The significance of acute phase graft injury on tumor recurrence and metastases in living donor liver transplantation

Abstract

Objective To investigate the significance of cell signaling pathwaysof acute phase injury, tumor cell invasion/migration and angiogene-sis on tumor recurrence in small-for-size liver grafts after LDLT.Patients and Methods 87 LDLT and 34 DDLT were included inthis study. The hepatic stellate cell (HSC) activation and intragraft protein expression of Rac, FAK and CAK were examined byimmunostaining before and after reperfusion. The intragraft mRNAexpressions of VEGF, ROCK, RhoA, Egr-1 and FAK were alsodetected by real time RT-PCR. Liver tumor recurrence/metastaseswere compared.Results The patients were grouped to Group 1 (n = 80) with theratio of the graft weight to SLV less than 0.6; and Group 2 (n = 41)with the ratio great than 0.6. 22 recipients (27.5%) in Group 1 and9 recipients (22%) in Group 2 were diagnosed with HCC. There wasno difference of the incidence of higher tumor staging (8/22 vs 4/9,p = 0.704) and tumor vascular permeation (7/22 vs 1/9, p = 0.379)in the HCC recipients between the two groups. More HCC recipi-ents developed tumor recurrence/metastases in Group 1 compared toGroup 2 (8/22 vs 0/9, p = 0.068). Significant activation of HSC wasfound in Group 1 together with stronger intragraft protein expressionof FAK and CAK. Intragraft mRNA levels of Egr-1, RhoA, FAK andVEGF was significantly higher in Group 1.Conclusion Significant activation of signaling pathways of acutephase injury and angiogenesis, cell invasion and migration in small-for-size liver grafts after LDLT might contribute to the higher inci-dence of liver tumor recurrence/metastases.