RESUMEN
BACKGROUND: A parotid abscess (PA) is a complication of an acute bacterial parotitis with a potentially life-threatening course. To date, data on the diagnosis and therapy of PA is sparse and mostly consists of case reports or case series. Therefore, this study aimed at comprehensively analyzing the microbiological spectrum and the therapeutic management in a bi-institutional setting. METHODS: A retrospective clinical chart review was performed to identify all patients surgically treated for PA at two tertiary care centers in Germany. Data on demographics, clinical management and microbiological data including species identification, pathogenicity, type of antibiotic therapy, adjustment of antibiotics, antibiotic sensitivity testing, and smear test results were extracted. Intervention-related variables and etiology were analyzed for their statistical association with outcome variables. RESULTS: Overall, 85 patients were included. Most patients (92.9%) underwent surgical incision. Around half of the patients (45.9%) were treated under local anesthesia. No facial nerve palsy was observed. The most frequently detected pathogens were Streptococci (n = 23), followed by Staphylococcus aureus (n = 6) including one case of methicillin-resistant Staphylococcus aureus. Most patients (68.2%) received an aminopenicillin ± beta-lactamase inhibitor as empiric antibiotic therapy. In 6 cases the antibiotic therapy was modified after receiving the antibiogram. Four patients (5.2%) presented with recurrent PA. Etiology was idiopathic (42.4%), followed by tumorous (12.9%), obstructive, and immunosuppressive (each 11.8%). Patients with a dental focus (p = 0.007) had a longer duration of hospitalization. CONCLUSION: The results show that the surgical therapy of PA under local anesthesia is safe. A dental examination should routinely be performed to rule out a dental focus. Obtaining a microbiological specimen in order to modify antibiotic therapy if necessary and a histopathological specimen to rule out a tumorous etiology is obligate.
Asunto(s)
Absceso , Antibacterianos , Humanos , Masculino , Estudios Retrospectivos , Femenino , Absceso/microbiología , Absceso/terapia , Absceso/cirugía , Absceso/tratamiento farmacológico , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Adulto , Anciano , Alemania , Parotiditis/microbiología , Parotiditis/tratamiento farmacológico , Parotiditis/cirugía , Parotiditis/terapia , Enfermedades de las Parótidas/microbiología , Enfermedades de las Parótidas/cirugía , Enfermedades de las Parótidas/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Adulto Joven , Anciano de 80 o más Años , Resultado del Tratamiento , AdolescenteRESUMEN
The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC. This requires sensitive and specific cfDNA detection as cfDNA levels can be very low. To study the predictive power of pre-diagnostic HPV-cfDNA, archived samples from epidemiological cohorts with limited plasma volume are an important source. To establish a cfDNA detection workflow for low plasma volumes, we compared cfDNA purification methods [MagNA Pure 96 (MP96) and QIAamp ccfDNA/RNA] and digital PCR systems (Biorad QX200 and QIAGEN QIAcuity One). Final assay validation included 65 low-volume plasma samples from oropharyngeal cancer (OPC) patients with defined HPV status stored for 2-9 years. MP96 yielded a 28% higher cfDNA isolation efficiency in comparison to QIAamp. Both digital PCR systems showed comparable analytical sensitivity (6-17 copies for HPV16 and HPV33), but QIAcuity detected both types in the same assay. In the validation set, the assay had 80% sensitivity (n = 28/35) for HPV16 and HPV33 and a specificity of 97% (n = 29/30). In samples with ≥750 µL plasma, the sensitivity was 85% (n = 17/20), while in samples with <750 µL plasma, it was 73% (n = 11/15). Despite the expected drop in sensitivity with decreased plasma volume, the assay is sensitive and highly specific even in low-volume samples and thus suited for studies exploring HPV-cfDNA as an early HPV-OPC detection marker in low-volume archival material.IMPORTANCEHPV-OPC has a favorable prognosis compared to HPV-negative OPC. However, the majority of tumors is diagnosed after regional spread, thus making intensive treatment necessary. This can cause lasting morbidity with a large impact on quality of life. One potential method to decrease treatment-related morbidity is early detection of the cancer. HPV cfDNA has been successfully used for therapy surveillance and has also been detected in pre-diagnostic samples of HPV-OPC patients. These pre-diagnostic samples are only commonly available from biobanks, which usually only have small volumes of blood plasma available. Hence, we have developed a workflow optimized for small-volume archival samples. With this method, a high sensitivity can be achieved despite sample limitations, making it suitable to conduct further large-scale biobank studies of HPV-cfDNA as a prognostic biomarker for HPV-OPC.
Asunto(s)
Ácidos Nucleicos Libres de Células , ADN Viral , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Reacción en Cadena de la Polimerasa , Humanos , ADN Viral/sangre , ADN Viral/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/virología , Ácidos Nucleicos Libres de Células/sangre , Reacción en Cadena de la Polimerasa/métodos , Neoplasias Orofaríngeas/virología , Neoplasias Orofaríngeas/sangre , Neoplasias Orofaríngeas/diagnóstico , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Femenino , Sensibilidad y Especificidad , Masculino , Persona de Mediana Edad , Anciano , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Virus del Papiloma HumanoRESUMEN
PURPOSE: The incidence of salivary duct carcinoma (SDC) seems to be underestimated due to inaccurate classification. Further, the frequency of SDC patients with targeted therapy options according to current guidelines is unclear. Therefore, this study aimed at (a) describing the proportion of SDC among salivary gland carcinoma (SGC) before and after reclassification of cases initially classified as adenocarcinoma, not otherwise specified (ANOS); and (b) quantifying the frequency of SDC patients with targeted therapy options. METHODS: All patients with SDC or ANOS treated in a tertiary care center between 1996 and 2023 were identified. Histopathological diagnosis was verified for patients primarily diagnosed with SDC and reviewed for patients initially diagnosed with ANOS. Clinical data for SDC patients were retrieved from clinical charts. Immunohistochemical (IHC) androgen receptor (AR) and HER2 staining was performed. RESULTS: Among 46 SDC, 34 were primarily diagnosed as SDC and 12 had initially been classified as ANOS. The proportion of SDC among SGC was 12.1% and was rising when comparing the time periods 2000-2015 (7.1-11.5%) versus 2016-2023 (15.4-18.1%). Nuclear AR staining in > 70% of tumor cells was found in 56.8% and HER2 positivity (IHC 3 +) in 36.4% of cases. 70.5% of patients showed AR staining in > 70% of tumor cells and/or HER2 positivity and therefore at least one molecular target. 5-year overall and disease-free survival (DFS) were 62.8% and 41.0%. Multivariate Cox regression revealed positive resection margins (HR = 4.0, p = 0.03) as independent negative predictor for DFS. CONCLUSIONS: The results suggest a rising SDC incidence and show that the extent of the AR and HER2 expression allows for targeted therapy in most SDC cases.
Asunto(s)
Receptor ErbB-2 , Receptores Androgénicos , Conductos Salivales , Neoplasias de las Glándulas Salivales , Centros de Atención Terciaria , Humanos , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/terapia , Receptores Androgénicos/metabolismo , Receptor ErbB-2/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Anciano , Conductos Salivales/patología , Adulto , Estudios Retrospectivos , Carcinoma Ductal/patología , Carcinoma Ductal/metabolismo , Carcinoma Ductal/terapia , Carcinoma Ductal/tratamiento farmacológico , Anciano de 80 o más Años , Terapia Molecular Dirigida , Inmunohistoquímica , Biomarcadores de Tumor/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/terapiaRESUMEN
Due to the association with the causal HPV-16 infection, the oropharyngeal carcinoma spreads into two separate entities depending on HPV-16 positivity. More recent data show a diversified picture of the importance and prevalence of the surrogate parameter p16 (discordance) for a definitive HPV-16 association, which varies worldwide. In the context of prevention options, vaccination is of major and HPV screening of healthy people only of little importance.
Asunto(s)
Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Neoplasias Orofaríngeas/epidemiología , Neoplasias Orofaríngeas/prevención & control , Papillomavirus Humano 16 , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , PrevalenciaRESUMEN
INTRODUCTION: For the diagnosis of Eustachian tube dysfunction (ETD), clinical procedures such as tympanometry, micro-otoscopy, and maneuvers according to Toynbee and Valsalva only allow an indirect assessment for the moment. With a prevalence of up to 5%, the selection of patients with ETD and its subtypes is clinically relevant. Dynamic methods of Eustachian tube function assessment include a hypo/hyperbaric pressure chamber and Estève's tubomanometer (TMM). One method of assessing ETD is the evaluation of Eustachian tube opening pressure (ETOP). MATERIAL AND METHODS: We performed a concordance analysis between pressure chamber and TMM to determine ETOP. For this purpose, we analyzed the measurements of both methods from 28 healthy subjects using Bland-Altman plots, regression according to Passing-Bablok and Lin's concordance correlations coefficient. The maximum tolerated clinical deviation of measured values was set at 10%. RESULTS: A maximum of 53 measurements of ETOP between pressure chamber and TMM were compared. Mean ETOP for TMM was 28.7 hPa, passive opening was 32 hPa, Toynbee maneuver was 28.4 hPa, and Valsalva maneuver was 54.6 hPa. Concordance analysis revealed following results: passive opening versus TMM: Bland-Altman mean difference 3.3 hPa, limits of agreement ±31.8 hPa; Passing-Bablok regression y = 0.67 x + 9.36; Lin's rccc = 0.18. Toynbee versus TMM: Bland-Altman mean difference 0.7 hPa, limits of agreement ±35.8 hPa; Passing-Bablok regression y = 0.47x + 14.03; Lin's rccc = 0.14. Valsalva versus TMM: Bland-Altman mean difference 24.2 hPa, limits of agreement ±117.5 hPa; Passing-Bablok regression y = 0.17x + 25.12; Lin's rccc = 0.18. CONCLUSION: Estève's tubomanometer and pressure chamber measurements of ETOP are not concordant. The two methods cannot be interchanged without reservation.
Asunto(s)
Trompa Auditiva , Presión , Humanos , Trompa Auditiva/fisiopatología , Adulto , Femenino , Masculino , Pruebas de Impedancia Acústica/métodos , Persona de Mediana Edad , Adulto Joven , Maniobra de Valsalva/fisiología , Manometría/métodos , Manometría/instrumentaciónRESUMEN
BACKGROUND: Using Otoplan software, it is possible to measure the cochlea before cochlear implant surgery. Until now, computed tomography (CT) of the cochlea has been necessary for this purpose. The aim of this study was to find out whether measuring the cochlea with magnetic resonance imaging (MRI) using Otoplan is possible with the same accuracy. METHODS: The cochlea of 44 patients of the local cochlear implant centre was measured by Otoplan using high-resolution CT-bone and MRI images, and the determined lengths were compared. RESULTS: No significant difference was found between the cochlear lengths measured, regardless of whether the length measurement was based on a CT or an MRI data set. CONCLUSION: For the determination of cochlear length prior to cochlear implant surgery, MRI images are just as suitable as CT images, therefore CT is not mandatory for length measurement by Otoplan, which could reduce the patient's radiation exposure.
RESUMEN
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.
RESUMEN
OBJECTIVE: Investigating the outcomes of a surgical approach to treat isolated defects of the stapes suprastructure, using a modified total ossicular replacement prosthesis (TORP) prosthesis as a PORP between the footplate and the incus, effectively creating a TORP-PORP configuration. PATIENTS: Eleven patients (mean age, 37.2 years; 36% male and 64% female) between the years 2007 and 2022. INTERVENTIONS: Therapeutic (ossiculoplasty). MAIN OUTCOME MEASURES: Hearing gain (in dB) in air conduction thresholds at 0.5, 1, 2, 3, and 4 kHz, stability of bone conduction, revision rate. RESULTS: Significant improvement in air conduction between the preoperative and the postoperative cohorts (p = 0.002) with a mean postoperative hearing level of 30.00 ± 5.25 dB. The bone conduction remained stable. We encountered no perioperative complications, and there were no revisions surgery. CONCLUSIONS: The described ossiculoplasty procedure is a safe and effective approach to treat isolated defects of the stapes suprastructure.
Asunto(s)
Prótesis Osicular , Reemplazo Osicular , Cirugía del Estribo , Humanos , Masculino , Femenino , Adulto , Estribo , Yunque/cirugía , Timpanoplastia/métodos , Reemplazo Osicular/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Cirugía del Estribo/métodosRESUMEN
BACKGROUND: Treatment of Epstein-Barr virus(EBV)-positive nasopharyngeal carcinoma (NPC) with cisplatin/5-fluorouracil (5-FU) induction chemotherapy, followed by radiochemotherapy and subsequent interferonß, has yielded high survival rates in children, adolescents, and young adults. A previous study has shown that reduction of radiation dose from 59.4 to 54.0â¯Gy appears to be safe in patients with complete response (CR) to induction chemotherapy. As immune checkpoint-inhibitors have shown activity in NPC, we hypothesize that the addition of nivolumab to standard induction chemotherapy would increase the rate of complete tumor responses, thus allowing for a reduced radiation dose in a greater proportion of patients. METHODS: This is a prospective multicenter phase 2 clinical trial including pediatric and adult patients with their first diagnosis of EBV-positive NPC, scheduled to receive nivolumab in addition to standard induction chemotherapy. In cases of non-response to induction therapy (stable or progressive disease), and in patients with initial distant metastasis, treatment with nivolumab will be continued during radiochemotherapy. Primary endpoint is tumor response on magnetic resonance imaging (MRI) and positron emission tomography (PET) after three cycles of induction chemotherapy. Secondary endpoints are event-free (EFS) and overall survival (OS), safety, and correlation of tumor response with programmed cell death ligand 1 (PD-L1) expression. DISCUSSION: As cure rates in localized EBV-positive NPC today are high with standard multimodal treatment, the focus increasingly shifts toward prevention of late effects, the burden of which is exceptionally high, mainly due to intense radiotherapy. Furthermore, survival in patients with metastatic disease and resistant to conventional chemotherapy remains poor. Primary objective of this study is to investigate whether the addition of nivolumab to standard induction chemotherapy in children and adults with EBV-positive NPC is able to increase the rate of complete responses, thus enabling a reduction in radiation dose in more patients, but also offer patients with high risk of treatment failure the chance to benefit from the addition of nivolumab. TRIAL REGISTRATION: EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) No. 2021-006477-32.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia de Inducción , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nivolumab , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/diagnóstico , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/terapia , Nivolumab/uso terapéutico , Nivolumab/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
The treatment of vestibular schwannomas (VS) has always posed a challenge for physicians. Three essential treatment principles are available: wait-and-scan, surgery, and stereotactic radiotherapy. In addition to the type of treatment, decisions must be made regarding the optimal timing of therapy, the combination of different treatment modalities, the potential surgical approach, and the type and intensity of radiation. Factors influencing the therapy decision include tumor location and size or stage, patient age, comorbidities, symptoms, postoperative hearing rehabilitation options, patient preferences, and, not least, the experience of the surgeons and the personnel and technical capabilities of the clinical site. This article begins with a brief overview of vestibular schwannomas, then outlines the fundamental interdisciplinary treatment options, and finally discusses the ENT (ear, nose, and throat)-relevant factors in the therapy decision.
Asunto(s)
Neuroma Acústico , Radiocirugia , Humanos , Audición , Neuroma Acústico/diagnóstico , Neuroma Acústico/terapia , Resultado del TratamientoRESUMEN
Manned spaceflight places special demands on the human body, including the organs in the ENT region. These organs play a critical role in maintaining the health and safety of astronauts in space. In this paper, we review common ENT problems of spaceflight, including upper airway edema, middle ear and mastoid effusions, hearing loss, and dizziness with nausea. We discuss the underlying mechanisms contributing to these complaints, their clinical manifestations, and potential treatment strategies. In addition, we examine the potential impact of these conditions on astronaut health and mission outcomes. Finally, we emphasize the importance of preventive measures and future research in this area to optimize astronaut health and safety on future missions.
Asunto(s)
Otolaringología , Vuelo Espacial , Humanos , AstronautasRESUMEN
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.
Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Masculino , Humanos , Femenino , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estudios de Cohortes , Neoplasias Orofaríngeas/patología , Estudios Retrospectivos , Estadificación de Neoplasias , Neoplasias de Cabeza y Cuello/patología , Pronóstico , Virus del Papiloma Humano , PapillomaviridaeRESUMEN
Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) represents an OPSCC subgroup with an overall good prognosis with a rising incidence in Western countries. Multiple lines of evidence suggest that HPV-associated tumors are not a homogeneous tumor entity, underlining the need for accurate prognostic biomarkers. In this retrospective, multi-institutional study involving 906 patients from four centers and one database, we developed a deep learning algorithm (OPSCCnet), to analyze standard H&E stains for the calculation of a patient-level score associated with prognosis, comparing it to combined HPV-DNA and p16-status. When comparing OPSCCnet to HPV-status, the algorithm showed a good overall performance with a mean area under the receiver operator curve (AUROC) = 0.83 (95% CI = 0.77-0.9) for the test cohort (n = 639), which could be increased to AUROC = 0.88 by filtering cases using a fixed threshold on the variance of the probability of the HPV-positive class - a potential surrogate marker of HPV-heterogeneity. OPSCCnet could be used as a screening tool, outperforming gold standard HPV testing (OPSCCnet: five-year survival rate: 96% [95% CI = 90-100%]; HPV testing: five-year survival rate: 80% [95% CI = 71-90%]). This could be confirmed using a multivariate analysis of a three-tier threshold (OPSCCnet: high HR = 0.15 [95% CI = 0.05-0.44], intermediate HR = 0.58 [95% CI = 0.34-0.98] p = 0.043, Cox proportional hazards model, n = 211; HPV testing: HR = 0.29 [95% CI = 0.15-0.54] p < 0.001, Cox proportional hazards model, n = 211). Collectively, our findings indicate that by analyzing standard gigapixel hematoxylin and eosin (H&E) histological whole-slide images, OPSCCnet demonstrated superior performance over p16/HPV-DNA testing in various clinical scenarios, particularly in accurately stratifying these patients.
RESUMEN
Many locally advanced and metastatic salivary gland carcinomas (SGC) lack therapeutic targets. Enfortumab vedotin, an antibody-drug conjugate binding to Nectin-4, recently gained FDA approval for third-line urothelial carcinoma. Therefore, the aim of this study was to assess the expression of Nectin-4 in primary SGC and corresponding lymph node metastases and to correlate it with clinicopathological data. Immunohistochemical staining for Nectin-4 was performed for patients who had undergone surgery with curative intent for primary SGC of the parotid or submandibular gland in a tertiary referral center between 1990 and 2019. One hundred twenty-two primary SGC and twenty corresponding lymph node metastases were included. Nectin-4 was expressed in 80.3% of primary SGC with a mean Histo(H-)score of 61.2 and in 90.0% of lymph node metastases with a mean H-score of 75.6. A moderate or high Nectin-4 expression was found in 25.9% of salivary duct carcinomas (SaDu) and in 30.7% of adenoid cystic carcinomas (ACC). SaDu patients with a lower T-stage (p = 0.04), no loco-regional lymph node metastases (p = 0.049), no vascular invasion (p = 0.04), and no perineural spread (p = 0.03) showed a significantly higher mean Nectin-4 H-score. There was a statistical tendency towards a more favorable disease-free survival among SaDu patients with a higher Nectin-4 expression (p = 0.09). Nectin-4 is expressed in SGC and therefore represents a potential therapeutic target, especially in entities with a high rate of local recurrence and metastatic spread such as SaDu and ACC.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de las Glándulas Salivales , Neoplasias de la Vejiga Urinaria , Humanos , Nectinas , Metástasis Linfática , Neoplasias de las Glándulas Salivales/tratamiento farmacológico , Biomarcadores , Moléculas de Adhesión CelularRESUMEN
Human papillomavirus (HPV) is an established etiologic factor for cancers in the head and neck region, specifically for Oropharyngeal Squamous Cell Carcinoma (OPSCC). The comparatively good overall survival justifies the current discussion regarding therapy de-escalation for patients with a low-risk profile. In addition to the immunohistochemistry-based biomarker p16INK4a, there is still a need for diagnostic and prognostic biomarkers that allow risk stratification and monitoring during therapy and follow-up of these patients. In recent years, liquid biopsy, especially in the form of plasma samples, has gained importance and is already used to monitor viral DNA in patients with Epstein-Barr virus-associated nasopharyngeal carcinoma. Circulating DNA (ctDNA) released by the tumor into the bloodstream is particularly suitable for a high specificity in detecting virus-associated tumors. Detection of viral E6 and E7 oncogenes in HPV-positive OPSCC is predominantly performed by droplet digital/quantitative PCR as well as next generation sequencing. Detection of circulating HPV-DNA derived from tumor cells (ctHPV-DNA) at diagnosis is associated with advanced tumor stage, locoregional and distant metastases. Longitudinal studies have further demonstrated that detectable and/or increasing ctHPV-DNA levels are associated with treatment failure and disease relapse. However, a standardization of the diagnostic procedure is necessary before introducing liquid biopsy into the clinical routine. In the future, this might allow a valid reflection of disease progression in HPV-positive OPSCC.
Asunto(s)
Carcinoma de Células Escamosas , Infecciones por Virus de Epstein-Barr , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Infecciones por Papillomavirus/diagnóstico , Recurrencia Local de Neoplasia , Herpesvirus Humano 4 , Medicina de Precisión , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello , ADN Viral/genética , ADN Viral/análisisRESUMEN
BACKGROUND: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUPHNSCC), much less is known. METHODS: We assessed a consecutive cohort of CUPHNSCC diagnosed from 2000-2018 for HPV DNA, mRNA, p16INK4a (p16) expression, and risk factors to identify prognostic classification markers. RESULTS: In 32/103 (31%) CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUPHNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption. CONCLUSIONS: Despite obvious differences, CUPHNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUPHNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles.
RESUMEN
With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients' status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log10 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine's potential as an antiviral treatment.Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Rociadores Nasales , Carga Viral , Método Doble Ciego , Resultado del TratamientoRESUMEN
The parotid gland is one of the major salivary glands producing a serous secretion, and it plays an essential role in the digestive and immune systems. Knowledge of peroxisomes in the human parotid gland is minimal; furthermore, the peroxisomal compartment and its enzyme composition in the different cell types of the human parotid gland have never been subjected to a detailed investigation. Therefore, we performed a comprehensive analysis of peroxisomes in the human parotid gland's striated duct and acinar cells. We combined biochemical techniques with various light and electron microscopy techniques to determine the localization of parotid secretory proteins and different peroxisomal marker proteins in parotid gland tissue. Moreover, we analyzed the mRNA of numerous gene encoding proteins localized in peroxisomes using real-time quantitative PCR. The results confirm the presence of peroxisomes in all striated duct and acinar cells of the human parotid gland. Immunofluorescence analyses for various peroxisomal proteins showed a higher abundance and more intense staining in striated duct cells compared to acinar cells. Moreover, human parotid glands comprise high quantities of catalase and other antioxidative enzymes in discrete subcellular regions, suggesting their role in protection against oxidative stress. This study provides the first thorough description of parotid peroxisomes in different parotid cell types of healthy human tissue.
Asunto(s)
Glándula Parótida , Peroxisomas , Humanos , Glándula Parótida/metabolismo , Proteínas/metabolismo , Microscopía Electrónica , Conductos SalivalesRESUMEN
BACKGROUND: The ORL-App, a smartphone app for further education and training for ORL doctors and those interested in ORL, complements existing offers in medical education and training. The principle of game-based e-learning can open up new perspectives in times of digitalisation and pandemic. The heart of the app is a large ORL quiz, in which app users compete against each other. This paper analyses the performance of app users in the quiz module, taking into account the questions' categories and the users' level of education. MATERIAL AND METHODS: Retrospectively, an evaluation of the quiz questions was carried out for the first 24 months after the introduction of the app. There were 3593 different questions to choose from in 16 different categories. Based on the level of training, a distinction was made between doctors in further training, specialists, senior physicians, chief physicians and professors in the field of ORL. In addition, data on students and non-medical staff were available. RESULTS: There was a significant difference in the level of knowledge of the users considering the level of training. The group of doctors in further training (n = 1013) represented the largest group, with an average of 244 questions per user and 65.1% of the questions answered correctly. They thus achieved a significantly better answer rate than the group of specialists (n = 566), who were able to answer 61.0 % of the questions correctly. CONCLUSION: The game-based form of training through the quiz-part of the ORL-App seems to be particularly attractive for doctors in further training. In addition, this user group achieved better answer rates than the specialists.
Asunto(s)
Educación Médica , Aplicaciones Móviles , Otolaringología , Médicos , Humanos , Estudios Retrospectivos , Otolaringología/educaciónRESUMEN
The extracellular matrix (ECM) is an integral part of the tumor microenvironment of carcinomas. Even though salivary gland carcinomas (SGCs) display a range of tumor cell differentiation and distinct extracellular matrices, their ECM landscape has not been characterized in depth. The ECM composition of 89 SGC primaries, 14 metastases, and 25 normal salivary gland tissues was assessed using deep proteomic profiling. Machine learning algorithms and network analysis were used to detect tumor groups and protein modules that explain specific ECM landscapes. Multimodal in situ studies to validate exploratory findings and to infer a putative cellular origin of ECM components were applied. We revealed two fundamental SGC ECM classes which align with the presence or absence of myoepithelial tumor differentiation. We describe the SGC ECM through three biologically distinct protein modules that are differentially expressed across ECM classes and cell types. The modules have a distinct prognostic impact on different SGC types. Since targeted therapy is rarely available for SGC, we used the proteomic expression profile to identify putative therapeutic targets. In summary, we provide the first extensive inventory of ECM components in SGC, a difficult-to-treat disease that encompasses tumors with distinct cellular differentiation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.