Role of immunosuppression in recurrence after liver transplantation for diethylnitrosamine-induced tumors in rats.
Hepatocellular carcinoma is one of the world's most common malignant diseases, with an increasing incidence related to liver cirrhosis. The purpose of the study was to evaluate the role of immunosuppression in recurrence in rats transplanted after liver tumor induction by diethylnitrosamine (DENA), which has proved to be a reliable carcinogen. In 14-week-old Lewis rats weighing 200 g, tumors were induced by the oral administration (5 mg/100 ml in drinking water ad libitum) of DENA for 13 weeks. Orthotopic liver transplantation (OLT) was performed after 4 weeks' latency. In the Lewis/Lewis rats weighing 200 g, tumors sporin A (CsA) treatment, median survival was 199-days with no recurrence or metastasis. In the BN/Lewis group with no CsA (5 ats) median survival was 144 days. All rats died due to rejection. In the other BN/Lewis group (10 rats), OLT was followed by CsA administration (7.5 mg/kg). Median survival was 161 days. In three rats (218 days), there was liver tumor recurrence; in two rats (137.5 days), kidney and lung metastases were found. The remaining rats died of septic complications. In the Lewis/Lewis + CsA group (10 rats), median survival was 131 days with 5 recurrencies and/or metastases. Two rats are still surviving at 84 and 88 days. Our results suggest that the DENA model is reliable; it proved to have a similar carcinologic pattern to HCC in man. Moreover, immunosuppression seems to play an important role in determining recurrence. Further studies are needed to investigate the efficacy of chemotherapy agents pre- and post-transplantation.
Liver Unit PMP Research Laboratory, Ospedale Cardarelli, Naples, Italy.
A
A
Ceriello
F
F
Mezza
S
S
Cozzolino
G
G
Pettinato
A
A
Mancini
W
W
Santaniello
F
F
Calise
O
O
Cuomo
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D004052:Diethylnitrosamine; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D008297:Male; D009362:Neoplasm Metastasis; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012008:Recurrence; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D007166:Immunosuppressive Agents; D004052:Diethylnitrosamine; D016572:Cyclosporine