Joo Kyung Park

Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer

Background Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy. Methodology/Principal Findings Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166–0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280–0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells. Conclusions Significance Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC.

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.

Survival and prognosis of invasive intraductal papillary mucinous neoplasms of the pancreas: comparison with pancreatic ductal adenocarcinoma.

Objectives: Invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is often considered to have a better prognosis than pancreatic ductal adenocarcinoma. The aim of this study was to evaluate and compare the prognosis and clinicopathologic features between 2 groups. Methods: Clinicopathologic features and long-term outcome of 32 patients with invasive IPMN were retrospectively evaluated and compared with those of 332 patients with pancreatic ductal adenocarcinoma. Results: Asymptomatic patients were more frequently observed in the group of invasive IPMN than ductal adenocarcinoma (28% vs 11%, P = 0.013). The distribution of stages of invasive IPMN was as follows: stage I (n = 10, 31%), II (n = 8, 25%), III (n = 3, 9%), and IV (n = 11, 34%). Among 19 patients who underwent resection for invasive IPMN, 10 (53%), 1 (5%), 1 (5%), and 2 (11%) had T1 stage tumors and tumor with lymph node metastasis, lymphatic, and perineural invasions, respectively, which were significantly infrequently observed compared with those with ductal adenocarcinoma. The 5-year survival rate of invasive IPMN was 33.9% compared with 9% of ductal adenocarcinoma (P = 0.011). The difference in the mean survival rates between invasive IPMN and ductal adenocarcinoma in patients without metastasis was also significant but not in patients with metastasis. During the median follow-up period of 18.4 months, 3 patients (16%) had a recurrence after resection for invasive IPMN. Conclusions: Both the less aggressive pathological factors concerned with tumor invasiveness and early diagnosis of invasive IPMN contribute to higher survival rates of invasive IPMN than ductal adenocarcinoma. However, the prognosis of metastatic invasive IPMN is as poor as that of ductal adenocarcinoma.

The efficacy of nonsurgical treatment of infected pancreatic necrosis.

Objectives: We conducted this study to evaluate the efficacy of nonsurgical treatment for patients with infected pancreatic necrosis (IPN). Methods: Among 224 patients with acute pancreatitis from 2000 to 2004, there were 31 patients diagnosed as having IPN complication. The diagnostic criteria for IPN were either a positive culture or free gas in the pancreas of patients with acute pancreatic necrosis. Nonsurgical management including percutaneous drainage or endoscopic drainage (ED) followed by vigorous irrigation was initially attempted in all patients. Surgery was planned only when there was no clinical improvement after the initial nonsurgical treatment. Results: Percutaneous drainage or ED was performed in 18 and 5 patients, respectively. Eight patients received antibiotics only. Four patients (12.9%) (3 from percutaneous drainage group and 1 from ED group) required surgery. Sepsis or fistula developed in 32% and 6% of patients, respectively, and was managed successfully. One patient (3.2%) died as a result of rapidly progressing multiorgan failure. The mean duration of hospitalization was 37 days. During the follow-up period, 7 patients were readmitted because of fever; they were managed by reposition of the drainage tube. Conclusions: Intensive nonsurgical treatment is very effective and safe and should be considered as an initial treatment modality for patients with IPN.

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 (

Survival and prognostic factors of unresectable pancreatic cancer.

1488.77 in the metal stent group vs

Preventive effects of ulinastatin on post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a prospective, randomized, placebo-controlled trial.

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.

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

Goals The aim of this study was to evaluate the prognostic significance of clinical and laboratory variables, and to investigate survival benefits for different treatment modalities in unresectable pancreatic cancer. Background The majority of pancreatic cancers are found to be unresectable. Therefore, estimations of prognosis and decisions of treatment modalities are important in optimizing the various aspects of care. Study Three hundred and forty unresectable locally advanced, or metastatic pancreatic cancer patients were enrolled from January 1998 to January 2005 at the Seoul National University Hospital. Results One hundred and five patients received chemotherapy only and 59 patients received concurrent chemoradiotherapy (CCRT). Age, performance status, tumor location, initial CA 19-9 level, American Joint Committee on Cancer stage, and treatment modality (supportive care only, chemotherapy, vs. CCRT) were found to have prognostic significance for overall survival (OS) by univariate analysis, whereas initial CA 19-9 level, stage, and treatment modality were identified as independent prognostic factors by multivariate analysis. In subgroup analysis, stage III patients treated by CCRT (median OS, 10.4 mo) or chemotherapy alone (11.3 mo) showed survival benefit over supportive care (6.4 mo), and stage IV patients treated by chemotherapy alone (6.4 mo) showed survival benefit over supportive care (3.1 mo). Conclusions Initial CA 19-9, American Joint Committee on Cancer stage, and treatment modality were independent prognostic factors of OS, and the patients who received chemotherapy or CCRT showed better survival than those who received supportive care only.

Feasibility of endoscopic papillectomy in early stage ampulla of Vater cancer

Objectives: Previous studies have shown that ulinastatin may be effective at preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, routine administration of ulinastatin is unlikely to be cost-effective. So the aim of this prospective study was to evaluate the effectiveness of low-dose ulinastatin at preventing pancreatitis in patients at high risk of post-ERCP pancreatitis. Methods: A total of 227 patients (mean age, 63 years; 54% men) were randomized to receive placebo (n = 108) or active drug (n = 119) immediately after ERCP and received active drug (100,000 U of ulinastatin) or placebo. Occurrence of post-ERCP pancreatitis and hyperamylasemia were compared between the 2 groups. Results: The overall incidence of pancreatitis was 6.2%, and no significant differences were observed between placebo- and ulinastatin-treated patients in terms of the frequencies of pancreatitis (5.6% vs 6.7%), abdominal pain, or hyperamylasemia. Pancreatic duct acinarization, papillectomy of ampulla of Vater adenoma, difficult cannulation, and female sex were identified as risk factors for pancreatitis in univariate analysis. Conclusions: Low-dose prophylactic treatment with ulinastatin immediately after ERCP did not show a beneficial influence on the incidence of post-ERCP pancreatitis and hyperamylasemia in high-risk patients.

Optimal interventional treatment and long-term outcomes for biliary stricture after liver transplantation.

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.