The efficacy of adjuvant cytostatic therapy after organ transplantation for malignancy: an experimental study with a combined transplantation/tumor model.
New data show that perioperative cytostatic therapy is beneficial in the case of liver transplantation for hepatic cancer. However, it has not been established clearly whether chemotherapy interferes with graft rejection. We therefore studied the interactions between tumor growth and graft rejection, especially with regard to chemotherapy, using a combined tumor/transplantation model. As a tumor model, we used the Novikoff hepatoma, a malignant hepatoma that was injected subcutaneously into the backs of rats. Heterotopic heart grafting served as the transplantation model. In a first step (a), we studied the effect of cytostatic therapy on tumor growth: tumor cells were injected, and in four groups epirubicin, cyclosporine, epirubicin + cyclosporine, and placebo were applied, in corresponding groups, transplantation was additionally performed. Tumor growth was measured and the resected tumors were examined by histology and immunohistology. In a second step (b), we studied the effect of chemotherapy on graft rejection: transplantation was performed and the above-mentioned drugs were applied; in corresponding groups, a solid tumor was additionally induced and resected immediately before transplantation. The results of these procedures were as follows: (a) Epirubicin decreased tumor growth and diminished the volume-increasing effect of cyclosporine significantly. After transplantation, tumor growth was similar. (b) Epirubicin prolonged graft survival significantly, and the combination with cyclosporine had an augmenting effect. In the corresponding groups, graft survival was similar. In conclusions. chemotherapy diminishes the tumor-increasing effect of cyclosporine and does not interfere negatively with graft survival. It might therefore be beneficial after transplantation for malignancy.
Zimmermann
T
T
Department of Surgery, University of Giessen, Germany.
Holtappels
M
M
Buhr
J
J
Berghäuser
K H
KH
Padberg
W M
WM
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use; D006084:Graft Rejection / Q000139:chemically induced* / Q000473:pathology*; D016027:Heart Transplantation; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology; D051381:Rats
D015251:Epirubicin; D016572:Cyclosporine