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Many researchers suggested that ultrathin endoscopy improves patient acceptance of endoscopic examinations. However, ultrathin endoscopy provides less image resolution and luminous intensity. Therefore, we focused on the visibility of early gastric cancer on ultrathin endoscopy with Flexible spectral imaging color enhancement (FICE) in this study. Thirty-six patients with early gastric cancer were prospectively enrolled. One endoscopist performed the endoscopic examinations by white light conventional endoscopy (W-CE), white light ultrathin endoscopy (W-UE), FICE ultrathin endoscopy (F-UE) and white light plus FICE ultrathin endoscopy (WF-UE) in the patients. Four other endoscopists were asked to evaluate the visibility of gastric cancer on the W-CE, W-UE, F-UE and WF-UE images with a 5-point Likert scale. The lesions were classified as uncolored, normocolored or reddish. We examined the color difference between early gastric cancer and the surrounding mucosa. To examine the relationship between the color difference and the vessel density, we also measured the difference in vessel density using pathologic specimens stained with hematoxylin and eosin. The Likert score of WF-UE was significantly higher than those of the other three methods ( p <0.001). The color difference of F-UE was higher than that of W-CE in the reddish group ( p =0.049). The difference in vessel density was higher in the reddish group than in the normocolored group ( p =0.048). In conclusion, the visibility of early gastric cancer from the surrounding mucosa using ultrathin endoscopy with FICE was better than that using white light conventional endoscopy, especially for reddish lesions., Competing Interests: No potential conflict of interest are disclosed.

Plummer-Vinson syndrome is a rare entity, characterized by dysphagia, esophageal web formation, and iron deficiency anemia. The patient was a 63-year-old woman with a clinical history of iron deficiency anemia and glossitis in her 20s to 40s and who had experienced swallowing difficulties for the past 20 years. A membranous stricture was found in the cervical esophagus during a fluoroscopic examination. An endoscopic examination conducted under general anesthesia revealed an oblique linear scar on the proximal surface of the stricture. Sequential balloon dilation was performed successfully. We suggest that the esophageal web formation might have been related to the healing of an esophageal ulcer.

Background: Linked color imaging (LCI) is a method of endoscopic imaging that emphasizes slight differences in red mucosal color., Aim: To evaluate LCI in diagnostic endoscopy of early gastric cancer and to compare LCI and pathological findings., Methods: Endoscopic images were obtained for 39 patients (43 lesions) with early gastric cancer. Three endoscopists evaluated lesion recognition with white light imaging (WLI) and LCI. Color values in Commission Internationale de l'Eclairage (CIE) 1976 L*a*b* color space were used to calculate the color difference (ΔE) between cancer lesions and non-cancer areas. After endoscopic submucosal dissection, blood vessel density in the surface layer of the gastric epithelium was evaluated pathologically. The identical region of interest was selected for analyses of endoscopic images (WLI and LCI) and pathological analyses., Results: LCI was superior for lesion recognition ( P < 0.0001), and ΔE between cancer and non-cancer areas was significantly greater with LCI than WLI (29.4 vs 18.6, P < 0.0001). Blood vessel density was significantly higher in cancer lesions (5.96% vs 4.15%, P = 0.0004). An a* cut-off of ≥ 24 in CIE 1976 L*a*b* color space identified a cancer lesion using LCI with sensitivity of 76.7%, specificity of 93.0%, and accuracy of 84.9%., Conclusion: LCI is more effective for recognition of early gastric cancer compared to WLI as a result of improved visualization of changes in redness. Surface blood vessel density was significantly higher in cancer lesions, and this result is consistent with LCI image analysis., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.

Background: Small bowel capsule endoscopy (CE) is a useful tool for evaluating the mucosal changes in patients with Crohn's disease (CD). The Lewis score (LS) on CE could be used to objectively assess the inflammatory activity of the small bowel mucosa. However, only few reports on the correlation between the LS and CD prognosis exist. This study is aimed at evaluating the clinical significance of the LS by determining the cutoff value of the LS that could predict CD-related emergency hospitalization., Methods: This retrospective single-center study included 125 patients who underwent CE for small bowel CD. Eighty-six patients whose treatment was not changed after CE were analyzed. Inflammatory activity was assessed with the LS. We examined the clinical course of the patients who could be observed for 1 year after CE and investigated the LS cutoff value that could predict CD-related emergency hospitalization within 1 year. We also examined the hospitalization-free and clinical relapse-free rates using the LS cutoff value and evaluated the factors related to emergency hospitalization., Results: The LS cutoff value that could predict CD-related emergency hospitalization within 1 year was 264 (area under the curve, 0.92 ( P < 0.001); sensitivity, 0.80; and specificity, 0.94). The cumulative hospitalization-free rate and cumulative clinical relapse-free rate were significantly higher in patients with a LS < 264 ( P < 0.001). Multivariate analysis showed that a LS < 264 was a statistically significant factor ( P = 0.001; 95% CI, 0.010-0.308)., Conclusion: A LS of 264 is a useful cutoff value that could predict CD-related emergency hospitalization. This LS cutoff value may help determine treatment strategies for CD.

Background and Aims: Several studies have shown the benefits of endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a Franseen needle for histological assessment. However, studies focusing on pancreatic diseases are limited and the safety of this method has not been well assessed. We aimed to assess the current status and issues of EUS-FNB in the diagnosis of pancreatic diseases., Materials and Methods: We retrospectively reviewed 87 consecutive EUS-FNB specimens using either a 22-gauge Franseen needle (Group A, N = 51) or a conventional 22-gauge fine-needle aspiration needle (Group B, N = 36) for pancreatic diseases, and the diagnostic accuracy and safety were compared. Final diagnoses were obtained based on surgical pathology or a minimum six-month clinical follow-up., Results: Although the diagnostic accuracy for malignancy was 96.1% in Group A versus 88.9% in Group B, with no statistically significant difference ( P = 0.19), the median sample area was significantly larger in Group A (4.07 versus 1.31mm 2 , P < 0.0001). There were no differences between the two needles in the locations from which the specimens were obtained. Adverse events occurred in one case (2%) in Group A (mild pancreatitis) and none in Group B with no statistical significance ( P = 0.586). Although there was no case of bleeding defined as adverse events, 2 cases in Group A showed active bleeding during the procedure with increase in the echo-free space, which required CT scanning to rule out extravasation. Eventually, the bleeding stopped spontaneously., Conclusions: Given its guaranteed ability to obtain core specimens and comparable safety, and although the risk of bleeding should be kept in mind, EUS-FNB using a Franseen needle is likely to become a standard procedure for obtaining pancreatic tissue in the near future.

Purpose: Abdominal ultrasound (US) can visualize the esophagogastric junction (EGJ) as a hyperechoic area in the dorsal portion of the lateral segment of the liver. We prospectively evaluated the EGJ using US elastography (US-EG) in patients with reflux esophagitis (RE) to examine prediction of distal esophageal function., Methods: Of 108 patients undergoing US-EG and esophagogastroduodenoscopy, 102 in whom the EGJ was observed for ≥ 15 s were included. The subjects were divided into a RE group (n = 41, Grade M/A/B:24/13/4 according to modified Los Angeles Classification) and a non-RE group (n = 61). Direct strain elastography (LOGIQ E9, GE Healthcare), which gives a semi-quantitative elasticity index within a region of interest including the lateral segment, was used as a standard for measurement of the change in stiffness (CS) at the EGJ., Results: The number of CS as determined by US-EG was 6.0 (5.5-6.7) in the RE group and 8.6 (6.6-10.0) in the non-RE group (P < 0.0001). In ROC analysis, the AUC was 0.8415 for diagnosis of RE using the number of CS. At a cut-off of 7.7, the sensitivity, specificity, and accuracy for diagnosis were 92.7, 65.6, and 74.5%, respectively., Conclusion: The presence of RE can be predicted based on US-EG.

Objective: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study., Methods: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events., Results: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741-1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044)., Conclusion: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified., (© 2018 S. Karger AG, Basel.)

Mucosal healing in Crohn's disease (CD) can be evaluated by capsule endoscopy (CE). However, only a few studies have utilized CE to demonstrate the therapeutic effect of medical treatment. We sought to evaluate the validity of using CE to monitor the effect of medical treatment in patients with CD. One hundred ( n = 100) patients with CD were enrolled. All patients had a gastrointestinal (GI) tract patency check prior to CE. Patients with baseline CE Lewis score (LS) ≤ 135 were included in the non-active CD group and ended the study. In those with LS > 135 (active CD group), additional treatment was administered, regardless of symptoms, as per the treating clinician's advice. Patients of the active CD group underwent follow-up CE assessment 6 months later. Out of 92 patients with confirmed GI patency who underwent CE, 40 (43.4%) had CE findings of active inflammation. Of 29 patients with LS > 135 who received additional medications and underwent follow-up CE, improvement of the LS was noted in 23 (79.3%) patients. Eleven patients were asymptomatic but received additional medications; 8 (72.7%) had improvement of the LS. This study demonstrated that additional treatment even for patients with CD in clinical remission and active small-bowel inflammation on CE can reduce mucosal damage.

The role of octamer-binding transcription factor 4 (OCT4) in human cancer is still debated. Although many studies have been published on human OCT4, determining which of the findings are accurate or which are false-positives is currently challenging. We thus developed the most reliable method to date for highly specific and comprehensive detection of genuine OCT4-transcript variants without false-positive results. Our results provided clear evidence that the transcripts of OCT4A, OCT4B, OCT4B1, and other novel splicing variants are indeed present in many cancer cell lines, but are rarely detected in normal tissue-derived differentiated cells. Using the tagged genomic transgene, we then verified endogenous OCT4A translation in cancer cell subpopulations. Moreover, analysis of possible other protein isoforms by enforced expression of OCT4B variants showed that the B164 isoform, designated human OCT4C, is preferentially produced in a cap-dependent manner. We confirmed that the OCT4C isoform, similar to OCT4A, can transform non-tumorigenic fibroblasts in vitro. Finally, ablation of OCT4-positive cells using promoter-driven diphtheria toxin A in high malignant cancer cells caused a significant decrease in migration and Matrigel invasion. These findings strongly suggest a significant contribution of OCT4 to the phenotype of human cancer cells. Stem Cells 2018., (© AlphaMed Press 2018.)

Background and Study Aims: To decrease complications associated with preoperative endoscopic nasobiliary drainage (ENBD) for perihilar cholangiocarcinoma patients, we developed a modified 6-Fr ENBD catheter with multiple side holes (m-ENBD). The aim of this retrospective study was to compare the m-ENBD catheter with a conventional 7-Fr ENBD catheter (c-ENBD)., Patients and Methods: This study involved 371 patients with suspected perihilar cholangiocarcinoma who underwent ENBD using a c-ENBD catheter or an m-ENBD catheter. The effectiveness of each catheter and the incidence of complications were evaluated. Univariate and multivariate analyses followed by propensity score matching were performed., Results: In 145 patients with total bilirubin levels ≥ 2.0 mg/dL prior to drainage, these levels decreased to < 2.0 mg/dL after ENBD in 81.1 % of the c-ENBD patients and in 74.0 % of the m-ENBD patients ( P  = 0.325). Post-ENBD cholangitis occurred in 24.9 % of the c-ENBD patients and in 12.4 % of the m-ENBD patients ( P  = 0.006). After propensity score matching, the rate of post-ENBD cholangitis ( P  = 0.007) and the number of patients requiring subsequent or additional drainage ( P  = 0.030) were significantly lower in the m-ENBD group., Conclusion: The modified 6-Fr ENBD catheter was associated with a lower incidence of post-ENBD cholangitis than the conventional 7-Fr ENBD catheter, and the incidence of subsequent or additional drainage procedures was also decreased.

Endoscopic ultrasound is increasingly being used for evaluation of pancreatic diseases and pancreatic tumors. Among various pancreatic cystic lesions, cystic degeneration of pancreatic neuroendocrine neoplasm is of the challenge in making diagnosis. Although unique characteristic of each type of pancreatic cystic lesions has been proposed abundantly, typical morphology of cystic degeneration of pancreatic neuroendocrine neoplasm is still unclear. We, herein, reported a case of 66-year-old woman who was incidentally found to have a cystic lesion in the tail of pancreas upon screening transabdominal ultrasonography. A well-defined cystic lesion with rim calcification was noted on subsequent abdominal computed tomography. Endoscopic ultrasound revealed a markedly thick-wall cystic lesion containing solid nodule inside which was not enhanced following contrast-enhanced study. A mucinous cystic neoplasm was suspected and the patient was proceeded with distal pancreatectomy. A definite diagnosis of neuroendocrine neoplasm was confirmed after staining with synaptophysin and chromogranin A. We performed a meticulous review on current literatures focusing on endoscopic characteristics of pancreatic neuroendocrine neoplasms with cystic degeneration.

Background and Aims:  We have previously shown that the increase in blood flow volume in jejunum villi after spraying of 10 % dextrose solution correlates with pancreatic exocrine function (PEF). The aim of this study was to establish an objective method to evaluate the amount of jejunum villous blood flow using a novel image analysis system., Patients and Methods:  The subjects were 26 patients who underwent upper gastrointestinal endoscopy with a newly developed small intestine endoscope (SIF-Y0007, Olympus, Tokyo, Japan). By defining the ratio of capillary occupancy in each villus at levels from 1 to 5, villous blood flow was evaluated subjectively on the villous blood flow scale (VBFS). Objective evaluation was performed based on luminance analysis. The morphological opening process was used to make images with leveled brightness. A histogram was prepared from the luminance information and the standard deviation was determined and defined as SDOV (Standard Deviation calculated from a histogram made by luminance analysis Of Villi). PEF was evaluated by measuring the BT-PABA (N-benzoyl-L-tyrosyl-p-aminobenzoic acid) excretion rate., Results:  There was a significant positive correlation between VBFS and SDOV ( P  < 0.0001, ρ = 0.5882). SDOV was also positively correlated with PEF ( P  = 0.0004, ρ = 0.6421)., Conclusions:  SDOV is a new objective index for evaluation of blood flow volume in jejunum villi. SDOV may be useful in clinical practice to estimate PEF and for clarification of the mechanisms underlying the functional correlation between the pancreas and small intestine.

Background: Prognosis of pancreatic cancer is poor with a 5-year survival rate of only 7%. Although several new chemotherapy treatments have shown promising results, all patients will eventually progress, and we need to develop newer chemotherapy treatments to improve response rates and overall survival (OS). HF10 is a spontaneously mutated oncolytic virus derived from a herpes simplex virus-1, and it has potential to show strong antitumor effect against malignancies without damaging normal tissue. We aimed to evaluate the safety and anti-tumor effectiveness in phase I dose-escalation trial of direct injection of HF10 into unresectable locally advanced pancreatic cancer under endoscopic ultrasound (EUS)-guidance in combination with erlotinib and gemcitabine administration. The mid-term results have been previously reported and here we report the final results of our study., Methods: This was a single arm, open-label Phase I trial. HF10 was injected once every 2 weeks and continued up to four times in total unless dose-limiting toxicity (DLT) appears. A total of nine subjects in three Cohorts with dose-escalation were planned to be enrolled in this trial. The primary endpoint was the safety assessment and the secondary endpoint was the efficacy assessment., Results: Twelve patients enrolled in this clinical trial, and ten subjects received this therapy. Five patients showed Grade III myelosuppression and two patients developed serious adverse events (AEs) (perforation of duodenum, hepatic dysfunction). However, all of these events were judged as AEs unrelated to HF10. Tumor responses were three partial responses (PR), four stable diseases (SD), and two progressive diseases (PD) out of nine subjects who completed the treatment. Target lesion responses were three PRs and six SDs. The median progression free survival (PFS) was 6.3 months, whereas the median OS was 15.5 months. Two subjects from Cohort 1 and 2 showed downstaging and finally achieved surgical complete response (CR)., Conclusions: HF10 direct injection under EUS-guidance in combination with erlotinib and gemcitabine was a safe treatment for locally advanced pancreatic cancer. Combination therapy of HF10 and chemotherapy should be explored further in large prospective studies., Trial Registration: This study was prospectively registered in UMIN-CTR (UMIN000010150) on March 4th, 2013.

Objectives: The aim of this study is to evaluate a functional correlation between the pancreas and the small intestine and the association of this relationship with nutritional status, using magnifying enteroscopy., Methods: The subjects were adults aged 20 years or older who underwent upper gastrointestinal endoscopy. An endoscope was inserted into the jejunum, and 10% glucose was sprayed under magnifying observation to evaluate changes in blood flow in the villous capillary network. Mucosal biopsy was performed before and after spraying to evaluate the incretin response in the jejunal mucosa., Results: A total of 124 patients participated in the study. There was a positive correlation between villous blood flow change and exocrine pancreas function (R = 0.4337, P < 0.0001). Changes of gastric inhibitory polypeptide and glucagon-like peptide messenger RNAs in biopsy samples were positively correlated with endocrine pancreas function in 88 patients without treatment for diabetes (R = 0.4314, P = 0.0012; R = 0.4112, P = 0.0081). In patients with lower villous blood flow change and decreased pancreatic exocrine function, the prognostic nutritional index were significantly lower (P = 0.0098), compared with other patients., Conclusions: This study provides the first evidence of a close functional correlation between the pancreas and the small intestine.

Fecal calprotectin (FC) has drawn attention as a biomarker in the evaluation of Crohn's disease (CD). However, few reports have provided a detailed examination of the relationship between small-bowel CD lesions and FC levels. The present study aimed to examine the entire small bowel using double-balloon endoscopy (DBE) and to determine the relationship between the endoscopic activity in small-bowel CD and FC levels. Twenty small-bowel CD patients, who underwent DBE, were prospectively enrolled. Endoscopic evaluation was based on the simple endoscopic score for CD, with the small bowel divided into four regions. This score was defined as the double-balloon endoscopic score for CD (DES-CD). Furthermore, to focus on mucosal membrane damage, we used the partial DES-CD (pDES-CD), in which presence of stenosis was excluded from DES-CD. DES-CD revealed a correlation with FC (γ = 0.691, P = 0.001) and C-reactive protein (CRP) (γ = 0.631, P = 0.003) levels. Furthermore, pDES-CD showed a correlation with the FC level (γ = 0.747, P < 0.001), erythrocyte sedimentation rate (γ = 0.492, P = 0.028), and the CRP level (γ = 0.605, P = 0.005). CD Activity Index and endoscopic score showed no correlation. Our results revealed a correlation between the endoscopic activity in small-bowel CD and FC levels. Furthermore, pDES-CD showed a strong correlation with FC levels. This may be because FC levels were elevated due to mucosal membrane damages, rather than stenoses.

Small bowel capsule endoscopy (SBCE) and balloon-assisted endoscopy (BAE) have revolutionized the diagnosis and treatment of small bowel bleeding (SBB), allowing access to the small bowel and identification of specific bleeding lesions. However, some patients experience rebleeding after small bowel investigation, and there are no definitive algorithms for determining the most appropriate follow-up strategy in SBB patients. We developed and validated a nomogram that can predict rebleeding risk and be used to develop a risk-stratified follow-up strategy in SBB patients. A retrospective study was performed using data from 401 SBB patients who underwent SBCE at Nagoya University Hospital. We developed and internally validated a predictive model for rebleeding in the form of a nomogram using Cox regression models and a bootstrap resampling procedure. Optimal risk factors were selected according to the least absolute shrinkage and selection operator (LASSO). The LASSO method identified 8 independent predictors of rebleeding that could be assessed to obtain a 'predicting rebleeding in SBB', or 'PRSBB' score: age, sex, SBB type, transfusion requirement, cardiovascular disease, liver cirrhosis, SBCE findings, and treatment. The c-statistic for the predictive model was 0.681. In conclusion, our PRSBB score can help clinicians devise appropriate follow-up plans.

Background/objectives: Time-intensity curve (TIC) under contrast-enhanced EUS (CE-EUS) allows continuous and quantitative evaluation of targeted area in the pancreas. However, TIC is not always available and the procedure is complicated. We aimed to propose a simplified method by evaluating multiple phases of CE-EUS in the diagnosis of pancreatic solid lesions., Methods: We retrospectively reviewed 210 patients with pancreatic solid lesions including 142 with pancreatic ductal cancer (PDAC), 31 with pancreatic neuroendocrine neoplasm, 13 with solid pseudopapillary neoplasm and 24 with mass-forming pancreatitis who underwent CE-EUS and achieved final diagnoses. The CE-EUS images were continuously recorded for 60 s, and each image at 20, 40 and 60 s was used for the evaluation. The images were classified into three patterns as hypoechoic, hyperechoic and isoechoic vascular patterns compared with the surrounding pancreas, and the relevance between the multiphase evaluation of CE-EUS and each disease group was investigated., Results: In PDAC group, majority of the lesions showed hypovascular pattern at 20 or 40 s after injection of contrast medium following early enhancement. The sensitivity, specificity and accuracy of PDAC pattern in the differentiation of PDAC from other lesions was 83.1%, 86.8% and 84.3%, respectively. On histopathological analysis, significant differences were seen in histologic types, infiltration (INF), and neural invasion (ne) between those who showed PDAC pattern and those who didn't., Conclusions: Multiphase evaluation of CE-EUS is convenient and useful method for the differentiation of pancreatic solid lesions which can be alternatively used for TIC., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Hydrogen is produced from unabsorbed carbohydrates in the intestine through degradation and metabolism by hydrogenase of intestinal bacteria. The hydrogen is then partially diffused into blood flow and released and detected in exhaled breath. Pancreatic juice production is decreased in patients with reduced pancreatic exocrine function, including those with pancreatic cancer, thus decreasing digestion and absorption of nutrients including carbohydrates, which may increase undigested carbohydrates in the intestine and increase breath hydrogen concentration (BHC). The aim of this study was to investigate the association between BHC and pancreatic diseases., Methods: A retrospective study was designed and 68 patients underwent morning fasting breath hydrogen test. Since there is no clear standard, normal BHC, the median of the measured values from the subjects (9 ppm) was adopted as the standard. The subjects were classified into those with a value exceeding the median (BHC high group: 32 patients) and a value equal to or below the median (BHC low group: 36 patients). Patients characteristics, blood test results and imaging findings characteristic of pancreatic diseases were compared between the groups., Results: The age was significantly higher (P = 0.010) and the incidences of pancreatic ductal adenocarcinoma and autoimmune pancreatitis were significantly higher (P = 0.018 and P = 0.004, respectively) in the BHC high group. With respect to the blood test items, the Alb level was significantly lower in the BHC high group (P = 0.005). With respect to the characteristic imaging findings of pancreatic diseases, the proportions of patients with pancreatic enlargement, the main pancreatic duct (MPD) stenosis, and the MPD dilatation were significantly higher in the BHC high group (P = 0.022, P < 0.001, and P = 0.002, respectively). On univariate analysis, only the MPD stenosis was extracted as an independent factor (P = 0.014)., Conclusion: It was suggested that the fasting BHC is associated with pancreatic diseases causing stenosis of the MPD, including pancreatic cancer (UMIN000020777).

Background and Aim: Chronic pancreatitis (CP) is sometimes diagnosed at the progressed stage. For the early diagnosis of CP, endoscopic ultrasonography (EUS) may be a useful method, but its diagnostic criteria is based on subjective judgment. Shear wave elastography (SW-EG) using transabdominal ultrasonography, which quantifies tissue elasticity as an absolute value, may be an objective and noninvasive method for the diagnosis of CP., Methods: Eighty-five patients with known or suspected CP who underwent both EUS and SW-EG from October 2012 to July 2016 were included in this study. Patients were categorized into four stages using Rosemont classification and into three stages using Japan Pancreas Society clinical diagnostic criteria 2009 that was EUS-based criteria for the diagnosis of CP. SW-EG was measured five times in the pancreatic parenchyma, and the median value was defined as the pancreatic elastic modulus (PEM)., Results: Pancreatic elastic modulus was significantly positively correlated with Rosemont classification stage (r s  = 0.54), Japan Pancreas Society stage (r s  = 0.41), and the number of EUS features (r s  = 0.47). Area under the receiver operating characteristic curve for the accuracy of SW-EG (consistent with CP and suggestive of CP vs normal and indeterminate for CP) was 0.77 (sensitivity 77.1%, specificity 64.9%). In a multivariate linear regression analysis including various EUS features related to PEM, hyperechoic foci with shadowing and lobularity with honeycombing were independent features related to PEM., Conclusions: Chronic pancreatitis may be diagnosed noninvasively and objectively using SW-EG without performing EUS., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Capsule endoscopy (CE) enables noninvasive visualization of the small bowel in Crohn's disease (CD), but should not be conducted in patients with bowel obstruction. Patency capsule (PC) can be ingested before conducting the CE examination to ensure patency of the gastrointestinal (GI) tract. This study aimed to evaluate the clinical significance of GI patency which the PC demonstrated. A retrospective review of the medical records was conducted with 99 consecutive patients with CD who underwent PC and CE at Nagoya University Hospital from January 2010 to May 2015. By using the Cox proportional hazards model, the association between the GI patency evaluated using the PC and the outcome in terms of the rate of patients who needed admission or surgery during the 2-year follow-up was examined. Of all 99 patients who ingested the PC, 84 (84.8%) were diagnosed as not having bowel obstruction, and therefore were eligible for CE (P group). Of the 15 patients in whom bowel obstruction was suspected (NP group), 12 patients underwent either the balloon-assisted endoscopy (n=10) or enteroclysis (n=2), and 11 were confirmed to have small bowel stricture. Non-admission rates of the P and NP groups during the 2-year observation period were 74/84 (88.0%) and 8/15 (53.3%), respectively ( P <0.001). Non-operation rates of the P and NP groups during the 2-year observation period were 80/84 (95.2%) and 9/15 (60.0%), respectively ( P <0.001). In conclusion, GI patency as diagnosed using the PC was associated with a significantly lower incidence of admission or surgical intervention.

Induced pluripotent stem (iPS) cells possess pluripotency and self-renewal ability. Therefore, iPS cells are expected to be useful in regenerative medicine. However, iPS cells form malignant immature teratomas after transplantation into animals, even after differentiation induction. It has been suggested that undifferentiated cells expressing Nanog that remain after differentiation induction are responsible for teratoma formation. Various methods of removing these undifferentiated cells have therefore been investigated, but few methods involve morphological approaches, which may induce less cell damage. In addition, for cells derived from iPS cells to be applied in regenerative medicine, they must be alive. However, detailed morphological analysis of live undifferentiated cells has not been performed. For the above reasons, we assessed the morphological features of live undifferentiated cells remaining after differentiation induction as a basic investigation into the clinical application of iPS cells. As a result, live undifferentiated cells remaining after differentiation induction exhibited a round or oval cytoplasm about 12 μm in diameter and a nucleus. They exhibited nucleo-cytoplasmic (N/C) ratio of about 60% and eccentric nuclei, and they possessed partially granule-like structures in the cytoplasm and prominent nucleoli. Although they were similar to iPS cells, they were smaller than live iPS cells. Furthermore, very small cells were present among undifferentiated cells after differentiation induction. These results suggest that the removal of undifferentiated cells may be possible using the morphological features of live iPS cells and undifferentiated cells after differentiation induction. In addition, this study supports safe regenerative medicine using iPS cells.

Background and Aim: The aim of this study is to elucidate the natural history of pancreatic cystic lesions (PCLs), including branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN), via midterm follow-up analysis of a multicenter prospective observational study (NSPINAL study)., Methods: From July 2011 to October 2016, 881 patients with PCLs were enrolled in NSPINAL study, and 664 patients with > 12 months of follow up were analyzed. Every patient was asymptomatic, and endoscopic ultrasound was performed at the initial diagnosis to exclude high-risk individuals. Follow up included endoscopic ultrasound, computed tomography, or magnetic resonance imaging at least once a year. Serial morphological changes and the pancreatic cancer (PC) incidence, including malignant progression of PCLs, were evaluated., Results: The 664 patients (358 men) were followed for a median of 33.5 months (interquartile range 29). The cyst and main pancreatic duct sizes were 16.6 ± 9.3 and 2.3 ± 1.0 mm, respectively. Morphologically, 518 cases were multilocular, 137 were unilocular, and 9 had a honeycomb pattern; 269 cases involved multifocal lesions. Ninety-six patients (14.5%) showed worsening progression on imaging. There were two resectable and four unresectable cases of pancreatic ductal adenocarcinoma and three cases of malignant BD-IPMN. The 3-year risk of developing PC was 1.2%. The standardized incidence ratio for PC among PCLs was 10.0 (95% confidence interval 3.5-16.5), and the standardized incidence ratio among BD-IPMN was 16.6 (95% confidence interval 5.1-28.1). Multivariate analysis showed that development of symptoms and worsening progression were significant predictors of PC., Conclusions: Malignant progression of PCLs, including PC development, is not uncommon. Patients with PCLs should be carefully monitored to detect pancreatic ductal adenocarcinoma at early stages., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Dendritic cell (DC)-based vaccines prepared using various antigen loading methods have been studied for cancer immunotherapy. The in vivo provocation of immunity by the direct injection of DCs without using tumor-specific antigens into tumors after apoptosis-inducing chemotherapy is more applicable. We previously reported that zoledronate-pulsed DCs (Zol-DCs) may induce tumor-antigen-specific CD8+ T cells by activating Vγ9γδT cells. In this report, we studied the feasibility, safety, and efficacy of a comprehensive immunotherapy involving the combined intratumoral injection of Zol-DC, gemcitabine (GEM) and αβT cells in locally advanced pancreatic carcinoma. Seven of 15 patients showed a stable disease (SD) and most of the patients showed long-term clinical responses. The FACT-BRM score was significantly higher in the patients with SD. Additionally the CD8+/Treg ratio significantly increased in SD patients after treatment. The median over-all survival and progression-free-survival of 15 patients were 12.0 months and 5.5 months, respectively. Patients with a pretreatment neutrophil/lymphocyte ratio (NLR) lower than 5.0 showed significantly longer survival. Even in an analysis limited to the patients with an NLR lower than 5.0, the patients whose CD8+/Treg ratio increased more than twofold tended to survive longer. In conclusion, the comprehensive immunotherapy using Zol-DCs, systemic αβT cells, and GEM may synergistically show a therapeutic effect on locally advanced pancreatic carcinoma. By using appropriate and precise biomarkers, such as NLR and CD8+/Treg ratio, the present comprehensive immunotherapy could be more beneficial for patients with pancreatic carcinoma., Competing Interests: CONFLICTS OF INTEREST None.

Background: Pancreatic fistula (PF) is a major complication following pancreatoduodenectomy (PD). Pancreatic texture is a risk factor for PF, but its evaluation depends on the subjective judgment. The aim of this study was to investigate whether preoperative endoscopic ultrasonography-elastography (EUS-EG), which objectively assesses tissue elasticity, predict the development of PF following PD., Methods: Fifty-nine patients who underwent EUS-EG before PD and had pancreas parenchyma histologically evaluated were included. Using histogram analysis, mean elasticity (ME), which represents tissue elasticity and is inversely correlated with pancreatic fibrosis, was calculated., Results: Among 59 patients, 19 developed PF (32.2%). The ME in patients with PF was significantly higher than that in patients without PF (85.4 vs. 55.6, P < 0.001). Area under the receiver operating characteristic curve for the accuracy of pancreatic texture and ME for predicting PF were 0.718 and 0.846, respectively. When a ME of 70.0 was used as a cut-off value for predicting PF, the sensitivity and specificity were 84.2% and 80.0%, respectively. In a multivariate logistic regression analysis, only a ME of >70.0 was an independent predictor of PF (odds ratio 10.02, P = 0.008)., Conclusions: Endoscopic ultrasonography-elastography may be an accurate and objective method for predicting PF following PD., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background and Study Aims: Endoscopic ultrasound (EUS) elastography (EUS-E) and contrast-enhanced harmonic EUS (CH-EUS) are useful methods for the diagnosis of pancreatic lesions. This study aims to compare the accuracy of combined EUS-E and CH-EUS with that of EUS-E or CH-EUS alone in the differential diagnosis of pancreatic solid lesions., Patients and Methods:  One hundred thirty-six patients with solid pancreatic lesions underwent EUS with both EUS-E and CH-EUS were included. Diagnoses were classified as adenocarcinoma, neuroendocrine tumor (NET), and inflammatory pseudotumor in 95, 22, and 19 patients, respectively. EUS records in each case were rearranged into 3 groups: EUS-E, CH-EUS, and combination. Each modality was randomly reviewed by 3 reviewers with different levels of clinical experience. Sensitivity, specificity, and accuracy of each modality according to each diagnosis group were evaluated. For the combined diagnosis populations, the proportions of correct diagnoses among the 3 modalities were compared by using the multivariate logistic regression analysis., Results: The accuracies of EUS-E, CH-EUS, and the combination of them were 68.4 %, 65.4 %, and 75.7 %, respectively, for adenocarcinoma group; 83.8 %, 82.4 %, and 86.8 % for NET group; 80.1 %, 78.7 %, and 81.6 % for inflammatory pseudotumor group. The multivariate logistic regression analysis for the combined diagnosis populations showed that the proportion of correct diagnoses when EUS-E and CH-EUS were combined was slightly higher than with the other 2 modalities, although the significant differences among them were not observed., Conclusion: EUS-E and CH-EUS combined may improve differential diagnosis of solid pancreatic lesions compared with use of the individual modalities.

Background: Small bowel capsule endoscopy (SBCE) is the recommended first-line procedure for obscure gastrointestinal bleeding (OGIB). However, a method for predicting the necessity of subsequent double-balloon endoscopy (DBE) has not been established., Aims: We aimed to develop a new scoring system that predicts the necessity of DBE in OGIB., Methods: A retrospective study was performed in 330 patients who underwent SBCE for OGIB at Nagoya University Hospital. The enrolled patients were randomly assigned to either a development or a validation dataset. The former was used to construct a prediction scoring system to assess the necessity of DBE using independent predictors selected by logistic regression. The diagnostic yield of the prediction model was assessed using the validation dataset., Results: Multivariate logistic regression analysis of the development dataset identified OGIB type, blood transfusion, and SBCE findings as independent predictors of the necessity of DBE. A prediction score gave an area under the receiver operating characteristics curve of 0.77. The sensitivity, specificity, positive predictive value, and negative predictive value at a cutoff ≥2.5 points were 72.5%, 74.6%, 72.6%, and 74.5%, respectively., Conclusion: Our scoring system may aid clinicians in deciding when to recommend DBE for patients with OGIB., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: To examine usefulness of virtual biopsy using endocytoscopy by comparing the in vivo endocytoscopic and histopathological images of gastric cancers., Methods: Endocytoscopy was performed in 30 patients with early gastric cancer. Of these, 26 patients showed well differentiated adenocarcinomas, while 4 patients showed poorly differentiated adenocarcinomas (including one signet ring cell carcinoma). Cancerous and non-cancerous areas were observed after double staining with 0.05% crystal violet and 0.1% methylene blue. The endocytoscopic images obtained were evaluated by an expert endoscopist and an expert pathologist without knowledge of patient clinical data, and endocytoscopic and histopathological diagnoses were compared., Results: The endocytoscopic images of the cancerous area were assessed as evaluable in 25 (83.3%) and 27 (90%) patients by endoscopist A and pathologist B, respectively, and those of the non-cancerous area as evaluable in 28 (93.3%) and 23 (76.7%) patients by the endoscopist and pathologist, respectively. The sensitivity, specificity, and diagnostic accuracy of gastric cancer diagnosis using evaluable endocytoscopic images were 88.0% and 92.9%, and 90.6% by endoscopist A, and 88.9% and 91.3%, and 90.0% by pathologist B, respectively. Evaluation of the diagnostic concordance rate between the endoscopist and the pathologist by inter-observer agreement calculation revealed no significant difference between the two observers. The inter-observer agreement ( κ -value) for endocytoscopic diagnosis was 0.745., Conclusion: Endocytoscopy is useful for the differentiation of cancerous from non-cancerous gastric mucosa, making it a promising tool for virtual biopsy., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest.

Objectives: Patients undergoing double-balloon enteroscopy require sedatives such as midazolam; however, patient's body motion often hampers the outcome of double-balloon enteroscopy. Recently, dexmedetomidine has been used for endoscopic sedation and was reported to effectively reduce body motion. This study aimed to evaluate the efficacy and safety of sedation with dexmedetomidine in double-balloon enteroscopy (UMIN ID000015785)., Methods: A prospective, observational study was conducted in 81 patients who underwent 111 double-balloon enteroscopy from July to December 2015 (dexmedetomidine group). The medical records of 112 patients who underwent 166 double-balloon enteroscopy with midazolam and pentazocine sedation from January 1 to October 31, 2014, were used for comparison (midazolam group). After propensity score matching, 182 double-balloon enteroscopy (91 double-balloon enteroscopy for each group) were analyzed., Results: There were 13 cases (11.7%) with body movements in the dexmedetomidine group. Comparison of the two groups matched by propensity score showed that the dexmedetomidine group had less body movement (12.1% vs 34.1%, p = 0.001) and less respiratory depression (50.5% vs 68.1%, p = 0.023). Hypotension (8.8% vs 4.4%, p = 0.232) and bradycardia (2.2% vs 0%, p = 0.497) were not significantly different in the two groups., Conclusion: Using dexmedetomidine for conscious sedation can reduce body motion and respiratory depression compared to our previous records., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Retention is the most common complication of capsule endoscopy (CE), and is reported to occur in 0-13% of cases. To avoid retention, a PillCam patency capsule (PC) is used in patients with suspected intestinal stenosis. However, a relatively low positive predictive value of the PC examination has been reported previously. The aims of this study were to clarify the accuracy of PC examination and to evaluate clinical factors related to cases of false-positive detection., Methods: We performed a retrospective single-center study of 282 consecutive patients referred for PC examination. Patients in which the PC could not pass through the small bowel within 33 h were classified into the 'no patency' group. The 'no patency' group was investigated for evidence of significant stenosis upon further examinations, including CE, double-balloon endoscopy, and small bowel follow-through after PC examination. Clinical factors related to small bowel patency and false-positive cases were evaluated., Results: We included 161 male (57.1%) and 121 female (42.9%) patients with a mean age of 47.5 ± 17.7 years. Of the 282 patients enrolled, 27 patients exhibited 'no patency' upon PC examination. Multivariate analysis showed that clinical factors related to 'no patency' included Crohn's disease, abdominal symptoms, stenosis upon imaging, and previous abdominal surgery. Upon further examination, nine cases in the 'no patency' group had significant stenosis. Sensitivity, specificity, and negative and positive predictive values of PC examination for detecting small bowel stenosis were 93.8%, 96.6%, 99.6%, and 62.5%, respectively, and the only clinical factor related to false-positive cases was constipation ( p < 0.05)., Conclusion: We found a relatively low positive predictive value of PC examination and that constipation was related to false-positive results. To extend the implications of CE indications, clinical study focusing on these results is expected., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Purpose: To evaluate the efficacy and safety of gemcitabine plus cisplatin in Japanese patients with unresectable gallbladder cancer (GBC)., Methods: Chemo-naïve patients with histologically proven unresectable GBC were enrolled in this study. The patients received gemcitabine (1000 mg/m 2 ) and cisplatin (25 mg/m 2 ) on days 1 and 8, every 21 days. A response assessment was done by CT scan every 4 weeks. The primary end points were to determine the response rates [RR; complete response (CR) + partial response (PR)] and the disease control rate [DCR; CR + PR + stable disease (SD)]. The secondary end points were to evaluate toxicity, progression-free survival (PFS), and overall survival (OS)., Results: From March 2012 to February 2015, 14 patients from seven different institutions were enrolled in the study, and 13 cases were evaluable for assessment. Eleven cases (84.6%) had distant metastases, and 8 cases (61.5%) had obstructive jaundice. There was no CR, 1 PR (7.7%), 11 SD (84.6%), and 1 progressive disease (PD) (7.7%). The RR was 7.7%, whereas the DCR was 92.3%. The median PFS was 3.1 months, the median OS was 6.2 months, and the one-year survival rate was 0%. Grade 3 hematologic toxicity was observed in three cases (23%), but all of them recovered upon drug withdrawal, and there was no treatment-related death., Conclusion: Although gemcitabine plus cisplatin has a high DCR (92.3%) and relatively low toxicity, the RR is less than 10%, and development of new therapies is desired for the treatment of unresectable GBC.

Background: It is difficult to diagnose chronic pancreatitis (CP) objectively because of a lack of standard diagnostic criteria. Endoscopic ultrasonography (EUS) has been used to assess the severity of CP, but the diagnosis of CP using EUS depends on an endosnonographer. The aim of this study was to establish an objective diagnostic method for CP using EUS elastography (EUS-EG)., Methods: A retrospective study was designed and 96 patients underwent EUS-EG for follow-up of known CP, or who were clinically suspected as having CP. CP patients were categorized CP patients as 4 stages using the Rosemont classification (RC). EUS-EG was performed and the "Mean value", which was negatively correlated with pancreatic fibrosis, was calculated using histogram analysis., Results: The "Mean value" of each RC stage (normal, indeterminate for CP, suggestive of CP, and consistent with CP) was 90.1 ± 19.3, 73.2 ± 10.6, 63.7 ± 14.2, and 56.1 ± 13.6, respectively, and showed significant differences for each stage (p < 0.001). There was a significant negative correlation between the "Mean value" and the number of EUS features (r s  = -0.59, p < 0.001). Multiple linear regression analysis was used to assess the diagnostic finding of the "Mean value" and showed that hyperechoic foci with shadowing and lobularity with honeycombing maintained their independent diagnostic findings., Conclusions: EUS-EG was an objective diagnostic apparatus for CP and provided objective information to support EUS features.

Background and study aims  There have been few evaluations of the diagnostic ability of new narrow band light observation blue laser imaging (BLI). The present prospective study compared the diagnostic ability of BLI magnification and pit pattern analysis for colorectal polyps. Patients and methods  We collected lesions prospectively, and the analysis of images was made by two endoscopists, retrospectively. A total of 799 colorectal polyps were examined by BLI magnification and pit pattern analysis at Nagoya University Hospital. The Hiroshima narrow-band imaging classification was used for BLI. Differentiation of neoplastic from non-neoplastic lesions and diagnosis of deeply invasive submucosal cancer (dSM) were compared between BLI magnification and pit pattern analysis. Type C2 in the Hiroshima classification was evaluated separately, because application of this category as an index of the depth of cancer invasion was considered difficult. Results  We analyzed 748 colorectal polyps, excluding 51 polyps that were inflammatory polyps, sessile serrated adenoma/polyps, serrated adenomas, advanced colorectal cancers, or other lesions. The accuracy of differential diagnosis between neoplastic and non-neoplastic lesions was 98.4 % using BLI magnification and 98.7 % with pit pattern analysis. In addition, the diagnostic accuracy of BLI magnification and pit pattern analysis for dSM for cancer was 89.5 % and 92.1 %, respectively. When type C2 lesions were excluded, the diagnostic accuracy of BLI for dSM was 95.9 %. The 18 type C2 lesions comprised 1 adenoma, 9 intramucosal or slightly invasive submucosal cancers, and 8 dSM. Pit pattern analysis allowed accurate diagnosis of the depth of invasion in 13 lesions (72.2 %). Conclusions  Most colorectal polyps could be diagnosed accurately by BLI magnification without pit pattern analysis, but we should add pit pattern analysis for type C2 lesions in the Hiroshima classification.

Patients with advanced hematological malignancies are less likely to be referred to specialist palliative care services compared with patients having solid tumors. It has been reported that one of the most important reasons for the lack of referral is difficulties in the prognostication of terminally ill patients with hematologic malignancies. The study objective was to evaluate the predictive accuracy of the Palliative Prognostic Index (PPI) and the prognostic model developed by Kripp et al in hospitalized patients under the care of a hematologist. Using clinical charts, we retrospectively calculated the above scores. We reviewed the records of 114 patients admitted to the hematology ward. The inclusion criterion was patient with disease considered incurable using standard treatments. The prognostic models were assessed according to the original reports. Using PPI cutoff points of 2 and 4, we divided the patients into 3 groups of significantly different survival times ( P < .01). Moreover, we confirmed the usefulness of predicting survival <3 and <6 weeks using PPI scores of 6 and 4 as cutoff points, respectively. When we classified patients according to the prognostic model of Kripp et al, the high-risk group survived significantly shorter times than the intermediate- and low-risk groups ( P < .001). However, there was no significant difference in survival between the intermediate- and low-risk groups. Use of these models might enable physicians to provide more appropriate end-of-life care and to refer patients to palliative care earlier.

Capsule endoscopy (CE) and double-balloon endoscopy (DBE) have revolutionized the diagnosis and treatment of obscure gastrointestinal bleeding (OGIB). Although CE and DBE provide access to the small bowel and OGIB can be effectively treated by the identification of specific bleeding lesions, some patients experience rebleeding after small bowel investigation. There are no definite algorithms to determine the best follow-up period for patients with OGIB. The purpose of this study was to investigate the long-term outcomes and risk factors for rebleeding and to develop a follow-up strategy for patients with overt OGIB. Among 386 patients who underwent CE for OGIB at Nagoya University Hospital between June 2004 and December 2015, 318 patients with overt OGIB were enrolled in this retrospective study. The clinical characteristics and risk factors for rebleeding were analyzed, and a predictive model for the same was developed. Rebleeding occurred in 45 patients (14.2%) during a median follow-up period of 16.8 months. Multivariable regression analysis identified the following factors as significant independent predictors of rebleeding:vascular lesions seen during CE, transfusion requirement, and patients aged ≥60 years. The predictive model for rebleeding was developed using these factors to identify patients who had a high risk of rebleeding and to provide useful information to physicians in clinical practice. The C-statistic of the predictive model was 0.698. A risk-based approach to follow-up patients with OGIB can help clinicians determine a follow-up period for patients after small bowel investigation.

Background/aims: Balloon-assisted endoscopy allows us to diagnose gastrointestinal (GI) stromal tumors (GISTs) in the small bowel including endoscopic ultrasonography and taking biopsy. The aim of this study was to retrospectively clarify clinical and endoscopic characteristics of small bowel GISTs using double-balloon endoscopy (DBE)., Methods: We reviewed 25 patients who underwent DBE and were diagnosed with GISTs. The risk of GISTs was stratified using the National Institute of Health (NIH) consensus criteria. We evaluated the available DBE route, the diagnostic yield of biopsy examination, and the relationship between endoscopic characteristics and recurrence-free survival (RFS)., Results: Of all 25 patients, 23 had any endoscopic findings related to GIST. They were detected using the antegrade approach in 91.3%. GISTs were classified into high risk (n = 7), intermediate risk (n = 4), low risk (n = 10), and very low risk (n = 4) based on surgical specimens. The diagnostic result of biopsy was 46.7% (7/15), but it was difficult to predict the NIH risk group. Endoscopic characteristics were not associated with RFS. The NIH risk group was significantly associated with RFS., Conclusions: Antegrade DBE was preferable for exploring small bowel GIST, but the diagnostic ability of biopsy examination was limited., (© 2017 S. Karger AG, Basel.)

Endoscopic ultrasound (EUS) has recently played an increasing role in the diagnosis of gallbladder diseases. This review aims to summarize the role of EUS in the diagnosis of gallbladder lesions. EUS provides high-resolution images that can improve the diagnosis of gallbladder polypoid lesions and microlithiasis, in addition to evaluating gallbladder thickness and staging of gallbladder carcinoma. Contrast-enhancing agents may be useful for the differential diagnosis of gallbladder lesions, but the evidence of their effectiveness is still limited and further studies are required in this area to establish its usefulness. Endoscopic ultrasound combined with fine needle aspiration has played an increasing role in providing histological diagnosis of gallbladder tumors in addition to gallbladder thickening.

Background: Colon capsule endoscopy (CCE) is a procedure in which capsule swallowing facilitates observation of the lumen of the entire digestive tract. It does not require an air supply, and is a noninvasive procedure with a markedly low risk of adverse events in comparison with conventional colonoscopy (CS). It reduces patient stress, and may be acceptable to patients. A limitation of this procedure is that the entire colon observation rate (CCE excretion rate, completed CCE rate) is not 100%. In this study, we prospectively investigated clinical factors important to achieve observation of the entire colon on CCE., Methods: The participants were 70 patients for whom CCE was scheduled, and from whom written informed consent regarding participation in this study was obtained. We selected patient background/examination factors, and analyzed all factors involved in observation of the entire colon and factors for completion of the CCE within 4 h after the start of examination using multivariate analysis., Results: Of the 70 enrolled patients, 64 were analyzed, excluding 6. On multiple logistic analysis, only a water intake of ⩾12.0 ml/min during examination [ p = 0.025, odds ratio (OR): 46.753, 95% confidence interval (CI): 1.630-1341.248] was identified as an independent predictive factor involved in observation of the entire colon. With respect to factors involved in the completion of CCE within 4 h, multiple logistic analysis showed that a body mass index (BMI) of ⩾25 ( p = 0.039, OR: 13.723, 95% CI: 1.135-165.913), the absence of constipation ( p = 0.030, OR: 13.988, 95% CI: 1.287-152.047), and a water intake of ⩾12.0 ml/min during examination ( p = 0.004, OR: 12.028, 95% CI: 2.225-65.029) were independent predictive factors., Conclusions: Completion of a CCE was most closely related to water intake per hour. In addition to water intake, CCE-promoting factors included a high BMI and the absence of constipation., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Background and study aims  Diagnosis of Meckel's diverticulum (MD) before surgery may be challenging; double-balloon endoscopy (DBE) facilitates identification of MD in the setting of a gastrointestinal bleeding; however, MD can be found incidentally without this condition. The purpose of this research was to determine specific characteristic of hemorrhagic MD and incidental MD at DBE. Patients and methods  Ectopic gastric mucosa enclosed in the MD and/or ulceration were defined as "major findings"; ring-like scar surrounding the MD was defined as "minor finding". We retrospectively reviewed the medical records of patients affected by MD and analyzed the findings that significantly affected the characterization of MD. Results  MD was diagnosed in 33 patients. The axis of the diverticulum was longer in hemorrhagic MD compared to incidental MD ( P  = 0.031). The amount of transfusion was significantly higher ( P  = 0.018) in the hemorrhagic MD group. Hemorrhagic MD was significantly more correlated with major findings ( P  = 0.01) and minor findings ( P  < 0.01). The specificity of major finding was 100 % while the sensitivity of major and/or minor findings was 96 %. Conclusions  The combination of major and minor findings appears to improve the diagnostic ability of hemorrhagic MD avoiding unnecessary diverticulectomy.

Background & Aims: There is no established non-invasive method for diagnosis of pancreatic fibrosis. Shear wave elastography (SW-EG) may be a candidate for this purpose. The aims of this study were to assess the reproducibility of SW-EG in the normal imaging pancreas (Phase 1) and to evaluate the diagnostic performance of SW-EG for pancreatic fibrosis classified histologically (Phase 2)., Methods: Phase 1: This included 127 cases that underwent SW-EG of the normal imaging pancreas. SW-EG was measured at least five times in the pancreatic parenchyma and the median of repeated measurements was defined as the pancreatic elastic modulus (PEM). Phase 2: This included 53 cases that underwent SW-EG of the pancreatic parenchyma preoperatively and in which pancreas parenchyma were evaluated histologically. Histological fibrosis was graded in 4 stages: normal, mild, moderate, and severe., Results: Phase 1: Median PEM in the head, body, and tail of the pancreas were 3.23, 3.17, and 2.91 kPa, respectively, with no significant difference among regions (P = 0.554). The intraclass correlation coefficient showed good reproducibility (ρ = 0.71) after 5 measurements. Phase 2: There was a significant positive correlation between PEM and the histological pancreatic fibrosis stage (r s  = 0.63, P < 0.001). Areas under the receiver operating characteristic curve for the accuracy of SW-EG for diagnosis of pancreatic fibrosis were 0.85 (≥mild), 0.84 (≥moderate), and 0.87 (severe)., Conclusion: SW-EG can be used to determine the stage of pancreatic fibrosis non-invasively with high accuracy and reproducibility., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background and Aims: In the International Consensus Diagnostic Criteria (ICDC), autoimmune pancreatitis (AIP) is classified into types 1 and 2, and its definite histopathology diagnosis can be made based only on surgical or core biopsy specimens. Although EUS-guided FNA (EUS-FNA) biopsy is a safe technique for the collection of pancreatic tissue, no consensus viewpoint has been reached with regard to the role of EUS-FNA biopsy in the diagnosis of AIP. This study investigated the utility of pancreatic tissue collected by EUS-FNA biopsy by using a standard 22-gauge aspiration needle in the diagnosis of AIP., Methods: Patients with suspected AIP were prospectively enrolled in Nagoya University Hospital and Nagoya University-affiliated institutions. Pancreatic tissue was collected from each by EUS-FNA biopsy with a standard 22-gauge aspiration needle., Results: Fifty patients were registered, including 45 with a final diagnosis of AIP. Lymphoplasmacytic infiltration and abundant immunoglobulin G4-positive plasmacyte infiltration (>10/high-power field) were detected in 36 (72%) and 27 (54%) patients, respectively. Obliterative phlebitis and storiform fibrosis were not detected in our study. Granulocytic epithelial lesions (GEL) were observed in 3 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNA biopsy to definitively diagnose AIP were 7.9% (3/38), 100% (12/12), 100% (3/3), and 25.5% (12/47), respectively. Pathology evaluation of pancreatic tissue collected by EUS-FNA biopsy improved the diagnostic accuracy in 8 (16%) of the 50 patients., Conclusions: In this study, EUS-FNA biopsy by using a standard 22-gauge aspiration needle is not an effective diagnostic method for most patients with AIP. The combination of level 2 histology diagnosis of AIP with other findings specified in the ICDC slightly improved the diagnostic accuracy, although it still remains insufficiently accurate for routine clinical use.(, Clinical Trial Registration Number: 000006297.)., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Double-balloon endoscopy (DBE) is useful for the diagnosis and treatment of small bowel diseases. Although fluoroscopy is used to confirm the position of endoscope at DBE, the endoscopist does not have the knowledge with regard to the radiation exposure dose. In this study, we evaluated the absorbed dose during DBE in patients with suspected or established small bowel diseases. This was a retrospective study in which the estimated fluoroscopic radiation absorbed doses loaded on the small bowel and skin were determined according to the data of the referential X-ray experiment with a human body phantom. The subjects were 415 DBEs preformed in total. The mean small bowel absorbed doses on antegrade and retrograde DBEs were 42.2 and 53.8 mGy, respectively, showing that the organ dose applied in retrograde DBE was significantly higher (P<0.0001). The mean skin absorbed doses of them were 79.2 and 101.0 mGy, respectively, showing that the dose was also significantly higher on retrograde DBE (P<0.0001). Of 27 cases who were applied endoscopic balloon dilation, the mean fluoroscopy time was 16.0 minutes, and mean small bowel and skin absorbed doses were 121.9 and 228.9 mGy, respectively. In conclusion, endoscopist should be careful for reducing the organ exposure dose at DBE, particularly for the lower abdominal region., Abbreviations: Double-balloon enteroscopy (DBE), endoscopic balloon dilation (EBD), endoscopic mucosal resection (EMR), double-balloon endoscopic retrograde cholangiopancreatography (DBERCP), percutaneous coronary intervention (PCI).

Background: Ultrasound strain elastography is one of the useful methods for evaluating pancreatic lesions. During aging, several pancreatic parenchymal changes occur that may interfere with the interpretation of the ultrasound images. We studied age-related changes in pancreatic elasticity using transabdominal ultrasound strain elastography in subjects without known pancreatic disease., Methods: This study was conducted at Nagoya University Hospital, which is an academic medical center, and included 102 subjects (66 women and 39 men) aged 20-85years (mean 58.6±17.5) who underwent transabdominal ultrasonography for screening and follow-up for non-pancreatic diseases. Strain elastography of the pancreas was performed, and the results were subjected to quantitative strain histogram analysis. The correlations of age with four elastographic parameters (Mean, Standard deviation, Skewness, and Kurtosis) and other findings, including hyperechoic pancreas, hyperechoic liver, and diabetes, were evaluated., Results: There was a significant correlation between increasing age and elastographic parameters such as the Mean (P=0.004), Skewness (P=0.007), and Kurtosis (P=0.03), and these differences became significant after the age of 40. The prevalence of hyperechoic pancreas increased with age (P<0.001), and the Means were lower in those with hyperechoic pancreas (P=0.004) and a higher body mass index (BMI, P=0.008). No significant correlations with diabetes, hyperechoic liver, or elastographic parameters were demonstrated., Conclusion: Strain elastography demonstrated elastographic changes in the pancreas with aging that included a decreasing Mean and increasing Skewness and Kurtosis after the age of 40. The prevalence of pancreatic hyperechogenicity increased, and the pancreatic hyperechogenicity was significantly negatively correlated with the Mean., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background and Aim: Patients with advanced pancreatic cancer have severe pain, anxiety, and depression, and these symptoms deteriorate quality of life (QOL). Previous study reported that early psychiatric intervention for advanced cancer patients may improve QOL. We evaluated the trajectory of health-related QOL (HRQOL) in patients with pancreatic cancer after an early psychiatric intervention., Methods: A prospective cohort study was performed in 108 pancreatic cancer patients who received consultation liaison psychiatry from November, 2011 to October, 2014 at Nagoya University Hospital. Longitudinal changes in HRQOL and the association between aspects of HRQOL and survival were evaluated using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 before treatment and every month after the start of treatment., Results: Physical functioning significantly decreased after 1, 3, and 6 months of treatment compared with baseline, but global health status (GHS), role functioning, emotional functioning, and social functioning showed a tendency to improve. Severe impairment of GHS, fatigue, and appetite loss were apparent at 3 months prior to death. In multivariate analysis, pain was a significant prognostic factor for survival (hazard ratio [HR], 1.109; 95% confidence interval [CI], 1.021-1.204; P = 0.013), in addition to poor performance status (HR, 5.473; 95%CI, 2.338-12.816; P < .0001) and distant metastases at diagnosis (HR, 3.274; 95%CI, 1.872-5.725; P < .0001)., Conclusions: Early psychiatric intervention in patients with pancreatic cancer may maintain HRQOL. More effective pain management and reduction of psychological distress are important for patients with pancreatic cancer., (© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

A 72-year-old man with the history of small bowel carcinoma was diagnosed to have a sessile polyp in the jejunum during a follow-up examination. We performed double-balloon endoscopy and removed the polyp by means of cold snare polypectomy. The follow-up endoscopy showed no residual lesion. Cold snare polypectomy has been established as a safe and effective method for the endoscopic treatment of colonic polyps with a low risk of causing electrocautery burns and perforation. However, this technique has not yet been applied for small bowel lesions. This case report, for the first time, shows the feasibility of performing cold snare polypectomy for small bowel polyps.

Endoscopic treatment for superficial non-ampullary duodenal tumors is technically difficult and challenging due to the anatomical characteristics of the duodenum. It is frequently complicated by procedural accidents, such as perforation. Surgical repair has long been the standard treatment for acute iatrogenic gastrointestinal perforation. However, endoscopic closure has recently emerged as an attractive alternative. In the patient presented herein, the over-the-scope-clipping system (OTSC system) was found to be useful for closing a duodenal perforation that had occurred during endoscopic submucosal dissection. For endoscopists who perform endoscopic treatment of the duodenum, endoscopic closure with the OTSC system is considered to be a technique that is necessary to master.

Background. Although the usefulness of capsule endoscopy (CE) and double-balloon endoscopy (DBE) for the evaluation of Crohn's disease (CD) is established, their capabilities in the differential diagnosis of small bowel stenosis have not been sufficiently addressed. The present study therefore aimed to retrospectively determine the types of patients for whom CE and DBE would confer the most benefit. Patients and Methods. We retrospectively reviewed data from 185 patients with established CD. A change of treatment based on CE or DBE results or successful DBE balloon dilation was defined as clinically useful indication. We then analyzed the factors significantly related to useful and poor indications. Results. CE results were assessed as useful indications in 28 (45%) of 62 patients. Multivariate analysis demonstrated that positive CRP and low IOIBD score are factors significantly related to a useful indication. DBE results were recognized as useful indications in 118 (77%) of 153 patients. Multivariate analysis indicated small bowel stenosis and abdominal pain as factors significantly associated with useful indications. All patients with a poor indication on CE had small bowel stenosis. Conclusions. CE was most useful for patients in clinical remission with positive CRP and without stenosis, whereas DBE was useful for patients with symptoms of stenosis.

Objective The objectives of this study were to investigate the mRNA and protein expression of biomarkers related to absorption in the small intestinal mucosa of humans and determine the relationships between small intestinal diseases and nutrition. Methods The study subjects consisted of patients scheduled to undergo double-balloon endoscopy (DBE) or total colonoscopy for suspected gastrointestinal disorder in a clinical practice. Biopsies were taken from apparently normal mucosa in the visible areas of 6 parts of the intestines from the duodenum to the colon. The mRNA expression of specific biomarkers (SGLT1, SGLT5, GIP, GLP, LAT1, LAT2, and NPC1L1) in the mucosa was compared among three patient groups: Inflammation, Tumor, and Control. Results Sixty-six patients participated in this study. Both routes of DBE were performed in 20 patients, in whom biopsy samples were obtained from the mucosa for all sections. There were no remarkable differences in the mRNA expression levels among the 3 groups. However, SGLT1, GIP, GLP, and NPC1L1 exhibited specific distribution patterns. The expression levels of GIP and NPC1L1 were highest in the upper jejunum, but were extremely low in the terminal ileum and colon. A comparison of the mRNA expression profile in each intestinal section revealed that the SGLT1 mRNA expression in the Tumor group and the GIP mRNA expression in the Inflammation group were significantly higher than the corresponding levels in the Control group in the upper jejunum. Conclusion The gastrointestinal mucosa of patients with small bowel diseases can maintain proper nutrient absorption, except in the upper jejunum.