Yoshio Jinno

Evaluation of Deep Small Bowel Involvement by Double-Balloon Enteroscopy in Crohn's Disease

OBJECTIVES:Double-balloon enteroscopy (DBE) enables inspection of deep small bowel, and total small bowel examination can be performed by either antegrade or retrograde DBE. The aim of this study was to evaluate ileal involvement, which cannot be achieved using conventional colonoscopy, by DBE in patients with Crohns disease.METHODS:From December 2003 to September 2005, a total of 44 patients with Crohns disease underwent 53 examinations using DBE.RESULTS:Forty patients with Crohns disease, seven women and 33 men, underwent DBE, and the ileum was investigated in 38 patients. There were 25 cases of ileitis, 2 of colitis, and 13 of ileocolitis. Jejunal lesions were found in two and ileal lesions proximal to the terminal ileum were found in 24 patients with Crohns disease. DBE was superior to radiological study to detect aphthae, erosions, and small ulcers in the ileum. Small bowel stricture was demonstrated in six and nine patients with DBE and small bowel barium study (SBBS), respectively. An additional mucosal finding was demonstrated in one of the eight patients who underwent wireless capsule endoscopy, and one patient had a capsule removed by DBE that had become lodged because of an ileal stricture. One ileal perforation because of overtube balloon pressure occurred in 53 examinations of patients with Crohns disease (1.9%).CONCLUSION:DBE is useful to evaluate small bowel lesions in patients with Crohns disease; however, special attention should be paid to mesenteric longitudinal ulcers during insertion and the overtube balloon should not be inflated if a clear intestinal view is not possible.

Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn's disease.

Saccharomyces cerevisiae may contribute to the pathophysiology of Crohn’s disease. We determined serum anti‐Saccharomyces cerevisiae antibody (ASCA) levels in patients with inflammatory bowel disease.

Prediction of Short-Term Outcome for Patients with Active Ulcerative Colitis

We report results of a retrospective chart review to evaluate factors predicting short-term outcome of patients with ulcerative colitis treated by corticosteroids. Between January 1992 and December 1997, we treated 71 patients with ulcerative colitis (44 with severe and 27 with moderately severe disease). Forty-nine patients were treated by conventional prednisolone therapy and 22 patients by steroid pulse therapy. There were no differences in clinical or endoscopic improvement between the two treatments. Clinical examination showed that 41 patients entered remission, 17 patients improved, and 13 patients did not respond. Endoscopically, 26 patients entered remission, 30 patients improved, and 15 patients did not respond. Extent of disease, type of disease (first attack, relapsing, or chronic active type), and endoscopic findings were factors useful in predicting short-term outcome of medical treatment.

Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn’s disease

Background: A dominant T helper type 1 (Th1) immune response is thought to be involved in Crohn’s disease (CD). SLC/CCL21 and ELC/CCL19, chemokines that regulate T cell homing and promote recirculating T and dendritic cell (DC) interactions, help control antigen specific T cell responses. Aims: To investigate the Th1 response and SLC and ELC in CD pathogenesis. Methods: Surgically resected intestine and mesenteric lymph nodes (MLNs) from controls and patients with CD and ulcerative colitis (UC) were investigated. CD3, CD83, HECA452, VEGFR3, SLC, ELC, and CCR7 expression was studied immunohistochemically. CCR7 mRNA was quantified using real time RT-PCR. Results: ELC was almost undetectable in intestinal samples. SLC was found sporadically in lymphoid follicles, lymphoid aggregate venules, and lymphatic vessels. In MLNs, SLC was highly expressed in high endothelial venules (HEVs), lymphatic vessels, and stromal DCs, predominantly in T cell areas. ELC was highly expressed in mature DCs. There were significantly more SLC positive HEVs and ELC positive mature DCs, important components of T cell areas, in CD. SLC, ELC, and CCR7 mRNA was significantly higher in CD MLNs compared with UC. CD MLNs had increased expression of SLC and ELC, mainly in HEVs, mature DCs, and lymphatic vessels, inducing T cell hyperplasia. CCR7 mRNA was increased in T cell areas. Conclusion: The dominant Th1 immune response is facilitated by interaction of SLC positive HEVs/lymphatic vessels, ELC positive mature DCs, and CCR7 positive T cells in hyperplastic T cell areas. In CD, memory T cells and mature DCs may home to MLN.

Role of Granuloma in the Immunopathogenesis of Crohn’s Disease

Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) are chronic long-lasting inflammatory diseases with yet unknown etiology. Recent advancement revealed that both diseases are associated with genetic predisposition and environmental factors such as luminal microorganisms and antigens. Crohn’s disease is associated with histopathologic features such as granuloma formation and longitudinal ulceration. In this article we describe the role of granuloma in the immunopathogenesis of Crohn’s disease. Granuloma of Crohn’s disease may play crucial roles as antigen-presenting cites to memory type T cells, which leads to activation and proliferation of T cells. Antigens presented at granuloma may be closely related to the disease.

Infiltration of CD19+ plasma cells with frequent labeling of Ki-67 in corticosteroid-resistant active ulcerative colitis

Abnormalities in humoral immunity are implicated in the pathogenesis of ulcerative colitis. However, the detailed mechanisms of B-cell activation in the locale remain unaccounted for. We analyzed ulcerative colitis from the standpoint of lymphocytic expansion in the loco. Intestinal specimens obtained at surgery from 30 patients with ulcerative colitis treated with corticosteroids and 15 with Crohn’s disease were analyzed by immunohistochemistry and flow cytometry. Ulcerative colitis was characterized by a diffuse distribution of Ki-67+ small round cells particularly in the ulcer base (that were CD19+ and CD20–), with a significant number of them also CD138+. Immunoelectron microscopy for CD19 revealed an abundance of rough endoplasmic reticulum in the cytoplasm. These indicated that they are of immature plasma lineage cells. By contrast, plasma cells in Crohn’s disease were negative for CD19, and the labeling for Ki-67 was infrequent, showing mature phenotype. Flow cytometry revealed an occurrence of CD19+ and CD20– cells in ulcerative colitis but not in Crohn’s disease. The labeling index of Ki-67 among CD19+ plasma cells was positively correlated with the clinical activity of ulcerative colitis. High labeling of Ki-67 in CD19+ plasma cells is specific for active ulcerative colitis that was resistant to medical treatment by corticosteroids.

IgG subclasses of anti Saccharomyces cerevisiae antibody in inflammatory bowel disease

Elevation of serum anti Saccharomyces cerevisiae antibody (ASCA) has been reported in patients with Crohns disease. We analysed the subclasses of Immunoglobulin (Ig) G reaction in ASCA in sera from patients with inflammatory bowel disease, healthy controls, and patients with intestinal Behçets disease.

A Suppository Chinese Medicine (Xilei-san) for Refractory Ulcerative Proctitis: A Pilot Clinical Trial

posed as a possible indication of peroral XS. We have hypothesized that XS might be a useful therapeutic option for active UP patients refractory to conventional topical therapies if it would be applied in suppository form. A prospective open-labeled clinical trial was held from April 1, 2005 to December 31, 2006 to evaluate the efficacy of SXS for active refractory UP patients. Mean ( 8 SD) age and duration of UP of the enrolled patients were 36.2 8 9.1 years and 56.3 8 47.4 months, respectively. All patients had an episode of treatment with a combination of either peroral 5Dear Sir, Six patients with active ulcerative proctitis (UP) (male/female = 2/4) were treated with an originally developed suppository Xilei-san (SXS), a traditional Chinese medicine, which is composed of watermelon frost, calcite, cow gallstone, peal powder, borax, borneol, indigo, and ammonium chloride. This mixed traditional medicine has a long history in China and it has been accepted as a medicine for erosions and ulcerations of the tongue, pharynx and oral cavity. The therapeutic mechanism of XS has never been fully understood, but some domestic reports inform that ulcerative colitis (UC) has been proPublished online: August 3, 2007

Crohn’s disease complicated by adult-onset Still’s disease

A 31-year-old man with Crohn’s disease developed arthritis, spiking fever, and skin rash indistinguishable from that of adult-onset Still’s disease. He was admitted to our hospital because of a periumbilical intestinal skin fistula. Crohn’s disease had been diagnosed in 1991, and had required intestinal resection twice, and schizophrenia had been diagnosed in 1993. He developed polyarthritis and spiking fever, accompanied by a macular skin rash on both forearms. Marked hepatosplenomegaly and bilateral pleural effusion were detected on computed tomography examination. These findings are indistinguishable from those of adult-onset Still’s disease. Because his mental status had deteriorated following high-dose prednisolone on a previous admission, he was treated with an immunosuppressive agent on this occasion, with the treatment being successful. This is the first report of adult-onset Still’s disease complicating Crohn’s disease. In patients with Crohn’s disease, polyarthritis and skin rash can easily be misdiagnosed as enteropathic arthritis with erythema nodosum associated with the Crohn’s disease. Although adult-onset Still’s disease may not be fatal, early diagnosis is important because it can, in rare cases, result in life-threatening complications.

Outpatient treatment of moderately severe active ulcerative colitis with pulsed steroid therapy and conventional steroid therapy.

Pulsed steroid therapy may induce rapid remission in patients with moderately severe ulcerative colitis in outpatient clinics. A total of 19 patients with moderately severe active ulcerative colitis who refused hospitalization were treated between October 1999 and September 2001 in the outpatient clinic. Patients were treated with either conventional oral steroid therapy or intravenous pulsed steroid therapy followed by conventional oral steroid therapy. Eight patients received conventional steroid therapy and 11 patients received pulsed steroid therapy followed by conventional steroid therapy. The efficacies of the two types of steroid therapy were equal, but patients with active colitis responded more quickly to pulsed steroid therapy than to conventional steroid therapy. No serious adverse effects were observed. Moderately severe colitis can be safely treated with either conventional or pulsed steroid therapy in the outpatient clinic, but pulsed steroid therapy may induce clinical remission more quickly than conventional steroid therapy.