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Background and Aims ERCP-guided biliary drainage (ERCP-BD) is a criterion standard treatment for malignant biliary obstruction when curative surgery is not an option. Alternative methods such as percutaneous transhepatic biliary drainage would significantly lower the quality of life. EUS-guided biliary drainage (EUS-BD) has been developed and performed by experienced endoscopists. Therefore, the aims of this study were to evaluate the efficacy and safety of EUS-BD compared with ERCP in malignant biliary obstruction. Methods The prospective randomized controlled study was conducted, and 30 patients were enrolled: 15 for each EUS-BD and ERCP-BD arms. The technical success, procedural time, clinical success, and adverse events were evaluated. Results Thirty patients had extrahepatic malignant biliary tract obstruction (19 men, 11 women). Twenty-seven patients had unresectable pancreatic ductal adenocarcinomas, 1 patient had distal common bile duct cancer, and 2 patients had metastatic malignant lymphadenopathy. There were no significant differences both in terms of technical success rate and clinical success rate (100% vs 93% and 93% vs 100% in ERCP-BD vs EUS-BD, respectively; P = 1.00, P = 1.00). Four patients (31%) had tumor ingrowth–caused stent dysfunction in the ERCP-BD group, whereas 2 patients had food impaction and 2 patients had stent migration in the EUS-BD group. No significant procedure-related adverse events occurred in either group. Conclusions This prospective randomized controlled study suggests that EUS-BD has similar safety to ERCP-BD. EUS-BD was not superior to ERCP-BD in terms of relief of malignant biliary obstruction. EUS-BD may have fewer cases of tumor ingrowth but may also have more cases of food impaction or stent migration. (Clinical trial registration number: NCT01421836.)

Angiogenesis occurs in response to tissue ischemia and wound healing, and contributes to the pathogenesis of a variety of diseases, such as benign and malignant neoplasia. Several studies have measured bone marrow microvessel density (MVD) in MDS patients and acute myeloid leukemia (AML) patients transformed from MDS, and MVD was higher in MDS patients than controls, but was lower than in AML patients. Vascular endothelial growth factor (VEGF) is expressed in bone marrow blast cells, and an autocrine VEGF signaling mechanism has been established in MDS. Increased bone marrow angiogenesis and VEGF concentrations are adverse prognostic features in all of these patients. In this study, 69 patients were treated in two groups: hypomethylating agents or supportive care with oxymetholone±pyridoxine. We evaluated the MVD and VEGF expression of paraffin-embedded bone marrow samples from patients. We also investigated the relationship between angiogenesis-related biomarkers including MVD, VEGF expression, and clinical factors. The patient median age was 65 years, and the median follow-up duration was 28 months. MVD assessment among subtypes of WHO MDS classification showed that the MVD of RCUD was significantly lower than in other types (p=0.02). However, there was no significant difference in VEGF expression according to the subtype of MDS. Although MVD and VEGF expression did not differ between risk groups based on the IPSS, the low risk group tended to have lower expression of angiogenesis-related biomarkers. MDS patients receiving hypomethylating agents had significantly lower MVD expression in responders than in non-responders (6.13±3.38 vs. 9.89±2.10, respectively, p=0.039). In a consecutive evaluation at the time of diagnosis and 3 months after the initial treatment, the group with a decrease or no change of MVD had a higher response rate compared to that in the group with an increase of MVD (92.9% vs. 58.8%, respectively, p=0.045). Adverse prognostic factors included older age, MDS type other than RCUD, a higher IPSS risk group, and abnormal cytogenetics. Although angiogenesis-related markers did not demonstrate any significant prognostic association with survival, MVD (≥10n/mm2) and a strong expression of VEGF seemed to be associated with lower survival rate. These data suggested that the MVD value might be helpful in predicting responsiveness to treatment, especially in MDS patients treated with hypomethylating agents. Although angiogenesis-related markers including VEGF did not demonstrate a significant association with survival outcomes, we observed that high MVD and strong VEGF expression seemed to be associated with lower survival rate. Therefore, biologic markers related to angiogenesis might have a potential as prognostic factors for MDS patients.

Summary Background/goals Bile is normally sterile, but the presence of organisms in the bile does not necessarily imply an active infection. We wonder what the significance of bile culture results on antibiotics choice in cholangitis with negative blood culture. The aim of this study was to compare organisms cultured from bile with those from blood in bacteremic biliary tract infection and to evaluate factors associated with concordance between blood and bile isolates. Methods Between 2000 and 2010, 266 positive blood cultures with concomitant bile culture in bacteremic biliary tract infection were identified. Follow-up bile specimens obtained after negative conversion of blood culture and clinical recovery from acute infection were collected for supplementary analysis. Results Of the 266 events, 258 showed positive bile culture. Of the 258 bile samples, 80 yielded the same organisms with blood, 129 showed partial agreement and 49 yielded completely different organisms with blood. Only the number of organism was found to be independently associated with concordance. Of the 529 organisms isolated from bile, 227 were found in blood and gram-negative organisms showed higher rate of coincidence than gram-positive organisms. Of the 84 follow-up bile sample, 94% showed persistent positive culture and higher rate of antibiotics resistance than initial bile culture. Conclusions More than half of the organisms isolated from bile, especially gram-positive organisms, are not likely to be true pathogens. But single organism cultured from bile has clinical significance. Routine follow-up bile culture in patients showing clinical improvement is not necessary.

Laser-assisted atom probe tomography has opened the way to three-dimensional visualization of nanostructures. However, many questions related to the laser–matter interaction remain unresolved. We demonstrate that the interface reaction can be activated by laser-assisted field evaporation and affects the quantification of the interfacial composition. At a vertical interface between Si and SiO2, a SiO2 molecule tends to combine with a Si atom and evaporate as a SiO molecule, reducing the evaporation field. The features of the reaction depend on the direction of the laser illumination and the inner structure of tip. A high concentration of SiO is observed at a vertical interface between Si and SiO2 when the Si column is positioned at the center of the tip, whereas no significant SiO is detected when the SiO2 layer is at the center. The difference in the interfacial compositions of two samples was due to preferential evaporation of the Si layer. This was explained using transmission electron microscopy observations before and after atom probe experiments.

Summary Background and objective An animal model for bile duct stenosis using intraductal thermal injury has not yet been established. The aims of the current study were to develop biliary stenosis in a swine model by inducing intraductal thermal injury using a heat probe or radiofrequency ablation electrode and to investigate an effective and safe energy dose. Methods Intraluminal thermal injury was applied to the common bile duct with a heat probe in three swines and a radiofrequency ablation electrode in the other three swines by either endoscopic retrograde cholangiography or open laparotomy. Cholangiography and histologic evaluation of common bile duct were taken 2 weeks after thermal injury. Results Thermal injury with a heat probe at 25 J for 40 seconds produced a stricture in all three animals. Application of a radiofrequency ablation electrode produced a stricture in two of three animals. An energy dose of 40 W at 80 °C for 30 seconds produced biliary stenosis without any complications initially and 2 weeks after thermal injury. Conclusions The application of a heat probe and a radiofrequency ablation electrode for intraductal thermal injury resulted in a reproducible animal model of biliary stenosis.

The goal of this study was to identify clinicoradiologic characteristics to distinguish metastatic cancer to the pancreas (MCP) from double primary pancreatic cancer (DPPC).From 2000 to 2011, we retrospectively identified MCP and DPPC patients among patients with histories of other primary malignancies.A total of 94 patients with histories of other primary malignancies were histologically confirmed to have pancreatic cancer. Among them, 34 patients had MCP and 60 patients had DPPC, which were ductal adenocarcinomas. The kidney was the most common primary cancer site that metastasized to the pancreas (12, 35.3%). In the DPPC group, the stomach was the most common primary cancer site (11, 18.3%). There were 21 patients (61.8%) with metachronous pancreatic cancer in the MCP group and 29 (48.3%) in the DPPC group (P=0.210). Among the metachronous pancreatic cancer patients, the disease-free interval was 88.3 months in the MCP group, and 49.6 months in the DPPC group (P=0.062). The number of the patients who showed elevated CA 19-9 levels was higher in the DPPC group than in the MCP group (39 (65%) vs. 9 (26.5%); P=0.001). Total bilirubin (P=0.006) and fasting plasma glucose (P=0.050) were also higher in the DPPC group. The numbers of patients who showed pancreatic duct dilatation (P=0.002) and pancreatic atrophy (P=0.008) on radiographs were meaningfully higher in the DPPC group than in the MCP group. On the other hand, the numbers of patients who showed well demarcated tumor margin (P0.000), tumor necrosis (P=0.002), enhancement (P=0.005) and distant metastasis (P=0.028) were significantly higher in the MCP group than in the DPPC group. We evaluated differences in survival between the two groups. The median survival time in the MCP group (55 months) was significantly longer than that in the DPPC group (20 months).Other than elevated levels of CA 19-9, total bilirubin and fasting glucose, radiologic findings were the most reliable factors for distinguishing the MCP from the DPPC.

Background/Aims The authors conducted a hospital-based case–control study to evaluate the role of Clonorchis sinensis infection as a risk factor for the development of cholangiocarcinoma (CC), including extrahepatic CC, in Korea. Methods Cases of 185 patients with CC (intrahepatic, 51; hilar, 53; and distal extrahepatic, 81) and matched controls underwent stool microscopy, pathological examinations, serologic test for C. sinensis using ELISA, skin test for C. sinensis, radiologic examinations, and interview concerning history of eating raw freshwater fish. Results Radiologic evidence of C. sinensis, history of eating raw freshwater fish, and positive serologic result for C. sinensis were found to be related to an increased risk of CC, with the odds ratios (OR)=8.615 (95% confidence interval [CI]=5.045–16.062), OR=2.385 (95% CI=1.527–3.832), and OR=2.272 (95% CI=1.147–4.811), respectively. The risk factors for distal extrahepatic CC were radiologic evidence of C. sinensis (OR=6.571; 95% CI=3.170–15.943) and history of eating raw freshwater fish (OR=2.6; 95% CI=1.294–5.66). Conclusions Radiologic evidence of C. sinensis, history of eating raw freshwater fish and positive serologic result for C. sinensis were significantly associated with CC, including extrahepatic CC.

Background Although endoscopic resection can provide a wide tumor resection with a negative resection margin, it is not yet recommended as a curative therapy for ampulla of Vater cancer. Methods To investigate the microinvasion rate and the diagnostic accuracy of endoscopic biopsy to properly judge the safety of endoscopic resection for ampulla of Vater cancer. Design Single-center, retrospective study. Setting Academic medical center. Patients One hundred fifty-nine patients who were finally diagnosed with ampulla of Vater cancer after curative surgical resection. Interventions We surveyed the pathologic concordance rate of endoscopic biopsy and the surgical pathology. For the 36 early stage (Tis or T1) cancers, we surveyed the presence of microlymphovascular invasion, gross appearance (intra-ampullary type, periampullary type, or mixed type), and pathologic subtype (intestinal type or pancreaticobiliary type). Main Outcome Measurements Presence of microinvasion in early staged ampulla of Vater cancer. Results Endoscopic biopsy failed to reveal malignancy in 15.9% of the 126 cases. Microlymphovascular invasion was present in 17 cases (56.7%) of the 30 T1 cancers but was absent in all cases of the 6 Tis cancers ( P = .02). Neither the gross appearance ( P = .51) nor the pathologic subtype ( P = .28) could predict the microinvasion rate. Limitations Single-center, retrospective study with small number of patients. Conclusions Although endoscopic resection improves the low predictability of endoscopic biopsy, surgical resection should be performed for the T1 stage ampulla of Vater cancer because of the high lymphovascular invasion rate. On the other hand, the safety of endoscopic resection should be evaluated by a large-scale study on Tis cancers to consider the absence of microinvasion.

s / Pancreatology 13 (2013) S1–S80 S45 Background/aim: Distinguishing pancreatic adenocarcinomas from other pancreatic masses remains challenging in clinical practice. Contrastenhanced harmonic endoscopic ultrasound (CEH-EUS) is a promising method for characterizing pancreatic lesions due to its noninvasiveness. The clinical significance according to the change of enhancement pattern from arterial to venous phaseswas not established. The purpose of this study is to investigate the accuracy of CEH-EUS in the differentiation of pancreatic solid lesions by visualizing enhancement pattern during contrast infusion time. Methods: Between July, 2011 and March, 2013, 116 patients who referred for EUS examination of pancreatic lesions were consecutively enrolled. CEH-EUS was performed with a conventional radial echoendoscope after intravenous bolus injection of contrast agent (SonoVue). Enhancement pattern of target lesion was classified into three groups (hypo-, isoor hyper-enhancement) and also described as contrast injection time; early (10w 30 seconds), late (30w 60 seconds) and delay phase (60 w 90 seconds). The enhancement pattern of pancreatic adenocarcinoma was compared with that of other pancreatic lesions. Results: A total of 83 patients (51 male, median age 68, range 25–91) were evaluated for pancreatic solid lesions. The final diagnoses were pancreatic adenocarcinoma in 63 (75.9%), neuroendocrine tumor in 8 (9.6%), chronic pancreatitis in 3 (3.6%), autoimmune pancreatitis in 3 (3.6%), pancreatic metastasis in 2 (2.4%), malignant lymphoma in 2 (2.4%) and each cases of pancreatic abscess and solid pseudopapillary neoplasm (2.4%). In 63 pancreatic lesions with adenocarcinoma, hypoenhancement during arterial, late and delay phase was observed in 52 (82.5%), 59 (93.7%), and 62 (98.4%), respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for adenocarcinoma as hypoenhancement at CEH-EUS showed at table 1. Conclusions: CEH-EUS could characterize pancreatic mass lesions with relatively high accuracy during late phase and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

Mo1491 Endoscopic Ultrasound-Guided Fine Needle Aspiration of Solid Masses: Histological and Immunohistochemical Evaluation Young Sik Woo*, Se-Ok Lee, Ki Joo Kang, Kwang Hyuck Lee, Jong Kyun Lee, Kyu Taek Lee, Poong-Lyul Rhee Department of Medicine, Division of Gastroenterology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea; Department of Medicine, Hallym University College of Medical School, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Objective: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been demonstrated to be useful in the diagnosis of lesions adjacent to the gastrointestinal tract. The aim of this study was to evaluate the clinical utility of histological and immunohistochemical (IHC) analyses of specimens obtained by EUS-FNA. Methods: This study was consisted of two parts; a retrospective and a prospective study. The retrospective study was performed on 116 patients who underwent EUS-FNA of solid masses for cytological smear, histological analysis, and combined analysis including IHC staining. In the prospective study, 79 patients were enrolled to evaluate quality and accuracy of EUS-FNA histological analysis and feasibility of IHC staining. Results: The final diagnosis of patients was 126 pancreatic cancer, 21 non-pancreatic cancer, 27 other neoplasm, and 21 benign lesions. In retrospective study, the combined analysis was more sensitive than cytological analysis alone (P 0.01). Overall sensitivity of cytology, histological analysis, and combined analysis were 69.8%, 67.2%, and 81.8% respectively. In the prospective study, 64.2% of all punctures were helpful to make a diagnosis and 40.7% showed tissues enough to perform IHC staining. Histological analysis was helpful for diagnosis in 74.7 % of patients and IHC stains were needed for definite diagnosis in 11.4% of patients, especially nonmalignant lesions. Conclusions: Histological analysis and IHC study of EUS-FNA specimen were useful to make a proper diagnosis of pancreatic and peripancreatic lesion. Combined analysis showed significant higher sensitivity than cytology alone because IHC stains was helpful for a diagnosis in some patients. Diagnostic accuracy of Cytological, Histological, and Combined Analyses in Retrospective data

Introduction A ABC-02 trial of gemcitabine plus cisplatin combination showed prolongation of overall survival in biliary tract cancer (BTC) patients. In this multicenter retrospective study, we evaluated the treatment outcomes of combination group compared with gemcitabine alone (G) in Korean BTC patients. Methods 151 patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 9 institutions between July 2000 and May 2011. 100 patients were treated with gemcitabine-platinum (GP) combination chemotherapy and the other 51 were treated with gemcitabine (G) monotherapy. Results With a median follow-up of 7.7 months (range, 0.4-38.3 months), the median overall survival was 9.2 months (95% Confidence Interval(CI) 7.5-10.9 months) among the 51 patients in the G group and 6.9 months (95% CI 5.9-7.9 months) among the 100 patients in the GP group (P Conclusion There is no difference in ORR, PFS and OS for patients treated with the G group or GP group. We showed the differences between this study and ABC-02 study. Gemcitabine monotherapy could also be effective in Korean BTC patients.

Background: Pancreatic mass in a patient with a history of another malignancy is confusing. As metastatic pancreatic cancer is relatively rare disease, there are no clinical or radiologic data comparing metastatic pancreatic cancer and double primary pancreatic cancer. The goal of this study is to suggest clinicoradiologic characteristics that could help distinguishing metastatic pancreatic cancer from double primary pancreatic cancer. Methods: From 2000 to 2011, we retrospectively identified metastatic or double primary pancreatic cancer patients among those who had a history of another primary malignancy. Results: A total of 94 patients with a history of another malignancy were histologically confirmed to have pancreatic cancers. Among them 34 patients had metastatic tumors to pancreas (MTPs) and 60 patients had double primary pancreatic adenocarcinoma (DPPAC). RCC was the most common primary cancers that metastasized to pancreas (12, 35.3%). In DPPAC group, gastric cancer and colorectal cancer were the most common primary cancer sites before the patients had pancreatic cancer (11, 18.3%; 10, 16.7%). The number of the patients who had a metachronous pancreatic cancer was 21 (61.8%) in MTP group and 29 (48.3%) in DPACC group (p= 0.210). Among the metachronous pancreatic cancer patients the disease free interval was 88.3 months in MTP group, which was 49.6 months in DPACC group (p=0.062). In the laboratory finding, the number of the patients who showed elevated CA 19-9 was higher in MTP group than DPPAC group (39 (65%) vs. 9 (26.5%), p=0.001). Also total bilirubin (p=0.006) and fasting glucose (0.050) were higher in DPPAC group. In the radiologic finding, the patients who showed pancreatic duct dilatation (p=0.002) and pancreatic atrophy (p= 0.008) were meaningfully higher in DPPAC group. On the other hand, the number of patients who showed well demarcated tumor margin (p

Su1376 Preoperative Evaluation of Longitudinal Tumor Extent by Intraductal Ultrasonography in Borderline Resectable Hilar Cholangiocarcinoma Da Min Kim, E Ryoung Choi, Jong Kyun Lee, Kyu Taek Lee, Kwang Hyuck Lee, Dong-Wook Choi, Sung Ho Choi, Jin-Seok Heo, Kee Taek Jang, Sang-Mo Park, Jae Hoon Lim Samsung medical center, Seoul, Republic of Korea Objective: In hilar cholangiocarcinoma (HC), longitudinal tumor extent is important issue for curative resection. The purpose of this study was to evaluate longitudinal tumor extent of HC with intraductal ultrasonography (IDUS) for optimal surgical plan. Materials and Methods: Patients with borderline resectable HC were prospectively enrolled. All patients were evaluated by multi-detector computed tomography (MDCT), endoscopic retrograde cholangiopancreatography (ERCP), IDUS, and/or magnetic resonance imaging (MRI). We used new modified Bismuth type (MBT) which divided traditional Bismuth type IV into IVa and IVb whether tumor invaded left lateral section. Accuracies of CT, ERCP, and IDUS for the longitudinal tumor extent were compared with postoperative histologic tumor extent. We also sub-analyzed the tumor extent as periductal infiltrative type (PDI) and intraductal papillary neoplasm of the bile duct (IPN-B). Results: A total of 42 patients were prospectively enrolled. Among 42 patients, 31 patients underwent surgery for curative intension. Tumor extent could be assessed histologically in 30 patients. When comparing preoperative and postoperative MBT, the accuracies of CT, ERCP and IDUS were 66.6%, 60%, and 90%, respectively. Overestimation was in one patient and underestimation was in two patients by IDUS. Accuracy of IDUS was 85.7% in 21 patients with PDI and 100% in 9 patients with IPN-B. Conclusion: The IDUS for assessing longitudinal tumor extent was highly accurate than other conventional images. IDUS can give advantage for optimal surgical plan in HC.