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OBJECTIVE: To analyze the growth trajectory of children with obesity before and after adenotonsillectomy (T&A). We hypothesize that T&A will not affect the growth trajectory but children in a multidisciplinary weight management program (MWMP) will have a healthier growth trajectory. STUDY DESIGN: Retrospective review. SETTING: Tertiary Children's Hospital. METHODS: Body mass index (BMI) trajectories of nonsyndromic children with obesity and obstructive sleep apnea (OSA) who underwent T&A were analyzed. A linear mixed effects model was fit to the BMI expressed as a percentage of the 95th percentile (%BMIp95 ) data. Covariates included demographic variables, pre- and postoperative participation in an MWMP, baseline obesity class, and time. We explored clinically meaningful interactions. BMI slope estimates before and after surgery were calculated and compared for baseline obesity classification and postoperative MWMP visits. RESULTS: A total of 177 patients, 58% male with a mean age of 9.7 years at the time of surgery, were studied. Higher baseline obesity class (II and III), time, the interaction between obesity class III and elapsed time relative to surgical date, and the interaction between obesity class III and the postsurgical period were all significantly associated with the outcome of %BMIp95 (P < .05). There was a significantly higher %BMIp95 trajectory following surgery in patients with baseline obesity class III who did not have any postoperative MWMP visits (P < .001). Preoperative obesity visits, however, were not significantly associated with postoperative growth. CONCLUSION: The association between T&A and weight trajectory depends upon obesity class and participation in a MWMP. Coordinated care of children with obesity between otolaryngologists and an MWMP may improve OSA and obesity outcomes. LEVEL OF EVIDENCE: The level of evidence: 3.
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Apnea Obstructiva del Sueño , Tonsilectomía , Niño , Humanos , Masculino , Femenino , Polisomnografía , Adenoidectomía , Obesidad/complicaciones , Estudios RetrospectivosRESUMEN
INTRODUCTION: Pediatric cystic sublingual masses often present a diagnostic dilemma for practitioners. Though uncommon, dermoid or epidermoid cysts can present in the sublingual space at any age and are often misdiagnosed as an inflammatory pseudocyst (ranula) or lymphatic malformation. Imaging may not always identify the underlying etiology, requiring physicians to maintain a high index of suspicion for these relatively rare oral cysts. OBJECTIVES: To describe the presentation and treatment of sublingual dermoid and epidermoid cysts presenting to a tertiary children's hospital over 20 years. METHODS: A retrospective review of all pathology specimens identified as dermoid or epidermoid cysts within the sublingual space from 1999 to 2019. Patient charts were then reviewed for relevant clinical, imaging, and operative data. RESULTS: Twelve pediatric patients were identified (8 female, 4 male) with a mean age of 7.2 years (SD 5.6). Eighty six percent (6/7) of dermoid cysts were found in female patients, while 60% (3/5) of epidermoid cysts were in male patients. Multiple dermoid and epidermoid cysts were each found in one patient (8%). Two epidermoid cysts presented in the neonatal period. Preoperative diagnosis included nondiagnostic "cystic mass" (33%), ranula (25%), lymphatic malformation (LM) (17%), and dermoid/epidermoid cyst (17%). Two thirds of patients (8/12) underwent imaging, with all receiving either MRI or CT. Although MRI was the most likely to suggest the possibility of a dermoid/epidermoid cyst (2/4), ranula was the most common primary radiographic diagnosis (5/8). One patient underwent sclerotherapy for presumed LM one year prior to surgical excision of the cyst. Eleven patients (92%) underwent intraoral excision, one (8.3%) underwent a combined intraoral/extraoral approach. CONCLUSIONS: To our knowledge, this review represents the largest case series of pediatric sublingual dermoid and epidermoid cysts to date. This series contained higher levels of epidermoid cysts and female patients than previously reported in the literature. Identifying more dermoid cysts in females and epidermoid cysts in males is also a new finding. MRI was superior to CT and US regarding the presence of a dermoid/epidermoid cyst. Frequently misdiagnosed, it is important to consider these relatively rare pathologies when treating children presenting with sublingual masses in order to avoid delayed and/or inappropriate treatment.
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Quiste Dermoide/diagnóstico , Quiste Dermoide/cirugía , Quiste Epidérmico/diagnóstico , Quiste Epidérmico/cirugía , Enfermedades de la Boca/diagnóstico , Adolescente , Niño , Preescolar , Quiste Dermoide/patología , Quiste Epidérmico/patología , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Enfermedades de la Boca/patología , Enfermedades de la Boca/cirugía , Suelo de la Boca/patología , Ránula/diagnóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
OBJECTIVE: To determine factors affecting outcomes for patients with sinonasal and nasopharyngeal adenoid cystic carcinoma (SNACC) treated using the endoscopic endonasal approach (EEA) with preservation of key structures followed by adjuvant radiotherapy (RT). METHOD: Retrospective case series of 30 patients treated at the University of Pittsburgh between 2000 and 2014. Hospital records were reviewed for clinical and pathologic data. Outcome measures included overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates. RESULTS: The majority of patients had T4a and T4b disease (23.3%, and 63.3%). Microscopically positive margins were present in 21 patients (63.6%). Positive margins were present in nine patients (30.0%). The mean and median follow-up were 3.97 and 3.29 years. Five-year OS, DFS, LRFS, and DMFS were 62.66%, 58.45%, 87.54%, and 65.26%. High-/intermediate-grade tumors had worse DFS (P = .023), and LRFS (P = .026) (HR = 4.837, 95% CI, 1.181-19.812). No factors were associated with significantly worse DMFS. No patient suffered CSF leak, optic nerve, or internal carotid injury. The mean and median length of hospital stay was 4.1 days and 2.0 days (range: 0-32 days). CONCLUSION: Organ-preserving EEA with adjuvant RT for low-grade SNACC offers 5-year survival similar to that reported by other studies, which include radical, open skull base surgery. Patients with high-grade disease do poorly and may benefit from novel treatment strategies. For low-grade disease, organ-preserving EEA with RT may be the best option, offering a balance of survival, quality of life, and decreased morbidity for patients with this difficult-to-cure disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1414-1421, 2020.
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Carcinoma Adenoide Quístico/terapia , Endoscopía/mortalidad , Neoplasias Nasales/terapia , Tratamientos Conservadores del Órgano/mortalidad , Neoplasias Faríngeas/terapia , Neoplasias de la Base del Cráneo/terapia , Adulto , Carcinoma Adenoide Quístico/mortalidad , Supervivencia sin Enfermedad , Endoscopía/métodos , Femenino , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Neoplasias Nasales/mortalidad , Tratamientos Conservadores del Órgano/métodos , Neoplasias Faríngeas/mortalidad , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias de la Base del Cráneo/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: Oncocytomas and oncocytic carcinomas are rare tumors of the sinonasal cavity with the propensity for local invasion. This report and systematic review details a case of a nasal oncocytoma involving the lacrimal sac and provides an update of the current literature. METHODS: A systematic literature review was performed using PubMed and Ovid databases. The data obtained from published articles with sinonasal oncocytoma/oncocytic carcinoma as the primary diagnosis included patient demographics, presentation, radiographic and histologic findings, management, and recurrence rates. RESULTS: Twenty cases were identified. The most common symptoms were epistaxis (n = 11) and nasal obstruction (n = 11). Involvement of the nasal cavity was most common (n = 17), followed by the paranasal sinuses (n = 13) and nasolacrimal apparatus (n = 4). Recurrence occurred in 55% of cases. Recurrence was associated with invasion or infiltration found on histology or the presence of both invasion/infiltration and mitotic figures/pleomorphism (p < 0.05), with no significant relationship between recurrence and age at diagnosis (p = 0.42), sex (p = 0.65), and location of tumor (p = 0.14). The authors present the case of a 73-year-old woman with a 5-month history of worsening epistaxis and biopsy-proven oncocytoma. Complete surgical resection of the tumor using combined endonasal endoscopic and anterior orbitotomy approach is described. CONCLUSION: Oncocytomas and oncocytic carcinomas are rare tumors of the sinonasal cavity with a high rate of local recurrence and orbital involvement. Surgical resection is the treatment of choice and complete resection can be achieved with an endoscopic endonasal approach.
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Adenoma Oxifílico , Carcinoma , Neoplasias de los Senos Paranasales , Adenoma Oxifílico/diagnóstico , Adenoma Oxifílico/patología , Adenoma Oxifílico/terapia , Carcinoma/diagnóstico , Carcinoma/patología , Carcinoma/terapia , Humanos , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Neoplasias de los Senos Paranasales/diagnóstico , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/terapiaRESUMEN
Previous studies indicate that extracts and purified components from Garcinia species inhibit the growth of human colon cancer cells. Garcinia benzophenones activate the expression of genes in the endoplasmic reticulum and cellular energy stress (mTOR) pathways. This study examines the growth inhibitory and synergistic effects of Garcinia benzophenones, alone or combined with chemopreventive agents, on human colon cancer cells. To find optimal combination treatments, HT29 colon cancer cells were treated with benzophenones alone, or combined with chemopreventive agents, and cell growth measured using the MTT assay. To reveal effects on signaling pathways, we assessed effects of the MEK inhibitor U0126 and the ER IP3 receptor antagonist heparin, as well as effects on the phosphorylation of 4E-BP-1 (mTOR pathway), using Western blot analysis. New and known benzophenones from Garcinia intermedia inhibited the growth of human colon cancer cells; an alcohol extract of Garcinia xanthochymus, as well as purified guttiferones (guttiferone E and xanthochymol), preferentially inhibited the growth of colon cancer versus nonmalignant intestinal epithelial cells. Guttiferone E exhibited synergy with the NSAID sulindac sulfide and xanthochymol, with the spice turmeric. Guttiferone A did not alter phosphorylation of 4E-BP-1, indicating that the mTORC1 pathway is not involved in its action. The effects of xanthochymol were enhanced by U0126, at low doses, and were blocked by heparin, indicating that the MEK pathway is involved, while the ER IP3 receptor is critical for its action. These studies indicate the potential of benzophenones, alone or combined with sulindac sulfide or turmeric, to prevent and treat colon cancer.
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Antineoplásicos Fitogénicos/química , Benzofenonas/química , Garcinia/química , Regulación Neoplásica de la Expresión Génica , Extractos Vegetales/química , Sulindac/análogos & derivados , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Benzofenonas/aislamiento & purificación , Benzofenonas/farmacología , Butadienos/farmacología , Celecoxib , Proteínas de Ciclo Celular , Línea Celular Tumoral , Curcuma , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Inhibidores Enzimáticos/farmacología , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Heparina/farmacología , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Nitrilos/farmacología , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Extractos Vegetales/farmacología , Pirazoles/farmacología , Transducción de Señal , Relación Estructura-Actividad , Sulfonamidas/farmacología , Sulindac/farmacología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Studies indicate that extracts and purified components, including carnosic acid, from the herb rosemary display significant growth inhibitory activity on a variety of cancers. PURPOSE: This paper examines the ability of rosemary/carnosic acid to inhibit the growth of human breast cancer cells and to synergize with curcumin. MATERIALS AND METHODS: To do this, we treated human breast cancer cells with rosemary/carnosic acid and assessed effects on cell proliferation, cell cycle distribution, gene expression patterns, activity of the purified Na/K ATPase and combinations with curcumin. RESULTS: Rosemary/carnosic acid potently inhibits proliferation of ER-negative human breast cancer cells and induces G1 cell cycle arrest. Further, carnosic acid is selective for MCF7 cells transfected for Her2, indicating that Her2 may function in its action. To reveal primary effects, we treated ER-negative breast cancer cells with carnosic acid for 6h. At a low dose, 5 µg/ml (15 µM), carnosic acid activated the expression of 3 genes, induced through the presence of antioxidant response elements, including genes involved in glutathione biosynthesis (CYP4F3, GCLC) and transport (SLC7A11). At a higher dose, 20 µg/ml, carnosic acid activated the expression of antioxidant (AKR1C2, TNXRD1, HMOX1) and apoptosis (GDF15, PHLDA1, DDIT3) genes and suppressed the expression of inhibitor of transcription (ID3) and cell cycle (CDKN2C) genes. Carnosic acid exhibits synergy with turmeric/curcumin. These compounds inhibited the activity of the purified Na-K-ATPase which may contribute to this synergy. CONCLUSION: Rosemary/carnosic acid, alone or combined with curcumin, may be useful to prevent and treat ER-negative breast cancer.
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Abietanos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Curcuma/química , Curcumina/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Rosmarinus/química , Abietanos/farmacología , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Proliferación Celular/efectos de los fármacos , Curcumina/farmacología , Sinergismo Farmacológico , Femenino , Expresión Génica/efectos de los fármacos , Glutatión/genética , Glutatión/metabolismo , Humanos , Proteínas Inhibidoras de la Diferenciación/metabolismo , Células MCF-7 , Proteínas de Neoplasias/metabolismo , Extractos Vegetales/farmacología , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismoRESUMEN
The gene encoding the plasma membrane proton pump (H+ -ATPase) of Aspergillus fumigatus, PMA1, was characterized from A. fumigatus strain NIH 5233 and clinical isolate H11-20. An open reading frame of 3,109 nucleotides with two introns near the N terminus predicts a protein consisting of 989 amino acids with a molecular mass of approximately 108 kDa. The predicted A. fumigatus enzyme is 89 and 51% identical to H+ - ATPases of Aspergillus nidulans and Saccharomyces cerevisiae, respectively. The A. fumigatus PMA1 is a typical member of the P-type ATPase family that contains 10 predicted transmembrane segments and conserved sequence motifs TGES, CSDKTGT, MLTGD, and GDGVN within the catalytic region. The enzyme represents 2% of the total plasma membrane protein, and it is characteristically inhibited by orthovanadate, with a 50% inhibitory concentration of approximately 1.8 microM. H+ -ATPases from Aspergillus spp. contain a highly acidic insertion region of 60 amino acids between transmembrane segments 2 and 3, which was confirmed for the membrane-assembled enzyme with a peptide-derived antibody. An increasing A. fumigatus PMA1 copy number confers enhanced growth in low-pH medium, consistent with its role as a proton pump. These results provide support for the development of the A. fumigatus H+ -ATPase as a potential drug discovery target.