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Objectives Sellar pathologies are frequently found on imaging performed to investigate headache. However, both headache and incidental sellar lesions are common. Hence, this study prospectively examined headache prevalence, phenotype, and severity in patients with sellar pathologies and the impact of transsphenoidal surgery on headache. Methods Patients undergoing transsphenoidal resection of sellar lesions were consecutively recruited. At baseline, participants were defined as having headache or not and headache phenotype was characterized using validated questionnaires. Headache severity was assessed at baseline and 6 months postoperatively using the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Score (MIDAS). Tumor characteristics were defined using radiological, histological, and endocrine factors. Primary outcomes included baseline headache prevalence and severity and headache severity change at 6 months postoperatively. Correlation between headache and radiological, histological, and endocrine characteristics was also of interest. Results Sixty participants (62% female, 47.1 ± 18.6 years) were recruited. Sixty-three percent possessed baseline headache. HIT-6 scores were higher in patients with primary headache risk factors, including younger age (R 2 = -0.417, p = 0.010), smoking history (63.31 ± 7.93 vs 54.44 ± 9.21, p = 0.0060), and family headache history (68.13 ± 7.01 vs 54.94 ± 9.11, p = 0.0030). Headaches were more common in patients with dural invasion (55.70 ± 12.14 vs 47.18 ± 10.15, p = 0.027) and sphenoid sinus invasion (58.87 ± 8.97 vs 51.29 ± 10.97, p = 0.007). Postoperative severity scores improved more with higher baseline headache severity (HIT-6: R 2 = -0.682, p < 0.001, MIDAS: R 2 = -0.880, p < 0.0010) and dural invasion (MIDAS: -53.00 ± 18.68 vs 12.00 ± 17.54, p = 0.0030). Conclusion Headaches in sellar disease are likely primary disorders triggered or exacerbated by sellar pathology. These may respond to surgery, particularly in patients with severe headache and dural invasion.
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BACKGROUND: Endoscopic sinus surgery with a middle meatal antrostomy is a common intervention in the treatment algorithm for maxillary sinus pathologies. However, this procedure has its origins in a time when simple ventilation of the sinus cavity was the primary (and only often) goal of surgery. In some patients, persistent mucociliary dysfunction occurs despite ventilatory surgery. Although the endoscopic modified medial maxillectomy (MMM) was originally described for tumour surgery, it provides a radical yet still functional option to overcome chronic sinus dysfunction. OBJECTIVE: The goal of this study was to describe the functional status of a post-MMM sinus cavity. METHODS: A consecutive series of patients who underwent at least a unilateral MMM by three tertiary rhinologists were retrospectively reviewed. Prospectively collected data included patient demographics (including age, gender, smoking status and comorbidities), disease-specific factors, microbiology, and preoperative patient-reported symptoms based on the 22-item Sinonasal Outcome Test-22 (SNOT-22) and radiology. The primary outcome of the study was the presence of sinus dysfunction, defined by mucostasis or pooling on endoscopic examination at the last follow-up. Secondary outcomes included the need for revision surgery as a result of sinus dysfunction and the improvement in SNOT-22 score. RESULTS: A total of 551 medial maxillectomies (47.0% female, 52.9 ± 16.8 years) were performed. Very few patients experienced post-operative sustained mucostasis following MMM (10.2%) and even fewer required revision surgery (5.0%). Chronic obstructive pulmonary disease (odds ratio (OR) = 6.82, P < 0.002.) and asthma (OR = 2.48, P = 0.03) were associated with mucostasis. Patients who underwent an MMM experienced a notable postoperative improvement in SNOT-22 score (45.9 ± 23.7 (pre-op) vs. 23.6 ± 19.4 (post-op); paired t-test, P < 0.0001). CONCLUSION: The MMM, whether performed for access to pathology or with the intent to avoid mucous 'sumping' with the sinus, can provide a long-term functional maxillary sinus cavity with minimal morbidity.
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Endoscopia , Seio Maxilar , Humanos , Feminino , Masculino , Estudos Retrospectivos , Seio Maxilar/cirurgia , Endoscopia/métodos , Maxila , Reoperação , Doença Crônica , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the range of incidental mucosal changes in a general sinonasally asymptomatic population on radiology. DATA SOURCES: Medline (1996-present) and Embase (1974-present) were searched on March 14, 2020, to identify articles that reported radiological sinus mucosal findings in asymptomatic population groups. Bibliographic search of included studies was conducted to identify additional articles. REVIEW METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane Handbook for Systematic Reviews of Interventions. A comprehensive search strategy was formulated and articles screened to extract data reporting Lund-Mackay (LM) score, presence of mucous retention cysts, and maxillary mucosal thickening. A random-effects model was used in meta-analysis. RESULTS: A total of 950 articles were identified, of which 33 manuscripts met the inclusion criteria. The included studies involved 16,966 sinonasally asymptomatic subjects. The mean LM score was 2.24 (95% CI, 1.61-2.87), and an LM score of ≥4 in 14.71% (95% CI, 6.86-24.82%) was present across all general asymptomatic population groups. Mucous retention cysts were noted in 13% (95% CI, 8.33-18.55%) and maxillary mucosal thickening of ≥2 mm in 17.73% (95% CI, 8.67-29.08%). CONCLUSION: The prevalence of incidental mucosal changes in a general asymptomatic population on radiology needs to be considered when making a diagnosis of chronic rhinosinusitis.
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Cistos , Seios Paranasais , Sinusite , Doença Crônica , Humanos , Maxila , Sinusite/diagnóstico por imagem , Sinusite/epidemiologia , Sinusite/cirurgiaRESUMO
BACKGROUND: Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. METHODS: A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. RESULTS: 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τb = -8.47, p < 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = -2.37, p = 0.02). CONCLUSION: Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.
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Antiasmáticos , Asma , Sinusite , Adulto , Antiasmáticos/uso terapêutico , Estudos Transversais , Eosinófilos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sinusite/tratamento farmacológicoRESUMO
BACKGROUND: Persistent mucosal inflammation in patients with chronic rhinosinusitis (CRS) often results in ongoing symptoms, recurrence of polypoid mucosa, infective exacerbations, and further systemic medication despite surgical intervention. Debate exists as to the most effective topical therapy in CRS. METHODS: The objective was to determine if corticosteroid delivered via a nasal irrigation or via a simple nasal spray would be more effective in controlling the symptoms and signs of CRS. A double-blind placebo-controlled randomized trial over 12 months was performed between 3 tertiary rhinologic clinics. After sinus surgery, all patients performed a nasal irrigation followed by a nasal spray once a day for 12 months. Groups were defined by corticosteroid (2 mg mometasone) delivered by either spray or irrigation. The primary outcomes were patient-reported symptoms: visual analogue score (VAS) and 22-item Sino-Nasal Outcome Test (SNOT-22), a global rating of sinonasal function. Secondary outcomes were also recorded from radiology (Lund-Mackay score [LMS]) and endoscopic (Modified Lund-Kennedy score [mLKS]) assessments. RESULTS: A total of 44 patients were randomized (age 50.3 ± 13.0 years; 40.9% female). Overall, patients improved significantly from either intervention. However, the corticosteroid nasal irrigation group had greater improvement in nasal blockage (-69.91 ± 29.37 vs -36.12 ± 42.94; p = 0.029), a greater improvement on LMS (-12.07 ± 4.43 vs -7.39 ± 6.94; p = 0.031) and less inflammation on mLKS at 12 months (7.33 ± 11.55 vs 21.78 ± 23.37; p = 0.018). One-year posttreatment blockage, drainage, fever, and total VAS scores were all lower in the corticosteroid irrigation group. CONCLUSION: In the setting of diffuse or patchy CRS disease, the use of corticosteroid delivered by nasal irrigation is superior to simple nasal spray in postsurgical patients.
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Corticosteroides/uso terapêutico , Lavagem Nasal , Sprays Nasais , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Adulto , Doença Crônica , Método Duplo-Cego , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Rinite/cirurgia , Sinusite/cirurgia , Resultado do TratamentoAssuntos
Rinite Alérgica , Rinite , Sinusite , Doença Crônica , Humanos , Rinite/diagnóstico , Sinusite/diagnósticoAssuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias da Língua/metabolismo , Língua/patologia , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Proteínas de Homeodomínio/genética , Humanos , Proteínas com Domínio LIM , Língua/metabolismo , Neoplasias da Língua/patologia , Fatores de Transcrição/genéticaRESUMO
PURPOSE: The INK4A-ARF locus at chromosome 9p21 is frequently altered in head and neck squamous cell carcinoma (SCC) and encodes two distinct tumor suppressors, p16(INK4A) and p14(ARF). This study addressed the role of p14(ARF) as a potential prognostic marker in this disease. EXPERIMENTAL DESIGN: p14(ARF) protein expression was assessed by immunohistochemistry in a cohort of 140 patients with SCC of the anterior tongue. Using univariate and multivariate Cox's proportional hazards models, the outcomes examined were time to disease recurrence or death, with or without clinicopathologic covariates, including nodal status, disease stage, treatment status, Ki-67 staining, and molecular markers with known functional or genetic relationships with p14(ARF) (p16(INK4A), p53, pRb, p21(WAF1/CIP1), E2F-1). RESULTS: On multivariate analysis, p14(ARF) positivity (nucleolar p14(ARF) staining and/or nuclear p14(ARF) staining in >/=30% of tumor cells) was an independent predictor of improved disease-free survival (DFS; P = 0.002) and overall survival (OS; P = 0.002). This was further enhanced when p14(ARF) positivity was cosegregated with positive (>/=1%) p16(INK4A) staining (DFS, P < 0.001; OS, P < 0.001). Patients whose cancers were p14(ARF) negative and p53 positive (>50%) had the poorest outcome (DFS, P < 0.001; OS, P < 0.001) of any patient subgroup analyzed. CONCLUSIONS: These data show that in patients with SCC of the tongue, combined nuclear and nucleolar expression of p14(ARF) protein predicts for improved DFS and OS independent of established prognostic markers.
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Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/patologia , Proteína Supressora de Tumor p14ARF/biossíntese , Carcinoma de Células Escamosas/metabolismo , Proteínas de Ciclo Celular/análise , Estudos de Coortes , Ciclina D1/análise , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Inibidor de Quinase Dependente de Ciclina p21 , Proteínas de Ligação a DNA/análise , Fatores de Transcrição E2F , Fator de Transcrição E2F1 , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Análise Multivariada , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Proteína do Retinoblastoma/análise , Análise de Sobrevida , Neoplasias da Língua/metabolismo , Fatores de Transcrição/análise , Proteína Supressora de Tumor p53/análiseRESUMO
PURPOSE: Despite promising initial results, recent Phase III trials of the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib ("Iressa"; AstraZeneca, Wilmington, Delaware) in advanced head and neck squamous cell carcinoma (HNSCC) have been equivocal. Cyclin D1, an EGFR target gene, is frequently overexpressed in HNSCC, has been implicated in its pathogenesis, and is strongly associated with poor prognosis in this disease. Therefore, we examined the relationship between deregulated cyclin D1 expression and sensitivity to gefitinib to determine whether this frequently occurring oncogenic change affected the cellular response to gefitinib. EXPERIMENTAL DESIGN: A panel of six EGFR-overexpressing HNSCC cell lines was used to correlate CCND1 gene copy number, cyclin D1 expression, and response to gefitinib. The effect of constitutive overexpression of cyclin D1 was assessed by establishing stably transfected clonal SCC-9 cell lines. RESULTS: Three of six cell lines displayed cyclin D1 amplification and/or overexpression, and these cell lines were resistant to gefitinib. SCC 9 clones overexpressing cyclin D1 continued to proliferate and maintained their S-phase fraction when treated with gefitinib, whereas empty vector control clones and the parental SCC 9 cells were profoundly inhibited and displayed marked reductions in S-phase. The resistance of cyclin D1-overexpressing clones and cyclin D1-amplified cell lines was associated with maintenance of cyclin D1 expression after gefitinib treatment. CONCLUSIONS: These data suggest that deregulated cyclin D1 overexpression may be associated with resistance of HNSCC to EGFR inhibitors. Therefore, the role of cyclin D1 as a marker of therapeutic response and its utility as a prognostic marker in HNSCC warrant additional analysis.
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Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Ciclina D1/biossíntese , Receptores ErbB/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Southern Blotting , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , DNA/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Fase G1 , Gefitinibe , Vetores Genéticos , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Concentração Inibidora 50 , Prognóstico , Fase S , Fatores de TempoRESUMO
PURPOSE: A better understanding of the molecular pathways underlying the development of epithelial ovarian cancer (EOC) is critical to identify ovarian tumor markers for use in diagnostic or therapeutic applications. The aims of this study were to integrate the results from 14 transcript profiling studies of EOC to identify novel biomarkers and to examine their expression in early and late stages of the disease. EXPERIMENTAL DESIGN: A database incorporating genes identified as being highly up-regulated in each study was constructed. Candidate tumor markers were selected from genes that overlapped between studies and by evidence of surface membrane or secreted expression. The expression patterns of three integral membrane proteins, discoidin domain receptor 1 (DDR1), claudin 3 (CLDN3), and epithelial cell adhesion molecule, all of which are involved in cell adhesion, were evaluated in a cohort of 158 primary EOC using immunohistochemistry. RESULTS: We confirmed that these genes are highly overexpressed in all histological subtypes of EOC compared with normal ovarian surface epithelium, identifying DDR1 and CLDN3 as new biomarkers of EOC. Furthermore, we determined that these genes are also expressed in ovarian epithelial inclusion cysts, a site of metaplastic changes within the normal ovary, in borderline tumors and in low-grade and stage cancer. A trend toward an association between low CLDN3 expression and poor patient outcome was also observed. CONCLUSIONS: These results suggest that up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of EOC and have potential application in the early detection of disease.
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Antígenos de Neoplasias/biossíntese , Moléculas de Adesão Celular/biossíntese , Proteínas de Membrana/biossíntese , Neoplasias Ovarianas/metabolismo , Ovário/metabolismo , Receptores Proteína Tirosina Quinases/biossíntese , Biomarcadores Tumorais , Adesão Celular , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Claudina-3 , Estudos de Coortes , DNA Complementar/metabolismo , Bases de Dados como Assunto , Receptor com Domínio Discoidina 1 , Progressão da Doença , Intervalo Livre de Doença , Molécula de Adesão da Célula Epitelial , Epitélio/metabolismo , Feminino , Marcadores Genéticos , Humanos , Imuno-Histoquímica , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: The infratemporal fossa is a well-concealed, complex anatomical space. Neoplasms arising in this area are heterogenous in nature and have an insidious onset and usually present late. METHODS AND RESULTS: We present a case of a 71-year-old woman who presented with worsening facial pain, trismus, and a large mass in her infratemporal fossa with minimal associated temporomandibular joint destruction. She underwent a surgical excision of the mass, which revealed a pseudogout deposit. CONCLUSION: The clinical and radiological features of patients with tophaceous pseudogout frequently mimic those of a benign or malignant neoplasm of the infratemporal fossa, often resulting in more radical surgery.
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Condrocalcinose/diagnóstico , Condrocalcinose/cirurgia , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Base do Crânio/cirurgia , Osso Temporal/cirurgia , Idoso , Condrocalcinose/complicações , Diagnóstico Diferencial , Dor Facial/etiologia , Feminino , Humanos , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Neoplasias da Base do Crânio/complicações , Osso Temporal/patologia , Articulação Temporomandibular/patologia , Resultado do Tratamento , Trismo/etiologiaRESUMO
The authors present two case studies on pediatric nasal obstruction that highlight the consequences of a delayed diagnosis and the complexities of managing obstructed lesions in children.
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Obstrução Nasal/cirurgia , Adolescente , Angiofibroma/complicações , Angiofibroma/fisiopatologia , Fissura Palatina/complicações , Encefalocele/etiologia , Encefalocele/cirurgia , Epistaxe , Feminino , Humanos , Lactente , Masculino , Meningites Bacterianas/complicações , Obstrução Nasal/etiologiaRESUMO
OBJECTIVE: To evaluate whether topical steroids provide symptomatic relief in patients with chronic rhinosinusitis without polyps. DATA SOURCES: MEDLINE, EMBASE, and Cochrane CENTRAL databases. REVIEW METHODS: Systematic review and meta-analysis was performed of the articles identified by two independent reviewers of all randomized controlled trials that had evaluated intranasal corticosteroids in patients with chronic rhinosinusitis (CRS) without polyps. The quality of included studies was evaluated, and results synthesized using standard random-effects meta-analytical methods. RESULTS: Of 424 potential studies, only nine randomized trials involving 657 patients in total were eligible. Quality of design and reporting was suboptimal, with only one trial adhering to accepted standards for reporting. Five trials combined outcome measures and reported on overall response of CRS without polyps to topical steroids. The summary estimate for overall response to treatment showed no significant benefit and substantial variability among studies (5 trials: RR 0.75, 95% CI 0.50-1.10, P = 0.14, chi(2) = 13.78, I(2) = 66.2%). Total symptom score was reported in three trials with a standardized mean difference favoring topical steroids (RR 0.63, 95% CI 0.16-1.09, P = 0.009), with no evidence of heterogeneity (chi(2) = 3.03, P = 0.22). Although the data were limited, there were no reports of increased adverse effects with topical steroids. CONCLUSION: There is insufficient evidence to demonstrate a clear overall benefit for topical steroids in CRS without polyps; however, their use appears safe and may show some symptomatic benefit. A class effect among different topical steroids cannot be assumed, and further trials are required.