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1.
J Thorac Cardiovasc Surg ; 161(5): 1639-1648.e2, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32331817

RESUMEN

OBJECTIVE: We hypothesize that segmentectomy is associated with similar recurrence-free and overall survival when compared with lobectomy in the setting of patients with clinical T1cN0M0 non-small cell lung cancer (NSCLC; >2-3 cm), as defined by the American Joint Committee on Cancer 8th edition staging system. METHODS: We performed a single-institution retrospective study identifying patients undergoing segmentectomy (90) versus lobectomy (279) for T1c NSCLC from January 1, 2003, to December 31, 2016. Univariate, multivariable, and propensity score-weighted analyses were performed to analyze the following endpoints: freedom from recurrence, overall survival, and time to recurrence. RESULTS: Patients undergoing segmentectomy were older than patients undergoing lobectomy (71.5 vs 68.8, respectively, P = .02). There were no differences in incidence of major complications (12.4% vs 11.7%, P = .85), hospital length of stay (6.2 vs 7 days, P = .19), and mortality at 30 (1.1% vs 1.7%, P = 1) and 90 days (2.2% vs 2.3%, P = 1). In addition, there were no statistical differences in locoregional (12.2% vs 8.6%, P = .408), distant (11.1% vs 13.9%, P = .716), or overall recurrence (23.3% vs 22.5%, P = 1), as well as 5-year freedom from recurrence (68.6% vs 75.8%, P = .5) or 5-year survival (57.8% vs 61.0%, P = .9). Propensity score-matched analysis found no differences in overall survival (hazard ratio [HR], 1.034; P = .764), recurrence-free survival (HR, 1.168; P = .1391), or time to recurrence (HR, 1.053; P = .7462). CONCLUSIONS: In the setting of clinical T1cN0M0 NSCLC, anatomic segmentectomy was not associated with significant differences in recurrence-free or overall survival at 5 years. Further prospective randomized trials are needed to corroborate the expansion of the role of anatomic segmentectomy to all American Joint Committee on Cancer 8th Edition Stage 1A NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonectomía/mortalidad , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
2.
J Thorac Dis ; 11(1): 308-318, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30863609

RESUMEN

The role of anatomic segmentectomy as an acceptable, lung parenchymal sparing alternative to pulmonary lobectomy for the small peripheral stage I lung cancer is under great scrutiny today. This is not a new consideration, particularly for the patient with impaired cardiopulmonary reserve where preservation of lung function may be a critical issue in deciding on surgical resection for local/regional control of their cancer. In this review, we discuss the oncologic issues along with past and present evidence supporting "anatomic" lung preservational surgery in the management of lung cancer.

3.
Lung Cancer ; 128: 145-151, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30642447

RESUMEN

OBJECTIVES: Anatomic lung resection provides the best opportunity for long-term survival in the setting of early-stage non-small cell lung cancer (NSCLC). However, 20-30% of patients develop recurrent disease following complete (R0) resection for Stage I disease. In the current study, we analyze the impact of patient, surgical and pathologic variables upon recurrence patterns following anatomic lung resection for clinical stage I NSCLC. PATIENTS AND METHODS: A total of 1132 patients (384 segmentectomies, 748 lobectomies) with clinical stage I NSCLC were evaluated. Predictors of recurrence were identified by proportional hazards regression. Differences in recurrence patterns between groups are illustrated by log rank tests applied to Kaplan-Maier estimates. RESULTS: A total of 227 recurrences (20.0%) were recorded at a median follow-up of 36.8 months (65 locoregional, 155 distant). There was no significant difference in recurrence patterns when comparing segmentectomy and lobectomy. Multivariate analysis demonstrated that angiolymphatic invasion, tumor size, tumor grade and the presence of only mild-moderate tumor inflammation were independent predictors of recurrence risk. CONCLUSIONS: Recurrence following anatomic lung resection is influenced predominantly by pathological variables (tumor size, tumor grade, angiolymphatic invasion, tumor inflammation). Optimization of surgical margin in relation to tumor size may improve outcomes. Extent of resection (segmentectomy vs. lobectomy) does not appear to have an impact on recurrence-free survival when adequate margins are obtained.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neumonectomía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neumonectomía/efectos adversos , Neumonectomía/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
4.
Ann Surg Oncol ; 25(1): 59-63, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28251378

RESUMEN

PURPOSE AND DESIGN: Standard treatment for early-stage non-small cell lung cancer has traditionally involved lobectomy. Historical data that demonstrates suboptimal results for sublobar resection compared to lobectomy have been challenged in recent years with retrospective data for patients with T1a disease. For patients who are not candidates for lobectomy, options for sublobar resection include wedge resection or anatomic segmentectomy. Segmentectomy has long been held to be a better cancer operation than wedge resection, and its role in treating early-stage lung cancer remains controversial in patients who are candidates for lobectomy. A review of available literature involving segmentectomy and possible predictors of failure for segmentectomy was performed in an attempt to clarify the role of segmentectomy for early-stage lung cancer. RESULTS AND CONCLUSIONS: Current evidence is conflicting regarding the optimal scenario for sublobar resection with segmentectomy. Two large-scale randomized trials are currently addressing the question. In the meantime, certain preoperative and intraoperative considerations should be taken into account when considering segmentectomy for the treatment of early-stage non-small cell lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Selección de Paciente
6.
Ann Surg ; 266(1): 91-98, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-27471841

RESUMEN

OBJECTIVE: The purpose of the current study is to determine the efficacy of a PI3K/mTOR dual inhibitor, LY3023414, on established EAC in an in vivo model. BACKGROUND: Esophageal adenocarcinoma (EAC) is a highly lethal cancer with limited treatment options. The PI3K/mTOR pathway is upregulated in EAC and may be a target for novel therapies. METHODS: Esophagojejunostomy was performed on Sprague-Dawley rats to induce carcinogenesis, and LY3023414 was cyclically administered intraperitoneally between 32 and 40 weeks postsurgery to treatment animals. Magnetic resonance imaging (MRI) and histology were used to determine clinical response. Immunohistochemistry, immunofluorescence, and Western blot were used to validate apoptosis by cleaved caspase-3, proliferation by Ki67, and pathway inhibition, respectively. RESULTS: Mean MRI tumor volume increased by 109.2% in controls (n = 32) and decreased by 56.8% in treatment animals (n=17) (P < 0.01). Treatment with LY3023414 demonstrated tumor volume increase in 0% (control = 46.4%) (P < 0.01), decrease in 58.8% (control = 7.1%) (P < 0.01), and stable volume in 41.2% (control = 46.4%) (P = 0.77). EAC prevalence in controls increased by 25%; whereas, prevalence in treatment animals decreased by 29.4% (P < 0.01). Approximately, 75% of treatment animals presenting with residual masses on MRI had a histological response >50%. Increased apoptosis by cleaved caspase-3 (P = 0.03) and decreased proliferation by Ki67 (P < 0.01) were demonstrated in the treatment arm, when compared with the control arm. On Western blot analysis of pathway checkpoints, p-mTOR (p=0.03) and PI3K-α (P = 0.04) were downregulated in treatment responsive residual tumors, when compared with controls. CONCLUSIONS: LY3023414 demonstrates efficacy against EAC in a preclinical model, establishing the rationale for clinical testing.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Proteínas Portadoras/antagonistas & inhibidores , Modelos Animales de Enfermedad , Neoplasias Esofágicas/tratamiento farmacológico , Piridinas/uso terapéutico , Quinolonas/uso terapéutico , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Animales , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Ratas Sprague-Dawley , Carga Tumoral
7.
BMC Cancer ; 16: 52, 2016 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-26841926

RESUMEN

BACKGROUND: Toll-like receptors (TLRs) recognize known molecules from microbes and have an established role in tumorigenesis. Using a rat model of esophageal adenocarcinoma, and human clinical samples, we investigated genes central to TLR-mediated signal transduction and characterized the esophageal microbiome across the spectrum of esophageal adenocarcinoma carcinogenesis. METHODS: We surgically induced bile/acid reflux in rats and their esophagi were harvested at 40 weeks post-surgery. Tissue samples from the model were selected for gene expression profiling. Additionally, for rat and human samples microbiome analysis was performed using PCR-ESI-MS-TOF technology with validation by fluorescence in situ hybridization. RESULTS: Gene expression results in the rat model indicated a significant upregulation of TLRs 1-3, 6, 7 and 9 in EAC compared to normal epithelium. PCR-ESI-MS-TOF analysis revealed a prevalence of Escherichia coli in Barrett's esophagus (60%) and esophageal adenocarcinoma (100%), which was validated by fluorescence in situ hybridization. In the human clinical samples, Streptococcus pneumonia was detected in high abundance in gastroesophageal reflux disease and Barrett's esophagus (50-70%) in comparison to tumor adjacent normal epithelium, dysplasia, and esophageal adenocarcinoma (20-30%). E. coli was detected in the Barrett's esophagus and esophageal adenocarcinoma groups but was absent in the tumor adjacent normal epithelium, dysplasia, and the gastroesophageal reflux disease groups. CONCLUSIONS: We demonstrated an association between the TLR signaling pathway and E. coli hinting towards possible early molecular changes being mediated by microbes in the rat model of esophageal adenocarcinoma carcinogenesis. Studies on human clinical samples also corroborate results to some extent; however, a study with larger sample size is needed to further explore this association.


Asunto(s)
Adenocarcinoma/genética , Esófago de Barrett/genética , Neoplasias Esofágicas/genética , Receptores Toll-Like/genética , Adenocarcinoma/microbiología , Adenocarcinoma/patología , Animales , Esófago de Barrett/microbiología , Esófago de Barrett/patología , Carcinogénesis/genética , Modelos Animales de Enfermedad , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Escherichia coli/patogenicidad , Neoplasias Esofágicas/microbiología , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Microbiota/genética , Ratas , Transducción de Señal/genética , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación , Streptococcus pneumoniae/patogenicidad , Receptores Toll-Like/biosíntesis
8.
Surg Endosc ; 30(1): 233-44, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25847137

RESUMEN

BACKGROUND: Peroral endoscopic myotomy (POEM) has been performed as a novel endoscopic procedure to treat achalasia with favorable outcome. The objective of this study was to assess the outcome of POEM in our initial series and to assess the safety and efficacy of POEM in a variety of esophageal motility-related clinical problems. METHODS: This is a retrospective cross-sectional study involving all patients with esophageal motility disorders defined by the Chicago classification, who had undergone consideration for POEM at our institution. Validated questionnaires such as gastroesophageal reflux disease health-related quality of life (GERD-HRQL), reflux symptom index (RSI) and achalasia disease-specific health-related quality of life were obtained pre- and postoperatively. RESULTS: From January 2013 to October 2014, a total of 35 POEMs (achalasia n = 25, non-achalasia n = 10) were performed on 33 patients (female n = 20, male n = 13, mean age 56.9 years). There was no mortality. The rate of inadvertent mucosotomy was 17.1%. The rate of complications requiring interventions was 5.7%. During a mean follow-up period of 7 months (range 0.5-17), 92% of patients with achalasia and 75% of those with non-achalasia motility disorders had a symptomatic improvement in dysphagia. Chest pain was completely resolved in all patients with achalasia (8/8) and 80% of patients with non-achalasia (4/5). The GERD-HRQL, RSI and dysphagia scores significantly improved after POEM in patients with achalasia. There was a significant improvement in GERD-HRQL and RSI scores, and a trend toward lower dysphagia score in patients with non-achalasia. CONCLUSIONS: The outcome of POEM to treat achalasia and non-achalasia motility disorders is consistent with previous studies. Potential benefit of POEM includes not only its flexibility to adjust the length and location of myotomy but also the ability to extend myotomy proximally without thoracoscopy or thoracotomy. POEM can be combined with laparoscopic procedures and used as "salvage" for localized esophageal dysmotility.


Asunto(s)
Acalasia del Esófago/cirugía , Esofagoscopía , Membrana Mucosa/cirugía , Cirugía Endoscópica por Orificios Naturales , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
9.
Ann Surg ; 264(2): 297-304, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26445473

RESUMEN

OBJECTIVE: To assess the efficacy of heat-shock protein 90 (Hsp90) inhibitor, NVP-AUY922-AG (AUY922), in the treatment of esophageal adenocarcinoma (EAC) in vitro and in vivo. BACKGROUND: EAC is a leading cause of cancer death, and current treatment options are limited. Hsp90, a chaperone protein that regulates several oncoproteins, is upregulated in EAC, and may be a novel target for therapy. METHODS: In vitro, EAC cell lines were utilized to evaluate AUY922, alone and in combination with 5-fluorouracil (5-FU) and cisplatin. BrdU ELISA and flow cytometry were used to assess proliferation and measure apoptosis, respectively. Western blot and RT-PCR were performed to quantitate Hsp90 pathway expression. In vivo, esophagojejunostomy was performed on rats and treatment animals received AUY922 32 to 40 weeks postoperatively. Drug efficacy was evaluated with magnetic resonance imaging (MRI), endoscopic biopsy, gross histological evaluation, and Hsp90 pathway expression. RESULTS: In vitro, AUY922 demonstrated antiproliferative activity in both cell lines and showed enhanced efficacy with cisplatin and 5-FU. Western Blot and RT-PCR demonstrated downregulation of CDK1 and CDK4 and upregulation of Hsp72. In vivo, AUY922 showed decrease in tumor volume in 36.4% of rats (control = 9.4%), increase in 9.1% (control = 37.5%), and stable disease in 54.5% (control = 43.7%). Necropsy confirmed the presence of EAC in 50% of treatment animals and 75% of control animals. mRNA expression, pre- and posttreatment, demonstrated significant downregulation of MIF, Hsp70, Hsp90ß, and CDK4, and upregulation of Hsp72. CONCLUSIONS: AUY922 exhibits antitumor efficacy in vitro and in vivo for EAC, suggesting the need for human clinical trials.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Isoxazoles/uso terapéutico , Resorcinoles/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Masculino , Ratas , Ratas Sprague-Dawley
10.
Ann Thorac Surg ; 100(6): 2019-24, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26387725

RESUMEN

BACKGROUND: A significant number of patients have recurrent or persistent lung cancer despite complete resection or treatment with definitive chemoradiation. Stereotactic radiosurgery (SRS)/stereotactic body radiation therapy is emerging as an important modality for the treatment of early-stage lung neoplasm; SRS may also offer an alternative treatment option for patients with recurrent lung disease. We evaluated outcomes after treatment with SRS for recurrent lung neoplasm in a large series of patients. METHODS: Selected patients with limited recurrent, persistent, or progressive disease after one or more prior treatments for lung cancer were offered SRS. Thoracic surgeons evaluated all patients, placed fiducials when needed, and planned treatment in close collaboration with radiation oncologists and medical physicists. In our early experience, a single fraction of 20 Gy radiation was prescribed and was subsequently increased to 45 to 60 Gy in three to five fractions. The primary endpoint evaluated was overall survival. RESULTS: We treated 100 patients with recurrent lung cancer (median age 72 years) with SRS. The postprocedure 30-day mortality rate was 0%; median follow-up was 51 months (range, 5 to 123). The median overall survival for the entire group was 23 months (95% confidence interval: 19 to 41). The probability of 2-year and 5-year overall survival was 49% (95% confidence interval: 40% to 60%) and 31% (95% confidence interval: 23% to 43%), respectively. CONCLUSIONS: Our experience indicates that SRS is safe, and offers an alternative modality for selected patients with recurrent oligometastatic or persistent lung cancer. Thoracic surgeons should actively participate in SRS and continue to evaluate the efficacy of this treatment strategy.


Asunto(s)
Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/cirugía , Radiocirugia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Relación Dosis-Respuesta en la Radiación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Pennsylvania/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento
12.
J Thorac Cardiovasc Surg ; 150(3): 523-8, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26319461

RESUMEN

OBJECTIVES: Accurate cancer localization and negative resection margins are necessary for successful segmentectomy. In this study, we evaluate a newly developed software package that permits automated segmentation of the pulmonary parenchyma, allowing 3-dimensional assessment of tumor size, location, and estimates of surgical margins. METHODS: A pilot study using a newly developed 3-dimensional computed tomography analytic software package was performed to retrospectively evaluate preoperative computed tomography images of patients who underwent segmentectomy (n = 36) or lobectomy (n = 15) for stage 1 non-small cell lung cancer. The software accomplishes an automated reconstruction of anatomic pulmonary segments of the lung based on bronchial arborization. Estimates of anticipated surgical margins and pulmonary segmental volume were made on the basis of 3-dimensional reconstruction. RESULTS: Autosegmentation was achieved in 72.7% (32/44) of preoperative computed tomography images with slice thicknesses of 3 mm or less. Reasons for segmentation failure included local severe emphysema or pneumonitis, and lower computed tomography resolution. Tumor segmental localization was achieved in all autosegmented studies. The 3-dimensional computed tomography analysis provided a positive predictive value of 87% in predicting a marginal clearance greater than 1 cm and a 75% positive predictive value in predicting a margin to tumor diameter ratio greater than 1 in relation to the surgical pathology assessment. CONCLUSIONS: This preoperative 3-dimensional computed tomography analysis of segmental anatomy can confirm the tumor location within an anatomic segment and aid in predicting surgical margins. This 3-dimensional computed tomography information may assist in the preoperative assessment regarding the suitability of segmentectomy for peripheral lung cancers.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Imagenología Tridimensional/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Cuidados Preoperatorios/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Cirugía Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasia Residual , Selección de Paciente , Proyectos Piloto , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Programas Informáticos , Resultado del Tratamiento
13.
Ochsner J ; 15(1): 83-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25829886

RESUMEN

BACKGROUND: Stress-induced cardiomyopathy, also known as takotsubo cardiomyopathy, is not fully understood. It is thought to occur in patients who have signs and symptoms consistent with acute myocardial infarction but display no obstructive coronary lesions during heart catheterization. Characteristics include transient left ventricular dysfunction, wall motion abnormalities on echocardiogram, new electrocardiographic ST-segment changes, and the occurrence of a precipitating stressor. CASE REPORT: We present a patient who underwent Heller myotomy and suffered acute heart failure in the immediate postoperative period. Left heart catheterization revealed clean coronary arteries, and the patient fully recovered days later. While difficult to fully exclude drug-related causes, we believe this case to be consistent with takotsubo cardiomyopathy. CONCLUSION: This unusual postoperative complication following uneventful laparoscopic surgery should be kept in mind when unsuspected cardiovascular compromise is seen in the early perioperative recovery period. In addition to the rare occurrence of acute coronary ischemia syndromes and possible perioperative pulmonary embolic events, cardiovascular decompensation related to acute stress syndromes or idiopathic pharmacologic responses must be considered. Even patients who seem most healthy can have complications that warrant immediate attention and treatment.

14.
PLoS One ; 10(3): e0122375, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25826212

RESUMEN

OBJECTIVE: To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC). BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies. METHODS: The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors. RESULTS: The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2. CONCLUSION: In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Esofágicas/patología , MicroARNs/genética , Metástasis de la Neoplasia/genética , Animales , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Masculino , Ratas , Ratas Sprague-Dawley
15.
J Cardiothorac Surg ; 10: 49, 2015 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-25888465

RESUMEN

BACKGROUND: A suggested benefit of sublobar resection for stage I non-small cell lung cancer (NSCLC) compared to lobectomy is a relative preservation of pulmonary function. Very little objective data exist, however, supporting this supposition. We sought to evaluate the relative impact of both anatomic segmental and lobar resection on pulmonary function in patients with resected clinical stage I NSCLC. METHODS: The records of 159 disease-free patients who underwent anatomic segmentectomy (n = 89) and lobectomy (n = 70) for the treatment of stage I NSCLC with pre- and postoperative pulmonary function tests performed between 6 to 36 months after resection were retrospectively reviewed. Changes in forced expiratory volume in one second (FEV1) and diffusion capacity of carbon monoxide (DLCO) were analyzed based upon the number of anatomic pulmonary segments removed: 1-2 segments (n = 77) or 3-5 segments (n = 82). RESULTS: Preoperative pulmonary function was worse in the lesser resection cohort (1-2 segments) compared to the greater resection group (3-5 segments) (FEV1(%predicted): 79% vs. 85%, p = 0.038; DLCO(%predicted): 63% vs. 73%, p = 0.010). A greater decline in FEV1 was noted in patients undergoing resection of 3-5 segments (FEV1 (observed): 0.1 L vs. 0.3 L, p = 0.003; and FEV1 (% predicted): 4.3% vs. 8.2%, p = 0.055). Changes in DLCO followed this same trend (DLCO(observed): 1.3 vs. 2.4 mL/min/mmHg, p = 0.015; and DLCO(% predicted): 3.6% vs. 5.9%, p = 0.280). CONCLUSIONS: Parenchymal-sparing resections resulted in better preservation of pulmonary function at a median of one year, suggesting a long-term functional benefit with small anatomic segmental resections (1-2 segments). Prospective studies to evaluate measurable functional changes, as well as quality of life, between segmentectomy and lobectomy with a larger patient cohort appear justified.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Pulmón/fisiopatología , Neumonectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Femenino , Volumen Espiratorio Forzado , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Retrospectivos
17.
J Thorac Cardiovasc Surg ; 149(3): 718-25; discussion 725-6, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25500100

RESUMEN

BACKGROUND: Prior studies have suggested that low baseline quality-of-life (QOL) scores predict worse survival in patients undergoing lung cancer surgery. However, these studies involved average-risk patients undergoing lobectomy. We report QOL results from a multicenter trial, American College of Surgeons Oncology Group Z4032, which randomized high-risk operable patients to sublobar resection (SR), or SR with brachytherapy, and included longitudinal QOL assessments. METHODS: Global QOL, using the 36-item Short-Form Health Survey (SF36), and the dyspnea score from the University of California, San Diego Shortness of Breath Questionnaire (SOBQ) scale, was measured at baseline, 3, 12, and 24 months. SF36 physical component summary (PCS) and mental component summary (MCS) scores were standardized and adjusted for age and gender normals, with scores <50 indicating below-average health status. SOBQ scores were transformed to a 0-100 (poor-excellent) scale. Aims were to: (1) determine the impact of baseline scores on recurrence-free survival, overall survival, and 30-day adverse events (AEs); and (2) identify subgroups (surgical approach, resection type. tumor location, tumor size, respiratory function) with a ≥ 10-point decline or improvement in QOL after SR. RESULTS: Two hundred twelve eligible patients were included. There were no significant differences in baseline QOL scores between arms. Median baseline PCS, MCS, and SOBQ scores were 42.7, 51.1, and 70.8, respectively. There were no differences in grade-3+ AEs, overall survival, or recurrence-free survival in patients with baseline scores ≤ median versus > median values, except for a significantly worse overall survival for patients with baseline SOBQ scores ≤ median value. There were no significant differences between the study arms in percentage change of QOL scores from baseline to 3, 12, or 24 months. Further comparison combining the 2 arms demonstrated a higher percentage of patients with a ≥ 10-point decline in SOBQ scores with segmentectomy compared with wedge resection (40.5% vs 21.9%, P = .03) at 12 months, with thoracotomy versus video-assisted thoracic surgery (VATS) (38.8% vs 20.4%, P = .03) at 12 months, and T1b versus T1a tumors (46.9% vs 23.5%, P = .020) at 24 months. A ≥ 10-point improvement in PCS score was seen at 3 months with VATS versus thoracotomy (16.5% vs 3.6%, P = .02). CONCLUSIONS: In high-risk operable patients, poor baseline QOL scores were not predictive for worse overall or recurrence-free survival, or for higher risk for AEs following SR. VATS was associated with improvement in physical function at 3 months, and improved dyspnea scores at 12 months, lending support for the preferential use of VATS when SR is undertaken.


Asunto(s)
Neoplasias Pulmonares/cirugía , Neumonectomía/psicología , Calidad de Vida , Anciano , Anciano de 80 o más Años , Braquiterapia , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Estado de Salud , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/psicología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neumonectomía/efectos adversos , Neumonectomía/mortalidad , Estudios Prospectivos , Radioterapia Adyuvante , Medición de Riesgo , Factores de Riesgo , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
18.
Ann Thorac Surg ; 98(6): 1905-11; discussion 1911-3, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25442998

RESUMEN

BACKGROUND: Intractable gastroesophageal reflux disease (GERD) after antireflux operations presents a challenge-particularly in obese patients and patients with esophageal dysmotility-and increases the complexity of the redo operation. This study evaluated the results of Roux-en-Y near esophagojejunostomy (RNYNEJ) in the management of recurrent GERD after antireflux operations. METHODS: We conducted a retrospective review of overweight patients with intractable GERD who underwent RNYNEJ for failed antireflux operations. We evaluated perioperative outcomes, dysphagia (ranging from 1 = no dysphagia to 5 = unable to swallow saliva), and quality of life (QOL) (assessed using the GERD health-related quality-of-life instrument (HRQOL). RESULTS: Over a 12-year period, 105 patients with body mass index (BMI) greater than 25 underwent RNYNEJ for failed antireflux operations. Most were obese (BMI > 30; 82 patients [78%]); esophageal dysmotility was demonstrated in more than one-third of patients. Forty-eight (46%) patients had multiple antireflux operations before RNYNEJ, and 27 patients had undergone a previous Collis gastroplasty. There was no perioperative mortality. Major complications, including anastomotic leak requiring surgical intervention (n = 3 [2.9%]), were noted in 25 patients (24%).The median length of stay was 6 days. During follow-up (mean, 23.39 months), median BMI decreased from 35 to 27.6 (p < 0.0001), and the mean dysphagia score decreased from 2.9 to 1.5 (p < 0.0001). The median GERD HRQOL score, assessed in a subset of patients, was 9 (classified as excellent). CONCLUSIONS: RNYNEJ for persistent GERD after antireflux operations in appropriately selected patients can be performed safely with good results in experienced centers. RNYNEJ should be considered an important option for the treatment of intractable recurrent symptoms after antireflux operations, particularly in obese patients.


Asunto(s)
Anastomosis en-Y de Roux/métodos , Esófago/cirugía , Reflujo Gastroesofágico/cirugía , Yeyunostomía/métodos , Yeyuno/cirugía , Laparoscopía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Predicción , Reflujo Gastroesofágico/psicología , Humanos , Tiempo de Internación/tendencias , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Calidad de Vida/psicología , Reoperación , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto Joven
19.
J Clin Oncol ; 32(23): 2449-55, 2014 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-24982447

RESUMEN

PURPOSE: Although anatomic segmentectomy has been considered a compromised procedure by many surgeons, recent retrospective, single-institution series have demonstrated tumor recurrence and patient survival rates that approximate those achieved by lobectomy. The primary objective of this study was to use propensity score matching to compare outcomes after these anatomic resection approaches for stage I non-small-cell lung cancer. PATIENTS AND METHODS: A retrospective data set including 392 segmentectomy patients and 800 lobectomy patients was used to identify matched segmentectomy and lobectomy cohorts (n = 312 patients per group) using a propensity score matching algorithm that accounted for confounding effects of preoperative patient variables. Primary outcome variables included freedom from recurrence and overall survival. Factors affecting survival were assessed by Cox regression analysis and Kaplan-Meier estimates. RESULTS: Perioperative mortality was 1.2% in the segmentectomy group and 2.5% in the lobectomy group (P = .38). At a mean follow-up of 5.4 years, comparing segmentectomy with lobectomy, no differences were noted in locoregional (5.5% v 5.1%, respectively; P = 1.00), distant (14.8% v 11.6%, respectively; P = .29), or overall recurrence rates (20.2% v 16.7%, respectively; P = .30). Furthermore, when comparing segmentectomy with lobectomy, no significant differences were noted in 5-year freedom from recurrence (70% v 71%, respectively; P = .467) or 5-year survival (54% v 60%, respectively; P = .258). Segmentectomy was not found to be an independent predictor of recurrence (hazard ratio, 1.11; 95% CI, 0.87 to 1.40) or overall survival (hazard ratio, 1.17; 95% CI, 0.89 to 1.52). CONCLUSION: In this large propensity-matched comparison, lobectomy was associated with modestly increased freedom from recurrence and overall survival, but the differences were not statistically significant. These results will need further validation by prospective, randomized trials (eg, Cancer and Leukemia Group B 140503 trial).


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/cirugía , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neumonectomía/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
20.
J Clin Oncol ; 32(23): 2456-62, 2014 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-24982457

RESUMEN

PURPOSE: A major concern with sublobar resection (SR) for non-small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB). PATIENTS AND METHODS: High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm. RESULTS: Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97). CONCLUSION: Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study.


Asunto(s)
Braquiterapia/métodos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología
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