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1.
Artigo em Inglês | MEDLINE | ID: mdl-38587651

RESUMO

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.

2.
Clin Exp Metastasis ; 40(5): 395-405, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37480387

RESUMO

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.


Assuntos
Carcinoma de Células de Transição , Neoplasias das Glândulas Salivares , Neoplasias da Bexiga Urinária , Humanos , Nectinas , Metástase Linfática , Neoplasias das Glândulas Salivares/tratamento farmacológico , Biomarcadores , Moléculas de Adesão Celular
3.
Laryngoscope ; 133(10): 2631-2637, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36734324

RESUMO

OBJECTIVE: The aim of this study was to evaluate the quality and the educational content of YouTube videos showing parotidectomy. METHODS: We searched for videos displaying parotidectomy on YouTube. To rate parotidectomy videos, we introduced the "Instructional Videos in Otorhinolaryngology by YO-IFOS (IVORY)-grading-system (GS)" derived from the IVORY Guidelines, which pose established consensus recommendations for the production of educational surgical videos in otolaryngology. The videos were rated using the IVORY-GS, and the total score was tested for statistical association with views, likes, likes/dislikes-ratio, age, and length of the videos for validation of the IVORY-GS. RESULTS: Overall, 50 parotidectomy videos were identified. Sixty-eight (68%) of the videos showed a superficial parotidectomy. The mean IVORY-GS total score was 24.9 (out of a maximum of 44 points). Video education quality was rated as moderate in 22% and high in 4%. There was a statistically significant correlation between the total score and the number of views (p = 0.03), the total score and the number of likes (p < 0.01), and the total score and the likes/dislikes ratio (p < 0.01). A higher total score was a significant predictor of more likes (p = 0.01) and a higher likes/dislikes ratio (p < 0.01). CONCLUSION: Our modification of the IVORY Guidelines is otolaryngology-specific, suitable, and recommended to evaluate parotidectomy videos. To date, most videos are of poor educational quality. Future efforts in otolaryngology surgical video education could focus on the establishment of an online video platform. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2631-2637, 2023.


Assuntos
Mídias Sociais , Humanos , Gravação em Vídeo , Disseminação de Informação
4.
J Pathol ; 260(2): 148-164, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36814077

RESUMO

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.


Assuntos
Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Proteômica , Matriz Extracelular/patologia , Neoplasias das Glândulas Salivares/metabolismo , Carcinoma/patologia , Diferenciação Celular , Glândulas Salivares , Microambiente Tumoral
5.
HNO ; 71(4): 223-231, 2023 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-35579673

RESUMO

BACKGROUND: Secondary malignancies of the parotid gland frequently have a cutaneous origin and the incidence in central Europe is increasing. OBJECTIVE: The aim of this review article was to present the epidemiology, (differential) diagnostics and treatment of secondary malignancies of the parotid gland. MATERIAL AND METHODS: A literature search of the current guidelines and evidence was carried out in the web-based databank PubMed. RESULTS: The incidence of secondary malignancies of the parotid gland seems to be increasing in Europe, mainly due to a rising incidence of metastases of cutaneous squamous cell carcinomas. Except for malignant lymphomas, parotidectomy is the treatment of choice in the curative situation. In the absence of clear evidence, in the case of an intact facial nerve lateral or total parotidectomy with ipsilateral neck dissection seems to be indicated, depending on the entity of the secondary malignancy. CONCLUSION: The differential diagnostics of squamous cell carcinoma (in) of the parotid gland can be complicated. When a squamous cell carcinoma of the parotid gland is diagnosed for the first time, a dermatological full body examination and a detailed medical history should be taken with respect to skin tumors of the head and neck region. In addition to surgical treatment of the parotid gland and neck, adjuvant radiotherapy is usually indicated.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Parotídeas , Neoplasias Cutâneas , Humanos , Glândula Parótida/cirurgia , Glândula Parótida/patologia , Neoplasias Parotídeas/diagnóstico , Neoplasias Parotídeas/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Cutâneas/cirurgia , Esvaziamento Cervical , Estudos Retrospectivos
6.
Braz J Otorhinolaryngol ; 89(1): 48-53, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34716112

RESUMO

OBJECTIVE: To assess the value of a morphine Patient Controlled Intravenous Analgesia (PCIA) after Tonsillectomies (TE). METHODS: 30 adult patients were treated with oral analgesics (protocol group) and compared to 30 patients treated with a morphine PCIA for the first 3 Postoperative Days (PODs) after TE. Average and maximum pain severities (Numeric Rating Scale - NRS: 0-10) on PODs 1-3, analgesic score, quality of life, patient satisfaction and side effects were defined as outcome measures. RESULTS: Average pain severities of the protocol and the PCIA group were of similar magnitude (NRS) (POD1: 4.48 vs. 4.71 [p = 0.68], POD2: 4.75 vs. 4.22 [p = 0.32] and POD3: 4.44 vs. 4.25 [p = 0.71]). Maximum pain intensities on POD1 (p = 0.92), POD2 (p = 0.51) and POD3 (p = 0.36) were also comparable between both groups. Patients with a PCIA consumed significantly more opioids (p = 0.001) without significant more side-effects. CONCLUSION: The PCIA did not provide a superior pain control compared to oral analgesics. In view of the considerable effort and the high opioid consumption, it cannot be recommended as a standardized application for pain control after TE.


Assuntos
Morfina , Tonsilectomia , Adulto , Humanos , Morfina/efeitos adversos , Tonsilectomia/efeitos adversos , Qualidade de Vida , Dor Pós-Operatória/tratamento farmacológico , Analgésicos Opioides/efeitos adversos , Analgesia Controlada pelo Paciente/efeitos adversos , Analgesia Controlada pelo Paciente/métodos , Analgésicos/uso terapêutico
7.
Braz. j. otorhinolaryngol. (Impr.) ; 89(1): 48-53, Jan.-Feb. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1420918

RESUMO

Abstract Objective: To assess the value of a morphine Patient Controlled Intravenous Analgesia (PCIA) after Tonsillectomies (TE). Methods: 30 adult patients were treated with oral analgesics (protocol group) and compared to 30 patients treated with a morphine PCIA for the first 3 Postoperative Days (PODs) after TE. Average and maximum pain severities (Numeric Rating Scale - NRS: 0-10) on PODs 1-3, analgesic score, quality of life, patient satisfaction and side effects were defined as outcome measures. Results: Average pain severities of the protocol and the PCIA group were of similar magnitude (NRS) (POD1: 4.48 vs. 4.71 [p = 0.68], POD2: 4.75 vs. 4.22 [p = 0.32] and POD3: 4.44 vs. 4.25 [p = 0.71]). Maximum pain intensities on POD1 (p = 0.92), POD2 (p = 0.51) and POD3 (p = 0.36) were also comparable between both groups. Patients with a PCIA consumed significantly more opioids (p = 0.001) without significant more side-effects. Conclusion: The PCIA did not provide a superior pain control compared to oral analgesics. In view of the considerable effort and the high opioid consumption, it cannot be recommended as a standardized application for pain control after TE.

8.
Int J Mol Sci ; 23(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36012301

RESUMO

Advanced salivary gland carcinomas (SGC) often lack therapeutic options. Agents targeting CD138 have recently shown promising results in clinical trials for multiple myeloma and a preclinical trial for triple-negative breast cancer. Immunohistochemistry for CD138 was performed for all patients who had undergone primary surgery for SGC with curative intent. Findings were validated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. Overall, 111 primary SGC and 13 lymph node metastases from salivary duct carcinomas (SaDu) were evaluated. CD138 expression was found in 60% of all SGC with differing expression across entities (p < 0.01). A mean of 25.2% of the tumor cells in mucoepidermoid carcinoma (MuEp) were positive, followed by epithelial-myoepithelial carcinoma (20.9%), acinic cell carcinoma (16.0%), and SaDu (15.2%). High-/intermediate-grade MuEp showed CD138 expression in a mean of 34.8% of tumor cells. For SaDu, lymph node metastases showed CD138 expression in a mean of 31.2% of tumor cells which correlated with CD138 expression in their primaries (p = 0.01; Spearman's ρ = 0.71). MALDI-MS imaging confirmed the presence of the CD138 protein in SGC. No significant association was found between clinicopathological data, including progression-free survival (p = 0.50) and CD138 expression. CD138 is expressed in the cell membrane of different entities of SGC and SaDu lymph node metastases and therefore represents a potential target for CD138 targeting drugs.


Assuntos
Carcinoma Mucoepidermoide , Carcinoma , Neoplasias das Glândulas Salivares , Biomarcadores Tumorais/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Humanos , Metástase Linfática , Neoplasias das Glândulas Salivares/metabolismo
9.
Medicina (Kaunas) ; 58(8)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35893115

RESUMO

Background and Objectives: The incidence of distant metastases in patients with head and neck cancer (HNC) is approximately 10%. Pulmonary metastases are the most frequent distant location, with an incidence of 70-85%. The standard treatment options are chemo-, immuno- and radiotherapy. Despite a benefit for long-term survival for patients with isolated pulmonary metastases, pulmonary metastasectomy (PM) is not the treatment of choice. Furthermore, many otorhinolaryngologists are not sufficiently familiar with the concept of PM. This work reviews the recent studies of pulmonary metastatic HNC and the results after pulmonary metastasectomy. Materials and Methods: PubMed, Medline, Embase, and the Cochrane library were checked for the case series' of patients undergoing metastasectomy with pulmonary metastases published since 1 January 2000. Results: We included the data of 15 studies of patients undergoing PM. The 5-year survival rates varied from 21% to 59%, with median survival from 10 to 77 months after PM. We could not identify one specific prognostic factor for long-term survival after surgery. However, at least most studies stated that PM should be planned if a complete (R0) resection is possible. Conclusions: PM showed reliable results and is supposedly the treatment of choice for patients with isolated pulmonary metastases. Patients not suitable for surgery may benefit from other non-surgical therapy. Every HNC patient with pulmonary metastases should be discussed in the multidisciplinary tumor board to optimize the therapy and the outcome.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Metastasectomia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Metastasectomia/métodos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
10.
Cancers (Basel) ; 14(6)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35326536

RESUMO

Adenoid cystic carcinoma (ACC) is a rare malignancy in the head and neck. The prognosis remains poor and late recurrences often occur after 5 years and later. To date, there are no reliable prognostic markers for ACC. In several solid tumors, tertiary lymphoid structures (TLS) are associated with improved survival. This study aims to investigate the role of distribution patterns of tumor infiltrating immune cells (TIL) in ACC. A cohort of 50 patients from three different cancer centers was available for analysis. Sections were stained for CD3, CD4, CD8 and CD20 and evaluated with regard to their distribution of TIL. Patterns were determined as infiltrated-excluded, infiltrated-inflamed and presence of tertiary lymphoid structures. About half of the cases showed an infiltrated-excluded TIL pattern and only a minority of six cases had TLS present within the tumor. Within the inflamed phenotype CD3+ cells were by far the most abundant lymphocyte subtype, and within this compartment, CD8+ T cells were predominant. There was no influence on overall or disease-free survival by any of the TIL patterns. This indicates that ACC is a tumor with very low immunogenicity and even abundance of lymphocytes does not seem to improve prognosis for this disease. Therefore, the observed lack of response towards immunotherapy is not surprising and other methods to induce recognition of ACC by the immune system must be found.

11.
Laryngorhinootologie ; 101(11): 876-881, 2022 11.
Artigo em Alemão | MEDLINE | ID: mdl-35320850

RESUMO

Novel therapeutic options for the treatment of salivary gland malignancies have emerged due to the improvement and distribution of molecular pathological testing methods and the availability of targeted therapies. Since they are less toxic, these new agents are a valuable alternative to conventional cytotoxic chemotherapy. On the one hand, there are new entity-specific therapies such as NTRK inhibitor therapy for secretory carcinomas and axitinib therapy for adenoid cystic carcinomas. Moreover, cross-entity therapeutics such as antiandrogenic therapy, HER2 inhibition, and PI3K inhibition are also coming to the fore. For metastatic/recurrent salivary gland carcinomas that cannot be treated with targeted therapy, platinum-based chemotherapies continue to be therapy of choice.


Assuntos
Carcinoma Adenoide Cístico , Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias das Glândulas Salivares/tratamento farmacológico , Neoplasias das Glândulas Salivares/genética , Carcinoma Adenoide Cístico/tratamento farmacológico , Carcinoma Adenoide Cístico/patologia , Carcinoma/patologia , Glândulas Salivares
12.
Eur J Cardiothorac Surg ; 62(2)2022 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-35171234

RESUMO

OBJECTIVES: Pulmonary metastasectomy (PM) is an established procedure for selected patients with metastatic head and neck cancer (HNC). Non-surgical therapy in the form of chemo- and immunotherapy and checkpoint inhibitors and radiation therapy are also treatment options. There are no randomized controlled trials comparing PM with non-surgical therapy. Here, we retrospectively compare the long-term survival of patients, undergoing PM with patients receiving non-surgical therapy. METHODS: All HNC patients with pulmonary metastases were included, if the primary HNC was treated curatively and distant metastases, apart from the lungs were excluded. The pulmonary metastases were confirmed by biopsy as metastases of the HNC primary tumour in the non-surgical therapy group. To further clarify that PM prolonged survival, a propensity score-matched analysis was performed. RESULTS: Between January 2010 and December 2020, 62 HNC patients with isolated pulmonary metastases were included in our analysis. Thirty-three underwent PM and 29 received non-surgical therapy. Histology, tumour stage and localization of the primary HNC did not differ between groups. The number of metastases, age and ASA classification did also not differ between the groups. Patients undergoing PM showed significantly better 1- (n = 31; 93.5% vs n = 19; 65.5%; P = 0.006), 3- (n = 17; 72.2% vs n = 9; 30.4%; P = 0.004) and 5-year (n = 10; 53.4% vs n = 4; 20.0%; P = 0.001) survival rates, compared to patients receiving non-surgical therapy. CONCLUSIONS: Patients with pulmonary metastatic HNC undergoing PM had a significantly better overall survival compared to patients receiving non-surgical therapy. Therefore, selected patients should undergo PM to improve survival.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Metastasectomia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Metastasectomia/métodos , Pneumonectomia/métodos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
13.
Eur Arch Otorhinolaryngol ; 279(4): 1843-1850, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34095963

RESUMO

INTRODUCTION: The Frenzel maneuver describes a technique for middle ear equalizing which is frequently used by apnea divers. It offers advantages compared to the most commonly used techniques such as the Valsalva or Toynbee maneuver. Until now, there is insufficient literature about the pressure dynamics and Eustachian tube (ET) function during the Frenzel maneuver. The aim of the present study was to characterize the ET function during the Frenzel maneuver. MATERIALS AND METHODS: By means of an established standardized profile of compression and decompression in a hypo/hyperbaric pressure chamber, we examined different parameters such as the ET opening pressure (ETOP), ET opening duration (ETOD), and ET opening frequency (ETOF) in 11 experienced apnea divers and compared them to the parameters during the Valsalva and Toynbee maneuver. RESULTS: Standard values for ETOP, ETOD, and ETOF could be established for the Frenzel maneuver under standardized conditions in a hypo/hyperbaric pressure chamber. Compared to the Frenzel maneuver, ETOP was higher and ETOD longer (both p < 0.001) during the Valsalva maneuver whereas ETOP was lower and ETOD shorter (both p < 0.001) during the Toynbee maneuver. No difference regarding ETOF was observed between the Frenzel, Valsalva, and Toynbee maneuver. DISCUSSION: The Frenzel maneuver was shown to be at least as effective as the Valsalva maneuver concerning ET opening. We believe that knowledge of the Frenzel technique might facilitate the pressure equalization during diving and recommend implementation of an appropriate equalization training in apnea and scuba diving education.


Assuntos
Mergulho , Tuba Auditiva , Orelha Média , Humanos , Estudos Prospectivos , Manobra de Valsalva
14.
Head Neck Pathol ; 16(2): 394-406, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34378164

RESUMO

Procollagen 11A1 (COL11A1) is a central component of the extracellular matrix in many carcinomas, which is considered to be mainly produced by cancer associated fibroblasts (CAFs). As COL11A1 expression correlates with adverse prognosis and is implicated in chemoresistance, it is a promising putative target. For the first time, we used RNA in-situ hybridization to systematically identify the cells that produce COL11A1 in the ten most prevalent carcinoma types, lymphomas (n = 275) and corresponding normal tissue (n = 55; panCancer cohort). Moreover, as most salivary gland carcinomas (SGC) display distinct stromal architectures, we also analysed 110 SGC. The corresponding protein formation of COL11A1 was determined by MALDI-TOF-MS-Imaging. We report that colon, breast and salivary duct carcinomas are highly infiltrated by COL11A1 positive CAFs (CAFsCOL11A1) and might thus be promising candidates for antidesmoplastic or COL11A1-targeted therapies. The amount of CAFsCOL11A1 correlated significantly with tumour grade, tumour stage and nodal spread in the panCancer cohort. Significant associations between CAFsCOL11A1 and vascular invasion, perineural spread and nodal spread were observed in the SGC cohort. Also, we discovered that tumour cells of intercalated duct derived SGC and CAFs produce COL11A1 in a mutually exclusive manner. Our findings represent a novel mode of extracellular matrix production in carcinomas and could be highly relevant in the future. Our findings elucidate the mode of COL11A1 expression in very different carcinoma types and may aid to categorise tumours in the setting of possible future COL11A1-related therapies.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma , Colágeno Tipo XI , Neoplasias das Glândulas Salivares , Biomarcadores Tumorais/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma/patologia , Colágeno Tipo XI/genética , Colágeno Tipo XI/metabolismo , Humanos , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia
16.
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.

17.
Cancers (Basel) ; 13(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298628

RESUMO

Treatment options of locoregional recurrent head and neck squamous cell cancer (HNSCC) include both local strategies as surgery or re-radiotherapy and systemic therapy. In this prospective, multi-center, non-interventional study, patients were treated either with platinum-based chemotherapy and cetuximab (CT + Cet) or re-radiotherapy and cetuximab (RT + Cet). In the current analysis, progression-free survival (PFS) and overall survival (OS) were compared in patients with locoregional recurrence. Four hundred seventy patients were registered in 97 German centers. After exclusion of patients with distant metastases, a cohort of 192 patients was analyzed (129 CT + Cet, 63 RT + Cet). Radiotherapy was delivered as re-irradiation to 70% of the patients. The mean radiation dose was 51.8 Gy, whereas a radiation dose of ≥60 Gy was delivered in 33% of the patients. Chemotherapy mainly consisted of cisplatin/5-flurouracil (40%) or carboplatin/5-flurouracil (29%). The median PFS was 9.2 months in the RT + Cet group versus 5.1 months in the CT + Cet group (hazard ratio for disease progression or death, 0.40, 95% CI, 0.27-0.57, p < 0.0001). Median OS was 12.8 months in the RT + Cet group versus 7.9 months in the CT + Cet group (hazard ratio for death, 0.50, 95% CI, 0.33-0.75, p = 0.0008). In conclusion, radiotherapy combined with cetuximab improved survival compared to chemotherapy combined with cetuximab in locally recurrent HNSCC.

18.
JAMA Otolaryngol Head Neck Surg ; 147(6): 553-560, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33830180

RESUMO

Importance: Up to 80% of patients with head and neck cancer undergoing ablative surgery and neck dissection develop postoperative pain with detrimental effects on quality of life that also contributes to neuropathic and chronic postoperative pain. Objective: To investigate the association of continuous local anesthetic wound infusion with pain management after head and neck surgery. Design, Setting, and Participants: This prospective, longitudinal, nonrandomized clinical study carried out in a single tertiary referral center (December 1, 2015, to July 1, 2017) included 2 groups of 30 patients. Patients were consecutively enrolled and presented for ablative head and neck surgery including selective neck dissection and studied from the preoperative through the fourth postoperative day. Interventions: The control group was treated according to a standardized escalating oral treatment protocol (ibuprofen, metamizole, opioids). The intervention group was treated with an intraoperatively applied pain catheter (InfiltraLong plus FuserPump, Pajunk, ropivacaine, 0.2%, 3 mL/h) that was removed 72 hours after operating. Main Outcomes and Measures: Average and maximum pain intensities on a numeric rating scale; quality of life using the acute version of the validated 36-Item Short Form Survey; and neuropathic pain using the validated 12-Item painDETECT questionnaire. Consumption of opioid and nonopioid analgesics and evaluation of catheter-associated complications. Results: During postoperative days 1 through 4, patients of the intervention group (mean [SD] age, 63.2 [13.3 years; 9 [30%] women) experienced lower mean (SD) (1.6 [1.4] vs 2.7 [1.8]; η2p = 0.09 [0.01-0.21]) and maximum (2.4 [2.2] vs 4.2 [2.0]; η2p = 0.11 [0.01-0.24]) pain intensities compared with the control group (mean [SD] age, 62.5 [13.6] years; 5 [17%] women). The intervention group also reported less neuropathic pain (mean [SD], 5.4 [3.4] vs 7.6 [5.1]; η2p = 0.09 [0.004 - 0.22]) and higher quality of life regarding vitality (56.2 [21.5] vs 43.8 [20.9], r = 0.29; 95% CI, 0.01-0.52) and pain (66.8 [27.3] vs 49.5 [27.7], r = 0.31; 95% CI, 0.04-0.54). Patients from the intervention group requested nonopioid analgesics considerably less often (n = 17 [57% ]vs n = 29 [97%]; ϕ = 0.47; 95% CI, 0.30-0.67) associated with a noticeably lower need to escalate pain treatment (n = 3 [10%] vs n = 9 [30%]; mean [SD] ibuprofen dose: 500 [173] mg vs 1133 [650] mg; r = 0.64; 95% CI, 0.02-0.91). No catheter-associated complications were observed. Conclusions and Relevance: Continuous anesthetic wound infusion is associated with reduced postoperative pain and decreased demand for analgesics. It therefore expands the treatment options for postoperative pain in head and neck cancer. Trial Registration: German Clinical Trials Register: DRKS00009378.


Assuntos
Anestésicos Locais/administração & dosagem , Neoplasias de Cabeça e Pescoço/cirurgia , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Administração Oral , Analgésicos/administração & dosagem , Feminino , Humanos , Infusões Intralesionais , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Qualidade de Vida
19.
Head Neck Pathol ; 15(4): 1147-1155, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33886073

RESUMO

Treatment options for unresectable, recurrent or metastatic salivary gland carcinomas (SGC) are scarce. Trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein that is involved in a variety of oncogenic cell signaling pathways. Its potential as a target for the antibody-drug conjugate sacituzumab govitecan has already been demonstrated in different tumor entities. The United States Food and Drug Administration approved this antibody-drug conjugate for the treatment of metastatic triple-negative breast cancer. Here, we aimed to investigate Trop-2 protein expression in different entities of SGCs. We retrospectively reviewed the medical records of all patients that underwent surgery for a primary SGC in a tertiary referral center between 1990 and 2014. Immunohistochemical (IHC) staining for Trop-2 was performed and rated as negative, weak, moderate or high using a semiquantitative score. Additionally, representative cases were analyzed using MALDI-mass spectrometry (MS) imaging to confirm the IHC results. The cohort consisted of 114 tumors of the parotid gland (90.4%) and submandibular gland (9.6%). It mainly included mucoepidermoid, salivary duct and adenoid cystic carcinomas. In IHC samples, 44% showed high, 38% moderate and 10% weak expression rates of Trop-2. MALDI-MS imaging confirmed the presence of Trop-2 protein in 80% of the tested tumor samples. This is the first study to demonstrate that several types of SGC express Trop-2 with variable intensity. Since there are currently few systemic treatment options for advanced SGCs, Trop-2 represents a promising target for further clinical studies, for instance, with sacituzumab govitecan.


Assuntos
Antígenos de Neoplasias/metabolismo , Carcinoma/metabolismo , Moléculas de Adesão Celular/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Adulto Jovem
20.
Otol Neurotol ; 42(3): 442-446, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33496427

RESUMO

INTRODUCTION: In round window vibroplasty the most efficient coupling technique for contact of the floating mass transducer (FMT) to the round window membrane (RWM) is yet to be determined. Various materials placed between the FMT and the RWM have been proposed to enable better stimulation of the cochlea. Collagenous scaffolds derived from decellularized extracellular cartilage matrices as a commercially available biomaterial are already used for other applications in ear surgery. We aimed to examine the coupling properties of collagen scaffolds compared with commonly used other materials (round window soft coupler, porcine perichondrium, and cartilage) as interponate between the FMT and the RWM in vibroplasty. METHODS: A well-established in vitro temporal bone model was used. Volume velocities were measured with collagen scaffold compared with different interponates (round window soft coupler, porcine perichondrium, and cartilage) at 800, 1000, 1250, 1600, 2000, 2500, 3150, and 4000 Hz levels. RESULTS: Statistical analysis revealed no superiority of commonly used materials compared with collagen scaffolds at all tested volume velocities (p > 0.05). DISCUSSION: We could demonstrate that collagenous scaffolds of decellularized extracellular cartilage matrices have similar vibrational properties as conventional coupling materials of the FMT to the RWM in vibroplasty. Therefore, as a commercially available new material they display a suitable coupling option for round window vibroplasty.


Assuntos
Prótese Ossicular , Procedimentos Cirúrgicos Otológicos , Animais , Colágeno , Janela da Cóclea/cirurgia , Suínos , Osso Temporal
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