These exploratory data suggest a positive influence of a palliative resection performed during the disease course of patients with advanced CRC. The increased frequency of utilization and the more prolonged duration of C in the surgically treated patients may in part contribute to this improved survival. This may also be reflective of performance status at the time of diagnosis. Future trials enrolling patients with advanced CRC should prospectively stratify for surgical intervention to further clarify the influence of this modality on the outcome of systemic therapy in this disease.

The effect of morphine on the degradation of the host defense barrier in rats and mice was studied. Mice received either 3 or 11 doses of morphine. Mice receiving 11 doses of morphine showed gram-negative bacteremia and bacterial growth in samples of peritoneal fluid (PF), liver, spleen, kidneys, heart, and lungs; PF and tissue samples from only 1 control mouse showed bacterial growth, and no control mice had bacteremia. Mice receiving 11 doses also had suppressed bone marrow macrophage colony formation. Monocytes and peritoneal macrophages harvested from morphine-treated mice showed greater injury than did those from control mice. Pretreatment of mice with naloxone inhibited morphine-induced macrophage injury and degradation of the host defense barrier. In in vitro studies, morphine attenuated the killing of bacteria phagocytosed by macrophages and also facilitated their escape. This study indicates that morphine-induced monocyte and macrophage injury may be linked to degradation of the host defense barrier.

Morphine inhibits macrophage migration both in vivo and in vitro. This attenuated transmigration of macrophages seems to be secondary to the apoptotic effect of morphine.

Oxidative stress plays an important role in the induction of mesangial cell (MC) injury. In the present study, we evaluated the molecular mechanism involved in hydrogen peroxide (H₂O₂)-induced MC apoptosis. In addition, we examined the role of heme oxygenase-1 (HO-1) in hepatocyte growth factor (HGF)-modulated, H₂O₂-induced MC injury. H₂O₂ promoted (p < 0.001) mouse MC (MMC) apoptosis. This effect of H₂O₂ was associated with translocation of cytochrome c from the mitochondrial to the cytosolic compartment. In addition, a caspase-9 inhibitor partially attenuated this effect of H₂O₂. These findings suggest that H₂O₂-induced MMC apoptosis is mediated through the mitochondrial pathway. HGF not only prevented H₂O₂-induced MMC apoptosis, but also inhibited H₂O₂-induced translocation of cytochrome c from the mitochondrial to the cytosolic compartment. HGF also promoted the expression of HO-1 by MMCs; interestingly, hemin inhibited (p < 0.001) H₂O₂-induced MMC apoptosis. On the other hand, zinc protoporphyrin inhibited the protective influence of HGF on H₂O₂-induced MMC apoptosis. These findings suggest that H₂O₂-induced apoptosis occurs through the mitochondrial pathway. HGF provides protection against H₂O₂-induced MMC apoptosis through induction of HO-1.

Given the high prevalence of chronic venous diseases (CVD), defining criteria to screen patients who are in need for intervention is attaining primacy. An important clinical criterion for treating CVD is incompetence of larger veins. We have assessed the association of size of afflicted veins with disease severity in patients with CVD to define an acceptable criterion to identify patients who need intervention. Demographic characteristics and risk factors were recorded from 6350 patients. Based on physical examination and venous duplex ultrasound study, patients were classified into clinical severity, etiology, anatomy, and pathophysiology (CEAP) classes and grouped according to the size of the veins which had varicosities. Patients with reflux in smaller veins (vein size <4 mm diameter) were considered as type I and those with varicosities in truncal veins (>4 mm diameter) as type II. Risk ratio was determined by multivariate regression analysis. About 47.67% of patients in this study were found to have CEAP class 3 disease. Compared with varicose veins of large truncal veins, patients with varicosities in smaller superficial veins had 2.85-fold (p < 0.01) more risk of edema and 5.71-fold (p < 0.01) higher prevalence of hyperpigmentation. Varicosities in small superficial veins were associated with higher risk of ulceration (odds ratio 3.93, 95% confidence interval 2.51–6.18) compared with truncal vein reflux. Our study reveals that presence of small varicose veins in patients without truncal saphenous reflux involvement is associated with severe manifestations of venous insufficiency such as edema and skin lesions even in the absence of varicosities in truncal saphenous veins.