RESUMO
Perineural invasion (PNI) has been implicated as a poor prognostic indicator in many cancers. The National Comprehensive Cancer Network recommends consideration of observation or adjuvant therapy in the presence of PNI in early colon cancer. These recommendations are based on single institutional studies that fail to evaluate PNI within the context of adjuvant chemotherapy. The US National Cancer Database (2004-2012) was reviewed for patients with node negative colon cancer, and stratified by PNI and receipt of chemotherapy. Of 21,488 patients evaluated, 55.2% had T3 disease (n = 11,852), 23.1% had T2 (n = 4,971), 14.4% had T1 (n = 3,088), and 7.3% had T4 disease (n = 1,577); 4.6% (n = 987) had PNI. Most patients (86.8%, n = 18,641) did not have PNI and did not receive chemotherapy; 8.7% (n = 1,860) did not have PNI but received chemotherapy; 3.7% (n = 785) had PNI and did not receive chemotherapy, and 0.9% (n = 202) had PNI and received chemotherapy. Among those with PNI, patients who received chemotherapy tended to be younger (P<0.001), covered by private insurance (P<0.001), with fewer comorbidities (P<0.001), and greater T stage disease (P<0.001). Those with PNI who received chemotherapy had significantly improved survival over those who did not in T3-4 disease (P<0.001), but not in T1-2 disease. On multivariate analysis, those with PNI had a 38% greater hazard of mortality (HR 1.38, P<0.001). Additionally, chemotherapy decreased the hazard of mortality by 43% (HR 0.57, P<0.001). PNI appears to be an independent poor prognostic indicator in stage T3-4 node negative colon cancer. Chemotherapy administered to this patient population is associated with improved survival.
Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Nervos Periféricos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/terapia , Comorbidade , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Adulto JovemRESUMO
RATIONALE: Oxidants are believed to play a major role in the development of emphysema. OBJECTIVES: This study aimed to determine if the expression of human copper-zinc superoxide dismutase (CuZnSOD) within the lungs of mice protects against the development of emphysema. METHODS: Transgenic CuZnSOD and littermate mice were exposed to cigarette smoke (6 h/d, 5 d/wk, for 1 yr) and compared with nonexposed mice. A second group was treated with intratracheal elastase to induce emphysema. MEASUREMENTS: Lung inflammation was measured by cell counts and myeloperoxidase levels. Oxidative damage was assessed by immunofluorescence for 3-nitrotyrosine and 8-hydroxydeoxyguanosine and lipid peroxidation levels. The development of emphysema was determined by measuring the mean linear intercept (Lm). MAIN RESULTS: Smoke exposure caused a fourfold increase in neutrophilic inflammation and doubled lung myeloperoxidase activity. This inflammatory response did not occur in the smoke-exposed CuZnSOD mice. Similarly, CuZnSOD expression prevented the 58% increase in lung lipid peroxidation products that occurred after smoke exposure. Most important, CuZnSOD prevented the onset of emphysema in both the smoke-induced model (Lm, 68 exposed control vs. 58 exposed transgenic; p < 0.04) and elastase-generated model (Lm, 80 exposed control vs. 63 exposed transgenic; p < 0.03). These results demonstrate for the first time that antioxidants can prevent smoke-induced inflammation and can counteract the proteolytic cascade that leads to emphysema formation in two separate animal models of the disease. CONCLUSIONS: These findings indicate that strategies aimed at enhancing or supplementing lung antioxidants could be effective for the prevention and treatment of this disease.
Assuntos
Enfisema Pulmonar/prevenção & controle , Fumar , Superóxido Dismutase/biossíntese , Animais , Biomarcadores/metabolismo , Contagem de Células , Modelos Animais de Doenças , Progressão da Doença , Peroxidação de Lipídeos , Pulmão/enzimologia , Pulmão/patologia , Macrófagos Alveolares/enzimologia , Macrófagos Alveolares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Elastase Pancreática/toxicidade , Peroxidase/metabolismo , Enfisema Pulmonar/enzimologia , Enfisema Pulmonar/etiologia , Fumar/efeitos adversos , Superóxido Dismutase/genéticaRESUMO
Many possible treatments for pulmonary fibrosis have been investigated, but except for some current clinical trials, none have succeeded in clinical trials. On the basis of the antioxidant action of bilirubin (BIL), we examined the effects of hyperbilirubinemia on the development of bleomycin (BLM)-induced pulmonary fibrosis in rats. The animals' plasma BIL level was kept within 3 and 10 mg/dl by repeated intravenous infusion of a high dose of BIL. We studied the inhibitory effects of hyperbilirubinemia on BLM-induced pulmonary fibrosis through histopathologic and biochemical analyses. Mortality of rats with BLM-induced pulmonary fibrosis was significantly lower in the three groups with hyperbilirubinemia. The ameliorating effect of hyperbilirubinemia on pulmonary fibrosis was shown by lung histology, as well as by a decreased lung content of hydroxyproline and reduced bronchoalveolar lavage fluid (BALF) concentration of transforming growth factor (TGF)-beta(1). The number of polymorphonuclear leukocytes and lymphocytes in BALF was also decreased in the groups with hyperbilirubinemia. Furthermore, oxidative metabolites of BIL in urine were present at significantly higher levels in BLM-treated rats with hyperbilirubinemia than in those without hyperbilirubinemia. These data suggest that the antioxidative action of BIL can attenuate BLM-induced pulmonary fibrosis, partly by inhibiting lung inflammation and production of TGF-beta1.