Volumetric and Functional Evaluation of Liver Regeneration for Cirrhotic Rats and Patients Following Portal Vein Ligation Using Single Photon Emission Computerized Tomography SPECT (I)

Backgrounds: Postoperative liver failure remains the nightmare of hepatobiliary surgens confronting with major hepatectomy for hepatocellular carcinoma associated with cirrhosis. Percutaneous transhepatic portal vein (PTPE) has been increasingly employed to enhance future liver remnant for those major hepatectomy is planned. Quantitative evaluation of liver regeneration following PTPE is largely on computer tomography-based volumetry, whereas the functional evaluation for future liver remnant preoperatively is lacking. Specific aims: 1. Establish a cirrhotic murine model of portal vein ligation (PVL). 2. Determine the regeneration index of cirrhotic liver following PVL 3. Volumetric and functional assessment of un-ligated lobes following PVL using sulfur colloid scan and DISIDA-SPECT, respectively. 4. Determine the molecular mechanism of impaired liver regeneration in cirrhotic subjects. Materials and Methods The first and second year 1. Sprague-Dawley rats fed thioacetamide to establish a murine cirrhotic model 2. Experimental animals underwent portal vein ligation (median and left lobe). The animals were sacrificed at day 1, 3, 5 and 7 following PVL. Liver enzymes (AST, ALT), BrdU assay, sulfur colloid scan and DISIDA-SPECT were performed before their sacrifice. 3. Cell cycles genes (including cyclin D1, cyclin B1, cyclin A2 and PCNA) and apoptosis-related genes (including Fas, Bcl- 2, BclXL, Bax, DAXX and JNK) were determined using real-time-PCR. The third year 4. Determine the phase fraction of rat hepatocytes entering into cell cycle using flow cytometry. 5. Ten cirrhotic patients prepared for portal vein embolization (PVE) followed by major hepatectomy are recruited. Sulfur colloid SPECT and DISIDA SPECT are employed before and 2-week after PVE to evaluate the restituted liver mass and liver function of embolized and non-embolized lobe, respectively. The data are correlated with serum functional profile, ICG 15’ retension test and CT-volumetry. Ten non-cirrhotic patients served as controls (We have enriched experience of portal vein embolization in clinical practice). Perspective 1. Volumetric and functional assessment of individual lobe of the liver following liver regeneration are of paramount significance. The results of the present study can be implicated in clinical practice of major hepatectomy for hepatocellular carcinoma associated with cirrhosis in the very near future. 2. We are the first team to develop this investigation model worldwide. Preliminary data Figure 1. Gross feature of a non-cirrhotic liver (SD rat) at day 7 following ligation of portal vein branch (median and left lobe). Ligated lobe (median and left lobe) became atrophic; whereas non-ligated lobes (right and caudate lobes) became hypertrophic. L, left lobe; M, median lobe; R, right lobe; C, caudate lobe. Figure 2. Gross feature of a cirrhotic liver (SD rat) at day 7 following ligation of portal vein branch (median and left lobe). Figure 3. Delayed bile secretion of the cirrhotic rat at 7 day following PVL detected by DISIDA-SPECT compared to that of the non-cirrhotic rat.

Project ID:PC9709-1228
External Project ID:NSC97-2314-B182-006