RESUMO
BACKGROUND: Bridge to surgery (BTS) using a self-expandable metallic stent (SEMS) for the treatment of obstructive colorectal cancer improves the patient's quality of life. This study aimed to examine prognostic factors of obstructive colorectal cancer. METHODS: We analyzed stage II-III resectable colon cancer cases (Cur A) retrospectively registered between January 2005 and December 2017. Overall, 117 patients with Cur A obstructive colorectal cancer were evaluated: 67 of them underwent emergency surgery (ES Group) and 50 of them after BTS with SEMS placement (BTS group). We compared surgical results and prognoses between the two groups. RESULTS: A total of 50 patients underwent endoscopic SEMS placement, which technical success of 96% and morbidity rate of 18%. Primary anastomosis rates were 77.6% in ES and 95.7% in BTS (p < 0.001); postoperative complication, 46.3% in ES and 10.5% in BTS (p < 0.001); pathological findings of lymphatic invasion, 66.7% in ES and 100% in BTS (p < 0.001); venous invasion were 66.8% in ES and 92% in BTS (p = 0.04); and recurrence of 25.4% in ES and 39.1% in BTS. The 3-year overall survival was significantly different between two groups (ES, 86.8%:BTS, 58.8%), BTS is worse than ES (log-rank test; p < 0.001). Venous invasion independently predicted worsened recurrence-free and overall survival. CONCLUSIONS: The vascular invasiveness was correlated with tumor progression after SEMS placement, and the survival rate was lower in BTS. SEMS potentially worsens prognostic outcomes in stage II-III obstructive colorectal cancer.
Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Stents Metálicos Autoexpansíveis , Adulto , Idoso , Colectomia , Colonoscopia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Implantação de Prótese , Qualidade de Vida , Estudos Retrospectivos , Stents , Análise de Sobrevida , Resultado do TratamentoRESUMO
TLR signaling is critical to innate immune system regulation; however, aberrant TLR signaling is involved in several diseases, including insulin resistance, Alzheimer's disease, and tumor metastasis. Moreover, a recent study found that TLR-4 signaling pathway inhibition might be a target for the suppression of chronic inflammatory disorders. In this article, we show that the green tea polyphenol epigallocatechin-3-O-gallate (EGCG) increases the expression of Toll interacting protein, a strong inhibitor of TLR4 signaling, by suppressing the expression of E74-like ETS transcription factor 1 (Elf-1). A mechanistic study revealed that EGCG suppressed Elf-1 expression via protein phosphatase 2A/cyclic GMP (cGMP)-dependent mechanisms. We also confirmed that orally administered EGCG and a cGMP inducer upregulated Toll interacting protein expression, increased intracellular levels of cGMP in macrophages, and suppressed Elf-1 expression. These data support EGCG and a cGMP inducer as potential candidate suppressors of TLR4 signaling.
Assuntos
Catequina/análogos & derivados , Proteínas de Ligação a DNA/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Proteínas Nucleares/imunologia , Sistemas do Segundo Mensageiro/imunologia , Chá/química , Fatores de Transcrição/imunologia , Regulação para Cima/imunologia , Animais , Catequina/química , Catequina/farmacologia , GMP Cíclico/genética , GMP Cíclico/imunologia , Proteínas de Ligação a DNA/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Nucleares/genética , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/imunologia , Sistemas do Segundo Mensageiro/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Fatores de Transcrição/genéticaRESUMO
In 95% of patients with pancreatic ductal adenocarcinoma, recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anticancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knock-in/knockdown experiments, and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase/peroxisome proliferator-activated receptor-γ co-activator-1ß (PGC-1ß)/pyruvate dehydrogenase-A1 pathway is essential for CD44 expression and CSC properties. We observed that patients exhibiting high pyruvate dehydrogenase-A1 expression have a poor prognosis. Systemic PGC-1ß knock-out mice are fertile and viable and do not exhibit an overt phenotype under normal conditions. This suggests that cGMP induction and PGC-1ß inhibition represent potential strategies for treating patients with pancreatic ductal adenocarcinoma.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Proteínas de Transporte/metabolismo , Proteína Forkhead Box O3/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais , Animais , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Feminino , Proteína Forkhead Box O3/genética , Humanos , Masculino , Camundongos Knockout , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas de Ligação a RNARESUMO
BACKGROUND: Some chemotherapeutic agents have been reported to promote lung metastasis. However, there have been no reports regarding chemotherapy-induced liver metastasis. We hypothesized that chemotherapy might also enhance liver metastasis. The present study aimed to create a chemotherapy-enhanced liver metastasis mouse model and investigate its mechanism. MATERIALS AND METHODS: Mice were pretreated with cisplatin, vincristine, or saline by intraperitoneal injection. Next, B16F10 mouse melanoma cells and BE(2)-C human neuroblastoma cells were injected into the spleens of C57BL/6 and BALB/c nu/nu mice, respectively, to induce experimental liver metastasis, and the number of liver nodules was determined. We also analyzed the effect of chemotherapy on changes of the liver tissue regarding representative metastasis-promoting factors using real-time quantitative polymerase chain reaction and immunohistochemical and histological analysis. RESULTS: Cisplatin increased the number of nodules by 4.7-fold in the B16F10 liver metastasis model. Vincristine increased the number of nodules by 3.8-fold in the BE(2)-C liver metastasis model. Cisplatin increased mRNA levels of matrix-metalloproteinase (MMP)-2 and periostin, while vincristine increased MMP-9 and S100A8/9 levels in liver tissues. Cisplatin induced fibrosis, whereas vincristine induced neutrophil recruitment in liver tissues according to histological and immunohistochemical analysis. CONCLUSIONS: We concluded that cisplatin or vincristine could enhance liver metastasis of mouse melanoma cells or human neuroblastoma cells, respectively. In addition, the mRNA expression of MMP-2 and periostin, or MMP-9 and S100A8/9 is increased by cisplatin or vincristine pretreatment, possibly resulting in fibrosis or neutrophil recruitment, respectively. These niche factors might be associated with increased liver metastasis.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Hepáticas/secundário , Neoplasias Experimentais/tratamento farmacológico , Animais , Medula Óssea/efeitos dos fármacos , Calgranulina A/genética , Linhagem Celular Tumoral , Cisplatino/efeitos adversos , Humanos , Neoplasias Hepáticas/induzido quimicamente , Metaloproteinase 2 da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/patologia , Vincristina/efeitos adversosRESUMO
Atrial natriuretic peptide (ANP) is a cardiac hormone released by the atrium in response to stretching forces. Via its receptor, guanylyl cyclase-A (GC-A), ANP maintains cardiovascular homeostasis by exerting diuretic, natriuretic, and hypotensive effects mediated, in part, by endothelial cells. Both in vivo and in vitro, ANP enhances endothelial barrier function by reducing RhoA activity and reorganizing the actin cytoskeleton. We established mouse endothelial cells that stably express GC-A and used them to analyze the molecular mechanisms responsible for actin reorganization. Stimulation by ANP resulted in phosphorylation of myosin light chain (MLC) and promotion of cell spreading. p21-activated kinase 4 (PAK4) and cerebral cavernous malformations 2 (CCM2), a scaffold protein involved in a cerebrovascular disease, were required for the phosphorylation of MLC and promotion of cell spreading by ANP. Finally, in addition to the GC domain, the kinase homology domain of GC-A was also required for ANP/GC-A signaling. Our results indicate that CCM2 and PAK4 are important downstream mediators of ANP/GC-A signaling involved in cell spreading, an important initial step in the enhancement of endothelial barrier function.
Assuntos
Citoesqueleto de Actina/metabolismo , Fator Natriurético Atrial/metabolismo , Proteínas de Transporte/agonistas , Endotélio Vascular/metabolismo , Receptores do Fator Natriurético Atrial/agonistas , Transdução de Sinais , Quinases Ativadas por p21/metabolismo , Animais , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Bovinos , Movimento Celular , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/enzimologia , Ativação Enzimática , Células HEK293 , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Camundongos , Mutação , Cadeias Leves de Miosina/metabolismo , Fosforilação , Domínios e Motivos de Interação entre Proteínas , Processamento de Proteína Pós-Traducional , Transporte Proteico , Interferência de RNA , Receptores do Fator Natriurético Atrial/química , Receptores do Fator Natriurético Atrial/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Quinases Ativadas por p21/antagonistas & inibidores , Quinases Ativadas por p21/química , Quinases Ativadas por p21/genéticaRESUMO
Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.
Assuntos
Fator Natriurético Atrial/farmacologia , Células Endoteliais/citologia , Neoplasias/metabolismo , Animais , Adesão Celular , Linhagem Celular Tumoral , Intervalo Livre de Doença , Proteínas de Fluorescência Verde/metabolismo , Humanos , Inflamação , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Melanoma Experimental , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Metástase Neoplásica , Recidiva Local de Neoplasia , Neoplasias/patologia , Estudos RetrospectivosRESUMO
PURPOSE: We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. METHODS: Patients with resectable c-stage IB-IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. RESULTS: Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CONCLUSIONS: CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain.
Assuntos
Carboplatina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Colágeno , Meios de Cultura , Técnicas de Cultura/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Paclitaxel/farmacologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimioterapia Combinada , Feminino , Géis , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Medicina de Precisão , Estudos Prospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Postoperative complications are associated with poor cancer-specific survival in various types of cancer surgery. Recent studies suggest that systemic inflammation induced by surgical trauma can accelerate the adhesion of circulating tumor cells to the vascular endothelium of distant organs, resulting in early cancer recurrence. We investigated the impact of postoperative cardiopulmonary complications on cancer recurrence following lung cancer surgery. METHODS: From a prospective database of 675 consecutive patients who underwent curative surgery for lung cancer between 2007 and 2012, the incidence of postoperative cardiopulmonary complications, white blood cell counts, and C-reactive protein levels were evaluated in the acute phase after surgery. Four patients had both cardiovascular and respiratory complications. The remaining 671 patients were divided into 3 groups: patients without cardiopulmonary complications; those with cardiovascular complications; and those with respiratory complications. The incidence of cancer recurrence was compared among the three groups. RESULTS: Postoperative cardiovascular or respiratory complications were identified in 94 (14%) or 25 (4%) patients, respectively. Postoperative white blood cell counts and C-reactive protein levels were significantly higher in those with postoperative respiratory complications than in those without. There was a significantly higher incidence of cancer recurrence in those with postoperative respiratory complications than in those without (48.0 vs. 16.8%; p < 0.0001). Multiple regression analysis adjusted for age, sex, and pathological staging showed that the incidence of postoperative respiratory complications was a significant predictor of cancer recurrence. CONCLUSIONS: The presence of respiratory complications following lung cancer surgery was a significant predictor of cancer recurrence.
Assuntos
Reação de Fase Aguda/etiologia , Doenças Cardiovasculares/etiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/etiologia , Reação de Fase Aguda/sangue , Idoso , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Complicações Pós-Operatórias/sangue , Período Pós-Operatório , Doenças Respiratórias/sangue , Doenças Respiratórias/etiologia , Fatores de TempoRESUMO
BACKGROUND: Pulmonary fibrosis is a life-threatening disease characterized by progressive dyspnea and worsening pulmonary function. Atrial natriuretic peptide (ANP), a heart-derived secretory peptide used clinically in Japan for the treatment of acute heart failure, exerts a wide range of protective effects on various organs, including the heart, blood vessels, kidneys, and lungs. Its therapeutic properties are characterized by anti-inflammatory and anti-fibrotic activities mediated by the guanylyl cyclase-A (GC-A) receptor. We hypothesized that ANP would have anti-fibrotic and anti-inflammatory effects on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: Mice were divided into three groups: normal control, BLM with vehicle, and BLM with ANP. ANP (0.5 µg/kg/min via osmotic-pump, subcutaneously) or vehicle administration was started before BLM administration (1 mg/kg) and continued until the mice were sacrificed. At 7 or 21 days after BLM administration, fibrotic changes and infiltration of inflammatory cells in the lungs were assessed based on histological findings and analysis of bronchoalveolar lavage fluid. In addition, fibrosis and inflammation induced by BLM were evaluated in vascular endothelium-specific GC-A overexpressed mice. Finally, attenuation of transforming growth factor-ß (TGF-ß) signaling by ANP was studied using immortalized mouse endothelial cells stably expressing GC-A receptor. RESULTS: ANP significantly decreased lung fibrotic area and infiltration of inflammatory cells in lungs after BLM administration. Furthermore, similar effects of ANP were observed in vascular endothelium-specific GC-A overexpressed mice. In cultured mouse endothelial cells, ANP reduced phosphorylation of Smad2 after TGF-ß stimulation. CONCLUSIONS: ANP exerts protective effects on BLM-induced pulmonary fibrosis via vascular endothelial cells.
Assuntos
Fator Natriurético Atrial/administração & dosagem , Células Endoteliais/imunologia , Pulmão/imunologia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/imunologia , Animais , Bleomicina , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Fatores Imunológicos/imunologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Pulmonary fibrosis has high rates of mortality and morbidity; however, no effective pharmacological therapy has been established. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, selectively binds to the transmembrane guanylyl cyclase (GC)-B receptor and exerts anti-inflammatory and anti-fibrotic effects in various organs through vascular endothelial cells and fibroblasts that have a cell-surface GC-B receptor. Given the pathophysiological importance of fibroblast activation in pulmonary fibrosis, we hypothesized that the anti-fibrotic and anti-inflammatory effects of exogenous CNP against bleomycin (BLM)-induced pulmonary fibrosis were exerted in part by the effect of CNP on pulmonary fibroblasts. METHODS: C57BL/6 mice were divided into two groups, CNP-treated (2.5 µg/kg/min) and vehicle, to evaluate BLM-induced (1 mg/kg) pulmonary fibrosis and inflammation. A periostin-CNP transgenic mouse model exhibiting CNP overexpression in fibroblasts was generated and examined for the anti-inflammatory and anti-fibrotic effects of CNP via fibroblasts in vivo. Additionally, we assessed CNP attenuation of TGF-ß-induced differentiation into myofibroblasts by using immortalized human lung fibroblasts stably expressing GC-B receptors. Furthermore, to investigate whether CNP acts on human lung fibroblasts in a clinical setting, we obtained primary-cultured fibroblasts from surgically resected lungs of patients with lung cancer and analyzed levels of GC-B mRNA transcription. RESULTS: CNP reduced mRNA levels of the profibrotic cytokines interleukin (IL)-1ß and IL-6, as well as collagen deposition and the fibrotic area in lungs of mice with bleomycin-induced pulmonary fibrosis. Furthermore, similar CNP effects were observed in transgenic mice exhibiting fibroblast-specific CNP overexpression. In cultured-lung fibroblasts, CNP treatment attenuated TGF-ß-induced phosphorylation of Smad2 and increased mRNA and protein expression of α-smooth muscle actin and SM22α, indicating that CNP suppresses fibroblast differentiation into myofibroblasts. Furthermore, human lung fibroblasts from patients with or without interstitial lung disease substantially expressed GC-B receptor mRNA. CONCLUSIONS: These data suggest that CNP ameliorates bleomycin-induced pulmonary fibrosis by suppressing TGF-ß signaling and myofibroblastic differentiation in lung fibroblasts. Therefore, we propose consideration of CNP for clinical application to pulmonary fibrosis treatment.
Assuntos
Citocinas/imunologia , Fibroblastos/imunologia , Fibroblastos/patologia , Peptídeo Natriurético Tipo C/administração & dosagem , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/imunologia , Animais , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Transgênicos , Peptídeo Natriurético Tipo C/farmacologia , Fibrose Pulmonar/patologia , Resultado do TratamentoRESUMO
BACKGROUND: C-type natriuretic peptide (CNP), secreted by vascular endothelial cells, belongs to a family of peptides that includes atrial and brain natriuretic peptides. CNP exhibits many vasoprotective effects against pulmonary hypertension and pulmonary fibrosis. The objective of this study was to investigate the prophylactic effects of CNP in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). MATERIALS AND METHODS: C57BL/6 mice were divided into three groups as follows: normal control mice (n = 13), LPS mice treated with vehicle (n = 12), and LPS mice treated with CNP (n = 12). Twenty-four hours after tail vein injection of LPS, histopathologic, gene expression, and bronchoalveolar lavage fluid (BALF) assessments were performed on the lungs. To examine the neutrophils in the lungs, cells positive for myeloperoxidase staining were detected by immunohistochemistry. BALF cytokine levels were analyzed by enzyme-linked immunosorbent assays. Gene expression in lung tissue was analyzed by real-time polymerase chain reaction. RESULTS: CNP significantly attenuated the elevation of leukocyte cell counts and levels of tumor necrosis factor-alpha, macrophage inflammatory protein-2, monocyte chemoattractant protein-1, interleukin-6, and keratinocyte-derived chemokine in the BALF after LPS injection. Furthermore, there were significantly fewer myeloperoxidase-positive cells in lungs treated with CNP after LPS injection. In lungs of CNP-treated mice, expression of the monocyte chemoattractant protein-1, S100A8, and E-selectin genes was significantly lower than that in vehicle-treated mice. CONCLUSIONS: CNP had a protective effect on ALI induced by LPS by reducing inflammatory cell infiltration. CNP may hold promise in therapeutic strategies for ALI after pulmonary resection surgery.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Peptídeo Natriurético Tipo C/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Calgranulina A/metabolismo , Quimiocina CCL2/metabolismo , Avaliação Pré-Clínica de Medicamentos , Selectina E/metabolismo , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Peptídeo Natriurético Tipo C/farmacologiaRESUMO
BACKGROUND: Since lung cancer surgery is still associated with a high complication rate, it is important to efficiently identify patients at high risk for postoperative complications following lung cancer surgery. We previously reported that elderly patients with elevated preoperative B-type natriuretic peptide (BNP) levels (>30 pg/mL) have an increased risk for postoperative atrial fibrillation and cardiopulmonary complications following lung cancer surgery. The objective of this study was to evaluate the clinical utility of BNP-guided risk classification for postoperative complications after lung cancer surgery. METHODS: A total of 675 consecutive patients who underwent curative surgery for lung cancer in two specialized thoracic centers between 2007 and 2011 were included in this retrospective study. We evaluated the association between the incidence of postoperative complications and preoperative BNP levels. RESULTS: Univariable and multivariable stepwise logistic regression analyses revealed that an elevated preoperative BNP level was the most significant predictor of postoperative complications. All patients were classified by their preoperative BNP levels into a normal group (<30 pg/mL), a mildly elevated group (30-100 pg/mL), and a severely elevated group (>100 pg/mL). The incidence of postoperative complications was significantly higher in the severely and mildly elevated groups than in the control group (85 % and 47 % vs. 11 %, P < 0.0001). Furthermore, there were more severe complications and a higher mortality rate in the severely elevated group. CONCLUSIONS: Risk assessment using preoperative BNP levels was clinically useful for the identification of patients at high risk for postoperative complications.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Peptídeo Natriurético Encefálico/sangue , Pneumonectomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Fibrilação Atrial/sangue , Fibrilação Atrial/etiologia , Biomarcadores/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Pneumonectomia/métodos , Pneumonia/sangue , Pneumonia/etiologia , Valor Preditivo dos Testes , Período Pré-Operatório , Curva ROC , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos , Medição de Risco/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Toracotomia/efeitos adversos , Adulto JovemRESUMO
PURPOSE: The impact of postoperative cardiopulmonary complications on long-term outcomes has not been established. We investigated the effects of acute postoperative cardiopulmonary complications not only on cancer recurrence, but also on cardiovascular or respiratory events in the chronic phase after lung cancer surgery. METHODS: From a prospective single-institution database of 496 consecutive patients, who underwent lung cancer surgery between August, 2008 and December, 2011, medical records, including information about cardiovascular or respiratory events and cancer recurrence in the chronic phase (>6 months) after surgery, were analyzed retrospectively. Results were compared between patients with vs. those without postoperative cardiopulmonary complications in the acute phase. RESULTS: Postoperative cardiopulmonary complications were identified in 90 (20%) patients. There were significantly more cardiovascular or respiratory events in the chronic phase after lung cancer surgery in the patients who had suffered postoperative cardiopulmonary complications in the acute phase than in those who had not (23 vs. 5%; p < 0.0001). CONCLUSIONS: Postoperative cardiopulmonary complications in the acute phase were associated with a higher incidence of cardiovascular or respiratory events in the chronic phase after lung cancer surgery. CLINICAL TRIAL REGISTRATION NUMBER: JPRN-UMIN2370.
Assuntos
Doenças Cardiovasculares/epidemiologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Complicações Pós-Operatórias/epidemiologia , Transtornos Respiratórios/epidemiologia , Reação de Fase Aguda , Idoso , Procedimentos Cirúrgicos Eletivos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: We recently reported that administration of atrial natriuretic peptide during the perioperative period has prophylactic effects with respect to not only cardiovascular but also respiratory complications following pulmonary resection. However, its mechanisms are not well understood. The objective of the present study was to investigate the mechanism of the prophylactic effects of atrial natriuretic peptide in an acute lung injury model. METHODS: For the evaluation of the early phase of pulmonary inflammation, in vitro and in vivo studies using lipopolysaccharide were used. In the in vitro study, the effects of atrial natriuretic peptide on the induction of E-selectin by lipopolysaccharide in human pulmonary artery endothelial cells were evaluated. In the in vivo study, the effects of atrial natriuretic peptide on lipopolysaccharide-induced inflammatory cell infiltration and cytokine levels including tumor necrosis factor-alpha and interleukin-6 in the bronchoalveolar lavage fluid in the lungs of C57/B6 mice were examined. The number of myeloperoxidase-positive staining cells in the tissue sections of the lung of lipopolysaccharide-administered C57/B6 mice was also evaluated. RESULTS: Atrial natriuretic peptide significantly attenuated the up-regulation of E-selectin expression induced by lipopolysaccharide in human pulmonary artery endothelial cells. There were significantly lower cell counts and levels of tumor necrosis factor-alpha and interleukin-6 in the bronchoalveolar lavage fluid of atrial natriuretic peptide-treated mice compared to control mice after lipopolysaccharide injection. In addition, there were significantly fewer myeloperoxidase-positive cells in atrial natriuretic peptide-treated mice than in control mice after lipopolysaccharide injection. CONCLUSIONS: Atrial natriuretic peptide had a protective effect in the lipopolysaccharide-induced acute lung injury model. Atrial natriuretic peptide may be of value in therapeutic strategies aimed at the treatment of acute lung injury such as pneumonia or acute respiratory distress syndrome.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Fator Natriurético Atrial/farmacologia , Células Endoteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Selectina E/genética , Células Endoteliais/metabolismo , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão/citologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
PURPOSE: A new diagnosis of chronic obstructive pulmonary disease is often made during the evaluation of patients requiring lung cancer surgery. The objective of the present study was to evaluate the clinical effects of inhaled tiotropium on the postoperative cardiopulmonary complications in patients with untreated chronic obstructive pulmonary disease requiring lung cancer surgery. METHODS: A retrospective study involving 104 consecutive patients with moderate to severe chronic obstructive pulmonary disease who underwent a lobectomy for lung cancer at two specialized thoracic centers between April 2008 and October 2011 was performed. The results were compared between patients who did and did not receive inhaled tiotropium during the perioperative period. The primary endpoint was the incidence of postoperative cardiopulmonary complications. The postoperative white blood cell counts and C-reactive protein levels as biomarkers of inflammation were also examined. RESULTS: The incidence of postoperative cardiopulmonary complications was significantly lower in the tiotropium group than in the control group (18 vs. 48 %, P = 0.001). Patients in the tiotropium group also showed significantly lower white blood cell counts and C-reactive protein levels postoperatively. CONCLUSIONS: Inhaled tiotropium treatment during the perioperative period had a prophylactic effect on postoperative cardiopulmonary complications in patients with newly diagnosed chronic obstructive pulmonary disease requiring lung cancer surgery.
Assuntos
Broncodilatadores/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/complicações , Transtornos Respiratórios/prevenção & controle , Derivados da Escopolamina/administração & dosagem , Administração por Inalação , Idoso , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Pneumonectomia , Complicações Pós-Operatórias/epidemiologia , Transtornos Respiratórios/epidemiologia , Estudos Retrospectivos , Brometo de TiotrópioRESUMO
Objectives Among patients with advanced non-small cell lung cancer (NSCLC), there are those who do not have a spouse, family members, or friends to support them in their cancer treatment and daily life: the kinless patients. Therefore, we designed an exploratory study of kinlessness and the prognosis of advanced NSCLC. Methods We retrospectively analyzed the prognosis of clinical factors and treatment and kinlessness in patients with advanced NSCLC with wild-type or unknown status for epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) and who visited our hospital from November 2018 to February 2023. In addition to the survival analysis by kinlessness, a multivariable analysis of survival was performed for all clinical factors. In a secondary analysis, a multivariable analysis of the choice of best supportive care (BSC) was performed for all clinical factors. Results One hundred forty-four patients are included in our cohort. There were 131 patients with kin, with a median survival of 1.34 years (95% CI of 1.01-1.79 years). There were 13 patients has no kin, with a median survival of 0.53 years (95% CI 0.23-0.76 years). The log-rank analysis showed that kinless patients had significantly shorter overall survival than patients who have kin. A Cox regression analysis showed that age, distant metastasis, performance status, and kinlessness were associated with overall survival. Secondary analysis showed that there was no statistical association between kinlessness and the choice of BSC in our cohort. Conclusions Kinless patients had shorter survival than patients who have kin in our single-center, retrospective study of patients with advanced NSCLC with wild-type or unknown status for (EGFR/ALK). Further research to evaluate the clinical impact of kinlessness in the treatment of advanced NSCLC is needed.
RESUMO
[This retracts the article DOI: 10.18632/oncotarget.18032.].