Upper GI and Oncology 02

Abstract

Traditional models of studying chemotherapy efficacy do not take into account microenvironment nor do they behave like naturally occurring human tumours. An isolated human liver model with tumour was developed to provide information for overcoming barriers to drug delivery and for developing novel therapeutic strategies. Liver specimens obtained from eight patients undergoing hemihepatectomy for hepatocellular carcinoma (HCC) or colorectal cancer (CRC) metastases were perfused via portal vein and hepatic artery branches (one control; three cisplatin: 23.3, 50 and 100 µm), two etoposide and two nitrogen mustard (NM; 50 and 100 µm). Chemotherapy-induced DNA damage was measured in individual tumour cells from fine needle aspiration biopsies using the Comet Assay. Thirteen tumours (median size 5 cm, range 2–17) were perfused (1 HCC, 12 CRC). Median duration of perfusion was 300 min (range 240–360), and median total perfusion flow was 300 mL min−1 (range 110–240). Laser Doppler imaging confirmed adequate perfusion, and livers remained viable on gross appearance, stable portal vein and hepatic artery pressures, bile production and maintenance of DNA integrity of the control. DNA damage increased linearly with cisplatin concentration (23.3, 50 and 100 µm caused 35, 45 and 60 per cent decrease in tail moment, respectively), but not with etoposide and NM. Seven of the 12 tumours demonstrated increased DNA damage superficially compared with deeper levels (three cisplatin; two etoposide and two NM). Perfusion of human livers obtained during hepatic resection is a simple procedure that provides new insights into the distribution patterns of chemotherapy within tumours in an ex vivo model.