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Background/aims For the management of hilar malignant biliary obstruction (HMBO), endoscopic biliary drainage (EBD) is preferred over percutaneous transhepatic biliary drainage (PTBD) because of its convenience. However, there is no established guideline for malignant hilar obstruction that requires multiple stenting. In this study, we compared the efficacy of bilateral metal stents (BMS) versus multiple plastic stents (MPS). Methods In this retrospective study, we analyzed 102 patients who underwent EBD with either BMS or MPS due to HMBO caused by hilar cholangiocarcinoma between 1996 and 2018 at Samsung Medical Center. We compared the successful drainage rates, cholangitis events, overall complications, mortality, and conversion rates to PTBD between the two groups. Results The successful drainage rates in the BMS group and the MPS group were 71.4% (25/35) and 65.6% (44/67), respectively, with no significant difference. The MPS group had a higher cholangitis risk (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.21 to 3.58) and higher 6-month mortality (HR, 2.91; 95% CI, 1.26 to 6.71) than the BMS group. There were no significant differences in overall complications or the conversion rate to PTBD between the groups. Conclusions In patients with malignant HMBO, the BMS group showed better outcomes in terms of the cholangitis rate and 6-month mortality than the MPS group. Therefore, if possible, bilateral metal stenting is recommended for HMBO caused by hilar cholangiocarcinoma.

Background/aims Recent advances in understanding the genetics of pancreatic ductal adenocarcinoma (PDAC) have led to the potential for a personalized approach. Several studies have described the feasibility of generating genetic profiles of PDAC with next-generation sequencing (NGS) of samples obtained through endoscopic ultrasound-guided tissue acquisition (EUS-TA). The aim of this study was to find the best EUS-TA approach for successful NGS of PDAC. Methods We attempted to perform NGS with tissues from 190 patients with histologically proven PDAC by endoscopic ultrasound-guided fine-needle aspiration and endoscopic ultrasound-guided fine-needle biopsy at Samsung Medical Center between November 2011 and February 2015. The medical records of these patients were retrospectively reviewed for parameters including tumor factors (size, location, and T stage), EUS-TA factors (needle gauge [G], needle type, and number of needle passes) and histologic factors (cellularity and blood contamination). The sample used for NGS was part of the EUS-TA specimen that underwent cytological and histological analysis. Results NGS could be successfully performed in 109 patients (57.4%). In the univariate analysis, a large needle G (p=0.003) and tumor located in the body/tail (p=0.005) were associated with successful NGS. The multivariate logistic regression analysis revealed that the needle G was an independent factor of successful NGS (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; p=0.031). Conclusions The needle G is an independent factor associated with successful NGS. This finding may suggest that the quantity of cells obtained from EUS-TA specimens is important for successful NGS.

Background/Aims: Biliary strictures remain one of the most challenging aspects after living donor liver transplantation (LDLT). The aim of this study was to assess long-term out ­come of endoscopic treatment of biliary strictures occurring after LDLT and to identify risk factors of recurrent biliary stric­ tures following endoscopic retrograde biliary drainage (ERBD) in LDLT. Methods: A total of 1,106 patients underwent LDLT from May 1995 to May 2014. We compared the risk factors between patients with and without recurrent biliary strictures. Results: Biliary strictures developed in 24.0% of patients. Technical success rate of ERBD for biliary stricture after LDLT was 66.2% (145/219). Among 145 patients managed by endoscopic drainage, stricture resolution occurred in 69 with median duration of stent indwelling of 13.6 months (range, 0.5 to 67.3 months), and stricture recurrence was seen in 20 (21.3%) out of 94. The median recurrence-free duration after final endoscopic success was 13.1 months (range, 0.5 to 67.3 months). Older donor age (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03 to 1.17; p=0.004) and non-B, non-C liver cirrhosis (HR, 5.10; 95% CI, 1.10 to 25.00; p=0.043) were associated with higher recurrence of biliary stricture. Conclusions: Long-term stricture resolution rate after ERBD insertion for biliary stricture occurring after LDLT was 73.4%. Clinicians should pay careful attention during following-up to decide when to remove ERBD in patients who have factors associated with recurrent biliary strictures. (Gut Liver 2020;14:125-134)

The incidence of colorectal cancer (CRC) has increased. CRC is the third most common cancer and the fourth most common cause of cancer-related deaths in Korea. Palliative chemotherapy can be used to shrink tumors and ease symptoms caused by the cancer when cure is not possible. It is important to identify chemotherapeutic agents that can be used to effectively treat metastatic CRC (mCRC) and thus improve the survival and quality of life of patients with mCRC. This review aimed to evaluate the recent developments in palliative chemotherapy for mCRC and the biological or targeted agents used based on genetic alterations.

Background/aims For the treatment of malignant biliary obstruction, endoscopic retrograde biliary drainage (ERBD) has been widely accepted as a standard procedure. However, post-ERBD complications can affect the lives of patients. The purpose of this study was to identify the predictive factors for these complications, including the patient's status, cancer status, and stent type. Methods This was a retrospective analysis conducted in a single tertiary hospital from January 2007 to July 2017. The following variables were evaluated: sex, age, body mass index, cancer type, history of pancreatitis, gallbladder stone, previous biliary stenting, precut papillotomy, stent type, contrast injection into the pancreatic duct or gallbladder, cystic duct invasion by the tumor, and occlusion of the cystic duct orifice by a metal stent. Results Multivariate analysis showed that contrast injection into the pancreatic duct was a risk factor for pancreatitis. Patients with a history of bile drainage showed a lower risk of pancreatitis. For cholecystitis, the analysis revealed contrast injection into the gallbladder and cystic duct invasion by the tumor as important predictive factors. Metal stents showed a greater risk of post-procedure pancreatitis than plastic stents, but did not affect the incidence of cholecystitis. Conclusion Considering that contrast injection is the most important factor for both complications, a careful approach by the physician is essential in preventing the occurrence of any complications. Further, choosing the type of stent is an important factor for patients at a risk of post-procedure pancreatitis.

The aim of this study was to investigate the clinical utility of minimal specimens acquired from endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) and perform targeted deep sequencing as a prognosis prediction tool for pancreatic ductal adenocarcinoma (PDAC). A total of 116 specimens with pathologically confirmed PDAC via EUS-FNB were tested using CancerSCAN® panel for a customized targeted deep sequencing. Clinical prognostic factors significantly associated with survival in PDACs were as follows: stage, tumor mass size, tumor location, metastasis, chemotherapy, and initial CA19-9 level. A total of 114 patients (98.3%) had at least a single genetic alteration, and no mutations were detected in two patients, although they were qualified for the targeted deep sequencing. The frequencies of major gene mutations responsible for PDACs were KRAS 90%, CDKN2A 31%, TP53 77%, and SMAD4 29%. A somatic point mutation of NF1, copy number alteration of SMAD4, and loss-of-function of CDKN2A were significantly associated genetic factors for overall survival. Moreover, BRCA2 point mutation was related to liver metastasis. Finally, a clinico-genomic model was developed to estimate the prognosis of patients with PDAC based on clinical parameters and genetic alterations affecting survival in patients, 20 single nucleotide variants and three copy number variations were selected. Targeted deep sequencing on minimal specimens of PDACs was performed, and it was applied to establish a clinico-genomic model for prognosis prediction.

Background:Clonorchis sinensis (CS) infection is considered a group 1 carcinogen of cholangiocarcinoma (CCA). There were very few studies regarding clinical characteristics of CS-associated CCA (CACC). This study aimed to investigate clinical characteristics of patients with CCA with or without CS infection.Methods: A total of 367 patients diagnosed with CCA who underwent diagnostic tests for CS infection were enrolled. CS infection was defined as follows: at least one positive serum ELISA test, skin test, stool microscopy, or bile microscopy.Results: There were 95 (26%) patients with CS infections. The median follow-up duration was 14.9 months (range, 6.07–36.17). The following significant differences were noted among patients with CACC compared to non-CACC; diagnosis at younger age (median 62 years vs. 65 years, p = 0.018), higher male to female ratio (83.2 vs. 61.8%, p < 0.001), and residence in CS-endemic area (46.3 vs. 25.4%, p = 0.014). Univariate analysis of prognostic factors indicated that tumor location, curative resection, tumor stage, and laboratory tests including CA 19-9, CEA, and bilirubin were significantly associated with overall survival, but CS infection was not. In multivariate analysis, tumor location, CEA, curative resection and tumor stage were identified as independent prognostic factors. Among patients under age 64, CACC group had lower survival rate than non-CACC group (p = 0.022).Conclusions: CACC had the following significant characteristics compared to non-CACC; diagnosis at younger age, higher male to female ratio, higher prevalence in CS endemic areas and poorer overall survival in patients under age 64.

BackgroundCirculating tumour cells (CTCs) have emerged as liquid biopsy biomarker providing non-invasive assessment of cancer progression and biology. We investigated whether longitudinal analysis of CTCs could monitor disease progression, response to chemotherapy, and survival in patients with unresectable pancreatic ductal adenocarcinoma (PDAC).MethodsCTCs were isolated using a centrifugal microfluidic disc from serially collected peripheral blood with clinical assessments. CTCs were enumerated with immunostaining against Epithelial cell adhesion molecule, Cytokeratin, Plectin-1 and CD45.ResultsCTCs were detected in 91.7% of 52 patients with unresectable PDAC at the time of diagnosis. CTC numbers were not statistically different across tumour sizes, stages and metastatic sites. The absolute CTC counts after chemotherapy was inversely related to survival, and the decreased number of CTCs after the first cycle of chemotherapy was significantly associated with longer survival.ConclusionsIdentifying CTCs and monitoring CTC changes after chemotherapy could be a useful prognostic marker for survivals in patients with unresectable PDACs.FundingThis work was supported by a grant from SK Chemical Research Fund of the Korean Society of Gastroenterology (Grant No.800-20130378) and a grant from Korean Gastroenterology Fund for Future Development. This study was granted by the Korean Health Technology R&D Project, Ministry of Health & Welfare funded by the Korean Government (Grant No. HI12C1845), and work by Y.K.Cho was partially supported by IBS-R020-D1 funded by the Korean Government. This research was supported by Collaborative Genome Program for Fostering New Post-Genome industry through the National Research Foundation (NRF) funded by the Korean government (MSIT) (Grant No. NRF-2017M3C9A5031002), and also supported by National Research Foundation (NRF) grant funded by the Korean government (MSIT) (Grant No. 2019R1C1C1008646).Clinical Trial NumberClinicalTrials.gov Identifier No. NCT02934984

Circulating tumor cells (CTCs) are useful biomarkers of many solid tumors, but are infrequently detected in early stage pancreatic ductal adenocarcinomas (PDACs). The first drainage of pancreatic venous blood flow come to portal vein and pass through the liver, and they finally go out for peripheral blood. We thought that comparing CTCs from portal vein and peripheral blood could enable us to understand the clinical meaning of CTCs from each different site in PDACs. Therefore, we aimed to determine 1) whether CTCs could be reliably identified in early stages (operable) of PDACs, 2) if there are any differences in the detected number of CTC in portal vein blood and peripheral blood, and 3) whether CTCs can be sensitive biomarkers for the prognosis of resectable PDAC patients. Newly diagnosed PDAC patients who underwent operation with curative intention between 2013 and 2015 were prospectively enrolled. Blood draws from portal and peripheral vein ran through the microfabricated porous filter, and anti-epithelial cell adhesion molecule (EpCAM) and anti-Plectin-1 antibodies were used for CTC identification. Baseline clinical characteristics, tumor characteristics, treatment, and clinical outcomes were assessed. The clinical stages of the 32 enrolled patients were as follows: IA/IB 1 (3.1%); IIA 9 (28.1%); IIB 17 (53.1%); III 5 (15.6%). Twenty-seven patients (84.4%) received R0 resection, while five patients (15.6%) received R1 resection. EpCAM+ CTCs were detected in 20 portal blood (62.5%) and 22 peripheral blood (68.8%). Plectin-1+ CTCs were identified in 14 portal blood (43.8%) and 16 peripheral blood (50%). Plectin-1-expressing CTCs were picked from CTC platform (microfabricated porous filter) and we could find out all KRAS mutation. Patients with detectable EpCAM+ CTC less than one in peripheral blood showed longer overall survival (OS) compared to patients with detectable CTCs more than one (35.5 months vs. 16.0 months). EpCAM and Plectin-1 successfully identified CTCs at the early stage of PDACs. Also, the number of CTCs could be a prognostic marker for survival in resectable PDACs.

Background Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are commonly used diagnostic modalities in biliary strictures. We compared the diagnostic yield of EUS and ERCP-based tissue sampling in intrinsic biliary strictures without extrinsic mass outside the bile duct. Methods A total of 85 patients who underwent ERCP and EUS for diagnosis of suspected biliary strictures confined to the bile duct were analyzed retrospectively at Samsung Medical Center, Seoul, Korea, between 2010 and 2018. Results Seventy-one patients were diagnosed with malignancy and 14 patients were diagnosed with benign strictures. EUS-based tissue sampling was more sensitive and accurate than ERCP-based tissue sampling (p = 0.038). The overall sensitivity and accuracy were 67.6% (95% confidence interval (CI) 56.1–77.3) and 72.9% (95% CI 62.7–81.2) for ERCP-based sampling, and 80.3% (95% CI 69.6–87.9) and 83.5% (95% CI 74.2–89.9) for EUS-based sampling, respectively. EUS-based sampling was superior to ERCP-based sampling in distal bile duct strictures (accuracy: 87.0% vs. 72.5%, p = 0.007), but not in perihilar strictures. In cases without intraductal mass, EUS-based tissue sampling was also superior to ERCP-based sampling (accuracy: 83.3% vs. 69.7%, p = 0.029), but not in cases with mass. Conclusion EUS-based tissue sampling was superior to ERCP-based method in intrinsic biliary stricture with no mass outside the bile duct, particularly in those without intraductal mass or those with strictures located in distal bile duct. Therefore, EUS-based sampling should be considered for making a pathological diagnosis of suspected distal bile duct strictures even in lesions without definite mass.

Backgrounds The placement of a self-expandable metal stent (SEMS) is widely used in patients with unresectable malignant biliary obstructions, but SEMSs are susceptible to occlusion by tumor ingrowth or overgrowth. The efficacy and safety of a novel paclitaxel-eluting biliary metal stent incorporating sodium caprate (MSCPM-III) were compared prospectively with those of a covered metal stent (CMS) in patients with malignant biliary obstructions. Methods Patients with unresectable distal malignant biliary obstructions (n = 106) were prospectively enrolled in this study at multiple treatment centers. Stents were placed endoscopically: MSCPM-III in 54 patients and CMS in 51 patients. The patients received systemic chemotherapy regimens according to their disease characteristics. Results The two groups did not differ significantly in basic characteristics or mean follow-up period. Stent occlusion occurred in 14 patients who received MSCPM-III and in 11 patients who received CMS. Time to recurrent biliary obstruction (RBO) and survival time did not differ significantly between the two groups (P = 0.84 and P = 0.29, respectively). However, tumor size at 2 months after stent insertion was significantly decreased in patients in the MSCPM-III group with bile duct cancers or those who experienced stent migration compared with the CMS group. Complications, including cholangitis and pancreatitis, were found to be acceptable in both groups. Conclusions Although compared with a CMS the MSCPM-III did not significantly influence time to RBO or survival duration in patients with malignant biliary obstructions, MSCPM-III reduced tumor volume and was used safely in humans.

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.)

Purpose Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. Methods A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. Results Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. Conclusion Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

// Jisook Park 1 , Eunjung Lee 2 , Kyoung-Jin Park 3 , Hyung-Doo Park 3 , Jong-Won Kim 3 , Hye In Woo 4 , Kwang Hyuck Lee 5 , Kyu-Taek Lee 5 , Jong Kyun Lee 5 , Joon-Oh Park 6 , Young Suk Park 6 , Jin Seok Heo 7 , Seong Ho Choi 7 , Dong Wook Choi 7 , Kee-Taek Jang 8 and Soo-Youn Lee 3, 9 1 Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States 3 Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea 5 Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 6 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 7 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 8 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 9 Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Correspondence to: Soo-Youn Lee, email: suddenbz@skku.edu Keywords: pancreatic cancer, biomarker, validation, proteomics, mass spectrometry Received: October 06, 2016 Accepted: April 15, 2017 Published: April 27, 2017 ABSTRACT We performed an integrated analysis of proteomic and transcriptomic datasets to develop potential diagnostic markers for early pancreatic cancer. In the discovery phase, a multiple reaction monitoring assay of 90 proteins identified by either gene expression analysis or global serum proteome profiling was established and applied to 182 clinical specimens. Nine proteins ( P < 0.05) were selected for the independent validation phase and quantified using stable isotope dilution-multiple reaction monitoring-mass spectrometry in 456 specimens. Of these proteins, four proteins (apolipoprotein A-IV, apolipoprotein CIII, insulin-like growth factor binding protein 2 and tissue inhibitor of metalloproteinase 1) were significantly altered in pancreatic cancer in both the discovery and validation phase ( P < 0.01). Moreover, a panel including carbohydrate antigen 19-9, apolipoprotein A-IV and tissue inhibitor of metalloproteinase 1 showed better performance for distinguishing early pancreatic cancer from pancreatitis (Area under the curve = 0.934, 86% sensitivity at fixed 90% specificity) than carbohydrate antigen 19-9 alone (71% sensitivity). Overall, we present the panel of robust biomarkers for early pancreatic cancer diagnosis through bioinformatics analysis that combined transcriptomic and proteomic data as well as rigorous validation on a large number of independent clinical samples.

Background/Aims The objective of this study was to investigate the value of cyst fluid carcinoembryonic antigen (CEA) in combination with cytology and viscosity for the differential diagnosis of pancreatic cysts. Methods We retrospectively reviewed our data for patients who underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and cyst fluid analysis. We investigated the sensitivity, specificity and accuracy of the combination of cyst fluid CEA, cytology and viscosity testing. Results A total of 177 patients underwent EUS-FNA and cyst fluid analysis. Of these, 48 subjects were histologically and clinically confirmed to have pancreatic cysts and were therefore included in the analysis. Receiver operator curve analysis demonstrated that the optimal cutoff value of cyst fluid CEA for differentiating mucinous versus nonmucinous cystic lesions was 48.6 ng/mL. The accuracy of cyst fluid CEA (39/48, 81.3%) was greater than the accuracy of cytology (23/45, 51.1%) or the string sign (33/47, 70.2%). Cyst fluid CEA in combination with cytology and string sign assessment exhibited the highest accuracy (45/48, 93.8%). Conclusions Cyst fluid CEA was the most useful single test for identifying mucinous pancreatic cysts. The addition of cytology and string sign assessment to cyst fluid CEA increased the overall accuracy for the diagnosis of mucinous pancreatic cysts.

Purpose Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. Methods We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. Results IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). Conclusion A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.

Background and aim Fully covered self-expandable metallic stent (FCSEMS) may be an effective modality for managing anastomotic biliary stricture (ABS) after liver transplantation. However, stent migration and stent-induced ductal injury are the main limitations. The objective of this study was to evaluate the usefulness of an unflared, intraductal FCSEMS that was designed to minimize migration and ductal injury for refractory ABS after living donor liver transplantation (LDLT). Methods A total of 32 consecutive patients with symptomatic ABS after LDLT unresolved by plastic stents with or without balloon dilation at four tertiary medical centers were prospectively enrolled. A short (3 or 5 cm) FCSEMS having long lasso (10 cm) used in this study had unflared convex ends to minimize tissue hyperplasia and smaller center portion to prevent migration. The FCSEMS was placed above the papilla and removed at 3-4 months after stenting. Results Technical and clinical success rates of intraductal placement with FCSEMS were 100% (32/32) and 81.2% (26/32), respectively. Early stent migration was observed in five (15.6%) patients. However, three patients with early stent migration had stricture resolution without needing additional intervention. Intended stent removal was successful in 27 (100%) patients (median, 101 days; range, 23-118 days). No stent-induced ductal change was observed in all patients. Stricture recurrence was observed in 11.5% (3/26) of patients during 639 days of median duration of follow-up (range, 366-2079 days). Conclusions Intraductal placement of an unflared short FCSEMS may be a promising option for refractory ABS after LDLT with minimal stent-induced ductal injury and stent migration.

Objective: Previous studies have revealed that biliary tract cancer (BTC) has different clinical characteristics depending on its anatomical location. However, clinical studies about the prognosis of BTC according to its anatomical location are lacking. We aimed to compare the prognosis of BTC according to its anatomical location. Methods: We retrospectively reviewed records of 311 patients with advanced BTC who received gemcitabine based palliative chemotherapy from January 2006 to December 2015 at Samsung medical Center. Results: During median follow-up of 7.67 months, the median overall survival (OS) times for patients with gallbladder (GB) cancer, intrahepatic cholangiocellular carcinoma (ICCC) and extrahepatic cholangiocellular carcinoma (ECCC) were 8.1 months, 7.7 months and 13.4 months, respectively. Median progression free survival (PFS) times for those with GB cancer, ICCC and ECCC were 4.1 months, 5.4 months and 7.2 months respectively. In multivariate analysis, anatomical location of cancer was a statistically significant factor for OS and PFS (p Conclusions: Prognosis and prognostic factors of BTC were significantly different depending on its anatomical location.

Background Proton pump inhibitor (PPI) use may alter the gut microbiome and increase the risk of cholangitis. However, the association of PPI use with the risk of incident cholangitis has not been evaluated. Aim To evaluate whether PPI use was associated with a higher risk of cholangitis. Methods This cohort study included a nationwide representative sample of the Korean general population followed up for 10 years (1 January 2003 to 31 December 2013). PPI use was identified from treatment claims and considered as a time-varying variable. Incident cholangitis was identified from hospitalisation and out-patient visit claims. Results During 4 212 003 person-years of follow-up, 58,863 participants had at least one PPI prescription and 1 834 participants developed cholangitis. The age-, sex-, residential area- and income-adjusted hazard ratio (HR) for incident cholangitis comparing PPI use with non-use was 6.06 (95% CI, 4.64-7.91). The association was essentially unchanged in fully adjusted models (HR 5.75; 95% CI, 4.39-7.54). The risk was highest during PPI treatment and decreased gradually after PPI discontinuation (Ptrend Conclusions In this large cohort, PPI use was associated with an increased risk of cholangitis. Physicians prescribing PPIs should consider cholangitis as a potential complication of PPI use.

// Joo Kyung Park 1 , Yoon Jung Lee 1 , Jong Kyun Lee 1 , Kyu Taek Lee 1 , Yoon-La Choi 2 , Kwang Hyuck Lee 1, 3 1 Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3 Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea Correspondence to: Kwang Hyuck Lee, email: lkhyuck@gmail.com Keywords: KRAS gene mutation, endoscopic ultrasound-guided fine needle aspiration, pancreatic ductal adenocarcinoma Received: December 19, 2015 Accepted: October 26, 2016 Published: December 10, 2016 ABSTRACT EUS-FNA becomes one of the most important diagnostic modalities for PDACs. However, acquired tissue specimens were sometimes insufficient to make a definite cytological diagnosis. On the other hand, KRAS mutation is the most frequently acquired genetic alteration found more than 90% of PDACs. To investigate the way to improve diagnostic accuracy for PDACs using both cytological examination and KRAS mutation analysis would be a great help. Therefore, the aims of this study were to evaluate usefulness of conventional cytological examination combined with KRAS mutation analysis with modified PCR technology to improve the sensitivity and the accuracy. We enrolled 43 patients with solid pancreatic masses and 86 EUS-FNA specimens were obtained. During the EUS-FNA, the needle catheter was flushed with 2 cc of saline and the washed fluid was collected for KRAS mutation analysis for the first 2 passes; PNAClamp™ KRAS Mutation Detection Kit. There were 46 specimens from the 23 PDACs and 40 specimens from the 20 other pancreatic diseases. The sensitivity, specificity and accuracy were as follows; conventional cytopathologic examination: 63%, 100% and 80%; combination of cytopathologic examination and K-ras mutation analysis: 87%, 100% and 93%. Furthermore, KRAS mutation was detected 11 out of 17 PDAC samples whose cytopathology results were inconclusive. KRAS mutation analysis with PNAClamp™ technique using washing fluid from EUS-FNA along with cytological examination may not only improve the diagnostic accuracy of PDACs, but also establish the platform using genetic analysis which would be helpful as diagnostic modality for PDACs.

Background/aims The covered self-expandable metal stent (CMS) was developed to prevent tumor ingrowth-induced stent occlusion during the treatment of malignant biliary obstruction. However, complications such as cholecystitis, pancreatitis, and stent migration can occur after the endoscopic insertion of CMSs. The aim of the present study was to assess the efficacy and safety of a double-layered CMS (DCMS) for the management of malignant bile duct obstruction. Methods DCMSs were endoscopically introduced into 59 patients with unresectable malignant extrahepatic biliary obstruction at four tertiary referral centers, and the patient medical records were retrospectively reviewed. Results Both the technical and functional success rates were 100%. Procedure-related complications including pancreatitis, cholangitis, stent migration, and liver abscess occurred in five patients (8.5%). The median follow-up period was 265 days (range, 31 to 752 days). Cumulative stent patency rates were 68.2% and 40.8% at 6 and 12 months, respectively. At the final follow-up, the rate of stent occlusion was 33.9% (20/59), and the median stent patency period was 276 days (range, 2 to 706 days). Conclusions The clinical outcomes of DCMSs were comparable to the outcomes previously reported for CMSs with respect to stent patency period and complication rates.

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.

Desmoid tumors are rare benign tumors with aggressive fibroblastic proliferation. Although desmoid tumors do not metastasize, they have locally aggressive features and can cause a urinary fistula. Here, we report a case of a 35-year-old woman with Gardner syndrome who was diagnosed with an intra-abdominal desmoid tumor 1 year previously and who presented with a newly developed cystic mass lesion on a computed tomography scan. The cystic mass lesion was clinically diagnosed as an urinoma from the right ureterotumoral fistula; thus, surgical resection of the mass lesion was planned. However, Tc-99m diethylenetriamine pentaacetic acid renal scintigraphy revealed bilateral ureterotumoral fistulas; hence, the treatment plan was changed to conservative management.

Objectives The American Society for Gastrointestinal Endoscopy (ASGE) guidelines offered the risk-stratified approach in suspected choledocholithiasis. Previous studies have raised concern about the insufficient accuracy of the guideline, especially in high probability group. The purposes of this study were to authenticate the stratification and clinical predictors of the guidelines for suspected choledocholithiasis with no visible choledocholithiasis on computed tomography (CT) and to make clear the clinical strategy of endoscopic ultrasonography (EUS). Materials and methods We carried out the retrospective single-center study of 156 patients with suspected choledocholithiasis but negative findings on CT who underwent EUS for about 8 years at Samsung Medical Center. We assessed the clinical predictors of the ASGE guidelines in predicting the presence of choledocholithiasis and the outcome of the EUS. Results Fifty-three of the 156 patients had positive findings on EUS that included choledocholithiasis (n = 43, 27.6%) or obstructive papillitis (n = 10, 6.4%). Among the 53 patients, 51 (96.2%) had choledocholithiasis or obstructive papillitis on ERCP. The 101 patients of 103 patients with negative finding on EUS did not show biliary events during follow-up period. EUS accuracy was 98.7% (sensitivity 100%; specificity 98.1%). Among the 49 patients with high probability, 21 (42.9%) had choledocholithiasis on ERCP. In 107 patients who were classified as intermediate probability, 30 (27.3%) had choledocholithiasis. There were no complications related to EUS. Conclusions Not only intermediate probability group but also high probability group without definite acute cholangitis may require EUS. Application of EUS for suspected choledocholithiasis is highly accurate, safe and reduces unnecessary invasive ERCP in 57.1% of patients with high probability group.

Background and aim Percutaneous cholecystostomy (PC) has been frequently used as an alternative treatment for acute cholecystitis in seriously ill patients unfit for surgery. The aim of this study was to investigate the recurrence rate and risk factors of recurrence. Methods Medical records of 102 patients who were followed up for more than 1 year after PC tube removal among 716 patients who underwent PC for acute cholecystitis treatment were retrospectively analyzed. Results The recurrence rate of acute cholecystitis after PC tube removal was 20.6% (21/102), and the mean time to recur was 660 days. Underlying cancer (odds ratio [OR]: 3.369; 95% confidence interval [CI]: 1.006-11.282; P = 0.0489), PC duration shorter than 44 days (OR: 5.596; 95% CI: 1.35-23.201; P = 0.0176), and the presence of common bile duct stone in initial imaging studies (OR: 24.393; 95% CI: 2.696-220.746; P = 0.0045) were positively correlated with recurrence. Tubogram before PC tube removal did not significantly lower the recurrence. However, PC tube clamping for several days significantly lowered the recurrence (OR: 0.108; 95% CI: 0.015-0.794; P = 0.0288). Fifty-nine (57.8%) had acalculous cholecystitis. Calculous cholecystitis was negatively correlated with recurrence (OR: 0.267; 95% CI: 0.074-0.967; P = 0.0444). Receiver operating characteristic curve of the prediction model for recurrence verified its accuracy (area under the curve: 0.8475). Conclusion We should try to keep PC more than 6 weeks and clamp for 1-2 weeks before removal. For those with the presence of common bile duct stones, calculous cholecystitis, and underlying malignancy, we should keep PC for longer duration and carefully observe symptoms and signs of recurrence.

ratio of cholangiocarcinoma (intrahepatic or extrahepatic), gall bladder cancer, and ampulla of Vater cancer was 41 (63.1%):18 (27.7%):6 (9.25%). Half of the patients (33 patients, 50.8%) were treated with gemcitabine-based and 28 patients (43.1%) with 5-fluo- rouracil-based therapy. The response rate was 3.0% and disease control rate was 21.5% in intention-to-treat analysis. Median overall survival (OS) was 7.2 months (95% confidence interval (CI), 3.9 to 10.5 months) and median progression free survival (PFS) was 3.7 months (95% CI, 2.5 to 4.9 months). In multivariate analysis, patients with good performance status (PS) (P = 0.001) and chemo-sensi- tive tumor to 2nd line chemotherapy (P = 0.000) had longer PFS as compared to the others. In addition, patients with good PS (P = 0.003), chemo-sensitive tumor to 1st line (P = 0.046), and 2nd line chemotherapy (P = 0.004) were good prognostic factors for OS. Conclusion: The effect of 2nd line chemotherapy in advanced BTC was modest and maybe beneficial in select patients.

Anastomotic biliary strictures are common in patients that undergo living donor liver transplantation. Although endoscopic management has the advantage over percutaneous approaches, the initial success rate for the endoscopic management is unsatisfactory. The SpyGlass system can be a useful device in patients with a severe anastomotic stricture.The SpyGlass cholangioscopy-assisted guidewire placement was performed in 15 patients with a difficult guidewire placement in which the guidewire could not transverse the stricture with conventional methods for 10 min or more.The visualization rate of the stricture orifice was 93.3 % (14 of 15 patients). The total success rate of the SpyGlass cholangioscopy-assisted guidewire placement was 60 % (9 of 15 patients). No procedure-related complications occurred during or after the SpyGlass cholangioscopy-assisted guidewire placement.This series demonstrated that the SpyGlass cholangioscopy-assisted guidewire placement is a useful method when the guidewire passage of the strictures site is impossible by conventional methods.

Background There has recently been increased interest in cancer incidence in electronics workers. Aims To determine the cancer incidence ratio in electronics workers and the potential factors affecting the risk for development of cancer. Methods Epidemiological study performed in electronics workers who were employed between 1999 and 2008 in South Korea. Cancer incidence ratio was analysed with respect to departments, divisions, job titles, gender, age, hepatitis B and C virus infection and work duration. We compared the incidence of haematological cancer in this cohort with that expected in the general population. Results The study population was 56283. Overall, the standardized incidence ratio (SIR) for haematological cancer was 0.85. In particular, the SIR for leukaemia was 0.86 and for non-Hodgkin lymphoma (NHL) was 0.93, which were not statistically significant. The SIR for NHL was significantly increased [SIR 5.23, 95% confidence interval (CI) 1.31-20.95] in female office workers. We also found that the SIR for NHL was significantly increased in female workers who tested positive for hepatitis virus infection (SIR 7.69, 95% CI 1.08-54.60). Conclusions The raised SIR for NHL among female workers was due to potential risk factors such as hepatitis virus infection although additional research and an ongoing, long-term, prospective epidemiological cohort study is needed.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is effective for tissue diagnosis of pancreatic mass. To improve diagnostic yield and drawbacks, 22-gauge (G) core biopsy (FNB) needle has been developed. This study aims to compare 22G FNA and FNB needles for EUS-guided sampling of suspected pancreatic cancer.This is a randomized controlled crossover trial. A total of 60 patients with suspected unresectable pancreatic cancer referred for EUS-guided sampling were randomly assigned to two groups. Both groups had 22G FNA and FNB needles performed in a randomized order. The primary endpoint was the cytological, histological and overall diagnostic accuracy of pancreatic cancer.FNA and FNB needles reported similar level of diagnostic accuracy (FNA needle 95% vs. FNB needle 93.3%; p = .564), and it was not statistically different. However, cytological cellularity was significantly higher in the FNB needles compared to FNA needles (odds ratio 2.75, 95% confidence interval (CI)). There were no procedure-related complications in both needles.The diagnostic accuracy of EUS-guided sampling for pancreatic cancer using 22G FNA is comparable to FNB needles. The cytological quality of specimen is better in the FNB needle.

Background Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. Methods A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1–2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan–Meier methods. Results We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5–6.0 months) and 8.5 months (95% CI 5.6–11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. Conclusion Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

To provide the statistical predictive model for neoplastic potential of gallbladder polyp (GBP).Many studies have attempted to define the risk factors for neoplastic potential of GBP. It remains difficult to precisely adapt the reported risk factors for the decision of surgery. Estimating the probability for neoplastic potential of GBP using a combination of several risk factors before surgical resection would be useful in patient consultation.We collected data of patients confirmed as GBP through cholecystectomy at Samsung Medical Center between January 1997 and March 2015. Those with a definite evidence for malignancy, such as adjacent organ invasion, metastasis on preoperative imaging studies, polyp15 mm, and absence of proper preoperative ultrasonographic imaging were excluded. A total of 1976 patients were enrolled. To make and validate the predictive model, we divided the cohort into the modeling group (n=979) and validation group (n=997). Clinical information, ultrasonographic findings, and blood tests were retrospectively analyzed.Clinical factors of older age, single lesion, sessile shape, and polyp size showed statistical significance for neoplastic potential of GBP in the modeling group. A predictive model for neoplastic potential of GBP was constructed utilizing the statistical outcome of the modeling group. Statistical validation was performed with the validation group to determine the optimal clinical sensitivity and specificity of the predictive model. Optimal cut-off value for neoplastic probability was 7.4%.The predictive model for neoplastic potential of GBP may support clinical decisions before cholecystectomy.

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 outcome of gemcitabine combined with platinum (GP) compared to that of gemcitabine (G) alone in Korean BTC patients. One hundred and fifty-one patients with histologically confirmed biliary tract adenocarcinoma were enrolled at nine institutions between July 2003 and May 2011, including 100 treated with GP and 51 treated with G. With a median follow-up of 7.7 months (range 0.4–38.3 months), the median overall survival (OS) was 12.4 months [95 % confidence interval (CI) 9.4–15.6 months] of the G group, which was not significantly different for the median OS of 11.0 months (95 % CI 9.7–12.3 months) of the GP group (p = 0.599). The median progression-free survival (PFS) was 3.9 months (95 % CI 0.8–7.0 months) in the G group and 3.3 months (95 % CI 2.6–4.0 months) in the GP group (p = 0.504). Overall response rates (ORR) were 18.8 % in G group and 23.9 % in GP group (p = 0.485). There was no significant difference in ORR, PFS, or OS for patients between the G group and the GP group, which was different from the ABC-02 trial. Therefore, gemcitabine monotherapy and GP combination are both effective regimens for Korean BTC 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.

Pneumatosis intestinalis (PI) is a rare condition that is characterized by multiple subserosal and submucosal gas-filled areas in the bowel wall. Gastric pneumatosis describes the presence of gas within the stomach wall. This is caused by a disruption in gastric mucosa leading to the dissection of air into the wall. The extract cause of PI is still unknown; however, it may be associated with coexisting disease. Gastric PI has been rarely documented. So, we report on a 75-year-old man with acute gastric pneumatosis following his palliative chemotherapy. He underwent 3rd cycle of gemcitabine and erlotinib 3 weeks prior to admission. The treatment was started with nasogastric tube insertion and parenteral nutrition. Then, gastric pneumatosis was improved. However, the patient was died because of worsening underline disease and general condition. We suggest that chemotherapy should be considered the case of pneumatosis and careful X-ray interpretation will be necessary for detecting the pneumatosis earlier.

The solid pseudopapillary tumor (SPT) of the pancreas is a rare but low-grade malignant tumor with a good prognosis after surgical excision. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is a minimally invasive, safe and reliable way of diagnosing SPT by providing characteristic cytological and immunochemical specimens. Definitive preoperative diagnosis leads to targeted and minimally invasive surgical resection. In this study, we report three cases of SPTs that were diagnosed through EUS-FNA and underwent successful laparoscopic surgery.

Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is widely performed for pancreatic masses. The 25-gauge needle (25G) might be easier to be manipulated and expected to be associated with fewer complications since it is thinner and more flexible than the 22-gauge needle (22G) although obtaining adequate specimens is questioned. In this randomized trial, the authors tried to compare prospectively 25G and 22G in diagnostic accuracy, manipulability from the operator's viewpoint and procedure-related complications.A total of 188 consecutive patients undergoing EUS-FNA for solid or cystic pancreatic masses were consecutively enrolled and 94 patients were randomized to either 25G or 22G group, respectively.Baseline characteristics were similar except that more masses of 25G group were located in the head or uncinate process of pancreas than those from 22G group. Although there was no difference in diagnostic accuracy (89.4% vs. 88.3% with p = 0.82), 25G was easier to be manipulated (p = 0.004) and related with fewer procedure-related complications (10.6% vs. 3.2% with p = 0.004).25G can be chosen in preference to 22G when performing pancreatic EUS-FNA because 25G was significantly superior to 22G in terms of manipulability and complications although both were effective for accurate diagnosis.

Background/Goals: The endoscopic treatment of ampullary adenomas is established; however, the false-negative rate of endoscopic biopsy for carcinoma is 20% to 30%, and it remains uncertain whether identifiable features predict malignancy. Our aim in this study was to evaluate the predictable factors of malignancy in ampullary adenomas on endoscopic biopsy. Study: Ninety-one subjects diagnosed with ampullary adenoma on endoscopic biopsy were confirmed after endoscopic or surgical resection of ampullary lesions between 1995 and 2011 respectively. Clinical, laboratory, radiologic, and endoscopic findings were compared between patients with adenoma and carcinoma after resection. We examined the predictors of malignancy in ampullary adenoma on endoscopic biopsy. Results: The malignancy rate in ampullary adenomas on endoscopic biopsy was 26.4%. Univariate analysis revealed that presence of symptoms, villous components, high-grade dysplasia (HGD), papilla enlargement on computed tomography, duct dilatation on radiologic imaging, bilirubin > 2mg/dL, aspartate aminotransferase > 40 IU/L, alanine aminotransferase > 40 IU/L, and alkaline phosphatase > 90U/L were associated with malignancy in patients over 65 years of age. HGD [odds ratio, 6.86 (95% confidence interval, 1.58-29.79)] and ductal dilatation [odds ratio, 11.12 (95% confidence interval, 2.27-54.37)] were independently associated with malignancy in multivariate analysis. The sensitivity and negative predictive value for >= 1 risk factors were 95.83% and 96.77%, respectively. The presence of 2 risk factors resulted in a high specificity (96%) and positive predictive value (84%) for malignancy. Conclusions: HGD and ductal dilatation are significant predictors of malignancy in ampullary adenomas. When these risk factors are present, precautions should be taken in the consideration of malignancy in patients with ampullary adenoma.

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/Objectives: No comparative study of 22-gauge biopsy needles (PC22) and 25-gauge biopsy needles (PC25) has been conducted. We prospectively compared the diagnostic accuracy of PC22 and PC25 in patients with pancreatic and peripancreatic solid masses. Methods: We conducted a randomized noninferiority clinical study from January 2013 to May 2014 at Samsung Medical Center. A cytological and histological specimen of each pass was analyzed separately by an experienced pathologist. The primary outcome was to assess the diagnostic accuracy using the PC22 or PC25. Secondary outcomes included the optimal number of passes for adequate diagnosis, core specimen yield, sample adequacy, and complication rates. Results: Diagnostic accuracy of combining cytology with histology in three cumulative passes was 97.1% (100/103) for the PC22 and 91.3% (94/103) for the PC25 group. Thus, noninferiority of PC25 to PC22 was not shown with a 10% noninferiority margin (difference, −5.8%; 95% CI, −12.1 to −0.5%). In a pairwise comparison with each needle type, two passes was non-inferior to three passes in the PC22 (96.1% vs. 97.1%; difference, −0.97%; 95% CI −6.63 to 4.69%) but noninferiority of two passes to three passes was not shown in the PC25 group (87.4% vs. 91.3%; difference, −3.88%; 95% CI, −13.5 to 5.7%). Conclusions: Non-inferiority of PC25 to PC22 diagnostic accuracy was not observed for solid pancreatic or peripancreatic masses without on-site cytology. PC22 may be a more ideal device because only two PC22 needle passes was sufficient to establish an adequate diagnosis, whereas PC25 required three or more needle passes.

Supplemental Digital Content is available in the text, Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become one of the most useful diagnostic modalities for the diagnosis of pancreatic mass. The aim of this study was to investigate the role of analyzing the minimal specimens obtained by EUS-FNA for the diagnosis of solid masses of pancreas. This study consisted of retrospective and prospective analyses. The retrospective study was performed on 116 patients who underwent EUS-FNA of solid masses for cytological smear, histological analysis, and combined analysis including immunohistochemical (IHC) staining. In the prospective study, 79 patients were enrolled to evaluate the quality and accuracy of EUS-FNA histological analysis and feasibility of IHC staining. The final diagnoses of all patients included pancreatic cancer (n = 126), nonpancreatic cancer (n = 21), other neoplasm (n = 27), and benign lesions (n = 21). In our retrospective study, the combined analysis was more sensitive than cytological analysis alone (P

The marked increase in the incidence of biliary tract infections due to antimicrobial-resistant pathogens in recent years is of great concern, as patients infected by these isolates might initially receive antibiotics ineffective against the responsible pathogens.A retrospective cohort study including 556 episodes of bacteremic biliary tract infection was designed to evaluate the impact of inappropriate initial antimicrobial therapy on the clinical outcomes of patients with biliary tract infections.Of 556 episodes, 257 (46.2%) received inappropriate initial antimicrobial therapy. Although Escherichia coli and Klebsiella species are the most common pathogens, the pathogens that were most frequently associated with inappropriate therapy were Pseudomonas aeruginosa and Enterococcus spp. In multivariable analysis, inappropriate initial antimicrobial therapy was found to be independently associated with increased mortality (odds ratio (OR) 2.25, 95% confidence interval (CI) 1.13-4.48; p = 0.021), along with pancreaticobiliary tract cancer, liver cirrhosis, Enterobacter infection, and a high Pitt bacteremia score (All p0.05). Subgroup multivariate analyses showed that inappropriate initial therapy was not a significant factor associated with mortality in cases where therapeutic decompression or drainage procedures were employed (OR 1.24, 95% CI 0.43-3.54; p = 0.691) or in cases with appropriate definitive antimicrobial therapy (OR 1.61, 95% CI 0.69-3.72; p = 0.270) after adjustment for other variables.Our findings suggest that the administration of inappropriate initial antimicrobial therapy might be associated with an adverse outcome in patients experiencing bacteremic biliary tract infections, and that the impact of inappropriate therapy on the outcome may be dependent on therapeutic drainage and appropriate definitive antimicrobial therapy.

Patients with gallbladder cancer usually have a poor prognosis, and effective standard chemotherapeutic regimens have not been established. The anticancer activities of guggulsterone have been demonstrated in various cancer cells. The aims of the study were to determine the effect of guggulsterone on gallbladder cancer cells and to investigate whether treatment with guggulsterone influences the antitumor activities of gemcitabine. The Dojindo Cell Counting Kit-8 assay was used to determine the inhibition of proliferation by drugs in TGBC1 and TGBC2 cells. Cell migration and invasion were examined using 24-well inserts and Matrigel™-coated invasion chambers. The activities of NF-κB p65, VEGF-C, and MMP-2 were measured by ELISA. Guggulsterone inhibited the proliferation and suppressed migration and invasion of gallbladder cancer cells in a dose-dependent manner. Guggulsterone significantly decreased NF-κB p65, VEGF-C, and MMP-2 activities in the gallbladder cancer cells examined. Gallbladder cancer cells treated with a combination of guggulsterone and gemcitabine demonstrated significant inhibition of cell proliferation and invasion when compared to treatment with gemcitabine alone. In addition, NF-κB p65 activation decreased significantly in cells treated with a combination of guggulsterone and gemcitabine when compared to treatment with gemcitabine alone. Guggulsterone exhibits anticancer activities and enhances the antitumor activities of gemcitabine through the suppression of NF-κB activation in gallbladder cancer cells. These results suggest that guggulsterone could be a potential therapeutic option for patients with gallbladder cancer.

The prevalence of antibiotic-resistant pathogens continues to increase steadily. The aim of this study was to analyze the changing patterns and risk factors of antibiotic resistance in patients with bacteremic biliary tract infections (BTIs). In addition, prognostic factors related to survival in patients with a bacteremic BTI were evaluated.Five hundred fifty-six biliary bacteremic events in 411 patients, treated from January 2000 to April 2010, were retrospectively analyzed. In addition, biliary bacteremic events were divided into nosocomial infections (N=396) and community-acquired infections (N=160).The resistance rate to third-generation cephalosporin was higher in 2005-2009 (35 out of 140, 25%, vs. 72 out of 151, 47.7%). The prevalence of extended-spectrum β-lactamase-producing organisms of Escherichia coli and Klebsiella strains increased markedly from 2.3% (2 out of 86) in 2000-2004 to 43.9% (58 out of 132) in 2005-2009. Nosocomial infection, hospital days before bacteremia, previous hospitalization within 90 days, previous use of antibiotics within 90 days, and an indwelling biliary drainage catheter were found to be independently associated with antibiotic resistance. However, no association was found between antibiotic resistance and mortality in patients with biliary bacteremia.Antibiotic resistance in bacteremic BTI has increased markedly during the past 10 years. Almost half of nosocomial bacteremic BTI caused by common Gram-negative pathogens during 2005-2009 (58.5%) could not be treated with third-generation cephalosporin. Clinical outcomes were found to be associated with bacteremia severity and underlying illness rather than antibiotic resistance.

Despite an increase in the reports of intraductal papillary neoplasm of the bile duct (IPN-B), the clinical characteristics and long-term prognosis of this disease are not well known compared with those of intraductal papillary mucinous neoplasms of the pancreas. The objective of our study was to compare the clinical features, radiologic findings, and clinical outcomes of IPN-B according to histologic subtype.A retrospective analysis was performed on the medical records of 97 patients diagnosed with IPN-B by pathologic analysis of their surgical specimens between May 1995 and May 2010. We compared the clinical manifestations, radiological findings, pathologic grade, curative resection rate, recurrence, and overall survival according to four histologic subtypes: gastric (n=15), intestinal (n=46), pancreaticobiliary (n=33), and oncocytic (n=3), which were classified on the basis of hematoxylin and eosin staining and the immunohistochemical profile of mucin core proteins.Mucin hypersecretion was significantly more frequent in patients with gastric and intestinal types than it was in those with oncocytic and pancreaticobiliary types (P=0.014). There were no significant differences between groups regarding the presence of bile duct stones or tumor location. The frequency of invasive carcinoma in the pancreaticobiliary type was significantly higher than those in the gastric and intestinal types (72.7 vs. 26.7 and 32.6%, P0.001 and P0.001). When comparing the survival curves according to histologic subtype, patients with pancreaticobiliary type demonstrated significantly worse survival compared to those with gastric and intestinal types (P=0.035).Gastric and intestinal types of IPN-B have similar clinical characteristics compared with the pancreaticobiliary type, which has a worse prognosis.

PURPOSE The prognosis of gastric cancer patients with bone marrow metastases is extremely poor. The current study was conducted to evaluate the clinical outcomes of advanced gastric cancer patients with bone marrow metastases. MATERIALS AND METHODS We retrospectively reviewed the medical records of 26 advanced gastric cancer patients with bone marrow metastases who were treated at Soonchunhyang University Hospital between September 1986 and February 2009. RESULTS The median age was 46 years (range, 24 to 61 years). All patients had poorly differentiated adenocarcinoma, including 17 signet ring cell carcinomas. The majority of the patients had thrombocytopenia, anemia, and elevated lactate dehydrogenase levels. Sixteen patients (61.5%) received palliative chemotherapy (median, 4 cycles; range, 1 to 13 cycles). The median overall survival after detection of bone marrow metastases for the cohort of patients was 37 days (95% confidence interval, 12.5 to 61.5 days). The median overall survival after detection of bone marrow involvement was 11 days in the best supportive care group (range, 2 to 34 days) and 121 days (range, 3 to 383 days) in the palliative chemotherapy group (p

Biliary strictures are a major cause of morbidity and mortality for liver transplant recipients. The endoscopic management of biliary strictures is not well established after living donor liver transplantation (LDLT) in comparison with deceased donor liver transplantation. The aims of this study were to assess the initial success rate of primary endoscopic treatment of biliary strictures after LDLT and to identify predictors of the feasibility of endoscopic management. One hundred thirty-seven adult patients who underwent LDLT and were confirmed to have biliary strictures by endoscopic retrograde cholangiopancreatography (ERCP) were enrolled. The biliary strictures were primarily managed endoscopically with internal drainage or nasobiliary catheterization. The initial success rate for the primary endoscopic management of biliary strictures after LDLT was 46.7% (64 of 137 patients), and the feasibility of endoscopic management was associated with the stricture-to-ERCP interval (the interval between the development of the total bilirubin, aspartate aminotransferase, or alanine aminotransferase level to >2 times the upper limit of normal and the performance of ERCP) as well as cholangiographic findings (eg, the stricture morphology and the tip shape of the distal duct). In conclusion, when biliary strictures are noticed after LDLT, prompt endoscopic interventions may improve the initial success rate of primary endoscopic management. In addition, the feasibility of primary endoscopic management can be predicted by the cholangiographic findings, which may help with the choice of the therapeutic modality. Liver Transpl, 2011. © 2011 AASLD.