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Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Background Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett’s esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society—Barrett’s esophagus working group (JES-BE) for superficial Barrett’s esophagus-related neoplasms. Methods The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. Results The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. Conclusion The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician’s experience level.

Background/Aims: Endoscopic transpapillary gallbladder drainage (ETGBD) is useful for the treatment of acute cholecystitis; however, the technique is difficult to perform. When intraductal ultrasonography (IDUS) is combined with ETGBD, the orifice of the cystic duct in the common bile duct may be more easily detected in the cannulation procedure. The aim of this study was to evaluate the efficacy of ETGBD with IDUS compared with that of ETGBD alone. Methods: A total of 100 consecutive patients with acute cholecystitis requiring ETGBD were retrospectively recruited. The first 50 consecutive patients were treated using ETGBD without IDUS, and the next 50 patients were treated using ETGBD with IDUS. Through propensity score matching analysis, we compared the clinical outcomes between the groups. The primary outcome was the technical success rate. Results: The technical success rate of ETGBD with IDUS was significantly higher than that of ETGBD without IDUS (92.0% vs. 76.0%, p=0.044). There was no significant difference in procedure length between the two groups (74.0 min vs. 66.7 min, p=0.310). The complication rate of ETGBD with IDUS was significantly higher than that of ETGBD without IDUS (6.0% vs. 0%, p

The bleeding complication risk of surgery or percutaneous transhepatic gallbladder drainage (PTGBD) may increase in patients with acute cholecystitis receiving antithrombotic therapy (ATT). Endoscopic gallbladder drainage (EGBD) may be recommended for such patients. English articles published between 1991 and 2018 in peer-reviewed journals that discuss cholecystectomy, PTGBD, and EGBD in patients with ATT or coagulopathy were reviewed to assess the safety of the procedures, especially in terms of the bleeding complication. There were 8 studies on cholecystectomy, 3 on PTGBD, and 1 on endoscopic transpapillary gallbladder drainage (ETGBD) in patients receiving ATT. With respect to EGBD, 28 studies on ETGBD (including 1 study already mentioned above) and 26 studies on endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) were also analyzed. The overall bleeding complication rate in patients with ATT who underwent cholecystectomy was significantly higher than that in patients without ATT (6.5% [23/354] vs. 1.2% [26/2,224], p

Given that risk factors for Barrett’s carcinogenesis are predictive, appropriate management and surveillance of Barrett’s esophagus (BE) may be provided. The presence of colorectal neoplasms (CRNs) is a possible predictor of the development of BE and the progression to esophageal adenocarcinoma (EAC). We evaluated the relationship between BE or EAC and colonic diseases, including neoplasms and diverticulosis. Patients (N = 5606) who underwent both colonoscopy and esophagogastroduodenoscopy between January 2016 and December 2017 at three institutions were enrolled. The relationships between the presence of colonic diseases and BE or EAC and other clinical or endoscopic predictors of the presence of BE were investigated retrospectively. The prevalence of BE ≥ 1 cm and ≥ 3 cm in length was 13.0% and 0.52%, respectively. BE was closely related with the presence of colorectal adenoma (48.4% vs. 37.2% in non-BE; P

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is typically associated with an extremely poor prognosis; however, small PDAC tumors show good prognosis. High-grade pancreatic intra-epithelial neoplasia (PanIN), which precedes invasive PDAC, is a primary target for improving the prognosis of PDAC. However, detection of high-grade PanIN without invasive carcinoma by existing imaging modalities is difficult because the lesions are only microscopically detectable. Recent studies have reported the characteristics of imaging findings associated with localized high-grade PanIN and the usefulness of serial pancreatic-juice aspiration cytologic examination as a method to confirm the pre-operative histopathology. In this review, we aimed to clarify recent clinical findings regarding detection of localized high-grade PanIN, which may contribute to improvement of the prognosis of patients with PDAC. Abstract Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions, such as pancreatic intra-epithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). The prognosis of high-grade precancerous lesions, including high-grade PanIN and high-grade IPMN, without invasive carcinoma is good, despite the overall poor prognosis of PDAC. High-grade PanIN, as a lesion preceding invasive PDAC, is therefore a primary target for intervention. However, detection of localized high-grade PanIN is difficult when using standard radiological approaches. Therefore, most studies of high-grade PanIN have been conducted using specimens that harbor invasive PDAC. Recently, imaging characteristics of high-grade PanIN have been revealed. Obstruction of the pancreatic duct due to high-grade PanIN may induce a loss of acinar cells replaced by fibrosis and lobular parenchymal atrophy. These changes and additional inflammation around the branch pancreatic ducts (BPDs) result in main pancreatic duct (MPD) stenosis, dilation, retention cysts (BPD dilation), focal pancreatic parenchymal atrophy, and/or hypoechoic changes around the MPD. These indirect imaging findings have become important clues for localized, high-grade PanIN detection. To obtain pre-operative histopathological confirmation of suspected cases, serial pancreatic-juice aspiration cytologic examination is effective. In this review, we outline current knowledge on imaging characteristics of high-grade PanIN.

Given that endoscopic findings can be used to predict the potential of neoplastic progression in Barrett’s esophagus (BE) cases, the detection rate of dysplastic Barrett’s lesions may become higher even in laborious endoscopic surveillance because a special attention is consequently paid. However, endoscopic findings for effective detection of the risk of neoplastic progression to esophageal adenocarcinoma (EAC) have not been confirmed, though some typical appearances are suggestive. In the present review, endoscopic findings that can be used predict malignant potential to EAC in BE cases are discussed. Conventional results obtained with white light endoscopy, such as length of BE, presence of esophagitis, ulceration, hiatal hernia, and nodularity, are used as indicators of a higher risk of neoplastic progression. However, there are controversies in some of those findings. Absence of palisade vessels may be also a new candidate predictor, as that reveals degree of intense inflammation and of cyclooxygenase-2 protein expression with accelerated cellular proliferation. Furthermore, an open type of mucosal pattern and enriched stromal blood vessels, which can be observed by image-enhanced endoscopy, including narrow band imaging, have been confirmed as factors useful for prediction of neoplastic progression of BE because they indicate more frequent cyclooxygenase-2 protein expression along with accelerated cellular proliferation. Should the malignant potential of BE be shown predictable by these endoscopic findings, that would simplify methods used for an effective surveillance, because patients requiring careful monitoring would be more easily identified. Development in the near future of a comprehensive scoring system for BE based on clinical factors, biomarkers and endoscopic predictors is required.

Background and aim Colonic diverticulosis (CD) has been reported to be associated with presence of colon neoplasms (CNs) in Western patients, since most of the associated risk factors are common between them. However, such correlation has not been fully investigated in Asian patients. In this study, the association of CNs with CD was evaluated in a multicenter investigation. Methods We enrolled 5633 patients who underwent both colonoscopy and esophagogastroduodenoscopy due to annual follow-up, screening for positive occult blood testing and abdominal symptoms between January 2016 and December 2017 at three institutions. The relationship between the presence of CNs and CD was investigated, and predictors for presence of CNs were determined by multivariate logistic analysis. Results The enrolled patients consisted of 1799 (31.9%) with CD (average age 70.0 years, male 64.0%) and 3834 without CD (66.0 years, male 52.9%), with the prevalence of CNs in those groups 46.6% and 44.2%, respectively (P = 0.090). Predictors for early colon cancer were shown to be age (OR 1.02, 95% CI 1.01-1.04, P = 0.010), laxatives use (OR 1.76, 95% CI 1.17-2.64, P = 0.007), gastric neoplasms (OR 2.16, 95% CI 1.23-3.81, P = 0.008), and CD (OR 1.64, 95% CI 1.16-2.31, P = 0.005). Early colon cancer in the distal colon was most frequently detected in patients with right-sided CD (RR 2.50, P = 0.001). Conclusion In Japanese patients, early colon cancer was more frequently found in those with as compared to those without CD. The presence of CD may be an important indicator for an index colonoscopy examination to detect colon cancer. (Clinical-trial-registry: UMIN000038985).

Background Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) as a treatment for patients with acute cholecystitis has been shown to obtain high technical and clinical success rates and a low recurrence rate. However, the safety of EUS-GBD for patients receiving antithrombotic therapy (ATT) has not been proven. The aim was to evaluate the safety and efficacy of EUS-GBD in patients receiving ATT. Methods Twelve patients with acute cholecystitis associated with gallstones who were receiving antithrombotic therapy and underwent EUS-GBD were enrolled in this retrospective study. Patients with grade II or III cholecystitis who had failed endoscopic transpapillary GBD (ETGBD) or developed recurrence after multiple ETGBD procedures underwent urgent drainage by EUS-GBD. The primary outcome was the rate of bleeding complications after the procedure and the secondary outcomes were the technical and clinical success rates, complications, and recurrence. Results Eleven (91.6%) patients underwent EUS-GBD with continuation of ATT (at least 1 agent). Five of 12 patients (41.7%) were receiving more than 1 agent for ATT. The rate of bleeding complications was 0% and the technical success rate was 100%, even though some patients had high-grade (severe) cholecystitis and/or several underlying diseases. Early complications were found in 2 (16.7%) patients. The clinical success rate was 91.7% (11/12). There were no recurrences of cholecystitis during the follow-up period (mean 261 [range 5-650] days). Conclusions EUS-GBD yielded high technical and clinical success rates and a low recurrence rate. No patients receiving ATT developed bleeding complications. EUS-GBD might be a good option for patients on ATT.

Aim and methods The Japan Esophageal Society created a working committee group consisting of 11 expert endoscopists and 2 pathologists with expertise in Barrett’s esophagus (BE) and esophageal adenocarcinoma. The group developed a consensus-based classification for the diagnosis of superficial BE-related neoplasms using magnifying endoscopy. Results The classification has three characteristics: simplified, an easily understood classification by incorporating the diagnostic criteria for the early gastric cancer, including the white zone and demarcation line, and the presence of a modified flat pattern corresponding to non-dysplastic histology by adding novel diagnostic criteria. Magnifying endoscopic findings are composed of mucosal and vascular patterns, and are initially classified as “visible” or “invisible.” Morphologic features were evaluated for “visible” patterns, and were subsequently rated as “regular” or “irregular,” and the histology, non-dysplastic or dysplastic, was predicted. Conclusion We introduce the process and outline of the magnifying endoscopic classification.

Background and study aims A 72-year-old man with complete situs inversus presented with early gastric cancer on the lesser curvature wall of the antrum of the stomach. Endoscopic submucosal dissection (ESD) was selected as a treatment. When the patient was positioned in the left decubitus position, the lesion was hidden by blood and gastric fluid because it was located on the gravitational side. Therefore, we decided to perform ESD with the patient in the right lateral decubitus position and use an inverted overtube, which provided a good endoscopic view without the need to rearrange the endoscopist, assistants, or endoscopic system. ESD was safe and feasible using the inverted overtube.

Background: Kawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3'-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients., Article, PEDIATRIC RHEUMATOLOGY.17:34(2019)

Background and study aims: We present a case of invasive micropapillary carcinoma (IMPC) of the colon treated by endoscopic resection following magnifying endoscopy. A 47-year-old woman visited our hospital for follow-up of a positive fecal occult blood test. Colonoscopy revealed a semi-pedunculated reddish polyp, the surface of which showed gentle irregularity, and mild tension in the sigmoid colon. Magnifying colonoscopy with narrow band imaging revealed an irregular surface pattern with heterogeneity in vascular diameter and distribution. Magnifying endoscopic findings using crystal violet staining showed an irregular pit pattern with an expansion of stromal areas. Endoscopic resection of the sigmoid colon tumor was performed, and the histology of the resected specimen primarily revealed a micropapillary component with a small moderately differentiated adenocarcinoma component that massively invaded into the submucosal layer, accompanied by lymphatic invasion, although the tumor was very small (7 mm in diameter, smaller than any in previous reports). Laparoscopy-assisted sigmoidectomy and regional lymph node resection were performed; neither cancer nor lymph node metastases were present. This is the first report of a case with early-stage colonic IMPC observed with magnifying colonoscopy.

We read with interest the article by van der Sommen et al ,1 and assert some important and relevant points of adopting artificial intelligence (AI)-assisted endoscopy in clinical practice. Computer-aided diagnosis systems have successfully applied to all segments of the GI tract, even the diagnosis of dysplasia in Barrett’s oesophagus which is the bane of expert endoscopists.2 Recently, colonoscopy with real-time computer-aided detection (CADe) systems achieved higher polyp detection as compared with the performance of expert endoscopists.3 However, in adopting CADe to conventional oesophagogastroduodenoscopy (OGD), related discussions for improving the detection of hard-to-find gastric cancers (GC) are inevitable. The stomach has a wider, bent lumen, implicating more laborious gastric observations without a blind spot, compared with other GI tract anatomical features such as the oesophagus and colon. In routine OGD, the endoscopists have to distinguish gastric neoplasms from surrounding gastritis mucosa at more distant view, as opposed to detection of colorectal neoplasms and Barrett-related dysplasia by near-view images. In addition, early GCs usually show subtle elevation or depression and their irregular appearances easily hide in the coarse background gastritis caused by Helicobacter pylori infection. Therefore, it is sometimes difficult even for experts to discover early GCs, particularly smaller sizes. …

Magnification endoscopy with narrow-band imaging (NBIME) and NBIME with acetic acid enhancement (A-NBIME) visualize the capillary and microstructure patterns of the gastric mucosal surface, respectively. This study aimed to compare the diagnostic accuracy and interobserver agreement for white-light endoscopy (WLE), NBIME, and A-NBIME in the different histologic types of gastric mucosal neoplasm.Consecutive gastric neoplasms (n = 220; 49 adenomas, 144 differentiated adenocarcinomas, and 27 undifferentiated adenocarcinomas) were photographed with WLE, NBIME, and A-NBIME. Macroscopic patterns using WLE, capillary patterns using NBIME, and microstructure patterns using A-NBIME were respectively classified into type M1/M2/M3, type C1/C2/C3/C4, and type S1/S2/S3, as the indicators of adenoma, differentiated adenocarcinoma, and undifferentiated adenocarcinoma (Type C4, unevaluable because of capillary invisibility), according to the previously reported classifications. Endoscopic images were independently reviewed by three experts and three non-experts. Diagnostic accuracy and interobserver diagnostic agreement were compared among the modalities.Kappa values (95 % confidence interval [CI]) for WLE, NBIME, and A-NBIME diagnosis were 0.36 (0.33 - 0.39), 0.58 (0.54 - 0.61), and 0.62 (0.55 - 0.68) for experts and 0.31 (0.29 - 0.33), 0.36 (0.34 - 0.38), and 0.52 (0.48 - 0.56) for non-experts, showing good reproducibility of A-NBIME diagnosis regardless of proficiency. All experts and non-experts diagnosed the histologic types statistically more accurately with A-NBIME than with WLE and NBIME (P 0.05). Overall the "experts-agreed" diagnostic accuracy (95 %CI) was 75.5 % (70.0 - 81.0) for WLE vs. 74.1 % (67.6 - 80.6) for NBIME vs. 90.5 % (86.7 - 94.1) for A-NBIME (P 0.05). WLE and NBIME were insufficient to predict the diagnosis of adenomas and undifferentiated adenocarcinomas.A-NBIME showed statistically significantly higher diagnostic accuracy for gastric mucosal neoplasms, with good reproducibility, compared with WLE and NBIME, which provided similar lower accuracy.

An asymptomatic 73-year-old man underwent a follow-up colonoscopy after a right hemicolectomy for advanced cancer. A larva was incidentally observed, the head of which was inserted into the ileal mucosa near the anastomosis. Mild mucosal oedema with erosions was observed in the mucosa surrounding the larva (figure 1A,B). The larva was removed with endoscopic forceps and identified as an anisakid larva. Two days earlier, he had eaten …

Aspiration pneumonia is an emerging problem in patients receiving gastrostomy feeding. This study is designed to clarify the therapeutic effects of mosapride citrate and lansoprazole for prevention of aspiration pneumonia in patients receiving gastrostomy feeding.The study subjects were 119 patients with dysphasia who required gastrostomy feeding. They were randomly assigned to the control (without medication), lansoprazole (15 mg, 1/day), and mosapride (5 mg, 3/day) groups. The number of days with fever (≥37.8 °C), vomiting, and antibiotics administration, as well as the occurrence of pneumonia were investigated during the 6-month observation period.The incidence of pneumonia during the observation period was significantly lower in the mosapride group as compared to the control (7/38 vs. 16/40, p = 0.038) and lansoprazole (vs. 20/41, p = 0.005) groups. The mosapride group also showed a significant decrease in days with fever and antibiotics administration as compared to the other groups. Multivariate analysis revealed that the presence of hiatal hernia was a significant risk factor and administration of mosapride was a significant preventive factor for pneumonia.Mosapride has a preventive effect on occurrence of pneumonia in patients receiving gastrostomy feeding.

Cdx2 expression in esophageal stem cells induced by reflux bile acids may be an important factor for development of Barrett's esophagus, whereas Notch signaling is a molecular signaling pathway that plays an important role in the determination of cell differentiation. ATOH1 (a factor associated with Notch signaling) plays an important role in differentiation of stem cells into goblet cells. However, the relationship between the Notch signaling pathway and Cdx2 expression in the development of Barrett's esophagus has not been explored. The aim of this study was to investigate the interrelationship between Notch signaling and Cdx2 in esophageal epithelial cells. The expressions of Cdx2, MUC2, and intracellular signaling molecules related to Notch signaling (Notch1, Hes1, and ATOH1) were examined using real-time polymerase chain reaction (PCR) and immunohistochemical staining with biopsy specimens obtained from esophageal intestinal metaplasia (IM) with goblet cells (IM⁺) and columnar epithelium not accompanied by goblet cells (IM⁻). For in vitro experiments, we employed human esophageal epithelial cell lines (OE33, OE19, and Het-1A). After forced Cdx2 expression by applying a Cdx2 expression vector to the cells, changes in the expressions of Notch1, Hes1, ATOH1, Cdx2, and MUC2 were analyzed by real-time PCR and western blot analysis. Changes in expressions of Notch1, Hes1, ATOH1, Cdx2, and MUC2 in cells were analyzed following stimulation with bile acids in the presence or absence of Cdx2 blocking with Cdx2-siRNA. Suppressed Hes1 and enhanced ATOH1 and MUC2 expressions were identified in IM⁺ specimens. Forced expression of Cdx2 in cells suppressed Hes1, and enhanced ATOH1 and MUC2 expressions, whereas bile acids suppressed Hes1, and enhanced ATOH1, Cdx2, and MUC2 expressions. On the other hand, these effects were blocked by siRNA-based Cdx2 downregulation. Enhanced expression of Cdx2 by stimulation with bile acids may induce intestinal differentiation of esophageal columnar cells by interaction with the Notch signaling pathway.

Background and Aim: Endoscopic definitions of Barrett's esophagus (BE) vary among countries, mainly because of the difficulty in diagnosing short-segment BE (SSBE) endoscopically. The aim of this study was to investigate whether the endoscopic identification of squamous islands and the specific position of columnar epithelium helps improve the diagnosis of SSBE. Methods: First, we prospectively enrolled 100 consecutive patients with SSBE and evaluated the number of identified squamous islands in the columnar epithelium with different modalities: white light (WL), narrow band imaging (NBI), and iodine chromoendoscopy. Second, in another group of 100 consecutive patients with tongue-like SSBE, the correlation of the location of Barrett's mucosa to the esophageal longitudinal folds (ridge or valley) was evaluated endoscopically. Results: It was possible to detect squamous islands in 48, 71, and 75 patients by WL, NBI, and iodine chromoendoscopy, respectively. The detection rate of squamous islands by NBI or iodine chromoendoscopy was significantly superior to that by WL. Tongue-like SSBEs were predominantly found on the ridge of mucosal folds (71%), similar to the location of mucosal breaks (84%). Conclusions: Squamous islands in the columnar epithelium were efficiently observed by NBI or iodine chromoendoscopy. SSBE was found more frequently on the ridges but not in the valleys of esophageal longitudinal mucosal folds. NBI endoscopic observation focusing on columnar epithelium with squamous islands on the ridges of distal esophageal folds may improve endoscopic detection of SSBE.

Background/Aims: Endoscopic definitions and management of Barrett’s esophagus vary widely among countries. To examine the current situation regarding diagnosis, epidemiology, management and treatment of Barrett’s esophagus in East Asian countries using a questionnaire-based survey. Methods: Representative members of the Committee of the International Gastrointestinal Consensus Symposium developed and sent a questionnaire to major institutions in China, South Korea, Japan, Thailand, Indonesia, and the Philippines. Results: A total of 56 institutions in the 6 countries participated in the survey. We found that the presence of specialized columnar metaplasia is considered to be important for diagnosing Barrett’s esophagus in East Asian countries except for Japan. C&M criteria have not been well accepted in East Asia. The palisade vessels are mainly used as a landmark for the esophagogastric junction in Japan. The prevalence of long segment Barrett’s esophagus is extremely low in East Asia, while the prevalence of short segment Barrett’s esophagus is very high only in Japan, likely due to different diagnostic criteria. Conclusion: Among East Asian countries, we found both similarities and differences regarding diagnosis and management of Barrett’s esophagus. The findings in the present survey are helpful to understand the current situation of Barrett’s esophagus in East Asian countries.

This collection of summaries on endoscopic diagnosis of Barrett's esophagus (BE) includes the best endoscopic markers of the extent of BE; the interpretation of the diagnosis of ultra-short BE; the criteria for endoscopic grading; the sensitivity and specificity of endoscopic diagnosis; capsule and magnifying endoscopy; narrow band imaging; balloon cytology; the distinction between focal and diffuse dysplasia; the techniques for endoscopic detection of dysplasia and the grading systems; and the difficulty of interpretation of inflammatory or regenerative changes.

Goals To investigate the relationship between fatty acid synthase (FASN) expression and the clinicopathological characteristics of Barrett's esophagus and its carcinogenesis. Background FASN, a key enzyme of the fatty acid biosynthetic pathway, is overexpressed not only in various types of cancer, but also in premalignant conditions. Therefore, FASN overexpression is considered to be indicative of a possible premalignant stage. Study Patients (N=354) with endoscopically and histologically proven Barrett's esophagus were enrolled. Mucin phenotyping of Barrett's esophagus, expression of FASN and COX-2, cellular proliferation, and apoptosis were evaluated immunohistochemically in biopsy samples, and factors influencing FASN expression were determined by multivariate logistic regression analysis. To evaluate if gastric reflux induces FASN expression, esophageal adenocarcinoma cells were treated with bile acid and low pH, and the effect of a FASN inhibitor on cell proliferation was assessed. Results Expression of FASN protein was observed in 52.2% of patients with Barrett's esophagus by immunohistochemistry; this expression pattern was retained in esophageal adenocarcinoma. Intestinal mucin phenotype, COX-2, increased stromal angiogenesis, and elevated proliferating cell nuclear antigen index were confirmed to be positive independent factors for FASN expression. In the esophageal adenocarcinoma cell line SEG-1, FASN mRNA was induced by bile acid with low pH. Cell proliferation was strongly suppressed by the FASN inhibitor C75. Conclusions FASN is strongly expressed in the intestinal mucin phenotype of Barrett's esophagus, in which Barrett's glandular cells display elevated cellular proliferation, angiogenesis, and COX-2 expression. Exposure of the lower esophagus to bile acid with low pH may induce FASN in Barrett's esophagus.

Eosinophilic esophagitis is a rare chronic disease that mainly occurs in middle-aged males. Treatment with a glucocorticoid and/or proton pump inhibitor is usually necessary to relieve unpleasant symptoms. An 83-year-old female patient with dysphagia and heartburn was diagnosed with eosinophilic esophagitis based on endoscopic findings, while histological examination identified dense infiltration of intraepithelial eosinophils. The symptoms and eosinophil infiltration spontaneously disappeared without any treatment approximately 2 months later. No obvious lifestyle or dietary changes to explain elimination of possible antigens were identified in this case. We report an atypical case of eosinophilic esophagitis with spontaneous regression.

Background and Aim: The purpose of the present study was to investigate the clinical significance of the highly sensitive fucosylated fraction of α-fetoprotein (hs-AFP-L3) in patients with chronic liver disease (CLD) and low serum α-fetoprotein (AFP) concentration. Methods: A total of 241 patients being treated at our institute with CLD and low serum AFP concentration (3–10 ng/mL) were investigated retrospectively. We measured total AFP and the percentage of AFP-L3 using a µTAS Wako i30 device. The possible presence of hepatocellular carcinoma (HCC) was thoroughly investigated by various examinations carried out from 1 month before to 1 month after measurements. In addition, hs-AFP-L3 elevated and non-elevated groups, divided by the cut-off value based on a receiver–operator characteristic (ROC) curve, were followed for possible future development of HCC. Results: hs-AFP-L3 was above the detectable range in 60 patients (24.9%). Among those AFP-L3 positive cases, 20 (33.3%) were found to be HCC prevalent, whereas HCC was found in just 16 patients (8.8%) with undetectable hs-AFP-L3 levels. We determined the cut-off value of hs-AFP-L3%, which shows the proportion of AFP L3 in total AFP, to be 5.75%. During the follow-up period, HCC was newly detected in six patients (22.2%) in the hs-AFP-L3% elevated group and in 10 (5.6%) in the non-elevated group. Analysis using the Kaplan–Meier method showed the HCC-free rate of the hs-AFP-L3% elevated group was significantly lower than that of the non-elevated group (P = 0.0038). Independent predicting variants were female sex (P = 0.0024) and hs-AFP-L3% elevation (P = 0.0036). Conclusion: Our results suggest hs-AFP-L3 level is a useful tumor marker for HCC in patients with CLD and low serum AFP concentration.

Background Kyphosis is a risk factor for the presence of hiatal hernia, which is a strong predictor of Barrett's esophagus. However, the association between kyphosis and Barrett's esophagus has not yet been clarified. To investigate this relationship, the Cobb angle, a marker of kyphosis, was measured in patients with and without Barrett's esophagus. Methods From January 2006 to December 2010, 26 patients with long-segment Barrett's esophagus (LSBE) were retrospectively enrolled. As the comparative groups, 100 consecutive patients with short-segment Barrett's esophagus (SSBE) and 100 consecutive control patients without Barrett's esophagus were also enrolled in this study. Cobb angles were measured on lateral chest radiographs, and kyphosis was defined as a Cobb angle of greater than 50°. Kyphosis, along with other patient characteristics, were evaluated as possible predictors for SSBE and LSBE. Results The mean Cobb angles in the non-BE, SSBE, and LSBE groups were 31.6° (95% CIs, 29.3°-33.9°), 34.8° (32.1°-37.4°) and 49.4° (44.9°-53.9°), respectively. Statistically significant differences were found between the LSBE and the other 2 groups (p

Objectives The mechanism of transformation to intestinal metaplasia in Barrett9s oesophagus has not been clarified. We previously reported that bile acids activate the Cdx2 promoter via nuclear factor kappa B (NF-κB) and stimulate production of Cdx2 protein in oesophageal keratinocytes, resulting in production of intestinal-type mucin. Kruppel-like factor 4 (KLF4) is an important transcription factor in the development of intestinal mucosa and has similar functions as Cdx2. In the present study, we investigated the direct effects of bile acids on KLF4 expression as well as the precise mechanisms of expression in cultured oesophageal squamous epithelial cells. Methods We investigated the expression of KLF4 in rat and human Barrett9s epithelium specimens, while the response of that expression to bile acids was studied using a KLF4 promoter luciferase assay. In addition, oesophageal squamous epithelial cells were transfected with a KLF4 expression vector, after which their possible transformation into intestinal-type epithelial cells was investigated. Results In both rat and human tissues, Barrett9s epithelium strongly expressed KLF4. Furthermore, a bile acids mixture increased KLF4 promoter activity, and mRNA and protein expression in oesophageal epithelial cells. Results from mutation analysis of the KLF4 promoter suggested that the NF-κB binding site is responsible for bile acid-induced activation of the KLF4 promoter. In addition, KLF4 and Cdx2 stimulated each other by directly binding to the promoter of the other, while transfection of the KLF4 expression vector in oesophageal epithelial cells induced production of MUC2 protein. Conclusion Bile acid-induced sequential expression of KLF4 followed by MUC2 production may have an important role in the development of Barrett9s epithelium.

The molecular basis of attaining columnar phenotype in Barrett's esophagus is poorly understood. One hypothesis states that factors locally produced by cells of mesenchymal origin in chronic reflux esophagitis induce metaplastic transformation. This study was performed to elucidate the factors secreted from fibroblasts that cause columnar phenotype in adjacent squamous epithelium. Human fibroblast cells were exposed to acidified medium for 20 min, followed by medium neutralization for 2 h, and then total RNA was hybridized to Sentrix Human-6 Expression BeadChips. Furthermore, esophageal mucosal biopsy specimens from reflux esophagitis patients were examined for HB-EGF expression using immunohistochemistry. In addition, cells from the human esophageal squamous epithelial cell line HET1A were treated with recombinant HB-EGF, and changes in expressions of Cdx2 and columnar markers were analyzed. The gene expression profile revealed significant upregulation of a variety of growth factors and inflammatory chemokines in response to acid exposure. Among them, HB-EGF was upregulated more than 10-fold. Biopsy specimens from reflux esophagitis patients showed a strong expression of HB-EGF in fibroblast cells underlying the damaged epithelium. Furthermore, in vitro stimulation of HET1A cells with HB-EGF increased Cdx2 in dose-dependent manners. Functional analysis of human Cdx2 promoter also revealed its upregulation by HB-EGF stimulation, showing the role of potential responsive elements (AP-1 and NF-kappaB) for its transcriptional activation. Moreover, the columnar markers cytokeratin 7 and villin were also upregulated by HB-EGF stimulation. HB-EGF induces several genes characteristics of columnar phenotypes of esophageal squamous epithelium in a paracrine manner.

Background/Aims: Newly developed autofluorescence (AF) imaging (AFI) endoscopy can detect AF emitted by the gastrointestinal wall and may reliably detect tumors or inflammation that block AF. However, the efficacy of AFI endoscopy has not been evaluated for diagnosing the depth of tumor invasion in gastric cancer. Methods: AF endoscopic images were split into three bands (R, G and B) and expressed as grayscale values. AF indices, defined as the ratio of the G band image grayscale value to that of the R band, were calculated preoperatively. Correlations of AF indices with invasion depth and tumor thickness were assessed. AF indices were calculated preoperatively for 72 gastric cancer lesions without ulceration in 67 patients. The invasion grade of the lesions was classified histologically into 5 groups: M, SM, MP, SS and SE. Results: The mean tumor AF indices for each depth stage were 0.99, 0.77, 0.75, 0.74 and 0.61, respectively. A statistically significant difference was found between group M and the other groups. Conclusion: AFI endoscopy may reliably determine the depth of gastric cancer tumor invasion, although an expanded study comprised of larger numbers of subjects and different types of cancers may be required to clearly demonstrate its validity.

Sustained virologic response with peg-interferon and ribavirin combination therapy for 48 weeks is still inadequate. Our study examined whether short-term administration of retinol clinically influences the anti-viral activity of interferon early during interferon and ribavirin combination therapy. The control group received 6 MIU of interferon alpha-2b every day for two weeks and then 3 times a week for 22 weeks intramuscularly plus 600 mg or 800 mg per day of ribavirin orally for 24 weeks. The retinol group, in addition to above treatment, received retinol 30,000 units per day orally for 3 weeks from one week before the start of interferon alpha-2b plus ribavirin combination therapy. The hepatitis C virus (HCV) RNA negativity rate at 1 week after the end of interferon alpha-2b and ribavirin combination therapy was 46.7% (28/60) for the retinol group and 31.7% (19/60) for the control group, which was significantly higher for the retinol group. The level of serum HCV RNA in the retinol group was significantly lower at 1 week after beginning treatment as compared to the control group (p0.01). Furthermore, serum 2,5'AS protein at 1 week after beginning treatment was significantly higher in the retinol group (p = 0.0002). The results suggest that retinol supplement increases the antiviral effect of interferon alpha-2b plus ribavirin only during the administration of IFN alpha-2b, ribavirin and retinol in patients with chronic hepatitis C.

The diagnosis of Barrett's esophagus (BE) requires an accurate recognition of the columnar-lined esophagus at endoscopy. However, a universally accepted standardized endoscopic grading system of BE was lacking prior to the development of the Prague 'circumferential and maximal' criteria. In this system, the landmark for the esophagogastric junction (EGJ) is the proximal end of the gastric folds, not the distal end of the palisade vessels, which are used to endoscopically identify the EGJ in Japan. Although the circumferential and maximal criteria are clinically relevant, an important shortcoming of this system may be failure to identify short-segment BE, a lesion that is found frequently in the Japanese. To compare the diagnostic yield for BE when using the palisade vessels versus gastric folds as a landmark for the EGJ, we evaluated interobserver diagnostic concordance. The endoscopic identification of the EGJ using both landmarks resulted in unacceptably low kappa coefficients of reliability. However, there was a statistically significant improvement after the participants were thoroughly trained in identification of the EGJ during the endoscopic study. Although it remains controversial which landmark is better for the endoscopic diagnosis of BE, it is important to systematically educate and train endoscopists in order to improve diagnostic consistency in patients with BE.

Several components of the gastrointestinal tract including the esophagogastric junction (EGJ) show circumferential asymmetry in the formation of pathological lesions, which is caused by the morphological and functional asymmetry of the gastrointestinal tract. Pressure in the lower esophageal sphincter (LES) is higher on the left posterior side as compared to the right anterior side, which may partly explain why Mallory-Weiss tears frequently occur on the right side wall of the EGJ. Lower LES pressure in the right anterior wall may not effectively prevent gastroesophageal reflux on this side and may be a reason why esophageal erosions in patients with reflux esophagitis, short segment Barrett's esophagus, and adenocarcinomas associated with short segment Barrett's esophagus are frequently found in the right anterior wall of the esophagus. In addition, acidic gastroesophageal reflux may also cause rupture of esophageal varices predominantly on that side. Thus, asymmetrical LES pressure may be a cause of the right anterior side predominance of diseases found in this part of the gastrointestinal tract.

MFG-E8 (milk fat globule-epidermal growth factor 8) deficiency is strongly associated with acquisition of immune-mediated disorders due to the loss of tissue homeostasis. However, comparatively little is known regarding its functions in gastrointestinal tract disorders, in which immune homeostasis is a major concern. Herein, we report altered MFG-E8 expression in inflamed colons during the acute phase of murine experimental colitis and found that treatment with recombinant MFG-E8, but not its arginine-glycine-aspartate mutant counterpart, ameliorated colitis by reducing inflammation and improving disease parameters. To reveal the MFG-E8-mediated antiinflammatory mechanism, we employed an in vitro system, which showed the down-regulation of NF-κB in an LPS-dependent manner. Additionally, MFG-E8 altered αvβ3 integrin-mediated focal adhesion kinase phosphorylation by impeding the binding of one of its potent ligands osteopontin, which becomes activated during colitis. Taken together, our results indicated that MFG-E8 has a novel therapeutic potential for treatment of colitis.

CD5(+) B cells comprise a unique subset of B cells that modulates innate as well as autoimmune systems. The aim of this study was to investigate alterations of the circulating CD5(+) B-cell subset in patients with inflammatory bowel disease (IBD) by evaluating various clinical parameters, including therapeutic regimens.Thirty-four patients with ulcerative colitis (UC), 19 patients with Crohn's disease (CD), and 46 healthy control subjects were enrolled in this study. CD5(+) B cells in peripheral blood collected from each subject were analyzed by flow cytometry. Multiple regression analysis was carried out to evaluate the factors related to the circulating CD5(+) B-cell subset in the IBD patients. In an in vitro examination, dexamethasone-induced apoptosis in peripheral blood B cells was examined by detecting cell surface binding of the annexin-V antibody.Age and gender in the control subjects did not influence the circulating CD5(+) B-cell subset. Multiple regression analysis showed that the presence of UC, corticosteroid therapy, and number of white blood cells in peripheral blood each had a significant influence in decreasing the number of circulating CD5(+) B cells in the IBD patients. Furthermore, in vitro results showed that dexamethasone treatment significantly induced apoptosis in CD5(+) B cells, though apoptosis was similarly observed in CD5(-) B cells.CD5(+) B cells may be involved in the pathogenesis of UC, and modulation of this subset by corticosteroid therapy may play a role in the treatment of IBD patients.

AIM To determine the prophylactic effect of antibiotics administration in the prevention of infection following an ultrasound-guided percutaneous liver biopsy or treatment of liver tumors, we performed an open-labeled randomized prospective study of patients who received prophylactic antibiotics after undergoing those procedures. METHODS We studied 101 patients, with ultrasound-guided percutaneous aspiration biopsies of the liver performed in 48 to diagnose diffuse liver diseases or liver tumors, while percutaneous ethanol-injection therapy was performed in two patients with malignant liver tumors and percutaneous radiofrequency ablation was performed in 51 patients. An oral administration of levofloxacin at 400 mg/day was given to 50 of the enrolled patients from the morning of the treatment day for three days. Preventive antibiotics were not administered to the remaining 51 patients. Body temperature, peripheral blood leukocyte number, c-reactive protein, alanine aminotransferase, and lactic dehydrogenase were measured daily for three days after treatment. RESULTS Most parameters changed following percutaneous treatments of liver tumors, though no significant differences were seen between the patients treated with antibiotics and those untreated. Most significantly, there was no difference in the frequency of post-procedure infection between the groups. CONCLUSION Our results suggest that prophylactic administration of antibiotics following a percutaneous liver biopsy and treatment of liver tumors does not have a significant impact on the post-procedure results or incidence of infection.

Background and Aim: Accelerated cellular proliferation in Barrett's esophagus has been implicated in Barrett's elongation and malignant transformation. Therefore, growth factors may play important roles in the pathophysiology of Barrett's esophagus. Regenerating gene (REG), an epithelial growth factor, has been reported to link mucosal inflammation and subsequent carcinogenesis in the gastrointestinal tract. The aim of this study was to investigate whether REG is expressed in Barrett's esophagus and to elucidate the relation- ship between REG protein expression and clinicopathological factors of Barrett's esophagus. Methods: Between July 2003 and June 2004, 266 patients with endoscopically and his- tologically proven Barrett's esophagus were enrolled in this study. Before endoscopic examination, all participants were requested to answer structured questionnaires on gas- troesophageal reflux symptoms and drugs usage. Mucin phenotype, cyclooxygenase-2 expression, cellular proliferation, apoptosis and REG Ia protein expression were investi- gated in the biopsy samples taken from Barrett's esophagus. Clinicopathological factors that correlated with REG Ia protein expression in patients with Barrett's esophagus were evaluated using multivariate logistic regression analysis. Results: REG Ia protein expression was observed in 48 (18.0%) of 266 patients with Barrett's esophagus by immunohistochemistry. Newly developed squamous re-epithelialization of Barrett's esophagus at biopsy sites, presence of hiatal hernia and aging were shown to correlate with REG Ia protein expression. Conclusions: The present study is the first to show REG expression in Barrett's esopha- gus. Expression of REG Ia was more frequently observed in patients who showed squa- mous re-epithelialization of Barrett's esophagus at biopsy sites.

Background and Aim: It has been reported that the prevalence of hiatal hernia (HH) and reflux esophagitis (RE) increases with age, as does the degree of arteriosclerosis. However, it has not been investigated whether or not arteriosclerosis is correlated with the presence of HH and RE. Therefore, we prospectively investigated the degree of arteriosclerosis in patients with HH and RE compared with subjects without HH and RE. Methods: We prospectively enrolled 1683 people who visited Shimane Environment and Health Public Corporation for annual medical check-ups. All subjects were investigated by upper gastrointestinal endoscopy for the possible presence of HH and RE. Factors used for assessing cardiovascular risk were sex, age, body mass index (BMI), smoking and drinking habits, serum total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol (HDLC). Arteriosclerosis was investigated by measuring systolic blood pressure, heart-carotid pulse wave velocity (HCPWV), bilateral ankle brachial index (ABI) and heart-ankle PWV (HAPWV). Results: The number of patients with HH and RE was 624 (37.1%) and 143 (8.5%), respectively. The HDLC level of the patients with HH was significantly lower, and the levels of BMI, TG and arteriosclerotic parameters were higher than those of the subjects without HH after adjusting for confounding factors (sex, age and smoking and drinking habits). Cardiovascular and arteriosclerosis parameters except for TG did not differ between the subjects with and without RE. Conclusion: Levels of arteriosclerosis parameters in patients with HH were higher than in those without HH. However, the association between arteriosclerosis and presence of RE was not clarified.

Background: Gastroesophageal reflux occurs mainly during the daytime in patients with Los Angeles grade A esophagitis, but predominantly during the night in patients with grade C and D esophagitis. The purpose of the present paper was to investigate whether this difference in the pattern of gastroesophageal reflux influences the circumferential localization of erosions in the esophageal wall. Methods: The subjects were 394 consecutive patients diagnosed endoscopically as having reflux esophagitis (grade A, n = 223; B, n = 93; C, n = 53; D, n = 25 cases). Their endoscopic films were reviewed retrospectively to determine the circumferential location of esophageal mucosal breaks, and also the prevalence and size of hiatal hernia (HH). Results: The numbers of mucosal breaks analyzed in patients with grade A, B and C esophagitis were 321, 173 and 54, respectively. Patients with grade A and B esophagitis had longitudinal mucosal breaks mainly in the right-anterior wall of the lower esophagus, whereas patients with grade C esophagitis had transverse mucosal breaks mainly in the posterior wall. The prevalence and size of HH was significantly higher and larger, respectively, in patients with grade C or D esophagitis than in those with grade A and B esophagitis. Conclusion: The circumferential location of esophageal mucosal breaks differs significantly among different grades of esophagitis.

Background and Aim: The size of radiofrequency ablation (RFA) in the liver can be negatively influenced by the surrounding blood flow. The indocyanine green (ICG) test can be used to evaluate the effective blood flow in the liver, and distance from the hilus can affect local blood flow. The aim of this study was to assess whether the ICG test or distance from the hilus could be used to predict the size of the ablated area in liver by RFA treatment of hepatocellular carcinoma (HCC) nodules. Methods: The RFA measurements of 44 HCC nodules in 39 patients were retrospectively studied. Cases were included if they met the following criteria: (i) no catheter treatment before RFA; (ii) no movement of the RFA device; (iii) strict ablation time; and (iv) only one ablation. In all patients, ICG-R15 testing was done immediately before RFA and the initial therapeutic efficacy was evaluated by dynamic computed tomography scanning 2–5 days after RFA. The correlation between the maximum size of the RFA area and the ICG test results or the distance of the target area from the hilus (site of first portal vein divergence) were analyzed statistically. Results: The ICG-R15 result was significantly correlated with the maximum diameter of the ablated area both in 2 cm-electrode tip length (R2 = 0.35, P = 0.0012), and in 3 cm-tip length (R2 = 0.26, P = 0.0377). Multiple-regression analysis showed that the electrode tip length (P = 0.0010) and ICG-R15 (P = 0.0046) were independent factors that could predict the maximum diameter of the RFA area. Conclusion: The results of ICG testing can be used to predict the size of the area that will be ablated at a target liver site before RFA treatment.

A 52-year-old woman presented to our hospital with dysphagia. The initial endoscopic examination revealed plaques on the esophageal mucosa that were consistent with candidiasis, as well as narrowing of the distal one-third of the esophagus. After 7 days of administration of antimycotic drugs, endoscopy and esophagography showed multiple small saccular diverticula in the lower esophagus. Dysphagia continued despite resolution of candidiasis. Based on a diagnosis of esophageal intramural pseudodiverticulosis, we performed endoscopic balloon dilatation of the stenosis, which resulted in the disappearance of clinical symptoms.

Background and Aim: Endoscopic retrograde cholangiopancreatography (ERCP) is a useful diagnostic and therapeutic procedure; however, ERCP occasionally causes post-ERCP pancreatitis. The administration of gabexate mesilate has been reported to be effective for the prevention for post-ERCP pancreatitis when given during and after the procedure. The aim of the present study was to investigate the preventive effect of the novel protease inhibitor ulinastatin on post-ERCP pancreatitis. Methods: One hundred and thirty-nine patients who underwent the ERCP procedure were studied. These patients were randomly divided into three groups based on the agent and dose given during and following the ERCP procedure: gabexate mesilate (900 mg), high-dose ulinastatin (450 000 units) and low-dose ulinastatin (150 000 units). Serum amylase, interleukin (IL)-6 and IL-8 levels and plasma polymorphonuclear leukocyte elastase (PMN-E) activity were measured after ERCP. In addition, post-ERCP hyperamylasemia and post-ERCP pancreatitis were recorded. Results: There were no significant differences in serum amylase, IL-6 and IL-8 levels and PMN-E activity after ERCP procedure between the three groups. Post-ERCP pancreatitis was observed in two (4.3%), three (6.5%) and four (8.5%) cases in the gabexate mesilate, high-dose ulinastatin and low-dose ulinastatin groups, respectively. Multiple logistic regression analysis showed that the addition of endoscopic sphincterotomy during the ERCP procedure was the only significant risk factor for the development of post-ERCP hyperamylasemia and post-ERCP pancreatitis (P = 0.03 and P = 0.04, respectively), but there was no significant difference in the occurrence of post-ERCP hyperamylasemia and post-ERCP pancreatitis between the three groups receiving different preventative treatments. Conclusion: The administration of low- and high-dose ulinastatin has similar effects to high-dose gabexate in the prevention of post-ERCP pancreatitis.

Eosinophilic esophagitis (EE) is a rarely diagnosed condition involving eosinophilic infiltration of the esophageal mucosa. Here we present a case of EE in a 69-year-old Japanese man, who presented with abdominal pain, appetite loss, and a history of bronchial asthma. Laboratory findings included peripheral eosinophilia and an increased serum immunoglobulin E level. Computed tomography showed diffuse severe thickening of the esophageal wall, and a barium esophagogram revealed a small caliber of the middle and lower portion of the esophagus, without normal peristaltic contractions. Endoscopy of the esophagus showed a pale mucosa, with adherent whitish exudates resembling fungal infection, and prominent ring-like contractions. Histologic examination of a biopsy specimen revealed marked eosinophil infiltration into the esophageal mucosa. Endoscopic ultrasonography (EUS) demonstrated marked circumferential thickening of the esophageal submucosal layer, and an esophageal manometry study showed a high percentage of ineffective esophageal peristalsis and high-amplitude esophageal body contractions. EUS findings showed no change even after oral corticosteroid therapy, although the histological findings were improved. This is thought to be the first documented Japanese case of EE. EE should be considered in the differential diagnosis in cases of esophageal motility disturbance, even if the patients do not complain of dysphagia.

We present a 72-year-old female patient with mucosal Barrett's cancer. Although preoperative diagnosis suggested tumor invasion throughout the mucosal layer, she was treated by endoscopic mucosal resection at her preference. The tumor invasion depth was “m-3.” However, tumor cells were observed along the endothelium of a small vein. Following endoscopic treatment, ultimately the patient underwent radical surgery. Neither residual tumor nor lymph node metastasis was found in the resected specimens. We also reviewed published reports regarding the relationship between tumor depth and vessel involvement in early-stage Barrett's cancer. In Barrett's cancer with a tumor invasion of m-3 where tumor had invaded throughout the mucosal layer, blood or lymphatic vessel invasion was observed in 12.5% of cases (6/48). However, no lymph node metastasis was found. Therefore, we considered that endoscopic mucosal ablation therapy may be applicable to treat intramucosal Barrett's cancer with a tumor invasion depth of m-3.

We recently demonstrated that the pattern recognition receptors (PRRs) toll-like receptor 2 (TLR2), TLR4, and CD14 are expressed in mouse colonic epithelium in a compartmentalized manner. Here we report the localization of TLR5, the receptor for bacterial flagellin, and its distinctive down-regulation during experimental colitis. Guts from normal BALB/c mice and those with dextran sodium sulfate (DSS)-induced colitis were compared. Each gut was divided into seven segments (stomach, small intestine [three parts], and colon [three parts]), and epithelial cells and crypt units were collected by scraping and EDTA treatment, respectively. Northern blotting showed that TLR5 mRNA was preferentially expressed in the epithelium of the proximal colon in normal mice. Laser capture microdissection coupled to reverse transcriptase PCR confirmed this localization. TLR5 protein expression reflected mRNA expression, as evidenced by Western blotting. In mice with acute colitis, inflammation occurred mainly in the distal colon. Interestingly, while TLR2, TLR4, and CD14 were up-regulated in the inflamed colon, TLR5 was down-regulated at both the mRNA and protein levels. Decreased TLR5 expression was more evident during chronic colitis. Additional in vitro studies using a mouse cell line, Colon-26, showed that gamma interferon (IFN-γ) time- and dose-dependently down-regulates TLR5. In conclusion, epithelial cells, mainly in the proximal colon, constitutively express TLR5. TLR5 expression is down-regulated in vivo during acute and chronic DSS-induced colitis, in contrast to the expression of TLR2, TLR4, and CD14. The mechanism governing TLR5 regulation may therefore differ from that controlling other PRRs. Finally, IFN-γ may be involved in down-regulating TLR5 expression.

M-typing was conducted for Streptococcus pyogenes strains isolated within 1 week of admission from patients admitted to the Tokyo Metropolitan Toshima Hospital for scarlet fever in the 23-year period between 1956 and 1978. M12 was detected in the largest number of patients, followed by M6, M4, M3, and M1. T-typing was also conducted for Streptococcus pyogenes strains isolated from healthy schoolchildren in three different parts of the 20-year period between 1977 and 1998. T12 was detected in the largest number of children, followed by T28, T1, T4, and T6. These results suggested that strains of similar types are prevalent in scarlet fever patients and healthy carriers, that these strains become prevalent at intervals of several years, and that they are detected every year, albeit in a small number of persons, indicating that they are endemic. Isolated strains were typed by M-typing and T-typing. The results of typing were identical in more than 90% of cases. Comparison of major Streptococcus pyogenes strains isolated in Tokyo and three other major cities abroad showed that M12 was detected in the largest number of persons in Tokyo and New York and that major types were similar in the four cities.

Hereditary spherocytosis is a disease with chronic hemolytic anemia found mostly in childhood. We encountered a rare case of sporadic hereditary spherocytosis in a 68-year-old woman who developed periodic jaundice caused by hemolytic crises. Since the hemolytic crises were caused by cholelithiasis-related biliary inflammation, administration of ursodeoxycholic acid was useful for the prevention of the hemolytic crises. In the differential diagnosis of periodic increases in indirect bilirubin, the possibility of hemolytic diseases, including hereditary ones, should be considered, even if the patients are elderly.

Background and Aim: The influence of Helicobacter pylori on gastric acid secretion differs with the status of gastritis. The histological characteristics of gastritis in H. pylori-positive patients with reflux esophagitis have not been fully investigated. We therefore studied the pattern of endoscopic gastric mucosal atrophy and degree of histological gastritis in such patients. Methods: Subjects comprised 41 H. pylori-positive patients with reflux esophagitis, 41 age- and sex-matched patients with duodenal ulcer, and 41 patients with early gastric cancer. The endoscopic pattern of gastric mucosal atrophy was reviewed, and the degree of histological gastritis in biopsy specimens from the antrum and corpus was assessed in accordance with the updated Sydney system. Results: The grade of endoscopic and histological gastric mucosal atrophy in patients with reflux esophagitis was significantly lower than that in patients with gastric cancer, and the histological scores for antral atrophy and metaplasia in patients with reflux esophagitis tended to be lower than those in patients with duodenal ulcer. In patients with reflux esophagitis and duodenal ulcer, the scores for antral inflammation and activity tended to be higher than those for the corpus. Conversely, the inflammation and activity score in patients with early gastric cancer showed a corpus-predominant gastritis pattern. Conclusion: In H. pylori-positive patients with reflux esophagitis, the degree of endoscopic gastric mucosal atrophy is low and histologically there is an antral-predominant gastritis pattern. Therefore, gastric acid secretion in H. pylori-positive patients with reflux esophagitis may be augmented by H. pylori infection.