宮原 良二

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.

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 1.31mm2, 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.

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: Primary intestinal diffuse large B-cell lymphoma (iDLBCL) is rare. In this study, we investigated the clinicopathological features of this disease to further understand the prognostic value of CD5, programmed cell death ligand 1 (PD-L1), and Epstein-Barr virus (EBV) on tumor cells. METHODS: Tumor specimens from 62 patients consecutively diagnosed with primary iDLBCL at a single institution were analyzed. RESULTS: Our series consisted of EBV-positive (EBV+ ) iDLBCL (n = 10), de novo CD5+ iDLBCL (n = 4), and DLBCL, not otherwise specified (DLBCL-NOS; n = 48). Notably, seven of 10 EBV+ cases had treated lymphoma-associated (n = 4) or iatrogenic immunodeficiency (n = 3). Two of 10 EBV+ cases expressed PD-L1 on tumor cells, whereas the remaining eight were positive for PD-L1 on microenvironment immune cells. Only one DLBCL-NOS case had neoplastic PD-L1 expression with a giant cell-rich appearance. Both EBV-harboring and PD-L1 expression on tumor cells, but not CD5, were associated with worse overall survival (OS) in iDLBCL patients receiving rituximab-containing chemotherapy (P = 0.0354, P = 0.0092, and P = 0.1097, respectively). Multivariate analysis identified PD-L1 positivity on tumor cells (P = 0.0106), PD-L1 negativity on microenvironment immune cells (P = 0.0193), and EBV positivity (P = 0.0324) as poor independent prognostic factors for OS. Among iDLBCL cases without any EBV association, CD5 positivity, or neoplastic PD-L1 expression, high PD-L1 expression (≥40%) on microenvironment immune cells predicted an extremely favorable outcome. CONCLUSION: EBV+ iDLBCL mainly comprised immunodeficiency-associated patients, which may highlight the specificity of the intestine. PD-L1 expression on tumor cells or microenvironment immune cells was found to have an opposite prognostic impact in iDLBCL.

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.

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 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.

BACKGROUND AND AIMS: The feasibility of magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD) using a neodymium magnet for gastric lesions has not been clarified. The aim of study was to evaluate the feasibility of MAG-ESD using neodymium magnets while treating gastric lesions. METHODS: This prospective trial was conducted at the Yamashita Hospital. MAG-ESD was performed for 50 gastric lesions using an insulated-tip knife. The magnetic anchor consisted of an internal neodymium magnet attached to a hemoclip with 3-0 silk. The external and internal magnets were made from the neodymium magnet. The feasibility of traction using MAG-ESD, en bloc resection rate, complete en bloc resection rate, time required for preparation and attaching the magnetic anchor, procedure time, rate of retrieval of the magnetic anchors, and adverse events were evaluated. RESULTS: Fifty patients (median lesion size, 20 mm [range, 5-100]) were enrolled. MAG-ESDs were successfully performed for all 50 gastric lesions. Adequate counter-traction was obtained using the external magnet. En bloc resections were achieved and complete en bloc resections confirmed in all cases without adverse events. Attaching the magnetic anchor required a median of 6 minutes (range, 2-14). The median procedure time was 49 minutes (range, 15-301), and the magnetic anchors could be retrieved in all cases. CONCLUSIONS: This study clearly demonstrated the feasibility of this MAG-ESD in the stomach. We hope this procedure will facilitate the resection of difficult lesions. (Clinical trial registration number: UMIN000024100.).

EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), often affects the gastrointestinal tract. However, the prognostic significance of EBV associated with primary gastric DLBCL (gDLBCL) has not been established. This retrospective study included 240 patients with primary gDLBCL, diagnosed between 1995 and 2015. Tumor specimens were analyzed with EBER in situ hybridization. In 25 (10%) cases, tumor cells harbored EBV. The EBV+ group more frequently exhibited programmed death-ligand 1 (PD-L1) expression in microenvironment immune cells, but not tumor cells, compared to the EBV- group (86% vs 43%, P = .006). Among 156 patients that received rituximab-containing chemotherapy, the EBV+ group had a significantly worse overall survival (OS) than the EBV- group (P = .0029). Multivariate analyses identified 3 independent adverse prognostic factors of OS: multiple gastric lesions (P = .002), EBER positivity (P = .003), and B symptoms (P = .018). These factors were combined to develop a gDLBCL prognostic (gDLP) model that significantly stratified the patients into 3 distinct risk groups (Scores: good = 0, intermediate = 1, and poor = 2/3, P < .0001) with 5-year OS rates of 100%, 81%, and 39%, respectively. Patients with EBV+ gDLBCL commonly exhibited microenvironmental PD-L1 expression and showed a significantly worse prognosis than subjects with EBV- gDLBCL. Our gDLP model, which included EBV+ tumor cells, provided good predictions of clinical outcome and may be useful for selecting patients in trials in the immune-oncology era.

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.

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 (rs  = 0.54), Japan Pancreas Society stage (rs  = 0.41), and the number of EUS features (rs  = 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.

BACKGROUND: The aim of this study was to evaluate the impact of the location of esophagogastrostomy on acid and duodenogastroesophageal reflux (DGER) in patients undergoing gastric tube reconstruction and intrathoracic esophagogastrostomy. METHODS: Thirty patients receiving transthoracic esophagectomy without cervical lymph node dissection and gastric tube reconstruction by intrathoracic anastomosis were enrolled. All patients underwent 24-h pH and bilirubin monitoring and gastrointestinal endoscopy one year after surgery. Patients were divided into three groups according to esophagogastrostomy location: group A (n = 9), above the top of the aortic arch; group B (n = 15), between the top and bottom of the aortic arch; and group C (n = 6), below the bottom of the aortic arch. The relations among the esophagogastrostomy location, 24-h pH and bilirubin monitoring results, endoscopic findings, and reflux symptoms were investigated. RESULTS: No acid reflux into the remnant esophagus was observed in group A, whereas it was observed in three of 15 patients (20%) in group B and in two of six patients (33%) in group C (P = 0.139). No DGER was found in group A, whereas DGER was observed in eight (53%) patients in group B and all patients in group C (P < 0.001). Reflux esophagitis was observed in one patient (11%) in group A, five patients (33%) in group B, and all patients in group C (P = 0.002). CONCLUSION: In gastric tube reconstruction via intrathoracic anastomosis, esophagogastrostomy should be performed above the top of the aortic arch to prevent postoperative DGER and reduce the incidence of reflux esophagitis.

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.

OBJECTIVES: We determined the outcomes of seton treatment through a series of techniques using biological agents (BIOs) in 18 patients with Crohn's disease (CD) who initially presented with perianal fistulas. METHODS: The patients underwent seton drainage using three seton types: a Penrose tube for fistulas with massive purulent discharge, a vessel loop for a small amount of discharge, and a rubber band for unproductive fistulas. If the distal end of the fistula extended more than 4 cm from the anal orifice, the skin and subcutaneous tissue were dissected along the outer edge of the anal sphincter to divide the fistulous tract into two portions. One seton encircled the sphincter from the primary opening throughout the anal canal (medial seton), and the other was inserted through the distal tract outside the sphincter (lateral seton). A BIO was then introduced immediately. When discharge ceased, the Penrose tube or vessel loop was replaced sequentially with a rubber band, which was tied fittingly and subsequently removed in medial to lateral order. RESULTS: The mean interval between fistula onset and CD diagnosis was 2.1 years, and that between CD diagnosis and introduction of BIOs was 0.5 years. The mean follow-up duration was 4 years. The BIOs currently used were infliximab in 10 patients, adalimumab in 7, and ustekinumab in 1. The overall success rate was 94.4%, including unproductive fistulas in 10 (55.6%) patients and fistula disappearance in 7 (38.9%). CONCLUSIONS: Our seton drainage techniques via the "top-down" approach represent a promising avenue for treating perianal fistulas in patients with CD.

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.

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.

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.

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.

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.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. It is well known that activating mutations in the receptor tyrosine kinases KIT and platelet-derived growth factor receptor-α have essential roles in the pathogenesis of GISTs. The activation of these receptor protein kinases triggers multiple signaling pathways that promote cell proliferation and survival; however, the exact mechanism by which the activation of these kinases promotes the progression of GISTs remains uncertain. The aim of the present was to search for genes that are associated with the progression of GIST. The present study used reverse transcription-quantitative polymerase chain reaction to demonstrate that adenosine monophosphate deaminase 3 (AMPD3) was highly expressed in GISTs. Furthermore, transfection of GIST-T1 cells with KIT-specific small interfering RNA (siRNA) demonstrated that the expression of AMPD3 was dependent on KIT expression, while the depletion of AMPD3 in human GIST-T1 cells using AMPD3-specific siRNA resulted in the suppression of cell migration and invasion. In addition, AMPD3 depletion sensitized GIST-T1 cells to the tyrosine kinase inhibitor imatinib. The results of the present suggested that the combined inhibition of tyrosine kinases and AMPD3 may be effective for the treatment of GISTs.

AIM: To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients. METHODS: We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage IV gastric cancer. In particular, 30 or 40 mg/m2 of docetaxel on day 1, 60 mg/m2 of cisplatin on day 1, and 2000 mg/m2 of capecitabine for 2 wk were administered every three weeks. RESULTS: Three patients were treated with modified DCX (mDCX) with 30 mg/m2 docetaxel, and five patients were treated with this regimen with 40 mg/m2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes. CONCLUSION: mDCX was well tolerated by Japanese patients with stage IV gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.

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.

<p>原因不明消化管出血（OGIB）の長期予後に基づくマネジメント方法について検討した．対象は，2004年6月から2015年12月にOGIBに対して当院にて小腸カプセル内視鏡（CE）を施行した386例のうち，可視的出血をともなうovert OGIB症例318例で，その臨床的特徴と再出血予測因子について後方視的に検討し，再出血予測モデルを作成した．Overt OGIBの再出血予測因子は，CEにおける小腸血管性病変の存在，輸血歴，年齢60歳以上であり，それらの予測因子の保有数を参考にすることで，再出血率の推測が可能となり，個々の症例に対する適切なフォローアップ期間を提案できる可能性が示唆された．</p>

<p>The technology of medical devices is making progress day by day. However, user skill to used such devices are still required. There is a similar problem in endoscopic examination, and from the shallow depth of field of endoscope, the user skill and experience are required to focus on a target surface. In this paper, we propose stable endoscopic image creation algorithm to solve above problems. The effectiveness and limitation of proposed algorithm were confirmed through the several experiments.</p>

PURPOSE: Polyps found during CT colonography can be removed by colonoscopic polypectomy. A colonoscope navigation system that navigates a physician to polyp positions while performing the colonoscopic polypectomy is required. Colonoscope tracking methods are essential for implementing colonoscope navigation systems. Previous colonoscope tracking methods have failed when the colon deforms during colonoscope insertions. This paper proposes a colonoscope tracking method that is robust against colon deformations. METHOD: The proposed method generates a colon centerline from a CT volume and a curved line representing the colonoscope shape (colonoscope line) by using electromagnetic sensors. We find correspondences between points on a deformed colon centerline and colonoscope line by a landmark-based coarse correspondence finding and a length-based fine correspondence finding processes. Even if the coarse correspondence finding process fails to find some correspondences, which occurs with colon deformations, the fine correspondence finding process is able to find correct correspondences by using previously recorded line lengths. RESULT: Experimental results using a colon phantom showed that the proposed method finds the colonoscope tip position with tracking errors smaller than 50 mm in most trials. A physician who specializes in gastroenterology commented that tracking errors smaller than 50 mm are acceptable. This is because polyps are observable from the colonoscope camera when positions of the colonoscope tip and polyps are closer than 50 mm. CONCLUSIONS: We developed a colonoscope tracking method that is robust against deformations of the colon. Because the process was designed to consider colon deformations, the proposed method can track the colonoscope tip position even if the colon deforms.

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.

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: 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.

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.

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 (rho = 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 &lt; 0.001). Areas under the receiver operating characteristic curve for the accuracy of SW-EG for diagnosis of pancreatic fibrosis were 0.85 (&gt;= mild), 0.84 (&gt;= 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. (C) 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

We report a case series of five patients with pancreatic acinar cell carcinoma who received surgical treatment and compared the preoperative contrast-enhanced endoscopic ultrasound (EUS) and EUS elastography patterns with the surgical specimens. The contrast-enhanced EUS indicated vascular tumors with gradual enhancement in four patients and a hypovascular tumor in one patient. The elastography indicated an elastic score of 3 (hard lesion with softer border) in two patients and a score of 5 (hard lesion, which included the surrounding area) in two patients. In tumors with an elastic score of 5, the pathology exhibited abundant hyalinizing fibrous stroma or massive tumor invasion to the surrounding tissue. We concluded that acinar cell carcinoma of the pancreas has various patterns of EUS contrast-enhancement and elastography, depending on the pathologic phenotype.

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&lt;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&lt;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.

The patient was a 72 year old man who had been given non-steroidal anti-inflammatory drug (NSAID) for two years. He repeatedly developed small intestinal ileus; therefore, he underwent several imaging examinations, but the cause was not identified. He subsequently underwent a double-balloon endoscopy (DBE). The membranous stenoses were detected in the jejunum, and the biopsy specimens were taken during the DBE. The membranous stenoses in the gastrointestinal tract were characteristic of NSAID-induced enteropathy, and he was endoscopically and histopathologically diagnosed with NSAID-induced small intestinal disorder. NSAID administration was withdrawn, and the balloon dilation was conducted for small intestinal stenosis. After that, no small intestinal ileus developed again. Some studies were conducted on the mechanism of NSAID-induced small intestinal dysfunction, but the drug that was administered to the patient was a highly selective NSAID for cyclooxygenase (COX)-2, and there are few studies that reported a dysfunctional mechanism induced by this drug. In the tissue sampled by DBE, apoptotic bodies were found; therefore, it was suggested that the stenoses in this case were caused by the COX-2 inhibitor from the relationship between COX-2 inhibition and apoptosis. Further studies are necessary to investigate the mechanism of NSAID enteropathy.