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1.
Acta Otorhinolaryngol Ital ; 34(4): 223-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25210215

RESUMO

Intraoperative nerve monitoring (IONM) aimed at reducing the injuries of recurrent laryngeal nerve during thyroidectomy is controversial. We conducted a meta-analysis to assess the incidence of nerve injuries with or without IONM. Studies published from January 1994 to February 2012 in English language on humans were identified. Heterogeneity of studies was checked by the Higgins test. Summary estimates of predictive values of injury were made using the Mantel-Haenszel test based on the fixed-effects model. Publication bias was assessed by a funnel plot and Egger's method. Eight articles were selected accounting a total of 5257 nerves at risk. IONM revealed a significant impact in preventing transient injuries (positive predictive value = 5% [95% CI: 2-8], negative = 96% [95% CI: 91-100], relative risk = 0.73 [95% CI: 0.54-0.98], p = 0.035), whereas they failed to demonstrate effect on permanent injuries (positive predictive value = 2% [95% CI: 0.6-3.8], negative 99% [95% CI: 97-100], relative risk = 0.73 [95% CI: 0.44-1.23], p = 0.235). This meta-analysis demonstrated the merit of IONM in preventing transient injury during thyroidectomy. No advantage was found in permanent injuries.


Assuntos
Complicações Intraoperatórias/etiologia , Monitorização Intraoperatória , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Tireoidectomia , Humanos , Traumatismos do Nervo Laríngeo Recorrente/prevenção & controle
2.
Oncogene ; 33(42): 5039-46, 2014 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-24186203

RESUMO

Activation of serine biosynthesis supports growth and proliferation of cancer cells. Human cancers often exhibit overexpression of phosphoglycerate dehydrogenase (PHGDH), the metabolic enzyme that catalyses the reaction that diverts serine biosynthesis from the glycolytic pathway. By refueling serine biosynthetic pathways, cancer cells sustain their metabolic requirements, promoting macromolecule synthesis, anaplerotic flux and ATP. Serine biosynthesis intersects glutaminolysis and together with this pathway provides substrates for production of antioxidant GSH. In human lung adenocarcinomas we identified a correlation between serine biosynthetic pathway and p73 expression. Metabolic profiling of human cancer cell line revealed that TAp73 activates serine biosynthesis, resulting in increased intracellular levels of serine and glycine, associated to accumulation of glutamate, tricarboxylic acid (TCA) anaplerotic intermediates and GSH. However, at molecular level p73 does not directly regulate serine metabolic enzymes, but transcriptionally controls a key enzyme of glutaminolysis, glutaminase-2 (GLS-2). p73, through GLS-2, favors conversion of glutamine in glutamate, which in turn drives the serine biosynthetic pathway. Serine and glutamate can be then employed for GSH synthesis, thus the p73-dependent metabolic switch enables potential response against oxidative stress. In knockdown experiment, indeed, TAp73 depletion completely abrogates cancer cell proliferation capacity in serine/glycine-deprivation, supporting the role of p73 to help cancer cells under metabolic stress. These findings implicate p73 in regulation of cancer metabolism and suggest that TAp73 influences glutamine and serine metabolism, affecting GSH synthesis and determining cancer pathogenesis.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/fisiologia , Serina/biossíntese , Proteínas Supressoras de Tumor/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glutaminase/genética , Glutaminase/metabolismo , Humanos , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Isoformas de Proteínas/fisiologia , Transaminases/genética , Transaminases/metabolismo , Transcrição Gênica , Proteína Tumoral p73
3.
Eur Respir J ; 36(2): 408-16, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20675780

RESUMO

Nutritional status deteriorates along with progression of emphysema, with the decline of body composition correlating with risk of disease-related events. Lung volume reduction surgery (LVRS), by improving respiratory function and recovering body composition, may influence long-term disease-related morbidity and mortality when compared to respiratory rehabilitation (RR). In this non-randomised study, 44 male patients with moderate-to-severe emphysema underwent LVRS, while 35 received RR. Respiratory parameters, body composition, number and time-to-occurrence of disease-related events were evaluated for 5 yrs. After LVRS, respiratory and nutritional parameters had significantly greater and longer lasting improvements than after RR. Disease-related events occurred later and less frequently after surgery than after rehabilitation, with better morbidity and mortality survival curves (p<0.01 and p<0.03, respectively). Body mass index (BMI) > or =23kg x m(-2), BODE (BMI, airflow obstruction, dyspnoea, exercise capacity) index < or =2 and fat-free mass index (FFMI) > or =16kg x m(-2) at 1 yr were the best positive predictors of post-operative outcomes (p<0.03, p<0.04 and p<0.005, respectively). Reduction in residual volume at 36 months after surgery was significantly correlated with the increase of BMI (rho = -0.56, p = 0.009) and FFMI (rho = -0.64, p = 0.001). LVRS significantly and durably improved respiratory function and body composition over RR. Relationships among residual volume, BMI, FFMI and disease-related events suggest that recovery in respiratory dynamics improves nutritional status, thus significantly reducing long-term disease-related morbidity and mortality.


Assuntos
Composição Corporal , Pneumonectomia/métodos , Enfisema Pulmonar/cirurgia , Enfisema Pulmonar/terapia , Idoso , Gasometria , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Análise de Regressão , Respiração , Esteroides/uso terapêutico , Resultado do Tratamento
4.
Int J Immunopathol Pharmacol ; 22(2): 389-401, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19505392

RESUMO

Placenta growth factor (PlGF) is a key regulator of pathological angiogenesis and its overexpression has been linked to neoplastic progression. To assess whether PlGF could have a role in malignant mesothelioma (MM), we analyzed the expression of PlGF, VEGF, and their cognate receptors (VEGF-R1 and VEGF-R2) and co-receptors (neuropilin-1 and neuropilin-2) in MM cell lines as well as in resected MM tissues, hyperplastic/reactive mesothelium and normal mesothelium. MM cell cultures expressed both ligands and the associated receptors to a variable extent and released different amounts of PlGF. As assessed by immunohistochemistry, PlGF expression was switched on in hyperplastic/reactive compared to normal mesothelium. Moreover, 74 and 94 percent of MM tissues overexpressed PlGF and VEGF-R1, respectively (p<0.05 MM vs normal mesothelium). Administration of recombinant PlGF-2 did not elicit a significant stimulation of MM cell growth, while it was associated with a transient phosphorylation of Akt, suggesting that PlGF-2 could activate downstream effectors of proliferative and cytoprotective signals via VEGF-R1 in MM cells. Indeed, the administration of an anti-PlGF antibody was found to cause a significant reduction of MM cell survival. In conclusion, our data demonstrate that, by acting as a survival factor, PlGF can play a role which goes beyond the stimulation of angiogenesis in MM. This evidence could help the rational design of new therapeutic interventions for this aggressive tumor.


Assuntos
Epitélio/metabolismo , Mesotelioma/metabolismo , Neoplasias Pleurais/metabolismo , Proteínas da Gravidez/metabolismo , Morte Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Epitélio/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Hiperplasia , Mesotelioma/irrigação sanguínea , Mesotelioma/genética , Mesotelioma/patologia , Neovascularização Patológica/metabolismo , Neuropilina-1/metabolismo , Neuropilina-2/metabolismo , Fosforilação , Fator de Crescimento Placentário , Neoplasias Pleurais/irrigação sanguínea , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Proteínas da Gravidez/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Proteínas Recombinantes/metabolismo , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
Anticancer Res ; 29(5): 1499-506, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19443357

RESUMO

BACKGROUND: Ductal intraepitelial neoplasia (DIN) represents a spectrum of disease that may progress from usual hyperplasia to ductal carcinoma in situ (DCIS) grade 3. The aim of the study was to asses the correlation between the DIN classification and the surgical treatment including sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS: In this retrospective study, 229 patients with DIN had undergone conservative or radical surgical treatment and SLNB in cases of DIN1C-DIN3. RESULTS: Breast conservative surgery was the definitive treatment in 80% of the cases. The H&E evaluation of excised sentinel nodes was negative for metastatic disease; nevertheless the immunohistochemical (IHC) evaluation revealed the presence of metastatic cells in 6 patients (3.7%). CONCLUSION: In cases of DIN lesions SLNB is not indicated. The only reason SLNB should be considered is when there is an evidence of invasive foci at definitive histology or when radical mastectomy is proposed.


Assuntos
Neoplasias da Mama/classificação , Carcinoma Intraductal não Infiltrante/classificação , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Biópsia de Linfonodo Sentinela
6.
Minerva Chir ; 63(6): 511-6, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19078883

RESUMO

Surgical resection of lung metastases has become routine and the introduction of video assisted thoracic surgery (VATS) has provided a mini-invasive option to this treatment. However, oncological radicality of VATS is criticized especially in the event of deeply located lesions requiring manual palpation and lymph node dissection. At today, VATS lung metastasectomy is performed with diagnostic purposes or with curative intent as initial resection in patients with one to a few, peripherally located lesions. New perspectives are represented by the transxiphoid port, which may allow hand palpation during VATS, and awake lung metastasectomy in epidural anesthesia, which can permit a reduction of global operating room time. In conclusion, VATS metastasectomy is valid in selected but increasing number of patients, without compromising oncologic radicality.


Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Cirurgia Torácica Vídeoassistida , Humanos
7.
Clin Ter ; 158(2): 127-33, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17566513

RESUMO

OBJECTIVE: We analyzed the overall results with our lung volume reduction surgery (LVRS) program, which entailed unilateral and bilateral LVRS, selectively performed on the basis of precise clinical and radiologic morphology criteria. MATERIALS AND METHODS: Between 1995 and 2005, 182 patients were operated on unilaterally (104 patients) or bilaterally (78 patients). Amongst bilateral procedures, 39 patients were operated in one-stage fashion and 39 in a staged fashion. RESULTS: Overall 90-day mortality was 2.8% (4 patients). Mean follow-up was 51 +/- 30 months. Six months absolute improvement in forced expiratory volume in one second (FEV1) was 0.27 +/- 0.2L in the unilateral group, 0.38 +/- 0.2L in the staged bilateral group, and 0.45 +/- 0.2L in the one-stage group. Residual volume decrease were 1.1 +/- 0.5L, 0.99 +/- 0.3L, and 1.75 +/- 0.5L in the unilateral, staged bilateral and one stage bilateral groups, respectively. Overall, improvements in FEV1 occurred for up to 36 months in the unilateral group and for up to 48 months in the bilateral group. Residual volume remained improved for up to 72 months in the unilateral and staged bilateral groups, and for up to 48 months in the one-stage group. The SF-36 health-related quality of life physical functioning domain score remained improved for more than 48 months in all groups and for up to 72 months in the staged group only. Five-year survival were 78%, 88% and 77%, in the unilateral, staged bilateral and one-stage bilateral groups, respectively. CONCLUSIONS: We conclude that highly satisfactory long-term survival and long lasting clinical improvements occurred in patients undergoing unilateral or bilateral LVRS.


Assuntos
Pneumonectomia/métodos , Enfisema Pulmonar/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo
8.
Surg Endosc ; 21(4): 587-91, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17180292

RESUMO

BACKGROUND: Foramen of Morgagni's hernia is an uncommon congenital diaphragmatic hernia. Repair is mostly performed through laparotomy. We prefer the transthoracic approach, which allows better and safer control during thoracic dissection, although it is considered more painful and related to greater morbidity. In recent years we introduced the transxiphoid hand-assisted videothoracoscopic approach, which combines the advantages of the thoracic route with a mini-invasive procedure facilitated by one hand inside the chest. METHODS: A retrospective review was performed over a 20-year period (1985-2005). Twenty-two patients who had a foramen of Morgagni's hernia repaired were identified and relevant data were collected. Average age was 57 +/- 10 years and one half of the patients were asymptomatic. Chest roentgenograms, chest computerized tomography, and barium enema were used as diagnostic utilities. Posterolateral thoracotomy was performed in 17 (15 right-sided) patients, whereas in 5 (all right-sided) the defect was repaired by transxiphoid hand-assisted videothoracoscopy. Operative time, pain scored by visual analog scale, hospital stay, and cosmetic results by acceptance score were reviewed for every patient. RESULTS: Hernial sac was present in all cases and contained only omentum (n = 13), omentum plus transverse colon (n = 7), omentum plus transverse colon and small bowel (n = 2). In 6 patients (2 videothoracoscopy) we repaired the large defects with polypropylene mesh. Videothoracoscopy achieved significant good results compared to thoracotomy in operative time (85 +/- 7.9 versus 110 +/- 11.3 min, p < 0.01), 24-h visual analog scale (3.5 +/- 1.1 versus 6.7 +/- 3.9, p < 0.01), hospital stay (2.6 +/- 0.5 versus 6.4 +/- 1.2 days, p < 0.01), and acceptance score (4.3 +/- 0.5 versus 3.1 +/- 0.8, p < 0.05). Postoperative course was always uneventful. Patients were followed for an average period of 58.6 +/- 14.7 and 109.7 +/- 43.5 months, respectively: no recurrences were found in any group. CONCLUSIONS: We believe that the transthoracic approach is a safe and effective method for repairing Morgagni's hernia. The videothoracoscopic approach is a promising alternative and it may be facilitated by introducing a hand inside the chest.


Assuntos
Hérnia Diafragmática/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Toracotomia/métodos , Adulto , Idoso , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Seguimentos , Hérnia Diafragmática/diagnóstico , Hérnias Diafragmáticas Congênitas , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/fisiopatologia , Probabilidade , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Cirurgia Torácica Vídeoassistida/efeitos adversos , Toracoscopia/métodos , Resultado do Tratamento
9.
Lung Cancer ; 44(3): 303-10, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15140543

RESUMO

The present study was designed to investigate whether a correlation exists between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8, adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group 65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l) patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels were significantly associated to positive TNF-alpha levels in patients without distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha might be responsible for an activation of fibrinolysis in patients with NSCLC.


Assuntos
Coagulação Sanguínea/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Neoplasias Pulmonares/imunologia , Fator de Necrose Tumoral alfa/análise , Idoso , Idoso de 80 Anos ou mais , Antitrombina III , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Fibrinólise/imunologia , Humanos , Interleucina-6/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Peptídeo Hidrolases/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia
10.
J Clin Pathol ; 57(6): 591-7, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15166262

RESUMO

AIMS: To evaluate the prognostic impact of tumour angiogenesis assessed by vascular endothelial growth factor (VEGF), microvessel density (MVD), and tumour vessel invasion in patients who had undergone radical resection for stage IB-IIA non-small cell lung cancer (NSCLC). METHODS: Fifty one patients (42 men, nine women; mean age, 62.3 years; SD, 6.9) undergoing complete surgical resection (35 lobectomy, 16 pneumonectomy) of pathological stage IB (n = 43) and IIA (n = 8) NSCLC were evaluated retrospectively. No patient underwent postoperative chemotherapy or neoadjuvant treatment. Tumour specimens were stained for VEGF and specific MVD markers: CD31, CD34, and CD105. RESULTS: VEGF expression significantly correlated with high CD105 expression (p < 0.0001) and tumour vessel invasion (p = 0.04). Univariate analysis showed that those patients with VEGF overexpression (p = 0.0029), high MVD by CD34 (p = 0.0081), high MVD by CD105 (p = 0.0261), and tumour vessel invasion (p = 0.0245) have a shorter overall survival. Furthermore, multivariate Cox regression analysis showed that MVD by CD34 (p = 0.007), tumour vessel invasion (p = 0.024), and VEGF expression (p = 0.042) were significant predictive factors for overall survival. Finally, the presence of both risk factors, tumour vessel invasion and MVD by CD34, was highly predictive of poor outcome (odds ratio, 3.4; 95% confidence interval, 1.7 to 6.5; p = 0.0002). CONCLUSIONS: High MVD by CD34 and tumour vessel invasion are more closely related to poor survival than the other neoangiogenetic factors in stage IB-IIA NSCLC. This may be because these factors are more closely related to the metastatic process.


Assuntos
Indutores da Angiogênese/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Neovascularização Patológica/metabolismo , Adulto , Idoso , Antígenos CD34/metabolismo , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Métodos Epidemiológicos , Feminino , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pneumonectomia , Período Pós-Operatório , Prognóstico , Resultado do Tratamento , Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Eur Respir J ; 23(2): 275-80, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14979503

RESUMO

This study aims at evaluating the effects of lung volume reduction versus respiratory rehabilitation on quality of life, assessed by three different questionnaires. Sixty emphysematous patients were randomised by computer to receive either surgery (n = 30) or rehabilitation (n = 30). Life quality was evaluated by the Nottingham Health Profile, the Short Form (SF)-36 item and the St George's questionnaires. As reported previously, dyspnoea index, forced expiratory volume in one second, residual volume, 6-min walk test and arterial oxygen tension improved after surgery more than after rehabilitation. Quality of life was significantly improved after surgery as follows Nottingham Health Profile physical mobility; SF-36 physical and social functioning, mental and general health, emotional role; St George's general, activity. At multivariate analysis 6- and 12-month changes after surgery of Short Form-36 physical functioning, general health, and St George's activity domains were significantly correlated with forced expiratory volume in one second, while Short Form-36 social functioning and Nottingham Health Profile isolation correlated with residual volume. Functional and especially symptomatic improvements persisted: dyspnoea index, residual volume, and Short Form-36 and St Georges's physical scores were still significant at 4 yrs. Surgery produces greater and longer effects than rehabilitation on quality of life by improving both physical and psychosocial domains. Symptomatic improvements persisted at 4 yrs.


Assuntos
Exercícios Respiratórios , Terapia por Exercício , Pneumonectomia , Enfisema Pulmonar/reabilitação , Enfisema Pulmonar/cirurgia , Qualidade de Vida , Cirurgia Torácica Vídeoassistida , Atividades Cotidianas/classificação , Atividades Cotidianas/psicologia , Idoso , Dispneia/etiologia , Dispneia/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto , Satisfação do Paciente , Pneumonectomia/psicologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/psicologia , Enfisema Pulmonar/psicologia , Qualidade de Vida/psicologia , Testes de Função Respiratória , Cidade de Roma
12.
Histopathology ; 44(1): 54-63, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14717670

RESUMO

AIMS: Some experimental evidence suggests that in lung cancer, development, progression and an increased proliferation rate can be linked to apoptosis-related factors. In this study we evaluated the possible role of p53 and Bcl-2 gene family members as prognostic factors for non-small-cell lung cancer. METHODS AND RESULTS: We investigated the immunohistochemical expression of p53 and Bcl-2 gene family members (bax, Bcl-2 and Bcl-xL) in 94 non-small-cell lung cancer specimens to establish the role of these genes in lung cancer pathogenesis, and to evaluate their prognostic importance. The expression of Bcl-2 was correlated with a shorter patient survival time and with the nodal status of the neoplasm. We also found frequent over-expression of bax and Bcl-xL to be of no prognostic significance. Finally, we found no correlation between frequent detection of aberrant p53 protein and expression of either Bcl-2, bax or Bcl-xL or with patient survival time. CONCLUSIONS: This study confirms a relevant role for apoptosis-regulatory proteins in the pathogenesis of lung cancer, and highlights the possible role of Bcl-2 as a prognostic factor for this tumour.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , Taxa de Sobrevida , Proteína X Associada a bcl-2 , Proteína bcl-X
13.
J Clin Pathol ; 57(1): 58-63, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14693837

RESUMO

BACKGROUND/AIMS: Abnormalities of the proteins involved in cell cycle checkpoints are extremely common among almost all neoplasms. This study aimed to investigate the expression of four components of the cell cycle machinery-p21, p16, p53, and proliferating cell nuclear antigen (PCNA)-in non-small cell lung cancer (NSCLC). METHODS: The expression of p21, p16, p53, and PCNA was examined in 68 well characterised NSCLC specimens using immunohistochemistry. The coregulation of these proteins and their influence on survival were analysed using both univariate and multivariate analyses. RESULTS: By univariate analysis, the expression of all the proteins examined, except for PCNA, was significantly correlated with survival. In multivariate analysis, the only immunohistochemical parameter able to influence overall survival was p16, confirming the hypothesis that the RB-p16 tumour suppressor pathway is inactivated in most lung cancer samples. Finally, the group of patients with NSCLC who were negative for both p21 and p16 had a significantly shorter overall survival. CONCLUSIONS: These results suggest that loss of control of cell cycle checkpoints is a common occurrence in lung cancers, and support the idea that functional cooperation between different cell cycle inhibitor proteins constitutes another level of regulation in cell growth control and tumour suppression.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Proteína Supressora de Tumor p53/metabolismo
15.
Minerva Chir ; 57(5): 625-33, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12370663

RESUMO

The aim of this study is to review the literature regarding reduction pneumoplasty (RP) or lung volume reduction surgery in order to assess the state of the art of this topic. Reduction pneumoplasty is a palliative surgical therapy that is offered to selected patients with severe non-bullous emphysema not responding to maximized medical therapy. The use of staple excision or plication of the most destroyed target areas of the lung appeared to be more effective than laser ablation. Currently, a one-stage bilateral procedure is the standard of care although a unilateral reduction can be preferable in patients with asymmetric emphysema and/or if a staged bilateral treatment strategy is planned. Randomized studies have suggested that RP is superior to medical therapy including respiratory rehabilitation for improving subjective dyspnea, exercise capacity, respiratory function and quality of life for up to 1 year. In addition, few long-term studies have suggested that the improvements obtained with RP can be maintained for several years in properly selected patients. Although several issues still await a definitive answer, the available literature data and our current experience have clearly indicated that RP works well and is a safe and effective procedure for palliating symptoms and improving respiratory function in severely disabled emphysematous patients.


Assuntos
Pneumonectomia/métodos , Enfisema Pulmonar/cirurgia , Análise Custo-Benefício , União Europeia , Seguimentos , Volume Expiratório Forçado , Humanos , Seleção de Pacientes , Pneumonectomia/economia , Complicações Pós-Operatórias , Enfisema Pulmonar/economia , Enfisema Pulmonar/mortalidade , Troca Gasosa Pulmonar , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Taxa de Sobrevida , Resultado do Tratamento
16.
Int J Biol Markers ; 17(1): 56-62, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11936588

RESUMO

Increased expression of selectins has been found on endothelial cells of venules and capillaries in the tumor stroma of non-small cell lung cancer, suggesting their functional role in the process of chemotaxis for tumor cells. The present study was aimed at analyzing the role of both soluble (s)P-selectin and sE-selectin levels in association with clinico-pathological variables in 116 patients with lung cancer, 38 patients with benign diseases and 59 healthy donors. The results obtained showed that sP-selectin and sE-selectin levels were higher in patients with lung cancer compared to normal donors (p<0.02 and p<0.005, respectively). No differences were observed among patients with various benign diseases for both selectins. Increased levels of sP-selectin and sE-selectin were significantly associated with squamous lung cancer at late stages (p<0.05), but not adenocarcinoma. Both sP- and sE-selectin were independently related to the stage of squamous lung cancer by stepwise regression analysis (p<0.02 and p<0.03, respectively), while only sE-selectin was independently related to the presence of distant metastasis in the same histotype (p<0.02). These results suggest that measurement of plasma soluble selectins might represent a useful laboratory parameter in the management of patients with squamous lung cancer.


Assuntos
Selectina E/biossíntese , Neoplasias Pulmonares/metabolismo , Selectina-P/biossíntese , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Humanos , Imunoensaio , Neoplasias Pulmonares/diagnóstico , Pessoa de Meia-Idade , Metástase Neoplásica
17.
Ann Surg Oncol ; 8(8): 663-6, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11569782

RESUMO

BACKGROUND: Combined resection of solitary synchronous brain metastases and non-small-cell lung cancer has been shown to be successful. Thus, we proposed combining the surgery of solitary, extracranial metastases, and resectable lung cancer. METHODS: Between March 1987 and December 1994, surgery was performed on nine patients with non-small-cell lung cancer with synchronous, solitary, extracranial, or distant metastasis: adrenal (n = 5), cutaneous (n = 2), axillary lymph node (n = 1) and kidney (n = 1). Criteria for operating on these patients included: primary tumor that was locally resectable in a radical manner, non-small-cell histology, no preoperative evidence of N2 disease, complete resection of histologically proven metastasis, and absence of other metastases found with computed tomography or bone scan. RESULTS: Resection of the primary tumor and solitary metastases was achieved in all patients. Primary tumor was always resected by lobectomy. No mortality or major morbidity was reported. Five-year survival rate was 55.6%. Five patients who had adrenal (n = 3), or skin (n = 1), or axillary (n = 1) metastases, survived more than 5 years. All N2 patients (n = 2) died. CONCLUSIONS: The presence of solitary, distant metastasis should not be considered, per se, a factor for denying surgery for locally resectable, non-small-cell lung cancer. Unexpected, prolonged survival was demonstrated in our limited series.


Assuntos
Neoplasias das Glândulas Suprarrenais/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Cutâneas/secundário , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/cirurgia , Idoso , Axila , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Análise de Sobrevida , Resultado do Tratamento
18.
Arch Surg ; 136(7): 783-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11448391

RESUMO

OBJECTIVE: To evaluate indications, limits, and merits of transxiphoid bilateral palpation during video-assisted thoracoscopy (VAT) lung metastasectomy. DESIGN: Survey retrospective study with a minimum follow-up of 1 year. SETTING: University hospital. PATIENTS: From December 1995 to September 1999, 29 of 45 patients operated on for pulmonary metastasectomy were approached through a transxiphoid VAT. Primary sites were colon-rectum (n = 13), kidney (n = 4), limb osteosarcoma (n = 3), uterus (n = 2), larynx (n = 2), breast (n = 1), skin melanoma (n = 1), prostate gland (n = 1), back fibrosarcoma (n = 1), and ovary (n = 1). Bilateral palpation was performed in 23 patients, although only 10 had radiological evidence of bilateral disease. RESULTS: No perioperative or 30-days postoperative mortality was recorded. Acute and chronic pain was similar to that of other VATs and significantly less than sternotomy. Mean +/- SD chest-drain time and hospital stay were 2.8 +/- 1.19 days and 4.3 +/- 1.78 days, respectively. Sixty-nine lesions, 60 of them metastatic, were resected by laser (n = 29) or stapler (n = 40). Bilateral exploration permitted the discovery of 15 radiologically undetected lesions, 11 of which were found to be malignant. Contralateral metastases were found in 5 patients predicted to have unilateral disease. Mean +/- SD follow-up was 22.89 +/- 10.87 months (range, 9-60 months). Six patients developed new pulmonary metastases after a mean interval of 13.6 months; 3 of these patients relapsed in the unexplored hemithorax after 6, 9, and 12 months, respectively. CONCLUSIONS: The use of the transxiphoid VAT approach was safe, applicable in many instances, and effective in detecting occult metastases by manual bilateral palpation. The advantages of a VAT procedure can be coupled with those provided by a radical operation.


Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Palpação/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento , Processo Xifoide
19.
Eur J Cardiothorac Surg ; 20(2): 378-84, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11463561

RESUMO

OBJECTIVE: Although surgical resection alone is considered adequate treatment in stage IB non-small-cell lung cancer (NSCLC), long-term survival is not satisfactory and the recurrence rate is quite high. The validity of postoperative chemotherapy at stage IB in terms of disease-free and overall survival was assessed in a randomised trial. METHODS: The trial was designed as a randomised, two-group study with postoperative adjuvant chemotherapy versus surgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure. Chemotherapy consisted of treatment with cisplatin (100 mg/m(2) on day 1) and etoposide (120 mg/m(2) on days 1--3) for a total of six cycles. RESULTS: Between January 1988 and December 1994, 66 patients were included in the study. Thirty-three belonged to the adjuvant chemotherapy group and 33 to the control group. Groups were homogeneous for conventional risk factors. There was no clinical significant morbidity associated to chemotherapy. Patients were followed for a minimum period of 5 years. The rates of locoregional recurrence and distant metastases were 18 and 30%, respectively, in the adjuvant chemotherapy group and 24 and 43%, respectively, in the control group. The 5-year disease-free survival rates were 59% in the adjuvant group and 30% in the control group (P = 0.02). The difference in the Kaplan--Meier survival between the groups was significant as assessed using the log-rank test (P = 0.04). CONCLUSIONS: Our results suggest that adjuvant chemotherapy may reduce recurrences and prolong overall survival in patients at stage IB NSCLC deemed radically operated. Despite being difficult to accept, the use of adjuvant chemotherapy might have better long-term results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
J Surg Oncol ; 76(1): 47-52, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11223824

RESUMO

BACKGROUND AND OBJECTIVES: Metastasectomy proved to be the choice treatment in the case of pulmonary metastasis. In this study we assessed the impact on survival of three types of resection: minimal by laser or conventional device and lobectomy. METHODS: We considered 85 patients who underwent lung metastasectomy for tumors that originated from various sites. Fifty-two minimal resections were accomplished in 34 patients by conventional (diathermy dissection or stapler suture line) device, 59 resections in 29 by Nd:YAG laser. Lobectomies were 22. Minimum follow up required was 2 years. RESULTS: The 3-year Kaplan-Meier survival rate was 63%, 44%, 53% for laser, conventional resections and lobectomy. The 5-year survival was 40%, 28%, 26% respectively. Among the groups there was no significant difference (P = 0.15). Laser patients showed shorter periods of air leakage and hospital stay. CONCLUSIONS: The type of resection did not disclose statistically significant differences on survival. Minimal surgery, especially by laser device, is recommended for less morbidity.


Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Pneumonectomia/mortalidade , Procedimentos Cirúrgicos Pulmonares/métodos , Neoplasias Ósseas/patologia , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Terapia a Laser , Tempo de Internação , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
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