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Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.

Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a lipid mediator that modulates the progression of various cancers. Based on the increasing evidence showing that LPA is abundant in malignant ascites, we focused on autotaxin (ATX), which is a secreted enzyme that is important for the production of LPA. This study aimed to elucidate the importance of the ATX‐LPA axis in malignant ascites in PDAC and to determine whether ATX works as a molecular target for treating peritoneal dissemination. In a PDAC peritoneal dissemination mouse model, the amount of ATX was significantly higher in ascites than in serum. An in vitro study using two PDAC cell lines, AsPC‐1 and PANC‐1, showed that ATX‐LPA signaling promoted cancer cell migration via the activation of the downstream signaling, and this increased cell migration was suppressed by an ATX inhibitor, PF‐8380. An in vivo study showed that PF‐8380 suppressed peritoneal dissemination and decreased malignant ascites, and these results were validated by the biological analysis as well as the in vitro study. Moreover, there was a positive correlation between the amount of ATX in ascites and the degree of disseminated cancer progression. These findings demonstrated that ATX in ascites works as a promotor of peritoneal dissemination, and the targeting of ATX must represent a useful and novel therapy for peritoneal dissemination of PDAC., We could detect the strong inhibitory effect of PF‐8380 on intraperitoneal dissemination of pancreatic ductal adenocarcinoma (PDAC) as it was clearly visualized by bioluminescence imaging and under white‐light imaging.

Acute mediastinitis is a life-threatening condition, and standard treatment is percutaneous drainage and/or surgical treatment with antibiotics. A 58-year-old male diagnosed with acute mediastinitis originating from pancreatic fistula, detected only by endoscopic-ultrasound. We inserted a transesophageal nasocystic tube under endoscopic ultrasound guidance and successfully controlled the infection. The root of the main pancreatic duct for pancreatic juice drainage was recanalized using a duodenal endoscope. Endoscopic diagnosis and treatment by ultrasound have improved significantly; therefore, clinicians should know the potential of these procedures. The results of the present case may aid in the future treatment of patients with acute mediastinitis.

A 70-year-old man was admitted to our hospital due to elevated levels of hepatobiliary and pancreatic enzymes. Computed tomography showed contrast-enhanced mucosal hypertrophy from the duodenal papilla to the distal bile duct. Endoscopic examinations revealed a laterally spreading granular tumor and ampullary swelling. After surgical resection, an examination revealed well-differentiated adenocarcinoma of the ampulla with tubular adenoma spreading from the distal common bile duct to the second part of the duodenum showing both bile duct and duodenal phenotypes. To our knowledge, this is the first case of a tumor spreading from the bile duct to the duodenum that exhibited multiple phenotypes.

The sentinel acute pancreatitis event (SAPE) hypothesis for pathogenesis of chronic pancreatitis (CP) postulates that acute pancreatitis (AP), especially recurrent AP (RAP), precedes development of CP. However, in a recent population-based study, 52/89 (58.4%) of CP had no prior episodes of AP. In a large clinic-based CP cohort, we aimed to determine the incidence and timing of prior AP in patients diagnosed with CP.We retrospectively identified 499 consecutive patients with classic CP diagnosed at our institution from January 2013 through December 2015. We abstracted their demographic and clinical data, especially regarding prior AP.We identified 3 cohorts: 1) CP with no AP (n = 231 [46.3%]), 2) AP before CP (n = 250 [50.1%]), and 3) AP after CP (n = 18 [3.6%]). At CP diagnosis, 249 patients (49.9%) had no prior AP. Compared with the "CP preceded by AP" cohort, the "CP without AP"' cohort was older (59.2 ± 13.9 vs 48.6 ± 15.7 years; P .001), had a higher prevalence of diabetes mellitus (30.3% vs 12.4%; P .001), reported less pain (52.8% vs 87.6%; P .001), and had a lower rate of endoscopic interventions (16.0% vs 39.2%; P .001). In the "CP preceded by AP" cohort, 117 (46.8%) had a single episode of AP and 133 (53.2%) had RAP.Nearly half the patients with classic CP did not have prior AP. Only a quarter of patients had CP that could potentially have evolved from prior RAP. Development of CP may be attributable to an altogether different pathogenesis (a non-SAPE pathway) for a considerable proportion of patients.

Migration of duodenal covered self-expandable metal stents (C-SEMSs) is the main cause of stent dysfunction in patients with malignant gastric outlet obstruction (mGOO). Because endoscopic SEMS placement is frequently selected in patients with poor performance status, we concurrently focused on the safety of the treatment. This pilot study included 15 consecutive patients with mGOO who underwent duodenal partially covered SEMS (PC-SEMS) placement with fixation using an over-the-scope-clip (OTSC). Technical feasibility, clinical success for oral intake estimated by the Gastric Outlet Obstruction Scoring System (GOOSS) score, and adverse events including stent migration were retrospectively assessed. All procedures were successful, and clinical success was achieved in 86.7% (13/15). Mean GOOSS scores were improved from 0.07 to 2.53 after the procedure (P P = 0.03), but we could provide the treatment safely and reduce mGOO symptoms even in patients with poor performance status. In conclusion, duodenal PC-SEMS fixation using an OTSC is feasible for preventing stent migration in patients with mGOO including those with poor performance status.

Endoscopic pancreatic stenting is used to prevent main pancreatic duct obstruction and relieve painful symptoms of chronic pancreatitis. However, the stent typically needs to be exchanged and the rate of adverse events is high. Few studies have evaluated the effect of stent shape on those outcomes. We evaluated the adverse events, stent patency, and total medical cost within 90 days of patients who received an 8.5 French (Fr) physiologically shaped pancreatic stent by comparing these features with those associated with a conventional straight-type stent for ≥ 90 days. The total stent-related adverse event rate was significantly lower for the physiologically shaped pancreatic stent (physiologically shaped, 6.7% [2/30]; straight-type, 50.6% [44/87]; P P P = 0.002) for the physiologically shaped stent. The stent-related adverse event rate was significantly higher for the 10 Fr straight type stent than for the 8.5 Fr physiologically shaped stent (10 Fr, straight-type vs. 8.5 Fr, physiologically shaped: 36.1% [13/36] vs. 6.7% [2/30]; P = 0.007). In conclusion, a physiologically shaped pancreatic stent was superior to a straight-type stent in terms of the patency rate and medical costs.

Endoscopic transpapillary brush cytology and forceps biopsy during endoscopic retrograde cholangiopancreatology are generally used to obtain pathological evidence of biliary strictures. Recently, the new endoscopic scraper Trefle® has been reported and demonstrated high cancer detectability in malignant biliary strictures. This device is used to scrape the stricture over the guidewire, and, in the original method, the tissue and/or cell samples obtained are subjected to histological and/or cytological analysis separately. However, discrimination of chunks of tissue is hampered by the opacity of the surrounding fluid. We have developed a cell block technique for the Trefle® device without dividing obtained specimens into tissue and cellular components, which is the simplest method and enables immunohistochemical analysis. We present a case of obstructive jaundice diagnosed immunohistochemically as pancreatic metastasis from colon cancer using cell block sections obtained with the Trefle® device, which procedure is as easy as conventional brush cytology.

Peritoneal dissemination is a major clinical issue associated with dismal prognosis and poor quality of life for patients with pancreatic cancer; however, no effective treatment strategies have been established. Herein, we evaluated the effects of photodynamic therapy (PDT) with maltotriose-conjugated chlorin (Mal3-chlorin) in culture and in a peritoneal disseminated mice model of pancreatic cancer. The Mal3-chlorin was prepared as a water-soluble chlorin derivative conjugated with four Mal3 molecules to improve cancer selectivity. In vitro, Mal3-chlorin showed superior uptake into pancreatic cancer cells compared with talaporfin, which is clinically used. Moreover, the strong cytotoxic effects of PDT with Mal3-chlorin occurred via apoptosis and reactive oxygen species generation, whereas Mal3-chlorin alone did not cause any cytotoxicity in pancreatic cancer cells. Notably, using a peritoneal disseminated mice model, we demonstrated that Mal3-chlorin accumulated in xenograft tumors and suppressed both tumor growth and ascites formation with PDT. Furthermore, PDT with Mal3-chlorin induced robust apoptosis in peritoneal disseminated tumors, as indicated by immunohistochemistry. Taken together, these findings implicate Mal3-chlorin as a potential next-generation photosensitizer for PDT and the basis of a new strategy for managing peritoneal dissemination of pancreatic cancer. Mol Cancer Ther; 16(6); 1124–32. ©2017 AACR.

Endoscopic metallic stenting is widely accepted as a palliation therapy for malignant gastric outlet obstruction (GOO). However, the predictors of stent dysfunction have not been clarified. We aimed to evaluate the predictors, especially tumor ingrowth in uncovered self-expandable metallic stents (U-SEMS) and migration of covered self-expandable metallic stents (C-SEMS), which are the main causes related to the stent characteristics. In this multicenter retrospective study, we compared patients with U-SEMS and C-SEMS in terms of clinical outcomes, and predictors of stent dysfunction. In total, 252 patients (126 with U-SEMS and 126 with C-SEMS) were enrolled. There were no significant differences in technical success, clinical success, GOO score, or time to stent dysfunction. Tumor ingrowth was significantly more frequent in U-SEMS (U-SEMS, 11.90% vs. C-SEMS, 0.79%; p = 0.002), and stent migration was significantly more frequent for C-SEMS (C-SEMS, 8.73% vs. U-SEMS, 0.79%; p = 0.005). Karnofsky performance status (p = 0.04), no presence of ascites (p = 0.02), and insufficient (

Background and aimsThe revised Atlanta classification is widely used for the evaluation of acute pancreatitis (AP) severity. However, this classification cannot be used within 48 hours of AP onset. The aim of this study was to investigate the predictive factors of mortality in patients with AP on admission.MethodsWe evaluated the association between AP mortality and clinical parameters at the time of admission in patients with AP from April 2013 to December 2017 at one university hospital and one tertiary care referral center.ResultsA total of 203 consecutive patients were enrolled. Nine patients (4.4%) died despite multidisciplinary treatment. In a multivariable analysis, hematocrit ≥ 40% (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01-1.13; P = 0.021), blood urea nitrogen (BUN) ≥ 40 mg/dL (OR, 1.26; 95% CI, 1.11-1.42; P < 0.001), base excess < -3.0 mmol/L (OR, 1.15; 95% CI, 1.04-1.26; P = 0.004), and inflammation extending to the rectovesical excavation (OR, 1.19; 95% CI, 1.10-1.30; P < 0.001) on admission were significantly associated with mortality.ConclusionAmong the imaging findings, inflammation extending to the rectovesical excavation was the only independent predictive factor for mortality in AP. This simple finding, obtained on computed tomography without contrast agent on admission, might be a promising prognostic factor for AP.

Background and Aims: The clinical features of acute obstructive suppurative pancreatic ductitis (AOSPD) have not been elucidated. We aimed to clarify the clinical features of AOSPD. Methods: We retrospectively reviewed the clinical features of 20 patients with AOSPD at two tertiary referral centers between 1993 and 2012. We compared 17 AOSPD patients with chronic pancreatitis (CP) and 42 patients with acute-on-CP in terms of clinical characteristics, presentation, and laboratory and imaging findings. Results: The etiology of AOSPD involved CP in 17 (85%) patients, pancreatic ductal adenocarcinoma in 2 (10%), and intraductal papillary mucinous neoplasm in 1 (5%). Endoscopic pancreatic drainage was effective in 19 (95%) patients. Body temperature was significantly higher in AOSPD with CP than acute-on-CP patients (median: 38.2 vs 36.9 °C; P

Objective The diagnostic yields of endoscopic transpapillary brush cytology and forceps biopsies for malignant biliary strictures (MBS) remain unclear and predictive factors for diagnosis have not been established. We aimed to clarify the diagnostic yields of both methods and the predictive factors Methods We reviewed 241 patients with biliary strictures who underwent transpapillary brush cytology (n = 202) or forceps biopsy (n = 208) between 2004 and 2014 at a single academic center. Results The sensitivity of forceps biopsy for MBS was significantly higher than that of brush cytology [60.6% (97/160) vs 36.1% (57/158), P

We herein report a case of a 56-year-old man with IgG4-related sclerosing cholangitis (IgG4-SC) with no biliary stricture, but with a severely thickened bile duct wall. Contrast-enhanced computed tomography showed diffuse swelling of the pancreas and thickening of the common bile duct (CBD) wall with delayed enhancement. Obvious diffuse wall thickening of the CBD was observed on endoscopic ultrasonography. However, endoscopic retrograde cholangiography showed no biliary stricture in the CBD that had thickened. Although IgG4-SC has been classified by a stenotic lesion on cholangiography, we should be aware of some IgG4-SC cases showing only bile duct wall thickness without any biliary stricture.

Migration of duodenal covered self-expandable metallic stents (C-SEMS) is the main cause of stent dysfunction in patients with malignant gastric outlet obstruction. However, the ideal method to prevent migration has not been clarified. We aimed to evaluate the feasibility and safety of duodenal C-SEMS fixation in this experimental study. We used the over-the-scope clip (OTSC), suture, and clip methods to fix duodenal C-SEMS and evaluated the gripping force of each device and invasion depth based on pathological findings. The OTSC and suturing systems had a significantly higher mean gripping force compared with the clipping system (OTSC vs. clip: 13.2 vs. 1.0 Newtons [N], P

Type 1 autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-retated disease that is often associated with IgG4-related sclerosing cholangitis (IgG4-SC). Autoimmune hemolytic anemia (AIHA) is an immune-related disease that causes hemolytic anemia. Although type 1 AIP/IgG4-SC and AIHA have a shared etiology as a presumed autoimmune disease, they rarely overlap, and their association has not been clarified. Secondary AIHA might not be diagnosed appropriately because the obstructive jaundice observed in type 1 AIP/IgG4-SC can obscure the presence of hemolytic jaundice. We herein report a case of type 1 AIP/IgG4-SC overlapping with secondary AIHA along with a review of the literature.

Despite progress in clinical cancer medicine in multiple fields, the prognosis of pancreatic cancer has remained dismal. Recently, chemopreventive strategies using phytochemicals have gained considerable attention as an alternative in the management of cancer. The present study aimed to evaluate the chemopreventive effects of resveratrol (RV) and apocynin (AC) in N-Nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamster. RV- and AC-treated hamsters showed significant reduction in the incidence of pancreatic cancer with a decrease in Ki-67 labeling index in dysplastic lesions. RV and AC suppressed cell proliferation of human and hamster pancreatic cancer cells by inhibiting the G1 phase of the cell cycle with cyclin D1 downregulation and inactivation of AKT-GSK3β and ERK1/2 signaling. Further, decreased levels of GSK3β(Ser9) and ERK1/2 phosphorylation and cyclin D1 expression in the nuclear fraction were observed in cells treated with RV or AC. Nuclear expression of phosphorylated GSK3β(Ser9) was also decreased in dysplastic lesions and adenocarcinomas of hamsters treated with RV or AC in vivo. These results suggest that RV and AC reduce phosphorylated GSK3β(Ser9) and ERK1/2 in the nucleus, resulting in inhibition of the AKT-GSK3β and ERK1/2 signaling pathways and cell cycle arrest in vitro and in vivo. Taken together, the present study indicates that RV and AC have potential as chemopreventive agents for pancreatic cancer.

Background and Aim Self-expandable metallic stents (SEMS) have been widely accepted as palliation therapy for malignant gastric outlet obstruction (GOO). However, the factors predictive of poor oral intake after SEMS placement have not been elucidated sufficiently. We aimed to clarify both the patient and stent-related predictive factors. Methods We retrospectively reviewed 126 consecutive patients who underwent uncovered SEMS placement for malignant GOO between April 2010 and March 2013 at a university hospital and two tertiary care referral centers. Results Technical success of SEMS placement was achieved in all 126 (100%) patients. Improved oral intake was observed in 111 (88.1%) patients. A Karnofsky performance status ≤ 40 (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.02–1.28; P = 0.041), peritoneal dissemination (OR, 1.20; 95% CI, 1.01–1.26; P = 0.038), and under-expansion of the SEMS on the procedure day (OR, 1.55; 95% CI, 1.26–1.62; P

Autoimmune pancreatitis (AIP) responds well to corticosteroid therapy (CST), and CST is essential to induce remission. However, the correlation between long-term outcome and CST has not been evaluated. We aimed to clarify the correlation between long-term outcome of AIP and CST.We retrospectively evaluated relapse, risk of malignancy and side effects of CST by focusing on the correlation with CST in 84 patients with type 1 AIP.The incidence of relapse was 23.8%. The frequency of relapse after CST administration was significantly lower in patients taking CST for6 months than in those who did not (22% versus 67%; p = 0.036). The incidence of malignancy was 10.7%. The standardized incidence ratio of malignancy was 2.14 [95% confidence interval 0.74-3.54]. There were no significant correlations between development of malignancy and CST. The incidences of total and serious side effects due to CST were 75% and 19.1%, respectively. Relapse was the only significant independent predictive risk factor for serious side effects in a multivariate analysis (odds ratio 4.065; 95% confidence interval 1.125-14.706; p = 0.032). The cumulative dose of corticosteroid was significantly higher in patients with serious side effects than in those without (12,645 mg versus 7322 mg; p = 0.041).CST reduces relapse of AIP. However, CST causes serious side effects, particularly in relapsing patients. Alternative maintenance therapy to prevent relapse is needed.

Background and Aim Comparisons of intraductal ultrasonography (IDUS) findings between primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis (IgG4-SC) have not been elucidated. We aimed to clarify the differences in transpapillary IDUS findings between PSC and IgG4-SC. Methods We retrospectively compared transpapillary IDUS findings between 15 patients with PSC and 35 patients with IgG4-SC between 2004 and 2014. Results IDUS findings of circular-asymmetric wall thickness, irregular inner margin, diverticulum-like outpouching, unclear outer margin, heterogeneous internal echo, and disappearance of three layers were significantly higher in PSC than in IgG4-SC (P

Locus and chromosome abnormalities have not been well clarified in intraductal papillary mucinous neoplasms (IPMNs). The aim of this study was to retrospectively examine these abnormalities using fluorescence in situ hybridization. IPMNs (n=28) were histopathologically classified into noninvasive IPMN (n=17) and IPMN with an associated invasive carcinoma (invasive IPMN, n=11) groups. Noninvasive IPMNs possessed non-neoplastic and noninvasive spots in their tissues, and invasive IPMN cases possessed non-neoplastic, noninvasive, and invasive spots. Non-neoplastic (n=28), noninvasive (n=28), and invasive (n=11) spots were then analyzed for aneuploidy of chromosomes 3, 6, 7, 8, 17, and 18 and deletions of p16 and p53 loci. Polysomy 6 and p16 deletion were significantly more frequent in noninvasive than in non-neoplastic spots. Polysomy 7, polysomy 18, p16 deletion, and p53 deletion were significantly more frequent in invasive than in noninvasive spots. Detection of polysomy 7 and p53 deletion gave a high diagnostic accuracy for invasive IPMN (sensitivity, 90.9%; specificity, 94.1%; and accuracy, 92.5%). Our study suggests that: (1) polysomy 6 and p16 deletion may contribute to adenomatous change of IPMN; (2) polysomy 7, polysomy 18, p16 deletion, and p53 deletion play roles in malignant transformation of noninvasive IPMN; and (3) polysomy 7 and p53 deletion may be excellent diagnostic markers for invasive IPMN.

Background and Aim The influence of chemotherapy on placement of self-expandable metallic stents (SEMS) for malignant gastric outlet obstruction (MGOO) has not been evaluated extensively. We investigated the influence of chemotherapy on the clinical outcomes of SEMS placement for MGOO. Methods A total of 152 cancer patients with MGOO from a university hospital and affiliate hospitals were included. The patients were classified according to chemotherapy status and evaluated for palliative efficacy and safety of SEMS placement. Results Technical success rate, time to oral intake, and parameters indicating improvement of physical condition did not differ between the with- and without-chemotherapy groups after stent placement. Re-intervention and stent migration were significantly more frequent in the with-chemotherapy group than in the without-chemotherapy group after stent placement (re-intervention, 32.4% vs 7.8%, P = 0.0005; stent migration, 13.5% vs 1.7%, P = 0.0097). The frequency of adverse events did not differ between the with- and without-chemotherapy groups. Although chemotherapy after stent placement was an independent predictive factor for shortening the stent patency period (hazard ratio [HR], 3.10; P = 0.0264), the use of additional stents facilitated uneventful recovery and further prolonged survival time (HR, 0.60; P = 0.0132). Conclusions Various cancer patients with MGOO can undergo SEMS placement safely regardless of chemotherapy, and concurrent chemotherapy after stent placement can prolong survival time, although re-intervention and stent migration may be increased.

Self-expandable metallic stents (SEMSs) may be used to effectively palliate malignant gastric outlet obstructions (GOOs), but their utility and efficacy in patients under best supportive care (BSC) have not been explored. In this multicenter retrospective study, we reviewed data on patients under BSC who underwent endoscopic SEMS placement to treat malignant GOO without chemotherapy. We evaluated the safety and efficacy of the procedure. We enrolled a total of 208 patients. SEMS placement was technically successful in 207 (99.5%) and clinically successful in 164 (78.8%). The mean procedure time was 25.6 ± 2.8 min. Stent dysfunction later developed in 30 (14.4%) patients, of whom 90% (27/30) underwent reintervention. The procedure-related mortality rate was 1.44%; all deaths were due to pneumonia. Subgroup analysis by Karnofsky performance status (KPS) revealed that neither technical success, stent dysfunction, reintervention rate, procedure-related pneumonia or death, nor death within 14 days differed between patients with good and poor KPS. However, the clinical success rate and the median survival time were significantly lower and shorter, respectively, in those with poor KPS (p

Background Extracorporeal shock wave lithotripsy is the first-line therapy for large pancreatic duct stones; however, it requires a long duration of therapy. Aims To clarify the effect of pancreatic stenting prior to extracorporeal shock wave lithotripsy on shortening the duration of therapy and reducing complications. Methods We retrospectively compared 45 patients who underwent pancreatic stenting prior to extracorporeal shock wave lithotripsy (stenting group) and 35 patients who did not undergo stenting prior to extracorporeal shock wave lithotripsy (non-stenting group) with regard to the cumulative number of shock waves required for stone fragmentation (stone size Results The stenting group was associated with a significantly lower cumulative number of shock waves in univariate analysis (log-rank, p = 0.046) and multivariate Cox proportional hazard analysis (hazard ratio, 1.88; 95% confidence interval, 1.13–3.14; p = 0.015) than the non-stenting group. The frequency of pancreatitis tends to be lower in the stenting group than the non-stenting group (2.2% [1/45] vs 11.4% [4/35]; p = 0.162). Conclusions Pancreatic stenting prior to extracorporeal shock wave lithotripsy reduced the cumulative number of shock waves required for pancreatic stone fragmentation, and could be useful to shorten the duration of therapy.

Background: Comprehensive immunostaining evaluation of the biopsy specimens from various organs with type 1 autoimmune pancreatitis (AIP) has not been elucidated. Our aim was to clarify which of these biopsy specimens and counting method could be a useful tool for supporting the diagnosis of AIP. Methods: We retrospectively evaluated biopsy specimens from pancreas (n ¼ 19), stomach (n ¼ 28), duodenum (n ¼ 27), duodenal papilla (n ¼ 25), colon (n ¼ 19), liver (n ¼ 11), bile duct (n ¼ 24), and minor salivary gland (n ¼ 13) in 36 patients with AIP. Positive IgG4 immunostaining (>10 plasma cells/highpower field [HPF]) and positive IgG4/IgG ratio (>40%) of biopsy specimens from 8 sites of 6 organs in one HPF and an average from 3 HPFs were compared between AIP and controls. Results: The sensitivity of IgG4 immunostaining for AIP in one HPF were 16% in pancreas,14% in stomach, 15% in duodenum, 52% in duodenal papilla, 11% in colon, 27% in liver, 21% in bile duct and 8% in minor salivary gland, respectively. The positive IgG4 immunostaining of the duodenal papilla in one HPF showed the highest sensitivity (52%) and accuracy (73%) among the 8 sites. It also showed the highest sensitivity among 4 different counting methods (IgG4 immunostaining in one HPF and 3 HPFs, both IgG4 immunostaining and IgG/IgG4 ratio in one HPF and 3 HPFs), but there were no significant differences with respect to specificity and accuracy. Conclusions: IgG4 immunostaining of swollen duodenal papilla with more than 10 IgG4-positive plasma cells in at least one HPF is useful for supporting the diagnosis of AIP.

Background and aim The opportunities of endoscopic retrograde cholangiopancreatography (ERCP)-related procedure for hemodialysis (HD) patients have been increasing recently. However, the complication rate of ERCPs in HD patients has not been evaluated sufficiently. We aimed to clarify the feasibility of ERCPs in HD patients. Methods We retrospectively reviewed 76 consecutive ERCPs for HD patients between January 2005 and December 2012 in one university hospital and three tertiary-care referral centers. Endoscopic sphincterotomy (EST) was performed in 21 HD patients. We evaluated the incidence and risk factors for complications of all ERCPs and EST in HD patients. Results The incidence of pancreatitis, cholangitis, and cardiopulmonary complications for ERCPs in HD patients was 7.9% (6/76), 1.3% (1/76), and 1.3% (1/76), respectively. The mortality rate was 2.6% (2/76), and it occurred after acute pancreatitis in one patient and pneumonia in the other patient. The incidence of hemorrhage and pancreatitis with EST was 19% (4/21) and 4.8% (1/21), respectively. The duration of HD was significantly longer in the patients with hemorrhage after EST than without (19.5 vs 6 years; P = 0.029). Conclusions ERCP is feasible in HD patients. However, EST is not advisable because of the high hemorrhage rate, particularly for patients with a long duration of HD.

An 80-year-old man was admitted with anorexia, a high fever and general icterus. Laboratory examinations revealed remarkable inflammation and elevation of liver/biliary enzymes. Computed tomography (CT) showed a high-density lesion in the bile duct, and endoscopic retrograde cholangiopancreatography (ERCP) disclosed an oval filling defect mimicking choledocholithiasis. Plastic stents were inserted to treat the acute cholangitis; however, the patient's symptoms recurred. An erythematous hypervascular mass obtained with a balloon catheter contained numerous pleomorphic histiocytic cells with eosinophilic cytoplasm, remarkable anisonucleosis and occasional mitoses. A diagnosis of histiocytic sarcoma (HS) was made based on the results of intensive immunohistochemistry. Monoclonal rearrangement of the IGH and TCRG genes, IGH split and IGH/BCL2 fusion was negative, although polysomy 8, 14, and 18 was detected. The patient was treated conservatively and died of the disease 20 months after the initial diagnosis. To the best of our knowledge, this is the first case of bile duct HS. This case, which involved numerical alterations of chromosomes, presented with CT and ERCP findings similar to those of choledocholithiasis.

Fe3O4 magnetic nanoparticles (MgNPs-Fe3O4) are widely used in medical applications, including magnetic resonance imaging, drug delivery, and in hyperthermia. However, the same properties that aid their utility in the clinic may potentially induce toxicity. Therefore, the purpose of this study was to investigate the cytotoxicity and genotoxicity of MgNPs-Fe3O4 in A549 human lung epithelial cells. MgNPs-Fe3O4 caused cell membrane damage, as assessed by the release of lactate dehydrogenase (LDH), only at a high concentration (100 μg/mL); a lower concentration (10 μg/mL) increased the production of reactive oxygen species, increased oxidative damage to DNA, and decreased the level of reduced glutathione. MgNPs-Fe3O4 caused a dose-dependent increase in the CD44+ fraction of A549 cells. MgNPs-Fe3O4 induced the expression of heme oxygenase-1 at a concentration of 1 μg/mL, and in a dose-dependent manner. Despite these effects, MgNPs-Fe3O4 had minimal effect on cell viability and elicited only a small increase in the number of cells undergoing apoptosis. Together, these data suggest that MgNPs-Fe3O4 exert little or no cytotoxicity until a high exposure level (100 μg/mL) is reached. This dissociation between elevated indices of cell damage and a small effect on cell viability warrants further study.

Background and Aim Pancreatitis and cholecystitis are major complications after self-expandable metal stent (SEMS) placement in distal malignant biliary obstruction. We aimed to clarify predictive factors for pancreatitis and cholecystitis after covered SEMS placement. Methods We retrospectively reviewed 74 consecutive patients with distal malignant biliary obstruction who underwent initial endoscopic drainage using covered SEMS. Predictive factors for pancreatitis and cholecystitis were evaluated in the 74 patients described above and in 66 patients who had not undergone cholecystectomy. Results The incidences of pancreatitis and cholecystitis were 10.8% (8/74) and 6.1% (4/66), respectively. Univariate analysis revealed that non-pancreatic cancer (P = 0.018) and contrast injection into the pancreatic duct (P = 0.030) were significant predictive factors for pancreatitis. Multivariate analysis revealed that non-pancreatic cancer (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.63–14.18; P = 0.007) and contrast injection into the pancreatic duct (OR, 3.34; 95% CI, 1.33–9.60; P = 0.016) were significant independent predictive factors for pancreatitis. On the other hand, univariate and multivariate analyses revealed that tumor involvement to the orifice of the cystic duct (OCD) was a significant independent predictive factor for cholecystitis (OR, 5.85; 95% CI, 1.91–27.74; P = 0.005). Conclusions Non-pancreatic cancer and contrast injection into the pancreatic duct were predictive factors for pancreatitis, and tumor involvement to the OCD was a positive predictive factor for cholecystitis after endoscopic covered SEMS placement for distal malignant biliary obstruction.

Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin.

We herein report the case of a 72-year-old man who underwent photodynamic therapy (PDT) with talaporfin sodium for recurrent cholangiocarcinoma after surgical resection. Endoscopic retrograde cholangiography (ERC) showed severe stenosis with an irregular surface measuring approximately 1 cm in length from the anastomotic site, and a recurrent nodular lesion was observed at the anastomotic site of the right anterior intrahepatic bile duct on gastrointestinal endoscopy. ERC after PDT revealed a dramatic improvement in the bile duct stenosis, and the nodular lesion had disappeared. No adverse events from the PDT were detected. PDT using talaporfin sodium may be a safe alternative treatment for cholangiocarcinoma.

Background and Aims Uncovered self-expandable metal stents (U-SEMSs) and covered self-expandable metal stents (C-SEMSs) are available for palliative therapy for malignant gastric outlet obstruction (GOO). However, clinical differences and indications between the 2 types of SEMSs have not been elucidated. Methods We retrospectively compared 126 patients with U-SEMS and 126 patients with C-SEMSs with regard to clinical outcome and factors predictive of clinical improvement after SEMSs placement. Results No significant difference was observed between the U-SEMS and C-SEMS groups with respect to technical success, clinical success, GOO score, or time to stent dysfunction. Stent migration was significantly more frequent in patients with C-SEMSs (U-SEMSs, .79%; C-SEMSs, 8.73%; P = .005). Karnofsky performance status, chemotherapy, peritoneal dissemination, and stent expansion ≤ 30% were associated significantly with poor GOO score improvement in multivariable analyses, but stent type was not ( P = .213). In subgroup analyses, insufficient (≤30%) stent expansion was an independent factor in patients with U-SEMSs ( P = .041) but not C-SEMSs. In the insufficient stent expansion subgroup, C-SEMSs was associated significantly with superior clinical improvement compared with U-SEMSs ( P = .01). Insufficient stent expansion was observed more frequently in patients with GI obstruction because of anastomotic sites or metastatic cancer (44.8% [13/29], P = .001). Conclusions No clinical difference, apart from stent migration, was observed between patients with U-SEMSs and C-SEMSs. GI obstruction because of an anastomotic site or metastatic cancer may be an indication for C-SEMS use to improve oral intake after SEMSs placement.

The objective of this study was to evaluate the International Consensus Diagnostic Criteria (ICDC) for type 1 autoimmune pancreatitis (AIP) in comparison with the Japanese criteria 2011 (JPS2011).We retrospectively investigated the usefulness of ICDC in comparison with JPS2011 in 64 patients with AIP and 90 patients with pancreatic cancer.The sensitivity and specificity of ICDC for AIP were 98.4% (63/64) and 100% (90/90), respectively. The sensitivities and specificities of ductal imaging, serology, other organ involvement, and pancreatic histology were 74.1%, 89.1%, 53.1%, and 26.1% and 94.7%, 94.5%, 100%, and 100%, respectively. On the other hand, the sensitivities and specificities of JPS2011 for AIP were 84.4% (54/64) and 100% (90/90), respectively. The condition of all the 10 patients who were deniable or possible under the JPS2011 could be diagnosed as definitive AIP under the ICDC. The sensitivities and specificities of Japanese criteria 2006, Asian Diagnostic Criteria, and HISORt criteria were 80.6%, 84.4%, and 92.2% and 95.8%, 87.8%, and 100%, respectively.The sensitivity and specificity of ICDC are higher than those of previous criteria. The JPS2011 is easy to handle for general practice, and specificity is very high. However, the sensitivity of JPS2011 is lower than that of ICDC, and improvement of sensitivity is to be hoped in the future.

Many epidemiological studies have shown that abdominal obesity was associated with an increased risk in several malignancies. The association between prostate cancer risk and obesity has been also investigated, but has been in dispute. The involvement of adipocytokines as putative molecular mediators between prostate cancer and obesity has been also investigated. We have already shown effects of conditioned medium (CM) from adipocyte culture in behaviors of prostate cancer cells (DU145). In this study, Phospho-peptide in DU145 cells cultured in CM was analyzed using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Zyxin was identified as a CM-related phosphor-peptide. Zyxin is a conserved protein that has two major domains, an N-terminal half containing proline-rich sequences and a C-terminal LIM domain region. Its functions are involved in regulation of cell adhesion and motility. This protein also appears to have tumor suppressor activity with a few reports, however in dispute. We analyzed the involvement of Zyxin in behavior of DU145 cells. Functional analysis of Zyxin in cell migration, invasive potential and others of DU145 cells was conducted using Zyxin siRNA. Knockdown of Zyxin by siRNA in DU145 cells inhibited cell migration and invasion. As for clinical paired samples, Zyxin expression in tumor tissues was higher than in normal tissues by real-time PCR. These results suggest that Zyxin may play an important role in aggressiveness of human prostate cancer. Citation Format: Kei Yamamoto, Yasuki Hori, Jieun Seo, Saho Hashimoto, Yoshihiro Endo, Tadashi Nittami, Yusuke Ito, Hitoshi Ishiguro, Hiroji Uemura, Masatoshi Watanabe. Involvement of Zyxin in aggressiveness of human prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 522. doi:10.1158/1538-7445.AM2015-522