RESUMO
Using the Serial Analysis of Gene Expression (SAGE) database from the Cancer Genome Anatomy Project, we identified heparin co-factor II (HCII), which is over-expressed in non-small cell lung cancer (NSCLC). Here, we investigated the clinical significance of HCII and provided molecular evidence to support the suggestion that HCII could enhance cancer metastasis in NSCLC. We found that high HCII expression in tumour tissue was associated with increased cancer recurrence and shorter overall survival times in 75 clinically operable NSCLC patients. High pretreatment plasma concentration of HCII was associated with reduced overall survival in 57 consecutive NSCLC patients. We over-expressed and knocked down HCII expression in lung cancer cell lines and confirmed that HCII could promote cell motility, invasion ability and filopodium dynamics in NSCLC cells in vitro and increased metastatic colonization in an in vivo mouse model. Exogenous treatment of HCII promoted cancer cell migration, and this promigratory effect of HCII was independent of thrombin. We further showed that HCII could up-regulate cancer cell migration through the activation of PI3K, which acts upstream of Rac1 and Cdc42, and this effect could be blocked by heparin. We suggest that HCII is a novel metastasis enhancer and may be used as a prognostic predictor for heparin treatment in NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Movimento Celular/genética , Cofator II da Heparina/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/fisiologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Fosfatidilinositol 3-Quinases/genéticaRESUMO
Human pulmonary dirofilariasis (HPD) is a rare zoonotic infection caused by Dirofilaria immitis. Dogs are the definite hosts and humans are infected occasionally via a vector, generally a mosquito. Most thoracic neurilemmoma arise in the mediastinum and fewer tumors originate peripherally from the intercostal nerves. Most patients with HPD or thoracic neurilemmoma are asymptomatic and these diseases are often discovered incidentally. We present a 53-year-old female who was found to have a pulmonary nodule and a chest wall nodule during a routine health examination. She underwent a video-assisted thoracoscopic surgery (VATS) with partial lung resection and local excision of the chest wall. The pathological examination revealed a coiled, degenerating Dirofilariasis immitis worm surrounded by granulomatous inflammation with caseous necrosis and a neurilemmoma composed of S-100 protein immunoreactive but smooth muscle actin negative spindle cells. Because these diseases are self-limiting and make further treatment unnecessary, video-assisted thoracoscopic surgery (VATS) is considered preferable and less invasive for definitive diagnosis and management.
Assuntos
Dirofilariose/complicações , Granuloma/parasitologia , Pneumopatias/parasitologia , Neurilemoma/cirurgia , Neoplasias do Sistema Nervoso Periférico/cirurgia , Animais , Dirofilaria immitis , Feminino , Granuloma/complicações , Granuloma/cirurgia , Humanos , Nervos Intercostais/patologia , Pneumopatias/complicações , Pneumopatias/cirurgia , Pessoa de Meia-Idade , Neurilemoma/complicações , Neoplasias do Sistema Nervoso Periférico/complicações , Cirurgia Torácica VídeoassistidaRESUMO
Lobar torsion is a rare complication after lung transplantation. Here we report a case of right middle lobe (RML) torsion after bilateral sequential lung transplantation (BLTx). This 30-year-old lady underwent BLTx for bronchiolitis obliterans due to paraneoplastic pemphigus. The right lower lobe of the donor lung was resected due to inflammatory change during procurement. The postoperative chest X-ray showed persisting RML infiltrates. Fever and leukocytosis were noted 1 week later. RML lobectomy was performed after the reconstructed chest computed tomography confirmed the diagnosis of RML torsion. Adult respiratory distress syndrome with unstable vital signs, refractory hypoxemia and respiratory acidosis occurred thereafter. After venoarterial extracorporeal membrane oxygenation support, the patient recovered slowly and was discharged 5 months after BLTx.
Assuntos
Transplante de Pulmão/efeitos adversos , Anormalidade Torcional/etiologia , Adulto , Oxigenação por Membrana Extracorpórea , Feminino , Humanos , Tomografia Computadorizada por Raios XRESUMO
Photodynamic therapy (PDT) is a treatment modality of early central located non-small-cell lung cancer, and in patients who are unsuitable for surgical intervention. Most complications of PDT reported in the literature are minor and can be easily handled. We report a case presenting with nearly fatal complication: airway obstruction following bronchoscopic photodynamic therapy for early endobronchial lung cancer, requiring extracorporeal membrane oxygenation. An 81-year-old man was admitted to thoracic surgery division due to an early centrally located lung cancer. Due to multiple comorbidity and high surgical risk we performed bronchoscopic PDT instead of aggressive lung resection for the patient. After the procedure, he developed severe airway obstruction by tumor debris and required temporary cardiopulmonary support with extracorporeal membrane oxygenation. The patient recovered smoothly after the episode and was free from tumor recurrence for >2 years without any neurological sequelae.
Assuntos
Obstrução das Vias Respiratórias/etiologia , Broncoscopia/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Fotoquimioterapia/efeitos adversos , Idoso de 80 Anos ou mais , Obstrução das Vias Respiratórias/terapia , Oxigenação por Membrana Extracorpórea , Humanos , MasculinoRESUMO
Nonsmall cell lung cancer (NSCLC) presenting with miliary intrapulmonary carcinomatosis (MIPC) is rare. We investigated the clinical characteristics and epidermal growth factor receptor (EGFR) mutation rate of NSCLC patients with MIPC at initial diagnosis. From June 2004 to December 2008, we screened newly diagnosed NSCLC patients for MIPC using image-based criteria. We recorded clinical data and analysed EGFR mutation status. For comparison, we collected specimens from stage IV NSCLC patients without MIPC tested for EGFR mutations from April 2001 to November 2008. From 3,612 NSCLC patients, 85 patients with MIPC at initial diagnosis were identified; 81 had adenocarcinoma. Of the 85 patients, 60 had specimen sequencing to detect EGFR mutation; 42 (70%) were positive. Compared with 673 stage IV patients without MIPC, patients with MIPC had higher EGFR mutation rate (p=0.036); even male smokers had a high EGFR mutation rate (91%). Multivariate analysis of prognostic factors for overall survival of the 85 patients with MIPC revealed that adenocarcinoma, absence of extrapulmonary metastasis and having EGFR mutation were associated with longer overall survival. NSCLC patients with MIPC at initial diagnosis had higher rates of adenocarcinoma and EGFR mutation. EGFR tyrosine kinase inhibition may be the treatment of choice for NSCLC patients with MIPC at initial diagnosis among Asians.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Gefitinibe , Humanos , Masculino , Pessoa de Meia-Idade , Quinazolinas/farmacologia , Radiografia Torácica , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Massive hemothorax in patients on extracorporeal membrane oxygenation (ECMO) is potentially life threatening and remains a medical challenge. In this study, we present the clinical results of using aggressive management to treat a consecutive series of patients on ECMO whose conditions were complicated by massive hemothorax. METHODS: Between November 2003 and February 2010, 14 adult patients on ECMO developed massive hemothorax that was unrelated to the cannulation problems of the ECMO circuit at National Taiwan University Hospital, Taipei, Taiwan. Information was obtained regarding patient demographics, disease course, and treatment. Aggressive treatment of hemothorax included blood component therapy, chest tube drainage, pleural epinephrine irrigation, and surgical intervention. The criteria for surgical intervention, video-assisted thoracoscopic surgery (VATS), or open-window thoracostomy included one-third or more of the thoracic cavity that had accumulated blood clots resulting in a compromised cardiopulmonary status, continuous blood loss > 300mL/hour for 4 hours or more, or continued bleeding for 24 hours after persistent blood transfusion. RESULTS: All hemothoraces were unilateral. With coagulopathic correction, control of bleeding was obtained in two patients after decompression of the pleural cavity, four patients after pleural epinephrine irrigation, and eight of 14 patients required surgical intervention for blood clot evacuation. There were no specific findings except blood clot accumulation in each of the patients who underwent thoracotomy or VATS. Three of the eight patients required multiple operations to treat persistent bleeding. The in-hospital mortality rate was 36% (5 of 14 patients); one patient died of intractable bleeding and four deaths were related to multiple organ failure. Blood transfusion (Mann-Whitney U test; p=0.039) and comorbidities such as bacteremia, septic shock, diabetic mellitus, and immunocompromised status (Fisher exact test; p=0.031) were found to be significant and independent predictors of mortality. However, other factors such as age, complicated pneumothorax, and ECMO circuit duration were not statistically correlated with mortality. CONCLUSION: ECMO-related massive hemothorax usually occurred unilaterally and presented as a life-threatening condition. With intensive treatment, nearly two-thirds of the patients were saved. The most significant risk factor for mortality was the presence of a comorbidity such as sepsis, diabetic mellitus, or immunocompromised status.
Assuntos
Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemotórax/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Transfusão de Componentes Sanguíneos , Estudos de Coortes , Técnicas de Apoio para a Decisão , Drenagem , Epinefrina/uso terapêutico , Feminino , Hemotórax/diagnóstico , Hemotórax/etiologia , Hemotórax/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida , Toracostomia , Resultado do Tratamento , Vasoconstritores/uso terapêutico , Adulto JovemRESUMO
We report a case of giant cell tumor of the left distal femur with simultaneous bilateral pulmonary metastases. Pathologic examination of the left lung nodule showed a metastatic giant cell tumor with a noncontinuous ossified rim, and the right lung nodules were totally hyalinized or ossified without residual giant cell tumor components. Hyalinization was a consistent finding in both the primary bone lesion and the pulmonary metastases. Because the patient did not receive chemotherapy or radiotherapy before her surgical procedure, we believe that these changes represent spontaneous tumor regression.
Assuntos
Neoplasias Femorais/cirurgia , Tumor de Células Gigantes do Osso/secundário , Tumor de Células Gigantes do Osso/cirurgia , Hialina , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/cirurgia , Ossificação Heterotópica/diagnóstico , Ossificação Heterotópica/cirurgia , Adulto , Diagnóstico Diferencial , Feminino , Neoplasias Femorais/diagnóstico , Neoplasias Femorais/patologia , Fêmur/patologia , Seguimentos , Tumor de Células Gigantes do Osso/diagnóstico , Tumor de Células Gigantes do Osso/patologia , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/patologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Regressão Neoplásica Espontânea , Ossificação Heterotópica/patologia , Pneumonectomia , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: In order to improve prognostic applications and treatment decisions, we report our experiences of visceral pleural surface invasion (VPSI) in non-small cell lung cancers (NSCLCs) with pleural retraction. METHODS: A total of 321 NSCLCs with pleural retraction were identified by carefully inspecting surgically resected specimens. The extent of pleural invasion, including the use of elastic stain, was evaluated. Patients with and without VPSI were compared for clinicopathologic parameters and survival. RESULTS: VPSI was identified in 170 (53.0 %) of the stage I-III cases and 98 (43.4 %) of the patients with stage I disease. VPSI was associated with a higher frequency of tumor size greater than 3 cm, moderate/poor differentiation, vascular invasion, mediastinal lymph node metastasis, extranodal involvement, and higher TNM stages. Multivariate analysis revealed VPSI to be a significant independent predictor of unfavorable prognosis. The 5-year survival of patients with and without VPSI was 57.9 and 83.0 %, respectively (P = 0.001), and was 74.3 and 88.5 % (P = 0.005) in stages I-III and stage I disease, respectively. CONCLUSIONS: VPSI is an independent factor for poor prognosis in NSCLCs, regardless of lymph node status. Stage IB NSCLCs with PL1 pleural invasion are associated with a survival rate similar to that of stage IA NSCLCs and could be classified as T1 lesions. While surgical treatment is adequate in these patients, stage IB NSCLCs with VPSI have poor prognosis, and these patients should be considered for adjuvant chemotherapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Pleura/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Pleura/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. MATERIALS AND METHODS: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. RESULTS: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. CONCLUSIONS: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.
Assuntos
Quimiorradioterapia/métodos , Cromossomos Humanos Par 2/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Polimorfismo de Nucleotídeo Único , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Progressão da Doença , Esofagectomia , Fluoruracila/administração & dosagem , Estudo de Associação Genômica Ampla/métodos , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Estudos Prospectivos , Dosagem Radioterapêutica , Indução de Remissão/métodos , Taiwan , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the feasibility and safety of thoracoscopic lobectomy without endotracheal intubation. SUMMARY BACKGROUND DATA: General anesthesia with single-lung ventilation is considered mandatory for thoracoscopic lobectomy for non-small cell lung cancer (NSCLC). Nonintubated thoracoscopic lobectomy has not been reported previously. METHODS: From August 2009 through June 2010, some 30 consecutive patients with clinical stage I or II NSCLC were treated by nonintubated thoracoscopic lobectomy using epidural anesthesia, intrathoracic vagal blockade, and sedation. To evaluate the feasibility and safety of this novel technique, they were compared with a control group consisting of 30 consecutive patients with clinical stage I or II NSCLC who underwent thoracoscopic lobectomy using intubated general anesthesia from August 2008 through July 2009. RESULTS: Collapse of the operative lung and inhibition of coughing were satisfactory in the nonintubated patients, induced by spontaneous breathing, and vagal blockade. Three patients in the nonintubated group required conversion to intubated-single lung ventilation because of persistent hypoxemia, poor epidural anesthesia pain control, and bleeding. One patient in each group was converted to thoracotomy because of bleeding. The 2 groups had comparable anesthesia durations, surgical durations, blood loss, and numbers of dissected lymph nodes. Patients who underwent nonintubated surgery had lower rates of sore throat (6.7% vs 40.0%, P = 0.002) and earlier resumption of oral intake (mean, 4.7 hours vs 18.8 hours, P < 0.001). Patients undergoing nonintubated surgery also had a trend toward better noncomplication rates (90% vs 66.7%, P = 0.057) and shorter postoperative hospital stays (mean, 5.9 days vs 7.1 days, P = 0.078). CONCLUSIONS: Nonintubated thoracoscopic lobectomy is technically feasible and is as safe as lobectomy performed with intubation in highly selected patients. It can be a valid alternative of single-lung-ventilated thoracoscopic surgery in managing early-stage NSCLC.
Assuntos
Anestesia Endotraqueal , Anestesia Epidural , Bloqueio Nervoso Autônomo , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Sedação Consciente , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Toracoscopia/métodos , Nervo Vago , Adulto , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Viabilidade , Feminino , Hospitais Universitários , Humanos , Tempo de Internação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , TaiwanRESUMO
Epidermal growth factor receptor (EGFR) is a novel target for therapy in subsets of non-small cell lung cancer, especially adenocarcinoma. Tumors with EGFR mutations showed good response to EGFR tyrosine kinase inhibitors (TKIs). We aimed to identify the discriminating capacity of immunohistochemical (IHC) scoring to detect L858R and E746-A750 deletion mutation in lung adenocarcinoma patients and predict EGFR TKIs response. Patients with surgically resected lung adenocarcinoma were enrolled. EGFR mutation status was genotyped by PCR and direct sequencing. Mutation-specific antibodies for L858R and E746-A750 deletion were used for IHC staining. Receiver operating characteristic (ROC) curves were used to determine the capacity of IHC, including intensity and/or quickscore (Q score), in differentiating L858R and E746-A750 deletion. We enrolled 143 patients during September 2000 to May 2009. Logistic-regression-model-based scoring containing both L858R Q score and total EGFR expression Q score was able to obtain a maximal area under the curve (AUC: 0.891) to differentiate the patients with L858R. Predictive model based on IHC Q score of E746-A750 deletion and IHC intensity of total EGFR expression reached an AUC of 0.969. The predictive model of L858R had a significantly higher AUC than L858R intensity only (pâ=â0.036). Of the six patients harboring complex EGFR mutations with classical mutation patterns, five had positive IHC staining. For EGFR TKI treated cancer recurrence patients, those with positive mutation-specific antibody IHC staining had better EGFR TKI response (pâ=â0.008) and longer progression-free survival (pâ=â0.012) than those without. In conclusion, total EGFR expression should be included in the IHC interpretation of L858R. After adjusting for total EGFR expression, the scoring method decreased the false positive rate and increased diagnostic power. According to the scoring method, the IHC method is useful to predict the clinical outcome and refine personalized therapy.
Assuntos
Receptores ErbB/genética , Receptores ErbB/metabolismo , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos/imunologia , Receptores ErbB/imunologia , Feminino , Genótipo , Humanos , Imuno-Histoquímica/métodos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reação em Cadeia da Polimerase , Prognóstico , Análise de Sequência de DNA , Deleção de Sequência , Resultado do TratamentoRESUMO
Metastasis is a predominant cause of death in patients with cancer. It is a complex multistep process that needs to be better understood if we are to develop new approaches to managing tumor metastasis. Tumor cell invasion of the local stroma is suppressed by collapsin response mediator protein-1 (CRMP-1). Recently, we identified a long isoform of CRMP-1 (LCRMP-1), expression of which correlates with cancer cell invasiveness and poor clinical outcome in patients with non-small-cell lung cancer (NSCLC). Here, we report that LCRMP-1 overexpression in noninvasive human cell lines enhanced filopodia formation, cancer cell migration, and invasion via stabilization of actin. This effect required a highly conserved N-terminal region of LCRMP-1 as well as the WASP family verprolin-homologous protein-1/actin nucleation pathway (WAVE-1/actin nucleation pathway). Furthermore, LCRMP-1 appeared to act downstream of Cdc42, a Rho family protein known to be involved in actin rearrangement. In addition, LCRMP-1 associated with CRMP-1, which downregulated cancer cell metastasis by interrupting the association of LCRMP-1 and WAVE-1. Finally, we found that high-level expression of LCRMP-1 and low-level expression of CRMP-1 were associated with lymph node metastasis and poor survival in patients with NSCLC. In sum, we show that LCRMP-1 and CRMP-1 have opposing functions in regulating cancer cell invasion and metastasis and propose that this pathway may serve as a potential anticancer target.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Pseudópodes/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Dimerização , Humanos , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias , Proteínas do Tecido Nervoso/fisiologia , Ligação Proteica , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo , CicatrizaçãoRESUMO
PURPOSE: To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. METHODS AND MATERIALS: We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. RESULTS: The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. CONCLUSIONS: ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal SCC. Pathological nodal metastasis predicted poor outcome.
Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Irradiação Linfática/métodos , Adulto , Idoso , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Cuidados Pré-Operatórios , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Falha de TratamentoRESUMO
OBJECTIVE: To investigate the association of the genetic variants in excision repair cross-complementation group 2 (ERCC2) R156R and ERCC4 rs3136038 with survival duration for patients with esophageal cancer. BACKGROUND: ERCC2 and ERCC4 are important molecules participating nucleotide excision repair system. The clinical relevance of the genetic variants of these genes is largely unknown currently. PATIENTS AND METHODS: A total of 400 patients with a diagnosis of esophageal cancer were included. The genetic variants in the promoter regions of ERCC2 on R156R and ERCC4 on rs3136038 were analyzed with the TaqMan assay from leukocyte DNA collected before treatment and correlated to survival of the patients. RESULTS: Presence with ERCC2 R156R C/C or ERCC4 rs3136038 C/T genotype of the patients could additively increase risk of death and disease progression. Under multivariate analysis, T, N staging and simultaneous presentation of these unfavorable genotypes were found significant for prognosis (P < 0.05). Accumulation of each unfavorable genotype would associate with adjusted HRs [95% CI] of 1.35 [1.10-1.65] and 1.37 [1.12-1.68] (P ≤ 0.05) for death and disease progression respectively. The prognostic impact of these genotypes were more evident in the subgroup of patients with early disease status including T staging (II or less), free from lymph node metastasis or being able to undergo surgical resection (P < 0.05 for both overall and disease progression-free survival duration, respectively). CONCLUSION: Genetic variants in ERCC2 and ERCC4 may provide further survival prediction in addition to TNM staging system of esophageal cancer, which is more evident in the patients with early disease status.
Assuntos
Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Predisposição Genética para Doença , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adulto , Idoso , China , Estudos de Coortes , Intervalos de Confiança , Progressão da Doença , Neoplasias Esofágicas/terapia , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Análise de SobrevidaRESUMO
BACKGROUND: Pleomorphic carcinomas of the lung are uncommon malignant tumors composed of carcinomatous and sarcomatous components and are distinguished from other non-small-cell lung carcinomas by a more aggressive clinical course with early distant metastases and far worse survival. Epidermal growth factor receptor (EGFR) and p53 are common genes involved in the pathogenesis of non-small-cell lung carcinomas, but their roles in pleomorphic carcinomas are unclear. The potential clinical activity of EGFR-targeted therapy is also unknown. METHODS: A total of 42 pleomorphic carcinomas were identified to investigate somatic mutations of EGFR and p53. Genomic DNA was extracted from microdissected cells of paraffin-embedded tumor tissues. Somatic mutations in EGFR (exons 18-21) and p53 (exons 5-8) were examined. RESULTS: EGFR mutations were detected in 10 of 42 cases. Five of these patients had point mutations in exon 21 majorly with L858R; this mutation was found in both adenocarcinomatous and sarcomatous components in 1 case. The other 5 cases harbored 4 deletions and 1 mutation in exon 19. p53 mutations were found in 12 patients. Notably, identical mutation was observed in carcinomatous and sarcomatous components in 3 patients, and this finding strongly supported the theory of monoclonal histogenesis. CONCLUSIONS: The occurrence (23.8%) of EGFR mutations, including the exons 19 and 21 mutations observed frequently in our series, suggests that the patients with inoperable pleomorphic carcinomas are likely to benefit from treatment with EGFR tyrosine kinase inhibitors.
Assuntos
Adenocarcinoma/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação/genética , Carcinoma de Pequenas Células do Pulmão/genética , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , DNA de Neoplasias/genética , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Proteínas ras/genéticaRESUMO
BACKGROUND: The benefit of using the laparoscopic approach in minimally invasive esophagectomy (MIE) has not been established. We therefore compared the outcome of esophagectomy for patients with esophageal cancer performed with open surgery, video-assisted thoracic surgery (VATS)/laparotomy (hybrid MIE), and VATS/ laparoscopy (total MIE). METHODS: Patients with esophageal cancer undergoing tri-incisional esophagectomy with three different approaches between 2005 and 2009 were analyzed from a prospective database. RESULTS: Three groups of patients underwent esophagectomy by open surgery (n = 64), hybrid MIE (n = 44), and total MIE (n = 30). The total MIE group had significantly longer operative times but had shorter postoperative ventilator usage times postoperative hospital stay, and they began jejunostomy feeding sooner (P < 0.05, compared with the other groups). There was a significant trend toward a decrease in postoperative pulmonary complications and anastomotic leakage in parallel to the proportion of minimally invasive procedures for esophagectomy (P < 0.05 for the trend test), with a significant difference between the open surgery and total MIE groups (30% vs. 6.7%, and 28% vs. 6.7%, respectively; P < 0.05). CONCLUSIONS: Use of a laparoscopic procedure in MIE for patients with esophageal cancer might provide benefit by facilitating postoperative recovery and reducing the rates of post-esophagectomy pulmonary complications and anastomotic leakage.
Assuntos
Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Laparoscopia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Esofagoscopia/métodos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Assistência Perioperatória , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Taiwan , Cirurgia Torácica Vídeoassistida/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The EGFR gene has been demonstrated to be an important factor influencing treatment response for various cancers, and its expression has been shown to be modified by the polymorphic CA repeat length at the 5'-regulatory sequence in intron 1. We investigated whether this EGFR polymorphism is associated with prognosis in patients with esophageal cancer after concurrent chemoradiotherapy (CCRT) and esophagectomy. METHODS: A cohort of 148 patients with esophageal cancer received cisplatin-based CCRT (concurrently combined with 40 Gy irradiation) and subsequent esophagectomy. Their EGFR genotypes were determined by polymerase chain reaction from leukocyte DNA, which was obtained before treatment and was correlated with patient survival. RESULTS: Patients with the homozygous short allele (<20 CA) of the EGFR gene in intron 1 were more likely to have a shorter duration of survival after CCRT and surgery than those with the homozygous long allele [adjusted hazard ratio (HR) (95% confidence interval [CI]) of death: 1.88 (1.02-3.49); P = 0.045]. This unfavorable prognostic effect of EGFR homozygous short CA repeat was mainly manifested in patients with good response to CCRT [adjusted HR (95% CI) of death 3.40 (1.06-10.89); P = 0.039]; it was less evident in those with poor response to CCRT [adjusted HR (95% CI) 1.40 (0.65-3.02); P = 0.384]. CONCLUSIONS: The EGFR CA repeat genetic polymorphism may act as a valuable molecular predictor of clinical outcome of esophageal cancer after CCRT and esophagectomy, especially in those with good response to CCRT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Neoplasias Esofágicas/genética , Esofagectomia , Íntrons/genética , Polimorfismo Genético/genética , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Cisplatino/administração & dosagem , Terapia Combinada , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Paclitaxel/administração & dosagem , Reação em Cadeia da Polimerase , Prognóstico , Taxa de SobrevidaRESUMO
p53 and epidermal growth factor receptor (EGFR) are common genes involved in the pathogenesis of lung cancer, but their roles in lymphoepithelioma-like carcinomas (LELC) are unclear. In this study, we investigate the roles of p53 and EGFR in LELC carcinogenesis. Forty-six pulmonary LELCs were identified to evaluate p53 and EGFR aberrations. p53 mutations were identified in three patients, which all occurred in exon 8. EGFR mutations were detected in 8 of 46 cases with a majority of exon 21 mutations but without L858R. The other cases harbored mutations in exons 20 and 18. Only one case gained a deletion in exon 19. Notably, EGFR mutation was more commonly observed in patients with tumor size ≤ 3 cm (P = 0.014). In addition, there was a trend of more common EGFR overexpression in female (22/30) than in male patients (7/16, P = 0.061). However, there was no correlation between p53/EGFR mutations and protein expressions, suggesting the presence of complex mechanisms. p53 and EGFR mutations are uncommon in LELCs, indicating that these genes are not the important events in carcinogenesis for this tumor subtype. The EGFR mutation in 35% patients with LELC tumors <3 cm in size suggests the potential benefits to EGFR tyrosine kinase inhibitors of inoperable LELCs.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Genes p53 , Neoplasias Pulmonares/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: We explored covariates of the quality of life (QOL) in non-small-cell lung cancer (NSCLC) patients and made a comparison with healthy controls. METHODS: We assessed the QOL of 220 consecutive NSCLC patients at a university hospital. The QOL data were measured by the brief version of the World Health Organization's Quality of Life and by utility using the standard gamble method. We selected demographically matched healthy controls from the 2001 National Health Interview Survey for comparison. Multiple linear regression models were constructed to explore significant factors of QOL after controlling for covariates. RESULTS: Patients with more advanced stages of NSCLC had poorer scores than did the healthy controls in the physical and psychological domains. Patients with disease duration of longer than 1 year tended to report higher physical and environment QOL than did those with NSCLC diagnosed for less than 1 year. Insight into one's own illness was associated with a higher utility, better social support, and improved financial resources. CONCLUSIONS: QOL was significantly associated with staging and duration of NSCLC. Disease insight appears to be a positive factor for operable NSCLC patients of the Taiwanese culture, which implies that clinicians should respect patient autonomy in diagnosis disclosure.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/psicologia , Pacientes/psicologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Autoimagem , Apoio Social , Inquéritos e Questionários , TaiwanRESUMO
BACKGROUND: The possible mechanisms of simvastatin attenuating pulmonary hypertension (PH) have been widely investigated in pulmonary vascular and hemodynamic systems, but few studies have examined the difference in respiratory response mediated by pulmonary C fibers (PCF) in animal models of PH. We hypothesized that PCF sensitivity would differ from normal in monocrotaline-induced pulmonary hypertension (MCT-PH) rats and the effects of simvastatin treatment would involve not only the pulmonary circulatory system, but also PCF sensitivity. METHODS: The PCF sensitivity was investigated by measuring the apneic durations evoked by 3 chemical stimulants: capsaicin; α,ß-methylene-adenosine triphosphate; and phenylbiguanide. The effects of simvastatin on PCF sensitivity were evaluated in the MCT-PH rat model. RESULTS: The sensitivity of PCF was increased significantly after monocrotaline (MCT) application for 21 days. Bilateral vagatomy and high-dose perivagal capsaicin (250 µg/ml) treatment both blocked the PCF hypersensitivity induced by MCT. Three days of simvastatin (5 mg/kg) treatment significantly reduced the hypersensitive status of PCF. In MCT-PH rats, reactive oxygen species (ROS) production was significantly elevated in both blood and bronchoalveolar lavage, but both showed a significantly decrease after simvastatin treatment. These potential benefits of simvastatin were all abolished by co-application of tin protoporphyrin-IX (SnPP), a specific heme oxygenase-1 (HO-1) inhibitor. CONCLUSION: Simvastatin treatment in MCT-PH rats not only attenuated pulmonary hypertension, but also desensitized PCF hypersensitivity and decreased the production of ROS. These cholesterol-independent effects were mainly through the HO-1 pathway and may all contribute to the therapeutic effects of PH treatment.