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Campylobacter jejuni is common cause of enteritis, but biliary infection rarely reported. An 82-year-old woman with pancreatic head cancer underwent endoscopic biliary drainage for malignant biliary obstruction. She was subsequently admitted for management of diarrhea. C. jejuni was identified in stool culture. Her symptoms resolved temporarily without antibiotics but flared up with a fever a few days later. She was diagnosed with acute cholangitis and bacteremia with C. jejuni. Endoscopic biliary drainage and antimicrobial administration improved her symptoms. As complications of C. jejuni diarrhea are rare, antibiotics are not necessarily indicated but sometimes are needed to prevent complications.

Background and Objectives: EUS-guided biliary drainage (EUS-BD) has recently been used for the treatment of not only malignant pancreaticobiliary diseases, but also for benign diseases. In most previous studies, EUS-BD was performed using a fully covered self-expandable metallic stent (SEMS), and data focusing on the usability of plastic stents for benign diseases are limited. We previously developed a plastic stent dedicated to EUS-guided hepaticoenterostomy (EUS-HES), and achieved favorable results in a feasibility study, although most of the patients had malignant diseases. Therefore, the aim of the present study was to evaluate the usability of dedicated plastic stents for EUS-HES in patients with benign pancreaticobiliary diseases. Patients and Methods: A total of 57 consecutive patients (28 men, median age: 68 years; range: 7–90 years) of normal and surgically altered anatomy with benign pancreaticobiliary diseases who underwent EUS-HES using the dedicated plastic stent between Jan. 2015 and Jun. 2020 were retrospectively analyzed. Results: The overall technical success rate of EUS-HES was 92.9% (53/57). Among the 4 cases of technical failure of plastic stent placement, a SEMS was placed in 1; percutaneous transhepatic biliary drainage was performed in 1; EUS-HES was reperformed 1 week later in 1; and observational management was selected in 1 patient. Adverse events associated with the procedure were seen in 15.7% (9/57) of the patients, namely, biliary peritonitis in 4, bleeding in 2, cholecystitis in 2, and pneumoperitoneum in 1 patient. Except for 1 patient who required blood transfusion owing to bleeding and 1 patient with cholecystitis who required percutaneous transhepatic gallbladder drainage, the other 7 patients were treated by conservative therapy. There were no intervention-associated deaths. Conclusion: Our results demonstrated that for patients with benign pancreaticobiliary diseases in whom conventional ERCP was unsuccessful, EUS-HES using a dedicated plastic stent was safe and feasible.

Background and Objectives: EUS-guided fine-needle biopsy (EUS-FNB) is considered a safe and useful method for preoperative diagnosis of resectable solid pancreatic masses. However, needle tract seeding (NTS) after EUS-FNB has recently been reported, which may affect long-term outcome. The aim of this study was to evaluate NTS after EUS-FNB. Materials and Methods: We reviewed 73 resected cases that underwent preoperative EUS-FNB for a pancreatic tumor from April 2014 to March 2016 and evaluated the utility and adverse events of EUS-FNB based on consecutively resected pathological specimens. Results: The final diagnoses were pancreatic ductal adenocarcinoma (n = 67), neuroendocrine neoplasm (n = 5), and acinar cell carcinoma (n = 1). The diagnostic accuracy of preoperative EUS-FNB was 98.6%. Clinical adverse events were observed in 4.1% of cases (bleeding, n = 2; acute pancreatitis, n = 1) and abnormal pathological findings in 4.1% (NTS, n = 2; acute focal pancreatitis, n = 1). Conclusions: Although EUS-FNB is useful for preoperative diagnosis of pancreatic tumors, we may need to reconsider the risk of NTS and use of EUS-FNB in patients with a resectable solid pancreatic mass unless the tract itself is planned to be resected.

High-intensity focused ultrasound (HIFU) is a novel advanced therapy for unresectable pancreatic cancer (PC). HIFU therapy with chemotherapy is being promoted as a novel method to control local advancement by tumor ablation. We evaluated the therapeutic effects of HIFU therapy in locally advanced and metastatic PC. PC patients were treated with HIFU as an optional local therapy and systemic chemotherapy. The FEP-BY02 (Yuande Bio-Medical Engineering) HIFU device was used under ultrasound guidance. Of 176 PC patients, 89 cases were Stage III and 87 were Stage IV. The rate of complete tumor ablation was 90.3%, while that of symptom relief was 63.8%. The effectiveness on the primary lesions were as follows: complete response (CR): n = 0, partial response (PR): n = 21, stable disease (SD): n = 105, and progressive disease (PD): n = 47, the primary disease control rate was 71.0%. Eight patients underwent surgery. The median survival time (MST) after diagnosis for HIFU with chemotherapy compared to chemotherapy alone (100 patients in our hospital) was 772.3 vs. 346.6 days (p &lt, 0.001). Compared with chemotherapy alone, the combination of HIFU therapy and chemotherapy demonstrated significant prolongation of prognosis. This study suggests that HIFU therapy has the potential to be a novel combination therapy for unresectable PC.

Although Spy DS (SpyGlass DS Direct Visualization System) is considered to be useful for the diagnosis of bile duct strictures and the treatment of bile duct stones, there is limited data to date validating its efficacy. We hence retrospectively evaluated the clinical outcomes of the use of Spy DS in a large number of patients. A total of 183 patients who underwent Spy DS-guided procedures for indeterminate bile duct strictures (n = 93) and bile duct stones (n = 90) were analyzed retrospectively. All patients (93/93) with bile duct strictures successfully underwent visual observation, and 95.7% (89/93) of these patients successfully underwent direct biopsy. The sensitivity, specificity, and overall accuracy were 94.7%, 83.3%, and 90.3%, respectively, for visual impression, 80.9%, 100%, and 89.2%, respectively, for histopathological analysis of a direct biopsy, and 96.5%, 91.7%, and 94.6%, respectively, for visual impression combined with biopsy. Successful visualization of the stones was achieved in 98.9% (89/90) of the patients, and complete stone removal was achieved in 92.2% (83/90) of the patients, with an average of 3.3 procedures. The adverse events rate was 17.5% (32/183, cholangitis in 15 patients, fever the following day in 25, pancreatitis in 1, hemorrhage in 1, and gastrointestinal perforation in 1). No administration of antibiotics before the procedure was found to be a statistically significant risk factor for the development of fever after the procedure (p &lt, 0.01). Spy DS-guided procedures are effective for the diagnosis and treatment of bile duct lesions and can be performed with a low risk of serious adverse events.

Primary Sjogren’s syndrome (pSS) is a chronic progressive autoimmune disease with clinical phenotypic “Sicca symptoms”. In some cases, the diagnosis of pSS is delayed by 6–7 years due to the inefficient differential diagnosis of pSS and non-SS “Sicca”. This study aimed to investigate the difference between these two diseases, and in particular, their immunopathogenesis. Based on their gene expression profiles, we systematically defined for the first time the predicted disease-specific immune infiltration pattern of patients with pSS differentiated from normal donors and patients with non-SS “Sicca”. We found that it was characterized by the aberrant abundance and interaction of tissue-infiltrated immune cells, such as a notable shift in the subpopulation of six immune cells and the perturbed abundance of nine subpopulations, such as CD4+ memory, CD8+ T-cells and gamma delta T-cells. In addition, we identified essential genes, particularly long non-coding RNAs (lncRNAs), as the potential mechanisms linked to this predicted pattern reprogramming. Fourteen lncRNAs were identified as the potential regulators associated with the pSS-specific immune infiltration pattern in a synergistic manner, among which the CTA-250D10.23 lncRNA was highly relevant to chemokine signaling pathways. In conclusion, aberrant predicted disease-specific immune infiltration patterns and relevant genes revealed the immunopathogenesis of pSS and provided some clues for the immunotherapy by targeting specific immune cells and genes.

We herein report three cases of patients with an ampullary neuroendocrine tumor (NET), who underwent endoscopic papillectomy (EP). No tumor recurrence or metastasis was detected in the patients for more than two years after EP. Generally, surgical resection is recommended for ampullary NETs by the European Neuroendocrine Tumor Society. However, as EP is less invasive than surgical resection, there are some reports of low-grade small ampullary NETs curatively treated by EP with long-term follow-up. We consider that EP may be a curative treatment for small and low-grade ampullary NETs without regional or distant metastasis.

Background/purpose The application of artificial intelligence to clinical diagnostics using deep learning has been developed in recent years. In this study, we developed an original computer-assisted diagnosis (CAD) system using deep learning analysis of EUS images (EUS-CAD), and assessed its ability to detect pancreatic ductal carcinoma (PDAC), using control images from patients with chronic pancreatitis (CP) and those with a normal pancreas (NP). Methods A total of 920 endosonographic images were used for the training and 10-fold cross-validation, and another 470 images were independently tested. The detection abilities in both the validation and test setting were assessed, and independent factors associated with misdetection were identified among participants' characteristics and endosonographic image features. Results Regarding the detection ability of EUS-CAD, the areas under the receiver operating characteristic curve were found to be 0.924 and 0.940 in the validation and test setting, respectively. In the analysis of misdetection, no factors were identified on univariate analysis in PDAC cases. On multivariate analysis of non-PDAC cases, only mass formation was associated with overdiagnosis of tumors. Conclusions Our pilot study demonstrated the efficacy of EUS-CAD for the detection of PDAC.

Background Peroral cholangioscopy (POCS) of indeterminate biliary strictures aims to achieve a diagnosis through visual examination and/or by obtaining targeted biopsies under direct visualization. In this large, prospective, multinational, real-life experience of POCS-guided evaluation of indeterminate biliary strictures, we evaluated the performance of POCS in this difficult-to-manage patient population. Methods This prospective registry enrolled patients, with indeterminate biliary strictures across 20 centers in Asia, the Middle East, and Africa. The primary end points were the ability to visualize the lesion, obtain histological sampling when intended, and an assessment of the diagnostic accuracy of POCS for malignant strictures. Patients were followed for 6 months after POCS or until a definitive malignant diagnosis was made, whichever occurred first. Results 289 patients underwent 290 POCS procedures with intent to biopsy in 182 cases. The stricture/filling defect was successfully visualized in 286/290 (98.6 %), providing a visual diagnostic impression in 253/290 (87.2 %) and obtaining adequate biopsies in 169/182 (92.9 %). Procedure-related adverse events occurred in 5/289 patients (1.7 %). POCS influenced patient management principally by elucidating filling defects or the causes of bile duct stricture or dilation. The visual impression of malignancy showed 86.7 % sensitivity, 71.2 % specificity, 65.8 % positive and 89.4 % negative predictive value, and 77.2 % overall accuracy compared with final diagnosis. Histological POCS-guided samples showed 75.3 % sensitivity, 100 % specificity, 100 % positive and 77.1 % negative predictive value, and 86.5 % overall accuracy. Conclusion In this large, real-life, prospective series, POCS was demonstrated to be an effective and safe intervention guiding the management of patients with indeterminate biliary strictures.

Objective Endoscopic papillectomy (EP) has been recognized to be a safe and reliable treatment modality for ampullary adenomas. The purpose of this study was to determine the safety and efficacy of endoscopic piecemeal resection for laterally spreading ampullary adenomas and to compare these findings with a control population of smaller conventional ampullary tumors treated in the same time period. Methods Between May 1999 and September 2015, 136 patients underwent EP at Tokyo Medical University hospital. A total of 125 patients underwent en bloc resection, and 11 patients underwent piecemeal resection. Results The final pathological diagnoses were 103 adenomas, 14 carcinomas in adenomas, 4 carcinomas, and 4 hyperplasia in the en bloc resection group, versus 7 adenomas, 3 carcinomas in adenoma, and 1 carcinomas in the piecemeal resection group. A single treatment session was possible in 104 (83.2%) of the 125 patients in the en bloc resection group and in 8 (72.7%) of the 11 in the piecemeal resection group. The total resection rate including additional treatments was 98.4% in the en bloc resection group and 100% in the piecemeal resection group. Conclusion Piecemeal resection for laterally spreading ampullary adenomas was sufficiently performed compared with en bloc resection.

AIM To evaluate the feasibility and reliability of endoscopic transpapillary bile duct biopsy for the diagnosis of biliary strictures. METHODS A total of 360 patients (241 men) who underwent endoscopic retrograde cholangiopancreatography for biliary strictures with biopsy from April 2012 to March 2016 at Tokyo Medical University Hospital were retrospectively reviewed. This study was approved by our Institutional Review Board (No. 3516). Informed consent was obtained from all individual participants included in this study. The biopsy specimens were obtained using a novel slim biopsy forceps (Radial Jaw 4P, Boston Scientific, Boston, MA, United States). RESULTS The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 69.6%, 100%, 100%, 59.1%, and 78.8%, respectively. The sensitivity was 75.6% in bile duct cancer, 64% in pancreatic cancer, 61.1% in gallbladder cancer, and 57.1% in metastasis. In bile duct cancer, a lower sensitivity was observed for perihilar bile duct stricture (68.7%) than for distal bile duct stricture (83.1%). In terms of the stricture lengths of pancreatic cancer, gallbladder cancer, and metastasis, a longer stenosis resulted in a better sensitivity. In particular, there was a significant difference between pancreatic cancer and gallbladder cancer (P < 0.05). One major complication was perforation of the extrahepatic bile duct with bile leakage. CONCLUSION Endoscopic transpapillary biopsy alone using novel slim biopsy forceps is feasible and reliable, but restrictive. Biopsy should be performed in consideration of the stricture level, stricture length, and cancer type.

Background and Aims EUS-guided transluminal drainage (EUS-TD) and sequential direct endoscopic necrosectomy (DEN) for pancreatic fluid collections (PFCs) by using a dedicated biflanged metal stent (BFMS) has been reported as a useful alternative to using plastic stents or a conventional metal stent. However, current dedicated BFMSs have limitations. Recently, a new BFMS with solidly constructed biflanges and various stent lengths matched to the PFC condition has been developed. Herein, we prospectively evaluated this new BFMS for the treatment of PFCs. Methods From July 2015 to July 2016, EUS-TD by using the new BFMS was performed in 12 patients for PFCs (4 patients with pancreatic pseudocysts, 8 patients with walled-off necrosis). When clinical resolution could not be achieved, DEN was performed the following day. Results The stent was deployed successfully with a median procedure time of 16 minutes (range 11-24 minutes) and with no procedure-related adverse events in any patients (12/12, 100%). DEN via the stent was achieved in all patients in whom they were attempted (4/4,100%). Spontaneous stent migration or stent dislocation during DEN was not observed in any patients. Two WON patients died from spontaneous pseudoaneurysm rupture and multiple organ failure. The PFCs in the other 10 patients completely resolved, and later the stent was removed with no difficulty in 9 patients after a median time of 48 days (range 30-180 days). Conclusions The new BFMS is technically feasible and safe for the treatment of PFCs. (Clinical trial registration number: UMIN000021347.)

Objective Endoscopic papillectomy is increasingly being used for ampullary adenoma treatment. However, it remains challenging despite increased safety with treatment advances. The ideal power output and electrosurgical current mode for mucosal resection are not established. We aimed to identify the ideal electrical pulse for use during resection. Methods This pilot randomized, single-blind, prospective, multicenter trial, recruited patients with ampullary adenomas and conventional anatomy who were scheduled to undergo endoscopic papillectomy. Endoscopic treatment was performed using a standardized algorithm and patients were randomized for endoscopic papillectomy with Endocut or Autocut. The primary outcome was the incidence of delayed bleeding. Incidence of procedure-related pancreatitis, successful complete resection, pathological findings, and other adverse events were secondary endpoints. Results Sixty patients were enrolled over a 2-year period. The incidences of delayed bleeding (13.3% vs. 16.7%, P = 1.00) and pancreatitis (27% vs. 30%, P = 0.77) were similar between both groups. The rate of crush artifacts was higher in the Endocut than in the Autocut group (27% vs. 3.3%, P = 0.03). Immediate bleeding when resecting tumors greater than 14 mm in diameter was more common in the Autocut than in the Endocut group (88% vs. 46%, P = 0.04). Conclusions The Autocut and Endocut modes have similar efficacy and safety for endoscopic papillectomy. The Endocut mode may prevent immediate bleeding in cases with large tumor sizes, although it causes more frequent crush artifacts. Registry and the registration number The Japanese UMIN Clinical Trials Registry (UMIN-CTR: 000021382).

Background and Objectives: Recently, a 22G Franseen needle for EUS-guided fine-needle biopsy (EUS-FNB) with three novel symmetric heels has been developed to adequately obtain a core tissue. Methods: All 38 consecutive patients with pancreatic masses who underwent EUS-FNB using a Franseen needle were investigated retrospectively to assess the efficacy and safety of EUS-FNB using the Franseen needle. Then, the EUS-FNB outcomes and histological assessments of the tissue obtained by EUS-FNB using the Franseen needle and EUS-FNA using the conventional end-cut type needle for each of the 30 pancreatic ductal adenocarcinoma cases were compared. Results: An accurate histological diagnosis of the Franseen needle was achieved with a mean of 2 passes in 97.4% of patients. Although the accurate histological diagnosis rate of pancreatic ductal adenocarcinoma was not significantly different (96.7% vs. 93.3%, P = 0.55), the mean number of passes in the Franseen needle was significantly less than that in the conventional needle (2.1 ± 0.4 vs. 3.2 ± 0.8, P < 0.001). The presence of desmoplastic fibrosis with neoplastic cellular elements and venous invasion were significantly higher (96.7% vs. 40.0%, P < 0.001 and 23.3% vs. 0%, P < 0.01, respectively) and the amount of obtained tissue was significantly larger with the Franseen needle (2.13 mm2 vs. 0.45 mm2, P < 0.001). Conclusions: EUS-FNB using the Franseen needle enables the acquisition of a larger amount of tissue sample and achieves an accurate histological diagnosis with a smaller number of passes than the conventional end-cut type needle.

Background and study aims Endoscopic ultrasonography-guided pancreatic duct drainage (EUS-PD) has been reported as an alternative for failed conventional endoscopic retrograde cholangiopancreatography (ERCP). However, there are few dedicated devices for EUS-PD. Recently, we have developed a new plastic stent dedicated to EUS-PD and have conducted a feasibility study to evaluate its efficacy. In the current study, we evaluated the long-term efficacy of this new plastic stent. Patients and methods Thirty patients (61 ± 14.3 years old, 14 men) with acute recurrent pancreatitis caused by a stricture in the main pancreatic duct (MPD) or stenotic pancreatoenterostomy were treated at our institution using our recently developed 7Fr plastic stent between August 2013 and April 2017. Results The stent was placed successfully in all patients (30/30) and early clinical success was achieved in all of them. Early adverse events (AEs) occurred in seven patients (23.3 %), namely, self-limited abdominal pain (n = 5), mild pancreatitis (n = 1), and bleeding which required transcatheter arterial embolization (n = 1). Two patients died of primary disease and three were lost to follow-up. The remaining 25 patients were followed up after initial EUS-PD for a median of 23 months (range, 6 – 44 months). Twenty patients required regular stent exchange (3 times; range, 1 – 12 times). Spontaneous stent dislodgement was observed in six patients. Four patients wanted their stents removed 1 year after the initial intervention. Twelve patients (48 %) had regular stent exchange 1 year after the initial intervention. Three patients converted to standard transpapillary pancreatic duct stenting by conventional ERCP. Finally, nine patients (36 %) had complete stent removal either intentionally or by spontaneous dislodgement without any symptoms. Conclusion The new plastic stent for EUS-PD was associated with not only short-term technical success but also long-term clinical success in the majority of patients evaluated in this study.

Objective Autoimmune pancreatitis (AIP) has been recognized as a benign disease, which that shows a prompt response to corticosteroid treatment (CST). It was previously believed to not be associated with cyst formation; however, a few cases of AIP-associated pancreatic cyst (PC) have been reported. Some cases were reported to have been effectively treated by CST, while others were refractory to CST. Many of the patients received interventional treatment. Until now, there has been no consensus on the therapeutic strategies for AIP-associated PC. The aim of the present study is to describe a therapeutic strategy for this condition. Methods We conducted a retrospective study of 5 cases of AIP-associated PC that were treated by endoscopic ultrasonography-guided pancreatic fluid collection drainage (ESPD) or CST at Tokyo Medical University Hospital between March 2012 and October 2016, analyzed the therapeutic outcomes, and performed a literature review. Results The initial treatments included CST (n=2) and ESPD (n=3). All of the PCs disappeared after treatment In 1 of the patients who received CST case and 3 of the patients who received ESPD; however, the PC did not disappear in one of the patients who received CST (corticosteroid maintenance therapy), even after the dose of corticosteroids was increased; ESPD was eventually performed and the PC disappeared. There were no procedure-related complaints. Conclusion We propose that CST be administered as the first-line treatment for AIP-associated PC, particularly in cases of PC without a history of CST. However, ESPD can be applied to treat cases of corticosteroid refractory PC.

Detection of pancreatic cancer (PC) at a resectable stage is still difficult because of the lack of accurate detection tests. The development of accurate biomarkers in low or non-invasive biofluids is essential to enable frequent tests, which would help increase the opportunity of PC detection in early stages. Polyamines have been reported as possible biomarkers in urine and saliva samples in various cancers. Here, we analyzed salivary metabolites, including polyamines, using capillary electrophoresis-mass spectrometry. Salivary samples were collected from patients with PC (n = 39), those with chronic pancreatitis (CP, n = 14), and controls (C, n = 26). Polyamines, such as spermine, N1-acetylspermidine, and N1-acetylspermine, showed a significant difference between patients with PC and those with C, and the combination of four metabolites including N1-acetylspermidine showed high accuracy in discriminating PC from the other two groups. These data show the potential of saliva as a source for tests screening for PC.

Surgical intervention and, more recently, endoscopic intervention have been performed for the treatment of malignant gastric outlet obstruction. Recently, endoscopic ultrasonography (EUS)-guided gastrojejunostomy using special devices has been established. In line with this, we have developed a novel EUS-guided double-balloon-occluded gastrojejunostomy (EBOG) using a lumen-apposing biflanged metal stent. Herein, we describe the technique and outcome of EBOG.

Background and Aims Pancreatic duct guidewire placement (P-GW) techniques include both the injection cannulation technique with a contrast medium and wire-guided cannulation without contrast injection for selective biliary cannulation; the latter is the so-called “double-guidewire technique” (D-GW). The aim of this study was to compare the outcomes between P-GW and D-GW for biliary cannulation. Methods The procedures for biliary cannulation with a naive papilla were performed in a total of 363 cases. We divided the patients chronologically, according to the time period during which the procedures were performed, into two groups: group A, P-GW performed from March 2008 to June 2009; and group B, D-GW performed from July 2009 to December 2010. The success rates and complication rates were evaluated in each group. Results Biliary cannulation was successful in 31 (81.6%) patients in the P-GW group and 34 patients (82.9%) in the D-GW group. The onsets of postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) occurred in the P-GW and D-GW groups were four (10.5%) and three (7.3%) patients, respectively, and all were mild cases (P = 0.616). The frequency of hyperamylasemia and the serum amylase level tended to be lower in the D-GW group than in the P-GW group (P = 0.213). There was a statistically significant difference on the onsets of PEP in the GW and non-GW groups (P = 0.04, 8.9% and 1.1%, respectively). Conclusions Both the D-GW and P-GW techniques were equally effective for difficult biliary cannulation. Furthermore, the complication rates, including PEP, were similar in both techniques. A prospective randomized trial is warranted.

Various approaches to biliary drainage, especially endoscopic ultrasonography (EUS)-guided drainage, have become commonly used as an alternative method for biliary decompression for malignant biliary obstruction. Occasionally, however, duodenal obstruction and non-dilated intrahepatic bile duct impede conventional EUS-guided biliary drainage. Herein, we describe a case of cholecystogastrostomy successfully carried out using a newly developed fully covered lumen-apposing self-expandable metallic stent (SEMS). EUS-guided cholecystogastrostomy should be considered an option for biliary decompression. This is aparticularly ideal alternative if the patient has duodenal strictures with or without a duodenal metal stent and a non-dilated intrahepatic bile duct, which suggests the impossibility of choledochoduodenostomy and hepaticogastrostomy. Furthermore, the newly developed fully covered lumen-apposing SEMS seems ideal for EUS-guided cholecystoenterostomy.

Biliary self-expandable metallic stent (SEMS) is the preferred and first-line therapy for unresectable malignant biliary obstruction. To date, several reports have revealed the relatively high incidence of acute complications such as pancreatitis and cholecystitis due to mechanical stent compression. In the present case, we encountered fatal pancreatitis following fully covered metal stent placement. An 85-year-old man had middle bile duct strictures due to cholangiocarcinoma. A 10-mm diameter fully covered SEMS was placed across the papilla for biliary decompression. Laboratory data and physical evidence the following day revealed acute pancreatitis. Therefore, antibiotics and protein degeneration enzyme inhibitors were given. However, his condition did not improve. Two days after the procedure, we removed the stent and returned him to his original hospital. Serum amylase level decreased below 400 mg/dL 6 h after the procedure. However, the acute pancreatitis worsened. Although we treated the patient in the intensive care unit, he died 32 days after the second admission.

Although empirical findings have indicated increase in bone fracture risk in type 2 diabetes patients, that has yet to be proven by results obtained at the material level. Here, we report evidence showing nanoscale time-dependent deformation/recovery of in vitro calcified nodules mimicking bone turnover in type 2 diabetes in respect to methylglyoxal (MG)-induced glycation. Nanoindentation test results revealed that calcified nodules cultured with MG did not show adequate dimensional recovery, despite a large creep rate during constant load indentation testing. This lesser recovery is likely based on the linear matrix polymerization network formed by advanced glycation end products (AGEs) as a secondary product of MG. Since elevated serum MG and abnormal bone turnover related to the amount of AGEs are observed in cases of type 2 diabetes, this time-dependent behavior may be one of the factors of the bone fracture mechanism at the material level in affected patients.

Background and Objectives: There have been few studies to date evaluating the effectiveness of contrast-enhanced endoscopic ultrasound (CE-EUS) for detecting mural nodules in patients with branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas. We aim to evaluate the effectiveness of CE-EUS for detecting mural nodules in BD-IPMN. Patients and Methods: Of the 427 BD-IPMN patients, 21 patients (4.9%) in whom the presence of mural nodules was suggested by CE computed tomography (CT) or magnetic resonance imaging (MRI), or in whom the presence of nodule-like lesions as shown by fundamental EUS, were examined by CE-EUS. Results: The mean diameter of cystic lesions was 29.8 ± 12.8 mm. The mean diameter of mural nodules was 9.5 ± 5.7 mm. BD-IPMN was detected in the pancreatic head in 16 cases, pancreatic body in 2 cases, and pancreatic tail in 3 cases. The mean follow-up period was 17.2 ± 11.9 months. The detection rates of mural nodule-like lesions in BD-IPMN patients on CT, MRI, and fundamental EUS were 36.8%, 63.2%, and 100%, respectively. The detection rates of true mural nodules in BD-IPMN patients on CT, MRI, and fundamental EUS were 85.7%, 71.4%, and 100%, respectively. The echo levels of mural nodule-like lesions on fundamental EUS were hyperechoic in 6 patients, isoechoic in 9 patients, and hypoechoic in 6 patients. The final diagnosis was mucus lumps in 14 patients and mural nodules in 7 patients. The contrast patterns observed were avascular, isovascular, and hypervascular in 14, 3, and 4 patients, respectively. No patients showed a hypovascular pattern. Fourteen patients showing an avascular pattern were diagnosed as having mucus lumps, and they were able to avoid surgical resection. Of the 7 patients who were diagnosed as having mural nodules, 5 underwent surgical resection. The pathological findings were adenocarcinoma in 2 patients and adenoma in 3 patients. Of the 3 adenoma patients, fundamental EUS demonstrated a hypoechoic area in 1 patient and an isoechoic area in 2 patients. Of the 2 adenocarcinoma patients, 1 each showed a hypoechoic area and a hyperechoic area. It was difficult to distinguish between patients with adenoma and patients with adenocarcinoma using the echo levels obtained from fundamental EUS. Conclusions: CE-EUS may be useful for avoiding the overdiagnosis of BD-IPMN with mural nodule-like lesions. However, it has difficulty in distinguishing between clearly benign and malignant lesions in BD-IPMN.

Traditionally, either surgical or percutaneous drainage is recommended for liver abscess. Recently, several endoscopists have reported the endoscopic ultrasound (EUS)-guided liver abscess drainage. Herein, we report a case of tuberculous liver abscess in which endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was useful for the diagnosis and therapy. A 78-year-old woman suffered from continuous epigastric pain and fever up. Computed tomography (CT) showed a 70 mm multilocular and multiseptate cystic lesion around the head of pancreas and caudate lobe of the liver. After confirming liver abscess by EUS-FNA, EUS-guided liver abscess drainage was carried out. Finally, a 7 Fr straight stent and a 5 Fr nasocystic catheter were inserted into the cyst. Four weeks later, we found that cultured microorganism obtained using drainage catheter was Mycobacterium tuberculosis. Although he was doing well during 5 days after the procedure, CT showed the size of another abscess increased. Then, additional EUS-guided abscess drainage was carried out at the body of the stomach into the abscess of the left lobe. Two weeks later, CT showed disappearance of abscesses. Then, she discharged with the internal stent still in place.

Self-expandable metallic stent (SEMS) placement is a widely used, effective therapy for unresectable malignant stricture of the lower bile duct.We evaluated the short-term outcome of the newly developed WallFlex(®) Biliary RX Partially Covered Stent in patients with malignant lower and middle biliary stricture in five tertiary referral centers.The subjects of this study were 52 patients in whom WallFlex(®) Biliary RX Stents were inserted into the bile duct for malignant stenosis of the middle and lower bile duct at five medical facilities between April 2009 and November 2009.The stent placement success rate was 100%. Effective biliary decompression was achieved in all patients. The incidence of early complications was 7.7% (4/52). Stent occlusion occurred in two patients (3.8%) (one dislocation, one migration); cholecystitis occurred in two patients (3.8%). Neither acute pancreatitis nor stent kinking in the bile duct occurred.The present results revealed that the new WallFlex(®) Biliary RX Partially Covered SEMSs were useful for the short-term relief of biliary obstruction due to unresectable distal biliary malignancies.

Introduction: Biliary stricture can occur following surgeries of the biliary tract and can cause biliary congestion and cholangitis. Recently, fully covered self-expandable metal stent (FCSEMS) has been utilized for postoperative hilar and anastomotic strictures that have conventionally been considered difficult to treat. On the other hand, there is no solid evidence regarding optimal metal stent placement period. Method: Retrospective review of patients treated for postoperative benign biliary stricture using a FCSEMS at our hospital between 2013 and 2015. Results: We performed a total of 14 metal stent placements for 12 patients with postoperative benign biliary stricture. In all the patients, the metal stents were placed endoscopically and removed safely after the placement. The mean duration of stent placement was 47.9 days (28-144), and there was no retrograde cholangitis observed during metal stent placement. Following metal stent removal, the stricture improved in 9 patients. Recurrence developed in 3 patients, recurring bile duct stones in 2 patients, and cholangitis in 1 patient. Adverse events included post-ERCP pancreatitis in 2 patients, which was alleviated by stent removal the following day and conservative treatment in 1 patient, and conservative treatment only in the other patient. Distal stent migration was observed in 2 patients. Conclusion: The present results suggest that stricture improvement can be expected in a shorter period by metal stent placement in patients with refractory postoperative biliary stricture. In patients with bile duct stones, lithectomy can be safely and effectively performed following metal stent expansion; however, further studies are required.

This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel–Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946–0.994, p < 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650–1.01, p = 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

Wire-guided cannulation has become a common biliary cannulation technique worldwide. Different guidewires with various tip shapes and materials have been reportedly used for wire-guided cannulation. However, there are apparently no studies reporting changes in the biliary cannulation rate according to the type of guidewire used. We evaluated the effectiveness of the J-tip guidewire for biliary cannulation. We conducted a prospective, multicenter, controlled study involving patients with a native papilla who required biliary cannulation. We allocated the patients to the J-tip guidewire or angled-tip guidewire groups (groups J and A, respectively). If biliary cannulation was not achieved within 10 min, the GW was changed and cannulation was continued. Groups J and A consisted of 66 and 65 enrolled patients, respectively. The biliary cannulation rate with a single guidewire for the first 10 min was 84.8 % (56/66) for group J and 80.0 % (52/65) for group A. The final success rate for biliary cannulation was 100 % in both groups. The mean times necessary for biliary cannulation were 285.8 and 267.6 s in group J and group A, respectively. The incidence rates of complications (i.e., all mild pancreatitis) were 3.0 % (2/66) and 6.2 % (4/65) in group J and group A, respectively. The mean amylase concentrations were 168.0 and 297.7 IU/L in group J and group A, respectively. There were no significant differences in any results between both groups. The biliary cannulation rate of the J-tip guidewire was not significantly different from those of standard guidewires.

To evaluate the safety and clinical application of high-intensity focused ultrasound (HIFU) therapy for unresectable pancreatic cancer (PC).Thirty PC patients (16 cases in stage III and 14 cases in stage IV) with visualized pancreatic tumors were admitted for HIFU therapy as an optional local therapy in addition to systemic chemotherapy or chemoradiotherapy. Informed consent was obtained. This study began at the end of 2008 and was approved by the ethics committee of our hospital [Institutional Review Board (IRB): 890]. The HIFU device used was the FEP-BY02 (Yuande Bio-Medical Engineering, Beijing, China).The mean tumor size after HIFU therapy changed to 30.9 ± 1.7 mm from 31.7 ± 1.7 mm at pre-therapy. There were no significant changes in tumor size, mean number of treatment sessions (2.7 ± 0.1 mm), or mean total treatment time (2.4 ± 0.1 h). The rate of symptom relief effect was 66.7%. The effectiveness of primary lesion treatment was as follows: complete response, 0; partial response, 4; stable disease, 22; progressive disease, 4. Treatment after HIFU therapy included 2 operations, 24 chemotherapy treatments, and 4 best supportive care treatments. Adverse events occurred in 10% of cases, namely pseudocyst formation in 2 cases and mild pancreatitis development in 1. However, no severe adverse events occurred in this study.We suggest that HIFU therapy is safe and has the potential to be a new method of combination therapy for PC.

Background There are currently no prospective, controlled trials of endoscopic transpapillary gallbladder drainage in patients with acute cholecystitis. Objective We evaluated the technical success rate and efficacy of endoscopic transpapillary gallbladder drainage by using either endoscopic nasogallbladder drainage (ENGBD) or endoscopic gallbladder stenting (EGBS) for patients with acute cholecystitis. Design Randomized, controlled study. Setting Tertiary-care referral centers. Patients Seventy-three consecutive patients with acute cholecystitis were randomized. Interventions ENGBD by using a 5F or 7F tube (n = 37) or EGBS (n = 36) by using a 7F stent. Main Outcome and Measurements Technical success, clinical success, adverse events, and procedure-related pain score. Results The overall technical success rates in the ENGBD and EGBS groups were 91.9% and 86.1%, respectively ( P > .05). The mean procedure times of ENGBD and EGBS were 20.3 ± 12.1 and 22.2 ± 14.5 minutes, respectively ( P > .05). The overall clinical success rates by per protocol analysis were 94.1% and 90.3% in the ENGBD and EGBS groups, respectively, whereas the rates by intention-to-treat analysis were 86.5% and 77.8%, respectively ( P > .05). Moderate adverse events were observed in the ENGBD (n = 2) and EGBS (n = 1) groups. The mean visual analog score of postprocedure pain in the ENGBD group was significantly higher than that in the EGBS group (1.3 ± 1.1 vs 0.4 ± 0.8, respectively; P Limitations Small sample size and the participation of multiple endoscopists who may have different levels of experience in endoscopic transpapillary gallbladder drainage. Conclusions Both ENGBD and EGBS appear to be suitable for the treatment of acute cholecystitis in patients who are poor candidates for emergency cholecystectomy. (Clinical trial registration number: UMIN000012316.)

Recently, several endoscopists have described the usefulness of the endoscopic ultrasonography (EUS)-guided, single transluminal gateway technique (SGT) using transmural placement of single or multiple plastic stents or metal stents for a pancreatic pseudocyst (PC) and walled-off necrosis (WON). Moreover, the uses of the multiple transluminal gateway technique (MTGT) and single transluminal gateway transcystic multiple drainages (SGTMD) for complicated pancreatic walled-off necrosis have recently been reported. The aim of this study is to evaluate retrospectively the feasibility and efficacy of endotherapy for the treatment of complicated PC and WON cases.Eighty-nine patients with a PC (n = 14) and WON (n = 75) were treated under EUS guidance.In a total of 89 cases using SGT in combination with MTGT or SGTMD, the present study showed a technical success rate of 100 %, a final clinical success rate of 97.8 %, an adverse event during procedure rate of 0 %, an early adverse event rate of 12.4 %, and a mortality rate of 2.2 %.Even complicated WON cases can be treated using combination endotherapies, although a surgical approach as well as a percutaneous approach should be considered in the cases refractory to endoscopic therapies.

Background. Recent diagnostic imaging tests contribute to improving the diagnosis of pancreatobiliary cancers. However, it is not practical to perform these tests for all patients as screening. Thus, less-invasive and simple screening tests are still required. A method to detect the IgG antibody induced in serum against the p53 protein accumulating due to p53 gene mutation, as a biomarker, was developed around 1990.Method. 35 patients with pancreatic cancer, 12 patients with biliary tract cancer, and 31 patients with benign pancreatobiliary diseases were entered into this study. Measurement of serum anti-p53 antibody was conducted in all patients. In addition, the rate of p53 protein overexpression was examined in those cases that could be examined pathologically.Result. Among all patients in the pancreatic cancer and biliary tract cancer groups, there was no patient with serum anti-p53 antibody positive value that exceeded the standard value. The rate of p53 protein overexpression was 48.0% in the patients with pancreatobiliary cancers and 0% in the benign pancreatobiliary diseases group.Conclusion. Serum anti-p53 antibody measurement does not contribute to the diagnosis of pancreatobiliary cancers. Instead, traditional p53 immunostaining still appears to be valuable in combination with standard procedures.

Recently, the usefulness of endoscopic ultrasound (EUS) elastography has been reported for the diagnosis of pancreatic lesions. In the present study, we retrospectively assessed EUS elastography as a diagnostic tool by evaluating tissue elasticity distribution and elasticity semiquantification, using the strain ratio (SR) of tissue elasticity, in patients with pancreatic masses. One hundred and nine patients who underwent EUS elastography between September 2006 and May 2009 were retrospectively evaluated. The final diagnosis was chronic pancreatitis (CP) in 20 patients [6 with non-mass-forming pancreatitis, 7 with mass-forming pancreatitis (MFP), and 7 with autoimmune pancreatitis (AIP)], pancreatic cancer (PC) in 72, pancreatic neuroendocrine tumor (PNET) in 9, and normal pancreas in 8. The tissue elasticity distribution calculation was performed in real time, and the results were represented in color in fundamental B-mode imaging. In addition, we performed quantification using the SR (non-mass area/mass area). Elastography for all PC patients showed intense blue coloration, indicating malignant lesions. In contrast, MFP presented with a mixed coloration pattern of green, yellow, and low-intensity blue. Normal controls showed an even distribution of green to red. The mean SR was 23.66 ± 12.65 for MFP and 39.08 ± 20.54 for PC (P

A 74-year old man was admitted to our hospital with right diffuse pleural thickening and effusion and with subcarinal lymph node swelling. The effusion obtained by thoracentesis showed no malignant cells, although positron emission tomography showed abnormal uptake in the right pleural thickening and subcarinal lymph node. Histopathological examination of the lymph node specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration showed a sheet of epithelioid-like large atypical cells. The tumor cells were immunohistochemically positive for calretinin and cytokeratin 5/6, and negative for CEA and TTF-1. Therefore, malignant pleural mesothelioma of epithelioid type was diagnosed.

916 Endoscopic Ultrasound-Guided Pancreatic Duct Rendezvous in Child With Traumatic PD Disruption Kentaro Ishii*, Takao Itoi, Atsushi Sofuni, Fumihide Itokawa, Takayoshi Tsuchiya, Toshio Kurihara, Shujiro Tsuji, Nobuhito Ikeuchi, Junko Umeda, Reina Tanaka, Ryosuke Tonozuka, Mitsuyoshi Honjo, Shuntaro Mukai, Fuminori Moriyasu Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan Background and Patient: Endoscopic retrograde cholangiopancreatography (ERCP) for a patient with traumatic pancreatic duct (PD) disruption is minimally invasive but always challenging. Here, we describe the successful PD stenting in a 9-year-old boy in whom the PD was disrupted by trauma and the initial ERCP failed. The boy fell down and seriously hurt his abdomen on the way home from school. He later developed pancreatic injury and complete PD disruption. Transpapillary PD stenting failed in the previous hospital. Endoscopic Methods: ERCP was re-attempted in our hospital. Endoscopic retrograde pancreatography revealed the complete PD disruption and pooling of contrast medium at the pancreatic body. A guidewire (GW) could not be advanced into the distal PD. Thus, a therapeutic curved linear array echoendoscope was positioned in the stomach. After excluding the blood vessels by Doppler ultrasonography, the distal PD was punctured transluminally using a 22-guage fine needle aspiration (FNA) needle under endoscopic ultrasound (EUS) guidance. PD access was confirmed by EUS imaging and fluoroscopy. A contrast agent was injected via the FNA needle. Then, a 0.018-inch GW was inserted into the PD. However, the GW could not be advanced to the proximal PD from the PD disruption site even with a hydrophilic GW. Therefore, the GW was left in the disruption cavity as long as possible and the echoendoscope was removed. The echoendoscope was then advanced to the major papilla. Thereafter, the GW could be grasped with a biopsy forceps and pulled out through the working channel. A 9-Fr dilation catheter was inserted into the PD over the rendezvous GW, and another wire could be inserted into the distal PD through the dilation catheter (i.e., over-thewire double GW technique). Finally, a 5-Fr PD stent was retrogradely inserted into the distal PD across the disruption cavity. The PD stent was changed every 1 or 2 months, and removed after 7 months. The patient has remained symptom-free. Clinical Implications: EUS-PD rendezvous appears to be useful even in a child in whom the PD was disrupted by trauma and the initial ERCP failed.

Safety and Effectiveness of Endoscopic Sphincterotmy Plus Large Balloon Dilation: Single Center Mid-Term Outcome Fumihide Itokawa*, Takao Itoi, Atsushi Sofuni, Takayoshi Tsuchiya, Nobuhito Ikeuchi, Reina Tanaka Tokyo Medical University, Tokyo, Japan Background: Endoscopic sphincterotmy plus large balloon dilation (ESLBD) would theoretically favorable for extracting large bile duct stones. Although there are many studies on the feasibility and short-term outcome, there is no midto long-term outcome after ESLBD. The aim of our study is to evaluate the mid-term outcome of ESLBD. Methods: 168 patients with large bile duct stones who underwent ESLBD from November 2006 through December 2011 were retrospectively reviewed. The patients were observed till November 2012. In the present study, inclusion criteria were used to select patients with large and/or multiple bile-duct stones: 1) bile duct stone, 13 mm or more in shortest dimensionor 2) multiple ( 3) bile-duct stones, with the smallest more than 10 mm in shortest dimension. Exclusion criteria included coagulopathy, marked thrombocytopenia, anticoagulation therapy, acute pancreatitis, septic shock. After endoscopic sphincterotomy or prior sphincterotomy, the papillary balloon catheter (maximum diameter 15 mm, 18 mm, or 20 mm) was passed over the guidewire and positioned across the main duodenal papilla. The size of balloon was matched to the diameters of the bile duct and the stones. Results: The patients mean age were 76.8 9.8years. The history of gastric operation was 140 with none (normal), 2 with Billroth 1, 11 with Billroth 2 and 15 with Rouxen Y. 70 patients (41.7%) had periampullary diverticulum. The presence of Gallstone was 65 (38.7%), the history of cholecystectomy was 42(25%), the previous sphincterotomy was 33 (19.6%). The mean follow up period were 39.85 13.7 months (range 11-69). 7 patients (4.2%) occurred stone recurrence (Mean age 72.8 7.8, surgically altered anatomy: none 6, Billroth 2 1, Gallstone 3, Periampullary diverticulum 1, History of sphincterotomy 6 (85.7%), History of stone recurrence 6 (85.7%)). There were no recurrence who had first ESLBD treatment. Conclusions: ESLBD can be safely and effectively performed. Furthermore, our mid-term outcome revealed that ESLBD is low risk of recurrence of bile duct stones. Thus, although further lon-term outcome seems to be mandatory, it will be promising treatment in patients with difficult bile duct stones.