Anti-angiogenic alternatives to VEGF blockade

Angiogenesis is a major requirement for tumour formation and development. Anti-angiogenic treatments aim to starve the tumour of nutrients and oxygen and also guard against metastasis. The main anti-angiogenic agents to date have focused on blocking the pro-angiogenic vascular endothelial growth factors (VEGFs). While this approach has seen some success and has provided a proof of principle that such anti-angiogenic agents can be used as treatment, the overall outcome of VEGF blockade has been somewhat disappointing. There is a current need for new strategies in inhibiting tumour angiogenesis; this article will review current and historical examples in blocking various membrane receptors and components of the extracellular matrix important in angiogenesis. Targeting these newly discovered pro-angiogenic proteins could provide novel strategies for cancer therapy

Fatores de risco de complicações pulmonares em pacientes com sarcoma após toracotomia para a ressecção de nódulos pulmonares Risk factors for pulmonary complications in patients with sarcoma after the resection of pulmonary nodules by thoracotomy

OBJETIVO: Identificar os fatores de risco para complicações pulmonares em pacientes com sarcoma após serem submetidos a toracotomia para a ressecção de nódulos pulmonares. MÉTODOS: Estudo de coorte retrospectivo com 68 pacientes consecutivos com diagnóstico de sarcomas e submetidos a 174 toracotomias para a ressecção de nódulos pulmonares. A variável dependente foi definida como a ocorrência de qualquer complicação pulmonar pós-operatória. As variáveis independentes foram relacionadas com o paciente, o diagnóstico de base e o tipo de procedimento cirúrgico. Os dados foram analisados segundo um modelo multivariado de estimação de equações generalizadas, com uma função de ligação logística e uma estrutura de correlação simétrica. RESULTADOS: Houve 24 complicações (13,8%; IC95%: 9,0-19,8), incluindo um óbito. Os pacientes que apresentaram complicações pós-operatórias tiveram um tempo médio de internação duas vezes superior àqueles sem complicações (18,8 ± 10,0 dias vs. 8,6 ± 6,0 dias; p < 0,05). As variáveis que se correlacionaram com o desfecho foram o tipo de ressecção (em cunha ou anatômica; OR = 3,6; IC95%: 1,5-8,8), necessidade de transfusão sanguínea (OR = 9,8; IC95%: 1,6-60,1) e número de nódulos ressecados (OR = 1,1; IC95%: 1,0-1,1). O modelo multivariado obtido exibiu uma área sob a curva ROC de 0,75 (IC95%: 0,65-0,85). CONCLUSÕES: As complicações pulmonares pós-operatórias após a ressecção de nódulos pulmonares em pacientes com sarcoma não foram raras, ocorrendo em cerca de 10% dos procedimentos. A ocorrência dessas complicações pode ser antecipada pelo uso de ressecção não em cunha, necessidade de hemotransfusão e maior número de nódulos ressecados. Assim, já no pós-operatório imediato, é possível identificar pacientes de risco, que devem ser estritamente monitorizados durante o período pós-operatório imediato. Para esses pacientes, todas as medidas preventivas devem ser tomadas.<br>OBJECTIVE: To identify the risk factors for pulmonary complications after thoracotomy for the resection of pulmonary nodules in patients with sarcoma. METHODS: A retrospective cohort study involving 68 consecutive patients diagnosed with sarcoma and submitted to a total of 174 thoracotomies for the resection of pulmonary nodules. The dependent variable was defined as the occurrence of any postoperative pulmonary complications. The independent variables were related to the patient, underlying diagnosis, and type of surgical procedure. We analyzed the data using a multivariate generalized estimating equations model with logistic link function and a symmetric correlation structure. RESULTS: Complications were observed in 24 patients (13.8%, 95% CI: 9.0-19.8), and there was one death. The mean length of hospital stay was twice as long in the patients with postoperative complications as in those without (18.8 ± 10.0 days vs. 8.6 ± 6.0 days; p < 0.05). The variables that correlated with the outcome measure were the type of resection (wedge vs. anatomic; OR = 3.6; 95% CI: 1.5-8.8), the need for blood transfusion (OR = 9.8; 95% CI: 1.6-60.1), and the number of nodules resected (OR = 1.1; 95% CI: 1.0-1.1). The multivariate model showed an area under the ROC curve of 0.75 (95% CI: 0.65-0.85). CONCLUSIONS: Postoperative pulmonary complications were common after pulmonary nodule resection in patients with sarcoma, occurring in approximately 10% of the procedures. The occurrence of such complications can be expected when techniques other than wedge resection are employed, when blood transfusion is required, and when a great number of nodules are resected. Therefore, it is possible to identify patients at risk for pulmonary complications, who should be closely monitored in the immediate postoperative period. In such patients, all preventive measures should be taken

The relationship between albumin, other plasma proteins and variables, and age in the acute phase response after liver resection in man

A large series of plasma albumin (ALB, g/dl) and simultaneous blood and clinical measurements were prospectively performed on 92 liver resection patients, and processed to assess the correlations between ALB, other plasma proteins, additional variables and clinical events. The measurements were performed preoperatively and at postoperative day 1, 3 and 7 in all patients, and subsequently only in those who developed complications or died. In patients who recovered normally ALB was 4.3 +/- 0.4 g/dl (mean +/- SD) preoperatively, 3.7 +/- 0.7 at day 1 and 3, and 3.9 +/- 0.4 at day 7. In patients with complications its decrease was more prolonged. In non-survivors it was 3.4 +/- 0.4 preoperatively, 3.0 +/- 0.4 at day 1, and then decreased further. Regression analysis showed direct correlations between ALB and pseudo-cholinesterase (CHE, U/l, nv 5300-13000), cholesterol (CHOL, mg/dl), iron binding capacity (IBC, mg/dl), prothrombin activity (PA, % of standard reference) and fibrinogen, an inverse correlation with blood urea nitrogen (BUN, mg/dl) for any given creatinine level (CREAT, mg/dl), and weaker direct correlations with hematocrit, other variables and dose of exogenous albumin. An inverse relationship found between ALB and age (AGE, years) became postoperatively (POSTOP) also a function of outcome, showing larger age-related decreases in ALB associated with complications (COMPL: sepsis, liver insufficiency) or death (DEATH). Main overall correlations: CHE = 287.4(2.014)(ALB), r = 0.73; CHOL = 16.5(1.610)(ALB) (1.001)(ALKPH), r = 0.71; IBC = 68.6(1.391)(ALB), r = 0.64; PA = 13.8 + 16.0(ALB), r = 0.51; BUN = 21.3 + 20.2(CREAT) - 6.2(ALB), r = 0.91; ALB = 5.0-0.013(AGE) - {0.5 + 0.003(AGE) (COMPL) + 0.012(AGE) (DEATH) } (POSTOP) , r = 0.74 [p < 0.001 for each regression and each coefficient; ALKPH = alkaline phosphatase, U/l, nv 98-279, independent determinant of CHOL; discontinuous variables in italics label the change in regression slope or intercept associated with the corresponding condition]. These results suggest that altered albumin synthesis (or altered synthesis unable to compensate for albumin loss, catabolism or redistribution) is an important determinant of hypoalbuminemia after hepatectomy. The correlations with age and postoperative outcome support the concept that hypoalbuminemia is a marker of pathophysiologic frailty associated with increasing age, and amplified by the challenges of postoperative illness