Induction of apoptosis in HepG2 human hepatocellular carcinoma cells by a novel derivative of ursodeoxycholic acid (UDCA)

The effects of ursodeoxycholic acid (UDCA) and its novel derivative, named as HS-1030, on the proliferation of HepG2, human hepatocellular carcinoma cells were investigated. Whereas UDCA had no significant effect in a concentration range we have tested, HS-1030 inhibited the proliferation of HepG2 cells in a concentration dependent manner. Surprisingly, HS-1030 had no effect on the proliferation of Human Chang liver cell which is a normal liver cell line. We also found that proliferation-inhibitory effect of HS-1030 was due to the induction of apoptosis of HepG2 cells, which was confirmed by observing the internucleosomal DNA fragmentation and morphological changes (i.e. cell shrinkage, nuclear condensation and the formation of apoptotic bodies). These results suggest that HS-1030 may be a good candidate as a drug for the treatment of liver cancer.     

Covered versus uncovered wallstent for malignant extrahepatic biliary obstruction: a cohort comparative analysis.

BACKGROUND & AIMS: We examined the use of both covered and uncovered Wallstents in patients with malignant extrahepatic biliary obstruction to determine whether use of covered Wallstents prolonged stent patency without increasing procedure-related complications. METHODS: Commercially available silicone-covered Wallstents were prospectively evaluated in 98 patients who underwent insertion from December 2002-December 2004. Those data were compared with data obtained by retrospectively studying 108 consecutive patients who underwent endoscopic insertion of uncovered Wallstents between January 2000-November 2002, and for whom accurate and complete follow-up details were available. RESULTS: The mean stent patency was similar for both groups, 148.9 days (range, 3-667 days) for covered Wallstents and 143.5 days (3-910 days) for uncovered Wallstents (P = .531). The 2 groups also did not significantly differ in terms of cumulative stent patency according to the Kaplan-Meier lifetime table. The incidence of mild pancreatitis was similar in both groups, occurring in 6 patients with covered stents (6/98, 6.1%) and 2 patients with uncovered stents (2/108, 1.9%) (P = .154). Excluding those patients who had previously undergone cholecystectomy, acute cholecystitis occurred in 5 of 88 patients with covered Wallstents (6.1%) and 1 of 100 patients with uncovered stents (1%) (P = .104). Stent migration occurred in 6 patients with covered stents (6.1%) and 0 patients with uncovered stents (P = .011). CONCLUSION: Covered Wallstents might not prolong stent patency compared with uncovered Wallstents when used in the management of malignant extrahepatic biliary obstruction.     

Clinicopathologic review of 58 patients with biliary papillomatosis

BACKGROUND: Biliary papillomatosis (BP) is a rare disease that is characterized by multiple numerous papillary adenomas in the biliary tree. The clinical features and outcome, however, are not well known. The authors retrospectively analyzed their clinicopathologic features and long-term follow-up results. METHODS: Between March 1995 and January 2003, 58 patients were diagnosed with BP by cholangioscopic and histologic findings at a tertiary referral center, Asan Medical Center (University of Ulsan College of Medicine, Seoul, Korea). The authors retrospectively reviewed the medical records to obtain demographic, radiologic, cholangioscopic, and pathologic data. RESULTS: The common clinical manifestations at the presentation of patients were repeated episodes of abdominal pain, jaundice, and acute cholangitis. Acute cholangitis was more common in patients with mucin-hypersecreting BP (MBP), whereas patients with nonmucin-producing BP (NMBP) were more asymptomatic (P < 0.05). Papillary adenocarcinoma and mucinous carcinoma were detected in 48 patients (83%) with papillary adenomas. Overall survival rates of NMBP and MBP were 89% and 69% at 1 year, 57% and 37% at 3 years, and 52% and 19% at 5 years, respectively. The mean survival period of NMBP and MBP was 52.27 +/- 6.72 months and 30.84 +/- 8.36 months, respectively. CONCLUSIONS: BP should be regarded as a premalignant disease with high malignant potential. The pathogenesis of progression from benign to malignant disease may follow the adenomacarcinoma sequence. Although clinical presentations were somewhat different for patients with NMBP and MBP, the long-term survival rate was similar.     

Comparative cytotoxicity of low-osmolar nonionic and high-osmolar ionic contrast media to dog gallbladder epithelial cells

BACKGROUND: Most studies of the adverse effects of x-ray contrast media used in ERCP have focused on post-ERCP pancreatitis. However, the biliary epithelial cells are also exposed to contrast media during ERCP and acute cholangitis is also a serious complication of ERCP. The present study compared the cytotoxicity with gallbladder epithelial cells of ionic and nonionic contrast agents. METHODS: A high-osmolar ionic contrast agent (meglumine ioxithalamate) and a low-osmolar nonionic contrast agent (iopromide) were tested. Monolayer cell cultures of dog gallbladder epithelial cells were used. The cells were exposed to the 2 contrast agents with increasing iodine concentration and osmolality for 2 days. Cell number, S-phase fraction, aneuploidy, and supernatant LDH activities were measured each day. RESULTS: Cell growth was more severely inhibited by ioxithalamate than iopromide (p < 0.05) and strongly dependent on the osmolality of contrast agent. The cytostatic effect estimated by S-phase fraction was more pronounced for ioxithalamate. Chromosomal damage determined by aneuploidy was more frequently detected with ioxithalamate. CONCLUSIONS: High-osmolar ionic contrast media are more cytotoxic than low-osmolar nonionic contrast media to gallbladder epithelial cells. Animal and clinical studies are needed to estimate the clinical implications of these findings.