RESUMO
OBJECTIVE: The goal of this project was to first address barriers to implementation of the Risk Analysis Index (RAI) within a large, multi-hospital, integrated healthcare delivery system, and to subsequently demonstrate its utility for identifying at-risk surgical patients. BACKGROUND: Prior studies demonstrate the validity of the RAI for evaluating preoperative frailty, but they have not demonstrated the feasibility of its implementation within routine clinical practice. METHODS: Implementation of the RAI as a frailty screening instrument began as a quality improvement initiative at the University of Pittsburgh Medical Center in July 2016. RAI scores were collected within a REDCap survey instrument integrated into the outpatient electronic health record and then linked to information from additional clinical datasets. NSQIP-eligible procedures were queried within 90 days following the RAI, and the association between RAI and postoperative mortality was evaluated using logistic regression and Cox proportional hazards models. Secondary outcomes such as inpatient length of stay and readmissions were also assessed. RESULTS: RAI assessments were completed on 36,261 unique patients presenting to surgical clinics across five hospitals from July 1 to December 31, 2016, and 8,172 of these underwent NSQIP-eligible surgical procedures. The mean RAI score was 23.6 (SD 11.2), the overall 30-day and 180-day mortality after surgery was 0.7% and 2.6%, respectively, and the median time required to collect the RAI was 33 [IQR 23-53] seconds. Overall clinic compliance with the recommendation for RAI assessment increased from 58% in the first month of the study period to 84% in the sixth and final month. RAI score was significantly associated with risk of death (HR=1.099 [95% C.I.: 1.091 - 1.106], p < 0.001). At an RAI cutoff of ≥37, the positive predictive values for 30- and 90-day readmission were 14.8% and 26.2%, respectively, and negative predictive values were 91.6% and 86.4%, respectively. CONCLUSIONS: The RAI frailty screening tool can be efficiently implemented within multi-specialty, multi-hospital healthcare systems. In the context of our findings and given the value of the RAI in predicting adverse postoperative outcomes, health systems should consider implementing frailty screening within surgical clinics.
Assuntos
Fragilidade/classificação , Período Pré-Operatório , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Pennsylvania , Estudos Prospectivos , Melhoria de QualidadeRESUMO
PIK3CA is the most commonly altered oncogene in head and neck squamous cell carcinoma (HNSCC). We evaluated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on survival in a PIK3CA-characterized cohort of 266 HNSCC patients and explored the mechanism in relevant preclinical models including patient-derived xenografts. Among subjects with PIK3CA mutations or amplification, regular NSAID use (≥6 mo) conferred markedly prolonged disease-specific survival (DSS; hazard ratio 0.23, P = 0.0032, 95% CI 0.09-0.62) and overall survival (OS; hazard ratio 0.31, P = 0.0043, 95% CI 0.14-0.69) compared with nonregular NSAID users. For PIK3CA-altered HNSCC, predicted 5-yr DSS was 72% for NSAID users and 25% for nonusers; predicted 5-yr OS was 78% for regular NSAID users and 45% for nonregular users. PIK3CA mutation predicted sensitivity to NSAIDs in preclinical models in association with increased systemic PGE2 production. These findings uncover a biologically plausible rationale to implement NSAID therapy in PIK3CA-altered HNSCC.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Carcinoma de Células Escamosas , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias de Cabeça e Pescoço , Mutação , Proteínas de Neoplasias , Adulto , Idoso , Animais , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Taxa de Sobrevida , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To test whether a clinical algorithm using routine cytological molecular testing (MT) promotes initial total thyroidectomy (TT) for clinically significant thyroid cancer (sTC) and/or correctly limits surgery to lobectomy when appropriate. BACKGROUND: Either TT or lobectomy is often needed to diagnose differentiated thyroid cancer. Determining the correct extent of initial thyroidectomy is challenging. METHODS: After implementing an algorithm for prospective MT of in-house fine-needle aspiration biopsy specimens, we conducted a single-institution cohort study of all patients (N = 671) with nonmalignant cytology who had thyroidectomy between October 2010 and March 2012, cytological diagnosis using 2008 Bethesda criteria, and 1 or more indications for thyroidectomy by 2009 American Thyroid Association guidelines. sTC was defined by histological differentiated thyroid cancer of 1 cm or more and/or lymph node metastasis. Cohort 2 patients did not have MT or had unevaluable results. In cohort 1, MT for a multigene mutation panel was performed for nonbenign cytology, and positive MT results indicated initial TT. RESULTS: MT guidance was associated with a higher incidence of sTC after TT (P = 0.006) and a lower rate of sTC after lobectomy (P = 0.03). Without MT results, patients with indeterminate (follicular lesion of undetermined significance/follicular or oncocytic neoplasm) cytology who received initial lobectomy were 2.5 times more likely to require 2-stage surgery for histological sTC (P < 0.001). In the 501 patients with non-sTC for whom lobectomy was the appropriate extent of surgery, lobectomy was correctly performed more often with routine preoperative MT (P = 0.001). CONCLUSIONS: Fine-needle aspiration biopsy MT for BRAF, RAS, PAX8-PPARγ, and RET-PTC expedites optimal initial surgery for differentiated thyroid cancer, facilitating succinct definitive management for patients with thyroid nodules.
Assuntos
Algoritmos , Biópsia por Agulha Fina/métodos , Guias de Prática Clínica como Assunto , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Tireoidectomia/métodos , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/cirurgiaRESUMO
BACKGROUND: In thyroid nodule fine-needle aspiration (FNA) cytology, the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category has a 5-15% malignancy risk that increases to 85-99% when mutation testing for BRAF, RAS, RET/PTC, or PAX8/PPARγ is positive. However, negative testing does not exclude malignancy. The study objective was to identify clinical and imaging features that predict cancer in mutation-negative AUS/FLUS thyroid nodules. METHODS: All patients were reviewed (April 2007 to April 2009) who had AUS/FLUS cytology, negative prospective molecular testing of FNA, and histopathology. RESULTS: Of the 230 nodules, 12 (5.2%) were malignant in 11 of 190 patients, and known clinical risk factors for thyroid cancer did not predict malignancy. On preoperative imaging, ≥1 suspicious ultrasound feature was identified in 33% of nodules and occurred regardless of histology (P = .23). Malignant mutation-negative AUS/FLUS nodules were larger than benign nodules (mean maximum diameter, 33.6 vs 24.0 mm; P = .007). On multivariate analysis, nodule size remained an independent predictor of malignancy (odds ratio, 1.043; P = .018). We observed no malignancies in 88 mutation-negative AUS/FLUS nodules <18.5 mm. CONCLUSION: Size is an independent predictor of malignancy in mutation-negative AUS/FLUS nodules and the risk increased 4.3% with every millimeter increase in nodule size. Selected patients with small, mutation-negative AUS/FLUS thyroid nodules may be managed with ultrasound surveillance in lieu of thyroidectomy.
Assuntos
Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Nódulo da Glândula Tireoide/genéticaRESUMO
Após a ressecçäo de carcinoma da hipofaringe, o cirurgiäo de cabeça e pescoço deve estar preparado para uma série de problemas de reconstruçäo. Em virtude da variabilidade dos defeitos, uma única soluçäo para todos os casos de reconstruçäo näo é viável. Necessidades funcionais devem se consideradas pelo cirurgiäo ao planejar a reconstruçäo da hipofaringe. Uma avaliaçäo pré-operatória, incluindo endoscopia e estudos radiográficos, é necessária para estimar a extensäo do tumor. Isto permite a formulaçäo de planos de acordo com a extensäo da ressecçäo e da reconstruçäo. Todavia, o cirurgiäo deve estar preparado para situaçöes que requeiram a ampliaçäo das ressecçöes planejadas as quais poderäo influenciar a reconstruçäo. A reconstruçäo do trato alimentar é quase sempre a consideraçäo primária. Apesar de uma sutura primária poder ser ocasionamente feita, a grande maioria dos defeitos criados pela ressecçäo de tumores da hipofaringe requer a mobilizaçäo adicional de partes moles a fim de prevenir limitaçöes funcionais. Além do mais, a tensäo das suturas, tanto nas suturas primárias quanto nas reconstruçöes complexas, pode resultar em deiscências e complicaçöes pós-operatórias. Nos casos nos quais os tumores hipofaríngeos podem ser removidos sem laringectomia, esforços especiais devem ser feitos para lograr a deglutiçäo sem o risco de aspiraçäo