Endoscopic ultrasound-assisted rendezvous by transgastric approach in malignant extrahepatic bile duct stricture.

Endoscopic ultrasonography rendezvous (EUS-RV) is useful in cases of difficult deep biliary cannulation. However, in malignant extrahepatic bile duct strictures (MEHBDS), transduodenal routes are challenging and the transgastric approach often requires fistula dilation. We report a case of resectable MEHBDS in which transgastric puncture from the antrum of the stomach as EUS-RV was useful.

Significance of Conducting 2 Types of Fecal Tests in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: We compared the diagnostic accuracy of the fecal calprotectin (FCP) test vs the fecal immunochemical blood test (FIT) in determining the endoscopic severity and predicting outcomes of patients with ulcerative colitis (UC). METHODS: We performed a nationwide study of 879 patients with UC, enrolled at medical centers across Japan, from March 2015 to March 2017. We collected data on fecal biomarkers, endoscopic severities, and other clinical indices from Cohort 1 (n = 427) and assessed the diagnostic accuracy of FCP measurement and FIT results in determining clinical severity, based on Mayo score, and endoscopic remission, based on Mayo endoscopic sub-score (MES) or UC endoscopic index of severity. We also followed 452 patients in clinical remission from UC (Cohort 2) for 12 months and evaluated the associations of FCP levels and FIT results with clinical recurrence. RESULTS: The levels of FCP and FIT each correlated with the MES and UC endoscopic index of severity. There were no significant differences in the areas under the curve of FCP vs FIT in distinguishing patients with MES≤1 from those with MES≥2 (P = .394) or in distinguishing patients with MES=0 from those with MES≥1 (P = .178). Among 405 patients in clinical remission at baseline, 38 (9.4%) had UC recurrences within 3 months and 90 (22.2%) had recurrences within 12 months. FCP≥146 mg/kg (hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.80-8.33) and FIT≥77 ng/mL (HR, 2.92; 95% CI, 1.76-4.83) were independently associated with clinical recurrence within 12 months. UC recurred within 12 months in 69% of patients with levels of FCP≥146 mg/kg and FIT ≥77 ng/mL; this value was significantly higher than the rate of recurrence in patients with levels of FCP≥146 mg/kg and FIT <77 ng/mL (31.5%, P < .001) or patients with levels of FCP<146 mg/kg and FIT ≥77 ng/mL (30.0%, P < .001). CONCLUSION: In a nationwide study of patients with UC in Japan, we found that the level of FCP and FIT could each identify patients with endoscopic markers of disease severity (MES≥2). The combination of FCP and FIT results can identify patients in remission who are at risk for disease recurrence. Clinical Trials Registry no: UMIN000017650 (http://www.umin.ac.jp/ctr/).

Crohn's Disease Accompanied with Small Intestinal Extramedullary Plasmacytoma.

We herein present the case of an immunocompetent 63-year-old man who had previously undergone resection of Crohn's disease (CD)-related small intestinal obstruction more than 30 years ago. He had not been receiving any medication for many years, but had recently started to suffer from ileus. A stenosed site of ileo-cecal anastomosis was identified and therefore was surgically resected, which was diagnosed as CD with small intestinal extramedullary plasmacytoma (EMP). The subsequent progression of CD was successfully controlled by anti-TNFα agents without any recurrence of EMP for over 3 years, implying the clinical benefit and safety of the biological therapy. This was the first known case of a patient who received anti-TNFα agents after a resection of small intestinal EMP accompanied with CD.

Atypical Clinical Presentation of Crohn's Disease with Superior Mesenteric Vein Obstruction and Protein-losing Enteropathy.

We herein report a 44-year-old man suffering from systemic edema due to protein-losing enteropathy (PLE) with superior mesenteric vein (SMV) obstruction and development of collateral veins, which subsequently proved to be a chronic result of thrombosis and a complication of Crohn's disease (CD). PLE was supposedly induced by both intestinal erosion and thrombosis-related lymphangiectasia, which was histologically proven in his surgically-resected ileal stenosis. Elemental diet and anti-TNFα agent improved his hypoalbuminemia after surgery. The rarity of the simultaneous coexistence of SMV obstruction and PLE and the precedence of these complications over typical abdominal symptoms of CD made the clinical course complex.

Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment.

The enhanced recruitment of leukocytes to the inflamed colon is a key feature of ulcerative colitis (UC). The gut-specific adhesion molecules involved in leukocyte recruitment have emerged as recent therapeutic targets. Nicotine absorbed from smoking has been reported to work protectively in UC patients. Our hypothesis is that nicotine may suppress the aberrant leukocyte recruitment and colonic inflammation via the suppression of the overexpressed gut-specific adhesion molecules in the inflamed colon. To test this hypothesis, the severity of colitis and the degree of leukocyte recruitment induced by gut-specific adhesion molecules were assessed in dextran sulfate sodium (DSS) colitis mice (C57BL/6J mice treated with 3% DSS) with or without nicotine treatment. We also studied the in vitro changes in the expression of adhesion molecules by using a vascular endothelial cell line. DSS-induced colitis was accompanied by increases in disease activity index (DAI), histological score, recruitment of leukocytes, and the expression of adhesion molecules, mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) and VCAM-1. Nicotine treatment significantly attenuated MAdCAM-1 expression, leukocyte recruitment, DAI, and histological score. The expression of ß7-integrin, the ligand for MAdCAM-1, on leukocytes was not affected by nicotine treatment. In vitro study, the TNF-α-enhanced mRNA expression of MAdCAM-1 was reduced by the coadministration of nicotine in a dose-dependent manner, possibly via nicotinic receptor activation. These results supported our hypothesis that nicotine treatment ameliorated colitis through the suppression of MAdCAM-1 expression on the microvessels in the inflamed colon. Further investigation is warranted on the role of nicotine in the treatment of UC.

Clinical differences between elderly-onset ulcerative colitis and non-elderly-onset ulcerative colitis: A nationwide survey data in Japan.

BACKGROUND AND AIM: Studies on the characteristics of elderly-onset ulcerative colitis (EOUC) and non-elderly-onset ulcerative colitis (NEOUC) have reported conflicting findings. The aim of this study was to compare disease characteristics of EOUC and NEOUC by analyzing the database of the Japanese nationwide inflammatory bowel disease (IBD) registry. METHODS: We analyzed the age of disease onset, sex, disease severity, and disease extent in patients with ulcerative colitis that were newly diagnosed and registered within 1 year between 2004 and 2009 (n = 28 179). We also analyzed the medical treatment, rate of IBD-related surgery, and postoperative complications. We compared them between younger than 65 years old (NEOUC group) and 65 years old or older (EOUC group) patients. RESULTS: A total of 25 401 (90.1%) and 2778 (9.9%) patients were included in the NEOUC and EOUC groups, respectively. In the EOUC group, disease activity was significantly higher, and extent of pathological changes in the colon more extended significantly. Laboratory findings showed that inflammatory markers were elevated significantly in the EOUC group. The proportion of those with IBD-related hospitalization was significantly higher in the EOUC group (54.2% vs 35.7%, P < 0.001). The proportion of patients who were treated with corticosteroids was significantly higher in the EOUC group (36.7% vs 30.8%, P < 0.001). Significantly more number of patients underwent IBD-related surgery in the EOUC group (0.68% vs 0.27%, P < 0.001). CONCLUSION: Elderly patients show higher disease activity, with a higher proportion requiring IBD-related hospitalization and IBD-related surgery, according to the nationwide registry in Japan.

Human intestinal spirochetosis mimicking ulcerative colitis.

Human intestinal spirochetosis (HIS) is a colorectal infection caused by the Brachyspira species of intestinal spirochetes, whose pathogenicity in humans remains unclear owing to the lack of or mild symptoms. We monitored the 5-year clinical course of a woman diagnosed with HIS in whom ulcerative colitis (UC) had been suspected. Following a positive fecal occult blood test, she underwent a colonoscopic examination at a local clinic where she was diagnosed with "right-sided" UC concomitant with incidentally detected HIS, and was referred to our hospital. Colonoscopic, histopathological, and cytological examination revealed localized erosive colitis in the ascending and the right transverse colon concomitant with HIS resembling skip lesions of UC. Initially, we chose the wait-and-watch approach; however, she gradually developed bloody diarrhea. Metronidazole improved her abdominal symptoms, as well as her colonoscopic and histopathological findings, suggesting that HIS was responsible for her colorectal inflammation. This case reveals (1) a possible pro-inflammatory role of HIS, (2) difficulties in diagnosing HIS in chronic proctocolitis, and (3) a possible inclusion of some HIS cases in "UC". HIS could mimic UC and might be included in differential diagnoses for UC. Antibiotic administration is necessary following the detection of HIS, particularly in patients demonstrating an atypical presentation of UC.

Novel probiotics isolated from a Japanese traditional fermented food, Funazushi, attenuates DSS-induced colitis by increasing the induction of high integrin αv/ß8-expressing dendritic cells.

BACKGROUND: We isolated two novel probiotics strains (s193 and s292) from Funazushi, which is a traditional Japanese fermented food, and evaluated its effects on DSS-induced colitis to determine the possible underlying mechanisms. METHODS: A single colony from homogenized Funazushi was isolated by its ability to suppress TNF-α in RAW 264.7. Effect of probiotics on colonic inflammation induced by DSS was evaluated. Effect of probiotics on Treg induction by CD11c+ dendritic cells (DCs) of MLNs were analyzed. RESULTS: Two novel probiotics strains classified into the genus Lactobacillus were isolated (s193 and s292), and those strains showed stronger anti-inflammatory effects on DSS-induced colitis than those of L. gasseri isolated from the gut. mRNA expression ß8 integrin in CD11c+DCs of MLNs and the number of Tregs in the large intestine were significantly increased by s193 and s292 administration compared with L. gasseri administration. Bone marrow DCs treated with s193 and s292 highly increased ß8 integrin, and those cells strongly induced differentiation of CD4+ T cells into Tregs. Differentiation of Tregs was remarkably inhibited by anti-ß8 integrin antibody treatment. CONCLUSIONS: Strains s193 and s292 demonstrate strong anti-inflammatory effects on DSS-induced colitis through induction of ß8 integrin expression on DCs. Our results suggested that Japanese traditional fermented foods are valuable sources for probiotics that are effective for IBD therapy and treatment.

Clinical features of inflammatory bowel disease of the elderly onset.

The incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally. IBD of the elderly is common with prevalence rates. Genetical background involve less in the pathophysiology older-onset of IBD. Response to drug therapies appears to be similar in elderly patients and younger patients. Corticosteroid treatment carries additional risk for elderly patients. In addition, poly-pharmacy and malignancies need to be taken into account. Pre-existing comorbidities and nutrition are important indicators of surgical outcomes. This article will review management of IBD in the elderly.

Psychological stress exacerbates NSAID-induced small bowel injury by inducing changes in intestinal microbiota and permeability via glucocorticoid receptor signaling.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are popular painkillers, but they have serious side effects, not only in the upper gastrointestinal tract but also in the small intestine. It is well known that psychological stress may exacerbate various gastrointestinal diseases. The aim of this study was to determine whether psychological stress exacerbates NSAID enteropathy and to determine the possible underlying mechanisms for this. METHODS: Experiment 1: mice were exposed to water avoidance stress (WAS) or sham stress for 1 h per day for 8 consecutive days, and then enteropathy was induced by indomethacin. Experiment 2: cecal contents from stress (-) or (+) mice were transplanted into mice that had received antibiotics and in which NSAID enteropathy had been induced without WAS. Experiment 3: mifepristone, a glucocorticoid receptor antagonist, was injected before WAS for 8 days. Small intestinal injury, mRNA expression of TNFα, intestinal permeability, and the microbial community were assessed. RESULTS: Psychological stress exacerbated NSAID enteropathy and increased intestinal permeability. Psychological stress induced changes in the ileal microbiota that were characterized by increases in the total number of bacteria and the proportion of Gram-negative bacteria. The increased susceptibility to NSAIDs and intestinal permeability due to WAS was transferable via cecal microbiota transplantation. The increased permeability and aggravation of NSAID enteropathy caused by WAS were blocked by the administration of mifepristone. CONCLUSIONS: This study demonstrated a relationship between NSAID enteropathy and psychological stress, and showed the utility of studying the intestinal microbiota in order to elucidate the pathophysiology of NSAID enteropathy. It also showed the impact of stress on the intestinal microbiota and the mucosal barrier in gastrointestinal diseases.

Platelet interaction with lymphatics aggravates intestinal inflammation by suppressing lymphangiogenesis.

Lymphatic failure is a histopathological feature of inflammatory bowel disease (IBD). Recent studies show that interaction between platelets and podoplanin on lymphatic endothelial cells (LECs) suppresses lymphangiogenesis. We aimed to investigate the role of platelets in the inflammatory process of colitis, which is likely to be through modulation of lymphangiogenesis. Lymphangiogenesis in colonic mucosal specimens from patients with IBD was investigated by studying mRNA expression of lymphangiogenic factors and histologically by examining lymphatic vessel (LV) densities. Involvement of lymphangiogenesis in intestinal inflammation was studied by administering VEGF-receptor 3 (VEGF-R3) inhibitors to the mouse model of colitis using dextran sulfate sodium and evaluating platelet migration to LVs. The inhibitory effect of platelets on lymphangiogenesis was investigated in vivo by administering antiplatelet antibody to the colitis mouse model and in vitro by coculturing platelets with lymphatic endothelial cells. Although mRNA expressions of lymphangiogenic factors such as VEGF-R3 and podoplanin were significantly increased in the inflamed mucosa of patients with IBD compared with those with quiescent mucosa, there was no difference in LV density between them. In the colitis model, VEGF-R3 inhibition resulted in aggravated colitis, decreased lymphatic density, and increased platelet migration to LVs. Administration of an antiplatelet antibody increased LV densities and significantly ameliorated colitis. Coculture with platelets inhibited proliferation of LECs in vitro. Our data suggest that despite elevated lymphangiogenic factors during colonic inflammation, platelet migration to LVs resulted in suppressed lymphangiogenesis, leading to aggravation of colitis by blocking the clearance of inflammatory cells. Modulating the interaction between platelets and LVs could be a new therapeutic means for treating IBD.

Endoscopic and clinical evaluation of treatment and prognosis of Cronkhite-Canada syndrome: a Japanese nationwide survey.

BACKGROUND: First reported in 1955, Cronkhite-Canada syndrome (CCS), a rare syndrome characterized by ectodermal abnormalities and inflammatory changes of the gastrointestinal tract mucosa, has been associated with a poor prognosis and life-threatening malignant complications. In a large population survey, we endeavored to characterize the course and treatment outcome of CCS through clinical and endoscopic assessment, and to explore its optimal treatment and surveillance strategy. METHODS: A retrospective analysis of 210 patients with CCS was conducted via a questionnaire-based nationwide survey of 983 teaching hospitals located throughout Japan. We assessed clinical features, endoscopic findings, treatments used, and short- and long-term outcomes. RESULTS: The average age at diagnosis was 63.5 years. In all cases, upper or lower gastrointestinal tract polyposis was confirmed, accompanied by characteristic ectodermal abnormalities. Of the treatments used, oral corticosteroids (30-49 mg/day) were the most effective treatment for active disease, with adjunctive nutritional support considered beneficial. With corticosteroid treatment, abdominal symptoms were relieved within a few months, whereas polyp regression often required more than 6 months. Maintenance of endoscopic remission with or without steroids for 3 years significantly lowered the development of CCS-related cancer, compared with relapsers or nonresponders, underscoring the importance of sustained endoscopic remission for cancer prevention. CONCLUSIONS: The prognosis of CCS has greatly improved through the use of improved medical treatment. Although CCS continues to be relentlessly progressive, carrying a high cancer risk, a sufficient dose and duration of corticosteroid therapy accompanied by nutritional support and periodic endoscopic surveillance appears to improve its natural history.

Lethal hemorrhage from duodenal ulcer due to small pancreatic cancer.

Gastrointestinal massive arterial hemorrhage is difficult to stop endoscopically, especially from a duodenal ulcer (DU), because of the anatomically narrow lumen. Here we report a rare case of small pancreatic cancer-induced lethal hemorrhagic DU. The 69-year-old patient was transferred due to massive hematemesis, hypotension and loss of consciousness. Emergency upper endoscopy revealed a DU with active bleeding from an unclear hemorrhagic spot, which stopped transiently by itself. Subsequently he began to vomit blood again and angiography showed extravasation from the gastroduodenal artery (GDA). Hemostasis by transcatheter arterial embolization (TAE) was achieved but the patient unfortunately died soon after because of hemorrhagic shock (10 h after his first hematemesis). The autopsy revealed a small pancreatic cancer (poorly differentiated adenocarcinoma, 10 × 25 mm in size) infiltrating into one-half of the penetrating DU with a nearby ruptured GDA wall, suggesting that the DU was caused by the pancreatic cancer. Our 7-year analysis of emergency endoscopies in our department for upper gastrointestinal bleeding revealed that TAE was performed in more cases of duodenal hemorrhage (5.7 %) than stomach hemorrhage (1.8 %), showing the difficulty in stopping hemorrhage from DU endoscopically. This case raises the possibility that intractable lethal hemorrhagic DU could be caused by a very small pancreatic tumor.

Recombinant Thrombomodulin Modulates Murine Colitis Possibly via High-Mobility Group Box 1 Protein Inhibition.

BACKGROUND AND AIM: Thrombomodulin (TM) is an anticoagulant cofactor protein. We hypothesized that its recombinant soluble TM (rhTM) form, widely used to treat disseminated intravascular coagulation, might have anti-inflammatory action in inflammatory bowel disease (IBD), possibly through its inhibition of high-mobility group box 1 protein (HMGB1). METHODS: We investigated inflammatory effects of HMGB1 and anti-inflammatory effect of rhTM in dextran sulfate sodium (DSS)-treated mice, some cell lines and ulcerative colitis (UC) patients, particularly focusing on changes of vascular endothelial adhesion molecules. RESULTS: Treatments with rhTM significantly attenuated DSS-treated mice clinically and histologically. The mRNA levels of proinflammatory cytokines and adhesion molecules were decreased by rhTM. Increased inflammatory cells in the colonic mucosa strongly expressed HMGB1 in the cytoplasm in the DSS-treated mice and UC patients' colonic mucosa, which were significantly decreased by rhTM in mice. In in vitro experiments, rhTM significantly decreased the mRNA levels of tumor necrosis factor-alpha (TNF-α) and adhesion molecules increased by endotoxin exposures in RAW 264.7 (macrophage cell line) and bEND.3 cells (endothelial cell line), suggesting the proinflammatory role of HMGB1 in TNF-α production from macrophages. CONCLUSIONS: These findings suggest that rhTM may be useful for the treatment of IBD by attenuating inflammatory cytokine production and adhesion molecule expression, partly because of its inhibition of HMGB1.

Toll-like receptor (TLR) 2 agonists ameliorate indomethacin-induced murine ileitis by suppressing the TLR4 signaling.

BACKGROUND AND AIM: Few drugs have been found satisfactory in the treatment of nonsteroidal anti-inflammatory drugs (NSAIDs)-induced enteropathy. Toll-like receptor (TLR) 4 and aberrant leukocyte migration to the intestinal mucosa are reported to be involved in the pathology of intestinal enteropathy and TLR2 agonists have been found to evoke hyposensitivity to TLR4 stimulation in vitro. In this study, we investigated whether and how lipoarabinomannan (LAM) or lipoteichoic acid (LTA), TLR2 agonists, attenuated indomethacin (IND)-induced intestinal damage. METHODS: LAM (0.5 mg/kg) or LTA (15 mg/kg) was administered intraperitoneally to mice before IND (10 mg/kg) administration. Disease activity was evaluated macroscopically and histologically. In the migration analysis, fluorescence-labeled leukocyte movement in the intestinal microvessels was observed by intravital microscopy. Expression of P-selectin, MAdCAM-1, TLR2, TLR4, and F4/80 was observed immunohistochemically. In the in vitro analysis, RAW264.7 macrophage cells were preincubated with LAM and stimulated with lipopolysaccharide (LPS), and the mRNA expression levels of TLR4, tumor necrosis factor-α, and interleukin-12p40 were measured. RESULTS: Pretreatment with LAM or LTA significantly decreased IND-induced injury as well as decreased leukocyte infiltration. Pretreatment with LAM decreased IND-induced TLR4 expression on F4/80(+) macrophages, the level of P-selectin expression, and leukocyte migration in the small intestinal vessels. In the in vitro study, a single administration of LAM decreased TLR4 mRNA expression and inhibited the increase in mRNA expression of inflammatory cytokines by LPS in a dose-dependent manner. CONCLUSION: TLR2 agonists attenuated IND-induced small intestinal lesions and leukocyte infiltration probably by suppressing the TLR4 signaling pathway in tissue macrophages.

Magnetic resonance enterocolonography in detecting erosion and redness in intestinal mucosa of patients with Crohn's disease.

BACKGROUND AND AIM: In Crohn's disease (CD), assessment of disease activity and extension is important for clinical management. Endoscopy is the most reliable tool for evaluating disease activity in these patients and it distinguishes between lesions based on ulcer, erosion, and redness. Magnetic resonance imaging (MRI) is less invasive than endoscopy; however, the sensitivity of MRI in detecting lesions is believed to be lower, and whether MRI can detect milder lesions has not been studied. The aim of this study was to compare the detection ability of magnetic resonance enterocolonography (MREC) with ileocolonic endoscopy in patients with CD. METHODS: A total of 27 patients with CD underwent both MREC and ileocolonoscopy. There were 55 lesions (18 ileum and 37 colon) endoscopically detected, and the findings of MREC were compared with each ileocolonoscopic finding to determine sensitivity and specificity. RESULTS: For a positive lesion defined as having at least one of the following: wall thickness, edema, diffusion-weighted imaging (DWI) high intensity and relative contrast enhancement (RCE) on MREC, the sensitivities were 100% for ulcer, 84.6% for erosion, and 52.9% for redness, suggesting an ability to detect milder lesions such as erosion or redness. Moreover, RCE values were well correlated with the severity of endoscopically identified active lesions. CONCLUSION: MREC findings may be useful not only for evaluation of ulcers, but also for detection of endoscopically identified milder lesions in CD, suggesting a clinical usefulness of MREC for disease detection and monitoring.

Pregnant woman with non-comatose autoimmune acute liver failure in the second trimester rescued using medical therapy: A case report.

We present the case of a 25-year-old woman at 16 weeks of gestation who presented with non-comatose autoimmune acute liver failure and was at high risk of developing fulminant hepatitis. Predictive formulas indicated a high probability of developing fulminant hepatitis. Unenhanced computed tomography showed marked hepatic atrophy and broadly heterogeneous hypoattenuating areas. The course of her illness was subacute, and the etiology of liver injury was unclear. Considering all of the above, we predicted a poor prognosis. Plasma exchange (PE) and continuous hemodiafiltration (CHDF) therapy were initiated just after admission. A few days after admission, a high titer (×80) of antinuclear antibody was noted. Because autoimmune hepatitis (AIH) was considered a cause of liver failure, treatment with moderate prednisolone (30 mg/day) doses was administrated, with careful consideration of her pregnancy. Thereafter, her laboratory findings and clinical course gradually improved without the need for liver transplantation. A liver biopsy at 18 days after admission indicated a diagnosis of AIH. She continued the pregnancy and delivered a healthy baby without any complications. Eventually, prednisolone doses were decreased to 10 mg, after which her liver function worsened. The second liver biopsy also indicated a diagnosis of AIH. Accordingly, low-dose prednisolone and azathioprine doses (50 mg/day) were administrated to recover her liver function, after which her liver function regained normalcy. This case illustrates that a pregnant woman with non-comatose autoimmune acute liver failure in the first or second trimester of pregnancy and her fetus can be rescued by PE/CHDF therapy and safe moderate doses of prednisolone.

Prevalence of serum celiac antibody in patients with IBD in Japan.

BACKGROUND: Although the incidence of inflammatory bowel diseases (IBD) in Japan has increased, the prevalence of celiac disease is considered very low with the lowest genetic disposition. IBD is reported as the most common comorbidity because of the high positive rate of serological celiac markers. The aim of this study was to examine the current incidence of celiac disease, especially in IBD patients in Japan, where both wheat consumption and incidence of IBD have increased. METHODS: A total of 172 patients with IBD and 190 controls in Japan were screened for serum antibody of tissue transglutaminase and deaminated gliadin peptide. In sero-positive patients, HLA testing and upper gastrointestinal endoscopy with duodenal biopsy was performed. Some of the sero-positive patients started a gluten-restricted or unrestricted diet, and serological change was determined. RESULTS: The positivity of both serum antibodies was significantly higher in IBD and correlated with disease activity. However, no biopsy-defined or HLA-defined true celiac disease was found. A decrease in serum antibody titers was observed with a gluten-restricted diet. CONCLUSIONS: Despite the increased incidence of IBD and high positivity for serum celiac antibody in Japanese IBD patients, no true-positive celiac disease was noted, suggesting the presence of gluten intolerance in these populations.

Phlebosclerotic colitis that was difficult to distinguish from collagenous colitis.

Phlebosclerotic colitis is a rare and recently known disease entity and its etiology is still to be elucidated. Some phlebosclerotic colitis cases are difficult to distinguish from collagenous colitis because of the similarity of pathological findings. In all Japanese case reports of phlebosclerotic colitis in which an association with the use of Chinese herbal medicine is suspected, sansisi (gardenia fruit) was included, suggesting pathogenesis of this disease. We report a case of phlebosclerotic colitis that wasdifficult to be distinguished from collagenous colitis, and an association with the use of Chinese herbal medicine was suspected as the cause of the disease.