大宮 直木

Previous studies have demonstrated the protective role of inducible heat-shock protein (HSP) 70 in intestinal cells. The HSP70-2 gene has a PstI site due to an A-G transition at the 1,267 position and different genotypes are associated with various levels of mRNA expression. The present study aimed to clarify the effect of the HSP70-2 polymorphism on the risk of ulcerative colitis (UC), including its clinical phenotypes. A total of 121 patients with UC and 500 healthy control (HC) subjects participated in the study. To assess the polymorphisms at the 1,267 position of the HSP70-2 gene, restriction fragment length polymorphism analysis was performed. The subjects in the study were classified by disease behavior, severity and extent of disease. Although no significant difference of the HSP70-2 genotype distribution was identified between the HC and UC groups, the BB genotype exhibited a lower risk of the steroid-dependent phenotype [odds ratio (OR), 0.12; 95% confidence interval (CI), 0.02-0.95; P=0.02]. The same genotype was also associated with a lower risk of the refractory phenotype (OR, 0.16; 95% CI, 0.04-0.73; P=0.01). There was no direct correlation between the polymorphism of the HSP70-2 gene and UC susceptibility. However, there was an association between a reduced risk of the steroid-dependent and refractory phenotypes of UC and the BB genotype.

A complex interaction of genetic and environmental factors is closely associated with the development of inflammatory bowel disease. Previous studies reported that the expression of the regulated upon activation, normal T-cell expressed and secreted (RANTES) gene is enhanced in the colonic mucosa of ulcerative colitis (UC). Quantitative differences in RANTES gene expression among numerous promoter genotypes have also been reported. The aim of the present study was to clarify the effect of RANTES promoter polymorphism on the risk of UC, including its clinical phenotypes. A total of 150 UC patients and 372 healthy control (HC) subjects participated in the study. The UC patients were classified by disease behavior, severity and extent of disease. Restriction fragment length polymorphism analysis was performed for polymorphisms at -28 C/G in the RANTES gene promoter region. Although no significant difference of the RANTES promoter genotype distribution was observed between the HC and UC groups, the G/G genotype was significantly higher among female (OR=3.95, 95% CI=1.22-12.82, P=0.03), non-steroid dependent (OR=3.37, 95% CI=1.16-9.85, P=0.03) and non-refractory (OR=3.76, 95% CI=1.29-10.98, P=0.02) UC patients. The G carrier was also found to be associated with an increased risk of rectal colitis (OR=2.21, 95% CI=1.12-4.39, P=0.03). The data indicate that the polymorphism of the RANTES promoter is not directly associated with the susceptibility to UC, but the -28 G allele is associated with female UC patients and mild clinical phenotypes of UC, including non-steroid dependency, non-refractory and rectal colitis.

UNLABELLED: Autophagy can degrade aggregate-prone proteins, but excessive autophagy can have adverse effects. It would be beneficial if autophagy could be enhanced in a cell type-specific manner, but this has been difficult because the basic mechanism of autophagy is common. In the present study we found that inhibition of Niemann-Pick-type C1-like 1 (NPC1L1) by ezetimibe activates autophagy only in hepatocytes and small intestinal epithelia, but not in other cells. Ezetimibe induced accumulation of free cholesterol in the late endosome/lysosome and increased partitioning of a Ragulator component, LAMTOR1, in rafts. The latter change led to down-regulation of mammalian target of rapamycin (mTOR)C1 activity by decreasing mTOR recruitment to the late endosome/lysosome and activated autophagy. A primary effect of ezetimibe was found to be a decrease of free cholesterol in the plasma membrane, because all the results caused by ezetimibe were suppressed by supplementation of cholesterol as a methyl-β-cyclodextrin complex. By enhancing autophagy in human primary hepatocytes with ezetimibe, insoluble mutant α1-antitrypsin Z was reduced significantly. CONCLUSION: Inhibition of NPC1L1 by ezetimibe activates autophagy in human hepatocytes by modulating cholesterol homeostasis. Ezetimibe may be used to ameliorate liver degeneration in α1-antitrypsin deficiency.

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.

Small bowel tumors (SBTs) are uncommon, insidious in presentation, and frequently represent a diagnostic challenge. The advent of video capsule endoscopy (VCE) and double-balloon endoscopy (DBE) is a significant breakthrough for visual diagnosis of SBTs throughout the small bowel. Contrast-enhanced computed tomography (CECT) and fluoroscopic enteroclysis had significantly lower diagnostic yields of tumors that were 10 mm or smaller in diameter, but VCE and DBE had high diagnostic yields regardless of tumor size. Regarding SBTs larger than 10 mm in diameter, CECT had a significantly lower diagnostic yield of epithelial tumors compared to subepithelial tumors, whereas fluoroscopic enteroclysis and DBE had high diagnostic yields regardless of the tumor type. VCE had a slightly lower diagnostic yield of subepithelial tumors (78%) compared to epithelial tumors. Therefore, a combined examination method by using CECT and VCE is useful for screening of SBTs. In case suspicious of stenosis, patency capsule should be performed to confirm passage before VCE. DBE is useful for further precise examination including biopsy and ultrasonography by using miniature probe, and enteroscopic treatment. After medical, enteroscopic, and surgical treatment, VCE is helpful for follow-up. DBE is safe and useful in resecting the SBTs deep within the small bowel without laparotomy. Indications of enteroscopic resection may be benign tumors regardless of epithelial or subepithelial type, localizing in the mucosal or submucosal layer, which are symptomatic at present or possibly symptomatic or transforming in the future. Malignant tumors localized in the mucosal layer may be indications although detecting at an early stage is challenging. In this review article, we describe management of SBTs/polyps by various modalities.

Background The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised. Aim To determine the risk factors of symptomatic NSAID-induced small intestinal injuries, including diaphragm disease. Methods Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double-balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2,*3 and*13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5'-nuclease assays. Results Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID-induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID-induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05-8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04-24.40, P = 0.002, respectively). The combination of aspirin and non-aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2,*3 and*13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34-1582.38 P &lt 0.0001 and adjusted OR: 12.94, 95% CI: 1.55-108.36, P = 0.018, respectively). Conclusion The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease. © 2014 John Wiley &amp Sons Ltd.

The patient was admitted to hospital with principal complaints of abdominal pain, diarrhea, and weight loss.

BACKGROUND AND AIM: Until the approval of patency capsule, capsule endoscopy (CE) has not been routinely applied for the diagnosis of Crohn's disease (CD) in Japan. We aimed to survey current situation of CE use for patients with CD in Japan. METHODS: The nationwide survey of 40 Japanese institutions identified 94 patients with established CD (eCD) and 80 patients with suspected CD (sCD), who were examined by CE. Types and positive rates of mucosal injury under CE and capsule retention rate were investigated. In sCD, final diagnosis after CE was also analyzed. RESULTS: Patients with eCD comprised 82 patients of ileitis or ileocolitis type, while 12 patients had CD of colitis type. CE identified mucosal injuries in 83 of 94 patients. Eight of 12 patients with eCD of colitis type had ileal lesions under CE, thereby being reclassified as ileocolitis type. In patients with sCD, CE detected mucosal injuries in 58 patients. Linear ulceration and cobblestone appearance were depicted in 22 and 3 patients, respectively, thereby resulting in established diagnosis of CD in 23 patients. Mucosal lesion was not found in 22 patients with sCD, who were diagnosed as not having CD. Capsule retention rate was not statistically different between patients with eCD and those with sCD (7.4% vs 6.3%, P = 1.0). CONCLUSIONS: CE is useful for the evaluation of small bowel mucosal injuries in Japanese patients with sCD and eCD. Possible intestinal stricture needs to be carefully evaluated before CE even in patients with sCD.

BACKGROUND: The neurochemical serotonin (5-HT) is an important signaling molecule in the gastrointestinal motor and sensory functions. A key regulator of 5-HT levels is the transmembrane serotonin transporter (5-HTT; SLC6A4) that governs the reuptake of 5-HT. Recent studies have indicated 5-HTT expression may be regulated by epigenetic mechanisms. We investigated DNA methylation status of SLC6A4 gene in the gastric mucosa from functional dyspepsia (FD) because of their potential role in dyspeptic symptoms. METHODS: Endoscopic gastric biopsies were obtained from 78 subjects with no upper abdominal symptoms and 79 patients with FD. Bisulfite Pyrosequencing was carried out to determine the methylation status of promoter CpG islands (PCGIs), promoter non-CpG islands (PNCGIs) and gene body non-CpG islands (NPNCGIs) in the SLC6A4 gene. Gene expression was examined by real-time PCR. RESULTS: In overall, methylation level of PCGIs was significantly lower in FD compared to control subjects (p = 0.04). On the other hand, methylation level of NPNCGIs was significantly higher in FD compared to control subjects (p = 0.03). Lower methylation level in PNCGIs was highlighted in the patients with PDS (p = 0.01), while higher methylation level in NPNCGIs was more prominent in the patients with EPS (p = 0.017). Methylation levels of PCGIs and PNCGIs were inversely correlated, while methylation levels of NPNCGIs was positively correlated with SLC6A4 mRNA levels in FD patients. CONCLUSIONS: Our data suggest that change in DNA methylation pattern of SLC6A4 in the gastric mucosa may have a role for developing FD. A role of epigenetics for developing FD needs to be further evaluated.

BACKGROUND/AIMS: We classified intestinal lymphangiectasia (IL) into two categories, the white and non-white villi types, and evaluated their clinical characteristics and therapeutic responses. METHODS: Of the 988 patients who underwent double-balloon enteroscopy, 14 consecutive patients (7 men and 7 women, median age at onset 34 years) were enrolled with immunohistochemically confirmed IL with protein-losing enteropathy. RESULTS: Enteroscopically the white villi type (n = 8) showed white plaques and white-tipped villi were scattered in the small bowel, while non-white villi type (n = 6) showed that apparently normal but under more detailed observation, low and round villi with a normal color were diffused. The serum albumin levels and fecal α1-antitrypsin clearance before treatment were significantly worse in the non-white villi type (p = 0.017 and 0.039, respectively), whereas the serum immunoglobulin A and M levels were significantly lower in the white villi type (p = 0.010 and 0.046, respectively). At gastroscopy, a non-cirrhotic snakeskin appearance was significantly observed in the non-white villi type (p = 0.015). The corticosteroid response was better in the non-white villi type (p = 0.015). CONCLUSION: Two distinct subgroups were found in IL. This classification was useful in pathophysiological clustering and in predicting the therapeutic response.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a phenomenon that allows the conversion of adherent epithelial cells to a mesenchymal cell phenotype, which enhances migratory capacity and invasiveness. Recent studies have suggested that EMT contributes to the pathogenesis of ulcerative colitis (UC). We investigated the promoter DNA methylation status of EMT-related genes in the colonic mucosa in UC. METHODS: Colonic biopsies were obtained from the rectal inflammatory mucosa of 86 UC patients and the non-inflammatory proximal colonic mucosa of 10 paired patients. Bisulfite pyrosequencing was used to quantify the methylation of 5 candidate CpG island promoters (NEUROG1, CDX1, miR-1247, CDH1, and CDH13) and LINE1. RESULTS: Using an unsupervised hierarchical clustering analysis, inflamed rectal mucosa was well separated from mucosa that appeared normal. The CDH1 and CDH13 promoters were significantly associated with patient age (p = 0.04, 0.03, respectively). A similar trend was found between those genes and the duration of disease (CDH1: p = 0.07, CDH13: p = 0.0002, mean of both: p<0.00001). Several positive associations were found between hypermethylation and severe clinical phenotypes (CDX1 and miR-1247 and a refractory phenotype: p = 0.04 and 0.006, respectively. miR-1247 and CDH1 hyper methylation and a more severe Mayo endoscopic subscore: miR-1247: p = 0.0008, CDH1: p = 0.03, mean of both: p = 0.003). When the severe clinical phenotype was defined as having any of five phenotypes (hospitalized more than twice, highest Mayo endoscopic subscore, steroid dependence, refractory, or a history of surgery) miR-1247 hypermethylation was associated with the same phenotype (p = 0.008). CONCLUSIONS: Our data suggest that variability in the methylation status of EMT-related genes is associated with more severe clinical phenotypes in UC.

OBJECTIVE: This Phase II trial was designed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy in patients with poor-risk rectal cancer. METHODS: Patients with magnetic resonance imaging-defined poor-risk rectal cancer received neoadjuvant oxaliplatin and capecitabine and bevacizumab followed by total mesorectal excision or more extensive surgery. RESULTS: Between February 2010 and December 2011, 32 patients were enrolled in this study. The completion rate of the scheduled chemotherapy was 91%. Reasons for withdrawal were refusal to continue therapy in two patients and disease progression in one, with two of these three patients not undergoing surgery. Among the 29 patients who completed the scheduled chemotherapy, one refused surgery within 8 weeks after the completion of chemotherapy, which was the period stipulated by the protocol, and another had rectal perforation, requiring urgent laparotomy. As a result, the completion rate of this experimental treatment was 84%. Of the 30 patients who underwent surgery, the R0 resection rate was 90% and a postoperative complication occurred in 43%. A pathological complete response was observed in 13% and good tumor regression was exhibited in 37%. CONCLUSIONS: Neoadjuvant oxaliplatin and capecitabine plus bevacizumab for poor-risk rectal cancer caused a high rate of anastomotic leakage and experienced a case with perforation during chemotherapy, both of which were bevacizumab-related toxicity. Although the short-term results with the completion rate of 84.4% and the pathological complete response rate of 13.3% were satisfactory, we have to reconsider the necessity of bevacizumab in neoadjuvant chemotherapy (UMIN number, 000003507).

The clinical introduction of double-balloon endoscopy (DBE) has brought about a revolution in the diagnosis and the treatment of diseases of the small intestine. DBE allows not only direct observation of the entire small intestine, but also interventional therapies, tissue sampling and India ink marking (tattooing). Single incision laparoscopic surgery (SILS) was developed from conventional laparoscopic surgery to further reduce the degree of invasiveness. SILS requires only one umbilical incision, thus resulting in almost scarless surgery. This report presents three cases of small intestinal bleeding successfully treated by SILS following tattooing under DBE. The average operative time was 67 min and average blood loss was 5 ml. All patients immediately recovered without any complications. SILS, in conjunction with presurgical tattooing by DBE for small intestinal bleeding is considered to be an ideal approach in terms of minimal surgical trauma and aesthetics.

OBJECTIVE: Acute low-tone sensorineural hearing loss (ALHL) has been reported to be associated with endolymphatic hydrops (EHs). However, evaluation of the size of the endolymphatic space has not been reported. We attempted to visualize EH in ALHL using magnetic resonance imaging (MRI). STUDY DESIGN: Prospective diagnostic study. SETTING: University hospital. METHODS: We evaluated 25 ears of 25 unilateral ALHL patients. Three-tesla MRI was obtained 24 hours after intratympanic injection of gadolinium (Gd) (n = 5) or 4 hours after intravenous injection of Gd (n = 20). A radiologist blinded to the patients' clinical data classified the degree of EH in the vestibule and cochlea into 3 groups: none, mild, and significant. RESULTS: On the affected sides, cochlear EH was recognized in 23 ears (92%) and was classified as significant EH (n = 15) or mild EH (n = 8); vestibular EH was detected in 22 ears (88%), classified as significant EH (n = 16) or mild EH (n = 6). Cochlear EH was more frequently observed in the affected ear than in the contralateral ear (90% versus 40%, p < 0.05). CONCLUSION: In ALHL, EH was observed not only in the cochlea but also in the vestibule as in Ménière's disease.

Hepatic portal venous gas is a rare condition that occurs when intraluminal gas or gas produced by intestinal bacteria enters the portal venous circulation. It has recently been recognized as a rare complication of colon procedures by endoscopy or barium enema. Given the frequency of these procedures in patients with inflammatory bowel disease, hepatic portal venous gas may occur more frequently in these patients than previously reported. Here, we report a woman with Crohn's disease who developed hepatic portal venous gas following colonoscopy who was treated with conservative therapy.

BACKGROUND/AIMS: To confirm the feasibility of using newly developed endoscopic ultrasound (EUS) with Zone sonography™ technology (ZST; Fujifilm Corp.). METHODS: Seventy-five patients with pancreatic disorders were enrolled: 45 with intraductal papillary mucinous neoplasm; 15 with ductal carcinoma; five with neuroendocrine tumors; three with serous cystic neoplasms; and seven with simple cysts. The endoscopes used were EG-530UR2 and EG-530UT2 (Fujifilm Corp.). Two items were evaluated: visualization depth among four frequencies and image quality after automatic adjustment of sound speed (AASS), assessed using a 5-scale Likert scale by two endosonographers blinded to disease status. Because sound speed could be manually controlled, besides AASS, image quality at sound speeds of 1,440 and 1,600 m/sec were also assessed. RESULTS: In all cases, sufficient images were obtained in the range of 3 cm from the EUS probe. Judgments of image quality before AASS were 3.49±0.50, 3.65±0.48, respectively. After AASS, A and B scored 4.36±0.48 and 4.40±0.49 (p<0.0001). There were significant differences in the data before and after AASS and plus 60 m/sec, but no significant difference between the datasets were seen after AASS and at sound speeds manually set for minus 100 m/sec. CONCLUSIONS: EUS with ZST was shown to be feasible in this preliminary experiment. Further evaluation of this novel technology is necessary and awaited.

BACKGROUND: Ulcerative colitis (UC) often occurs in women of childbearing age. Compared to Western countries, however, few studies have investigated the impact of UC on the progress of pregnancy in Asian populations. METHODS: We retrospectively examined 91 pregnancies in 64 patients with UC experienced at our hospital and related institutions from 1991 to 2011, focusing on the relationship between the progression of UC during pregnancy, progress of the pregnancy itself, and the treatment of UC. RESULTS: In 80 of 91 pregnancies the patient had already been diagnosed with UC at the time she became pregnant, of whom 31 (38.8%) experienced exacerbation during pregnancy. Regarding severity, moderate or severe active-stage disease during pregnancy was seen in 13.7% of those who had been in remission at the onset of pregnancy versus 58.6% of those who had been in the active stage at onset (OR 8.9: 95%CI 3.0~26.4; P<0.01). The incidence of miscarriage or abortion was 9.8% in pregnancies in which UC was in remission at onset versus 31% in those in which it was in the active stage at onset (OR 4.1: 95%CI 1.2~13.9; P=0.02). Among patients, 62.5% were receiving pharmaceutical treatment at onset of pregnancy. Exacerbation during pregnancy occurred in 26.5% of the group who continued to receive the same treatment during pregnancy versus 56.3% of those with a dose decrease or discontinuation after onset (OR 3.6: 95%CI 1.0~12.4; P=0.04). CONCLUSIONS: UC patients wishing to conceive should do so when in remission and continue appropriate pharmaceutical treatment during pregnancy.

BACKGROUND: Because the biopsy specimen of extrahepatic bile duct carcinoma (EHBDC) is small and shows reactive changes, the histological distinction between malignant and benign tissue can be difficult. Recent studies reported that S100P and insulin-like growth factor II mRNA-binding protein 3 (IMP3) were not only diagnostic molecules but also prognostic biomarkers in several organs. The objective of this study is to clarify the diagnostic and prognostic value of immunohistochemical expression of S100P and IMP3 in transpapillary biliary forceps biopsy (TBFB) samples. METHODS: The TBFB samples were collected from 80 patients (EHBDC, 68 patients; benign, 12 patients), retrospectively. RESULTS: When using cytoplasmic-positive staining for IMP3 as a marker of malignancy, the sensitivity and specificity reached 79.4 and 91.7 %, respectively. The sensitivity, specificity and accuracy achieved 89.7, 91.7 and 90.0 %, respectively, when using positive staining for IMP3 and/or positive histology as a maker of malignancy. While univariate (P = 0.033) and multivariate (P = 0.039) analysis revealed that S100P-positive EHBDC patients showed significantly shorter survival. CONCLUSIONS: The results of this study suggest that immunohistochemical staining for IMP3 is useful in the diagnosis of EHBDC and that of S100P is useful as a prognostic marker for EHBDC.

BACKGROUND: The distal esophagus harbors a complex bacterial population. We hypothesized that a better understanding of bacterial communities in the esophagus would facilitate understanding of the role of bacteria in esophageal disease. Here, we investigated bacterial composition in the distal esophagus in subjects with a normal esophagus, reflux esophagitis, and Barrett's esophagus. METHODS: Two biopsy specimens were obtained from the distal esophagus at 1 cm above the gastroesophageal junction under endoscopic examination in 18 patients (6 each with normal esophagus, reflux esophagitis, and Barrett's esophagus) and used for histological examination and DNA extraction. Fragments of 16S rDNA genes were amplified by PCR using general bacterial primers, and bacterial populations were examined. A third biopsy specimen was taken from the patients with Barrett's esophagus to histologically confirm the replacement of squamous epithelium with columnar epithelium in the distal esophagus. RESULTS: Endoscopic diagnoses of normal esophagus, esophagitis, and Barrett's esophagus were confirmed by histological findings. The total amount of bacterial DNA detected did not significantly differ among groups (p > 0.1). On average, each of the 18 subjects yielded about 350 clones, of which 40 were randomly picked and sequenced. Analysis of 147 16S rDNA sequences from 240 clones of 6 subjects with normal esophagus yielded four phyla, Proteobacteria (49%), Firmicutes (40%), Bacteroidetes (8%), and Actinobacteria (3%). Similar analysis of 139 16S rDNA sequences from 240 clones of 6 patients with reflux esophagitis yielded 6 phyla, Proteobacteria (43%), Firmicutes (33%), Bacteroidetes (10%), Fusobacteria (10%), Actinobacteria (2%), and TM7 (2%). while that of 138 16S rDNA sequences from 240 clones of 6 cases of Barrett's esophagus yielded 5 phyla, Firmicutes (55%), Proteobacteria (20%), Bacteroidetes (14%), Fusobacteria (9%), and Actinobacteria (2%). Thus, microbial communities differed among patients with a normal esophagus, reflux esophagitis and Barrett's esophagus. CONCLUSIONS: Esophageal bacterial composition differs under conditions of normal esophagus, reflux esophagitis, and Barrett's esophagus. Diverse bacterial communities may be associated with esophageal disease.

Intestinal phlebectasias are venous varicosities, without portal hypertension, consisting of a markedly dilated tortuous vein with a normal vascular wall and scant connective tissue stroma. The jejunum is the most commonly involved site, and so the lesions had usually been beyond the reach of a conventional endoscope before the advent of videocapsule endoscopy (VCE) and double-balloon endoscopy (DBE). This case series demonstrated that VCE was useful for screening and DBE enabled diagnosis and endoscopic treatment for bleeding lesions deep within the small bowel. Heretofore, surgery had been the only definitive therapy for intestinal phlebectasias, but is employed sparingly because of their multiplicity and extent. Enteroscopic injection sclerotherapy using polidocanol proved beneficial for extinguishing phlebectasias. Although intestinal phlebectasias relapse, repeated enteroscopic injection sclerotherapy might preclude bleeding and anemia. This article is part of an expert video encyclopedia. © 2013 Elsevier GmbH.

BACKGROUND: A close association between patterns identified by magnifying narrow-band imaging (M-NBI) and histological type has been described. M-NBI patterns were also recently reported to be related to the mucin phenotype; however, detials remain unclear. MATERIALS AND METHODS: We investigated the cellular differentiation of gastric cancer lesions, along with their mucosal distribution observed by M-NBI. Ninety-seven depressed-type early gastric cancer lesions (74 differentiated and 23 undifferentiated adenocarcinomas) were visualized by M-NBI. Findings were divided into 4 patterns based on abnormal microvascular architecture: a chain loop pattern (CLP), a fine network pattern (FNP), a corkscrew pattern (CSP), and an unclassified pattern. Mucin phenotypes were judged as gastric (G-type), intestinal (I-type), mixed gastric and intestinal (M-type), and null (N-type) based on 4 markers (MAC5AC, MUC6, MUC2, and CD10). The relationship of each pattern of microvascular architecture with organoid differentiation indicated by cancer cell differentiation and its distribution in each histological type of early gastric cancer was investigated. RESULTS: All CLP and FNP lesions were differentiated. The cancer cell distribution showed organoid differentiation in 84.2% (16/19) and 61.1% (22/36) of the two types of lesions, respectively, and there was a significant difference from the unclassified pattern with organoid differentiation (p<0.001). Almost all (94.7%; 18/19) CSP lesions were undifferentiated, and organoid differentiation was observed in 72.2% (13/18). There was a significant difference from the unclassified pattern with organoid differentiation (p<0.05). CONCLUSIONS: Cellular differentiation and distribution are associated with microvascular architecture observed by M-NBI.

BACKGROUND AND AIM: Although peripancreatic vascular lesions are occasionally encountered in autoimmune pancreatitis (AIP), there are few reports focusing on these involvements. We aimed to investigate the peripancreatic vascular involvements associated with AIP. METHODS: We retrospectively analyzed 54 AIP patients who met the International Consensus Diagnostic Criteria for AIP between July 2003 and October 2010. All of the 54 patients were subjected to multiphasic multidetector computed tomography, and the prevalence, location and prognosis of peripancreatic vascular involvements were investigated. RESULTS: Of the 54 AIP patients, 24 (44.4%) exhibited involvements in the form of peripancreatic vascular lesions (stenoses of the splenic vein in 22 and of the superior mesenteric-portal vein in 13, development of perigastric collateral circulation in 18, gastric varices with a red color sign in one and thrombosis inside the portal vein in one). Diffuse-type AIP was associated with a significantly higher prevalence of vascular involvements compared with focal-type AIP (P = 0.033). A total of 14 out of 16 patients who underwent corticosteroid treatment showed improvement in vascular lesions. One case followed up without corticosteroid treatment and presenting an obstruction of the splenic vein exhibited involvements in the form of an infarction and hemorrhagic cysts of the spleen and ultimately underwent distal pancreatectomy and splenectomy. CONCLUSIONS: Autoimmune pancreatitis patients show a high prevalence of peripancreatic vascular involvements. Thus, patients with vascular involvements are suitable candidates for steroid therapy with evaluation of its potential merits and demerits, even if they are asymptomatic.

Contrast-enhanced endoscopic ultrasonography (CE-EUS) was introduced in the early 1990s. The concept of the injection of carbon dioxide microbubbles into the hepatic artery as a contrast material (enhanced ultrasonography) led to "endoscopic ultrasonographic angiography". After the arrival of the first-generation contrast agent, high-frequency (12 MHz) EUS brought about the enhancement of EUS images in the diagnosis of pancreatico-biliary diseases, upper gastrointestinal (GI) cancer, and submucosal tumors. The electronic scanning endosonoscope with both radial and linear probes enabled the use of high-end ultrasound machines and depicted the enhancement of both color/power Doppler flow-based imaging and harmonic-based imaging using second-generation contrast agents. Many reports have described the usefulness of the differential diagnosis of pancreatic diseases and other abdominal lesions. Quantitative evaluation of CE-EUS images was an objective method of diagnosis using the time-intensity curve (TIC), but it was limited to the region of interest. Recently developed Inflow Time Mapping™ can be generated from stored clips and used to display the pattern of signal enhancement with time after injection, offering temporal difference of contrast agents and improved tumor characterization. On the other hand, three-dimensional CE-EUS images added new information to the literature, but lacked positional information. Three-dimensional CE-EUS with accurate positional information is awaited. To date, most reports have been related to pancreatic lesions or lymph nodes. Hemodynamic analysis might be of use for diseases in other organs: upper GI cancer diagnosis, submucosal tumors, and biliary disorders, and it might also provide functional information. Studies of CE-EUS in diseases in many other organs will increase in the near future.

AIM: To investigate the usefulness of endoscopic ultra-sound-guided fine needle aspiration (EUS-FNA) in the differentiation of autoimmune pancreatitis (AIP). METHODS: We retrospectively reviewed 47 of 56 AIP patients who underwent EUS-FNA and met the Asian diagnostic criteria. On 47 EUS-FNA specimens, we evaluated the presence of adequate material and characteristic features of lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) mentioned in the International Consensus Diagnostic Criteria and examined if these findings make a contribution to the differential diagnosis of type 1 and type 2 AIP. A disposable 22-gauge needle was used for EUS-FNA. RESULTS: Adequate specimens including pancreatic tissue for differentiating AIP from cancer were obtained from 43 of 47 patients who underwent EUS-FNA. EUS-FNA was performed from the pancreatic head in 21 cases, which is known to be technically difficult when performed by core biopsy; there was no significant difference in the results compared with pancreatic body-tail. Nine of 47 patients met level 1 findings of LPSP and 5 patients met level 2 findings of LPSP. No one met level 1 findings of IDCP, but 3 patients met level 2 findings of IDCP. Of 10 seronegative cases, 2 cases were diagnosed with "definitive type 1 AIP", and 3 cases were diagnosed with "probable type 2 AIP" when considering both the level 2 histological findings and response to steroids. CONCLUSION: EUS-FNA is useful in the differentiation of type 1 and type 2 AIP, particularly in seronegative cases.

OBJECTIVES: Protein-losing enteropathy (PLE) is often difficult to diagnose. We evaluated the diagnostic yields of underlying diseases of PLE among esophagogastroduodenoscopy, colonoscopy, fluoroscopic conventional enteroclysis (FCE), videocapsule endoscopy (VCE), and double-balloon enteroscopy (DBE) and prognosis after treatment. METHODS: Between June 2003 and August 2010, 25 consecutive patients with PLE confirmed by fecal α1-antitrypsin clearance (n=18) and technetium 99m human serum albumin scintigraphy (n=19) were enrolled, investigated, and treated. RESULTS: Of 25 patients, 4 (16%) with intestinal lymphangiectasia secondary to macroglobulinemia (n=1), amyloidosis (n=2), and strongyloidiasis (n=1) were diagnosed at preceding esophagogastroduodenoscopy or colonoscopy, and 7 (32%) with primary intestinal lymphangiectasia and chronic nonspecific multiple ulcers unrelated to nonsteroidal anti-inflammatory drugs of the small intestine were newly diagnosed at FCE or VCE. Other 11 (44%) patients with primary intestinal lymphangiectasia, small-bowel tumors, amyloidosis, chronic nonspecific multiple ulcers unrelated to nonsteroidal anti-inflammatory drugs of the small intestine, Crohn's disease, and small-bowel ulcers due to polyarteritis nodosa were diagnosed only at DBE with biopsy. Three patients with primary intestinal lymphangiectasia, cirrhosis after living donor liver transplantation, and congestive heart failure were not diagnosed at any small-bowel examination. The overall diagnostic yield of FCE, VCE, and DBE was 62% (8/13), 83% (14/17), and 88% (22/25), respectively. Eight patients (32%) died of underlying disorders regardless of medical treatment over the follow-up period. CONCLUSIONS: DBE with pathologic findings of biopsy specimens was useful for the differential diagnosis of PLE. Noninvasive VCE might be preferable and useful for screening and follow up of PLE without stricture. Prognosis of a subgroup of PLE was poor regardless of treatment.

OBJECTIVES: The natural history of branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas remains unclear. We conducted a retrospective long-term follow-up study for malignant transformation (MT) of BD-IPMNs focusing on morphological changes. METHODS: The subjects consisted of 142 patients who underwent contrast-enhanced endoscopic ultrasonography for initial diagnosis from January 2001 with more than 12 months of follow-up. The MT rate, including the co-occurrence of invasive ductal cancer, was evaluated by univariate and multivariate analysis. In addition, on the basis of morphological changes in patients who underwent surgery, the predictive factors for malignant IPMNs were evaluated. RESULTS: Median follow-up term was 42.5 months (range, 12-105 months). Thirty patients who exhibited morphological changes underwent surgery. Malignant transformation occurred in 9 patients (6.3%), and 5-year MT rate was 10.7%. The co-occurrence of invasive ductal cancer was seen in 5 patients. Multivariate analysis showed that the existence of mural nodules at initial diagnosis and involvement of main pancreatic duct were significant predictors of MT of BD-IPMN. CONCLUSIONS: Malignant transformation of BD-IPMN is not rare. The observation of morphological changes of main pancreatic duct and nodules, mainly on contrast-enhanced endoscopic ultrasonography, is practical and useful for predicting MT of BD-IPMN itself.

BACKGROUND: Small-bowel tumors (SBTs) represent a diagnostic challenge. OBJECTIVE: To evaluate the usefulness of contrast-enhanced CT (CECT), fluoroscopic enteroclysis (FE), videocapsule endoscopy (VCE), and double-balloon endoscopy (DBE) and the outcome after treatment. DESIGN: Single-center, retrospective study. SETTING: Tertiary-care referral hospital. PATIENTS: Between June 2003 and May 2011, 159 consecutive patients with SBTs (93 malignant and 66 benign) were enrolled. MAIN OUTCOME MEASUREMENTS: Comparison of diagnostic yields among CECT, FE, VCE, and DBE and the prognosis. RESULTS: CECT and FE had significantly lower diagnostic yields of SBTs ≤ 10 mm, but VCE and DBE had high yields of SBTs regardless of size. CECT had a significantly lower diagnostic yield of epithelial tumors compared with subepithelial tumors. When stratified by the site, the diagnostic yield of VCE for SBTs located only in the distal duodenum/the proximal jejunum (73%) was significantly lower than that for SBTs located in other areas (90%). Comparisons among the 4 methods revealed that VCE and DBE had significantly higher diagnostic yields than CECT, and DBE had significantly higher diagnostic yields than VCE, but a combination of CECT and VCE had a diagnostic yield similar to that of DBE. The histologic diagnostic yield of SBTs by DBE was 92%, and 25% of SBTs were enteroscopically treated. Metastatic tumors had the poorest overall survival, followed by adenocarcinomas and malignant lymphomas. LIMITATIONS: Retrospective comparative study. CONCLUSION: For the detection of SBTs, a combination screening method by using VCE and CECT is recommended. DBE is useful for histologic diagnosis and endoscopic treatment.

US elastography(EG-US)の登場により、従来の超音波診断(Bモード診断、ドプラ診断)に組織弾性情報が付加された。Real-time Tissue Elastography(RTE)は日本で開発され、世界で最初に製品化されたEG-USであるが、膵疾患の診療ではRTE所見の二つの考え方を理解する必要がある。すなわち、"病変部が周囲組織に比して高硬度あるいは低硬度"という考え方と"病変内の硬度分布が均一あるいは不均一"という考え方であり、前者は膵腫瘍の診断に、後者は膵び漫性疾患の診断に有用と考えられる。当施設では2003年の発売当初から膵疾患に対しRTEを実施し、多くの膵疾患が正常組織と比較して高硬度に描出されることを経験し、その原因が線維化や細胞稠密性、浮腫等の影響であることを病理組織学的に確認した。また病変の種類や進行度によって硬度や均一性/不均一性が異なることも経験し、RTEが膵疾患の鑑別および進行度診断に有用であることも確認している。EG-USの原理および、その所見を正確に理解することで、膵疾患の質的診断能は飛躍的に向上する。EG-USが日常診療に積極的に導入されることを期待する。(著者抄録)

AIM: To evaluate the effectiveness of our proposed bowel preparation method for colon capsule endoscopy. METHODS: A pilot, multicenter, randomized controlled trial compared our proposed "reduced volume method" (group A) with the "conventional volume method" (group B) preparation regimens. Group A did not drink polyethylene glycol electrolyte lavage solution (PEG-ELS) the day before the capsule procedure, while group B drank 2 L. During the procedure day, groups A and B drank 2 L and 1 L of PEG-ELS, respectively, and swallowed the colon capsule (PillCam COLON® capsule). Two hours later the first booster of 100 g magnesium citrate mixed with 900 mL water was administered to both groups, and the second booster was administered six hours post capsule ingestion as long as the capsule had not been excreted by that time. Capsule videos were reviewed for grading of cleansing level. RESULTS: Sixty-four subjects were enrolled, with results from 60 analyzed. Groups A and B included 31 and 29 subjects, respectively. Twenty-nine (94%) subjects in group A and 25 (86%) subjects in group B had adequate bowel preparation (ns). Twenty-two (71%) of the 31 subjects in group A excreted the capsule within its battery life compared to 16 (55%) of the 29 subjects in group B (ns). Of the remaining 22 subjects whose capsules were not excreted within the battery life, all of the capsules reached the left side colon before they stopped functioning. A single adverse event was reported in one subject who had mild symptoms of nausea and vomiting one hour after starting to drink PEG-ELS, due to ingesting the PEG-ELS faster than recommended. CONCLUSION: Our proposed reduced volume bowel preparation method for colon capsule without PEG-ELS during the days before the procedure was as effective as the conventional volume method.

BACKGROUND AND AIMS: The number of patients with Crohn's disease (CD) and the number of cases of intestinal cancer associated with CD have both been increasing in Japan. However, the number of reported cases is lower than for ulcerative colitis-associated cancer. The aim of this study was to identify the clinical picture of CD-associated intestinal cancer in a consecutive series of patients with CD and to stress the importance of surveillance. METHODS: We enrolled 174 consecutive patients (130 men, 44 women, mean age 25 years) diagnosed with CD and investigated the development of intestinal cancer from October 1998 to July 2010. There were 104 cases of the ileocolitis type, 47 of ileitis, and 23 of colitis. RESULTS: Intestinal cancer developed in two male patients (1.5% of the total), whose respective ages at onset of CD were 41 and 19 years, and 55 and 37 years at onset of cancer. Both cases were of ileocolitis-type CD; one cancer developed in the rectum and the other in the small bowel, and both were accompanied by severe stricture. Histopathological results revealed well and moderately differentiated adenocarcinoma, respectively. CONCLUSIONS: Intestinal cancer developed in patients with ileocolitis-type CD of more than 10 years' duration. Our findings suggest that patients with chronic, widespread CD should be under cancer surveillance.

OBJECTIVES: This study aimed to investigate the usefulness of contrast-enhanced endoscopic ultrasonography (EUS) with time-intensity curve (TIC) in differentiating pancreatic diseases. METHODS: Patients who underwent contrast-enhanced EUS between January 2007 and June 2009 were analyzed retrospectively, including 48 with pancreatic ductal cancer (PC), 14 with autoimmune pancreatitis (AIP), 13 with mass-forming pancreatitis (MFP), and 16 with pancreatic endocrine tumor (PET). After intravenous injection of contrast agent, contrast imaging pattern, TIC-based quantitative evaluation, and diagnostic ability of EUS in combination with TIC to diagnose benignancy or malignancy were assessed. RESULTS: Hypovascular and heterogeneous pattern (42/48) in PC, isovascular and homogenous (21/27) in AIP and MFP, and hypervascular and rapid stained (16/16) in PET were observed. The echo intensity reduction rate from the peak at 1 minute was the greatest in PC followed by MFP, AIP, and PET (P < 0.05). The diagnostic accuracies based on contrast imaging pattern (84.0%) and TIC (88.0%) were higher than those based on B-mode imaging (82.6%) and dynamic computed tomography (81.3%). In EUS in combination with TIC, sensitivity, specificity, and accuracy rose up to 95.8%, 92.6%, and 94.7%, respectively. CONCLUSIONS: Contrast-enhanced EUS with the dynamic quantitative analysis preparing TIC increased the diagnostic accuracy for pancreatic diseases.

OBJECTIVE: The objectives of this study were to retrospectively evaluate the lesion detection rate of gastric cancer using only virtual gastroscopy generated from MDCT images and the accuracy of invasion depth diagnosis (T staging) using virtual gastroscopy together with contrast-enhanced MDCT with multiplanar reconstruction (MPR) images (virtual gastroscopy with MPR), and to compare the diagnostic performance between virtual gastroscopy with MPR images and endoscopic ultrasound. MATERIALS AND METHODS: The subjects consisted of 175 patients with a total of 186 endoscopically proven gastric cancer lesions. All patients underwent dynamic MDCT (arterial and venous phase) for preoperative staging and underwent surgery or endoscopic treatment. In 129 patients (135 lesions) who were also examined using endoscopic ultrasound, the T staging accuracy was also compared between the two modalities. Two endoscopists independently evaluated the lesion detection rate on virtual gastroscopy images alone and determined the T stage on virtual gastroscopy with MPR images. The T staging included the ability to differentiate T1a from T1b lesions. RESULTS: The overall lesion detection rate was 67.7% (126/186). The detection rates of T1a, T1b, and T2 or deeper were 37.8% (28/74), 75.0% (39/52), and 98.3% (59/60), respectively, showing statistically significant differences (p < 0.001). The T staging accuracies were 82.2% (111/135) using virtual gastroscopy with MPR images and 83.7% (113/135) using endoscopic ultrasound, showing no statistically significant difference (p = 0.850). The main causes of over- and understaging were an ulcer or ulcer scar and poorly differentiated adenocarcinomas, non-solid type, respectively. CONCLUSION: Virtual gastroscopy with MPR imaging is a useful modality in the T staging of gastric cancer.

We used contrast-enhanced endoscopic ultrasonography (CE-EUS) to diagnose a case of solid-pseudopapillary neoplasm (SPN) in an adult man. A 58-year-old man was referred to our hospital because of a pancreatic mass found by positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) during a medical checkup in 2009. Trans-abdominal ultrasonography revealed a 24-mm hypoechoic mass at the pancreatic tail with calcification inside. Multiphasic computed tomography (CT) showed a solid mass with delayed enhancement. EUS revealed a hypoechoic mass without lateral shadowing, and neither a septum nor cystic component was detected. CE-EUS using Sonazoid(®) showed a hypovascular mass compared with the surrounding pancreatic parenchyma, and the inside of the mass was enhanced like an alveolus nest, suggesting pseudopapillary change. Diagnosis of a solid-pseudopapillary neoplasm and a concomitant small neuroendocrine tumor was made by distal pancreatectomy.

PURPOSE: S-1 is one of the second-line candidate agents for gemcitabine-refractory unresectable pancreatic cancer. Two phase II studies have been reported for second-line chemotherapy with S-1, but these studies did not investigate introduction rate and suitable dose of second-line S-1. Therefore, we conducted a prospective multicenter study in which chemo-naïve patients were enrolled and had two levels of S-1 dose. METHODS: Chemo-naïve patients with unresectable pancreatic cancer were enrolled. This study started with 80 mg/m(2)/day dose of S-1 as second-line chemotherapy and tolerability was checked. When tolerability was not confirmed in initial patients, the dose of S-1 was shifted to 60 mg/m(2)/day. When tolerability was confirmed at 80 or 60 mg/m(2)/day, the study continued, and up to 20 patients were accumulated with the dose. In addition, the introduction rate of second-line S-1 was examined. RESULTS: Six of the initial 7 patients with 80 mg/m(2)/day dose of S-1 completed one course of second-line chemotherapy. Twenty patients were accumulated with an 80 mg/m(2)/day dose of S-1. With the exception of one patient continued gemcitabine chemotherapy, two of the remaining 19 patients withdrew from this study because of toxicity during the period of gemcitabine chemotherapy. Fifteen of the remaining 17 gemcitabine-refractory patients could complete one course of S-1 as second-line chemotherapy with acceptable toxicity. CONCLUSIONS: This prospective multicenter study showed that 15 (78.9%) out of 19 chemo-naïve unresectable pancreatic cancer patients could complete one course of 80 mg/m(2)/day dose of S-1 as second-line chemotherapy after first-line gemcitabine chemotherapy failure with tolerable toxicity.

In Western countries, the standard treatment for locally advanced rectal cancer is preoperative chemoradiotherapy followed by total mesorectal excision. On the other hand, in Japan, treatment results without radiotherapy are by no means inferior; therefore, extrapolation of results of preoperative treatment in Western countries to Japan is controversial. We consider that survival may be improved by preoperative treatment with new anticancer agents as they are expected not only to decrease the local recurrence rate but also to prevent distant metastases. We are conducting a multicentre Phase II study to evaluate the safety and efficacy of neoadjuvant chemotherapy using XELOX plus bevacizumab without radiotherapy in patients with locally advanced rectal cancer. The primary endpoint of the study is treatment compliance. Secondary endpoints are overall survival, disease-free survival, local recurrence-free survival, objective response rate, R0 resection rate and adverse events. Thirty patients are required for this study.

We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II(1) GI-FL. Of the 125 patients, the small intestine was examined in 70 patients, with double-balloon endoscopy and/or capsule endoscopy. The most frequently involved GI-FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP-positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression-free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI-FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course.

Double-balloon endoscopy (DBE) is very useful for the diagnosis and treatment of non-steroidal anti-inflammatory drugs (NSAIDs)-associated enteritis. In cases of long-term NSAIDs administration, aphtha, specific diaphragm-like strictures and circular ulcers are pointed out into details by DBE. Even if on-demand use of NSAIDs, some patients have small bowel injuries when NSAIDs are administered for over several years. Moreover, there are variations for the type and indication of NSAIDs among patients. The cytolysis image and the apoptosis in the base of mucosa were reported as the characteristic histological findings of NSAIDs-associated enteritis. In consideration of widespread use of NSAIDs, a strategy for the management of NSAID-associated enteritis should be discussed and established.

In the early 2000s, the main stream of endoscopic ultrasonography (EUS) changed from a mechanical scanning method to electronic radial or linear scanning methods. Subsequently, useful applications in trans-abdominal ultrasonography came within reach of EUS. In particular, contrast-enhanced EUS (CE-EUS) and EUS-elastography became cutting-edge diagnostic modalities for pancreatic disorders. Each type of pancreatic disorder has characteristic hemodynamics. CE-EUS uses color Doppler flow imaging and harmonic imaging to classify pancreatic lesions. EUS-elastography can assess tissue hardness by measuring its elasticity. This parameter appears to correlate with the malignant potential of the lesions. Tissue elasticity studies can provide information on both its pattern and distribution. The former is the conventional method of morphological diagnosis, but it is restricted to observations made in a region of interest (ROI). The latter is an unbiased analysis that can be performed by image analysis software and is theoretically constant, regardless of the ROI. Though EUS-fine needle aspiration (FNA) is also a very useful diagnostic tool, there are several limitations. Diagnostic EUS-FNA of pancreatic cystic lesions has marginal utility mainly due to low sensitivity. Therefore, in particular, endoscopists should keep this limitation in mind.

In this case, narrow-band imaging helped to distinguish esophagitis. The case involved an 81-year-old female was being seen as an outpatient because of Gastroesophageal Reflux Disease (GERD) symptoms associated with an esophageal hiatal hernia. Endoscopy showed long reddish lesions on the posterior wall of the lower thoracic esophagus. Non-magnifying endoscopic images with white light initially suggested reflux esophagitis. Magnifying endoscopy with narrow-band imaging showed proliferation of intraepithelial papillary capillary loop-like vessels as well as irregular widening and narrowing of vessels, so the patient's condition was diagnosed as superficial esophageal cancer. Endoscopic submucosal dissection was carried out.

BACKGROUND: Real-time tissue sonoelastography (EG) is a new non-invasive technique that visualizes differences in tissue strain. We evaluated the usefulness of EG in patients with ulcerative colitis (UC) by investigating the association between EG and colonoscopic findings and disease activity. METHODS: Thirty-seven UC patients undergoing EG and colonoscopy were invited to enroll. EG findings were classified as normal, homogeneous, random, or hard, and colonoscopic findings as normal, mucosal edema and erosion, punched-out ulcer, and extensive mucosal abrasion. Clinical findings were evaluated using clinical activity index (CAI) scores for each patient at colonoscopy. RESULTS: On EG, 10 cases were classified as normal, 11 as homogeneous, 6 as random, and 10 as hard. EG findings showed a significant correlation those of colonoscopy (p < 0.001). Seven of 10 (70%) normal-type patients were in the remission phase, while all 6 random-type patients were in the active phase. Among active-phase patients, 4 of 7 (57%) homogeneous-type patients responded to steroid or leukocytapheresis therapy, while 3 of 6 (50%) random-type patients required treatment with cyclosporine. Three of 10 (30%) hard-type patients required colectomy. CONCLUSIONS: In this small series, EG findings reflected colonoscopic findings and correlated with disease activity among patients with UC.

BACKGROUND: Management of small-bowel polyps in Peutz-Jeghers syndrome (PJS) by using fluoroscopic enteroclysis (FE), double-balloon enteroscopy (DBE), and videocapsule enteroscopy (VCE) remains incompletely determined. OBJECTIVE: To evaluate the usefulness of FE, VCE, and DBE and compute the polyp growth rate. DESIGN: Single-center retrospective study. SETTING: Tertiary referral hospital. PATIENTS: Between June 2003 and January 2010, 18 consecutive patients with PJS were enrolled. MAIN OUTCOME MEASUREMENTS: Polyp detection rates among FE, VCE, and DBE, histology of resected polyps, and the polyp growth rate. RESULTS: Total enteroscopy rate was higher at VCE (89%) than at DBE (52%; 27% in patients with ≥2 previous laparotomies and 90% in patients with ≤1 [P = .001]). FE demonstrated fewer polyps than DBE, whereas VCE had detection rates similar to those of DBE. Of 387 DBE-resected and 22 surgically resected polyps, histologic analysis of 110 retrieved polyps showed adenoma or adenocarcinoma in 30.0% of polyps >20 mm and in only 1.3% of polyps ≤20 mm (P < .0001). Multiple linear regression analysis showed that the number of small-bowel polyps >10 mm (X1; P = .0366) and colorectal polyps >5 mm (X2; P = .002) were independent predictors of the growth rate of small-bowel polyps (Y), and a forward stepwise selection model was constructed: Y = 0.136 × X1 + 0.289 × X2 - 0.589 (R(2) = 0.665). LIMITATIONS: Small sample size. CONCLUSIONS: DBE and VCE were useful for the management of small-bowel polyps in PJS. VCE may replace barium examinations for surveillance after polyp resection at intervals depending on the polyp growth rate.

BACKGROUND: Double-balloon endoscopy (DBE) utilizes both oral and anal routes. The proper selection of the initial route is important for more rapid management of obscure gastrointestinal bleeding (OGIB). The aim of this retrospective study was to clarify the accuracy of the transit time of video capsule endoscopy (VCE) to the lesion as a predictive indicator for the decision on the initial DBE route. METHODS: Of 172 patients who underwent both DBE and VCE, 65 who were diagnosed with small-intestinal hemorrhagic lesions by both means were enrolled. The relation between VCE transit time to the lesion and the DBE route by which the lesion was discovered was analyzed, distinguishing between 46 complete and 19 incomplete VCEs. RESULTS: Among the 46 patients with a complete VCE, the transit time and position of the lesion were strongly correlated. The best cutoff values for route selection by the VCE transit time from capsule intake and from the duodenal bulb to the lesion, determined using a receiver operating characteristic (ROC) curve, were 60% and 50%, respectively, of the transit time to the cecum. At that point, the accuracy of route selection was 90% and 94%, respectively. Positions shown by VCE for ileal lesions tended to be more proximal than those shown by surgery. In the 19 patients with incomplete VCEs, the best cutoff for transit time was 180 min from the duodenal bulb. CONCLUSIONS: The VCE transit time was useful for determining the route for DBE in OGIB. This parameter was most accurate when the cutoff value for the selection was half of the small-bowel transit time in the complete VCE examination.

BACKGROUND: Pancreatic endocrine tumors (PETs) develop in relatively few patients, but they are often difficult to diagnose because of their small size and various clinical symptoms. OBJECTIVE: The aim of this study was to investigate the usefulness of EUS combined with contrast enhancement (CE-EUS) in the preoperative localization of PETs and the differentiation between malignant and benign PETs. DESIGN AND SETTING: Single-center retrospective study. PATIENTS: Sixty-two pathologically certified PETs of 41 patients who underwent EUS, multiphasic multidetector computed tomography (MDCT), and transabdominal US at our institute since 2001. INTERVENTIONS: Intravenous injection of US contrast media. MAIN OUTCOME MEASUREMENTS: Comparison of EUS, MDCT, and US in the preoperative identification of PETs, and the characteristic findings of EUS with malignancy. RESULTS: EUS showed high sensitivity (95.1%) in identifying PETs compared with MDCT (80.6%) and US (45.2%). Multivariable logistic regression analysis showed that heterogeneous ultrasonographic texture was the most significant factor for malignancy (OR = 53.33; 95% CI, 10.79-263.58). Most heterogeneous hypoechoic areas and anechoic areas corresponded to hemorrhage or necrosis on pathologic examination. They were identified as filling defects in CE-EUS and were more clearly recognized than in conventional EUS. LIMITATIONS: Retrospective study. CONCLUSION: EUS has higher sensitivity in preoperative localization of PETs compared with MDCT and US. The characteristics of EUS and CE-EUS findings in malignant PETs were clarified, and they will improve the diagnostic accuracy of PETs.