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Background/aims: We evaluated the efficacy and cost-effectiveness of endoscopic papillary large balloon dilation (EPLBD) for large common bile duct (CBD) stone removal compared with endoscopic sphincterotomy (EST)., Methods: A total of 1,580 patients who underwent endoscopic CBD stone extraction between January 2001 and July 2010 were reviewed. The following inclusion criteria were applied: choledocholithiasis treated by EPLBD with minor EST or EST with mechanical lithotripsy; and follow-up >9 months after treatment., Results: Forty-nine patients with EPLBD and 41 with EST were compared. There was no significant difference in the complication rates and stone recurrence rates between the two groups. However, significantly more endoscopic retrograde cholangiopancreatography (ERCP) sessions were required in the EST group to achieve the complete removal of stones (1.7 times vs 1.3 times; p=0.03). The mean cost required for complete stone removal per patient was significantly higher in the EST group compared to the EPLBD group (USD $1,644 vs $1,225, respectively; p=0.04). Dilated CBD was the only significant factor associated with recurrent biliary stones (relative risk, 1.09; 95% confidence interval, 1.02 to 1.17; p=0.02)., Conclusions: EPLBD is the better treatment (compared to EST) for removing large CBD stones because EPLBD requires fewer ERCP sessions and is less expensive.

Pancreatic cancer may present as a peri-arterial soft tissue cuff (PSTC) around the superior mesenteric artery or celiac axis without an identifiable pancreatic mass. We evaluated the diagnostic yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with a PSTC without definite pancreas involvement and those with a typical pancreatic mass. The patients who underwent EUS-FNA of a PSTC without pancreatic involvement were prospectively enrolled. The patients who underwent EUS-FNA for a pancreatic mass were recruited as a control group. A total of 224 patients underwent 247 EUS-FNAs. Among the 13 patients with a PSTC, 11 were positive for malignancy as determined by EUS-FNA, with 5 diagnosed after the first session and 6 after the second session. The diagnostic yield of PSTCs by EUS-FNA was significantly lower than that for typical pancreatic masses (65% vs. 87%, p = 0.02). An on-site cytopathologist and repeated EUS-FNA are recommended to improve the diagnostic accuracy of this disease entity., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the success rates, procedural time and adverse event rates of the modified methods in endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS)., Methods: Twenty-eight patients in a prospective case series who underwent EUS-HGS (phase I). Forty-six patients in a matched case-control study (phase II). The simplified technique for fistula dilation was the primary use of a 4 mm balloon catheter with a stainless steel stylet. The stent deployment was modified by deploying the metal stent inside a bile duct (half of the stent) under EUS and fluoroscopic guidance and gently pulling the echoendoscope after full deployment of the stent inside the echoendoscope channel (remaining portion of the stent) under fluoroscopic guidance. This cohort was compared with a matched historical cohort., Results: In phase I, the technical and clinical success with the modified method was 96% (27/28) and 89% (24/27 as per-protocol analysis). The overall adverse event rate was 7%. In phase II, there was no difference in technical and clinical success, stent patency and overall adverse events in each group. However, the procedural time (15.3 ± 5.2 min vs 22.3 ± 6.0 min, P < 0.001) and early adverse events (0% vs 26%, P = 0.02) were statistically improved in case cohort compared with control cohort., Conclusion: Compared with the conventional EUS-HGS technique, the procedural time was shorter and early adverse events were less frequent with our simplified and modified technique.

Background and Aims: Endoscopic ultrasound-guided fine needle aspiration (EUSFNA) is a safe and effective technique for tissue diagnosis in patients with pancreatic or peripancreatic solid masses. However, the procedure is difficult to accomplish without an on-site cytopathologist. The aims of this study were to examine the outcomes of EUS-FNA for pancreatic or peripancreatic solid masses without an on-site cytopathologist and to determine the factors associated with diagnostic accuracy., Methods: From December 2005 to November 2011, 230 patients with pancreatic or peripancreatic solid masses had 240 EUS-FNAs performed without an on-site cytopathologist. The medical records of the 230 patients from a single tertiary center were retrospectively reviewed., Results: Among the 230 patients who underwent EUS-FNA, 201 patients (88%) had malignancy, which included 171 adenocarcinomas (74%). Assuming that the cytopathological malignancy was positive or suspicious for malignant cells with cytology, the accuracy without an on-site cytopathologist was 67.9%. However, the accuracy increased from 40.0% for the first 30 cases (from 2006 to 2008) to 83.3% for the last 30 cases (in 2011) and was constantly over 80.0% starting from the sixth octile onwards for every 30 cases (in 2011). From the analysis of factors associated with the accuracy of the diagnosis using logistic regression analysis, the number of needle passes and the experience of endosonographer were statistically associated with the diagnostic accuracy., Conclusions: In the case of performing EUS-FNA for pancreatic or peripancreatic solid masses without an on-site cytopathologist, the experience of the endosonographer, and the number of needle passes were associated with the diagnostic accuracy.

Hilar cholangiocarcinoma is a tumor of the extrahepatic bile duct involving the left main hepatic duct, the right main hepatic duct, or their confluence. Biliary drainage in hilar cholangiocarcinoma is sometimes clinically challenging because of complexities associated with the level of biliary obstruction. This may result in some adverse events, especially acute cholangitis. Hence the decision on the indication and methods of biliary drainage in patients with hilar cholangiocarcinoma should be carefully evaluated. This review focuses on the optimal method and duration of preoperative biliary drainage (PBD) in resectable hilar cholangiocarcinoma. Under certain special indications such as right lobectomy for Bismuth type IIIA or IV hilar cholangiocarcinoma, or preoperative portal vein embolization with chemoradiation therapy, PBD should be strongly recommended. Generally, selective biliary drainage is enough before surgery, however, in the cases of development of cholangitis after unilateral drainage or slow resolving hyperbilirubinemia, total biliary drainage may be considered. Although the optimal preoperative bilirubin level is still a matter of debate, the shortest possible duration of PBD is recommended. Endoscopic nasobiliary drainage seems to be the most appropriate method of PBD in terms of minimizing the risks of tract seeding and inflammatory reactions.

Background: Life expectancy of pancreatic ductal adenocarcinoma (PDAC) patients is usually short and selection of the most appropriate treatment is crucial. The aim of this study was to investigate the usefulness of serum CA 19-9 as a surrogate marker under no impress excluding other factors affecting CA 19-9 level other than tumor itself., Methods: We recruited 1,446 patients with PDACs and patients with Lewis antigen both negative or obstructive jaundice were excluded to eliminate the false effects on CA 19-9 level. The clinicopathologic factors were reviewed including initial and post-treatment CA 19-9, and statistical analysis was done to evaluate the association of clinicopathologic factors with overall survival (OS)., Results: The total of 944 patients was enrolled, and205 patients (22%) underwent operation with curative intention and 541 patients (57%) received chemotherapy and/or radiotherapy. The median CA 19-9 levels of initial and post-treatment were 670 IU/ml and 147 IU/ml respectively. The prognostic factors affecting OS were performance status, AJCC stage and post-treatment CA 19-9 level in multivariate analysis. Subgroup analysis was done for the patients who underwent R0 and R1 resection, and patients with normalized post-operative CA 19-9 (≤37 IU/mL) had significantly longer OS and DFS regardless of initial CA 19-9 level; 32 vs. 18 months, P<0.001, 16 vs. 9 months, P = 0.004 respectively., Conclusions: Post-treatment CA 19-9 and normalized post-operative CA 19-9 (R0 and R1 resected tumors) were independent factors associated with OS and DFS, however, initial CA 19-9 level was not statistically significant in multivariate analysis.

Aim: To identify clinical and pathological differences between serum immunoglobulin G4 (IgG4)-positive (SIP) and IgG4-negative (SIN) type 1 autoimmune pancreatitis (AIP) in South Korea., Methods: AIP was diagnosed by the international consensus diagnostic criteria. The medical records and pathology were retrospectively reviewed and IgG4-positive cells were counted in a high power field (HPF). Type I AIP was defined as a high serum level of IgG4 or histological finding. SIN type 1 AIP was defined as a histological evidence of type 1 AIP and a normal serum IgG4 level. The clinical and pathological findings were compared between the two groups. The analysis was performed using Student's t test, Fischer's exact test and Mann-Whitney's U test. A P value of < 0.05 was considered statistically significant. As repeated comparison was made, P values of less than 5% (P < 0.05) were considered significant., Results: Twenty five patients with definite type 1 AIP (19 histologically and six serologically diagnosed cases) were enrolled. The mean tissue IgG4 concentrations were significantly higher in SIP than SIN group (40 cells per HPF vs 18 cells per HPF, P = 0.02). Among eight SIN patients, the tissue IgG4 concentrations were less than 15 cells per HPF in most of cases, except one. The sensitivity of serum IgG4 was 68% (17 SIP and eight SIN AIP). Other organ involvement was more frequently associated with SIP than SIN AIP (59% vs 26%, P = 0.016). However, the relapse rate and diffuse swelling of the pancreas were not associated with serum IgG4 level. The concentrations of IgG4-positive cells per HPF were higher in SIP than SIN AIP (40 vs 18, P = 0.02)., Conclusion: The sensitivity of serum IgG4 was 68% in type 1 AIP. High serum IgG4 level was associated with other organ involvement and tissue IgG4 concentration but did not affect the relapse rate in type 1 AIP.

Chromogranin A (CgA) is widely used as an immunohistochemical marker of neuroendocrine neoplasms and has been measurable in plasma of patients. We assessed the clinical role of plasma CgA in diagnosing pancreatic neuroendocrine neoplasm (PNEN). CgA was checked in 44 patients with pancreatic mass who underwent surgical resection from 2009 through 2011. The cutoff value for diagnosing PNEN and the relationships between CgA and clinicopathologic variables were analyzed. Twenty-six patients were PNENs and 18 patients were other pancreatic disorders. ROC analysis showed a cutoff of 60.7 ng/mL with 77% sensitivity and 56% specificity, and the area under the curve (AUC) was 0.679. Among PNEN group, the sensitivity and specificity of diagnosing metastasis were 100% and 90% respectively when CgA cutoff was 156.5 ng/mL. The AUC was 0.958. High Ki-67 index (160.8 vs 62.1 ng/mL, P = 0.001) and mitotic count (173.5 vs 74.6 ng/mL, P = 0.044) were significantly correlated with plasma CgA, but the tumor size was not. In conclusion, CgA has a little value in diagnosing PNEN. However, the high level of CgA (more than 156.5 ng/mL) can predict the metastasis. Also, plasma CgA level correlates with Ki-67 index and mitotic count which represents prognosis of PNENs.

Background/aim: Overexpression of microRNA-21 (miR-21) indicates chemoresistance in pancreatic cancer. We evaluated the change of chemosensitivity to gemcitabine through the down-regulation of miR-21 in human pancreatic cancer cells (Panc-1)., Materials and Methods: The efficacy of indole-3-carbinol (I3C) in suppressing miR-21 expression and its anticancer effect in combination with gemcitabine were investigated., Results: Down-regulation of miR-21 by I3C was positively-correlated in a time- and dose-dependent manner. I3C and gemcitabine combination therapy increased cytotoxicity in Panc-1 cells. Transfection of miR-21 mimic abrogated I3C-induced sensitivity to gemcitabine. DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays showed that pre-treatment with I3C enhanced apoptosis and this effect was attenuated by miR-21 transfection. The expression of programmed cell death-4 (PDCD4) was increased by I3C and reduced by miR-21 transfection., Conclusion: I3C would be effective for enhancing sensitivity of pancreatic cancer cells to gemcitabine via down-regulation of miR-21. Such enhanced chemosensitivity might be explained by the increased expression of PDCD4, which is a downstream target which miR-21 negatively regulates.

Biliary cast syndrome (BCS) is an uncommon complication of orthotopic liver transplantation (OLT), so the long-term treatment outcomes of BCS are not well characterized. The purpose of this study was to evaluate the long-term treatment outcomes and prognosis of BCS after OLT. The medical records of 1097 patients who underwent OLT from January 2000 to September 2009 were reviewed. Those patients who had BCS were evaluated with respect to the treatment method, overall survival and relapse rates, and relapse-free time. Twenty-three patients (2.1%) were diagnosed with BCS with a mean overall follow-up of 59.9 months. All the patients had benign biliary strictures and repeatedly underwent balloon dilatation by an endoscopic or percutaneous approach. Primary biliary cast removal was tried with the endoscopic method from 11 patients and with the percutaneous methods from 12 patients. Casts were completely removed by repetitive procedures in 22 patients, but BCS relapsed in 12 patients (55%). Persistent biliary strictures were significantly associated with the BCS relapse frequency (0.37 versus 0.05 times per year, P = 0.006). The 5-year overall survival rate for BCS patients after OLT was 87%. The risk factors associated with early relapse were female sex, hepatic artery stenosis, and acute cellular rejection. In a multivariate analysis, acute cellular rejection was the only significant risk factor for early relapse (hazard ratio = 11.1, 95% confidence interval = 1.9-63.2, P = 0.007). In conclusion, patients with BCS frequently relapse, and multiple interventions and the treatment of biliary strictures are needed. Acute cellular rejection after OLT is a significant risk factor for early relapse., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Background: Perforation after endoscopic retrograde cholangiopancreatography (ERCP) is a rare but severe complication. The purpose of this study was to assess the clinical outcomes with perforations after ERCP from a large number of cases., Methods: Among 11,048 patients who underwent ERCP during 10 years, medical records from 68 patients (0.62 %) who experienced post-ERCP perforation with radiologic, endoscopic, or surgical evidence were retrospectively reviewed. We assessed the clinical outcomes of patients and analyzed the factors associated with poor outcomes, which were defined as mortality, prolonged hospital stay due to complications, or loss of chance of cure in the case of cancer., Results: Twenty-nine patients were male, and the median age was 65.0 years. Therapeutic ERCP was performed in 52 cases (77 %). Common mechanisms of perforation were endoscopic sphincterotomy (37 %), catheter or guidewire (34 %), and endoscope (19 %). In contrast to 9 patients who underwent emergent operation, 59 patients (87 %) were conservatively treated. In 44 patients, perforation was detected during the procedure; however, detection after 24 h or permitted oral intake before detection occurred in 18 cases (27 %). Although 58 patients recovered without poor outcomes, 10 patients (15 %) experienced poor outcomes, which consisted of mortality (n = 4), loss of chance of cure (n = 2), and prolonged hospital stay without surgery more than 1 month due to complications (n = 4). By multiple logistic regression analysis, perforation by endoscope and rebound tenderness was statistically associated with poor outcomes (odds ratio: 13.7 and 7.3, respectively)., Conclusions: Most patients fully recovered from perforation; however, some patients experienced grave outcomes, including mortality. Perforation by endoscope and rebound tenderness was significantly associated with poor outcomes.

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 ($1488.77 in the metal stent group vs $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.

Background and Objective: Endoscopic or percutaneous biliary drainage with self-expandable metallic stents (SEMS) is widely used for the palliation of cholestasis in patients with advanced hilar cholangiocarcinoma. However, little is known about which is the better option in patients with advanced hilar cholangiocarcinoma. We compared the clinical outcomes of these 2 methods of biliary decompression in these patients., Design and Setting: Multicenter retrospective study., Patients: A total of 85 patients with newly diagnosed advanced hilar cholangiocarcinoma (Bismuth III or Bismuth IV) and who did not receive an operation, chemotherapy, or radiotherapy were retrospectively reviewed. Forty-four of the 85 received endoscopic SEMS and 41 received percutaneous SEMS., Interventions: Endoscopic SEMS or percutaneous SEMS., Main Outcome Measurements and Results: Baseline characteristics were similar in the 2 groups, but the rate of successful biliary decompression was significantly higher in the percutaneous SEMS group than in the endoscopic SEMS group (92.7% vs 77.3%, respectively, P= .049). Overall rates of procedure-related complications were similar for the 2 groups, but 1 death (from biliary sepsis) occurred in the endoscopic SEMS group. Median survival of patients in whom biliary drainage was successful initially, regardless of which procedure was performed, was much longer than that of patients who had failed biliary drainage (8.7 months vs 1.8 months, respectively, P< .001). Once successful biliary decompression had been achieved, median survival and stent patency duration were similar in the 2 study groups., Limitation: Retrospective study., Conclusions: Percutaneous SEMS may be chosen for initial biliary drainage in patients with advanced type III or IV hilar cholangiocarcinoma, given higher initial success rate and low level of procedure-related cholangitis.

Background/aims: Since pancreatic endocrine tumors (PET) are rare and heterogeneous diseases, their survival and prognosis are not well known. Due to recent advances in CT/MRI technology, incidentalomas of the pancreas are detected with increasing frequency. This study presents results of clinical manifestations of PET and predictive factors associated with survival., Methods: From year 1990 through 2006, medical records of 98 patients (56 men, 42 women) who were diagnosed as PET pathologically at Seoul National University Hospital were reviewed retrospectively., Results: Ages ranged from 17 to 76 years (mean 51.6+/-1.3 years) with a mean follow-up of 3.6+/-0.4 years (range 0-10.1 years). Overall 5-year survival rate was 68.1%, and 5-year survival rate of the patients who had distant metastases at initial diagnosis was 43.9%. Functioning tumors [hazard ratio (HR) 0.229, 95% confidence interval (CI) 0.056-0.943, p=0.041] and lymph node or liver metastases (HR 5.537, 95% CI 2.106-14.555, p<0.001) were the significant prognostic factors associated with survival rate. However, tumor size and pathology showed no significant association with survival., Conclusions: Because small and pathologically benign nature do not predict good prognosis in PET, aggressive treatment such as curative resection would be considered initially even in the case of incidental PET.

The pharmacokinetic and tissue distribution changes of adriamycin (ADM) and adriamycinol were investigated after intravenous (i.v.) administration of ADM, 16 mg/kg, to the control and the uranyl nitrate-induced acute renal failure (U-ARF) rats. After 1 min i.v. infusion of ADM, apparent 'constant' plasma levels of ADM were maintained from 2 to 12 hr in the U-ARF rats, whereas the levels were detected for only up to 3 hr in the control rats. Adriamycinol was detected in plasma for up to 180 min for the U-ARF rats, but, it was detected for only up to 1 min for the control rats with significantly higher levels in the U-ARF rats. The mean amount of both ADM and adriamycinol excreted in urine were significantly smaller in the U-ARF rats than those in the control rats due to the decreased kidney function in the U-ARF rats. In tissue distribution studies, the amount of ADM obtained from the heart, liver, spleen, small intestine, large intestine, and fat were significantly higher in the U-ARF rats than those in the control rats. The tissue to plasma ratios of the liver, spleen, large intestine, and fat also increased significantly in the U-ARF rats than those in the control rats. The amount of adriamycinol obtained from the heart, spleen, and liver were significantly higher in the U-ARF rats. All 7 control rats survived over 48 hr whereas 6 out of 8 U-ARF rats died between 36-48 hr after i.v. administration of ADM, suggesting that the i.v. doses of ADM in acute renal failure patients may need modification if the present rat data could be extrapolated to humans.

The pharmacokinetic and tissue distribution changes of adriamycin (ADM) were investigated after intravenous (i.v.) administration of ADM, 16 mg/kg, to the control rats and alloxan-induced diabetes mellitus rats (AIDRs). After 1 min i.v. infusion of ADM, apparent 'constant' plasma levels of ADM were maintained from 2 to 12 h in the AIDRs, whereas the levels were detected only up to 3 h in the control rats. Adriamycinol was detected only up to 1 and 5 min for the control rats and AIDRs, respectively, with significantly higher levels in the AIDRs. In tissue distribution studies, the amount of ADM obtained from the heart, lung, stomach, liver, small intestine, large intestine, fat, and lymph nodes were significantly higher in the AIDRs than that in the control rats. The tissue to plasma ratios of the liver, fat, and muscle also increased significantly in the AIDRs than those in the control rats. The amount of adriamycinol obtained from the lung, kidney, and liver was significantly higher in the AIDRs. All 7 control rats survived longer than 48 h, however 7 out of 9 AIDRs died between 36-48 h after i.v. administration of ADM, suggesting that the i.v. doses. of ADM in diabetes mellitus patients may need to be modified if the present rat data could be extrapolated to human.

An experimental program aimed at measuring critical channel parameters of atmospheric optical communication channels under low-visibility weather conditions is described. Multipath and angular spectrum measurements made under a variety of weather conditions over a 13.6-km line-of-sight propagation path are reported. The latter measurements are used to examine the dependence of scattered plus unscattered optical transmission on optical thickness.