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1.
Laryngoscope ; 134(8): 3587-3594, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38401116

RESUMO

OBJECTIVES: To evaluate the therapeutic effect of post-operative radiotherapy (PORT) with respect to nodal status among patients with head and neck Merkel cell carcinoma (HNMCC). METHODS: In this retrospective study, we queried Surveillance, Epidemiology, and End Results (SEER) dataset from 2000 through 2019. We included all adult patients who received primary surgical resection for histologically confirmed treatment naive HNMCC. Entropy balancing was used to reweight observations such that there was covariate balance between patients who received PORT and patients who received surgical resection alone. Doubly robust estimation was achieved by incorporating weights into a multivariable cox proportional hazards model. Planned post hoc subgroup analysis was performed to evaluate the impact of PORT by pathological node status. RESULTS: Among 752 patients (mean age, 73.3 years [SD 10.8]; 64.2% male; 91.2% White; 41.9% node-positive), 60.4% received PORT. Among node-positive patients, we found that PORT was associated with improved overall survival (OS) (aHR, 0.55; 95% CI, 0.37-0.81; p = 0.003) and improved disease-specific survival (DSS) (aHR, 0.57; 95% CI, 0.35-0.92; p = 0.022). Among node-negative patients, we found that PORT was not associated with OS and was associated with worse DSS (aHR, 2.34; 95% CI, 1.30-4.23; p = 0.005). CONCLUSIONS: We found that PORT was associated with improved OS and DSS for node-positive patients and worse DSS for node-negative patients. For HNMCC treated with primary surgical resection, these data confirm the value of PORT for pathologically node-positive patients and support the use of single modality surgical therapy for pathologically node-negative patients without other adverse risk factors. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3587-3594, 2024.


Assuntos
Carcinoma de Célula de Merkel , Neoplasias de Cabeça e Pescoço , Programa de SEER , Humanos , Carcinoma de Célula de Merkel/radioterapia , Carcinoma de Célula de Merkel/mortalidade , Carcinoma de Célula de Merkel/cirurgia , Carcinoma de Célula de Merkel/patologia , Masculino , Feminino , Idoso , Estudos Retrospectivos , Radioterapia Adjuvante , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Metástase Linfática , Idoso de 80 Anos ou mais , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Pessoa de Meia-Idade , Linfonodos/patologia , Linfonodos/cirurgia
2.
Otolaryngol Head Neck Surg ; 170(3): 987-988, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37890052

RESUMO

Airway balloons are widely used by otolaryngologists to treat laryngotracheal stenosis. We review an adverse event and interventions that may prevent similar occurrences. There are no other reports of similar incidents in the Food and Drug Administration Manufacturer and User Facility Device Experience. We implore Acclarent to redesign their airway balloon device to prevent accidental airway irrigation.


Assuntos
Laringoestenose , Estenose Traqueal , Humanos , Criança , Dilatação , Endoscopia , Laringoestenose/cirurgia , Laringoestenose/etiologia , Cateterismo/efeitos adversos , Estenose Traqueal/terapia , Estenose Traqueal/etiologia
3.
Ear Nose Throat J ; 102(9): 580-583, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37309202

RESUMO

Deep neck infections are common in infants and occur in several anatomic subsites including the retropharyngeal space. Retropharyngeal abscesses are significant given their propensity for mediastinal extension and can have life-threatening sequelae. We present 3 cases of retropharyngeal abscess with mediastinal extension in infants. In one case, an incompletely vaccinated 10-month-old boy presented with cough, rhinorrhea, and fever. Despite antibiotic treatment, he developed Horner's syndrome and hypoxia. A computed tomography (CT) scan showed a C1-T7 retropharyngeal abscess. He underwent transoral incision and drainage and recovered fully. In another case, a 12-month old infant presented with 8 days of fever and neck pain. A CT scan showed a retropharyngeal collection extending to the mediastinum and right hemithorax. Transoral incision and drainage and video-assisted thoracoscopic surgery thoracotomy were performed for abscess drainage. He recovered fully with antibiotics. In the third case, an 8-month-old boy presented to the emergency room following several days of fever, lethargy, and decreased neck range of motion. A CT scan showed a large retropharyngeal abscess that required both transoral and transcervical drainage. His case was complicated by septic shock, yet the patient eventually made a full recovery.


Assuntos
Abscesso Retrofaríngeo , Masculino , Lactente , Humanos , Abscesso Retrofaríngeo/cirurgia , Mediastino , Pescoço , Antibacterianos/uso terapêutico , Drenagem/métodos
4.
Indian J Otolaryngol Head Neck Surg ; 75(2): 784-788, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37275117

RESUMO

Objective: Quantitatively compare the ergonomics of traditional tonsillectomy versus an endoscopic-assisted tonsillectomy. Methods: The physical positioning of the senior author was studied during a simulation of two different operative approaches to tonsillectomy: one using an endoscope and one using direct visualization without the aid of an endoscope. Whole-body postural data was collected and analyzed using the validated Rapid Upper Limb Assessments (RULA) tool to calculate the risk of musculoskeletal injuries. Results: Severe neck and trunk flexion are high-risk postures unique to the traditional approach. The RULA score for the traditional, non-endoscopic approach was 5, with a Neck, Trunk, and Leg Score of 6 and a Wrist/Arm score of 1. The RULA score for the endoscopic-assisted approach was 3, with a Neck, Trunk, and Leg score of 4 and a Wrist/Arm score of 1. The difference between the two approaches narrowed down to the effect on neck positioning (angle decreased from > 20 degrees with traditional to nearly 0 degrees with endoscopic) and trunk positioning (angle decreased from 20 to 60 degrees with traditional to 0 degrees with endoscopic). Conclusion: An endoscopic-assisted approach to tonsillectomy allowed for a lower RULA score compared to the traditional tonsillectomy. This study suggests that an endoscopic approach may decrease the potential for musculoskeletal strain and reduce occupational-related pain and injury seen in practicing otolaryngologists.

5.
Laryngoscope Investig Otolaryngol ; 8(2): 577-583, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37090873

RESUMO

Objective: To evaluate how pediatric indications for tonsillectomy or adenotonsillectomy relate to gender, race/ethnicity, and age. Methods: Included consecutive pediatric patients who underwent tonsillectomy or adenotonsillectomy from a single tertiary academic institution between 2012 and 2019. Logistic regression analysis was used to measure association between the indication for tonsillectomy and the demographic variables gender, race/ethnicity, and age. Results: Of the 1106 children included in this study, 53% were male and 47% were female. Half of the children were White, 40% were African American, 6% were Hispanic and 4% were other. The most common indication for surgery was upper airway obstruction alone (66%), followed by obstruction and infection (22%), and recurrent infections (12%). We found that male gender (OR 1.59, 95% CI 1.24-2.04), African American race (OR 2.76, 95% CI 2.08-3.65), and younger age were associated with greater odds of presenting with upper airway obstruction as the indication for tonsillectomy. Conversely, male gender (OR 0.63, 95% CI 0.44-0.92), African American race (OR 0.4, 95% CI 0.26-0.61), and younger age were associated with lower odds of presenting with recurrent infection as the indication for tonsillectomy. Conclusions: Male gender, African American race, and young age are risk factors for tonsillar surgery due to airway obstruction. Female gender, White race, and older age are risk factors for tonsillar surgery due to recurrent throat infections. Level of Evidence: 3.

6.
Laryngoscope ; 133(1): 79-82, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35560994

RESUMO

OBJECTIVE: To describe the academic impact and author characteristics of open-access journals in otolaryngology. METHODS: Original articles from three open-access (OTO Open, Laryngoscope Investigative Otolaryngology, and World Journal of Otorhinolaryngology) and three conventional subscription-based otolaryngology specific journals (Otolaryngology - Head & Neck Surgery, The Laryngoscope, JAMA Otolaryngology - Head & Neck Surgery) were assessed. Publication dates of articles from January 2017 to July 2020 were included. Google Scholar and Web of Science citation counts were recorded. H-indexes of first and last authors were included according to Google Scholar and Web of Science and analyzed. RESULTS: This analysis included 3284 articles. Articles published in open-access otolaryngology-specific journals had significantly fewer citations on average (6.8) than articles published in subscription-based journals (12.4, p < 0.0001). The last authors of articles published in subscription-based journals had significantly higher h-indexes (23.50) compared with the last authors of articles published in open-access journals (19.53, p < 0.0001). The first authors of articles published in open-access journals had similar h-indexes (10.26) as the first authors of articles published in subscription-based journals (10.33). CONCLUSIONS: Articles published in open-access journals in otolaryngology were cited significantly less than those published in subscription-based journals. The h-index of the last authors was significantly lower in open-access journals; however, the h-index of the first authors was similar between open-access and subscription-based journals. As measured by citations, open-access publications do not yet appear to have the impact of subscription-based publications. LEVEL OF EVIDENCE: NA Laryngoscope, 133:79-82, 2023.


Assuntos
Otolaringologia , Publicações Periódicas como Assunto , Humanos , Bibliometria
7.
Otolaryngol Head Neck Surg ; 166(6): 1161-1165, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35133915

RESUMO

The field of otolaryngology has one of the lowest rates of racial and ethnic diversity. An anonymous survey was distributed to members of the Student National Medical Association at different medical schools to identify factors that may contribute to this disparity. Responses were received from 104 students at 36 allopathic medical schools. Most respondents identified as black (86.5%). One-third of students (34.6%) noted that they were discouraged from pursuing otolaryngology due to lack of mentorship, and among these students, most noted that they lack mentors of the same race (75%). One-fourth of respondents (25%) indicated that they lack a home otolaryngology program. The most common reasons for participants' disinterest in otolaryngology included competitiveness, inadequate exposure, research, and the high board scores needed to match. This hypothesis-generating, proof-of-concept study highlights potential barriers that may discourage underrepresented medical students from pursuing a career in otolaryngology.


Assuntos
Internato e Residência , Otolaringologia , Estudantes de Medicina , Humanos , Mentores , Otolaringologia/educação , Inquéritos e Questionários
9.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1865(11): 158653, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32035229

RESUMO

Mammals and higher vertebrates including humans have only three members of the carotenoid cleavage dioxygenase family of enzymes. This review focuses on the two that function as carotenoid oxygenases. ß-Carotene 15,15'-dioxygenase (BCO1) catalyzes the oxidative cleavage of the central 15,15' carbon-carbon double of ß-carotene bond by addition of molecular oxygen. The product of the reaction is retinaldehyde (retinal or ß-apo-15-carotenal). Thus, BCO1 is the enzyme responsible for the conversion of provitamin A carotenoids to vitamin A. It also cleaves the 15,15' bond of ß-apocarotenals to yield retinal and of lycopene to yield apo-15-lycopenal. ß-Carotene 9',10'-dioxygenase (BCO2) catalyzes the cleavage of the 9,10 and 9',10' double bonds of a wider variety of carotenoids, including both provitamin A and non-provitamin A carotenoids, as well as the xanthophylls, lutein and zeaxanthin. Indeed, the enzyme shows a marked preference for utilization of these xanthophylls and other substrates with hydroxylated terminal rings. Studies of the phenotypes of BCO1 null, BCO2 null, and BCO1/2 double knockout mice and of humans with polymorphisms in the enzymes, has clarified the role of these enzymes in whole body carotenoid and vitamin A homeostasis. These studies also demonstrate the relationship between enzyme expression and whole body lipid and energy metabolism and oxidative stress. In addition, relationships between BCO1 and BCO2 and the development or risk of metabolic diseases, eye diseases and cancer have been observed. While the precise roles of the enzymes in the pathophysiology of most of these diseases is not presently clear, these gaps in knowledge provide fertile ground for rigorous future investigations. This article is part of a Special Issue entitled Carotenoids: Recent Advances in Cell and Molecular Biology edited by Johannes von Lintig and Loredana Quadro.


Assuntos
Carotenoides/metabolismo , Dioxigenases/genética , Estresse Oxidativo/genética , Oxigenases/genética , beta-Caroteno 15,15'-Mono-Oxigenase/genética , Animais , Catálise , Dioxigenases/química , Humanos , Camundongos , Camundongos Knockout , Oxigenases/química , Vertebrados/genética , beta-Caroteno 15,15'-Mono-Oxigenase/química
10.
Clin Oncol (R Coll Radiol) ; 32(6): 382-389, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32089356

RESUMO

AIMS: De-escalation trials are challenging and sometimes may fail due to poor recruitment. The OPTIMA Prelim randomised controlled trial (ISRCTN42400492) randomised patients with early stage breast cancer to chemotherapy versus 'test-directed' chemotherapy, with a possible outcome of no chemotherapy, which could confer less treatment relative to routine practice. Despite encountering challenges, OPTIMA Prelim reached its recruitment target ahead of schedule. This study reports the root causes of recruitment challenges and the strategies used to successfully overcome them. MATERIALS AND METHODS: A mixed-methods recruitment intervention (QuinteT Recruitment Intervention) was used to investigate the recruitment difficulties and feedback findings to inform interventions and optimise ongoing recruitment. Quantitative site-level recruitment data, audio-recorded recruitment appointments (n = 46), qualitative interviews (n = 22) with trialists/recruiting staff (oncologists/nurses) and patient-facing documentation were analysed using descriptive, thematic and conversation analyses. Findings were triangulated to inform a 'plan of action' to optimise recruitment. RESULTS: Despite best intentions, oncologists' routine practices complicated recruitment. Discomfort about deviating from the usual practice of recommending chemotherapy according to tumour clinicopathological features meant that not all eligible patients were approached. Audio-recorded recruitment appointments revealed how routine practices undermined recruitment. A tendency to justify chemotherapy provision before presenting the randomised controlled trial and subtly indicating that chemotherapy would be more/less beneficial undermined equipoise and made it difficult for patients to engage with OPTIMA Prelim. To tackle these challenges, individual and group recruiter feedback focussed on communication issues and vignettes of eligible patients were discussed to address discomforts around approaching patients. 'Tips' documents concerning structuring discussions and conveying equipoise were disseminated across sites, together with revisions to the Patient Information Sheet. CONCLUSIONS: This is the first study illuminating the tension between oncologists' routine practices and recruitment to de-escalation trials. Although time and resources are required, these challenges can be addressed through specific feedback and training as the trial is underway.


Assuntos
Neoplasias da Mama/terapia , Comunicação , Tomada de Decisões , Pessoal de Saúde/psicologia , Seleção de Pacientes , Projetos de Pesquisa , Feminino , Humanos , Pesquisa Qualitativa , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
J Emerg Med ; 57(3): 399-404, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31375369

RESUMO

BACKGROUND: Several types of injuries associated with electronic cigarette malfunction have been reported in the literature since their introduction to the U.S. market in 2007. The traumatic consequences of electronic nicotine delivery system (ENDS) malfunction remain an under-researched topic. OBJECTIVES: Using information from a national database of emergency department (ED) visits, we sought to characterize the nature and frequency of ENDS injuries over a 10-year study period. METHODS: Archived information from the National Electronic Injury Surveillance System was accessed for the years 2008 to 2017. Incidents related to ENDS-related trauma were manually identified. Data extracted included patient demographics, injury type and location, and patient disposition. RESULTS: A total of 49 incidents were recorded during the years 2008 to 2017, including 18 cases in 2017, 25 cases in 2016, five cases in 2015, and one case in 2013. There were no identified ED visits for an e-cigarette-related burn or explosion prior to 2013. Using statistical weights, the estimated annual national incidence is 835 cases. Most of the injuries were thermal burns. The primary location of injury was in the lower extremity, followed by the upper extremity and hand. CONCLUSIONS: Our study demonstrates a significant increase in the number of ENDS-related injuries over the study period, particularly in males under the age of 45 years. This rise mirrors the growth of the ENDS market and this trend can be expected to continue. As the use of ENDS is expected to increase, physicians should become familiar with the nature of associated injuries.


Assuntos
Queimaduras , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adulto , Distribuição por Idade , Queimaduras/epidemiologia , Queimaduras/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
13.
Int J Pediatr Otorhinolaryngol ; 117: 138-142, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30579068

RESUMO

OBJECTIVE: To determine the demographics, treatment modalities, and overall survival of pediatric Ewing sarcoma of the head and neck. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify cases of pediatric Ewing sarcoma of the head and neck between 1973 and 2015. Additional variables collected included age, gender, ethnicity, tumor grade, staging, treatment modality, and follow-up time. Kaplan-Meier survival curves were generated and overall survival was calculated. RESULTS: One hundred and twenty-seven cases of pediatric Ewing sarcoma were identified. The majority of patients were male (52.8%), white (88.2%), and non-Hispanic (75.6%), and the mean age at diagnosis was 10.5 years. The most common tumor sites were bones and joints of the skull and face (45.5%), followed by soft tissue of the head, face, and neck (25.2%), followed by the mandible (13.4%). Most patients (69.2%) had some type of surgery, 70.0% received radiation, and 92.1% received chemotherapy as part of their treatment. Overall 1-, 5-, and 10-year survival was 91.1%, 72.9%, and 68.2%, respectively. There was no significant difference in survival based on patient gender, age, tumor location, radiation, or chemotherapy treatment. CONCLUSION: This study demonstrates that pediatric patients with Ewing sarcoma of the head and neck most commonly have stage II disease, no distant metastasis, and are treated with chemotherapy, with or without radiation. One, five, and ten-year survival are 91.1%, 72.9%, and 68.2%, respectively, and age, gender, and radiation do not seem to affect prognosis.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Faciais/mortalidade , Sarcoma de Ewing/mortalidade , Crânio , Neoplasias de Tecidos Moles/mortalidade , Adolescente , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Criança , Pré-Escolar , Face , Neoplasias Faciais/patologia , Neoplasias Faciais/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pescoço , Estadiamento de Neoplasias , Prognóstico , Radioterapia/estatística & dados numéricos , Estudos Retrospectivos , Programa de SEER , Sarcoma de Ewing/patologia , Sarcoma de Ewing/terapia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Taxa de Sobrevida , Estados Unidos/epidemiologia
14.
Int J Pediatr Otorhinolaryngol ; 115: 94-96, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30368402

RESUMO

OBJECTIVE: To determine whether adenoid epithelium is superior to nasal mucosa for biopsy of ciliated epithelium for electron microscopy (EM) to evaluate pediatric patients with rhinosinusitis for primary ciliary dyskinesia (PCD). METHODS: A retrospective review compared electron microscopic results in children with chronic or recurrent rhinosinusitis who underwent both adenoidectomy or nasopharyngeal biopsy and nasal mucosa biopsy in the course of evaluation for PCD at a tertiary care institution. RESULTS: Forty pediatric patients met inclusion criteria for this study. Nine of these patients had a prior adenoidectomy and therefore underwent nasopharyngeal biopsy for collection of adenoid tissue. All nine of the nasopharyngeal biopsies and 25 of the 31 (80.6%) adenoid biopsies had sufficient cilia for EM evaluation of the ultrastructure. Of the 40 patients who also had a nasal biopsy, only 12 (30.0%) had sufficient cilia for EM analysis. The distribution of sufficient versus insufficient cilia for analysis between adenoid and nasal mucosa was statistically significant (P < 0.05). Abnormal cilia were found in only 2.5% of our patients. CONCLUSIONS: In current practice, the nasal cavity is a common location for obtaining ciliated epithelium for EM analysis, as it is easily accessible for biopsy and the procedure itself causes relatively low patient morbidity. Chronic rhinosinusitis, however, has been associated with decreased cilia density on nasal respiratory epithelium. Given that adenoidectomies are often performed in children with chronic rhinosinusitis, our data suggest that adenoid tissue is a better source of ciliated tissue for analysis compared to turbinate epithelium.


Assuntos
Tonsila Faríngea/patologia , Síndrome de Kartagener/patologia , Mucosa Nasal/patologia , Rinite/patologia , Sinusite/patologia , Adenoidectomia , Biópsia/métodos , Criança , Pré-Escolar , Doença Crônica , Cílios/patologia , Humanos , Lactente , Microscopia Eletrônica , Recidiva , Estudos Retrospectivos
15.
Laryngoscope ; 128(5): 1126-1132, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28990673

RESUMO

OBJECTIVES/HYPOTHESIS: Determine demographics, clinical characteristics, and survival rates for children with primary salivary gland malignancies. STUDY DESIGN: Retrospective, population-based cohort study. METHODS: All cases of primary salivary gland malignancies diagnosed between the years of 2002 and 2013 in patients ages 0 to 19 years were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Additional variables collected included age, gender, ethnicity, tumor histological subtype, tumor size, treatment modality, vitality status, and follow-up time. Kaplan-Meier survival curves were generated. RESULTS: Two hundred forty-five primary salivary gland malignancies were identified (220 parotid, 25 submandibular). Median age at diagnosis was 15 years. Most patients were female (59%), white (74%), and non-Spanish/Hispanic/Latino (81%). Among parotid tumors, mean tumor size was 2.3 cm, and there were 109 (50%) mucoepidermoid carcinomas and 86 (39%) acinic cell carcinomas. Most patients underwent surgery (n = 212, 96%) and 64 (29%) received adjuvant radiation. At a mean follow-up of 62.4 months, 10 patients (5%) were deceased. Kaplan-Meier survival curves illustrated that black children exhibited higher mortality rates than white children (15.8% vs. 4.6%, log-rank = 0.0260) as did those who underwent adjuvant radiation (15.73% vs. 3.2%, log-rank = 0.0209). Among submandibular tumors, mean tumor size was 3.1 cm, and there were 11 (44%) mucoepidermoid carcinomas. All patients underwent surgery and most received adjuvant radiation (n = 15, 60%). At a mean follow-up of 51.25 months, one patient was deceased. CONCLUSIONS: Salivary gland malignancies in children and adolescents are rare. Overall survival for both parotid and submandibular tumors in children is good. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1126-1132, 2018.


Assuntos
Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Programa de SEER , Neoplasias das Glândulas Salivares/terapia , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
16.
Ann Oncol ; 28(8): 1832-1835, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28525534

RESUMO

BACKGROUND: We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown. PATIENTS AND METHODS: The ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed. RESULTS: Of the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78-4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24-3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033-0.31; P < 0.001). CONCLUSIONS: Lymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients. CLINICALTRIALS.GOV: NCT01093235.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Biologia Computacional , Linfócitos do Interstício Tumoral/patologia , Linfócitos/patologia , Terapia Neoadjuvante , Neoplasias da Mama/patologia , Ciclofosfamida/uso terapêutico , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Contagem de Linfócitos , Reação em Cadeia da Polimerase , Indução de Remissão
17.
Ann Oncol ; 28(8): 1817-1824, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28459938

RESUMO

BACKGROUND: The ARTemis trial previously reported that addition of neoadjuvant bevacizumab (Bev) to docetaxel (D) followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC) in HER2 negative breast cancer improved the pathological complete response (pCR) rate. We present disease-free survival (DFS) and overall survival (OS) with central pathology review. PATIENTS AND METHODS: Patients were randomized to 3 cycles of D followed by 3 cycles of FEC (D-FEC), ±4 cycles of Bev (Bev + D-FEC). DFS and OS were analyzed by treatment and by central pathology reviewed pCR and Residual Cancer Burden (RCB) class. RESULTS: A total of 800 patients were randomized [median follow-up 3.5 years (IQR 3.2-4.4)]. DFS and OS were similar across treatment arms [DFS hazard ratio (HR)=1.18 (95% CI 0.89-1.57), P = 0.25; OS HR = 1.26 (95% CI 0.90-1.76), P = 0.19). Both local pathology report review and central histopathology review confirmed a significant improvement in DFS and OS for patients who achieved a pCR [DFS HR = 0.38 (95% CI 0.23-0.63), P < 0.001; OS HR = 0.43 (95% CI 0.24-0.75), P = 0.003]. However, significant heterogeneity was observed (P = 0.02); larger improvements in DFS were obtained with a pCR achieved with D-FEC than a pCR achieved with Bev + D-FEC. As RCB class increased, significantly worse DFS and OS was observed (P for trend <0.0001), which effect was most marked in the ER negative group. CONCLUSIONS: The addition of short course neoadjuvant Bev to standard chemotherapy did not demonstrate a DFS or OS benefit. Achieving a pCR with D-FEC is associated with improved DFS and OS but not when pCR is achieved with Bev + D-FEC. At the present time therefore, Bev is not recommended in early breast cancer. CLINICALTRIALS.GOV NUMBER: NCT01093235.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Taxoides/uso terapêutico , Neoplasias da Mama/patologia , Ciclofosfamida/uso terapêutico , Docetaxel , Diagnóstico Precoce , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Genes erbB-2 , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Indução de Remissão , Análise de Sobrevida
18.
J Lipid Res ; 58(5): 1021-1029, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28250025

RESUMO

Consumption of the tomato carotenoid, lycopene, has been associated with favorable health benefits. Some of lycopene's biological activity may be due to metabolites resulting from cleavage of the lycopene molecule. Because of their structural similarity to the retinoic acid receptor (RAR) antagonist, ß-apo-13-carotenone, the "first half" putative oxidative cleavage products of the symmetrical lycopene have been synthesized. All transformations proceed in moderate to good yield and some with high stereochemical integrity allowing ready access to these otherwise difficult to obtain terpenoids. In particular, the methods described allow ready access to the trans isomers of citral (geranial) and pseudoionone, important flavor and fragrance compounds that are not readily available isomerically pure and are building blocks for many of the longer apolycopenoids. In addition, all of the apo-11, apo-13, and apo-15 lycopenals/lycopenones/lycopenoic acids have been prepared. These compounds have been evaluated for their effect on RAR-induced genes in cultured hepatoma cells and, much like ß-apo-13-carotenone, the comparable apo-13-lycopenone and the apo-15-lycopenal behave as RAR antagonists. Furthermore, molecular modeling studies demonstrate that the apo-13-lycopenone efficiently docked into the ligand binding site of RARα. Finally, isothermal titration calorimetry studies reveal that apo-13-lycopenone acts as an antagonist of RAR by inhibiting coactivator recruitment to the receptor.


Assuntos
Carotenoides/síntese química , Carotenoides/farmacologia , Receptores do Ácido Retinoico/antagonistas & inibidores , Carotenoides/química , Carotenoides/metabolismo , Técnicas de Química Sintética , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Licopeno , Simulação de Acoplamento Molecular , Conformação Proteica , Receptores do Ácido Retinoico/química , Receptores do Ácido Retinoico/metabolismo
19.
Int J Pediatr Otorhinolaryngol ; 89: 121-6, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27619041

RESUMO

OBJECTIVE: To update the medical literature regarding the incidence, disease specific survival, and treatment modalities utilized in pediatric patients diagnosed with thyroid carcinomas. STUDY DESIGN: Cross Sectional Analysis of a National Database. STUDY SETTING: SEER Database. METHODS: The National Cancer Institute's Surveillance Epidemiology and End Results (SEER) Database was queried for all cases of pediatric thyroid cancer between the years 2007 and 2012. Patients ages 0-19 were grouped by histological subtypes and demographic data, overall incidence rate, and disease specific survival after surgery and surgery with radiation therapy. Fifteen-Year Disease Specific Survival Curves were generated and treatment modalities were compared to assess for statistical differences at each yearly interval. RESULTS: A total of 1723 pediatric patients were identified and the average age-adjusted rate of malignancy was determined to be 0.59 per 100,000 patients. The incidence of pediatric thyroid cancer was approximately 4.4:1 when comparing females to males, respectively. Papillary subtype was the most common (n = 1014, 58.8%), followed by follicular variant subtype (n = 397, 23%), follicular subtype (n = 173, 10.1%) and medullary subtype (n = 139, 8.1%). As pediatric patients reached fifteen to nineteen years of age, the incidence of papillary and follicular variant subtypes increased. Analysis of medullary thyroid cancer data revealed that incidence was highest in the zero to four age group and declined at later years. Pediatric patients presenting with metastatic medullary thyroid carcinoma maintained significantly poorer fifteen-year disease specific survival when compared to other histologic subtypes (p < 0.05). Intervention with surgery and radiation therapy provided significant benefit across all histologic subtypes when evaluating disease specific survival at fifteen-years past the initial diagnoses (p < 0.05). CONCLUSIONS: Pediatric thyroid carcinoma remains an uncommon diagnosis despite an annual increase in incidence of approximately one percent since the development of the SEER database. Overall, pediatric thyroid carcinomas demonstrate an excellent prognosis if identified early and appropriate management is available. Caucasian female patients have higher incidence of carcinoma diagnoses when compared to males. Medullary histologic subtype, especially when metastatic at initial diagnoses, demonstrates statistically poorer outcomes when compared to other subtypes.


Assuntos
Neoplasias da Glândula Tireoide/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Incidência , Lactente , Masculino , Prognóstico , Programa de SEER , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Adulto Jovem
20.
Int J Pediatr Otorhinolaryngol ; 80: 49-52, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26746612

RESUMO

OBJECTIVE: To determine if Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) patients demonstrate a significantly different number of B-Cells or markers of activity when compared to recurrent Group A Streptococcus or Obstructive Sleep Apnea patients. STUDY DESIGN: Prospective Cohort Study. STUDY SETTING: Academic University Hospital. METHODS: Tonsil tissue was collected from twenty-two patients in the operating room and organized into three groups. Ten clinically diagnosed PANDAS, six Group A Streptococcus and six Obstructive Sleep Apnea patients were included in this study. Each tissue sample was extracted with MSD Tris Lysis Buffer and protein lysates were analyzed for CD 19, B-Cell Activating Factor and B-Cell Activating Receptor by western blot methods. RESULTS: Based on ANOVA analysis, there was no significant difference in the expression of B-Cell Activating Factor, B-Cell Activating Receptor or CD 19 when comparing the three study groups by western blot analysis methods. CONCLUSIONS: In this prospective cohort study, it appears that PANDAS patients do not demonstrate increased number of B-Cells, expression of B-Cell Activating Factor or B-Cell Activating Receptor when compared to Group A Streptococcus or Obstructive Sleep Apnea cohorts. As a result, further evaluation of the cell-mediated immune system is warranted to provide further insight into the pathophysiology of PANDAS. In addition, we must investigate if PANDAS patients only demonstrate increased B-Cell number or activity when undergoing an acute Tic/OCD exacerbation.


Assuntos
Doenças Autoimunes/imunologia , Linfócitos B/química , Tonsila Palatina/química , Infecções Estreptocócicas/imunologia , Streptococcus pyogenes , Antígenos CD19/análise , Doenças Autoimunes/microbiologia , Doenças Autoimunes/psicologia , Fator Ativador de Células B/análise , Receptor do Fator Ativador de Células B/análise , Linfócitos B/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/etiologia , Tonsila Palatina/patologia , Estudos Prospectivos , Apneia Obstrutiva do Sono/imunologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/psicologia
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