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Objectives In recent years, knowledge concerning the mechanical properties of self-expandable metallic stents (SEMS) has increased. In a previous study, we defined traction force and traction momentum and reported that these characteristics are important for optimal stent deployment. However, traction force and traction momentum were represented as relative values and were not evaluated in various conditions. The purpose of this study was to measure traction force in various situations assumed during SEMS placement. Methods Traction force and traction momentum were measured in non-stricture, stricture, and angled stricture models using in-house equipment. Results The stricture and angled stricture models had significantly higher traction force and traction momentum than those of the non-stricture model (stricture vs. non-stricture: traction force, 7.2 N vs. 1.4 N, p < 0.001; traction momentum, 237.8 Ns vs. 62.3 Ns, p = 0.001, angled stricture vs. non-stricture: traction force, 7.4 N vs. 1.4 N, p < 0.001; traction momentum, 307.2 Ns vs. 62.3 Ns, p < 0.001). The traction force was variable during SEMS placement and was categorized into five different stages, which were similar in both the stricture and angled stricture models. Conclusions We measured traction force and traction momentum under simulated clinical conditions and demonstrated that strictures and the angular positioning of the stent influenced the traction force. Clinicians should be aware of the transition of the traction force and should schedule X-ray imaging during SEMS placement. This article is protected by copyright. All rights reserved.

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.

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.

Background We aimed to clarify the clinical benefits of using 8-mm versus 10-mm diameter self-expandable metallic stent (SEMS) in bilateral endoscopic stent-in-stent (SIS) deployment for malignant hilar biliary obstruction (MHBO). Methods A total of 72 consecutive patients with MHBO treated by endoscopic bilateral SIS deployment were enrolled. The 8-mm and 10-mm diameter SEMSs were used in 37 patients (8-mm group) and 35 patients (10-mm group), respectively. We retrospectively compared technical success, functional success, complications, successful re-intervention, time to recurrent biliary obstruction (RBO) and survival time between two groups. Results There were no significant inter-group differences in terms of technical success (8-mm vs. 10-mm group, both 100%), functional success (96% vs. 100%), early (5% vs. 9%) and late (19% vs. 14%) complications other than RBO, and successful endoscopic re-intervention (94% vs. 100%), respectively. Time to RBO (median: 198 days vs. 222 days; log-rank, P = 0.440) and survival time (median: 186 days vs. 235 days; log-rank, P = 0.883) did not differ significantly between the two groups. However, the success rate of endoscopic bilateral revisionary stent insertion for RBO was significantly higher in the 10-mm compared to the 8-mm group (68% vs. 31%; P = 0.044). Conclusions The 10-mm diameter SEMS is more suitable with regard to endoscopic re-intervention.

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.

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.

Background and study aims: Various mechanical properties of self-expandable metallic stents (SEMSs) have been reported. They can be classified into the device behavior during and after deployment. While there have been several reports on the latter, information on the former is insufficient. During deployment, the position is maintained by retracting the delivery catheter. We propose that this pulling force be called the traction force and that the magnitude of traction force is termed the traction momentum. The aim of this study was to measure these parameters in order to clarify the properties of SEMSs in terms of their deployment. Material and methods: The traction force, traction momentum, and shortening rate of 10 different SEMSs were measured. Traction force was measured using in-house equipment, and the shortening rate was determined by measuring the stents. Results: The shortening rate was closely related to the stent structure. The traction force varied between 1.5 N and 9.4 N, and the traction momentum was significantly elevated in covered and braided stents. A high traction force did not imply a high traction momentum. Conclusions: A low or constant traction force and a minimal shortening rate significantly facilitated SEMS deployment to optimal positions. Traction force could be an important element for new ideal SEMS design.

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.

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.

Three years have passed since the publication of the Tokyo Guidelines for the management of acute cholangitis and cholecystitis, and we believe that the time has come to assess their validity. In this study, we validated the diagnostic accuracy of these criteria in 74 patients with an initial diagnosis of acute cholangitis and 81 patients with an initial diagnosis of acute cholecystitis. We also statistically compared the accuracy of the diagnosis made based on the Tokyo Guidelines with that based on the presence of Charcot’s triad for acute cholangitis and Murphy’s sign for acute cholecystitis with use of the sign test to assess differences. The results revealed that the diagnostic sensitivity and specificity of the Tokyo Guidelines for suspected or definitive acute cholangitis were 72.1 and 38.5%, respectively, and the corresponding values for definitive cholangitis alone were 63.9 and 69.2%, respectively. For definitive acute cholecystitis, the diagnostic sensitivity and specificity of the Tokyo Guidelines were 84.9 and 50.0%, respectively. The accuracy of diagnosis based on the Tokyo Guidelines was significantly higher than that based on the presence of Charcot’s triad (acute cholangitis, p

A 78-year-old male was admitted to our hospital because of choledocholithiasis. ERC demonstrated choledocholithiases with a maximum diameter of 13 mm, and we performed endoscopic papillary large balloon dilation (EPLBD) with a size of 15 mm. Immediately following the balloon deflation, spurting hemorrhage occurred from the orifice of the duodenal papilla. Although we performed endoscopic hemostasis by compressing the bleeding point with the large balloon catheter, we could not achieve hemostasis. Therefore, we placed a 10 mm fully covered self-expandable metallic stent (SEMS) across the duodenal papilla, and the hemorrhage stopped immediately. After 1 wk of SEMS placement, duodenal endoscopy revealed ulcerative lesions in both the orifice of the duodenal papilla and the lower bile duct. A direct peroral cholangioscopy using an ultra-slim upper endoscope revealed a visible vessel with a longitudinal mucosal tear in the ulceration of the lower bile duct. We believe that the mucosal tear and subsequent ruptured vessel were caused by the EPLBD procedure.