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1.
J Natl Cancer Inst ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39250754

RESUMO

BACKGROUND: The rate of primary surgery for human papillomavirus-related oropharynx cancer (HPVOPC) has recently declined, while utilization of transoral robotic surgery (TORS) has lagged at community cancer centers (CCs). We hypothesize that differences in overall survival (OS) exist between patients undergoing surgery for HPVOPC at CCs and low (<15 TORS/year; LVACs) and high (≥15 TORS/year; HVACS) TORS volume academic centers. METHODS: Cases from the US National Cancer Database with a diagnosis of HPVOPC from 2010-2019 that underwent primary surgical treatment were included. Trends in TORS utilization, rates of positive surgical margins (PMs), quality of adjuvant treatment and 5-year OS were compared between CCs, LVACs and HVACs. RESULTS: 5,406 cases met study criteria. A significantly lower proportion of cases at CCs utilized TORS than at LVACs or HVACs (26.2% vs 44.0% vs 73.9%, respectively, p < .001). The rate of PMs was significantly higher at CCs than at LVACs or HVACs (25.7% vs 15.3% vs 9.2%, p < .001). A greater proportion of cases undergoing adjuvant radiotherapy (RT) received prolonged courses (23.6% vs 13.1% vs 8.8%, p < .001) or excessive doses (16.5% vs 11.5% vs 8.7%, p < .001) of RT at CCs than at LVACs or HVACs, respectively. 5-year OS was lowest at CCs (85.2%, 95%CI: 81.7-88.2%), intermediate at LVACs (88.9%, 95%CI: 87.2-90.4%), and highest at HVACs (91.4%, 95%CI: 89.5-92.9%; pLR<0.01). CONCLUSIONS: Significant differences in the type and quality of surgical and adjuvant treatment for HPVOPC exist between facility types based on TORS volume. Overall survival was lowest at CCs, intermediate at LVACs and highest at HVACs.

3.
bioRxiv ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38979305

RESUMO

Mechanisms of tumorigenesis in sinonasal squamous cell carcinoma (SNSCC) remain poorly described due to its rare nature. A subset of SNSCC are associated with the human papillomavirus (HPV); however, it is unknown whether HPV is a driver of HPV-associated SNSCC tumorigenesis or merely a neutral bystander. We hypothesized that performing the first large high-throughput sequencing study of SNSCC would reveal molecular mechanisms of tumorigenesis driving HPV-associated and HPV-independent SNSCC and identify targetable pathways. High-throughput sequencing was performed on 64 patients with HPV-associated and HPV-independent sinonasal carcinomas. Mutation annotation, viral integration, copy number, and pathway-based analyses were performed. Analysis of HPV-associated SNSCC revealed similar mutational patterns observed in HPV-associated cervical and head and neck squamous cell carcinoma, including lack of TP53 mutations and the presence of known hotspot mutations in PI3K and FGFR3. Further similarities included enrichment of APOBEC mutational signature, viral integration at known hotspot locations, and frequent mutations in epigenetic regulators. HPV-associated SNSCC-specific recurrent mutations were also identified including KMT2C , UBXN11 , AP3S1 , MT-ND4 , and MT-ND5 . Mutations in KMT2D and FGFR3 were associated with decreased overall survival. We developed the first known HPV-associated SNSCC cell line and combinatorial small molecule inhibition of YAP/TAZ and PI3K pathways synergistically inhibited tumor cell clonogenicity. In conclusion, HPV-associated SNSCC and HPV-independent SNSCC are driven by molecularly distinct mechanisms of tumorigenesis. Combinatorial blockade of YAP/TAZ and vertical inhibition of the PI3K pathway may be useful in targeting HPV-associated SNSCC whereas targeting MYC and horizontal inhibition of RAS/PI3K pathways for HPV-independent SNSCC. One Sentence Summary: This study solidifies HPV as a driver of HPV-associated SNSCC tumorigenesis, identifies molecular mechanisms distinguishing HPV-associated and HPV-independent SNSCC, and elucidates YAP/TAZ and PI3K blockade as key targets for HPV-associated SNSCC.

4.
Sci Total Environ ; 940: 173526, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-38825199

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent upper respiratory condition that manifests in two primary subtypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). While previous studies indicate a correlation between air pollution and CRS, the role of genetic predisposition in this relationship remains largely unexplored. We hypothesized that higher air pollution exposure would lead to the development of CRS, and that genetic susceptibility might modify this association. METHODS: This cohort study involving 367,298 adult participants from the UK Biobank, followed from March 2006 to October 2021. Air pollution metrics were estimated at residential locations using land-use regression models. Cox proportional hazard models were employed to explore the associations between air pollution exposure and CRS, CRSwNP, and CRSsNP. A polygenic risk score (PRS) was constructed to evaluate the joint effect of air pollution and genetic predisposition on the development of CRS. RESULTS: We found that the risk of CRS increased under long-term exposure to PM2.5 [the hazard ratios (HRs) with 95 % CIs: 1.59 (1.26-2.01)], PM10 [1.64 (1.26-2.12)], NO2 [1.11 (1.04-1.17)], and NOx [1.18 (1.12-1.25)], respectively. These effects were more pronounced among participants with CRSwNP, although the differences were not statistically significant. Additionally, we found that the risks for CRS and CRSwNP increased in a graded manner among participants with higher PRS or higher exposure to PM2.5, PM10, or NOx concentrations. However, no multiplicative or additive interactions were observed. CONCLUSIONS: Long-term exposure to air pollution increases the risk of CRS, particularly CRSwNP underscoring the need to prioritize clean air initiatives and environmental regulations.


Assuntos
Poluição do Ar , Rinossinusite , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poluição do Ar/efeitos adversos , Doença Crônica , Exposição Ambiental/efeitos adversos , Predisposição Genética para Doença , Pólipos Nasais/epidemiologia , Pólipos Nasais/genética , Material Particulado , Estudos Prospectivos , Rinossinusite/epidemiologia , Biobanco do Reino Unido , Reino Unido/epidemiologia
5.
JAMA Otolaryngol Head Neck Surg ; 150(7): 609-618, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38842800

RESUMO

Importance: Sinonasal squamous cell carcinoma (SNSCC) is the most commonly encountered cancer within the sinonasal cavity. Ongoing research has sought to ascertain the potential role of human papillomavirus (HPV) in the pathogenesis of SNSCC. Objective: To assess trends in HPV-associated and HPV-independent SNSCC over time, including assessment of clinical demographics, treatment patterns, and survival. Design, Setting, and Participants: This cohort study used patient data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database between 1975 and 2018. Anatomic sites with a greater predilection for HPV positivity (ie, nasal cavity, ethmoid sinus) were used as a surrogate for HPV-associated SNSCC; meanwhile, patients with SNSCC in the other subsites were classified into the HPV-independent group. Data were analyzed from August 2022 to May 2023. Main Outcomes and Measures: Clinical demographics and mortality trends over time were described for the HPV-associated and HPV-independent groups and further stratified according to stage on presentation. Results: The study population consisted of 3752 patients with SNSCC (mean [SD] age at diagnosis, 65.7 [13.3] years; 2417 [64.4%] male), with 1983 (52.9%) having HPV-associated SNSCC and 1769 (47.1%) with HPV-independent SNSCC. Patients with HPV-associated subsites compared with patients with HPV-independent SNSCC were more likely to present with localized disease (838 [42.3%] vs 162 [9.2%]), whereas more patients in the HPV-independent group than HPV-associated group presented with regional disease (1018 [57.5%] vs 480 [24.2%]). Incidence-based mortality was stable over time within the HPV-associated group (0.32%) and, conversely, showed a significant decrease within the HPV-independent group (-2.29%). Patients with HPV-associated SNSCC had a higher 5-year overall survival when compared with the HPV-independent group (62% vs 35% [difference, 27 percentage points; 95% CI, 23-31 percentage points]). The better 5-year overall survival in the HPV-associated group vs HPV-independent group was present across all disease stages (localized: hazard ratio [HR], 2.67; 95% CI, 1.96-3.65; regional: HR, 1.53; 95% CI, 1.29-1.82; and distant: HR, 1.97; 95% CI, 1.52-2.55). Conclusions and Relevance: This cohort study showed that the proportion of HPV-associated SNSCC rose over time associated with both a rise in the proportion of nasal cavity SNSCC and a decrease in HPV-independent maxillary sinus SNSCC. These data suggest that HPV-associated SNSCC has a distinct demographic and prognostic profile, given the improved survival seen in patients with HPV-associated SNSCC.


Assuntos
Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias dos Seios Paranasais , Humanos , Masculino , Feminino , Idoso , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Neoplasias dos Seios Paranasais/epidemiologia , Neoplasias dos Seios Paranasais/virologia , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/epidemiologia , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Programa de SEER , Taxa de Sobrevida , Estudos de Coortes , Estadiamento de Neoplasias , Papillomaviridae , Papillomavirus Humano
6.
Front Oncol ; 14: 1376622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741774

RESUMO

Introduction: Cancer stem cells (CSCs), a group of tumor-initiating and tumor-maintaining cells, may be major players in the treatment resistance and recurrence distinctive of chordoma. Characterizing CSCs is crucial to better targeting this subpopulation. Methods: Using flow cytometry, six chordoma cell lines were evaluated for CSC composition. In vitro, cell lines were stained for B7H6, HER2, MICA-B, ULBP1, EGFR, and PD-L1 surface markers. Eighteen resected chordomas were stained using a multispectral immunofluorescence (mIF) antibody panel to identify CSCs in vivo. HALO software was used for quantitative CSC density and spatial analysis. Results: In vitro, chordoma CSCs express more B7H6, MICA-B, and ULBP1, assessed by percent positivity and mean fluorescence intensity (MFI), as compared to non-CSCs in all cell lines. PD- L1 percent positivity is increased by >20% in CSCs compared to non-CSCs in all cell lines except CH22. In vivo, CSCs comprise 1.39% of chordoma cells and most are PD-L1+ (75.18%). A spatial analysis suggests that chordoma CSCs cluster at an average distance of 71.51 mm (SD 73.40 mm) from stroma. Discussion: To our knowledge, this study is the first to identify individual chordoma CSCs and describe their surface phenotypes using in vitro and in vivo methods. PD-L1 is overexpressed on CSCs in chordoma human cell lines and operative tumor samples. Similarly, potential immunotherapeutic targets on CSCs, including B7H6, MICA-B, ULBP1, EGFR, and HER2 are overexpressed across cell lines. Targeting these markers may have a preferential role in combating CSCs, an aggressive subpopulation likely consequential to chordoma's high recurrence rate.

7.
J Transl Med ; 22(1): 524, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822345

RESUMO

BACKGROUND: Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurrent, or metastatic disease oftentimes respond poorly to standard treatment methods. We hypothesized that an in-depth evaluation of the olfactory neuroblastoma tumor immune microenvironment would identify mechanisms of immune evasion in high-grade olfactory neuroblastoma as well as rational targetable mechanisms for future translational immunotherapeutic approaches. METHODS: Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed. RESULTS: A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration. CONCLUSION: These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.


Assuntos
Quimiocina CXCL10 , Quimiocina CXCL9 , Estesioneuroblastoma Olfatório , Antígenos HLA-DR , Imunoterapia , Microambiente Tumoral , Humanos , Estesioneuroblastoma Olfatório/terapia , Estesioneuroblastoma Olfatório/patologia , Estesioneuroblastoma Olfatório/imunologia , Quimiocina CXCL10/metabolismo , Imunoterapia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Quimiocina CXCL9/metabolismo , Microambiente Tumoral/imunologia , Antígenos HLA-DR/metabolismo , Idoso , Neoplasias Nasais/terapia , Neoplasias Nasais/patologia , Neoplasias Nasais/imunologia , Adulto , Regulação Neoplásica da Expressão Gênica
8.
Transl Oncol ; 44: 101943, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38593586

RESUMO

PURPOSE: Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of the sinonasal cavity with poor prognosis and limited treatment options. To investigate the potential for SNUC sensitivity to combinatory immunotherapy, we performed in vitro studies with SNUC cell lines and used multi-spectral immunofluorescence to characterize the in vivo patient SNUC tumor immune microenvironment (TIME). EXPERIMENTAL DESIGN: Human-derived SNUC cell lines were used for in vitro studies of tumor cell susceptibility to natural killer (NK) cell-based immunotherapeutic strategies. Tumor samples from 14 treatment naïve SNUC patients were examined via multi-spectral immunofluorescence and clinical correlations assessed. RESULTS: Anti-PD-L1 blockade enhanced NK cell lysis of SNUC cell lines ∼5.4 fold (P ≤ 0.0001). This effect was blocked by a CD16 neutralizing antibody demonstrating activity through an antibody-dependent cellular cytotoxicity (ADCC) mediated pathway. ADCC-dependent lysis of SNUC cells was further enhanced by upregulation of PD-L1 on tumor cells by exogenous interferon-gamma (IFN-γ) administration or interleukin-15 (IL-15) stimulated IFN-γ release from NK cells. Combination treatment with anti-PD-L1 blockade and IL-15 superagonism enhanced NK-cell killing of SNUC cells 9.6-fold (P ≤ 0.0001). Untreated SNUC patient tumor samples were found to have an NK cell infiltrate and PD-L1+ tumor cells at a median of 5.4 cells per mm2. A striking 55.7-fold increase in CKlow tumor cell/NK cell interactions was observed in patients without disease recurrence after treatment (P = 0.022). Patients with higher CD3+CD8+ in the stroma had a significantly improved 5-year overall survival (P = 0.0029) and a significant increase in CKlow tumor cell/CD8+ cytotoxic T cell interactions was noted in long-term survivors (P = 0.0225). CONCLUSION: These data provide the pre-clinical rationale for ongoing investigation into combinatory immunotherapy approaches for SNUC.

9.
Mod Pathol ; 37(5): 100448, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38369189

RESUMO

Sinonasal tumors with neuroepithelial differentiation, defined by neuroectodermal elements reminiscent of olfactory neuroblastoma (ONB) and epithelial features such as keratin expression or gland formation, are a diagnostically challenging group that has never been formally included in sinonasal tumor classifications. Recently, we documented that most of these neuroepithelial neoplasms have distinctive histologic and immunohistochemical findings and proposed the term "olfactory carcinoma" to describe these tumors. However, the molecular characteristics of olfactory carcinoma have not yet been evaluated. In this study, we performed targeted molecular profiling of 23 sinonasal olfactory carcinomas to further clarify their pathogenesis and classification. All tumors included in this study were composed of high-grade neuroectodermal cells that were positive for pankeratin and at least 1 specific neuroendocrine marker. A significant subset of cases also displayed rosettes and neurofibrillary matrix, intermixed glands with variable cilia, peripheral p63/p40 expression, and S100 protein-positive sustentacular cells. Recurrent oncogenic molecular alterations were identified in 20 tumors, including Wnt pathway alterations affecting CTNNB1 (n = 8) and PPP2R1A (n = 2), ARID1A inactivation (n = 5), RUNX1 mutations (n = 3), and IDH2 hotspot mutations (n = 2). Overall, these findings do demonstrate the presence of recurrent molecular alterations in olfactory carcinoma, although this group of tumors does not appear to be defined by any single mutation. Minimal overlap with alterations previously reported in ONB also adds to histologic and immunohistochemical separation between ONB and olfactory carcinoma. Conversely, these molecular findings enhance the overlap between olfactory carcinoma and sinonasal neuroendocrine carcinomas. A small subset of neuroepithelial tumors might better fit into the superseding molecular category of IDH2-mutant sinonasal carcinoma. At this point, sinonasal neuroendocrine and neuroepithelial tumors may best be regarded as a histologic and molecular spectrum that includes core groups of ONB, olfactory carcinoma, neuroendocrine carcinoma, and IDH2-mutant sinonasal carcinoma.


Assuntos
Biomarcadores Tumorais , Proteínas de Ligação a DNA , Estesioneuroblastoma Olfatório , Neoplasias dos Seios Paranasais , Fatores de Transcrição , Via de Sinalização Wnt , Humanos , Idoso , Pessoa de Meia-Idade , Masculino , Fatores de Transcrição/genética , Feminino , Via de Sinalização Wnt/genética , Proteínas de Ligação a DNA/genética , Estesioneuroblastoma Olfatório/patologia , Estesioneuroblastoma Olfatório/genética , Estesioneuroblastoma Olfatório/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/genética , Neoplasias dos Seios Paranasais/metabolismo , Adulto , Proteínas Nucleares/genética , Mutação , Idoso de 80 Anos ou mais , Neoplasias Nasais/patologia , Neoplasias Nasais/genética , Neoplasias Nasais/metabolismo , Imuno-Histoquímica
10.
Ear Nose Throat J ; : 1455613231222370, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38279791

RESUMO

Objectives: The ascending pharyngeal artery (APA) travels with the parapharyngeal internal carotid artery (pICA) in the parapharyngeal space (PPS). This study aimed to investigate the anatomical variations of the APA, and to explore their implications for endoscopic surgery in the PPS. Methods: Dissection of the APA in the PPS was performed on 10 cadaveric specimens (20 sides). The relationship between APA and PPS tumors was retrospectively reviewed in 20 patients, attempting to ascertain the APA during the resection of 10 pre-styloid and 10 retro-styloid PPS tumors. Results: During the cadaveric dissections, the APA was identified at the medial, posteromedial, or bilateral aspects of the pICA in 12 (60%) and 4 (20%) sides, respectively. In the remaining 4 sides (20%), the APA branched into several subcategory arteries lying at the medial and lateral aspects of the pICA. Branches of the APA were observed in 13/20 sides (65%). Two branches were found in 9/13 sides and 3 branches in 4/13, respectively. The APA was only identifiable in 1/10 (10%) of pre-styloid tumors, a patient with basal cell adenoma. In contrast, the APA was encountered surrounding the pICA in 8/10 (80%) of patients with retro-styloid tumors, all of which were schwannomas. No inadvertent injury of the APA or the pICA occurred in this cohort. Conclusions: With identification of the ascending pharyngeal artery on preoperative magnetic resonance imaging, it may serve as an additional landmark during the endoscopic extirpation of tumors arising in the PPS.

11.
J Natl Cancer Inst ; 116(7): 1051-1062, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38167712

RESUMO

BACKGROUND: Studies have shown lower overall survival for patients with head and neck cancer treated at low-volume or community cancer centers. As the incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma steadily rises in the United States, we hypothesized that a greater proportion of patients with HPV-related oropharyngeal squamous cell carcinoma is being treated at community cancer centers, with a shift toward primary nonsurgical treatment. METHODS: This cohort study included patients from the US National Cancer Database who received a diagnosis of HPV-related oropharyngeal squamous cell carcinoma from 2010 to 2019 and underwent treatment at a community cancer center or academic cancer center. The proportion of patients with HPV-related oropharyngeal squamous cell carcinoma treated at community cancer centers and receiving primary nonsurgical treatment was analyzed over time. Four-year overall survival was compared between community cancer centers and academic cancer centers. RESULTS: The majority (67.4%) of 20 298 patients were treated at an academic cancer center, yet the proportion of patients treated at community cancer centers increased by 10% from 2010 to 2019 (P < .01 for trend). The proportion of patients undergoing primary nonsurgical treatment increased from 62.1% to 73.7% from 2010 to 2019 (P < .01 for trend), and patients were statistically significantly more likely to undergo nonsurgical treatment at community cancer centers than at academic cancer centers (adjusted odds ratio = 1.20, 95% confidence interval = 1.18 to 1.22). Treatment at community cancer centers was associated with worse survival overall (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09 to 1.31), specifically for patients receiving primary nonsurgical treatment (adjusted hazard ratio = 1.22, 95% confidence interval = 1.11 to 1.34). CONCLUSIONS: Treatment of HPV-related oropharyngeal squamous cell carcinoma has recently shifted to community cancer centers, with an increase in the proportion of nonsurgical treatment and worse overall survival at these centers compared with academic cancer centers. Concentration of care for HPV-related oropharyngeal squamous cell carcinoma at academic cancer centers and dedicated head and neck cancer centers may increase access to all available treatment modalities and improve survival.


Assuntos
Institutos de Câncer , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/virologia , Idoso , Institutos de Câncer/estatística & dados numéricos , Estados Unidos/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Taxa de Sobrevida , Papillomavirus Humano
12.
Int Forum Allergy Rhinol ; 14(2): 149-608, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37658764

RESUMO

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.


Assuntos
Neoplasias de Cabeça e Pescoço , Hipersensibilidade , Neoplasias dos Seios Paranasais , Humanos , Qualidade de Vida , Neoplasias dos Seios Paranasais/terapia , Neoplasias dos Seios Paranasais/patologia
13.
Ear Nose Throat J ; : 1455613231197730, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37786236

RESUMO

Objective: Tumors arising from the upper parapharyngeal space (UPPS) may have intimate relationships with the internal carotid artery (ICA) and the internal jugular vein (IJV). The significance of the ICA in UPPS has been sufficiently articulated, whereas the relevance of the IJV has not been addressed. This study aimed to assess the anatomical variations of the IJV within the UPPS, and to explore its implications for surgical procedures. Methods: An endoscopic dissection of the IJV was performed on 10 cadaveric specimens. In addition, 30 patients who underwent transoral or transcervical resection of UPPS tumors were retrospectively reviewed to characterize the IJV and its relation to the tumor. Results: On the cadaveric specimens, the IJV was located at the posteromedial and posterolateral aspects of the styloid process in 13 (65%) and 7 (35%) sides, respectively. In our clinical series, the IJV was not encountered in 18 patients with pre-styloid tumors. In 12 patients harboring retro-styloid tumors, the IJV was partially (n = 5) or completely (n = 7) compressed and was displaced into the posterolateral aspect of the tumor. The IJV was injured intraoperatively in 1 patient, requiring an immediate conversion to an open transcervical corridor that allowed its exposure and ligation without difficulty. Conclusion: This study characterizes the IJV and its relationship with adjacent neurovascular structures in the UPPS, which may provide further safeguards during transoral and transcervical procedures in the UPPS.

14.
J Neurol Surg Rep ; 84(3): e68-e70, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37457039

RESUMO

Recurrent nasopharyngeal carcinoma (rNPC) presents unique challenges as reirradiation comes with significant treatment-related morbidity in swallowing, middle ear function, and large-vessel integrity. Advances in endoscopic technology have made surgery for rNPC an increasingly viable option for select patients and may play a role in providing a better quality of life to patients with this challenging disease. In carefully selected patients, endoscopic and open surgical approaches may provide comparable disease control while mitigating long-term treatment-related morbidity.

16.
Curr Oncol Rep ; 25(4): 269-278, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36753024

RESUMO

PURPOSE OF REVIEW: During the past few years there has been an expansion in our understanding of gene fusions and translocations involved in cancer of the sinonasal tract. Here we review the downstream biologic effects, clinical characteristics, and pathologic features of these tumors. The molecular consequences and neo-antigens resulting from these chromosomal aberrations are considered and targets for current and future clinical trials discussed. RECENT FINDINGS: Several new, clinically relevant, chromosomal aberrations have been discovered and evaluated to varying degrees in sinonasal tumors including DEK::AFF2, BRD4::NUT, ADCK4::NUMBL, and ETV6::NTRK3. Sinonasal malignancies demonstrate a diverse genetic landscape and varying clinical courses. Recent studies illustrate that gene fusions and translocations may play a role in carcinogenesis in certain sinonasal tumor subtypes and may be used to develop new biomarker-driven and patient-centered treatments.


Assuntos
Neoplasias , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Proteínas Nucleares/genética , Neoplasias/genética , Translocação Genética , Fusão Gênica , Proteínas de Fusão Oncogênica/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Proteínas de Ciclo Celular
17.
JAMA Netw Open ; 6(2): e2255971, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36787144

RESUMO

This case series assesses the incidence of human papillomavirus (HPV)-associated sinonasal squamous cell carcinoma (SNSCC) and the prevalence of HPV-positive SNSCC among US adults.


Assuntos
Carcinoma de Células Escamosas , Seios Paranasais , Humanos , Adulto , Papillomavirus Humano , Incidência , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia
18.
Ear Nose Throat J ; 102(6): 362-368, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33829883

RESUMO

INTRODUCTION: Extirpation of multiple head and neck paragangliomas carries challenge due to close anatomic relationships with critical neurovascular bundles. OBJECTIVES: This study aims to assess whether the application of 3-D models can assist with surgical planning and treatment of these paragangliomas, decrease surgically related morbidity and mortality. METHODS: Fourteen patients undergoing surgical resection of multiple head and neck paragangliomas were enrolled in this study. A preoperative 3-D model was created based on radiologic data, and relevant critical anatomic relationships were preoperatively assessed and intraoperatively validated. RESULTS: All 14 patients presented with multiple head and neck paragangliomas, including bilateral carotid body tumors (CBT, n = 9), concurrent CBT with glomus jugulare tumors (GJT, n = 4), and multiple vagal paragangliomas (n = 1). Ten patients underwent genomic analysis and all harbored succinate dehydrogenase complex subunit D (SDHD) mutations. Under guidance of the 3-D model, the internal carotid artery (ICA) was circumferentially encased by tumor on 5 of the operated sides, in 4 (80%) of which the tumor was successfully dissected out from the ICA, whereas ICA reconstruction was required on one side (20%). Following removal of CBT, anterior rerouting of the facial nerve was avoided in 3 (75%) of 4 patients during the extirpation of GJT with assistance of a 3-D model. Two patients developed permanent postoperative vocal cord paralysis. There was no vessel rupture or mortality in this study cohort. CONCLUSION: The 3-D model is beneficial for establishment of a preoperative strategy, as well as planning and guiding the intraoperative procedure for resection of multiple head and neck paragangliomas.


Assuntos
Tumor do Corpo Carotídeo , Tumor do Glomo Jugular , Neoplasias de Cabeça e Pescoço , Paraganglioma Extrassuprarrenal , Paraganglioma , Humanos , Neoplasias de Cabeça e Pescoço/cirurgia , Paraganglioma Extrassuprarrenal/cirurgia , Paraganglioma/cirurgia , Paraganglioma/patologia , Tumor do Corpo Carotídeo/cirurgia , Tumor do Corpo Carotídeo/patologia
19.
Ear Nose Throat J ; 102(1): 46-51, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33491478

RESUMO

INTRODUCTION: Resection of carotid body tumor (CBT) in patients of advanced ages has not been appreciated. OBJECTIVES: This study aims to assess the clinical characteristics and perioperative comorbidities for CBT resection in patients of advanced age and to validate the application of an "isolated island" technique for extirpation of CBT. METHODS: Eight patients of advanced age (≥60 years) who underwent CBT resection were enrolled as the study group (SG). Another 29 patients of younger age (<45 years old) underwent CBT extirpation were assigned as the control group (CG). The perioperative issues were compared between these 2 groups. RESULTS: The "isolated island" technique was successfully applied for resection of CBT in all 37 patients. The prevalence of Shamblin classification I, II, and III tumors in the SG was 12.5%, 62.5%, and 25%; whereas in the CG was 10.3%, 55.2%, and 34.5%, respectively. Bilateral CBT was observed in 7 patients of the CG and none in the SG. Vascular reconstruction was required for 1 (12.5%) patient in the SG, while it was required for 8 (27.6%) patients in the CG. Postoperative vocal cord palsy occurred in 37.5% of patients in SG, whereas the vocal cord palsy (34.5%) and dysphagia (6.9%) were commonly encountered in CG. In addition to postoperative length of stay (P = .004), no significant difference for operative time, intraoperative blood loss, or mortality were observed between these 2 groups (P > .05). CONCLUSION: Extirpation of CBT in patients of advanced age is rationale in appropriately selected patients. The "isolated island" technique is safe for CBT resection with seemingly low complication rates.


Assuntos
Procedimentos Cirúrgicos Cardiovasculares , Tumor do Corpo Carotídeo , Paralisia das Pregas Vocais , Humanos , Pessoa de Meia-Idade , Tumor do Corpo Carotídeo/cirurgia , Procedimentos Cirúrgicos Cardiovasculares/métodos
20.
Head Neck ; 45(1): 294-301, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36333984

RESUMO

The lateral poststyloid space (LPSS) located at the posterolateral aspect of the styloid process. This study aims to explore the anatomical relationships in LPSS via a transoral corridor, providing reference for addressing lesions extending to this region. An endoscopic transoral approach for exposure of the LPSS was performed on 6 cadaveric specimens (12 sides). Related landmarks were explored, and transoral extirpation of tumors extended into LPSS was employed in 12 patients. The deep lobe of the parotid gland, extratemporal facial nerve, and the accompanying artery in the LPSS were sufficiently exposed via the transoral corridor in all 12 cadaveric sides. The transoral corridor provided adequate exposure for tumors extending to the LPSS, and en bloc resection was achieved in these 12 patients. No facial nerve or vascular injury occurred, and no recurrence observed in this cohort with an average follow-up of 26 months. An endoscopic transoral approach provides a direct access to the LPSS. Appreciation of the anatomical relationships within the LPSS is valuable for employing a transoral extirpation of tumors extending to this specific region.


Assuntos
Cirurgia Endoscópica por Orifício Natural , Neoplasias , Humanos , Cirurgia Endoscópica por Orifício Natural/métodos , Artérias
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