Jeong Kyun Seo

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

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.

Appropriate diagnosis of biliary cystic tumors: comparison with atypical hepatic simple cysts.

Background Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are often confused with other intrahepatic cystic diseases. Aims The aims of this study were to investigate predictive factors of biliary cystic tumor (BCT) and clinical characteristic of BCAC. Methods We retrospectively reviewed preoperative diagnoses, overall characteristics and postoperative outcome of 20 BCTs and 19 cystadenoma-mimicking simple cysts that were pathologically confirmed. Results Comparing with atypical simple cysts, symptoms, left-lobe cyst, thick wall, septation, mural nodule, bile duct dilatation and an increase of serum alkaline phosphatase were associated with BCTs. However, on multivariate analysis, mural nodule, left-lobe cyst, and an increase of serum alkaline phosphatase were significantly frequent in BCTs with odds ratios of 75.5, 13.8, and 33.0, respectively. Among the 20 BCTs, seven BCACs were diagnosed. The characteristics of BCACs were mural nodule (P<0.01), intrahepatic cyst debris (P<0.01), and bile duct dilation (P=0.04). Cystic fluid analysis provided no significant differences between BCT and simple cyst. After fine needle aspiration cytology of BCTs, all except one BCAC with atypical cell showed nonspecific findings. After complete surgical excision (97.4% of patients), only one patient with BCAC had recurrence during 29 months of follow-up period. Conclusion In hepatic cysts with mural nodule, left-lobe cyst or increment of serum alkaline phosphatase seem to be indicative of BCTs in the diagnosis of suspicious hepatic cyst. Intracystic debris, bile duct dilation, and mural nodule may be suggestive clinical features of malignancy in BCTs.

Enhanced antitumor effect of combination therapy with gemcitabine and guggulsterone in pancreatic cancer.

Objectives Guggulsterone is a dietary plant sterone possessing therapeutic potential against cancers. However, the antitumor effect of this natural compound on pancreatic cancer has not been determined yet. This study was designed to investigate the therapeutic efficacy of guggulsterone in pancreatic cancer. Methods In this study, we examined the effect of guggulsterone on cell proliferation and apoptosis in pancreatic cancer cell lines, and then, we investigated the mechanisms responsible for the effect of guggulsterone. Finally, we investigated whether the combination of guggulsterone and gemcitabine had an additional therapeutic effect compared to gemcitabine single regimen in pancreatic cancer cell lines (in vitro) and in a xenograft model using nude mice (in vivo). Results In vitro, the combination treatment resulted in more growth inhibition and apoptosis through the down-regulation of nuclear factor &kgr;B activity with suppression of Akt and BcL-2 and through the activation of c-Jun NH2-terminal kinase and Bax in pancreatic cancer cell lines. In vivo, the combination therapy augmented tumor growth inhibition through the same mechanisms in tumor tissue. Conclusions The combination of guggulsterone to gemcitabine enhanced antitumor efficacy through apoptosis induction by suppressing Akt and nuclear factor &kgr;B activity and by modulating apoptosis-related protein expression in pancreatic cancer.

S1298 Clinicopathological Study of Solid Pseudopapillary Neoplasm of the Pancreas

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.

S2027 Molecular Genetic Characteristics and Prognosis of Pancreatic Cancer

(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.