Published papers

Intestinal lamina propria dendritic cells (LPDCs) in mice are known to extend dendrites between the intestinal epithelia and the luminal side when processing luminal antigens. We conducted intrarectal cell transfer experiments of bone marrow-derived dendritic cells (BMDCs) in mice to assess dendritic cell penetration of the intestine. Intrarectally administered GFP+ BMDCs localized in the colonic LP within 3h and the spleen within 12h after administration. 72h after administration, recipient C57BL/6 mice showed acute diarrhea, and administration of BMDCs (once weekly for 3 weeks) induced intestinal inflammation with increased numbers of recipient macrophages and CD4+ T cells exhibiting a Th2-mediated immune response. These results demonstrate that DCs actively communicate across the intestinal barrier, and highlight a potential technique for controlling colonic immune tolerance. © 2013 Elsevier B.V.

Background: Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that regulates apoptosis sensitivity in a variety of cell types. Here we evaluate the roles of Mcl-1 in chemotherapy-associated apoptosis in gastric cancer cells. In addition, our study examined whether Mcl-1 contributed to apoptosis resistance in so-called cancer stem cell (CSC)-like populations in gastric cancer. Methods: Seven gastric cancer cell lines were used. The expression of Mcl-1 was assessed by either real-time polymerase chain reaction or Western blot analysis. Apoptosis was quantitated by morphological observation and caspase activity measurement. Adenovirus-mediated RNA interference (RNAi) technology was used to knockdown the expression of Mcl-1. The release of cytochrome c was evaluated by subcellular fractionation and immunoblot analysis. To identify and isolate the CSC-like populations, we used the CSC-associated cell surface marker CD44 and flow cytometry. Results: Six out of the 7 gastric cancer cell lines overexpressed Mcl-1 protein. These Mcl-1-expressing cell lines were relatively resistant to chemotherapeutic agents such as 5-fluorouracil (5-FU) and cisplatin (CDDP). Depletion of Mcl-1 protein by RNAi technology effectively sensitized the cells to anticancer drug-induced mitochondrial cytochrome c release, caspase activation, and apoptosis. In addition, vast amounts of Mcl-1 mRNA were expressed in CD44-positive CSC-like cells. Mcl-1 suppression enhanced the apoptosis in CD44-positive cells to a level equivalent to that in CD44-negative cells, suggesting that Mcl-1 mediates chemotherapy resistance in CSC-like populations. Conclusion: These results suggest that Mcl-1 mediates the resistance to apoptosis in gastric cancer cells by blocking the mitochondrial pathway of cell death. Mcl-1 depletion appears to be an attractive strategy to overcome chemotherapy resistance in gastric cancer cells. © 2012 The International Gastric Cancer Association and The Japanese Gastric Cancer Association.

Behçet's disease is a chronic relapsing disease with multiple organ system involvement, including the gastrointestinal tract, which is known as intestinal Behçet's disease. Intestinal Behçet's disease is often resistant to empirical treatments such as 5-aminosalicylic acid, immunomodulators and steroids and often causes a perforation, requiring surgical resection. Therefore, intestinal lesions are considered to be a poor prognostic factor in Behçet's disease. Recently, several reports have demonstrated the efficacy of anti-TNFα monoclonal antibodies, such as infliximab, against intestinal Behçet's disease, however, it remains unknown whether anti- TNFα therapy can improve the prognosis of patients with intestinal Behçet's disease. We herein report the case of an adult female patient with intestinal Behçet's disease who responded well to the induction therapy with infliximab, and has been maintained in remission by scheduled administration of infliximab. Her C- reactive protein level has been sustained at a negative level, and endoscopic findings revealed complete mucosal healing. Therefore, infliximab may have the potential to induce "sustained deep remission" in patients with intestinal Behçet's disease. © 2012 The Japanese Society of Internal Medicine.

Background and Aim: In Japan, patient acceptance of bowel preparation methods before colonoscopy remains unknown. This study was conducted to evaluate the patient acceptance of sodium phosphate (NaP) tablets and polyethylene glycol solution (PEG) with sodium picosulfate. Methods: One hundred patients were randomized into one of the following two groups: the NaP tablet first-use group or the PEG with sodium picosulfate first-use group in a crossover design trial. Patient acceptance and incidence of adverse events were evaluated using a questionnaire. Colon-cleansing effectiveness was also evaluated. Results: Patients' overall impressions of the preparations were significantly different between the NaP tablet (77.9%, 67/86) and PEG with sodium picosulfate (60.5%, 52/86; P=0.001). Nausea incidence as an adverse event was significantly different between the two regimens (P=0.03). Colon-cleansing effectiveness was not significantly different between the two regimens. Conclusions: The results of this crossover study showed that patient acceptance was similar to those previously reported in a parallel-group comparison. In Japanese patients, preference for and acceptance of NaP tablets was significantly higher than that for PEG with sodium picosulfate solution. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Mesenteric venous thrombosis is an insidious disease, with a high mortality rate typically attributed to the long delay in diagnosis. Rapid diagnosis and treatment are important. Here, we present a patient with idiopathic inferior mesenteric venous (IMV) thrombosis. A 65-year-old man presented with constant abdominal pain associated with fever and bloody diarrhea. He was diagnosed with severe ulcerative colitis and was treated with mesalazine and prednisolone. The prednisolone was tapered because of liver dysfunction, and he received total parenteral nutrition for a month. His abdominal pain and bloody diarrhea worsened, and he lost 5 kg of weight. He was then transferred to our institute. Computed tomography showed thickening of the left colon. Colonoscopy showed diffuse colitis with multiple ulcers, large edematous folds, congested mucosa, and stenosis of the sigmoid colon, with sparing of the rectum, raising the possibility of IMV thrombosis. Angiography confirmed IMV thrombosis. Anticoagulation therapy was initiated with intravenous heparin followed by oral warfarin. His abdominal pain and diarrhea resolved, and he was discharged from hospital. Six months later, he remained asymptomatic with normal colonoscopic findings. © 2012 Springer Japan.

We explored the role of the MyD88 signaling pathway. This pathway mediates the recognition of pathogen-associated molecular patterns and damage-associated molecular patterns via Toll-like receptors (TLRs) and/or IL-1/IL-18 via each cytokine receptor in a murine model of acute pancreatitis induced by cerulein administration. Our analysis revealed that: various TLRs and MyD88 molecules were constitutively expressed in the pancreas of cerulein-treated and untreated wild-type (WT) mice. MyD88-/- mice administered cerulein developed severe pancreatitis as compared with MyD88+/+ WT mice. The number of IL-10-expressing CD11b+Gr-1high cells in cerulein-administered MyD88-/- mice was significantly decreased. This was in accordance with a reciprocal increase in the infiltration of CD4+ T cells as compared with that in control MyD88+/+ mice. WT mice pretreated with antibiotics and administered cerulein developed milder pancreatitis as compared with control cerulein-administered mice without antibiotic treatment. The MyD88 signaling pathway contributes to the induction of regulatory IL-10-producing macrophages/myeloid-derived suppressor cells, possibly in response to non-bacterial components in the damaged pancreas. These results provide a new concept for therapeutic strategies against acute pancreatitis. © 2012 Elsevier B.V.

Background & Aims: T helper (Th) 17 cells that express the retinoid-related orphan receptor (ROR) γt contribute to the development of colitis in mice, yet are found in normal and inflamed intestine. We investigated their development and functions in intestines of mice. Methods: We analyzed intestinal Th17 cells in healthy and inflamed intestinal tissues of mice. We analyzed expression of lymphotoxin (LT)α by Th17 cells and lymphoid tissue inducer-like cells. Results: LTα-/- and RORγt-/- mice had significantly lower percentages of naturally occurring Th17 cells in the small intestine than wild-type mice. Numbers of CD3-CD4+/-interleukin-7Rα+c-kit +CCR6+NKp46- lymphoid tissue inducer-like cells that produce interleukin-17A were increased in LTα-/- and LTα-/-×recombination activating gene (RAG)-2 -/- mice, compared with wild-type mice, but were absent from RORγt-/- mice. Parabiosis of wild-type and LTα -/- mice and bone marrow transplant experiments revealed that LTα-dependent gut-associated lymphoid tissue structures are required for generation of naturally occurring Th17 cells. However, when wild-type or LTα-/- CD4+CD45RBhigh T cells were transferred to RAG-2-/- or LTα-/-×RAG-2 -/- mice, all groups, irrespective of the presence or absence of LTα on the donor or recipient cells, developed colitis and generated Th1, Th17, and Th17/Th1 cells. RAG-2-/- mice that received a second round of transplantation, with colitogenic but not naturally occurring Th17 cells, developed intestinal inflammation. The presence of naturally occurring Th17 cells in the colons of mice inhibited development of colitis after transfer of CD4+CD45RBhigh T cells and increased the numbers of Foxp3+ cells derived from CD4+CD45RBhigh T cells. Conclusions: Gut-associated lymphoid tissue structures are required to generate naturally occurring Th17 cells that have regulatory activities in normal intestines of mice, but not for colitogenic Th17 and Th17/Th1 cells during inflammation. © 2012 AGA Institute.

Retinoid-related orphan receptor (ROR) γt-expressing and IL-22-producing NKp46+ innate lymphoid (ILC22) cells reside in the lamina propria of the intestine in mice, suggesting that ILC22 cells contribute to host defense during intestinal damage in models of colitis in mice. Nevertheless, another set of pathological interferon (IFN)-γ and/or IL-17A-producing innate lymphoid cells (ILC1 and ICL17) may participate in the pathogenesis in different models of colitis. We here showed that RORγt+IL-22+ ILC22 cells were localized in Thy-1highSCA-1high and/or Thy-1highSCA-1low subpopulations of the intestine in normal and dextran sodium sulfate (DSS)-induced colitic RORγt-sufficient Rag-2-/- mice. RORγt-deficient Rag-2-/- mice developed more severe DSS-induced colitis accompanied with lower expression of REG3β and REG3γ in the colon, but with a lower ratio and absolute number of IFN-γ-producing ILC1 cells as compared to control RORγt-sufficient Rag-2-/- mice. Collectively, not only the presence of ILC22 cells but also the balance of protective and pathogenic ILCs may be involved in the prevention of colitis. © 2012 Elsevier Inc.

Background & Aims: The tumor suppressor p53 is a primary sensor of stressful stimuli, controlling a number of biologic processes. The aim of our study was to examine the roles of p53 in non-alcoholic steatohepatitis (NASH). Methods: Male wild type and p53-deficient mice were fed a methionine- and choline-deficient diet for 8 weeks to induce nutritional steatohepatitis. mRNA expression profiles in normal liver samples and liver samples from patients with non-alcoholic liver disease (NAFLD) were also evaluated. Results: Hepatic p53 and p66Shc signaling was enhanced in the mouse NASH model. p53 deficiency suppressed the enhanced p66Shc signaling, decreased hepatic lipid peroxidation and the number of apoptotic hepatocytes, and ameliorated progression of nutritional steatohepatitis. In primary cultured hepatocytes, transforming growth factor (TGF)-β treatment increased p53 and p66Shc signaling, leading to exaggerated reactive oxygen species (ROS) accumulation and apoptosis. Deficient p53 signaling inhibited TGF-β-induced p66Shc signaling, ROS accumulation, and hepatocyte apoptosis. Furthermore, expression levels of p53, p21, and p66Shc were significantly elevated in human NAFLD liver samples, compared with results obtained with normal liver samples. Among NAFLD patients, those with NASH had significantly higher hepatic expression levels of p53, p21, and p66Shc compared with the group with simple steatosis. A significant correlation between expression levels of p53 and p66Shc was observed. Conclusions: p53 in hepatocytes regulates steatohepatitis progression by controlling p66Shc signaling, ROS levels, and apoptosis, all of which may be regulated by TGF-β. Moreover, p53/p66Shc signaling in the liver appears to be a promising target for the treatment of NASH. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Purpose Peginterferon (PEG-IFN) and ribavirin (RBV) combination treatment for patients with chronic hepatitis C (CHC), infected by genotype-1 hepatitis C virus with high viral loads, results in a sustained viral response (SVR) in 50%. However, a trend of decreasing SVR in the older patients has been reported. In the present study, we verified this trend of treatment efficacy in older patients using the propensity score (PS). Methods We conducted a survey of 327 patients with CHC (genotype 1 and high viral loads) who were treated with PEG-IFN and RBV for 48 weeks. The SVR rate was compared between patients =60 and <60 years of age. Because backgrounds of these patients differed considerably, we verified this efficacy between the older (n = 102) and younger (n = 102) patients matched for gender, body weight, platelets (PLT), and red blood cell (RBC) counts using PS. Results The total SVR rate was 42.9% (161/327); this rate decreased with increasing age and was lower in the older patients (C60 years: 41.5%, <60 years: 54.3%, P = 0.0245). Moreover, younger age was a significant factor for SVR. After correction by PS, the SVR in older patients remained significantly lower (C60 years: 43.1%, <60 years: 57.8%, P = 0.0497). In addition, RBC counts and hemoglobin (Hgb) concentrations, as well as RBV adherence in the older patients, decreased with this treatment, although there were no significant differences in pretreatment RBC and Hgb levels. Conclusions The analysis using PS indicated that RBV adherence in the older patients decreased even if they did not have lower pretreatment RBC and Hgb levels. © Asian Pacific Association for the Study of the Liver 2011.

Sepsis is a systemic inflammatory response to infection associated with multiple organ dysfunction syndrome and a high mortality rate. In septic shock induced by severe peritonitis, early response of peritoneal macrophages against infected microbes is vital in preventing the spread of infection. We found that the mucosal homing receptor CCR9, is induced in peritoneal macrophages in response to inflammatory stimulation. We used a cecal ligation and puncture (CLP) model of sepsis to determine the role of CCR9 with respect to peritoneal macrophages, and controlling peritoneal infection and systemic inflammation. CCR9-/- mice showed aggravated septic shock with higher mortality rates compared with wild-type (WT) mice. Six hours after CLP, CCR9-/- mice demonstrated a greater inflammatory response. This was associated with higher production of inflammatory cytokines, such as IL-6, TNF and IP-10 in peritoneal lavage compared with WT mice. Although the numbers of peritoneal bacteria were elevated in CCR9-/- mice subjected to CLP compared with WT mice, this was normalized in CCR9-/- mice subjected to CLP through the adoptive transfer of WT peritoneal macrophages. We conclude that CCR9 is required for recruitment of peritoneal macrophages in the steady state to control systemic sepsis during early phases of peritoneal infection. © 2012 Elsevier B.V.

Background The development of a supportive diagnostic method has long been required to differentially diagnose ulcerative colitis (UC) and Crohn's disease (CD). Several antibodies circulate in the sera of patients with inflammatory bowel disease. We previously identified the high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1 and HMGB2) as novel antigens of perinuclear type anti-neutrophil cytoplasmic antibodies (pANCA) and discovered anti-HMGB1/HMGB2 antibodies in sera from patients with UC. Here, we evaluated the ability of anti-HMGB1/HMGB2 antibodies combined with anti-Saccharomyces cerevisiae antibodies (ASCA) to differentially diagnose UC and CD. Methods We measured titers of anti-HMGB1/HMGB2 antibodies and ASCA in the sera of 213 patients with UC and 93 with CD, using enzyme-linked immunosorbent assays. Results Among the patients with UC, 26.8% were positive for anti-HMGB1/HMGB2 antibodies, with 85.0% specificity towards CD and a positive predictive value of 80.3%. Corticosteroids significantly suppressed the titer of anti- HMGB1/HMGB2 antibodies. Among the patients with CD, 24.7% were positive for ASCA, with 96.2% specificity towards UC and a positive predictive value of 74.2%. Interestingly, the positivity rate of anti-HMGB/HMGB2 antibodies was higher (35.7%) in patients with the ileitis type ofCDthan in patients withCDin the colon (6.2%; significant difference, P0.01). The specificity of anti-HMGB1/ HMGB2 antibodies in UC for CD in the colon was 93.8%. Conclusions CD in the colon and UC can be differentially diagnosed using anti-HMGB/HMGB2 antibodies combined with ASCA. © 2012 Springer.

Background: Although previous studies indicate that gastrointestinal (GI) cancer may originate from cells recruited from bone marrow (BM) in mice, whether similar phenomena occur in humans is controversial. In the current study, we evaluated two female patients who developed colonic adenocarcinoma more than 10 years after gender-mismatched BM transplantation, and followingly underwent successful endoscopic mucosal resection. Materials and Methods: Fluorescent in situ hybridization (FISH) analysis was used to determine whether the tumours contained donor-derived BM cells. Results: Approximately 1.2% of the tumour cells contained Y-chromosome-positive signals, and a comparable percentage of normal colonic epithelial cells close to the tumour also contained Y-chromosome-positive signals. Conclusion: These results do not support the concept that GI cancer can originate from BM-derived cells.

To maintain immune homeostasis in the intestine, the intestinal immune system has evolved several tolerogenic mechanisms toward intestinal microflora and food antigens. Although programmed cell death-1 (PD-1) protein has been implicated in immunological tolerance in the intestine and gut-associated lymphoid tissues (GALTs), distribution of its ligands PD-L1 and PD-L2 in the small intestine lamina propria (LP) are unknown. We investigated PD-L1 expression in intestinal LP and found that IgA plasma cells (PCs) were major PD-L1 expressing cells. PD-L1 expression levels on IgA PCs were higher than that on IgG PCs in peripheral lymphoid tissues. IgA PCs expressed antigen-presenting molecule MHC class II and co-stimulatory molecules CD80, CD86, and PD-L2. IgA PCs isolated from intestinal LP exhibited antigen presentation activity, and in the presence of TGF-β induced FoxP3+ regulatory T cells, but not IFN-γ+ Th1 cells, from naïve T cells. Thus, IgA PCs in the intestine may be involved in an immune regulatory role in the intestinal immune system. © 2012 Elsevier Inc.

Almost all mice lacking specific molecules associated with regulatory T cells or barrier function develop intestinal inflammation in the colon, but not in the small intestine (SI). Therefore, intestinal homeostasis of the SI may be tightly controlled by other mechanisms. To determine the role of CCR9+ plasmacytoid dendritic cells (pDCs) in intestinal homeostasis of the SI we transferred CD4+CD45RBhigh T cells into ccr9-/-×rag-2-/- mice. We showed that CCL25, a counterpart chemokine for CCR9, is constitutively expressed in the SI but not the colon and spleen of rag-2-/- or ccr9-/-×rag-2-/- mice before or after transfer of CD4+CD45RBhigh T cells. The ccr9-/-×rag-2-/- mice did not develop spontaneous intestinal inflammation in the SI and colon. Mice of both genotype where CD4+CD45RBhigh T cells were transferred developed colitis. However, the ccr9-/-×rag-2-/- mice also developed ileitis with marked infiltration of Th1 cells. These results suggest that CCR9+ pDCs are possibly small, regulatory, antigen-presenting cells of the intestine that suppress intestinal inflammation. © 2012 Elsevier B.V.

Background/Aims: In capsule endoscopy (CE), the capsule does not always reach the cecum within its battery life, which may reduce its diagnostic yield. We evaluated the effect of mosapride citrate, a 5-hydroxytryptamine-4 agonist that increases gastrointestinal motility, on CE completion. Methods: In a retrospective study, we performed univariate and multivariate analyses for 232 CE procedures performed at our hospital. To identify factors that affect CE completion, the following data were systematically collected: gender, age, gastric transit time (GTT), nonsteroidal anti-inflammatory drug administration, previous abdominal surgery, hospitalization, use of a polyethylene glycol solution, use of mosapride citrate (10 mg), body mass index (BMI), and total recording time. Results: The univariate analysis showed that oral mosapride citrate, GTT, and BMI were associated with improved CE completion. Multivariate analyses showed that oral mosapride citrate (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.01 to 3.91) and GTT (OR, 2.34; 95% CI, 1.13 to 4.87) were significant factors for improving the CE completion. Oral mosapride citrate significantly shortened the GTT and small bowel transit time (SBTT). Conclusions: Oral mosapride citrate reduced the GTT and SBTT during CE and improved the CE completion rate.

Dendritic cells (DCs) are known as antigen-presenting cells and play a central role in both innate and acquired immunity. Peripheral blood monocytes give rise to resident and recruited DCs in lymph nodes and non-lymphoid tissues. The ligands of nuclear hormone receptors can modulate DC differentiation and so influence various biological functions of DCs. The role of bile acids (BAs) as signalling molecules has recently become apparent, but the functional role of BAs in DC differentiation has not yet been elucidated. We show that DCs derived from human peripheral blood monocytes cultured with a BA produce lower levels of interleukin-12 (IL-12) and tumour necrosis factor-α in response to stimulation with commensal bacterial antigens. Stimulation through the nuclear receptor farnesoid X (FXR) did not affect the differentiation of DCs. However, DCs differentiated with the specific agonist for TGR5, a transmembrane BA receptor, showed an IL-12 hypo-producing phenotype. Expression of TGR5 could only be identified in monocytes and was rapidly down-regulated during monocyte differentiation to DCs. Stimulation with 8-bromoadenosine-cyclic AMP (8-Br-cAMP), which acts downstream of TGR5 signalling, also promoted differentiation into IL-12 hypo-producing DCs. These results indicate that BAs induce the differentiation of IL-12 hypo-producing DCs from monocytes via the TGR5-cAMP pathway. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

Background: Endoscopic submucosal dissection (ESD) is more difficult for rectal cancer than for gastric cancer. Objective: To evaluate the feasibility and safety of an ESD procedure by using external forceps for early rectal cancer. Design: A case series. Setting: A tertiary medical center. Patients: Thirteen patients with early-stage rectal cancer were enrolled. Twelve of the 13 lesions were granular-type laterally spreading tumors and 1 was a protruding tumor. Interventions: After circumferential incision around the lesion with a dual-knife or a flex-knife, bendable external forceps were introduced with the help of grasping forceps inserted through the accessory channel and anchored at the anal margin of the lesion. After the forceps were bent, they were locked. With gentle anal traction and bending applied with the forceps, the lesion was elevated, the submucosal layer was opened, and the submucosal layer was dissected from the grasped side, facilitating dissection of the submucosal layer under direct vision. Main Outcome Measurements: Technical success, complication rates. Results: The mean lesion size was 33.0 mm (range 20-80 mm), and the mean operating time was 60 minutes (range 20-150 minutes). All lesions could be resected en bloc with tumor-free margins. Major bleeding after ESD occurred in only 1 patient (7.7%), who did not require blood transfusion. Perforation did not occur in any patient. Limitations: Single-center experience, small number of patients. Conclusion: This ESD procedure using external forceps for early-stage rectal cancers is feasible and safe. © 2012 American Society for Gastrointestinal Endoscopy.

The hypothesis of helper T(T h)1/T h2 cytokine balance proposed by Mosmann and Coffman is often invoked to explain the development of inflammatory diseases, including inflammatory bowel diseases (IBD). Recently, however, a newly identified class of T h cells - T h17 cells, which produce T h17 family cytokines - has been recognized as an essential subpopulation in the development of almost all kinds of human and animal inflammatory diseases, rather than T h1 and T h2 cells. A representative T h17 family cytokine, interleukin (IL)-17A, is produced by not only T h17 cells, but also by other types of cells, such as T-cell receptor γδ T cells, natural killer (NK) T cells, NK cells, myeloid cells, and innate lymphoid cells, which may also be critically involved in the initiation and persistence of IBD. Here we review recent advances in the study of such IL-17A-producing cells in the pathogenesis of IBD. © 2012 Society for Mucosal Immunology.

Background/Aims: A flexible spectral imaging color enhancement system was installed in new capsule software for video capsule endoscopy. Contrast image capsule endoscopy (CICE) is a novel technology using light-emitting diodes selected for the main absorption range of hemoglobin. We assessed the feasibility and diagnostic effi cacy for small bowel surveillance in patients with polyposis syndromes. Methods: Six patients with polyposis syndromes, four with familial adenomatous polyposis and one each with Cowden syndrome (CS) and Cronkhite-Canada syndrome (CCS) were examined using CICE. We conducted three evaluations to assess the effect on the numbers of the detected polyps; compare polyp diagnostic rates between adenoma and hamartoma; and assess polyp visibility. Results: The numbers of detected polyps and diagnostic accuracy did not differ signifi cantly between pre-contrast and contrast images. However, 50% of the adenomatous polyps displayed enhanced visibility on contrast images. CICE contrast images exhibited clearly demarcated lesions and improved the visibility of minute structures of adenomatous polyps. Hamartomatous polyp micro-structures in patients with CS and CCS were more clearly visualized on contrast than pre-contrast images. Conclusions: CICE is an effective tool for enhancing the visibility of polyps in patients with polyposis syndrome.