PO-33 - Heparin suppresses progression of small cell lung cancer (SCLC) in an orthotopic mouse model.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death worldwide. Small cell lung cancer (SCLC) is thereby a highly aggressive neuroendocrine carcinoma representing about 15% of all lung cancer cases. Due to the highly metastatic behavior and multidrug resistance, the long-term survival of patients is very low. AIM: Current clinical studies revealed an increased survival of SCLC patients treated with heparin. Thus, the role of heparin in SCLC progression was analyzed with the focus on cell adhesion, cell survival and metastasis formation. MATERIALS AND METHODS: Heparins were tested for their capacities to alter migration, adhesion and viability of SCLC cells in vitro as well as tumor growth and metastasis formation in vivo. RESULTS: Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) both strongly inhibited migration as well as adhesion of SCLC cells to fibronectin and stromal cells. In addition, Heparin induced cellular apoptosis and also increased apoptotic effects of conventional chemotherapeutics in vitro. To investigate the role of LMWH on metastasis formation in vivo, an orthotopic xenograft mouse model with spontaneous metastasis formation has been established. The primary tumors in this mouse model show a marked capacity to metastasize to characteristic distant organs, reflecting advanced steps of malignant progression. Treatment of tumor-bearing mice with LMWH suppressed progression of SCLC. CONCLUSIONS: Administration of LMWH in addition to the conventional treatment might reduce metastasis formation and development of chemoresistance, leading to an improved survival rate of patients suffering from SCLC.

Effect of elastic compression on venous hemodynamics in postphlebitic limbs.

To determine whether elastic compression alters the venous hemodynamics in the postphlebitic limb, we measured venous pressure patterns in 11 postphlebitic limbs with and without elastic compression stockings. Following cannulation of a dorsal vein of the foot, the patients underwent measurements of basal resting pressure, maximum percent decrease in venous pressure with exercise (delta VPex), peak systolic venous pressure during exercise (SVPmax), the amplitude of the pressure swing, and venous return time. Elastic compression did not alter basal resting pressure, delta VPex, or venous return time. By contrast, SVPmax decreased from 139 +/- 0.3 mm Hg to 11 +/- 8 mm Hg with elastic compression. If venous ulcers are related to the high pressure developed in the superficial veins during calf muscle systole, then elastic compression may be beneficial by decreasing systolic venous pressure and its subsequent deleterious consequences.

Prophylactic interruption of the inferior vena cava: immediate and long-term hemodynamic effects.

Two hundred patients were evaluated retrospectively to determine the clinical effects of prophylactic inferior vena cava (IVC) interruption in association with aortic reconstruction. No pulmonary embolism occurred in the group with IVC interruption, but embolisms did occur in seven of 68 patients who had aortic reconstruction performed without IVC interruption. In two patients, the pulmonary embolism was fatal. Postoperative incidence of deep vein thrombosis was fatal. Postoperative incidence of deep vein thrombosis was 9% in both groups. Clinical and hemodynamic effects of prophylactic IVC interruption were studied in 20 additional patients. Venous hemodynamics (maximum venous outflow, inferior vena cava pressure, and ambulatory venous pressure) showed no change following interruption in 19/20. Sixteen patients from the original group of patients with prophylactic interruption were studied hemodyamically. No pulmonary embolism was clinically evident. One new case of deep vein thrombosis was seen. Again, venous hemodynamics showed no change as a result of IVC interruption. Prophylactic IVC interruption is a safe means of decreasing the incidence of pulmonary embolism without increasing venous-related morbidity.