Volume 114, Issue 6, Pages (December 1998)

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Volume 114, Issue 6, Pages 1668-1675 (December 1998) Vascular Endothelial Growth Factor Increased by Pulmonary Surgery Accelerates the Growth of Micrometastases in Metastatic Lung Cancer Yoshimasa Maniwa, MD, Masayoshi Okada, MD, Noboru Ishii, MD, Kazue Kiyooka, MD CHEST Volume 114, Issue 6, Pages 1668-1675 (December 1998) DOI: 10.1378/chest.114.6.1668 Copyright © 1998 The American College of Chest Physicians Terms and Conditions

FIGURE 1 Cumulative survival rate of 120 patients who underwent surgery for lung metastases at Kobe University Hospital from January 1975 to May 1997 (Kaplan-Meier method). The prognosis of 12 patients (▪) in whom second lung metastatic lesions developed within 6 months after the first lung resection was significantly worse compared with the other 108 patients (▪). CHEST 1998 114, 1668-1675DOI: (10.1378/chest.114.6.1668) Copyright © 1998 The American College of Chest Physicians Terms and Conditions

FIGURE 2 A, serum VEGF165 concentration before surgery and the maximum value after surgery in each case. Paired values are connected with lines. VEGF was higher postoperatively than before surgery in all cases except one. B, each point represents the mean ± SE concentration of serum VEGF. The peak VEGF concentration was 33.1 ± 19.9 pg/mL at 12 h after surgery, which was significantly higher compared with the concentration before surgery (12.9 ± 3.9 pg/mL; p < 0.05) or just after surgery (10.8 ± 2.8 pg/mL; p < 0.005). CHEST 1998 114, 1668-1675DOI: (10.1378/chest.114.6.1668) Copyright © 1998 The American College of Chest Physicians Terms and Conditions

FIGURE 3 Hematoxylin-eosin staining of dormant lung micrometastases on day 11. Scale bar = 250 μm. CHEST 1998 114, 1668-1675DOI: (10.1378/chest.114.6.1668) Copyright © 1998 The American College of Chest Physicians Terms and Conditions

FIGURE 4 Lung metastases were observed in all animals on day 20 (white arrows). CHEST 1998 114, 1668-1675DOI: (10.1378/chest.114.6.1668) Copyright © 1998 The American College of Chest Physicians Terms and Conditions

FIGURE 5 The number of metastases > 2.0 mm in diameter was 0.8 ± 0.3 in the control groups, 0.5 ± 0.5 in group A, 5.2 ± 1.7 in group B, 7.5 ± 2.0 in group C, and 1.2 ± 0.4 in group D (group B vs control; p < 0.001; group C vs control, p < 0.0001). CHEST 1998 114, 1668-1675DOI: (10.1378/chest.114.6.1668) Copyright © 1998 The American College of Chest Physicians Terms and Conditions

FIGURE 6 Staining of endothelial cells with Factor VIII-related antigen. A, In tumors that were > 2.0 nun in diameter, dense infiltration of microvessels was observed. B, Few microvessels were detected in the metastases 2.0 mm. Scale bars = 50 μm. CHEST 1998 114, 1668-1675DOI: (10.1378/chest.114.6.1668) Copyright © 1998 The American College of Chest Physicians Terms and Conditions

FIGURE 7 The microvessel density in each group. Group A, 28.8 ± 2.7/mm2 in tumors ≤ 2.0 mm vs 39.3 ± 3.5/mm2 in tumors > 2.0 mm (p < 0.05). Group B, 26.0 ± 1.9 vs 34.0 ± 2.1/mm2 (p < 0.05). Group C, 22.8 ± 2.1 vs 31.8 ± 2.1/mm2 (p < 0.01). Group D, 29.0 ± 1.7 vs 37.5 ± 3.5/mm2 (p < 0.05). There were no significant differences among these groups. CHEST 1998 114, 1668-1675DOI: (10.1378/chest.114.6.1668) Copyright © 1998 The American College of Chest Physicians Terms and Conditions