to participate in a web-based survey. General data on infections and concomitant parameters were evaluated. RESULTS: Since the start of the pandemic, 129 ORLs reported testing positive for SARS-CoV­2 in Germany. The ORLs infected during the first wave had a relative risk (RR) of 4.07 (95% CI: 3.20; 5.19) of contracting SARS-CoV­2. During the second wave, the RR decreased to 0.35 (95% CI: 0.28; 0.45). The availability of personal protective equipment (PPE) increased from the first to the second wave along with an increased perception of protection in the professional environment. The source of infection shifted from infections via medical staff during the first wave to patients and household exposure during the second wave. Regular medical practice was resumed by clinicians and general practitioners in the second wave. Nevertheless, a proportionally lower infection rate was observed compared with the German population as a whole. CONCLUSION: The data reflect a unique long-term survey of ORLs during the pandemic. Differences in the source of infection were seen between the first and second wave, confirming the need for appropriate PPE for medical professionals working in high-risk environments. Further strategies to reduce the risk of infection include consistent testing for SARS-CoV­2 in healthcare professionals, patients, and the general public as well as vaccination of high-risk medical groups.


Asunto(s)
COVID-19 , SARS-CoV-2 , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Internet
6.
Laryngorhinootologie ; 98(S 01): S129-S172, 2019 Mar.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-31096297

RESUMEN

Telemedicine is a generic term summarizing all communication techniques assisting to provide medical services over distance. This rapidly developing medical area provides especially for the field of otorhinolaryngology with its high dependency on endoscopy and microcopy vaulable options. For clinical examination of ear, nose, throat and larynx, but also for postoperative care and surveillance of head and neck tumor patients data exist using the telemedical approach. Furthermore, audiological telemedical measurements even after Cochlear implantation are deemed feasible. While first data indicate interesting approaches, they also demonstrate problems, if a telemedical approach is used without proper preparation. Especially the observers at the remote location of the patients and their training are highly important in this regard. This review summarizes the current state of science of this rapidly changing are of research and clinical care.


Asunto(s)
Otolaringología , Telemedicina , Humanos
7.
Am J Respir Cell Mol Biol ; 58(4): 482-491, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29111771

RESUMEN

Exposure of cultured human airway epithelial model cells (16HBE14o-, S9) to Staphylococcus aureus α-toxin (hemolysin A, Hla) induces changes in cell morphology and cell layer integrity that are due to the inability of the cells to maintain stable cell-cell or focal contacts and to properly organize their actin cytoskeletons. The aim of this study was to identify Hla-activated signaling pathways involved in regulating the phosphorylation level of the actin-depolymerizing factor cofilin. We used recombinant wild-type hemolysin A (rHla) and a variant of Hla (rHla-H35L) that is unable to form functional transmembrane pores to treat immortalized human airway epithelial cells (16HBE14o-, S9) as well as freshly isolated human nasal tissue. Our results indicate that rHla-mediated changes in cofilin phosphorylation require the formation of functional Hla pores in the host cell membrane. Formation of functional transmembrane pores induced hypophosphorylation of cofilin at Ser3, which was mediated by rHla-induced attenuation of p21-activated protein kinase and LIM kinase activities. Because dephosphorylation of pSer3-cofilin results in activation of this actin-depolymerizing factor, treatment of cells with rHla resulted in loss of actin stress fibers from the cells and destabilization of cell shape followed by the appearance of paracellular gaps in the cell layers. Activation of protein kinase A or activation of small GTPases (Rho, Rac, Cdc42) do not seem to be involved in this response.


Asunto(s)
Citoesqueleto de Actina/efectos de los fármacos , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Toxinas Bacterianas/farmacología , Células Epiteliales/efectos de los fármacos , Proteínas Hemolisinas/farmacología , Mucosa Respiratoria/efectos de los fármacos , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/patología , Línea Celular , Forma de la Célula/efectos de los fármacos , Cofilina 1/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/patología , Humanos , Quinasas Lim/metabolismo , Fosforilación , Proteínas Recombinantes/farmacología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patología , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Quinasas p21 Activadas/metabolismo
8.
HNO ; 66(6): 447-454, 2018 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-29797020

RESUMEN

Only about 8% of head and neck tumors affect the midface. This anatomical area is characterized by an enormous number of functionally important structures, and it is frequently only possible to achieve small resection margin distances. To avoid complications and unfavorable results, a dedicated preparation of both patient and surgeon is warranted. This review aims to provide encouragement for the postgraduate training of interested ENT specialists. Following the clinical course and based on recent literature, strategies to avoid complications of tumor surgery to the midface are given.


Asunto(s)
Cara , Neoplasias de Cabeza y Cuello , Cara/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Complicaciones Posoperatorias
9.
Laryngorhinootologie ; 97(S 01): S279-S311, 2018 Mar.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-29905360

RESUMEN

The microbiome is defined as the total of cellular microorganisms of baczerial, viral or e. g., parasite origin living on the surface of a body. Within the anatomical areas of otorhinolaryngology, a significant divergence and variance can be demonstrated. For ear, nose, throat, larynx and cutis different interactions of microbiome and common factors like age, diet and live style factors (e. g., smoking) have been detected in recent years. Besides, new insights hint at a passible pathognomic role of the microbiome towards diseases in the ENT area. This review article resumes the present findings of this rapidly devloping scientific area.


Asunto(s)
Microbiota , Enfermedades Otorrinolaringológicas , Oído/microbiología , Femenino , Humanos , Masculino , Nariz/microbiología , Otolaringología/tendencias , Enfermedades Otorrinolaringológicas/fisiopatología , Enfermedades Otorrinolaringológicas/terapia , Faringe/microbiología
11.
Am J Respir Cell Mol Biol ; 52(1): 14-24, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24918472

RESUMEN

Treatment of primary or immortalized human airway epithelial cells (16HBE14o-, S9) or alveolar cancer cells (A549) with recombinant hemolysin A (rHla), a major virulence-associated factor of Staphylococcus aureus, induces alterations in cell shape and formation of paracellular gaps in the cell layer. Semiquantitative Western blotting using extracts of freshly isolated airway tissue (nasal epithelium) or 16HBE14o- model cells revealed that phosphorylation levels of focal adhesion kinase (Fak) and paxillin were altered upon treatment of tissue or cells with rHla. Immune fluorescence analyses showed that rHla treatment of 16HBE14o- cells results in losses of vinculin and paxillin from focal contacts and a net reduction in the number of focal contacts. The actin cytoskeleton was strongly remodeled. We concluded that treatment of cells with rHla activates Fak signaling, which accelerates focal contact turnover and prevents newly formed focal contacts (focal complexes) from maturation to focal adhesions. The inability of rHla-treated cells to form stable focal adhesions may be one factor that contributes to gap formation in the cell layer. In vivo, such changes may disturb the defensive barrier function of the airway epithelium and may facilitate lung infections by S. aureus.


Asunto(s)
Células Epiteliales/metabolismo , Matriz Extracelular/metabolismo , Neumonía Estafilocócica/metabolismo , Mucosa Respiratoria/metabolismo , Staphylococcus aureus/metabolismo , Toxinas Bacterianas/genética , Adhesión Celular/genética , Línea Celular , Células Epiteliales/patología , Matriz Extracelular/genética , Femenino , Quinasa 1 de Adhesión Focal/genética , Quinasa 1 de Adhesión Focal/metabolismo , Adhesiones Focales/genética , Adhesiones Focales/metabolismo , Adhesiones Focales/patología , Proteínas Hemolisinas/genética , Humanos , Masculino , Paxillin/genética , Paxillin/metabolismo , Fosforilación/genética , Neumonía Estafilocócica/genética , Neumonía Estafilocócica/patología , Mucosa Respiratoria/patología , Transducción de Señal/genética , Staphylococcus aureus/genética , Vinculina/genética , Vinculina/metabolismo
12.
Otol Neurotol ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39143671

RESUMEN

OBJECTIVES: The aim is to investigate the influence of the anatomy-based fitting (ABF) in cochlear implants (CI) on the perception of specific musical features. DESIGN: The Montreal Battery of Evaluation of Amusia (MBEA) test battery was performed with a collective of 16 CI users with and without an anatomy-based fitting and 9 normal hearing subjects. The insertion angles of the intracochlear electrode arrays were calculated using Otoplan® (MED-EL, Innsbruck, Austria) software. RESULTS: CI users with an anatomy-based fitting achieve better results in the MBEA in all categories, especially in rhythm, meter, and memory. There is no effect of insertion depth alone on the ability to perceive musical features, even after anatomy-based fitting. CONCLUSIONS: The results of the CI users in comparison to normal hearing people confirm previous studies. Apart from better speech understanding in CI users, which has been demonstrated in other studies, the anatomy-based fitting also contributes to a better perception of musical features. Currently, there are no comparable studies on this relationship. Investigations with further parameters with the help of the MBEA are pending. SIGNIFICANCE: Our results show that anatomy-based fitting of cochlear implants significantly improves the perception of specific musical attributes and thus leads to an increased enjoyment of music.

13.
Otol Neurotol ; 45(3): e214-e220, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38238925

RESUMEN

HYPOTHESIS: The insertion angle of the electrode array has an influence on the perception of different musical features. BACKGROUND: A deeper insertion of the electrodes is associated with a greater coverage of the cochlea with possible stimulus locations. This could lead to an improved or extended perception of pitches and pitch changes as well as to a better perception of contours in musical pieces. METHODS: A Montreal Battery of Evaluation of Amusia test battery was conducted with a collective of 19 cochlear implant (CI) users and 9 normal-hearing subjects. For the CI users, the insertion angles of the intracochlear electrode arrays were calculated using Otoplan software. RESULTS: Compared with normal-hearing users, CI users performed worse in the detection of melodic features of music. CI users performed better with temporal features than with melodic features. An influence of the insertion depth of the electrodes on the results of the Montreal Battery of Evaluation of Amusia could be proven neither for Cochlear nor for MED-EL CI users. CONCLUSION: Deeper insertion of electrode arrays may only better approximate the spatial-frequency map. Alone, it does not have an effect on better detection and identification of pitch and tonality and, consequently, better perception of musical attributes. Anatomy-based calculation of electrode locations and matching to characteristic frequencies will be sought in subsequent studies.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Música , Humanos , Percepción de la Altura Tonal , Implantación Coclear/métodos , Cóclea
14.
Allergol Select ; 8: 26-39, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38549814

RESUMEN

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

15.
Laryngoscope ; 133(7): 1576-1583, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36222438

RESUMEN

BACKGROUND: ELOM-080 is a phytomedicine approved for the treatment of acute and chronic inflammatory diseases of the respiratory tract, sinusitis, and bronchitis in particular. This prospective, randomized, placebo-controlled, double-blind clinical trial was conducted to assess efficacy and safety of ELOM-080 in the treatment of acute viral rhinosinusitis (AVRS). METHODS: Patients with AVRS received oral treatment (4 × 1 capsule per day) with either ELOM-080 or matching placebo. Primary endpoints were the change in major symptom score (MSS) after 7 and 14 days of treatment assessed by the investigator (MSSINV ). Secondary endpoints were changes in MSS assessed by the patients (MSSPAT ), olfactory function (12-item Sniffin' Sticks), 20-Item Sino-Nasal Outcome Test (SNOT-20 GAV; German adapted version), influence of treatment on viral load, and safety. RESULTS: Four hundred and sixty-three patients were randomized. At day 4, subjective burden of disease (MSS) was significantly ameliorated compared to placebo (p = 0.012). During the first treatment week MSS scores improved about 1 day earlier, and 3 days earlier in the second week. Effect with ELOM-080 on mean MSSINV was statistically significantly superior to placebo at visit 3 (p = 0.016) and visit 4 (p = 0.014). In chemosensory testing identification scores improved comparably in both treatments. The improvement of the SNOT-20 GAV was more pronounced in ELOM-080 patients. Treatment with ELOM-080 indicated a potential for decreasing viral load. Both treatments were well tolerated. CONCLUSION: ELOM-080 improves the burden of AVRS significantly in comparison to placebo, remission of symptoms occurred 3 days earlier. The results confirm the efficacy and safety of ELOM-080 for treatment of AVRS. LEVEL OF EVIDENCE: 1 Laryngoscope, 133:1576-1583, 2023.


Asunto(s)
Rinitis , Sinusitis , Humanos , Estudios Prospectivos , Rinitis/tratamiento farmacológico , Enfermedad Crónica , Enfermedad Aguda , Sinusitis/tratamiento farmacológico , Resultado del Tratamiento , Método Doble Ciego
17.
Head Neck ; 43(11): 3314-3323, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34337814

RESUMEN

BACKGROUND: Precise risk stratification models are necessary to determine patient selection for deintensifying treatment trials in human papilloma virus (HPV)-associated oropharyngeal squamous cell cancer (HPV+ OPSCC). METHODS: We examined 526 cases with OPSCC treated at our department between 2002 and 2017. Every patient was classified after the 7th and 8th edition UICC staging manual. For HPV+ OPSCC, we calculated a simple risk score with four risk groups based on multivariable Cox regression analysis of clinical and lifestyle parameters (UICC 8th edition stage, tobacco/alcohol abuse, age, gender). RESULTS: Two hundred and thirty-nine patients with OPSCC (45.4%) showed a positive histological HPV status. In comparison to UICC 8th edition stages, our proposed risk model showed a tendency for better stratification between risk strata I/III, I/IV, and II/IV (each p < 0.002) and I/II, II/III, and III/IV (each p < 0.09). CONCLUSION: Age, gender, tobacco, and alcohol abuse should be added to the current UICC staging system in order to improve risk stratification in HPV+ OPSCC.


Asunto(s)
Alphapapillomavirus , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Estadificación de Neoplasias , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/terapia , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello
19.
World Neurosurg ; 143: e391-e399, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32745642

RESUMEN

OBJECTIVE: Surgical resection is the therapy of choice in head and neck paraganglioma but is associated with considerable morbidity. For treatment of inoperable or progressive disease, less aggressive adjuvant options are warranted. This study assessed effectiveness and safety of peptide receptor radionuclide therapy (PRRT) with lutetium-177-DOTATATE for head and neck paraganglioma with emphasis on response assessment. METHODS: A retrospective analysis of 7 patients with head and neck paraganglioma treated with PPRT between May 2014 and October 2016 was performed. Three patients had jugulotympanic paraganglioma, 3 patients had carotid body tumors, and 1 patient had a combination of both. Patients underwent PRRT after discussion in the local tumor board regarding progressive disease, inoperability, or lack of other adjuvant options. All patients underwent 3-5 cycles of PRRT. Treatment response was evaluated by gallium-68-DOTATATE positron emission tomography/computed tomography and contrast-enhanced computed tomography or magnetic resonance imaging. Outcome measures were two-dimensional tumor diameters and total tumor volumes. RESULTS: Median patient age was 60 years (interquartile range: 14-84 years). All patients had stable disease at posttherapy assessment. Decreasing tumor volumes were found in 4 patients. Clinical symptoms improved in 2 patients. No progression or adverse events occurred during a median follow-up of 39 months (interquartile range: 35-47 months). CONCLUSIONS: Somatostatin receptor-targeted therapy using lutetium-177-DOTATATE shows promising effectiveness with a high safety profile. Patients in whom surgical morbidity outweighs oncologic benefit should be informed about PRRT as a treatment option.


Asunto(s)
Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/radioterapia , Octreótido/análogos & derivados , Compuestos Organometálicos/metabolismo , Paraganglioma/metabolismo , Paraganglioma/radioterapia , Receptores de Somatostatina/metabolismo , Adolescente , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Octreótido/administración & dosificación , Octreótido/metabolismo , Compuestos Organometálicos/administración & dosificación , Paraganglioma/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radiofármacos/administración & dosificación , Radiofármacos/metabolismo , Estudios Retrospectivos
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