The Wnt signaling pathway is essential for development and organogenesis. Wnt signaling stabilizes beta-catenin, which accumulates in the cytoplasm, binds to 1-cell factor (TCF; also known as lymphocyte enhancer-binding factor, LEF) and then upregulates downstream genes. Mutations in CTNNB1 (encoding beta-catenin) or APC (adenomatous polyposis coli) have been reported in human neoplasms including colon cancers and hepatocellular carcinomas (HCCs). Because HCC5 tend to show accumulation of beta-catenin more often than mutations in CTNNB1, we looked for mutations in AXIN1, encoding a key factor for Wnt signaling, in 6 HCC cell lines and 100 primary HCC5. Among the 4 cell lines and 87 HCC5 in which we did not detect CTNNB1 mutations, we identified AXIN1 mutations in 3 cell lines and 6 mutations in 5 of the primary HCCs. In cell lines containing mutations in either gene, we observed increased DNA binding of TCF associated with beta-catenin in nuclei. Adenovirus mediated gene transfer of wild-type AXINI induced apoptosis in hepatocellular and colorectal cancer cells that had accumulated beta-catenin as a consequence of either APC, CTNNB1 or AXIN1 mutation, suggesting that axin may be an effective therapeutic molecule for suppressing growth of hepatocellular and colorectal cancers.

Background and Objectives:The clear delineation between tumor and normal tissue is ideal for real-time surgical navigation imaging. We present a novel indocyanine green (ICG) fluorescence imaging technique to visualize hepatocellular carcinoma (HCC). Methods: Ten patients with solitary HCC underwent hepatectomy between February and September 2007 at Osaka Medical Center for Cancer and Cardiovascular Diseases. ICG had been injected intravenously several days before surgery at a dose of 0.5 mg/kg body weight. After laparotomy, the liver was inspected with intraoperative ultrasonography (IOUS), and then with a near-infrared (NIR) fluorescence imaging system (PDE; Hamamatsu Photonics K.K. Hamamatsu, Japan). Results: All the 10 primary tumors showed bright fluorescent signals and could be completely removed with negative margins under the guide of PDE. In four cases (40.0%), new HCC nodules that were not detected by use of any preoperative examinations including IOUS were detected by PDE. These newly identified HCC nodules were very small in size and most of the tumors were well-differentiated HCCs. Conclusions: This novel technique is simple and safe, and is therefore considered to be a promising tool for routine intraoperative imaging during a hepatic resection and further clinical exploration for HCC.

We performed a retrospective review of 59 pancreatic resections for ductal carcinoma of the pancreas head performed between 1971 and 1983. In addition to pancreaticoduodenectomy, 37 consecutive patients (from 1971 to 1981) received lymphatic dissection adjacent to the pancreatic head (Group R1), whereas another 22 patients (from 1981 to 1983) received a wider range of lymphatic and soft tissue dissection, including the para-aortic region (Group R2). These groups did not differ with regard to operative mortality rate or background factors in the patients who tolerated operation. The 3-year cumulative survival rate was 13% in the R1 group vs. 38% in the R2 group (p less than 0.05). Almost all of the deaths from cancer recurrence occurred within 3 years after operation; the cumulative rate of death from local recurrence decreased from 67 to 16% (p less than 0.05) at 3 years. Among the patients with nodal involvement, there was no 3-year survivor in the R1 group, but four (27%) in the R2 group (p less than 0.05) survived. Among the patients whose tumor size exceeded 4 cm with retroperitoneal invasion, there was no 3-year survivor in either group and most patients died of distant metastasis. Extended clearance of regional lymph nodes and soft tissue appears to benefit patients with ductal carcinoma of the pancreatic head whose tumor size is less than 4 cm without severe invasion to the retroperitoneal space.

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