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1.
Ann Surg ; 261(4): 702-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25575253

RESUMO

OBJECTIVE: The primary aim of this trial was to assess the feasibility of minimally invasive esophagectomy (MIE) in a multi-institutional setting. BACKGROUND: Esophagectomy is an important, potentially curative treatment for localized esophageal cancer, but is a complex operation. MIE may decrease the morbidity and mortality of resection, and single-institution studies have demonstrated successful outcomes with MIE. METHODS: We conducted a multicenter, phase II, prospective, cooperative group study (coordinated by the Eastern Cooperative Oncology Group) to evaluate the feasibility of MIE. Patients with biopsy-proven high-grade dysplasia or esophageal cancer were enrolled at 17 credentialed sites. Protocol surgery consisted of either 3-stage MIE or Ivor Lewis MIE. The primary end point was 30-day mortality. Secondary end points included adverse events, duration of hospital-stay, and 3-year outcomes. RESULTS: Protocol surgery was completed in 95 of the 104 patients eligible for the primary analysis (91.3%). The 30-day mortality in eligible patients who underwent MIE was 2.1%; perioperative mortality in all registered patients eligible for primary analysis was 2.9%. Median intensive care unit and hospital stay were 2 and 9 days, respectively. Grade 3 or higher adverse events included anastomotic leak (8.6%), acute respiratory distress syndrome (5.7%), pneumonitis (3.8%), and atrial fibrillation (2.9%). At a median follow-up of 35.8 months, the estimated 3-year overall survival was 58.4% (95% confidence interval: 47.7%-67.6%). Locoregional recurrence occurred in only 7 patients (6.7%). CONCLUSIONS: This prospective multicenter study demonstrated that MIE is feasible and safe with low perioperative morbidity and mortality and good oncological results. This approach can be adopted by other centers with appropriate expertise in open esophagectomy and minimally invasive surgery.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Laparoscopia/métodos , Toracoscopia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/epidemiologia , Comorbidade , Cuidados Críticos/estatística & dados numéricos , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Incidência , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
2.
Ann Surg Oncol ; 19(13): 4223-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22752374

RESUMO

BACKGROUND: Esophageal stents provide immediate palliation of malignant dysphagia; however, radiotherapy (RT) is a superior long-term option. We review the outcomes of combined esophageal stenting and RT for patients with malignant dysphagia. METHODS: We retrospectively reviewed patients with esophageal stents placed for palliation of malignant dysphagia from esophageal stricture, esophageal extrinsic compression, or malignant tracheoesophageal fistula (TEF). We excluded patients with radiation-induced TEF in the absence of tumor. We analyzed and compared outcomes between patients with no RT, RT before stent placement, and RT after stent placement. RESULTS: We placed stents in 45 patients for esophageal stricture from esophageal cancer (n = 30; 66.7 %), malignant TEF (n = 8; 17.7 %), and esophageal compression from airway, mediastinal, or metastatic malignancies (n = 7; 15.6 %). Twenty patients (44.4 %) had no RT; 25 patients had RT before stent placement (n = 16; 35.6 %), RT after stent placement (n = 8; 17.8 %), or both (n = 1; 2.2 %). Median follow-up was 30 days. Complications requiring stent revision were similar with or without RT. Subjective symptom relief was achieved in 68.9 % of all patients, with no differences noted between groups (p = 0.99). The 30-day mortality was 15.6 %. Patients with RT after stent placement had a longer median survival compared to those without RT (98 vs. 38 days). CONCLUSIONS: Esophageal stent placement with RT is a safe approach for malignant dysphagia.


Assuntos
Carcinoma de Células Escamosas/terapia , Transtornos de Deglutição/terapia , Neoplasias Esofágicas/terapia , Cuidados Paliativos , Radioterapia , Stents , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/complicações , Terapia Combinada , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Neoplasias Esofágicas/complicações , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
3.
J Surg Res ; 177(2): 185-90, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22921916

RESUMO

BACKGROUND: The effect of tumor location on long-term survival after lobectomy for stage I non-small-cell lung cancer is unclear. Current data are limited to a retrospective single-institution series. We sought to determine if tumor anatomic location (i.e., the particular lobe that was involved) confers a survival advantage based on population-based data. METHODS: Using the Surveillance, Epidemiology and End Results database (1988-2007), we identified patients who underwent lobectomy for pathologic T1/T2 adenocarcinoma or squamous cell carcinomas. Wedge resections, segmentectomies, and pneumonectomies were excluded. We evaluated the association between the particular lobe that was involved, lymph node (LN) yield, and survival using the Kaplan-Meier method. To adjust for potential confounders, we used a Cox proportional hazards regression model. RESULTS: We identified 13,650 patients who met our inclusion criteria. There were significant differences in unadjusted overall (P=0.03) and cancer-specific survivals (P=0.03) based on tumor location. However, after adjusting for patient factors, geographic location of treatment, and tumor characteristics, we found that tumor location was not associated with significant differences in survival. We found that male gender, black race, squamous cell histology, increasing grade, and age were independent negative predictors of survival. Higher LN yields were independently associated with improved survival. Although adjusted survival rates were not significantly different, there were significant differences (P<0.0001) in LN yield based on tumor location; right middle lobe had the lowest yield (5.1 nodes), and left upper lobe had the highest yield (eight nodes). CONCLUSIONS: LN counts are independent predictors of survival. Although it is associated with significant difference in LN yield, tumor location is not an independent predictor of survival. Age, race, gender, tumor size, histology, and grade appear to be more important prognostic factors. These data suggest that treatment of T1/T2 non-small-cell lung cancer should be dictated by the same oncologic principles, regardless of tumor location.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Pulmão/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Programa de SEER , Fatores Sexuais , Estados Unidos/epidemiologia
4.
Ann Surg ; 254(2): 368-74, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21617585

RESUMO

OBJECTIVE: Surgical morbidity may influence long-term cancer survival. Because resection of early stage nonsmall cell lung cancer (NSCLC) is primary therapy, we sought to determine the survival impact of surgical complications for elderly patients undergoing resection of stage I NSCLC. METHODS: Using the linked Surveillance Epidemiology and End Results-Medicare database (2000-2005), we identified elderly patients who underwent lobectomy for stage I NSCLC. We then assessed the unadjusted association between in-hospital, postoperative complications, and long-term survival for patients who survived more than 30 days after resection using the Kaplan-Meier method. Finally, we used Cox proportional hazards regression to evaluate the relationship between postoperative complications and 5-year cancer-specific (CSS) and overall survival (OS) after adjusting for patient, tumor, and treatment characteristics. RESULTS: We identified 3996 eligible patients. The overall in-hospital, postoperative complication rate was 54.2%. Pulmonary complications were the most common (n = 1464) followed by cardiac (n = 916). Unadjusted 5-year CSS was significantly worse for those who had an in-hospital, postoperative complication (70.9%) compared to those who did not (78.9%, P < 0.001). OS was also significantly worse (P < 0.001) for patients who developed a complication. Complications continued to predict worse 5-year CSS and OS after adjusting for patient, tumor, and treatment characteristics (HR: 1.38, 95% CI, 1.17-1.64). CONCLUSIONS: The occurrence of in-hospital postoperative complications was an independent predictor of worse 5-year CSS after resection of stage I NSCLC. Importantly, the impact of surgical complications extends well after the initial perioperative period. These findings may help identify important targets for best practice guidelines and quality-of-care measures.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Mortalidade Hospitalar , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Complicações Pós-Operatórias/mortalidade , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma Bronquioloalveolar/mortalidade , Adenocarcinoma Bronquioloalveolar/patologia , Adenocarcinoma Bronquioloalveolar/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Causas de Morte , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Programa de SEER , Estados Unidos
5.
Thorac Surg Clin ; 21(3): 359-68, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21762859

RESUMO

Training in thoracic surgical residencies has evolved in the past several years, with significant advances in simulation technology, heightened pressure regarding work-hour reforms, and initiation of integrated training programs. This article highlights current concepts in surgical education and methods of incorporating teaching opportunities into practice. General strategies on how to be a better teacher and increase student feedback evaluation scores are addressed. Finally, the evolving roles and responsibilities of a mentor in assisting residents and colleagues in developing successful thoracic surgical careers are explored.


Assuntos
Internato e Residência/organização & administração , Cirurgia Torácica/educação , Certificação/organização & administração , Simulação por Computador , Docentes de Medicina , Humanos , Relação entre Gerações , Ensino/métodos
6.
Surg Obes Relat Dis ; 5(2): 181-93, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18996756

RESUMO

BACKGROUND: Minimally invasive surgery (MIS) has several potential benefits compared with the open approach, including potentially less perioperative immunosuppression. Data characterizing the differential stress responses have been limited to serum cytokine analyses and animal studies. We hypothesized that the open approach to Roux-en-Y gastric bypass (RYGB) has a more deleterious, negative, quantifiable effect on the peripheral blood mononuclear cells than does the MIS approach. METHODS: Patients undergoing open and MIS RYGB for morbid obesity had blood samples collected preoperatively and postoperatively on days 1 and 2 and at the first follow-up visit. The peripheral blood mononuclear cells were isolated and analyzed for phenotype using flow cytometry, natural killer cell cytotoxicity using 51-chromium release assay, and gene expression using Affymetrix U133 Plus 2.0 microarray. RESULTS: Patient age and body mass index were similar between the 2 groups. Postoperatively, differences within the open group were seen for CD3+/CD16- (T lymphocytes), CD3-/CD16+ (natural killer cells), CD3+/CD4+ (T-helper lymphocytes), and CD4/CD8 subsets (P<.05). No differences were seen within the open group CD3+/CD8+ (cytotoxic T lymphocytes) or within the MIS subsets. Between the 2 approaches, no phenotypic differences were found, except for the postoperative day 1 CD3+/CD16- (P<.05). Within each group, significant decreases were found in cytotoxicity on days 1 and 2 compared with preoperatively (P<.05). The cytotoxicity seen after MIS had returned to the preoperative levels at the first follow-up visit, but the cytotoxicity after open RYGB had not (P<.05). Between the 2 groups, the open group had greater cytotoxic decreases than did the MIS group at postoperative days 1 and 2 (P<.05). Microarray analysis of the preoperative (n=20) and day 2 (n=20) specimens identified a 20-gene signature that correlated with the surgical approach. CONCLUSION: Open RYGB surgery causes greater inhibition of innate immunity than does MIS. This inhibition was not accounted for by phenotypic changes. Gene expression changes from surgical stress might represent the molecular basis of this differential immune response.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citotoxicidade Imunológica/imunologia , Derivação Gástrica/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Obesidade Mórbida/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Complexo CD3/imunologia , Citotoxicidade Imunológica/genética , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunidade Celular/genética , Imunidade Celular/imunologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/cirurgia , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Reação em Cadeia da Polimerase , Período Pós-Operatório , Estudos Prospectivos , RNA/genética , Receptores de IgG/imunologia , Linfócitos T Auxiliares-Indutores/imunologia
7.
Lung Cancer ; 61(2): 177-85, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18280614

RESUMO

Appropriate clinical staging of mediastinal lymph nodes in non-small-cell lung cancer (NSCLC) patients has important therapeutic and prognostic implications. Because of the wide variations in practice patterns among community and academic physicians, we reviewed the literature so that we could provide evidence-based recommendations on the use of imaging studies in the pretreatment clinical staging of NSCLC patients. We concluded that the most sensitive and accurate method of noninvasive mediastinal nodal staging is a positron emission tomography/computed tomography fusion scan; we believe this tool should be a component of clinical staging of all NSCLC patients. Given insufficient sensitivity with currently available imaging studies, mediastinal nodal staging should also include histologic evaluation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico , Mediastino/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Custos de Cuidados de Saúde , Diretrizes para o Planejamento em Saúde , Humanos , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , PubMed , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão/economia , Tomografia Computadorizada de Emissão/normas , Tomografia Computadorizada por Raios X/economia , Tomografia Computadorizada por Raios X/normas , Estados Unidos
8.
Thorac Surg Clin ; 18(4): 349-61, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19086605

RESUMO

In conclusion, accurate pretreatment staging of NSCLC patients is essential so that they undergo the most appropriate treatment. Imaging studies play an integral part in clinical staging. The preferred imaging method for staging the mediastinum is PET/CT, preferably integrated. Until the sensitivity and accuracy of imaging studies are equivalent to the available MLN biopsy techniques, all candidates for definitive therapy require histologic assessment of the mediastinum.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X/métodos , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Mediastino , Estadiamento de Neoplasias
9.
Am Surg ; 73(3): 279-80, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17375787

RESUMO

Invasive pulmonary aspergillosis (IPA) is associated with a high mortality rate in immunocompromised patients. Surgery has a therapeutic role for selected patients when the main objective is to achieve infection control with minimal lung resection. Large or deep-seated lesions may require an anatomic resection such as segmentectomy, lobectomy, or pneumonectomy. Thoracoscopic lobectomy has been described as a treatment of localized IPA; however, thoracoscopic anatomic segmentectomy has not been reported until now. Herein, we describe a case of thoracoscopic lingulectomy for localized IPA in an immunocompromised patient: this operation minimized the delay in resuming therapy for the patient's underlying acute myeloid leukemia. Video-assisted thoracoscopic segmentectomy can be safely performed for localized IPA.


Assuntos
Aspergilose/cirurgia , Pneumopatias Fúngicas/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida , Idoso , Seguimentos , Humanos , Masculino
10.
Thorac Surg Clin ; 17(2): 203-15, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17626398

RESUMO

Until additional multi-institutional, randomized, controlled trials provide evidence to the contrary, open lobectomy with mediastinal lymphadenectomy should be considered the gold standard for treating patients with stage I NSCLC with sufficient cardiopulmonary reserve, including older patients. It is the operation with which alternative pulmonary resections, including video-assisted thoracoscopic lobectomy and sublobar resection, should be compared. In treating stage I NSCLC patients, sublobar resection should be reserved for patients with inadequate physiologic reserve to tolerate lobectomy and for those enrolled in clinical trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
Surg Laparosc Endosc Percutan Tech ; 17(4): 287-90, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17710050

RESUMO

BACKGROUND: Severe hyperhidrosis is treated by thoracic sympathetic chain interrupting through chain transection or clipping. Our study compared the efficacy of these 2 methods. METHODS: Retrospectively, patients who underwent thoracoscopic sympathectomy from 1999 to 2005 had demographic, operative, and postoperative data analyzed. RESULTS: Fifty-four operations were performed for refractory sweating of the palm (72%), axilla (66%), foot (53%), and head/neck (19%). Thirty-seven (69%) underwent clipping; 17 (31%) underwent chain transection. There was no difference in age, sex, or blood loss. One ganglion level was interrupted in 24.1% and 2 levels in 75.4%. Bothersome compensatory hyperhidrosis occurred in 13% (5-clipping and 2-transection). One patient underwent clip removal for debilitating symptoms. Three small pneumothoraces occurred (all in the transection group); all treated expectantly. CONCLUSIONS: Thoracoscopic sympathectomy is a safe outpatient procedure. Both methods yield excellent results with minimal compensatory hyperhidrosis. Thoracoscopic sympathetic chain clipping and transection are equivalent.


Assuntos
Hiperidrose/cirurgia , Simpatectomia/métodos , Toracoscopia , Adulto , Eletrocoagulação , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
12.
Thorac Surg Clin ; 16(4): 345-52, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17240822

RESUMO

Recent progress in the molecular analysis of NSCLC tumors and lymph node status will likely translate into a clearer understanding of the variables and predictors of tumor recurrence. This understanding may lead to more appropriate therapeutic decisions both in the operating room and in the clinic. With these analyses at the molecular level, a more precise molecular classification is on the horizon which includes a molecular substaging. All of these aspects of NSCLC biology await testing or final analysis of prospective multi-institutional trials such as that set forth in CALGB 9761.


Assuntos
Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Metástase Linfática , Metástase Neoplásica , RNA Mensageiro/metabolismo
13.
Cancer Res ; 64(20): 7479-85, 2004 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-15492273

RESUMO

Molecular mechanisms active in transforming human pleural cells remain incompletely understood. Our previous microarray analysis of malignant pleural mesothelioma revealed alterations in components of the insulin-like growth factor (IGF) system, implicating this signaling axis in tumorigenesis. Therefore, in this current study, we characterized the molecular phenotype and investigated the key signaling pathways of the IGF system in malignant pleural mesothelioma specimens. For the major IGF components, we assessed mRNA abundance and total protein levels. We measured IGF-I ligand-dependent activation of signaling pathways downstream of the type I IGF receptor in a subset of malignant pleural mesothelioma cell lines and determined the corresponding biological consequences. At the transcriptional level, we observed consistent changes in IGF components that may contribute to a malignant phenotype. IGF-I stimulation of cells resulted in enhanced activation of type I IGF receptor and IRS adaptor proteins. Differential activation of IRS-1 signaling was associated with cell growth, whereas IRS-2 signaling was associated with cell motility. Thus, these data suggest that multiple mechanisms likely contribute to malignant pleural mesothelioma tumorigenesis. Therefore, IGF system components represent novel malignant pleural mesothelioma therapeutic targets for investigation.


Assuntos
Mesotelioma/metabolismo , Fosfoproteínas/metabolismo , Neoplasias Pleurais/metabolismo , Linhagem Celular Transformada , Expressão Gênica , Humanos , Proteínas Substratos do Receptor de Insulina , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like I/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular , Sistema de Sinalização das MAP Quinases , Mesotelioma/genética , Mesotelioma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Somatomedinas/biossíntese , Somatomedinas/genética
14.
J Clin Oncol ; 34(13): 1484-91, 2016 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-26926677

RESUMO

PURPOSE: Outcomes after resection of stage I non-small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM. MATERIALS AND METHODS: Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen. RESULTS: Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity. CONCLUSION: NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Lung Cancer ; 48(2): 241-6, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15829324

RESUMO

PURPOSE: A major problem with the staging system for non-small cell lung cancer (NSCLC) is clinical underestimation of the extent of disease. Many patients with clinical stage 1 disease do not retain that designation following surgical resection. Herein, we present data from Cancer and Leukemia Group B (CALGB) protocol 9761 evaluating the correspondence between clinical and pathologic analysis in early stage NSCLC. METHODS: Five hundred and two patients with suspected or biopsy-proven NSCLC classified as clinical stage 1 (T1-2, N0) by computed tomography (CT) scan or cervical mediastinoscopy were prospectively enrolled in CALGB 9761. The purpose of CALGB 9761 was to prospectively evaluate molecular markers of micrometastatic disease in stage 1 NSCLC. Enrollment occurred at 11 selected institutions within the CALGB. Patients with clinically suspected resectable early stage lung cancer were eligible for enrollment if they had no evidence of mediastinal or hilar adenopathy on CT scan or if they had CT evidence of potential N2 or N3 disease (lymph node > or =1.0 cm) but with negative mediastinoscopy. No prior chemotherapy or radiotherapy was permitted. RESULTS: Of the 502 patients felt to have clinical stage 1 NSCLC enrolled in CALGB 9761, 489 underwent resection with complete surgical staging and routine histopathologic analysis. From these 489 patients, only 422 (86.3%) turned out to have pathologically documented NSCLC. Of these 422 patients, 302 (71.6%) had pathologic stage 1 disease (173 stage 1A and 129 stage 1B). Despite clinical assessment of stage 1 disease, 59 (14%) patients had pathologic stage 2 disease, 57 (13.5%) had stage 3 disease, and four (0.9%) patients had stage 4 disease. Of the patients undergoing resection for clinical stage 1 NSCLC, 65 patients did not have NSCLC (44 had benign disease and 21 had malignancies other than NSCLC) and two additional patients had dual synchronous primary NSCLC tumors and were not eligible for the study. Overall, only 61.7% (302 of 489) of patients with suspected stage 1 NSCLC disease retained that stage and diagnosis after complete surgical staging, while 38.3% had an inaccurate pre-operative clinical stage or diagnosis. CONCLUSIONS: The results from this prospective trial demonstrate the poor predictive value of current clinical staging techniques in early stage NSCLC. These findings will serve as a benchmark for comparison of future clinical imaging modalities and other tests evaluating early stage NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/normas , Biópsia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Mediastinoscopia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Tomografia Computadorizada por Raios X
16.
Surg Clin North Am ; 85(3): 433-51, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15927642

RESUMO

Short esophagus and peptic esophageal stricture are complications of chronic severe GERD. Short esophagus is properly diagnosed by an objective,intraoperative assessment after appropriate dissection of the GEJ. A laparoscopic Collis gastroplasty combined with an antireflux procedure comprises effective therapy. Peptic stricture should be addressed with an initial course of dilator therapy and optimization of antiacid medication. Consideration is given to an antireflux procedure if conservative therapy fails. Laparoscopic techniques have proven to be safe and effective in treating short esophagus and peptic stricture.


Assuntos
Estenose Esofágica/fisiopatologia , Esofagoscopia/métodos , Esôfago/anormalidades , Esôfago/fisiopatologia , Doença Crônica , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/prevenção & controle , Estenose Esofágica/complicações , Estenose Esofágica/cirurgia , Esofagoplastia/métodos , Esôfago/cirurgia , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/fisiopatologia , Gastroplastia/métodos , Azia/etiologia , Hérnia Hiatal/etiologia , Humanos , Monitorização Intraoperatória , Toracotomia
17.
Clin Cancer Res ; 9(15): 5630-5, 2003 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-14654545

RESUMO

PURPOSE: Our purpose was to study the detection of occult metastases (OM) in regional lymph nodes using immunohistochemical stain for cytokeratin, and for this study we targeted clinical stage I patients with non-small cell lung cancer. EXPERIMENTAL DESIGN: The study comprised the first 193 patients entered onto Cancer and Leukemia Group B protocol 9761. All had clinically staged T(1-2)N(0)M(0) non-small cell lung cancer, and all underwent curative resections of their primary tumors. Samples of the primary tumor and lymph nodes were taken from lymph node stations 2-12 and shipped to a central laboratory, where each lymph node was histologically processed and stained with H&E as well as with immunohistochemical stain using antibodies to cytokeratin (AE1/3). RESULTS: Altogether, we examined 825 lymph nodes. Whereas routine H&E staining allowed us to detect 18 positive lymph nodes, immunohistochemical staining allowed us to detect 45 positive lymph nodes (P < 0.0001). There were 28 OM [i.e., those detectable only by immunohistochemistry (IHC)], and there was 1 metastasis detected only by H&E staining. The OM included 9 OM in N1 stations and 19 OM in N2 stations. Twelve patients with OM had skip metastases. Routine H&E staining upstaged six patients to N1, and IHC added another five. Routine H&E upstaged 9 patients to N2, and IHC added another 11. We also uncovered new details about the way in which H&E detection depends on metastatic tumor burden. Specifically, for the probability of detecting metastases by H&E to exceed 0.50, the maximum diameter of the metastasis must be greater than 0.23 mm. CONCLUSIONS: IHC detects greater than twice as many positive regional lymph nodes as does H&E staining, and the foci of tumor it detects are significantly smaller than those detected by H&E staining.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Metástase Neoplásica/patologia , Humanos , Imuno-Histoquímica/métodos , Estadiamento de Neoplasias
18.
J Thorac Cardiovasc Surg ; 127(5): 1332-41; discussion 1342, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15115990

RESUMO

OBJECTIVE: This study hypothesized that non-small cell lung carcinoma cells from primary tumors isolated by laser capture microdissection would exhibit gene expression profiles associated with graded lymph node metastatic cell burden. METHODS: Non-small cell lung carcinoma tumors (n = 15) were classified on the basis of nodal metastatic cell burden by 2 methods, obtaining 3 groups: no metastasis, micrometastasis, and overt metastasis. We then performed microarray analysis on microdissected primary tumor cells and identified gene expression profiles associated with graded nodal tumor burden using a correlation-based selection algorithm coupled with cross-validation analysis. Hierarchical clustering showed the regrouping of tumor specimens; the classification inference was assessed with Fisher's exact test. We verified data for certain genes by using another independent assay. RESULTS: The 15 specimens clustered into 3 groups: cluster A predominated in specimens with overt nodal metastasis; cluster B had more specimens with nodal micrometastases; and cluster C included only specimens without nodal metastases. Cluster assignment was based on a validated 75-gene discriminatory subset. Notably, genes not previously associated with positive non-small cell lung carcinoma lymph node status were encountered in the profiling analysis. CONCLUSIONS: Microdissection, combined with microarray analysis, is a potentially powerful method to characterize the molecular profile of tumor cells. The 75-gene expression profiles representative of clusters A and B may define genotypes prone to metastasize. Overall, the 3 groups of tumor specimens clustered separately, suggesting that this approach may identify graded metastatic propensity. Further, genes singled out in clustering may yield insights into underlying metastatic mechanisms and may represent new therapeutic targets.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Análise por Conglomerados , Genótipo , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática , RNA Neoplásico/isolamento & purificação , Taxa de Sobrevida
19.
Chest ; 125(5): 1843-52, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15136399

RESUMO

STUDY OBJECTIVE: We investigated the gene expression profiles of malignant pleural mesothelioma (MPM) specimens to identify novel genes that are potentially involved in the oncogenic transformation of human pleural cells. DESIGN: Complementary DNA (cDNA) microarray transcriptional profiling studies of 10 MPM cell lines and 4 MPM primary tumor specimens were performed using hierarchic clustering. To confirm microarray data, we used real-time polymerase chain reaction and immunoblotting. RESULTS: Cluster analysis differentiated among epithelial (E), sarcomatoid, and biphasic MPM variants. Expression profiling identified common overexpressed or underexpressed genes in MPM. Notably, matriptase messenger RNA was found to be overexpressed by 826-fold in E MPM, with protein expression subsequently confirmed by immunoblot analysis. This recently characterized trypsin-like serine protease has been implicated in tumor invasion and metastasis of E-derived cancers, but has not been described until now in MPM. We also identified other novel genes, such as insulin-like growth factor binding protein 5 and a cDNA clone similar to proteolipid MAL2. CONCLUSIONS: Thus, further large-scale profiling of MPM may elucidate previously unrecognized molecular mechanisms by identifying novel genes that are involved in malignant transformation. Our study has now found matriptase to be one of these mesothelioma-associated genes, with potential pathogenic and therapeutic significance.


Assuntos
Regulação Neoplásica da Expressão Gênica , Mesotelioma/enzimologia , Mesotelioma/genética , Neoplasias Pleurais/enzimologia , Neoplasias Pleurais/genética , Serina Endopeptidases/biossíntese , Linhagem Celular Tumoral , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
20.
J Thorac Cardiovasc Surg ; 124(4): 828-32, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12324743

RESUMO

Synovial sarcomas are rare soft tissue malignancies that most commonly affect the extremities in the vicinity of large joints. These malignancies typically occur in adolescents and young adults between the ages of 15 and 40 years.(1,2) Historically they are believed to originate from primitive pluripotent mesenchyme capable of synovial differentiation. This belief is consistent with the malignancy's origin from sites devoid of normal synovium, such as the pleural cavity. A variety of pleural cavity sarcomas have been described, including liposarcoma,(3) chondrosarcoma,(4) osteosarcoma,(5) and malignant schwannoma.(6) Pleural synovial sarcoma, however, is a much rarer entity. In fact, pleural synovial sarcoma was first described only 6 years ago(7) and has not yet been reported in the surgical literature. Because of its rarity, pleural synovial sarcoma is often mistaken for the histologically similar malignant mesothelioma, the most common of the pleural neoplasms. This is a critical distinction, because synovial sarcoma may be extremely aggressive. Studies in the last 10 years have shown it to be extremely sensitive to ifosfamide-based chemotherapy, and survival of patients with synovial sarcoma has recently increased with chemotherapy, with 5-year survivals now as high as 57%.(8-10) In this report, we describe 3 cases of synovial sarcoma of the pleura. Clinical findings are correlated with pathologic features, including immunohistochemical stains and fluorescence in situ hybridization (FISH) for the identification of the diagnostic chromosomal translocation, t(X;18)(p11.2;q11.2). This delineation of the clinical and pathologic aspects of this rare, newly recognized tumor should increase awareness among the surgical community.


Assuntos
Neoplasias Pleurais/patologia , Sarcoma Sinovial/patologia , Adulto , Evolução Fatal , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/cirurgia , Sarcoma Sinovial/diagnóstico por imagem , Sarcoma Sinovial/cirurgia , Tomografia Computadorizada por Raios X
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