RESUMEN
We investigate the effects of structural damping on the interaction of a turbulent eddy with flexible plates with respect to the efficiency of aerodynamic noise generation. Potential benefits are studied using a model based on a point-reacting compliant semi-infinite plate on a spring-damper foundation. This scattering problem is solved using the Wiener-Hopf technique. We compare results for semi-infinite compliant plates with finite ones. In both cases, plate vibration lead to reductions of sound radiation, especially at resonance; damping tends to reduce such acoustic benefits. We also present a formulation that considers the effect of structural damping on the acoustic properties of finite elastic plates. Numerical results are obtained by applying a boundary element method to solve the Helmholtz equation subject to the boundary conditions imposed by the plate vibration. Under specific conditions, such as high fluid loading factor and low bending-wave Mach number, the acoustic power scattered by an edge tends to be smaller than that which propagates over the plate as bending waves. Results show that structural damping attenuates these waves and may modify the far-field acoustic pressure, mostly by reducing the scattered sound at structural resonances. All models show that large damping coefficients lead to locally over-damped responses. There is thus an ideal range of structural damping to reduce both plate vibration and acoustic scattering.
RESUMEN
Progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is uncommon but the consequences are serious. Predictors of progression are essential to optimize resource utilization. This study assessed the utility of a promising panel of biomarkers applicable to routine paraffin embedded biopsies (FFPE) to predict progression of BE to EAC in a large population-based, nested case-control study.We utilized the Amsterdam-based ReBus nested case-control cohort. BE patients who progressed to high-grade dysplasia (HGD)/EAC (n = 130) and BE patients who never progressed (n = 130) were matched on age, sex, length of the BE segment, and duration of endoscopic surveillance. All progressors had minimum 2 years of endoscopic surveillance without HGD/EAC to exclude prevalent neoplasia. We assessed abnormal DNA content, p53, Cyclin A, and Aspergillus oryzae lectin (AOL) in FFPE sections. We performed conditional logistic regression analysis to estimate odds ratio (OR) of progression based on biomarker status.Expert LGD (OR, 8.3; 95% CI, 1.7-41.0), AOL (3 vs. 0 epithelial compartments abnormal; OR, 3.6; 95% CI, 1.2-10.6) and p53 (OR, 2.3; 95% CI, 1.2-4.6) were independently associated with neoplastic progression. Cyclin A did not predict progression and DNA ploidy analysis by image cytometry was unsuccessful in the majority of cases, both were excluded from the multivariate analysis. The multivariable biomarker model had an area under the receiver operating characteristic curve of 0.73.Expert LGD, AOL, and p53 independently predict neoplastic progression in BE patients and are applicable to routine practice. These biomarkers can aid in selecting patients for endoscopic ablation or more intensive surveillance.
Asunto(s)
Adenocarcinoma/etiología , Esófago de Barrett/complicaciones , Esófago de Barrett/patología , Neoplasias Esofágicas/etiología , Esófago/patología , Vigilancia de la Población/métodos , Medición de Riesgo/métodos , Adenocarcinoma/patología , Anciano , Área Bajo la Curva , Biomarcadores de Tumor/análisis , Biopsia/métodos , Estudios de Casos y Controles , Progresión de la Enfermedad , Neoplasias Esofágicas/patología , Esofagoscopía/estadística & datos numéricos , Femenino , Humanos , Hiperplasia , Masculino , Persona de Mediana Edad , Países Bajos , Adhesión en Parafina/métodos , Valor Predictivo de las Pruebas , Curva ROCRESUMEN
BACKGROUND AND AIMS: No prospective studies substantiate 15 eos/hpf as an appropriate endpoint for treatment of eosinophilic esophagitis (EoE). We aimed to determine a histologic cutpoint that identifies successful treatment of EoE by assessing symptomatic and endoscopic improvement. METHODS: We performed a prospective cohort study of 62 consecutive adult patients undergoing outpatient esophagogastroduodenoscopy at the University of North Carolina from 2009 through 2014. At diagnosis of EoE and after 8 weeks of standard treatment, symptom and endoscopic responses were measured using a visual analogue scale and an endoscopic severity score (ESS), and eosinophil counts were assessed. Receiver operator curves and logistic regression models evaluated the histologic threshold that best predicted symptomatic and endoscopic response. For symptoms, analysis was limited to patients without baseline esophageal dilation. RESULTS: The mean eosinophil count at diagnosis was 124 eos/hpf, falling to 35 eos/hpf after treatment. The mean visual analogue scale decreased from 3.4 at baseline to 1.7 after treatment, and the mean ESS decreased from 3 to 1.6. Twenty-nine patients had symptom responses (47%) and 34 had endoscopic responses (55%). Post-treatment eosinophil count thresholds of 8, 15, and 5 eos/hpf best predicted symptom, endoscopic and combined responses, respectively. On logistic regression, decreasing eosinophil count was significantly associated with the probability of symptomatic (P = .01) and endoscopic response (P < .001). CONCLUSIONS: In a prospective study of patients with EoE, we found that a cutpoint of <15 eos/hpf identifies most patients with symptom and endoscopic improvements, providing support for the current diagnostic threshold. A lower threshold (<5 eos/hpf) identifies most patients with a combination of symptom and endoscopic responses; this cutpoint might be used in situations that require a stringent histologic threshold.
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Biomarcadores/análisis , Técnicas Citológicas/métodos , Determinación de Punto Final , Esofagitis Eosinofílica/patología , Esofagitis Eosinofílica/terapia , Esófago/patología , Corticoesteroides/administración & dosificación , Adulto , Animales , Antiinflamatorios/administración & dosificación , Dieta/métodos , Endoscopía del Sistema Digestivo , Femenino , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , North Carolina , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Topical corticosteroids or six-food elimination diet is recommended as initial therapy for eosinophilic esophagitis (EoE). AIMS: We aimed to summarize published manuscripts that report outcomes of these therapies for EoE. METHODS: We performed a systematic review in MEDLINE, Web of Science, and Embase of published manuscripts describing topical fluticasone, topical budesonide, and six-food elimination diet as therapies for EoE. We conducted meta-analysis of symptom improvement and the change in peak mucosal eosinophil count, with heterogeneity between studies examined with meta-regression analysis. RESULTS: Systematic review yielded 51 articles that met inclusion criteria. Summary histologic response rates were 68.3% [95% prediction limits (PL) 16.2-96.0%] for fluticasone, 76.8% (95% PL 36.1-95.1%) for budesonide, and 69.0% (95% PL 31.9-91.4%) for six-food elimination diet. Corresponding decreases in eosinophil counts were 37.8 (95% PL 19.0-56.7), 62.5 (95% PL 125.6 to -0.67, and 44.6 (95% PL 26.5-62.7), respectively. Symptom response rates were 82.3% (95% PL 68.1-91.1%), 87.9% (95% PL 42.7-98.6%), and 87.3% (95% PL 64.5-96.3%), respectively. Meta-regression analyses decreased the initially large estimate of residual heterogeneity and suggested differences in histologic response rate associated with study populations' baseline eosinophil count and age. CONCLUSIONS: The literature describing topical corticosteroids and six-food elimination diet consists of small studies with diverse methods and population characteristics. Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.
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Esofagitis Eosinofílica/dietoterapia , Esofagitis Eosinofílica/tratamiento farmacológico , Esteroides/administración & dosificación , Administración Tópica , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: The goal of treatment for Barrett's esophagus (BE) with dysplasia is complete eradication of intestinal metaplasia (CEIM). The long-term durability of CEIM has not been well characterized, so the frequency and duration of surveillance are unclear. We report results from a 5-year follow-up analysis of patients with BE and dysplasia treated by radiofrequency ablation (RFA) in the randomized controlled Ablation of Intestinal Metaplasia Containing Dysplasia (AIM) trial. METHODS: Participants for the AIM Dysplasia trial (18-80 years old) were recruited from 19 sites in the United States and had endoscopic evidence of non-nodular dysplastic BE ≤8 cm in length. Subjects (n = 127) were randomly assigned (2:1 ratio) to receive either RFA (entire BE segment ablated circumferentially) or a sham endoscopic procedure; patients in the sham group were offered RFA treatment 1 year later, and all patients were followed for 5 years. We collected data on BE recurrence (defined as intestinal metaplasia in the tubular esophagus) and dysplastic BE recurrence among patients who achieved CEIM. We constructed Kaplan-Meier estimates and applied parametric survival analysis to examine proportions of patients without any recurrence and without dysplastic recurrence. RESULTS: Of 127 patients in the AIM Dysplasia trial, 119 received RFA and met inclusion criteria. Of those 119, 110 (92%) achieved CEIM. Over 401 person-years of follow-up (mean, 3.6 years per patient; range, 0.2-5.8 years), 35 of 110 (32%) patients had recurrence of BE or dysplasia, and 19 (17%) had dysplasia recurrence. The incidence rate of BE recurrence was 10.8 per 100 person-years overall (95% CI, 7.8-15.0); 8.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI, 4.9-14.0), and 13.5 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 8.8-20.7). The incidence rate of dysplasia recurrence was 5.2 per 100 person-years overall (95% CI 3.3-8.2); 3.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI 1.5-7.2), and 7.3 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 4.2-12.5). Neither BE nor dysplasia recurred at a constant rate. There was a greater probability of recurrence in the first year following CEIM than in the following 4 years combined. CONCLUSIONS: In this analysis of prospective cohort data from the AIM Dysplasia trial, we found BE to recur after CEIM by RFA in almost one third of patients with baseline dysplastic disease; most recurrences occurred during the first year after CEIM. However, patients who achieved CEIM and remained BE free at 1 year after RFA had a low risk of BE recurrence. Studies are needed to determine when surveillance can be decreased or discontinued; our study did not identify any BE or dysplasia recurrence after 4 years of surveillance.
Asunto(s)
Esófago de Barrett/epidemiología , Esófago de Barrett/cirugía , Esófago/patología , Membrana Mucosa/patología , Vigilancia de la Población , Anciano , Ablación por Catéter , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Metaplasia/cirugía , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Factores de TiempoRESUMEN
BACKGROUND: While symptom scores have been developed to evaluate dysphagia in eosinophilic oesophagitis (EoE), their complexity may limit clinical use. AIM: To evaluate a visual analogue scale (VAS) and a 10-point Likert scale (LS) for assessment of dysphagia severity before and after EoE treatment. METHODS: We conducted a prospective cohort study enrolling consecutive adults undergoing out-patient endoscopy. Incident cases of EoE were diagnosed per consensus guidelines. At diagnosis and after 8 weeks of treatment, symptoms were measured using the VAS, LS and the Mayo Dysphagia Questionnaire (MDQ). The percentage change in scores before and after treatment were compared overall, in treatment responders (<15 eos/hpf) and non-responders, and in patients without baseline dilation. RESULTS: In 51 EoE cases, the median VAS decreased from 3.6 at baseline to 1.4 post-treatment (71% decrease), the LS decreased from 6 to 2 (67%) and the MDQ decreased from 20 to 10 (49%). The VAS correlated with both the LS (R = 0.77; P < 0.0001) and MDQ (R = 0.46, P = 0.001). After stratification by histological response, the LS decreased 70% in responders vs. 13% in non-responders (P = 0.02). In patients who did not receive baseline dilation, both the VAS and LS decreased significantly more in the histological responders. CONCLUSIONS: Both the VAS and LS were responsive to successful treatment as measured by histologic improvement. Because the VAS and LS are simple to administer and are responsive to treatment, they can provide an efficient and objective method for assessing dysphagia severity in EoE in clinical practice.
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Trastornos de Deglución/diagnóstico , Endoscopía/métodos , Esofagitis Eosinofílica/tratamiento farmacológico , Adulto , Trastornos de Deglución/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Dimensión del Dolor , Estudios Prospectivos , Encuestas y Cuestionarios , Escala Visual AnalógicaAsunto(s)
Adenocarcinoma/epidemiología , Adenocarcinoma/mortalidad , Esófago de Barrett/complicaciones , Esófago de Barrett/terapia , Ablación por Catéter/métodos , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/mortalidad , Adenocarcinoma/prevención & control , Anciano , Anciano de 80 o más Años , Neoplasias Esofágicas/prevención & control , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Análisis de SupervivenciaRESUMEN
BACKGROUND & AIMS: Topical corticosteroids or dietary elimination are recommended as first-line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6-food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective. METHODS: We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort-member level. Simulation parameters were defined by systematic review and meta-analysis to determine the base-case estimates and bounds of uncertainty for sensitivity analysis. Meta-regression models included adjustment for differences in study and cohort characteristics. RESULTS: In the base-case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5-year time horizon ($9261.58 vs $5719.72 per person). SFED was more effective and less expensive than topical fluticasone and topical budesonide in the base-case scenario. Probabilistic sensitivity analysis revealed little uncertainty in relative treatment effectiveness. There was somewhat greater uncertainty in the relative cost of treatments; most simulations found SFED to be less expensive. CONCLUSIONS: In a cost utility analysis comparing topical corticosteroids and SFED for first-line treatment of eosinophilic esophagitis, the therapies were similar in effectiveness. SFED was on average less expensive, and more cost effective in most simulations, than topical budesonide and topical fluticasone, from a payer perspective and not accounting for patient-level costs or quality of life.
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Antiinflamatorios/economía , Análisis Costo-Beneficio , Dieta/economía , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/economía , Esteroides/economía , Administración Tópica , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Estudios de Cohortes , Dieta/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esteroides/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Because eosinophilic esophagitis (EoE) causes dysphagia, esophageal narrowing, and strictures, it could result in low body mass index (BMI), but there are few data assessing this. AIM: To determine whether EoE is associated with decreased BMI. METHODS: We conducted a prospective study at the University of North Carolina from 2009 to 2013 enrolling consecutive adults undergoing outpatient EGD. BMI and endoscopic findings were recorded. Incident cases of EoE were diagnosed per consensus guidelines. Controls had either reflux or dysphagia, but not EoE. BMI was compared between cases and controls and by endoscopic features. RESULTS: Of 120 EoE cases and 297 controls analyzed, the median BMI was lower in EoE cases (25 vs. 28 kg/m2, p = 0.002). BMI did not differ by stricture presence (26 vs. 26 kg/m2, p = 0.05) or by performance of dilation (26 vs. 27 kg/m2 for undilated; p = 0.16). However, BMI was lower in patients with narrow caliber esophagus (24 vs. 27 kg/m2, p < 0.001). EoE patients with narrow caliber esophagus also had decreased BMI compared to controls with narrow caliber esophagi (24 vs. 27 kg/m2, p = 0.001). On linear regression after adjustment for age, race, and gender, narrowing decreased BMI by 2.3 kg/m2 [95% CI -4.1, -0.6]. CONCLUSIONS: BMI is lower in EoE cases compared to controls, and esophageal narrowing, but not focal stricture, is associated with a lower BMI in patients with EoE. Weight loss or low BMI in a patient suspected of having EoE should raise concern for esophageal remodeling causing narrow caliber esophagus.
Asunto(s)
Trastornos de Deglución/epidemiología , Esofagitis Eosinofílica/epidemiología , Estenosis Esofágica/epidemiología , Delgadez/epidemiología , Adulto , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios de Cohortes , Trastornos de Deglución/etiología , Dilatación , Endoscopía del Sistema Digestivo , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/patología , Estenosis Esofágica/etiología , Estenosis Esofágica/patología , Estenosis Esofágica/cirugía , Esófago/patología , Esófago/cirugía , Femenino , Hernia Hiatal/epidemiología , Humanos , Incidencia , Modelos Lineales , Masculino , Persona de Mediana Edad , North Carolina/epidemiología , Estudios ProspectivosRESUMEN
The six-food elimination diet (SFED), where dairy, wheat, eggs, soy, nuts, and seafood are avoided, is an effective treatment for eosinophilic esophagitis (EoE). Patient-related costs of this approach, however, are unknown. We aimed to assess the cost of and ease of shopping for an SFED compared to an unrestricted diet. A dietitian with expertise in EoE generated menus meeting dietary requirements for a week's worth of meals for the SFED and an unrestricted diet. We compared prices and the number of missing items for both diets at standard and specialty grocery stores. The average weekly price of the SFED at a standard supermarket was $92.54 compared to $79.84 for an unrestricted diet (p = 0.0001). A patient shopping at a standard grocery store needed a higher proportion of items from a second store compared to an unrestricted diet (32 vs. 3 %, p = 0.0001). The prices of the SFED and unrestricted diet using a specialty supermarket were comparable ($106.47 vs. $105.96, p = 0.81), as was the percentage of items requiring a trip to a second store (6 vs. 2 % items, p = 0.03). Shopping at a specialty grocery store increased weekly grocery costs by $13.93 (p = 0.04) for the SFED and $26.12 (p = 0.03) for the unrestricted diet. In conclusion, for patients shopping at standard grocery stores, the cost of an SFED is higher, and an SFED requires more items from a second store. These differences disappear at specialty grocery stores, but costs were significantly higher. This cost and logistical burden can inform patients when selecting dietary therapy.
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Dieta/economía , Esofagitis Eosinofílica/dietoterapia , Alimentos/economía , Comercio , Costos y Análisis de Costo/estadística & datos numéricos , Dieta/métodos , Esofagitis Eosinofílica/economía , Humanos , Estados UnidosRESUMEN
We present a numerical method to compute the acoustic field scattered by finite perforated elastic plates. A boundary element method is developed to solve the Helmholtz equation subjected to boundary conditions related to the plate vibration. These boundary conditions are recast in terms of the vibration modes of the plate and its porosity, which enables a direct solution procedure. A parametric study is performed for a two-dimensional problem whereby a cantilevered perforated elastic plate scatters sound from a point quadrupole near the free edge. Both elasticity and porosity tend to diminish the scattered sound, in agreement with previous work considering semi-infinite plates. Finite elastic plates are shown to reduce acoustic scattering when excited at high Helmholtz numbers k0 based on the plate length. However, at low k0, finite elastic plates produce only modest reductions or, in cases related to structural resonance, an increase to the scattered sound level relative to the rigid case. Porosity, on the other hand, is shown to be more effective in reducing the radiated sound for low k0. The combined beneficial effects of elasticity and porosity are shown to be effective in reducing the scattered sound for a broader range of k0 for perforated elastic plates.
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Esofagitis Eosinofílica/etiología , Esofagitis Eosinofílica/inmunología , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina G/metabolismo , Adulto , Alérgenos/inmunología , Especificidad de Anticuerpos , Estudios de Casos y Controles , Esofagitis Eosinofílica/dietoterapia , Esófago/inmunología , Alimentos/efectos adversos , Hipersensibilidad a los Alimentos/dietoterapia , Humanos , Inmunoglobulina G/sangreRESUMEN
BACKGROUND: Substantial racial disparities exist in colorectal cancer (CRC) survival. OBJECTIVE: This was an exploratory study to assess the racial differences in dietary changes in relation to quality of life (QoL), recurrence, and survival after a CRC diagnosis. DESIGN: Four hundred fifty-three stage II CRC patients were enrolled in the cohort study through the North Carolina Central Cancer Registry. Self-reported diet, physical activity, treatment, comorbidities, demographic characteristics, and QoL were collected at diagnosis and 12 and 24 mo after diagnosis. QoL was assessed with the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and the Medical Outcomes 12-Item Short Form Health Survey (SF-12) inventories. An overall dietary index score was calculated. Generalized estimating equations and logistic regression models were used to explore potential associations. Statistical power for this study was â¼50%. RESULTS: African Americans (n = 81) were more likely to increase intakes of reduced-fat milk, vegetables, and fruit and decrease intakes of regular cheese, red meat, fried food, fast food, and fat (P < 0.05) than were Caucasians (n = 184) 24 mo after diagnosis. The least-squares means ± SEs for changes in dietary index were 6.05 ± 0.40 and 4.07 ± 0.27 for African Americans and Caucasians, respectively (P < 0.001). African Americans exhibited higher scores on portions of the FACT-C (colorectal cancer subscale: ß = 1.04; 95% CI: 0.26, 1.82) and the SF-12 (Physical Component Summary: ß = 2.49; 95% CI: 0.51, 4.48). Those who improved their dietary quality over 24 mo had lower risk of recurrence and mortality combined (OR: 0.42; 95% CI: 0.25, 0.72). CONCLUSIONS: African Americans made more healthful changes in diet and had a higher QoL than did Caucasians in this underpowered study that used self-reported dietary data. No racial differences in recurrence or survival were evident, although improvements in dietary quality did reveal survival benefits overall. More prospective research on racial disparities in health behavior changes after diagnosis is desperately needed.
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Neoplasias Colorrectales/terapia , Dieta Saludable/etnología , Dieta , Conductas Relacionadas con la Salud/etnología , Calidad de Vida , Grupos Raciales , Negro o Afroamericano , Anciano , Estudios de Cohortes , Neoplasias Colorrectales/mortalidad , Grasas de la Dieta/administración & dosificación , Comida Rápida , Femenino , Frutas , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/etnología , Carne Roja , Tasa de Supervivencia , Verduras , Población BlancaRESUMEN
Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from â¼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.
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Bases de Datos Genéticas , Variación Genética , Genómica , Farmacogenética , Anciano , Registros Electrónicos de Salud , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medicina de Precisión/métodosRESUMEN
BACKGROUND AND AIMS: Some patients with eosinophilic esophagitis (EoE) have an extremely narrow esophagus, but the characteristics of this group have not been extensively described. We aimed to characterize the narrow-caliber phenotype of EoE, determine associated risk factors, and identify differences in treatment response in this subgroup of patients. METHODS: This retrospective cohort study from 2001 to 2014 included subjects with a new diagnosis of EoE per consensus guidelines. Demographic, endoscopic, histologic, and treatment response data were extracted from medical records. An extremely narrow-caliber esophagus was defined when a neonatal endoscope was required to traverse the esophagus due to the inability to pass an adult endoscope. Patients with and without an extremely narrow-caliber esophagus were compared. Multivariable logistical regression was performed to assess treatment outcomes. RESULTS: Of 513 patients with EoE, 46 (9%) had an extremely narrow-caliber esophagus. These patients were older (33 vs 22 years; P < .01), had longer symptom duration (11 vs 3 years; P < .01), more dysphagia (98% vs 66%; P < .01), and food impactions (53% vs 31%; P < .01). Dilation was more common with extreme narrowing (69% vs 17%; P < .01). Patients with a narrow-caliber esophagus were more refractory to steroid treatment, with lower symptom (56% vs 85%), endoscopic (52% vs 76%), and histologic (33% vs 63%) responses (P < .01 for all), and these differences persisted after multivariate analysis. CONCLUSION: The extremely narrow-caliber esophagus is a more treatment-resistant subphenotype of EoE and is characterized by longer symptom duration and the need for multiple dilations. Recognition of an extremely narrow-caliber esophagus at diagnosis of EoE can provide important prognostic information.
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Trastornos de Deglución/patología , Esofagitis Eosinofílica/patología , Estenosis Esofágica/patología , Esófago/patología , Corticoesteroides/uso terapéutico , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Trastornos de Deglución/tratamiento farmacológico , Trastornos de Deglución/etiología , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/tratamiento farmacológico , Estenosis Esofágica/etiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tamaño de los Órganos , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND & AIMS: Radiofrequency ablation (RFA) is commonly used to treat Barrett's esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS: We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS: Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS: Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.
Asunto(s)
Adenocarcinoma/mortalidad , Adenocarcinoma/prevención & control , Esófago de Barrett/mortalidad , Esófago de Barrett/cirugía , Ablación por Catéter/mortalidad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/prevención & control , Adenocarcinoma/diagnóstico , Anciano , Anciano de 80 o más Años , Esófago de Barrett/diagnóstico , Ablación por Catéter/efectos adversos , Causas de Muerte , Distribución de Chi-Cuadrado , Neoplasias Esofágicas/diagnóstico , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Factores Protectores , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: Surveillance endoscopy detects dysplasia within Barrett's esophagus (BE) and dictates treatment. Current biopsy regimens recommend uniformly spaced random biopsies. We assessed the distribution of dysplasia in BE to develop evidence-based biopsy regimens. METHODS: We performed analysis of the distribution of dysplasia within BE using pretreatment biopsy data from two randomized controlled trials (RCTs) of radiofrequency ablation for dysplastic BE: the SURF (Surveillance vs. Radiofrequency Ablation) trial and the AIM Dysplasia (Ablation of Intestinal Metaplasia (AIM) Containing Dysplasia) trial. We used generalized linear models with generalized estimating equations (GEE) to estimate prevalence differences for dysplasia depending on the standardized location of biopsies. We performed Monte Carlo simulation of biopsy regimens to estimate their yield for any dysplasia within segments. RESULTS: Dysplasia preferentially resides in the proximal-most half of the BE segment that is almost twice as likely to demonstrate dysplasia as the distal-most quartile. In pooled analysis, compared with the distal-most quarter, the prevalence difference in the proximal-most quarter was 22.6%, in the second proximal-most quarter 23.1%, and in the second distal-most quarter 15.3%. The best performing biopsy regimen in simulation studies acquired 8 biopsies in the most proximal cm of BE, 8 biopsies in the second cm, and 2 biopsies in each cm thereafter (q1cm: 8, 8, 2, 2 ). A slightly simpler q2cm (every 2 cm) regimen (q2cm: 12, 12, 4 ) was nearly as effective. CONCLUSIONS: The post hoc analysis of two RCTs reveals a substantially increased prevalence of dysplasia proximally in BE segments. Our simulations suggest an altered biopsy regimen could increase sensitivity of biopsies in short-segment BE by >30%.
Asunto(s)
Esófago de Barrett/patología , Neoplasias Esofágicas/patología , Esófago/patología , Lesiones Precancerosas/patología , Anciano , Esófago de Barrett/cirugía , Biopsia/métodos , Ablación por Catéter , Estudios de Cohortes , Endoscopía del Sistema Digestivo , Neoplasias Esofágicas/cirugía , Esófago/cirugía , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Método de Montecarlo , Lesiones Precancerosas/cirugíaRESUMEN
BACKGROUND & AIMS: Complete eradication of Barrett's esophagus (BE) often requires multiple sessions of radiofrequency ablation (RFA). Little is known about the effects of case volume on the safety and efficacy of RFA or about the presence or contour of learning curves for this procedure. METHODS: We collected data from the US RFA Patient Registry (from 148 institutions) for patients who underwent RFA for BE from July 2007 to July 2011. We analyzed the effects of the number of patients treated by individual endoscopists and individual centers on safety and efficacy outcomes of RFA. Outcomes, including stricture, bleeding, hospitalization, and complete eradication of intestinal metaplasia (CEIM), were assessed using logistic regression. The effects of center and investigator experience on numbers of treatment sessions to achieve CEIM were examined using linear regression. RESULTS: After we controlled for potential confounders, we found that as the experience of endoscopists and centers increased with cases, the numbers of treatment sessions required to achieve CEIM decreased. This relationship persisted after adjusting for patient age, sex, race, length of BE, and presence of pretreatment dysplasia (P < .01). Center experience was not significantly associated with overall rates of CEIM or complete eradication of dysplasia. We did not observe any learning curve with regard to risks of stricture, gastrointestinal bleeding, perforation, or hospitalization (P > .05). CONCLUSIONS: Based on analysis of a large multicenter registry, efficiency of the treatment, as measured by number of sessions needed to achieve CEIM, increased with case volume, indicating a learning curve effect. This trend began to disappear after treatment of approximately 30 patients by the center or individual endoscopist. However, there was no significant association between safety or efficacy outcomes and previous case volume.
Asunto(s)
Adenocarcinoma/cirugía , Esófago de Barrett/cirugía , Ablación por Catéter , Competencia Clínica , Neoplasias Esofágicas/cirugía , Esofagoscopía , Curva de Aprendizaje , Adenocarcinoma/diagnóstico , Anciano , Esófago de Barrett/diagnóstico , Ablación por Catéter/efectos adversos , Neoplasias Esofágicas/diagnóstico , Esofagoscopía/efectos adversos , Femenino , Hospitales de Alto Volumen , Hospitales de Bajo Volumen , Humanos , Análisis de los Mínimos Cuadrados , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Prospectivos , Sistema de Registros , Inducción de Remisión , Reoperación , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Radiofrequency ablation (RFA) is a safe and effective treatment for Barrett's esophagus (BE) that results in high rates of complete eradication of intestinal metaplasia (CEIM). However, recurrence is common after CEIM, and surveillance endoscopy is recommended. Neither the anatomic location nor the endoscopic appearance of these recurrences is well-described. OBJECTIVE: Describe the location of histologic specimens positive for recurrence after CEIM and the testing performance of endoscopic findings for the histopathologic detection of recurrence. DESIGN: Retrospective cohort. SETTING: Single referral center. PATIENTS: A total of 198 patients with BE with at least 2 surveillance endoscopies after CEIM. INTERVENTIONS: RFA, EMR, surveillance endoscopy. MAIN OUTCOME MEASUREMENTS: The anatomic location and histologic grade of recurrence. RESULTS: In a mean 3.0 years of follow-up, 32 (16.2%; 95% confidence interval [CI], 11.0%-22.0%) patients had recurrence of disease, 5 (2.5%; 95% CI, 0.3%-4.7%) of whom progressed beyond their worst before-treatment histology. Recurrence was most common at or near the gastroesophageal junction (GEJ). Recurrence>1 cm proximal to the GEJ always was accompanied by endoscopic findings, and random biopsies in these areas detected no additional cases. The sensitivity of any esophageal sign under high-definition white light or narrow-band imaging for recurrence was 59.4% (42.4%, 76.4%), and the specificity was 80.6% (77.2%, 84.0%). LIMITATIONS: Single-center study. CONCLUSION: Recurrent intestinal metaplasia often is not visible to the endoscopist and is most common near the GEJ. Random biopsies>1 cm above the GEJ had no yield for recurrence. In addition to biopsy of prior EMR sites and of suspicious lesions, random biopsies oversampling the GEJ are recommended.