Ki Young Yang

Endoscopic treatment for biliary stricture after adult living donor liver transplantation

Endoscopic intervention is considered to be the primary treatment for biliary stricture after adult living donor liver transplantation (LDLT) with duct‐to‐duct biliary reconstruction. The aim of this study was to investigate the risk factors of biliary stricture and the clinical outcomes and predictors of failure after endoscopic retrograde cholangiography with balloon dilation (ERC‐D). We enrolled 239 adult patients who underwent LDLT between 2000 and 2006. Sixty‐eight patients (28.4%) developed biliary stricture. Twenty‐nine patients with anastomotic biliary stricture were treated with ERC‐D and stenting. We retrospectively analyzed the risk factors of biliary stricture and the clinical outcomes of ERC‐D. The median follow‐up period was 31 months. The risk factors of biliary stricture on multiple logistic regression analysis were a graft with multiple bile ducts, a previous history of bile leakage, and hepatic artery stenosis. The overall success rate of ERC‐D was 64.5%. On simple logistic regression, the failure of primary ERC‐D was associated with late biliary stricture over 24 weeks and more than 8 weeks between a 2‐fold increase of serum alkaline phosphatase from the stable level and ERC‐D, even though these were not statistically significant on multiple logistic regression. The relapse rate of stricture after successful ERC‐D was 30%. The duration of stenting in the recurrence group was shorter than that in the nonrecurrence group (11.8 ± 5.03 versus 29.0 ± 11.6 weeks, P = 0.004). ERC‐D is effective for the management of anastomotic biliary stricture. However, the failure rate of primary ERC‐D may be high in patients with late onset and delayed diagnosis of biliary stricture. The recurrence seems to occur frequently in patients with a short duration of stenting. Liver Transpl 15:369–380, 2009.

A comparison of metal and plastic stents for the relief of jaundice in unresectable malignant biliary obstruction in Korea: an emphasis on cost-effectiveness in a country with a low ERCP cost

BACKGROUND In countries where ERCP costs are low relative to those of metal stents (eg, Korea), initial endoscopic retrograde biliary drainage (ERBD) with a plastic stent is thought to be more economical. OBJECTIVE We conducted this study to compare metal and plastic stent-based ERBD in efficacy, complications, and total cost of biliary drainage. DESIGN Retrospective study. SETTING Tertiary referral center. PATIENTS A total of 112 patients who had not undergone previous biliary drainage procedures and who underwent ERBD for unresectable malignant biliary obstruction. INTERVENTIONS Endoscopic sphincterotomy was performed, and covered or uncovered Wallstents were used in 56 patients and plastic stents in 56 patients. RESULTS Stent occlusion occurred in 31 patients after a mean of 278 days in the metal stent group and in 39 patients after a mean of 133 days in the plastic stent group (P = .0004). The incidence of and length of hospitalization for cholangitis were significantly lower in the metal stent group. There was no difference in the total number of drainage procedures between the 2 groups. There was no statistical difference in the mean cost of the relief of jaundice between the 2 groups (

A comparison of the Niti-D biliary uncovered stent and the uncovered Wallstent in malignant biliary obstruction

1488.77 in the metal stent group vs

Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells

1319.26 in the plastic stent group, P = .422). LIMITATIONS Nonrandomized, retrospective study. CONCLUSION Even in countries where ERCP costs are lower than those of metal stents, ERBD with metal biliary stents as the first-line treatment may offer better palliation without a significant increased cost in patients with unresectable malignant biliary obstruction.

Effects and mechanisms of the combination of suberoylanilide hydroxamic acid and bortezomib on the anticancer property of gemcitabine in pancreatic cancer.

BACKGROUND The conformability of uncovered self-expandable metal stents (SEMSs) plays an important role in maintaining stent patency. However, whether increased conformability can prolong the duration of SEMS patency remains to be proved. OBJECTIVE The aim of this study was to examine the efficacy and complication rates of the Niti-D biliary uncovered metal stent (NDS), which is more conformable than the uncovered Wallstent. DESIGN Nonrandomized, retrospective study. SETTING Tertiary-care academic medical center. PATIENTS From March 2005 to July 2007, 101 patients received an NDS (41 cases) or a Wallstent (60 cases) for malignant biliary obstruction. INTERVENTIONS SEMS placement. RESULTS Stent occlusion occurred in 11 patients (26.8%) with the NDS and 17 patients (28.3%) with the Wallstent. The median duration of stent patency tended to be longer for the NDS group (153 days) than for the Wallstent group (124 days); however, the difference was not statistically significant (P = .204). The median duration of overall survival of patients was 160 days for the NDS and 148 days for the Wallstent. The subgroup analysis showed that 27 patients had hilar obstruction (NDS 13, Wallstent 14). The median duration of stent patency was 249 days for the NDS group and 76 days for the Wallstent group; this difference was statistically significant (P = .006). The complications included pancreatitis in 3 NDS cases and 5 Wallstent cases. LIMITATION The absence of prospective randomized recruitment. CONCLUSION The results of this study showed no significant differences between the NDS and the Wallstent for the palliative endoscopic management of malignant biliary obstruction. There were no significant differences in patency, complication rates, and patient survival between the more conformable NDS and the conventional Wallstent. However, the NDS, which has good conformability, may be preferred for hilar obstruction.

A Multicenter Phase II Trial of Gemcitabine Plus Oxaliplatin in Unresectable Gallbladder Cancer

Background/Aims Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. Methods Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. Results Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. Conclusions Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.

S1298 Clinicopathological Study of Solid Pseudopapillary Neoplasm of the Pancreas

Objectives: Earlier studies that dealt with the combination therapy of gemcitabine and histone deacetylation inhibitors for pancreatic cancer revealed unsatisfactory results. The activation of nuclear factor &kgr;B (NF-&kgr;B) was referred as one of the attributable causes, and we attempted to overcome this resistance by the addition of a proteasome inhibitor. Methods: The influences of suberoylanilide hydroxamic acid (vorinostat, SAHA), a histone deacetylase inhibitor, and bortezomib, a novel selective antagonist of 26S proteasome, with or without gemcitabine on cell growth and apoptosis and the expressions of related proteins were observed in pancreatic cancer cell lines (MiaPaCa-2 and ASPC-1). The xenograft model of pancreatic cancer was used to notice effects in vivo. Results: Vorinostat and bortezomib had independent inhibitory effects and potentiated the antitumor property of gemcitabine in vitro. In the xenograft model, more augmented effects were achieved when bortezomib was combined with gemcitabine than gemcitabine alone. The down-regulation of pAkt and suppression of NF-&kgr;B activity was induced by the triple combination. Conclusions: The triple combination of vorinostat, bortezomib, and gemcitabine resulted in the strongest antitumor effects both in vitro and in vivo and pAkt and NF-&kgr;B seems to be involved in this process.

S2027 Molecular Genetic Characteristics and Prognosis of Pancreatic Cancer

Background/Aims No standard chemotherapy has been established for advanced gallbladder cancer. The authors studied the activity and tolerability of a gemcitabine and oxaliplatin (GEMOX) combination in unresectable gallbladder cancer (GBC). Methods Adult patients with pathologically confirmed unresectable GBC were prospectively recruited at three centers. No patient had received prior chemotherapy or radiotherapy. Patients received cycles of gemcitabine at 1,000 mg/m2 on day 1, followed by oxaliplatin at 100 mg/m2 on day 2, every 2 weeks. The primary study endpoint was time to progression. Results Forty patients with unresectable GBC were enrolled. The median age was 60 years (range, 38 to 79 years). All patients showed good performance status. Of the 33 analyzable patients, 12 achieved partial response (36%), 17 stable disease (52%), and four progressive disease (12%). No patient achieved a complete response. The tumor control rate was 88%. At a median follow-up of 6.8 months, the median time to progression was 5.3 months (95% confidence interval [CI], 3.7 to 6.9), and median overall survival was 6.8 months (95% CI, 6.1 to 7.5). Nine of the 40 patients (23%) experienced at least a grade-3 adverse event, but no patient experienced a grade-4 adverse event. Conclusions GEMOX combination therapy is a feasible option and is well tolerated in unresectable GBC.

Does endoscopic sphincterotomy reduce the recurrence rate of cholangitis in patients with cholangitis and suspected of a common bile duct stone not detected by ERCP

BACKGROUND: The current Consensus Guidelines for management of IPMN-Br recommend surgical resection of suspected IPMN-Br with cyst size >3 cm cysts irrespective of symptoms, and 3 cm, and 65% <3 cm in size. Among IPMN <3 cm, 72 % (28/39) had associated worrisome features. The prevalence of high-risk lesions in our study was 35% (21/60). A total of 82 % (49/60) of IPMN-Br met guidelines recommendation for surgical resection including 57% (18 of 26) of low-risk lesions and 100% (21/21) of highrisk lesions. All 11 cases of IPMN-Br that would have been recommended for conservative management were low-risk lesions. Sensitivity, specificity, positive predictive value, negative predictive value consensus guidelines for correctly defining high and low risk IPMN-Br was 100%, 28%, 43 %, 100%, respectively. CONCLUSIONS: Application of Consensus Guidelines to our patients would have recommended surgical resection to all histology proven high-risk IPMN-Br. All IPMN-Br which would have recommended for conservative management, were histologically low-risk lesions. The risk of high risk pathology among <3 cm IPMN without other worrisome features, is almost nonexistent and these lesions may selected for observation.

Clinical outcomes of early gastric cancer with lymphovascular invasion or positive vertical resection margin after endoscopic submucosal dissection

(Introduction) Heat Shock Protein 47 (HSP 47) is a collagen-specific (collagen type I-V) chaperone molecular residing in the endoplasmic reticulum (ER) and it has been thought to be a marker of fibroblasts. It was reported that HSP 47 was expressed in cancer cells as well as fibroblasts of pancreatic cancer tissues. However, its function in cancer cells has not been investigated. (Materials and Methods) In order to investigate the presence of HSP 47 and collagen type I-V in human pancreatic cancer tissues, immunohistochemistry was performed. Expression of HSP 47 in pancreatic cancer cell lines, KMP-4,-5 and -6cells, was examined by western blot. Colocalization of HSP 47 and collagens ( type I-V ) were investigated by double immunofluorostaining. To deplete the expression of HSP 47 in cells, two kinds of siRNAs were transfected. At 120 h after transfection, attached cell number were assayed by CyQuant assay kit. Cell invasion ability was assay with Matrigel coated culture insert system. Expression of MMP -2, -9, TIMP-1, and -2 and collagens were examined by QRT-PCR. (Results) In 3 of 4 pancreatic cancer tissues, cancer cells were HSP47 positive. In one of 4 tissues, HSP47 was negative. In one metastatic lymph node, cancer cells was HSP 47 negative. Among collagens, immunoreactivity for collagen V was found in pancreatic cancer cells. Immunofluorostaining in cells showed that HSP 47 colocalize with collagen type V. At 120 h after transfection of siRNA into KMP-6 cells, attached cell number was not affected by depletion of HSP47. Cell invasion assay showed that depletion of HSP47 reduce migration cells. Expression of MMP -2, -9 and TIMP-1 at the RNA levels were not affected by depletion of HSP 47, but that of collagen type V and TIMP-2 was reduced by 70% and 40% of control, respectively. (Conclusion) HSP47 colocalize with collagen type V and regulates gene expression of collagen V in pancreatic cancer cells. HSP47 depletion downregulated expression of TIMP2 of cancer cells, but not affect cell survaival. These data indicates that HSP47 may be a chaperone molecular for collagen type V and inhibit cell invasion by regulating expression of TIMP2.