To examine the role of the loss of heterozygosity (LOH) in hepatitis-related carcinogenesis, we performed a genomewide scan of LOH in 44 tumors of hepatocellular carcinoma (HCC) using 216 microsatellite markers throughout all human chromosomes. A high frequency of LOH (G30% of informative cases) was observed at 33 loci on chromosome arms 4q, 6q, 8p, 8q, 9p, 9q, 13q, 16p, 16q, 17p, and 19p. LOH on 19p has not yet been reported, and that appears to be a new candidate in the search for tumor suppressor genes. High rates of LOH are correlated with hepatitis B virus (HBV) positivity, poorly differentiated tumors, vascular invasion, and intrahepatic metastasis (P F .0001). LOH on 13q and 16q occurred more frequently in HBV(؉) patients (P F .0001), and LOH on 6q occurred more frequently in virus-negative patients (P F .001). The frequency of LOH on 4q and 13q was significantly lower in well-differentiated tumors than in moderately and poorly differentiated tumors (P F .01). In contrast, LOH on 6q was frequently detected in well-differentiated tumors compared with other histological subclasses (P F .001). Our results suggest that LOH on 6q may play an important role in the early stage of hepatocarcinogenesis in virus-negative patients, but different mechanisms might underlie the initial step to carcinogenesis in HBV ( Primary hepatocellular carcinoma (HCC) is one of the most common causes of death from cancer in many countries of the world, especially in Asia and Africa. Among risk factors such as hepatitis virus infection, exposure to aflatoxin B1, heavy alcohol consumption, and several genetic diseases, epidemiological studies have shown that the hepatitis B virus (HBV) plays a major role in the carcinogenesis of HCC. [1][2][3] Histological findings suggest that the development of HCC is a multistep process involving qualitative and quantitative changes in expressed genes. 4 The molecular genetic approach has shown that multiple carcinogenic steps correspond to the accumulation of sequentially occurring genetic aberrations such as the activation of oncogenes and the inactivation of tumor suppressor genes. 5 Although the multistep mechanism of carcinogenesis is well defined in colorectal cancer, the detailed mechanism for HCC remains unidentified.In Japan, more than 70% of patients with HCC are hepatitis C virus (HCV) positive, 10% to 20% are HBV positive, and the rest are virus negative. 6,7 HCC can be induced in HBx transgenic mice and HCV core protein transgenic mice, indicating that both HBV and HCV could play a direct role in hepatocarcinogenesis. 8,9 However, no clinical evidence exists to show that the pathway to HCC differs among HBVpositive, HCV-positive, and virus-negative patients.Only a limited number of studies on the activation of proto-oncogenes in HCC have been reported. These include amplifications of the cyclin D1 gene and the c-myc gene in some HCCs. 10,11 These studies suggest that inactivation of tumor suppressor genes is imperative for hepatocarcinogenesis. The frequent loss of heterozygosity (LOH...

This hepatocyte culture method facilitates the prolonged culture of primary human hepatocytes with preservation of hepatocyte differentiation, function, and proliferative capacity.

No abstract

We aimed to assess the efficacy of transversus abdominis plane (TAP) block and rectus sheath (RS) block in patients undergoing laparoscopic inguinal hernia surgery. Few studies have addressed the efficacy and safety associated with TAP block and RS block for laparoscopic surgery. Thirty-two patients underwent laparoscopic inguinal hernia surgery, either with TAP and RS block (Block þ group, n ¼ 18) or without peripheral nerve block (Block À group, n ¼ 14). Preoperatively, TAP and RS block were performed through ultrasound guidance. We evaluated postoperative pain control and patient outcomes. The mean postoperative hospital stays were 1.56 days (Blockþ group) and 2.07 days (Block À group; range, 1-3 days in both groups; P ¼ 0.0038). A total of 11 patients and 1 patient underwent day surgery in the Block þ and Block À groups, respectively (P ¼ 0.0012). Good postoperative pain control was more commonly observed in the Block þ group than in the Block À group (P ¼ 0.011). TAP and RS block was effective in reducing postoperative pain and was associated with a fast recovery in patients undergoing laparoscopic inguinal hernia surgery.

We examined whether small hepatocytes (SHs), which are hepatic progenitor cells, could be isolated from a normal human liver and whether human hepatic cells could form hepatic organoids in a collagen sponge. Normal liver tissues were obtained from resected specimens from nine patients who underwent hepatic resection. Isolated hepatic cells were plated on dishes and a collagen sponge. More than 1 month later, SH-like cells appeared and proliferated on the dishes, whereas cell aggregates were formed in the sponge and showed characteristic tissue architecture: columnar and/or cuboidal epithelial cells lined the surface of the sponge. Clusters of epithelial cells with a large cytoplasm and ductular structures were observed under the lining cells. The lining and ductular cells were positive for cytokeratins 7 and 19, which indicated they were biliary epithelial cells (BECs), and the epithelial cells forming clusters were positive for the anti-human hepatocyte antibody, identifying them as hepatocytes. Some lining cells were positive for both the hepatic marker and the BEC markers. The cells in the collagen sponge actively proliferated and the hepatocytes excreted albumin into the medium. Thus, hepatic organoids could be reconstructed in a collagen sponge by normal human liver cells.