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Neoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel.From 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors.Eighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)].In patients with pre-treatment CA19-9500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients.

Background Peritoneal metastasis is one of the most important poor prognostic factors in advanced pancreatic cancer (PC). Whether the prognosis of PC with peritoneal metastasis has improved with the advent of gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX) is uncertain. The aim of this study was to evaluate the improvements in treatment outcomes of PC with peritoneal metastasis. Methods We retrospectively investigated consecutive PC patients with peritoneal metastasis treated with chemotherapy at our institution between 2010 and 2019. We compared the clinical characteristics and survival outcomes according to the period of diagnosis (group A, 2010–2014; group B, 2015–2019) and chemotherapy regimen. We also examined the prognostic factors for overall survival (OS). Results Among 180 patients included (GnP 88; mFFX 14; other regimens 78), distant metastasis was confined to the peritoneum in 89 patients. Although group B had a worse performance status compared to group A, median OS was significantly longer in group B. GnP and mFFX showed a significantly higher objective response rate and disease control rate in addition to longer progression free survival and OS compared to other regimens. The administration of GnP or mFFX, performance status, and neutrophil to lymphocyte ratio ≥5 were identified as independent prognostic factors for OS. Furthermore, the amount of ascites and extent of peritoneal metastasis were significantly associated with OS in patients with distant metastasis confined to the peritoneum. Conclusions The prognosis of PC with peritoneal metastasis has significantly improved over time with the advent of GnP and mFFX.

Background The prognosis of borderline resectable (BR) pancreatic cancer (PC) has improved by multidisciplinary therapy. However, the differences in clinical course between pancreatic head (Ph) and pancreatic body and tail (Pbt) cancer has not been fully elucidated. Therefore, we conducted this study to compare the clinical course of BR PC patients according to tumor location. Methods We retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics, treatment, recurrence pattern and post recurrence treatment between Ph and Pbt cancer patients. We also compared recurrence free survival (RFS) and overall survival (OS) according to tumor location. Results A total of 108 patients with BR PC were included. Tumor location was Ph 74 and Pbt 34, respectively. Initial regimen of NAC was nab-paclitaxel/gemcitabine in 106 and gemcitabine in 2, respectively. Although Pbt location was associated with more advanced T stage, it showed similar N stage, pathological stage, RFS, OS, and details of adjuvant chemotherapy compared to Ph location. The most common site of postoperative recurrence was liver-only recurrence in Ph tumor (32% vs. 6%, p = 0.04) and peritoneal dissemination-only recurrence in Pbt tumor (35% vs. 11%, p = 0.06). Furthermore, Ph cancer patients received a higher rate of monotherapy compared to Pbt cancer patients (19% vs. 0%, p = 0.08). Conclusions In our experience tumor location was not a prognostic factor for OS in BR PC. Postoperative recurrence pattern and treatment after recurrence were different according to tumor location.

Wire-guided cannulation (WGC) was reported to decrease post-ERCP pancreatitis (PEP), but risk factors for PEP in WGC are not fully elucidated.To evaluate the incidence and risk factors of PEP in WGC.Single-center retrospective study.Academic center.A total of 800 consecutive patients with a native papilla.Biliary therapeutic ERCP by using WGC.The rate of PEP and its risk factors.Biliary cannulation was successful by using WGC alone in 70.5%, and the final cannulation rate was 96.1%. Unintentional guidewire insertion and contrast material injection into the pancreatic duct (PD) during cannulation occurred in 55.3% and 21.8%, respectively. The incidence of PEP was 9.5% (mild 5.6%, moderate 2.9%, severe 1.0%). Multivariate analysis revealed a common bile duct (CBD) diameter of 9 mm (odds ratio [OR] 2.03; P = .006) and unintentional guidewire insertion into the PD (OR 2.25; P = .014) as risk factors for PEP. PD opacification was not a risk factor for PEP (OR 1.15; P = .642), but the incremental increase of the PEP rate was seen in patients with CBDs 9 mm: 4.6% without any PD manipulation, 8.3% with contrast material alone, 16.9% with guidewire alone, and 22.1% with both contrast material and guidewire.Retrospective design in a single center.Unintentional PD manipulation was not uncommon in WGC. Guidewire insertion into the PD and a small CBD were risk factors for PEP in biliary therapeutic ERCP with the use of WGC.

Objectives Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is diagnosed on the basis of pancreatic pain and hyperamylasemia. However, because the diagnosis of abdominal pain is not objective, there may be some cases of painless pancreatitis among patients with post-ERCP hyperamylasemia (PEH). We reviewed the computed tomography (CT) findings of PEH cases to determine the incidence of painless pancreatitis. Methods Between July, 2005 and December, 2011, CT was performed in 91 patients with hyperamylasemia 18 h after ERCP. We reviewed the CT findings and graded the severity of pancreatitis according to the Balthazar grading system. Grades C, D, and E were defined as pancreatitis. Results Thirty-four patients (37%) had pancreatitis according to the CT findings. There was a significant difference in the serum amylase levels between the positive- and negative-CT finding groups (1306 ± 833 vs. 786 ± 315 IU/L, respectively; p = 0.0012). Receiver operating characteristic curve analysis showed that the amylase cut-off value for discriminating between the 2 groups was 795 IU/L (6.36 times the upper normal limit). Conclusions Thirty-seven percent of PEH patients had painless pancreatitis. CT is useful to determine pancreatitis in patients taking analgesics, steroids, or anti-immunological drugs and those with diabetes mellitus and 18-h serum amylase levels of >6 times the normal upper limit.

Background Precision medicine using next gene sequencing (NGS) of tumor tissues has become mainstream of cancer therapy. Liquid biopsy is minimally invasive Method of sampling to assess tumor genotypes, and would be useful for detecting targetable mutations, follow-up during therapy, and detecting relapse, but more data are needed to clarify its significance. We show some preliminary data for liquid biopsy to detect actionable mutations in various cancer patients. Method We analyzed peripheral blood (14 ml) of patients with various cancers resistant to or without standard therapy and purified circulating cell-free DNA and RNA, then sequenced with customized Oncomine Pan-cancer cell free assay to detect actionable mutations in 95 genes. Data would be confirmed with sequencing of cancer tissues if possible, and be followed during therapy. Results From September 2018 to February 2019, 41 patients were analyzed. Of the 41 patients, primary loci of cancer are breast (n = 12), pancreas (n = 7), soft tissue sarcoma (n = 6), uterine (n = 5), head and neck (n = 3), ovary (n = 3), urothelial (n = 2), others (n = 3). The median age was 57 (25-78) years, performance status was 0-1 in all patients. No actionable mutation was detected in 7 patients. In other 34 patients, some significant mutations could be detected. Of those mutations, TP53 mutations were detected in 20 patients, PIK3CA mutations in 10, KRAS mutations in 7, AKT1 mutation in 1, BRAF mutation in 1, MTOR mutation in 1, FGFR3 amplification in 3. Conclusion The results suggest that actionable or druggable mutation can be detected by liquid biopsy using NGS. Further validation with tumor tissue examination and targeting therapy is needed.

Diabetes mellitus (DM) is recognized as a risk factor for pancreatic cancer (PaC) and expected to be a clue for early diagnosis. However, it is still obscure whether a diagnostic strategy using DM as a clue can improve the prognosis or not.We retrospectively reviewed 540 patients with PaC, and investigated the prognosis with regard to the reasons for diagnosis. We compared patients diagnosed by imaging studies performed when DM was newly diagnosed or deteriorated, and patients diagnosed by symptoms.The prevalence of DM in PaC patients was 45% (256/540) and did not differ between disease stages. More than half of DM in PaC patients (150/256) were new-onset (2 years in duration). One hundred sixty one patients (30%) were asymptomatic at PaC diagnosis. There were 38 patients diagnosed in association with DM (by new-onset DM, 16; by aggravation of long-standing DM, 22). Asymptomatic patients had smaller primary tumor and were diagnosed at an earlier stage. The prognosis of PaC patients complicated with DM did not differ from that of patients without DM; however, patients had better prognosis if they were diagnosed in association with DM alone (median survival time, 20.2 months), compared with patients diagnosed by symptoms (10.2 months, P 0.01).Our analysis revealed that patients diagnosed in association with DM had better survival than symptomatic patients. Given the high prevalence of DM in PaC patients, DM can be a useful diagnostic clue for screening and lead to improvement of prognosis in PaC patients.

Endoscopic biliary stent placement is widely accepted as palliation for malignant biliary obstruction or as a treatment of benign biliary stricture. Although various biliary stent designs have become available since self-expandable metallic stents were introduced, no single ideal stent has been developed. An ideal stent should be patent until death, or surgery, in patients with resectable malignant biliary obstruction. Fewer complications, maneuverability, cost-effectiveness, and removability are also important factors. Alternatively, should we develop a novel method for biliary drainage other than biliary stenting via endoscopic retrograde cholangiopancreatography? This article reviews the current status of biliary stenting for malignant biliary obstructions.

Background Although the placement of self-expandable metal stents (SEMSs) has been widely accepted as palliation for distal malignant biliary obstruction, the risk factors for their early dysfunction remain unclear. Objective To identify risk factors for early ( Design A multicenter retrospective study. Setting Five tertiary referral centers. Patients Patients were included who underwent first-time SEMS placement for distal malignant biliary obstruction caused by pancreatic cancer between April 1994 and August 2010. Main Outcome Measurements Rates and causes of early dysfunction were evaluated, and risk factors were analyzed. Results In all, 317 eligible patients were identified. Covered SEMSs were placed in 82% of patients. Duodenal invasion was observed endoscopically in 37%. The median time to dysfunction was 170 days. The rates of all and early SEMS dysfunction were 55% and 31%, respectively. The major causes of SEMS dysfunction were food impaction and nonocclusion cholangitis (21% each) in early dysfunction and sludge (29%) in nonearly dysfunction. The rate of early dysfunction was 42% with duodenal invasion and 24% without duodenal invasion ( P = .001). Early dysfunction caused by food impaction was more frequent in patients with duodenal invasion (10% and 4%, P = .053). Duodenal invasion was a risk factor (odds ratio 2.35; 95% CI, 1.43–3.90; P = .001) in a multiple logistic regression model. Limitations A retrospective design. Conclusions Duodenal invasion is a risk factor for early SEMS dysfunction in patients with pancreatic cancer.

Intrapancreatic bile duct stricture in autoimmune pancreatitis (AIP) is usually diagnosed as sclerosing cholangitis even if the stricture is limited to the intrapancreatic area. However, it is not known whether compression caused by pancreatic edema or biliary wall thickening causes such a biliary stricture.Our purpose was to clarify the factor that contributes to intrapancreatic biliary stricture in AIP: pancreatic head lesion or biliary wall thickening.Single-center retrospective study.This study was performed in a tertiary care academic medical center.Fifty-six patients with AIP were included.The relationship between the presence of a pancreatic head lesion and intrapancreatic biliary stricture was examined. In addition, the relationship between the extent of the intrapancreatic biliary stricture and the wall thickening was evaluated.Among 44 patients with a pancreatic head lesion, 41 (93%) had intrapancreatic bile duct stricture. Among 12 patients without a pancreatic head lesion, only 2 had such a stricture (P.0001). Intraductal US showed average intrapancreatic biliary wall thickening with severe stricture of 2.7 +/- 1.0 mm, significantly thicker than that with mild stricture (1.9 +/- 0.35 mm; P = .0200).Intraductal US was not performed in all patients.Both pancreatic edema and biliary wall thickening influenced intrapancreatic biliary stricture in AIP. This type of stricture should be differentiated from extrapancreatic biliary stricture that may be caused by biliary wall thickening only.

Background & Aims: K-ras mutation is frequently detected in pancreatic juice of patients with pancreatic small cystic lesions, as well as those with pancreatic cancer. Those cystic lesions are often found by chance with modern radiologic imaging modalities. In this study, we prospectively examined the prognosis of patients with pancreatic cystic lesions, focusing on pancreatic cancer development. Methods: A total of 197 patients with pancreatic cystic lesions, 80 with intraductal papillary mucinous neoplasm (IPMN) and 117 with non-IPMN cysts, were followed up for 3.8 years on average. Blood tests and imaging diagnosis were performed twice a year. The observed incidence of pancreatic cancer was compared with the expected incidence calculated on the basis of age- and gender-matched mortality of pancreatic cancer in the general Japanese population. Results: Pancreatic cancer developed in 7 patients during the observation period (0.95% per year), infiltrating ductal carcinoma in 5 and intraductal papillary mucinous carcinoma in 2. Three of the ductal cancer cases had pancreatic non-IPMN cyst as preexisting lesion. At least 2 of the carcinomas arose in regions remote from preexisting lesions. The observed incidence of pancreatic cancer was 22.5 times higher (95% confidence interval, 11.0–45.3) than expected mortality from this cancer among general population. Conclusions: Patients with pancreatic cystic lesions are at a considerably high risk for pancreatic cancer, with a standardized incidence rate of 22.5. Cancer might develop in regions remote from the preexisting cystic lesion, suggesting diffuse pathologic changes predisposing to malignant transformation in the entire pancreas harboring cystic lesions.

Background & Aims: Cholecystitis after metallic stent (MS) placement is an issue requiring attention. From our experience, cholecystitis seemed to occur mainly in patients with tumor involvement to the cystic duct orifice. The aim of the present study was to identify risk factors for cholecystitis in patients treated with covered or uncovered MS. Methods: We analyzed 246 patients who received MS placement (covered MS in 171 and uncovered in 75) between August 1997 and May 2005 for the treatment of unresectable distal malignant biliary obstruction. Causative diseases were as follows: pancreatic cancer in 162, papillary cancer in 10, bile duct cancer in 41, and metastatic nodes in 33 patients. Tumor involvement to orifice of the cystic duct (OCD) was diagnosed based on cholangiography and intraductal ultrasonography. Results: Cholecystitis after MS placement was found in 13 patients (5.3%). There was no significant difference in the incidence of cholecystitis between covered (5.8%) and uncovered (4.0%) MS. By univariate analysis, tumor involvement of the OCD, MS placed above the papilla, and stricture located at midportion were associated significantly with cholecystitis. By multivariate analysis, only tumor involvement of the OCD was a risk factor, with an odds ratio of 47.206 (95% confidence interval, 5.84–381.60). Conclusions: Cholecystitis after MS placement is associated with tumor involvement to the orifice of the cystic duct, regardless of the type of stent.

Objectives: New modalities, namely, endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), and helical computed-tomographic cholangiography (HCT-C), have been introduced recently for the detection of common bile duct (CBD) stones and shown improved detectability compared to conventional ultrasound or computed tomography. We conducted this study to compare the diagnostic ability of EUS, MRCP, and HCT-C in patients with suspected choledocholithiasis. Methods: Twenty-eight patients clinically suspected of having CBD stones were enrolled, excluding those with cholangitis or a definite history of choledocholithiasis. Each patient underwent EUS, MRCP, and HCT-C prior to endoscopic retrograde cholangio-pancreatography (ERCP), the result of which served as the diagnostic gold standard. Results: CBD stones were detected in 24 (86%) of 28 patients by ERCP/IDUS. The sensitivity of EUS, MRCP, and HCT-C was 100%, 88%, and 88%, respectively. False negative cases for MRCP and HCT-C had a CBD stone smaller than 5 mm in diameter. No serious complications occurred while one patient complained of itching in the eyelids after the infusion of contrast agent on HCT-C. Conclusions: When examination can be scheduled, MRCP or HCT-C will be the first choice because they were less invasive than EUS. MRCP and HCT-C had similar detectability but the former may be preferable considering the possibility of allergic reaction in the latter. When MRCP is negative, EUS is recommended to check for small CBD stones.

Background & Aims: Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP), and hyperenzymemia after ERCP is common. Because ulinastatin, a protease inhibitor, has proved effective in the treatment of acute pancreatitis, the aim of this study was to assess the efficacy of ulinastatin for the prevention of post-ERCP pancreatitis and hyperenzymemia. Methods: In a multicenter, randomized, double-blind, placebo-controlled trial, patients undergoing a first ERCP were randomized to receive ulinastatin (150,000 U) or placebo by intravenous infusion for 10 minutes starting immediately before ERCP. All patients were hospitalized at least 24 hours after ERCP for evaluation of clinical symptoms. Serum pancreatic enzyme levels were measured before and at 4 and 18 hours after ERCP. The primary end point was the incidence of post-ERCP pancreatitis and the secondary objective was the occurrence of hyperenzymemia. Results: A total of 406 patients were enrolled (204 in the ulinastatin group and 202 in the placebo group). There were no differences between the 2 groups regarding baseline characteristics, details of fluoroscopic findings, or endoscopic procedure. The incidence of hyperenzymemia was significantly lower in the ulinastatin group than in the placebo group (amylase, P = .011; lipase, P = .008). Six patients in the ulinastatin group and 15 patients in the placebo group developed pancreatitis (2.9% vs. 7.4%, P = .041). There was no case of severe pancreatitis in either group. Patients who received ulinastatin did not present any side effects related to the medication. Conclusions: Prophylactic short-term administration of ulinastatin decreases the incidence of pancreatitis and hyperenzymemia after ERCP.

Background & Aims: The aim of this study was to define the bile duct changes associated with autoimmune pancreatitis. Methods: Eight patients with autoimmune pancreatitis were followed for a mean of 4 years. The clinical features of these patients, including extrapancreatic bile duct changes, were examined by using biochemical parameters and several imaging modalities. Pathologic features of the pancreas and liver were examined by using the biopsy specimens of 7 patients. Results: Diffuse or focal narrowing of the main pancreatic duct was observed in all patients. Histologic examination of the pancreas showed lymphoplasmacyte infiltration with severe fibrosis and acinar cell depletion. In 6 patients extrapancreatic bile duct changes such as stricture of the bile duct at hilus or intrahepatic area were observed. In 2 patients abnormalities in the bile duct and pancreas were detected simultaneously at diagnosis, and changes in the bile duct were observed later in 4 patients. Lymphoplasmacyte infiltration and fibrosis were observed in the portal area of all 7 liver biopsy samples. Five of the patients with bile duct changes received steroid therapy, and the pathological changes improved. Conclusions: Extrapancreatic bile duct changes are frequently associated with autoimmune pancreatitis. Similar pathogenic mechanism might produce the biliary tract and pancreatic abnormalities in autoimmune pancreatitis resulting in a similar histopathology in the liver and pancreas and response to steroid therapy.

Background: Two types of quantitative assay kits for K-ras mutations, PCR–preferential homoduplex formation assay (PHFA) and enriched PCR and enzyme-linked mini-sequence assay (ELMA), were recently developed. The K-ras mutations were analyzed using these assays. Materials and methods: DNA was extracted from the pancreatic juice which was obtained by endoscopy from 38 patients with pancreatic neoplasms (23 adenocarcinomas and 15 intraductal papillary neoplasms) and from 62 without it. Results: The results of the two methods were mutually correlative. K-ras mutation was detected at high levels (mutant ras genes occupied >2% of all K-ras genes) in 25 of the 38 cases (66%) with pancreatic neoplasm. It was also detected at high levels in 9 of the 14 cases (64%) with pancreatic cyst. In contrast, the mutant gene was detected at a lower level (

Su1682 Risk Factors for Post-ERCP Pancreatitis in Therapeutic Biliary ERCP Using Wire-guided Cannulation Yousuke Nakai*, Hiroyuki Isayama, Naoki Sasahira, Hirofumi Kogure, Takashi Sasaki, Natsuyo Yamamoto, Miho Matsukawa, Kei Saito, Gyotane Umefune, Shuhei Kawahata, Dai Akiyama, Tomotaka Saito, Tsuyoshi Hamada, Naminatsu Takahara, Suguru Mizuno, Koji Miyabayashi, Ryota Takahashi, Keisuke Yamamoto, Dai Mohri, Kenji Hirano, Minoru Tada, Kazuhiko Koike Department of Gastroenterology, The University of Tokyo, Tokyo, Japan Background: Wire-guided cannulation (WGC) reportedly improves biliary cannulation and decreases post-ERCP pancreatitis (PEP) by preventing contrast injection to the pancreatic duct (PD). However, little is known whether unintentional guidewire (GW) insertion into PD increases PEP or not. The aim of the study is to evaluate risk factors for PEP in therapeutic ERCP using WGC. Patients: Patients with native papilla undergoing therapeutic biliary ERCP using WGC were enrolled. In cases with difficult cannulation, any cannulation method including contrast injection was allowed at discretion of endoscopists. Exclusion criteria were prior history of ERCP, concomitant acute pancreatitis, balloon-assisted ERCP and planned pancreatic intervention. Logistic regression analyses were performed to evaluate risk factors for PEP. Potential risk factors analyzed in the model were as follows: age, gender, BMI, reason for ERCP, pancreatic cancer, ERCP by trainees, periampullary diverticulum, jaundice at ERCP, CBD diameter, procedure time, catheter type, GW type, number/ time of cannulation attempt, final cannulation failure, biliary sphincterotomy, papillary balloon dilation, stone extraction, transpapillary brushing and biopsy, intraductal ultrasonography, nasobiliary drainage, plastic stent, metallic stent, GW insertion into PD, PD opacification, prophylactic PD stent. Factors with p!0.10 by univariate analysis and known risk factors for PEP (age, gender, PD opacification, jaundice at ERCP and EPBD) were further analyzed in a multivariate analysis. Results: Among 5234 ERCPs performed at the University of Tokyo Hospital between January 2008 and October 2013, a total of 800 ERCPs met the inclusion criteria. Reason for ERCP was CBD stone (54.1%), biliary malignancy (36.1%), benign biliary diseases (9.8%). Median procedure time was 40 min. Median cannulation attempts and time to cannulation were 5 attempts and 5 min. Cannulation was successful by WGC alone in 70.5% and final cannulation rate was 96.1%. PD GW insertion and opacification occurred in 55.3% and 21.6%, respectively, and prophylactic PD stent was placed in 12.9%. Overall PEP rate was 9.5% (mild 5.6%, moderate 2.9%, severe 1.0%). Multivariate analysis revealed CBD diameter! 9mm (Odds ratio [OR] 2.03, pZ0.006), GW insertion into PD (OR 2.25, pZ0.014) as risk factors for PEP. In cases with CBD R9 mm, PEP rate did not increase by unintentional PD manipulation, but in cases with CBD!9 mm, PEP rate was 4.6% without PD manipulation, 8.3% with PD opacification alone, 16.9% with PD GW insertion alone and 22.1% with GW insertion and opacification. Conclusion: PEP rate was 9.8% in therapeutic biliary ERCP using WGC. A small CBD diameter and GW insertion into PD were risk factors for PEP. There was an incremental increase of PEP by PD opacification in addition to GW insertion in cases with CBD diameter!9 mm.

decreases in mean DAP and mean Effective Radiation Dose. A significant decrease was also noted in the number of images. Prior to education, LVE had significantly a higher mean DAP and mean Effective Radiation Dose compared to HVE. Following education, no significant differences were seen between the two groups. None of the endoscopists reported any compromise in their ability to interpret and perform ERCP despite incorporating fluoroscopy best practices. Conclusion: Educating endoscopists in fluoroscopy best practices significantly reduces patient radiation exposure during ERCP. This benefit is more pronounced in LVE. All endoscopists (HVE and LVE) benefited from fluoroscopy education, allowing reduction in patient radiation exposure, without compromising their ability to interpret and perform ERCP.

vs. 10%, P 0.05, odds ratio (OR) 7.3, 95% confidence interval (CI) 1.3, 51.8). Normal bilirubin level at admission was also a risk factor (P 0.03, OR 9.9, 95% CI 1.2, 83.6). Perforation occurred in one patient after ERCP and bile peritonitis occurred in one patient after ESBD, both of them were improved with conservative therapy. Drainage tube dislodgement occurred in 3 patients (EBS 2, NBD 1). Of the 76 patients who underwent EBS, stent dysfunction was observed in 16% (12 patients). The mean days from EBS to stent dysfunction were 16 days (6-42). Multivariate analysis revealed that the normal CRP level (P 0.03, OR 6.1, 95% CI 1.2, 31.3) and gallbladder sludge/stones (P 0.04, OR 7.9, 95% CI 1.1, 54.4) were significant risk factors for stent dysfunction. Stent diameter did not influence the stent dysfunction rate. NBD tube dysfunction was not observed in this study. Conclusions: Patients with superior/hilar bile duct stenosis or normal bilirubin level are at risk of PEP. In patients with gallbladder sludge/ stones, NBD instead of EBS should be considered.

SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly post-translational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand–glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.

Purpose The aim of this study was to evaluate the efficacy and safety of S-1 and Oxaliplatin (Ox) combination chemotherapy for patients with refractory pancreatic cancer. Methods Between March 2009 and October 2011, 30 patients with pancreatic cancer refractory to previous chemotherapy were included. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by a 7-day rest, and Ox was administered at 100 mg/m2 on day 1 every 3 weeks until disease progression or unacceptable toxicity was observed. Results The patients consisted of 22 men (73.3%) and 8 women with a median age of 64 years; 11 patients (36.7%) were in performance status (PS) of 0, 16 patients (53.3%) were in PS of 1, and 3 patients (10.0%) were in PS of 2. Seven patients (23.3%) had locally advanced disease, 19 patients (63.3%) had metastatic disease, and 4 patients (13.3%) had recurrent disease after surgical resection. A partial response was achieved in 3 (10.0%) and stable disease in 12 patients (40.0%), giving a disease control rate of 50.0% with a median of two courses (range from 1 to 8). The median time to progression (TTP) and overall survival (OS) were 3.4 (95% CI: 1.3–5.3) months and 5.2 (95% CI, 2.4–6.8) months, respectively. Eleven patients (36.7%) were previously treated with gemcitabine monotherapy and received this combination chemotherapy as a second-line treatment. Nineteen patients (63.3%) had previously undergone monotherapy or combination chemotherapy containing gemcitabine, S-1, and/or irinotecan and recieved this combination chemotherapy as a third- or fourth-line treatment. TTP was significantly longer in patients without history of S-1 use (5.6 versus 2.8 months; P = 0.005). The relative dose intensity of S-1 and Ox was 89.0 and 96.7% of the scheduled dose, respectively. Major grade 3/4 adverse events included neutropenia (10.0%), anemia (3.3%), and diarrhea (6.7%). Peripheral neuropathy (limited to grade1/2) was observed in 43.3% of patients. There were no treatment-related deaths. Conclusions Combination chemotherapy with S-1 and Ox was moderately effective and well-tolerated in patients with refractory pancreatic cancer.

6, and negative (class I, II, III, and non-informative) in 6. The sensitivity and specificity of the cytologic diagnosis were 86 % and 100 %, respectively. Procedure induced mild pancreatitis occurred in 1 patient (8%). Conclusion: Pancreatic duct lavage cytology with cell block method may be useful for the differentiation between benign and malignant IPMN of the branch duct type. Further studies in a larger population are required to confirm our results.