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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

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.

Aim Cytotoxic chemotherapy-based treatment of multiple myeloma (MM) is not curative, and the disease eventually recurs. This is partially because although currently available anti-MM strategies are effective in targeting the bulk of tumor cells, they do not target the tumor-initiating subpopulation of cancer stem cells. This study investigated the prevalence and biological functions of side population (SP) cells in MM cell lines including RPMI8226, ARH77, MM.1R and IM 9. Materials and methods Flow cytometry-based Hoechst 33342 staining was used to evaluate the existence of SP cells. In addition, the ability of SP cells to regenerate the original population was determined. Results The frequency of SP cells was heterogeneous. Most cell lines (ARH77, IM9, and MM.1R) contained fewer than 1% SP cells; however, RPMI8226 contained approximately 10% SP cells. Sorted SP cells showed a higher proliferative ability and clonogenicity than the MP in the RPMI8226 myeloma cell line. The activity of ATP-binding cassette subfamily G member 2 (ABCG2), which is associated with high rates of proliferation, was higher in SP cells. However, the expression of specific surface markers such as cluster of differentiation (CD)138, CD34, CD38, CD19, CD20, and CD27 did not differ between SP and MP cells. Bortezomib was the only agent that significantly affected proliferation of both SP and MP cells. Conclusion Our studies demonstrated that the SP fraction of myeloma cells possessed clonogenic tumor-initiating potential and revealed new mechanisms of action for bortezomib on SP cells.

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.

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.

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/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.

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.

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.

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.

Lymph node (LN) metastasis is one of the most important risk factors for the prognosis of pancreatic cancer. This study aimed to identify novel LN metastasis-associated markers and therapeutic targets for pancreatic and gallbladder cancers. DNA microarray analysis was carried out to identify genes differentially expressed between 17 pancreatic cancer tissues with LN metastasis and 17 pancreatic cancer tissues without LN metastasis. The expression of LZIC, FXR, SCAMP1, and SULT1E1 is significantly higher in pancreatic cancer tissues with LN metastasis than in pancreatic cancer tissues without LN metastasis. We recently reported that FXR plays an important role in LN metastasis of pancreatic cancer, and in this study, we selected the secretory carrier membrane protein 1 (SCAMP1) gene. To determine that function of the SCAMP1 gene, we examined the effects of SCAMP1 knockdown on pancreatic and gallbladder cancer proliferation, migration, and invasion using SCAMP1 small interfering RNA (siRNA) and the activity of vascular endothelial growth factor (VEGF) was measured by enzyme-linked immunosorbent assay. SCAMP1 overexpression is associated with LN metastasis in pancreatic cancer patients. The siRNA-mediated downregulation of SCAMP1 resulted in a marked reduction in cell migration and invasion, but not proliferation in MIA-PaCa2, PANC-1, TGBC-1, and TGBC-2 cells. In addition, downregulation of SCAMP1 inhibited VEGF levels of conditioned medium from SCAMP1 siRNA-transfected cells. These results suggest that downregulation of SCAMP1 could be a potential therapeutic target for patients with pancreatic and gallbladder cancer.

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.

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 In recent years, a large number of micro-ribonucleic acids (miRNAs) have been identified as putative prognostic biomarkers for solid cancers because of their role in controlling the expression of oncogenes and tumor suppressor genes. The aim of this study was to verify the utility of miRNA 141 as a prognostic biomarker of biliary tract cancers. Methods From June 2010 to June 2012, common bile duct cancer tissue samples and matched noncancerous tissues from the ampulla of Vater were obtained from patients with biliary tract cancer undergoing endoscopic retrograde cholangiopancreatography. Using quantitative real-time polymerase chain reaction assays, we measured the mean relative expression levels of miRNA 141 in both groups of tissues. Overexpression of miRNA 141 was defined as a greater than 2-fold increase in expression levels as determined by the 2−ΔΔCt method. Results In a cohort of 38 patients with biliary tract cancers (seven gallbladder, 13 hilar, and 18 distal bile duct cancers), 26 patients (68.4%) were male, and the median age was 69.5 (52 to 85) years. Nineteen patients (50%) had undergone R0 resection procedures, including three Whipple operations, seven pylorus-preserving pancreaticoduodenectomies, six bile duct resections, and three extended lobectomies. Among the patients who had undergone R0 resection, the overexpression of miRNA 141 was significantly associated with shorter disease-free survival and a greater risk of angiolymphatic invasion. Among the patients who did not undergo R0 resection, miRNA 141 overexpression was significantly associated with reduced overall survival. Conclusions Overexpression of miRNA 141 is an indicator of a poor prognosis in patients with biliary tract cancer, suggesting that miRNA 141 may be a valuable prognostic biomarker of this disease.

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

Background/Aims: The aim of this study was to evaluate the usefulness of health screening for early detection and improved prognosis in pancreatic cancer. Methods: Between 1995 and 2008, 176,361 examinees visited the Health Promotion Center (HPC). Twenty patients diagnosed with pancreatic cancer were enrolled. During the same period, 40 patients were randomly selected from 2,202 patients diagnosed with pancreatic cancer at the Out Patient Clinic (OPC) for comparison. Results: Within the HPC group, 10 patients were initially suspected of having pancreatic cancer following abnormal ultrasonographic fi ndings, and 9 patients had suspected cases following the detection of elevated serum CA 19-9. The curative resection rate was higher in the HPC group than in the OPC group (p=0.011). The median survival was longer in the HPC group than in the OPC group (p=0.000). However, there was no significant difference in the 3-year survival rate between the two groups. Asymptomatic patients (n=6/20) in the HPC group showed better curative resection and survival rates than symptomatic patients. However, the difference was not statistically signifi cant. Conclusions: Health screening is somewhat helpful for improving the curative resection rate and median survival of patients with pancreatic cancer detected by screening tests. However, the benefi t of this method in improving long-term survival is limited by how early the cancer is detected. (Gut Liver 2011;5:194199)

PURPOSE This phase II clinical trial was conducted to evaluate the activity and safety of a combination treatment of paclitaxel (Genexol®) plus carboplatin in patients with advanced non-small cell lung cancer. MATERIALS AND METHODS Chemotherapy-naive patients having histologically confirmed advanced or metastatic non-small cell lung cancer were enrolled. Genexol® was administered at 225 mg/m(2) intravenous (IV) infusion over 3 hours, followed by carboplatin (area under the concentration-time curve=6) IV on day 1 every 3 weeks. RESULTS Twenty-eight patients were enrolled between January 2003 and January 2005. A total of 110 cycles of chemotherapy were given. The median number of chemotherapy cycles was 4. A total of 25 study patients were evaluable. On an intent-to-treat basis, there were ten partial responses (response rate 35.7%). The median time-to-progression was 3.2 months (95% confidence interval [CI], 1.5 to 4.9) and the median overall survival was 8.2 months (95% CI, 4.1 to 12.3). The main hematologic grade 3/4 toxicity was neutropenia, which was observed in 14 (50.0%) patients. The main non-hematologic toxicity was peripheral neuropathy, which was observed in 12 patients (42.9%). Grade 3/4 neuropathy occurred in 8 patients (28.6%) and three patients discontinued treatment because of neuropathy. CONCLUSION In this trial, the combination of Genexol® and carboplatin showed significant activity as first line treatment for patients with advanced or metastatic non-small cell lung cancer. However, a modest dose reduction of Genexol® is needed due to sensory neuropathy.

To clarify the clinical and pathophysiological characteristics of autoimmune pancreatitis (AIP) in Asia.A retrospective, actual situation survey of AIP diagnosed by Asian criteria was conducted in 10 centers of Japan, Korea, Taiwan, China, and India.A total of 327 AIP cases (258 male and 69 female subjects; average age, 60.0 years) were enrolled. Obstructive jaundice was the most frequent initial symptom (46%-74%), followed by weight loss (4%-51%) and abdominal pain (19%-44%). Diffuse swelling of the pancreas was frequent in Japan (64%) and Korea (81%), but segmental swelling of the pancreas was more frequent in Taiwan (70%) and China (72%) (P0.01). Serum immunoglobulin G4 levels were elevated in 58%-100% of cases in Japan, Korea, and Taiwan. Pathologically, almost all AIPs in Asia were lymphoplasmacytic sclerosing pancreatitis. Sclerosing cholangitis was the most frequent extrapancreatic lesion (60%-81%). Steroid therapy was a major and effective therapeutic strategy in Japan, Korea, and Taiwan. However, the rate of resection or bypass operation was higher in Taiwan (40%) and China (72%) (P0.01).Features of AIP are fundamentally similar in Japan, Korea, Taiwan, and China. Knowledge of emerging AIP should be more widespread in Asia to avoid unnecessary operation.

Objective: Our aim was to devise a prognostic model for advanced pancreatic cancer based on clinical parameters. Methods: We retrospectively analyzed the medical records of 298 patients who received gemcitabine-based chemotherapy from January 1999 to November 2008. Results: The median survival of all patients was 7 months [95% confidence interval (CI) 6.2–7.8]. Multivariate analysis revealed poor prognostic factors for overall survival such as the presence of liver metastasis [p < 0.001, hazard ratio (HR) 2.628, 95% CI 1.620–4.264], the presence of ascites or peritoneal carcinomatosis (p = 0.005, HR 1.783, 95% CI 1.194–2.661), serum C-reactive protein levels >1.2 mg/dl (p = 0.021, HR 1.568, 95% CI 1.070–2.300), and serum albumin levels Conclusions: This prognostic model could help to select treatment for patients in clinical practice, and these risk-adapted treatment strategies should be further investigated in prospective studies in such patient populations.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are classified into the following four histopathologic subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. However, the clinicopatholgic characteristics of IPMN subtypes have not been fully clarified. Recently, a subgroup classification of minimally invasive intraductal papillary mucinous carcinomas (MI-IPMCs) was suggested in contrast to overt invasive carcinoma from IPMCs (IC-IPMCs). The purpose of this study was to determine whether or not the pathologic subtype classification can predict prognosis and to validate the usefulness of the newly proposed diagnostic criteria of MI-IPMCs. We reviewed the clinicopathologic characteristics of 142 surgically resected cases of IPMNs. There were 54, 56, 30, and two cases of the gastric, intestinal, pancreatobiliary, and oncocytic types of IPMNs, respectively. The intestinal and pancreatobiliary types were more likely to have a main duct type. All gastric type tumors were adenomas or moderate dysplasia, whereas greater than one half of the intestinal and pancreatobiliary types were carcinomas in situ or invasive carcinomas. A significant difference in recurrence and death rate was noted for invasive carcinoma between the intestinal and pancreatobiliary types. The majority of MI-IPMCs were the intestinal type, whereas the majority of IC-IPMCs were the pancreatobiliary type. The IC-IPMC group showed a decreased recurrence-free and overall survival with statistically significance (p < 0.001 and p = 0.001, respectively). Our results suggest that the pathologic subtype classification and the newly proposed diagnostic criteria for minimal invasion may also be useful to predict prognosis of IPMNs of the pancreas.

Xanthogranulomatous cholecystitis (XGC) mimics early-stage gallbladder (GB) cancer with wall thickening on computed tomography (CT), both clinically and radiologically. Preoperative differentiation of XGC from early-stage GB cancer is important for selecting the most appropriate surgical management. Therefore, we evaluated the clinical features and multidetector CT (MDCT) findings of XGC to determine whether it can be distinguished from early-stage GB cancer.We retrospectively evaluated 25 patients with XGC and 56 patients with the wall-thickening type of T1- and T2-stage GB cancer, where all of the diagnoses were pathologically confirmed by surgical treatment. All of the patients underwent preoperative MDCT. The clinical symptoms, laboratory findings, and CT findings were compared.Abdominal pain, fever, and jaundice were noted more frequently in the patients with XGC. Serum aspartate aminotransferase and alanine aminotransferase levels were more elevated in patients with XGC, whereas carbohydrate antigen (CA 19-9) was higher in the patients with GB cancer. When the T-category cancer staging of XGC and early-stage GB cancer were compared, diffuse GB wall thickening, intramural hypoattenuated nodule, gallstone, and pericholecystic infiltration were consistent significant findings associated with XGC, regardless of the cancer staging.MDCT findings such as diffuse GB wall thickening, intramural hypoattenuated nodule, gallstone, and pericholecystic infiltration together with the clinical symptoms, can provide clues for physicians to differentiate XGC from early-stage GB cancer with wall thickening on CT.

Background and Aim: This study aimed to determine the clinical characteristics of immunoglobulin G4 (IgG4)-associated sclerosing cholangitis (ISC) and provide clinical clues differentiating ISC from primary sclerosing cholangitis (PSC) or hilar cholangiocar- cinoma (CCC). Methods: Sixteen patients with ISC manifesting as hilar/intrahepatic strictures were ana- lyzed for clinical characteristics and compared with patients with PSC and hilar CCC as disease controls for histology and serum IgG4 levels. Results: Distinguished biliary imaging findings of ISC included multifocal biliary tree involvement (n = 14), concentric bile duct thickening with preserved luminal patency (n = 13), and relatively mild proximal dilatation, despite prominent bile duct thickening (n = 11). Serum IgG4 levels were elevated in 12 patients (75%), but not in any of the 25 patients with hilar CCC.Ten patients (63%) had a past or concurrent history of autoimmune pancreatitis (AIP). The significant infiltration of IgG4-positive cells was observed with endobiliary or liver biopsy in 11 of 16 patients (69%) with ISC, but not in any patients with PSC or hilar CCC. Extrabiliary organ involvement, including sialadenitis, inflammatory pseudotumor of the liver and kidney, and retroperitoneal fibrosis, was present in seven patients. Marked improvement of biliary strictures and/or extrabiliary involvement was observed in all ISC patients after steroid therapy. Conclusions: ISC should be considered in the differential diagnosis of hilar/intrahepatic biliary strictures. Past or concurrent AIP or extrabiliary organ involvement strongly sug- gests the possibility of ISC. Significant infiltration of IgG4-positive cells on endobiliary or liver biopsy specimens, and/or elevated serum IgG4 levels, highly support the diagnosis of ISC and provide the rationale for steroid therapy.

This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catheterization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catheterization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC.

Mammary serine protease inhibitor (maspin, SERPIN-B5) is expressed in normal human mammary epithelial cells and is known to be down-regulated during cancer progression. Aberrant maspin expression has been reported in a number of cancers, including pancreatic and ovarian cancer. Recently, we identified several genes that may be tumor markers for gallbladder (GB) cancer using a DNA microarray method. There are no published data regarding maspin expression in GB cancer. The aims of this study were to determine maspin expression in normal mucosa, adenoma, dysplasia and carcinoma of GB, and to compare the pattern of maspin expression in early and advanced GB cancers. One hundred one patients with primary GB cancer who underwent resection between March 1999 and May 2008 were included. Twenty-five adenomas and 10 normal GB specimens were also included. We performed tissue microarray construction and immunohistochemical staining to evaluate maspin expression. The immunostaining results were estimated semiquantitatively by one pathologist. The positive rate of maspin expression was 59.4% (60/101) in GB cancer, whereas no maspin was expressed in adenomas and normal mucosa of GB. In case of positive maspin expression, it was gradually increased from dysplasia to carcinoma. No significant difference in the positive rate of maspin expression between early and advanced cancer was detected (49% versus 60%; P = 0.731). This result suggests that maspin expression may be involved in dysplasia-carcinoma sequence and the early steps of GB carcinogenesis.