宮原 良二

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.).

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).

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.

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.

BACKGROUND AND STUDY AIMS: Endoscopic tissue acquisition techniques using needle-knife and biopsy forceps allow abundant tissue acquisition from upper gastrointestinal subepithelial lesions; however, these techniques cannot capture real-time intratumor information. The aim of this study was to evaluate the feasibility of endoscopic ultrasound-guided forceps biopsy (EUS-FB) from upper gastrointestinal subepithelial lesions using a forward-viewing echoendoscope. PATIENTS AND METHODS: This study was a prospective case series. After mucosal cuts, several specimens were taken using a hot biopsy forceps under real-time EUS visualization. The incision was closed using hemoclips. Diagnostic yield, rate of diagnosable samples obtained under EUS visualization, procedure time, and adverse events were assessed. RESULTS: Ten patients (median lesion size 16 mm, range 15 - 44 mm) underwent EUS-FB. The overall rate of histological diagnosis by EUS-FB was 100 % (10/10). The rate of diagnosable samples among all cases was 97.6 % (41/42). The median procedure times for EUS-FB and complete closure were 28.5 and 4.5 minutes, respectively. No adverse events occurred. CONCLUSIONS: This newly developed EUS-FB is feasible and allowed forceps biopsy from upper gastrointestinal subepithelial lesions. STUDY REGISTRATION: UMIN000015364.

AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus (CMV)-associated colitis in patients with active ulcerative colitis (UC). METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis. RESULTS: Multivariate analysis indicated independent associations with the extent of disease (pancolitis) and use of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC (odds ratio = 12.672, 95%CI: 4.210-38.143). CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.

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.

This paper presents detailed evaluations of a colonoscope tracking method in order to clarify relationships between landmark correspondence parameters used in the method and tracking errors. Based on these evaluations, we implement a colonoscope tracking method whose correspondence finding conditions are adjusted for each position in the colon. An electromagnetic sensor-based colonoscope tracking method has been proposed. This method performs a landmark-based coarse correspondence finding and a length-based fine correspondence finding processes to find the colonoscope tip position. The landmark-based coarse correspondence finding finds corresponding landmark pairs by using distance thresholds. The distance thresholds used in the landmark-based coarse correspondence finding affects tracking errors. However relationships between the landmark-based coarse correspondence finding and tracking errors are not clarified. In this paper, we investigate the relationships between the distance threshold and tracking errors. To evaluate the tracking errors, we measure tracking errors at 52 points in the colon phantom. Based on the measurement results, we change the distance thresholds for each position in the colon phantom. The experimental results showed small distance threshold values caused smaller tracking errors. However, colonoscope tracking using small distance threshold was unstable. Large tracking errors were caused in some colon segments in the colonoscope tracking using small distance threshold.

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.

<p>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. </p>

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.

BACKGROUND: It is unclear which reconstructive route (retrocolic or antecolic) is more effective in preventing postoperative gastroesophageal reflux disease (GERD) in Roux-en-Y reconstruction following distal gastrectomy. METHODS: Eighty-one eligible patients (retrocolic, n = 39; antecolic, n = 42) underwent endoscopies before surgery and 1 year after surgery to evaluate reflux esophagitis according to the Los Angeles classifications. The relative anatomical position of gastrojejunostomy to the cardia was measured by CT imaging. RESULTS: The proportion of patients with reflux esophagitis was also significantly higher in the antecolic group than in the retrocolic group (38.1 vs. 10.3%, p = 0.005). Multivariate analysis revealed that antecolic reconstruction and body mass index (BMI) were independent risk factors for reflux esophagitis. The relative position of gastrojejunostomy to the cardia in the antecolic group was shifted to the left laterally (59.0 vs. 28.8 degree, p < 0.001) and ventrally (65.4 vs. 39.8 degree, p < 0.001) than in the retrocolic group. There was a positive correlation between BMI and left lateral and ventral shifts of gastrojejunostomy in the antecolic group. CONCLUSION: Retrocolic reconstruction may be superior to antecolic reconstruction in preventing postoperative GERD, especially in obese patients. The left lateral and ventral shifts of gastrojejunostomy after antecolic reconstruction may aggravate the occurrence of GERD.

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.

OBJECTIVES: The aim of this study was to investigate the relationship between pancreas and small intestine evaluating the endoscopic and histopathologic findings of the proximal small intestine in pancreatic diseases. METHODS: Fifty patients (18 patients with chronic pancreatitis, 17 patients with pancreatic cancer, 15 control subjects) underwent enteroscopy using a prototype enteroscope. The villous height of the jejunum on bioptic specimens was measured, and the mean values of the villi were compared among the 3 groups. Exocrine function was calculated by the pancreatic function diagnostic test, and the correlation between the recovery rate of p-aminobenzoic acid and the villous height was assessed. Finally, the distribution of the K cells secreting glucose-dependent insulinotropic polypeptide and the L cells secreting glucagon-like peptide 1 in the duodenum and jejunum was investigated using immunohistochemistry for glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1. RESULTS: The mean villous height in chronic pancreatitis (328 ± 67 μm) was significantly lower than that in pancreatic cancer (413 ± 57 μm) and control subjects (461 ± 97 μm) (P = 0.004 and P < 0.0001, respectively). A positive correlation was found between the recovery rate of p-aminobenzoic acid and the villous height (r = 0.52, P = 0.0001). The presence of K and L cells was verified in the duodenum and the jejunum. CONCLUSIONS: Close relationship between pancreas and small intestine was demonstrated.

AIM: To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease (mSES-CD). METHODS: Seventy-six Crohn's disease (CD) patients who underwent transanal double balloon endoscopy (DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new mSES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE, in addition to the activity of four colorectal segments. To compare the usefulness of mSES-CD with SES-CD, we similarly divided the patients into two groups according to total mSES-CD score (low disease activity group, < 4; high disease activity group, ≥ 4). The clinical value of mSES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint. RESULTS: Median age of the 76 CD patients was 36 years (range, 16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm (range, 3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE, of which 62 (83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients (2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high mSES-CD scores showed significantly shorter surgery-free survival than those with low scores (P < 0.05). In contrast, surgery-free survival did not significantly differ between the low and high SES-CD groups (P > 0.05). Multivariate analysis by a Cox proportional hazards model identified mSES-CD as an independent factor for surgery-free survival. CONCLUSION: mSES-CD is useful in evaluating the risk of surgery-free survival in patients with CD.

Cancer remains one of the leading causes of human mortality worldwide. Radiation and chemotherapy are commonly used for cancer treatment; however, the combination of these therapies and surgery do not completely eradicate cancer cells. Near-infrared radiation (NIR) is a low-energy form of radiation that exerts multiple effects on mammalian cells. Previous studies have reported that NIR induces DNA double-strand breaks and apoptosis of cancer cells. In the present study, a 915-nm laser was used to examine the effects of NIR on pancreatic cancer cells. Irradiation of pancreatic cancer cells using a 915-nm laser significantly induced caspase-3 activation and apoptosis. In addition, the combination of gemcitabine treatment and a 915-nm laser synergistically increased the number of apoptotic cells. The results of the present study indicate the use of infrared irradiation and chemotherapy may be a possible therapy for the treatment of cancer.

Double-balloon endoscopy (DBE) has enabled precise diagnosis and endoscopic intervention deep within the small bowel. In this study, we determine the factor related to the risk of endoscopic and clinical recurrences in the diagnosis of postoperative lesions including anastomosis for the patients with Crohn's disease. Forty-eight patients (40 men and 8 women) had undergone small bowel resection previously and anastomotic sites were evaluated by Rutgeerts' endoscopic scoring. The factors related to endoscopic and clinical recurrences at anastomosed sites were investigated. The analyzed items included the disease type, anastomosis procedure, frequency of surgery, time to endoscopy after surgery, the presence or absence of treatment with 5-aminosalicylic acid (5-ASA), immunomodulators, steroids, maintenance administration of infliximab, and an elemental diet that required the ingestion of 900 kcal or more per day. Outcome of the anastomosed lesions was analyzed in the groups treated with and without postoperative anti-TNF alpha antibody including infliximab and adalimumab. DBE was performed 133 times, and 168 anastomosed lesions were observed for enrolled patients. Univariate analysis showed that time to DBE after surgery of 1.5-year or longer and the absence of 5-ASA administration were found to be significant factors leading to both endoscopic and clinical recurrences. The results of Kaplan-Meier estimate and the log rank test demonstrated that the clinical recurrence was avoided more often in the anti-TNF alpha antibody-treated group compared with the non-treated group. In conclusion, DBE was useful for accurate diagnosis of small-bowel lesions after surgery. Anti-TNF alpha antibody may help to decrease the postoperative recurrence rate of Crohn's disease.

BACKGROUND: The role of the forward-viewing echoendoscope compared with the oblique-viewing echoendoscope for EUS-guided FNA (EUS-FNA) of upper GI subepithelial lesions has not been defined. OBJECTIVE: To compare the diagnostic yield and clinical efficacy of EUS-FNA by using the 2 echoendoscopes in the same upper GI subepithelial lesion. DESIGN: Prospective, randomized, crossover study. SETTING: Tertiary-care medical center. PATIENTS: Forty-one patients with an upper GI subepithelial lesion. INTERVENTIONS: All patients first underwent EUS-FNA with a 19-gauge needle by using both echoendoscopes, based on random selection. When required, 22-gauge or 25-gauge needles were used additionally. MAIN OUTCOME MEASUREMENTS: Comparison of diagnostic yield, tissue sample area, puncture success rates, procedure time, and adverse events. RESULTS: Forty-one patients (median lesion size 22 mm, range 15-63 mm) were enrolled. Rates of histologic diagnosis were 80.5% (33/41) and 73.2% (30/41) (P=.453) by using forward-viewing and oblique-viewing echoendoscopes, respectively. Median tissue sample area in GI stromal tumors (n=22) obtained with the forward-viewing echoendoscope was larger than with the oblique-viewing echoendoscope (2.46 mm2 vs 1.00 mm2; P=.046). Puncture success rates were 39 of 41 (95.1%) and 35 of 41 (85.4%; P=.289) with forward-viewing and oblique-viewing echoendoscopes, respectively. Median procedure time was 21 minutes with the forward-viewing echoendoscope and 27 minutes with the oblique-viewing echoendoscope (P=.009). An infectious adverse event occurred in a patient and was treated with antibiotics. LIMITATIONS: Small sample size. CONCLUSION: Diagnostic yield did not differ between the 2 echoendoscopes. However, tissue sample area and procedure time were superior with the forward-viewing echoendoscope.

Double-balloon endoscopy (DBE) has enabled precise diagnosis and endoscopic intervention deep within the small bowel. In this study, we determine the factor related to the risk of endoscopic and clinical recurrences in the diagnosis of postoperative lesions including anastomosis for the patients with Crohn's disease. Forty-eight patients (40 men and 8 women) had undergone small bowel resection previously and anastomotic sites were evaluated by Rutgeerts' endoscopic scoring. The factors related to endoscopic and clinical recurrences at anastomosed sites were investigated. The analyzed items included the disease type, anastomosis procedure, frequency of surgery, time to endoscopy after surgery, the presence or absence of treatment with 5-aminosalicylic acid (5-ASA), immunomodulators, steroids, maintenance administration of infliximab, and an elemental diet that required the ingestion of 900 kcal or more per day. Outcome of the anastomosed lesions was analyzed in the groups treated with and without postoperative anti-TNFα antibody including infliximab and adalimumab. DBE was performed 133 times, and 168 anastomosed lesions were observed for enrolled patients. Univariate analysis showed that time to DBE after surgery of 1.5-year or longer and the absence of 5-ASA administration were found to be significant factors leading to both endoscopic and clinical recurrences. The results of Kaplan-Meier estimate and the log rank test demonstrated that the clinical recurrence was avoided more often in the anti-TNFα antibody-treated group compared with the non-treated group. In conclusion, DBE was useful for accurate diagnosis of small-bowel lesions after surgery. Anti-TNFα antibody may help to decrease the postoperative recurrence rate of Crohn's disease.

BACKGROUND: To assess the diagnostic ability and safety of endoscopic retrograde cholangiopancreatography (ERCP) in in-depth preoperative examination of children patients with pancreaticobiliary maljunction (PBM). METHODS: In 63 patients with a definite diagnosis of PBM, the ability to visualize the bile and main pancreatic ducts was compared between ERCP, which was performed in 63 patients with a definite diagnosis of PBM, and magnetic resonance cholangiopancreatography (MRCP), which was performed before ERCP in 29 patients. For ERCP, its complications were also evaluated. RESULTS: The intrahepatic bile ducts could be visualized using ERCP in 44 patients (69.8%) and using MRCP in 18 (62.1%). The extrahepatic bile ducts could be visualized using ERCP in 59 patients (93.7%) and using MRCP in 29 (100%). The rates of the visualization of the main pancreatic duct and pancreaticobiliary ductal union were significantly higher in using ERCP than in using MRCP (96.8 vs. 41.4% and 90.5 vs. 37.9%, respectively; P<0.0001). As complications, hyperamylasemia developed in 12 patients (19%), but no other severe complications such as pancreatitis were observed. CONCLUSIONS: ERCP as part of an in-depth preoperative examination of children with PBM is useful and safe.

Surveillance colonoscopy (SC) is considered important for the early detection and treatment of colorectal cancer (CRC) in patients with ulcerative colitis (UC). Here, we investigated whether current guidelines are appropriate in preventing UC patients from being diagnosed with CRC at an incurable stage. Among 1583 patients under treatment for UC, 27 patients were diagnosed with CRC. Of these, we excluded two patients who had not undergone colonoscopy before CRC diagnosis. We then divided the remaining patients into three groups based on colonoscopy interval (A, 1 year or less; B, between 1 and 2 years; and C, 2 years or longer). Fifteen patients had tubular adenocarcinomas, and 10 had other types (8 poorly differentiated adenocarcinomas, 1 mucinous adenocarcinoma, 1 endocrine cell carcinoma). Five (20%) of 25 patients developed CRC within 8 years after the onset of UC, of which one case was detected at stage IV. Six patients were classified into group A, 8 into group B, and 11 into group C. On distribution by histologic type, tubular adenocarcinomas were detected in stages 0 - II in 100% in group A, 100% in group B, and 57.1% in group C. In contrast, other types of carcinomas were detected in stage 0 - II in 100% in group A, 40% in group B, and 0% in group C. Current guideline recommendations for SC are not sufficient for the detection of early stage CRC in patients with UC. SC should be commenced earlier than recommended in the current guidelines and repeated annually.

Surveillance colonoscopy (SC) is considered important for the early detection and treatment of colorectal cancer (CRC) in patients with ulcerative colitis (UC). Here, we investigated whether current guidelines are appropriate in preventing UC patients from being diagnosed with CRC at an incurable stage. Among 1583 patients under treatment for UC, 27 patients were diagnosed with CRC. Of these, we excluded two patients who had not undergone colonoscopy before CRC diagnosis. We then divided the remaining patients into three groups based on colonoscopy interval (A, 1 year or less; B, between 1 and 2 years; and C, 2 years or longer). Fifteen patients had tubular adenocarcinomas, and 10 had other types (8 poorly differentiated adenocarcinomas, 1 mucinous adenocarcinoma, 1 endocrine cell carcinoma). Five (20%) of 25 patients developed CRC within 8 years after the onset of UC, of which one case was detected at stage IV. Six patients were classified into group A, 8 into group B, and 11 into group C. On distribution by histologic type, tubular adenocarcinomas were detected in stages 0 - II in 100% in group A, 100% in group B, and 57.1% in group C. In contrast, other types of carcinomas were detected in stage 0 - II in 100% in group A, 40% in group B, and 0% in group C. Current guideline recommendations for SC are not sufficient for the detection of early stage CRC in patients with UC. SC should be commenced earlier than recommended in the current guidelines and repeated annually.

AIM: To evaluate long-term prognosis following cyclosporine treatment by examining the rate of surgery avoidance among cyclosporine responders. METHODS: We retrospectively reviewed clinical records for 29 patients diagnosed with severe steroid-refractory ulcerative colitis in our hospital from August 1997 to August 2008 and treated with cyclosporine by continuous intravenous infusion. All patients were treated with intravenous corticosteroids for more than 5 d prior to cyclosporine therapy. Administration was continued for up to 21 d under serum monitoring to maintain cyclosporine levels between 400 and 600 ng/mL. Clinical activity was assessed before and after cyclosporine therapy using the clinical activity index score, with a reduction of ≥ 5 considered to indicate a response. Among responders, we defined cases not requiring surgery for more than 5 years as exhibiting long-term efficacy of cyclosporine. Factors considered to be possibly predictive of long-term efficacy of cyclosporine were sex, age, disease duration, clinical activity index score, C-reactive protein level, hemoglobin level, disease extent, endoscopic findings, and clinical course. RESULTS: Cyclosporine was not discontinued due to side effects in any patient. Nineteen (65.5%) of 29 patients were considered responders. A statistically significant (P = 0.004) inverse association was observed between an endoscopic finding of "mucosal bleeding" and responsive cases. Fifteen (9 males, 6 females) of these 19 patients were followed for 5 years or more, of whom 9 (60%) exhibited long-term efficacy of cyclosporine. Of the 10 non-responders, 9 (90%) underwent surgery within 6 mo of cyclosporine therapy. None of the following factors had a significant impact on the long-term efficacy of cyclosporine: sex, age, duration of disease, clinical activity index score, C-reactive protein level, hemoglobin level, extent of disease, endoscopic findings, or clinical course. In contrast, a significant association was observed for maintenance therapy with azathioprine after cyclosporine therapy (P = 0.0014). CONCLUSION: Maintenance therapy with azathioprine might improve the long-term efficacy of continuously infused cyclosporine for severe steroid-refractory ulcerative colitis patients.

CT colonography (CTC) is performed for polyp diagnosis. If a polyp is found during CTC, optical colonoscopy is performed. It is expected to develop a navigation system that navigates the optical colonoscope to the place of polyp found by CTC. To achieve such system, we present a method that registers the colonoscope shape and the colon shape for estimating the colonoscope tip location in the CT coordinates. The colonoscope shape is obtained by an electromagnetic tracking device. Both shapes are represented as curve lines and registration is performed by an ICP-based method. Phantom-based experiments revealed good tracking performance enough for assisting colonoscopic examination.

BACKGROUND AND AIM: The Agile patency capsule (PC; Given Imaging Ltd, Yoqneam, Israel) is used as a dummy prior to capsule endoscopy (CE) to avoid retention of the CE capsule. However, impaction of the PC's inner radio frequency identification (RFID) tag in a stricture could cause small-bowel ileus. Recently, the RFID tag-less PC was introduced into clinical practice. Herein, we aimed to retrospectively evaluate the usefulness of the tag-less PC. METHODS: Of 154 patients who were scheduled to undergo CE, 100 consecutive patients (65%) who underwent PC evaluation were enrolled in the present study. Primary study end point was the retention rate of the CE capsule after successful passage of the PC. Secondary end point was analysis of the significant factors affecting the passage of the PC. RESULTS: In total, 87 patients (87%) had bowel patency confirmed by PC evaluation. There was no capsule retention in any of these 87 patients during CE. Abnormal findings were obtained from 60 CE, and 41 patients received new or modified treatment. Multivariate analysis of factors related to the confirmation of patency demonstrated that stenosis on imaging was the most influential factor (P = 0.002, odds ratio 16.387). The results confirmed that passage of the PC depends on stenosis on imaging. CONCLUSIONS: Use of the tag-less PC confirmed gastrointestinal tract patency for most of the patients who did not have stenosis on imaging and allowed estimation of the patency for patients who did have stenosis on imaging.

The striatin family of proteins, comprising STRN, STRN3 and STRN4, are multidomain-containing proteins that associate with additional proteins to form a large protein complex. We previously reported that STRN4 directly associated with protein kinases, such as MINK1, TNIK and MAP4K4, which are associated with tumor suppression or tumor progression. However, it remains unclear whether STRN4 is associated with tumor progression. In this report, we examined the role that STRN4 plays in cancer malignancy. We show that depletion of STRN4 suppresses proliferation, migration, invasion and the anchorage-independent growth of cancer cells. In addition, STRN4 knockdown increases the sensitivity of pancreatic cancer cells to gemcitabine. Finally, we show that STRN4 knockdown suppresses the proliferation and metastasis of cancer cells in mice. Our results demonstrate a possible role of STRN4 in tumor progression.

BACKGROUND AND AIM: Secondary stomach cancer in lesions of the remnant stomach occurs relatively soon after distal gastrectomy using the Billroth I reconstruction procedure. Prophylactic eradication of Helicobacter pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma. However, the effect of H. pylori eradication on the gastric remnant has not been clearly determined. METHODS: Eight patients who were H. pylori-positive after distal gastrectomy for primary gastric cancer underwent eradication therapy and were followed by endoscopy for 9 years. Upper gastroenteroscopy series were done before and at 1, 3, 5, 7 and 9 years after eradication, and biopsy specimens were taken from the lesser and greater curvatures, respectively. Histological changes, including chronic inflammation, activity, atrophy, and intestinal metaplasia, were evaluated using the updated Sydney system. RESULTS: Successful eradication was confirmed using the urea breath test in all eight patients. Chronic inflammation scores were improved after eradication at both the lesser (mean scores ± SD: before eradication, 2.9±0.5; 1 year after, 2.3±0.4; 3 years, 1.8±0.3; 5 years, 1.5±0.3; 7 years, 1.3±0.3; and 9 years, 1.0±0.3) and greater curvatures (before, 2.9±0.4; 1 year after, 1.9±0.3; 3 years, 1.4±0.4; 5 years, 1.3±0.3; 7 years, 1.1±0.2; and 9 years, 0.6±0.3). Atrophy scores improved more quickly after eradication than chronic inflammation scores at both the lesser (before, 2.4±0.5; 1 year after, 1.8±0.4; 3 years, 0.8±0.3; 5 years, 0.3±0.1; 7 years, 0.0; and 9 years, 0.0) and greater curvatures (before, 2.2±0.4; 1 year after, 1.3±0.3; 3 years, 0.5±0.3; 5 years, 0.0; 7 years, 0.0; and 9 years, 0.0). No secondary stomach cancers were found on endoscopy. CONCLUSIONS: Undergoing H. pylori eradication improved possible precancerous lesions of the gastric remnant among patients who had undergone distal gastrectomy. Prophylactic H. pylori eradication in the gastric remnant may be useful in preventing the development of metachronous gastric carcinoma.

Malignant ascites due to peritoneal metastasis is one of the major problems caused by advanced gastrointestinal cancer. Although drainage of a large amount of ascitic fluid improves symptoms such as abdominal fullness, it may lead to protein loss and renal dysfunction. Cell-free and concentrated ascites reinfusion therapy (CART) may help avoid such complications due to paracentesis. The purpose of this study was to evaluate the safety of CART. We performed a total of 51 sessions of CART in 5 patients, 4 of whom had gastric cancer and 1 appendiceal cancer. We retrospectively evaluated laboratory data immediately prior to CART, on the following day, 1 week later and 2 weeks later. We also measured the amount of total protein and albumin in collected and concentrated ascites. The mean amount of collected ascites was 4,007 ml. All the patients exhibited improvement of symptoms such as abdominal fullness. Four patients developed fever (>38°C) immediately after reinfusion of the concentrated ascites and 3 of these patients required corticosteroid administration. The mean total protein and albumin in the collected ascites were 122 and 64 g, respectively, and those in the concentrated ascites 75 and 39 g, respectively. The serum levels of total protein, albumin and creatinine after CART were almost identical to those prior to CART. Blood hemoglobin concentration was significantly decreased 1 day after CART and returned to baseline levels in 1-2 weeks. CART does not cause renal dysfunction and does not decrease serum albumin; therefore, repeated CART is safe and may be used to improve the symptoms of malignant ascites from gastrointestinal cancer.

BACKGROUND: Magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD) was developed to reduce adverse events such as bleeding and perforation and to facilitate ESD. However, the external electromagnet required miniaturization to make it suitable for daily clinical practice. OBJECTIVE: To evaluate the feasibility of simplified MAG-ESD using permanent magnets. DESIGN: Case series. SETTING: Nagoya University Hospital. SUBJECTS: Beagle dogs. INTERVENTIONS: The simplified MAG-ESD was performed on 10 representative areas of the stomachs of beagle dogs. The magnetic anchor consisted of an internal magnet attached to a hemoclip. The external and internal magnets were made from the rare earth neodymium. MAIN OUTCOME MEASUREMENTS: The feasibility of countertraction with good visualization using simplified MAG-ESD. The rate of perforation, the time required for preparation, and attaching the magnetic anchor were also evaluated. RESULTS: All lesions were successfully resected without perforation. The magnetic anchor could be controlled easily, and direct visualization was maintained by adequate counter traction. Preparing the magnetic anchor and grasping the mucosal edge using the hemoclip was easy and required a median of only 4 minutes (range, 2-7 minutes). LIMITATIONS: Animal experiment, low number and lesion size. CONCLUSIONS: This simplified MAG-ESD is feasible and allowed excellent visualization in the dog stomach. The feasibility of this system should be assessed in humans.

A 75-year-old woman was diagnosed with esophageal cancer with difficulty in swallowing. She had a past history of rheumatoid arthritis, scleroderma, interstitial pneumonia, angina pectoris (with coronary artery bypass surgery) and arrhythmia (with pacemaker implantation). She refused surgery, and chemotherapy and radiotherapy were not performed because of the high risk accompanied with multiple comorbidities. She received proton therapy at another hospital and the primary lesion shrank. Bone metastasis in the thoracic vertebrae was diagnosed 10 months after diagnosis of esophageal cancer. Non-steroidal anti-inflammatory drugs and zoledronic acid were administered for back pain. Oxycodone was also administered but discontinued due to nausea. After strontium-89 ((89)Sr) chloride administration, her back pain was relieved. (89)Sr was administered five times every 3 months, and the pain did not worsen until her death due to pneumonia 2 years after diagnosis of esophageal cancer. (89)Sr was effective for pain from bone metastasis of esophageal cancer, and its repeated administration was safe.

Endoscopic exploration of the small bowel after pelvic radiation has limitations related to strong abdominal adhesion. It is often difficult to demonstrate the findings of radiation enteritis endoscopically, even with video capsule endoscopy (VCE) or double-balloon enteroscopy (DBE). We present our experience with three cases of radiation enteritis that were diagnosed using VCE and DBE, including their effective aspects. Radiation enteritis has not been diagnosed using conventional methods, and DBE may not accomplish deeper insertion into the ileum, although it is capable of both diagnosis and hemostasis. Therefore, VCE is thought to be the initial tool for the diagnosis of radiation enteritis when small bowel stenosis has not been previously detected and the risk of retention has been discussed.

BACKGROUND AND AIM: Transabdominal ultrasonography (US) is commonly used for the initial screening of bilio-pancreatic diseases in Asian countries due to its widespread availability, the non-invasiveness and the cost-effectiveness. However, it is considered that US has limits to observe the area, namely the blind area. The observation of the pancreatic tail is particularly difficult. The goal of this study was to examine the pancreatic tail region that cannot be visualized on transverse scanning of the upper abdomen using US with spatial positional information and factors related to visualization, and observation of the tail from the splenic hilum. METHODS: Thirty-nine patients with pancreatic/biliary tract disease underwent CT and US with GPS-like technology and fusion imaging for measurement of the real pancreatic length and the predicted/real unobservable (PU and RU) length of the pancreatic tail. RU from US on transverse scanning and the real pancreatic length were used to determine the unobservable area (UA: RU/the real pancreatic length). Relationships of RU with physical and hematological variables that might influence visualization of the pancreatic tail were investigated. RESULTS: The real pancreatic length was 160.9 ± 16.4mm, RU was 41.0 ± 17.8mm, and UA was 25.3 ± 10.4%. RU was correlated with BMI (R=0.446, P=0.004) and waist circumferences (R=0.354, P=0.027), and strongly correlated with PU (R=0.788, P<0.001). The pancreatic tail was visible from the splenic hilum in 22 (56%) subjects and was completely identified in 13 (33%) subjects. CONCLUSIONS: Combined GPS-like technology with fusion imaging was useful for the objective estimation of the pancreatic blind area.

Endoscopic exploration of the small bowel after pelvic radiation has limitations related to strong abdominal adhesion. It is often difficult to demonstrate the findings of radiation enteritis endoscopically, even with video capsule endoscopy (VCE) or double-balloon enteroscopy (DBE). We present our experience with three cases of radiation enteritis that were diagnosed using VCE and DBE, including their effective aspects. Radiation enteritis has not been diagnosed using conventional methods, and DBE may not accomplish deeper insertion into the ileum, although it is capable of both diagnosis and hemostasis. Therefore, VCE is thought to be the initial tool for the diagnosis of radiation enteritis when small bowel stenosis has not been previously detected and the risk of retention has been discussed.

BACKGROUND: An accurate diagnosis of pancreatic fibrosis is clinically important and may have potential for staging chronic pancreatitis. The aim of this study was to diagnose the grade of pancreatic fibrosis through a quantitative analysis of endoscopic ultrasound elastography (EUS-EG). METHODS: From September 2004 to October 2010, 58 consecutive patients examined by EUS-EG for both pancreatic tumors and their upstream pancreas before pancreatectomy were enrolled. Preoperative EUS-EG images in the upstream pancreas were statistically quantified, and the results were retrospectively compared with postoperative histological fibrosis in the same area. For the quantification of EUS-EG images, 4 parameters (mean, standard deviation, skewness, and kurtosis) were calculated using novel software. Histological fibrosis was graded into 4 categories (normal, mild fibrosis, marked fibrosis, and severe fibrosis) according to a previously reported scoring system. RESULTS: The fibrosis grade in the upstream pancreas was normal in 24 patients, mild fibrosis in 19, marked fibrosis in 6, and severe fibrosis in 9. Fibrosis grade was significantly correlated with all 4 quantification parameters (mean r = -0.75, standard deviation r = -0.54, skewness r = 0.69, kurtosis r = 0.67). According to the receiver operating characteristic analysis, the mean was the most useful parameter for diagnosing pancreatic fibrosis. Using the mean, the area under the ROC curves for the diagnosis of mild or higher-grade fibrosis, marked or higher-grade fibrosis and severe fibrosis were 0.90, 0.90, and 0.90, respectively. CONCLUSIONS: An accurate diagnosis of pancreatic fibrosis may be possible by analyzing EUS-EG images.

The mechanisms of drug resistance in cancer are not fully elucidated. To study the drug resistance of gastric cancer, we analyzed gene expression and DNA methylation profiles of 5-fluorouracil (5-FU)- and cisplatin (CDDP)-resistant gastric cancer cells and biopsy specimens. Drug-resistant gastric cancer cells were established with culture for >10 months in a medium containing 5-FU or CDDP. Endoscopic biopsy specimens were obtained from gastric cancer patients who underwent chemotherapy with oral fluoropyrimidine S-1 and CDDP. Gene expression and DNA methylation analyses were performed using microarray, and validated using real-time PCR and pyrosequencing, respectively. Out of 17,933 genes, 541 genes commonly increased and 569 genes decreased in both 5-FU- and CDDP-resistant AGS cells. Genes with expression changed by drugs were related to GO term 'extracellular region' and 'p53 signaling pathway' in both 5-FU- and CDDP-treated cells. Expression of 15 genes including KLK13 increased and 12 genes including ETV7 decreased, in both drug-resistant cells and biopsy specimens of two patients after chemotherapy. Out of 10,365 genes evaluated with both expression microarray and methylation microarray, 74 genes were hypermethylated and downregulated, or hypomethylated and upregulated in either 5-FU-resistant or CDDP-resistant cells. Of these genes, expression of 21 genes including FSCN1, CPT1C and NOTCH3, increased from treatment with a demethylating agent. There are alterations of gene expression and DNA methylation in drug-resistant gastric cancer; they may be related to mechanisms of drug resistance and may be useful as biomarkers of gastric cancer drug sensitivity.

This paper presents a new colonoscope navigation system. CT colonography is utilized for colon diagnosis based on CT images. If polyps are found while CT colonography, colonoscopic polypectomy can be performed to remove them. While performing a colonoscopic examination, a physician controls colonoscope based on his/her experience. Inexperienced physicians may occur complications such as colon perforation while colonoscopic examinations. To reduce complications, a navigation system of colonoscope while performing the colonoscopic examinations is necessary. We propose a colonoscope navigation system. This system has a new colonoscope tracking method. This method obtains a colon centerline from a CT volume of a patient. A curved line (colonoscope line) representing the shape of colonoscope inserted to the colon is obtained by using electromagnetic sensors. A coordinate system registration process that employs the ICP algorithm is performed to register the CT and sensor coordinate systems. The colon centerline and colonoscope line are registered by using a line registration method. The position of the colonoscope tip in the colon is obtained from the line registration result. Our colonoscope navigation system displays virtual colonoscopic views generated from the CT volumes. A viewpoint of the virtual colonoscopic view is a point on the centerline that corresponds to the colonoscope tip. Experimental results using a colon phantom showed that the proposed colonoscope tracking method can track the colonoscope tip with small tracking errors. © 2014 SPIE.

OBJECTIVE. Inflammatory bowel disease (IBD) is a chronic debilitating disease associated with severe damage to the intestinal mucosa. Glucagon-like peptide-2 (GLP-2) is a potent and specific gastrointestinal growth factor. GLP-2 released from enteroendocrine cells is inactivated by dipeptidyl peptidase-4 (DPP-4). The aim of this study was to examine whether the DPP-4 inhibitor anagliptin improves experimental murine colitis. MATERIAL AND METHODS. Male C57BL/6 mice aged 8 weeks were exposed to 1.5% dextran sulfate sodium (DSS) in drinking water for 7 days to induce experimental colitis. Anagliptin (0.1% in diet) was administrated from 2 days before the beginning of DSS to 7 days after the end of DSS. Changes in body weight and disease activity index were evaluated daily. Histological colitis severity, cellular proliferation and gene expression were determined in colonic tissues. RESULTS. Treatment with anagliptin clearly improved body weight loss and disease activity index in the recovery phase. Histological score in the DSS + anagliptin group at day 14 was significantly lower than that in the DSS alone group. Treatment with anagliptin increased the Ki67-positive rate at days 10 and 14, and tended to increase insulin-like growth factor-1 mRNA expression in the DSS + anagliptin group. CONCLUSION. In this model of experimental colitis, the DPP-4 inhibitor anagliptin facilitated the restoration of mucosal damage, thereby resulting in the acceleration of healing. These findings suggest a new and novel therapeutic approach for the treatment of IBD.