Ulcerative Colitis: Watanabe K

Matsumoto T, Iwao Y, Igarashi M, Watanabe K, Otsuka K, Watanabe T, Iizuka B, Hida N, Sada M, Chiba T, Kudo SE, Oshitani N, Nagawa H, Ajioka Y, Hibi T. · Department of Lower Gastroenterology, Hyogo College of Medicine, Nishinomiya, Japan. · Inflamm Bowel Dis. · Pubmed #17973300 links to  free full text

Abstract: Clinical and epidemiological studies have revealed that the incidence of colorectal cancer associated with ulcerative colitis increases with long-term chronic inflammation. Careful endoscopic observation and histological studies to check for dysplasia in the colon are important in detecting neoplasia. Current surveillance protocols mainly involve frequent step biopsies to yield a reasonable rate of dysplasia detection. However, recent studies using chromoendoscopy or magnifying endoscopy have proposed that neoplastic changes may be detected efficiently. Therefore, it is very important to understand the typical endoscopic findings found in neoplastic changes in patients proven to have long-standing ulcerative colitis. In this review, we demonstrate the typical endoscopic findings by conventional endoscopy and chromoendoscopy.

Watanabe K, Mikamo H, Tanaka K. · Division of Anaerobe Research, Life Science Research Center, Gifu University. · Nippon Rinsho. · Pubmed #17642254 No free full text.

Abstract: Ulcerative colitis(UC) is colon localized disease. Broad epithelial cell damage, crypt abscesses and accumulation of neutrophils are recognized for UC. Although the cause of UC is indistinct at this time, there is a growing consensus that abnormal intestinal microflora would be related with UC. There have been several evidences that excessive production of hydrogen sulfide by bacteria in colon would be associated with UC. Sulfate reducing bacteria are able to utilize sulfate as an electron receptor for dissimilation of organic substrate and hydrogen gas, resulting in generating toxic hydrogen sulfide. This review is dealt with the association between sulfate reducing bacteria and UC in aetiology and bacterial pathogenesis.

Ono M, Murakami K, Oda M, Miyajima H, Watanabe K, Sato R, Nasu M, Kashima K. · Second Department of Internal Medicine, Faculty of Medicine, Oita University. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #16038436 No free full text.

This publication has no abstract.

Watanabe K, Nakamura S, Oshitani N, Higuchi K, Arakawa T. · Department of Gastroenterology, Graduate School of Medicine, Osaka City University. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #16004348 No free full text.

This publication has no abstract.

Oshitani N, Watanabe K, Nakamura S, Higuchi K, Arakawa T. · Department of Gastroenterology, Osaka City University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #15881184 No free full text.

Abstract: Extraintestinal complications of patients with ulcerative colitis contribute to quality of life and mortality of the patients. Extraintestinal complications involve many organ systems. Skin, mucocutaneous, hepatobiliary, and joints complications are major extraintestinal complications. Some disorders correspond the activity of the colitis, other complications develop independently of the bowel inflammation. The purpose of this review is to update the clinicians concerning the etiology, clinical course and the therapy of the extraintestinal manifestations associated with ulcerative colitis.

Kawa K, Hida N, Ohda Y, Watanabe K, Miwa H, Matsumoto T. · Division of Lower Gastroenterology, Hyogo College of Medicine. · Nippon Rinsho. · Pubmed #15881174 No free full text.

Abstract: It has been widely accepted that long-standing cases with ulcerative colitis, especially pancolitis have higher risk of complicating colitic cancer. Colitic cancer often appears as multi-focal invasive features with un-differentiated histology. Therefore, endoscopic diagnosis of precancerous or cancer associated dysplastic lesions. Surveillance colonoscopy has preventing effects for developing colitic cancer. In western world, annual surveillance colonoscopy with multiple stepwise has been adopted. In Japan, surveillance colonoscopy with targeted biopsies assisted by chromoendoscopy and/or magnifying endoscopy has proven to be efficacious in finding such lesions.

Matsumoto T, Andoh A, Okawa K, Ito H, Torii A, Yoshikawa S, Nakaoka R, Okuyama Y, Oshitani N, Nishishita M, Watanabe K, Fukunaga K, Ohnishi K, Kusaka T, Yokoyama Y, Sasaki M, Tsujikawa T, Aoki T, Kusaka T, Takeda Y, Umehara Y, Nakamura S, Fujiyama Y. · Division of Lower Gastroenterology Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan. · Ther Apher Dial. · Pubmed #19140847 No free full text.

Abstract: Leukocytapheresis (LCAP) has been advocated as a treatment for moderate to severe active ulcerative colitis (UC) in Japan. To clarify the predictive factors for a rapid response to LCAP treatment, we conducted a multicenter prospective open-label study. A total of 105 patients with UC were analyzed. LCAP was performed using a Cellsorba EX column once a week for 5-10 sessions. The response was evaluated by the clinical activity index (CAI). When the CAI score decreased to less than half the pretreatment value or to less than 5 points within 3 weeks, the patient was considered to be a rapid responder. The average CAI significantly decreased from 11.7 to 4.2 (P < 0.01). Seventy-four percent of the patients responded to the therapy, and 53% of these patients were rapid responders. The following significant factors correlated with the rapid LCAP response: (i) steroid resistance (P < 0.05), (ii) severe disease indicated by a CAI score greater than 11 (P = 0.05), (iii) disease duration of less than 1 year (P < 0.05), and (iv) C-reactive protein levels before treatment (P < 0.01). These results suggest that the early initiation of LCAP is beneficial in patients with steroid-resistant UC.

Watanabe K, Funayama Y, Fukushima K, Shibata C, Takahashi K, Sasaki I. · Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Japan. · Dis Colon Rectum. · Pubmed #19404068 No free full text.

Abstract: PURPOSE: This study aimed to assess the feasibility and safety of undergoing emergency subtotal colectomy with hand-assisted laparoscopic surgery in patients with severe ulcerative colitis. METHODS: We reviewed the medical records of 60 patients who underwent emergency subtotal colectomy with hand-assisted laparoscopic technique (30 cases) or open technique (30 cases) for severe ulcerative colitis. RESULTS: No intraoperative complications occurred in either group. One patient in the laparoscopic group required conversion to open surgery. The median operative time was significantly longer in the laparoscopic group (242 vs. 191 minutes; P < 0.001). The rate of early postoperative complications in the laparoscopic group was significantly less than that in the open group (37 percent vs. 63 percent; P = 0.041). In the open group, four patients required relaparotomy because of peritoneal abscess or strangulation ileus, whereas no patient required relaparotomy in the laparoscopic group (P = 0.040). In the laparoscopic group, the median duration of postoperative food prohibition was significantly shorter (4.8 vs. 5.9 days; P = 0.007), and the median length of hospital stay was significantly shorter (23.0 vs. 33.0 days; P = 0.001). CONCLUSIONS: Although the operative time was elongated in the laparoscopic group, intraoperative safety and postoperative recovery were satisfactory. For severe ulcerative colitis, hand-assisted laparoscopic surgery can be an alternative to conventional open surgery.

Hirata N, Oshitani N, Kamata N, Sogawa M, Yamagami H, Watanabe K, Watanabe T, Tominaga K, Fujiwara Y, Maeda K, Hirakawa K, Arakawa T. · Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. · Inflamm Bowel Dis. · Pubmed #18452202 links to  free full text

Abstract: BACKGROUND: Pouchitis is the most common complication of restorative proctocolectomy in patients with ulcerative colitis (UC). The etiology of pouchitis is not known. We have previously reported the specific and significant proliferation of immature plasma lineage cells in the ulcer bases and inflamed mucosa of UC. In the present study we report the results of a phenotypic study of ileal pouch mucosa. METHODS: Biopsy samples were taken from the ileal pouch of 22 patients with UC (12 with pouchitis, 10 with a normal pouch) and 5 patients with familial adenomatous polyposis (FAP) (with a normal pouch) who underwent restorative proctocolectomy, and normal ileum of 10 patients with UC yet to undergo pouch surgery. Frozen sections were cut from fixed samples and reacted with various lymphocyte markers and anti-Ki-67 antibodies. Ki-67+ cells, CD19+ cells, and CD138+ cells were significantly increased in the pouchitis mucosa of patients with UC. RESULTS: Immunological double staining revealed significantly increased numbers of CD19+Ki-67+ cells and CD138+Ki-67+ cells in the pouchitis mucosa of patients with UC compared to noninflamed UC pouch, FAP pouch, and normal ileum of UC patients. The number of CD19+CD138+ cells was significantly increased in inflamed pouch mucosa. The increased number of CD19+CD138+ cells we observed represents proliferation of immature plasma cells. Moreover, the increase in labeling for Ki-67 among CD19 cells and CD138 cells suggests proliferative activity of these cells, consistent with their immaturity. CONCLUSIONS: Proliferation of these immature plasma cells suggests the possibility of involvement of UC-derived abnormality in the pathogenesis of pouchitis.

Hosomi S, Oshitani N, Kamata N, Sogawa M, Yamagami H, Watanabe K, Tominaga K, Watanabe T, Fujiwara Y, Maeda K, Hirakawa K, Arakawa T. · Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. · Inflamm Bowel Dis. · Pubmed #18425803 No free full text.

Abstract: BACKGROUND: Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor (GHSR), has been demonstrated to possess multiple functions including antiinflammatory effects. The aim of this study was to investigate the expression of ghrelin and GHSR and the function of ghrelin in inflammatory bowel disease (IBD). METHODS: The expression of ghrelin and GHSR mRNA was quantified in mucosal biopsy specimens from 9 controls, 15 patients with Crohn's disease (CD), and 15 patients with ulcerative colitis (UC) using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The locations of ghrelin and GHSR were investigated immunohistochemically in surgically resected specimens. We also evaluated the percentage of GHSR-positive peripheral blood mononuclear cells (PBMCs) in healthy controls and patients with CD by flow cytometry. In addition, we investigated the immunoregulatory function of ghrelin in peripheral blood T cells. RESULTS: Ghrelin mRNA levels in colonic mucosa of IBD were higher than control level. The GHSR-1a mRNA level in active CD was also significantly higher than the control level. Ghrelin and GHSR-1a were expressed on CD3- and CD68-positive cells. The percentage of GHSR-1a-positive peripheral blood T cells in patients with CD was significantly higher than the control level. Stimulation of human T cells with ghrelin increased levels of IL-4 and IL-13 proteins and decreased levels of IFN-gamma protein. Reactivity to ghrelin was low in CD compared with the control level. CONCLUSIONS: Our findings demonstrate that ghrelin may play an important role in the immune system in CD. The dysregulation of reactivity of T cells induced by ghrelin suggests that ghrelin might participate in the pathogenesis of CD.

Noguchi A, Watanabe K, Narumi S, Yamagami H, Fujiwara Y, Higuchi K, Oshitani N, Arakawa T. · Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. · J Gastroenterol. · Pubmed #18085351 No free full text.

Abstract: BACKGROUND: To clarify which types of cells produce interferon-gamma-inducible protein 10 (IP-10) and whether IP-10 is associated with the development of ulcerative colitis (UC), we investigated IP-10 production in UC patients. METHODS: Serum IP-10 levels were measured using enzyme-linked immunosorbent assay in 29 patients with active and 21 with inactive UC and in 20 controls. The production of IP-10 by granulocytes and monocytes adsorbed to G-1 beads was examined. In 21 active UC patients treated with granulocyte and monocyte/macrophage adsorptive apheresis (GMA), serum IP-10 levels were measured before and after treatment. IP-10-positive cells in UC mucosa were also examined immunohistochemically using tissues obtained by surgical resection and colonoscopic biopsies. RESULTS: Serum IP-10 levels in active UC patients were significantly higher than those in inactive patients, although even in the latter the levels were increased compared with those in controls. IP-10 production by granulocytes and monocytes in active UC patients was significantly higher than that in controls. Furthermore, the number of IP-10-positive cells was elevated in the colonic mucosa of patients with active UC, and one of the main subpopulations of IP-10-positive cells was granulocytes. Serum IP-10 levels decreased following GMA treatment in responders, but not in nonresponders. Interestingly, serum IP-10 levels before GMA were higher in responders than in nonresponders. In parallel with the serum levels, IP-10-positive cells also decreased following GMA treatment. CONCLUSIONS: Serum IP-10 levels reflected UC disease activity, and the source of IP-10 was granulocytes and monocytes. Furthermore, serum IP-10 levels may be a marker for the responsiveness of patients to GMA treatment.

Yukawa T, Oshitani N, Yamagami H, Watanabe K, Higuchi K, Arakawa T. · Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan. · Int J Mol Med. · Pubmed #17611633 No free full text.

Abstract: There is conflicting evidence regarding the significance of vasoactive intestinal peptide (VIP) in inflammatory bowel disease (IBD). Involvement of the VIP receptor in IBD has not been reported. We examined the expression and localization of the VIP receptor in IBD. We determined the location of VIP receptor 1 (VIPR1) immunohistologically in surgically resected intestinal samples from 10 controls, 15 patients with ulcerative colitis, and 10 patients with Crohn's disease. A fluorescein-linked immunohistological study was performed using anti-VIPR1 antibody, with double-staining with antibodies to CD3, CD19, and CD68. Correlations with interleukin (IL)-4 and TNF-alpha expression were also investigated. Results showed that the number of VIPR1-positive cells was significantly increased in the inflammatory mucosa. VIPR1 was expressed in CD3-, CD19-, and CD68-positive cells. The proportion of VIPR1-positive cells among CD3-positive cells was significantly higher in the lamina propria of patients with ulcerative colitis than in those with Crohn's disease and the controls. The proportion of VIPR1-positive cells among CD68-positive cells was significantly higher in patients with ulcerative colitis and Crohn's disease than in the controls. A correlation between the numbers of VIPR1- and IL-4-positive cells was found in patients with ulcerative colitis, and between the numbers of VIPR1- and TNF-alpha-positive cells in patients with Crohn's disease. In conclusion, VIPR1 was widely expressed in infiltrating inflammatory cells, especially CD3- and CD68-positive cells in ulcerative colitis mucosa and CD68-positive cells in Crohn's disease mucosa. The differential expression of VIPR1 in ulcerative colitis and Crohn's disease mucosa suggests that the VIP system plays different roles in the pathogenesis of IBD.

Suzuki K, Kawauchi Y, Palaniyandi SS, Veeraveedu PT, Fujii M, Yamagiwa S, Yoneyama H, Han GD, Kawachi H, Okada Y, Ajioka Y, Watanabe K, Hosono M, Asakura H, Aoyagi Y, Narumi S. · Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan. · Pathol Int. · Pubmed #17587240 No free full text.

Abstract: The role of chemokines, especially CXCL10/interferon-gamma-inducible protein 10 kDa (IP-10), a chemokine to attract CXCR3(+) T-helper 1-type CD4(+) T cells, is largely unknown in the pathophysiology of inflammatory bowel disease; ulcerative colitis and Crohn's disease. The authors have earlier shown that IP-10 neutralization protected mice from acute colitis by protecting crypt epithelial cells of the colon. To investigate the therapeutic effect of neutralization of IP-10 on chronic colitis, an anti-IP-10 antibody was injected into mice with newly established murine AIDS (MAIDS) colitis. Anti-IP-10 antibody treatment reduced the number of colon infiltrating cells when compared to those mice given a control antibody. The treatment made the length of the crypt of the colon greater than control antibody. The number of Ki67(+) proliferating epithelial cells was increased by the anti-IP-10 antibody treatment. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)(+) apoptotic cells were observed in the epithelial cells of the luminal tops of crypts in control MAIDS colitis, whereas TUNEL(+) apoptotic epithelial cells were rarely observed with anti-IP-10 antibody treatment. In conclusion, blockade of IP-10 attenuated MAIDS colitis through blocking cellular trafficking and protecting intestinal epithelial cells, suggesting that IP-10 plays a key role in the development of inflammatory bowel disease as well as in chronic experimental colitis.

Shibata C, Funayama Y, Fukushima K, Takahashi K, Ogawa H, Haneda S, Watanabe K, Kudoh K, Kohyama A, Hayashi K, Sasaki I. · Division of Biological Regulation and Oncology, Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Sendai, Japan. · Dig Dis Sci. · Pubmed #17394081 No free full text.

Abstract: The aim of the present study was to determine if calcium polycarbophil ameliorates diarrhea after ileal J-pouch anal anastomosis for ulcerative colitis. Twenty-one randomized patients were given either bifidobacterium (3 g/day) plus calcium polycarbophil (3 g/day), in the polycarbophil group (11 patients), or bifidobacterium (3 g/day), in the control group (10 patients), p.o. for 6 months. Anal manometry was performed and bowel function (stool frequency, stool consistency, and nighttime soiling) was assessed via a questionnaire before and 1, 3, and 6 months after drug administration. Eight patients were deemed eligible in each group; five patients were excluded from the study, including two patients whose stool consistency was too firm and who experienced difficulty in defecating attributed to polycarbophil. Anal manometry and stool consistency did not change with time and did not differ between the polycarbophil and the control groups. Stool frequency decreased with time in both groups and did not differ between the groups. Nighttime soiling improved with time in the polycarbophil group but did not change in the control subjects. These results suggest that polycarbophil might be able to improve nighttime soiling without obviously affecting stool frequency and consistency after ileal J-pouch anal anastomosis for ulcerative colitis.

Watanabe K, Ohira H, Orikasa H, Saito K, Kanno K, Shioya Y, Obara K, Sato Y. · Department of Internal Medicine II, Fukushima Medical University School of Medicine, Japan. · Fukushima J Med Sci. · Pubmed #16995349 No free full text.

Abstract: PURPOSE: Although the pathogenesis of inflammatory bowel disease (IBD) is unclear, autoimmune processes seem to play roles in IBD because several types of autoantibodies have been found in it. Calreticulin (CRT) is a soluble Ca2+ binding protein which is present in a wide variety of cells. CRT is localized mainly in the endoplasmic reticulum and is often a target for autoantibodies. The aim of this study was to evaluate the clinical significance of anti-CRT antibodies measured by enzyme-linked immunosorbent assay (ELISA) using the sera of patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We measured the serum anti-CRT antibodies of 31 Japanese patients with UC and 24 with CD by ELISA. The controls were 105 subjects: 30 healthy persons, 44 patients with primary biliary cirrhosis (PBC), 21 with systemic lupus erythematosus (SLE) and 10 with acute colitis (AC). RESULTS: The mean titer of anti-CRT antibodies was significantly higher in patients with UC than in healthy individuals (p <0.05). The prevalence of anti-CRT antibodies in these patients was significantly higher during the initial phase than during the passing phase (p <0.05). In patients with CD, the mean titer of anti-CRT antibodies was not significantly higher than in healthy individuals. The positivity for anti-CRT antibodies, however, was about 30% in those patients, which was as high as in patients with UC, SLE and PBC. In patients with AC, anti-CRT antibodies were all negative. CONCLUSIONS: The positivity of anti-CRT antibodies may have a diagnostic value for IBD, especially in the initial phase of UC.

Watanabe K, Funayama Y, Fukushima K, Shibata C, Takahashi K, Ogawa H, Haneda S, Kudo K, Kohyama A, Sasaki I, Anonymous00097. · Department of Surgery, Division of Biological Regulation and Oncology (GI & Colorectal Surgery), Tohoku University Graduate School of Medicine, 1-1 Seiryou-machi, Aoba-ku, Sendai, 980-8574, Japan. · J Gastroenterol. · Pubmed #16933003 No free full text.

Abstract: BACKGROUND: The Inflammatory Bowel Disease Questionnaire (IBDQ) is the most widely used disease-specific health-related quality of life questionnaire for patients with inflammatory bowel disease. However, little has been reported about the validation of IBDQ for patients with ulcerative colitis after surgery. The aim of this study was to assess the validity and reliability of the Japanese version of IBDQ in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis (IPAA). METHODS: The validity and reliability of the Japanese IBDQ were assessed in patients with ulcerative colitis who had received IPAA in our hospital. We mailed them the Japanese IBDQ and a supplemental questionnaire on bowel function, which was developed at our institution. Internal consistency, discriminative validity, and factor validity were assessed. RESULTS: Of the 121 patients to whom we sent the questionnaires, 64 patients (53%) participated in this study. The Japanese IBDQ scores correlated well with Cronbach's alpha value (0.800 to 0.923) and daily life satisfaction score (Pearson's r, 0.492 to 0.700). The total IBDQ score and two subscale scores of the IBDQ, "bowel symptoms" and "systemic symptoms," correlated well with daily bowel-movement frequency (Pearson's r, -0.256 to -0.329). Factor analysis revealed a four-factor structure, and all correlations among factors were moderately positive (0.337 to 0.465). Although the factor distribution was not clearly divided into the four IBDQ subscales, these four factors showed a marked tendency to represent the IBDQ subscales independently. CONCLUSIONS: The Japanese IBDQ is a valid and reliable instrument for the assessment of Japanese patients with ulcerative colitis after IPAA.

Kayo S, Ikura Y, Suekane T, Shirai N, Sugama Y, Ohsawa M, Adachi K, Watanabe K, Nakamura S, Fujiwara Y, Oshitani N, Higuchi K, Maeda K, Hirakawa K, Arakawa T, Ueda M. · Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan. · Inflamm Bowel Dis. · Pubmed #16917228 No free full text.

Abstract: BACKGROUND: Neutrophils are considered to play a causative role in inflammatory mucosal injury in ulcerative colitis (UC), and an association between platelets and neutrophils may contribute to the progression of the inflammatory processes. To test this hypothesis, we performed immunohistochemical and flow cytometric analyses on tissue and blood samples from patients with UC. MATERIALS AND METHODS: Colonic mucosal tissues of patients with active (n = 27) or inactive (n = 16) UC and normal controls (n = 11) were subjected to immunohistochemical staining for markers of activated platelets (glycoprotein IIb/IIIa and P-selectin) and neutrophils (neutrophil elastase, myeloperoxidase, and CD66b). The amounts of stained cells were evaluated by computer-aided morphometry. Peripheral blood samples from patients (n = 8) and healthy volunteers (n = 8) were subjected to comparative flow cytometric analysis of activated platelets. RESULTS: P-selectin-positive activated platelets were frequently aggregated in the inflamed mucosa, especially in ulcerative lesions, and were close to regions of dense neutrophil infiltration. An increase in the number of activated platelets in the colonic lesions was associated with an increase in infiltrating neutrophils and was related to the severity of the disease. The flow cytometric analysis indicated that circulating platelets of patients with UC were highly activated. CONCLUSIONS: The present study demonstrated that a close association between activated platelets and neutrophils is a prominent pathological change in both the affected colonic mucosa and peripheral blood of patients with active-phase UC. This suggests that platelet-neutrophil association may play an important role in the progression of inflammatory processes in UC.

Shibata C, Funayama Y, Fukushima K, Takahashi K, Saijo F, Nagao M, Haneda S, Watanabe K, Kudoh K, Kohyama A, Sasaki I. · Division of Biological Regulation and Oncology, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. · J Gastrointest Surg. · Pubmed #16843879 No free full text.

Abstract: The aim was to study determinants of postoperative bowel function after restorative proctocolectomy for ulcerative colitis. Medical records of patients who underwent proctocolectomy with ileal J pouch-anal anastomosis (IPAA) in two- or three-stage operations and whose status of defecation was known via a questionnaire were retrospectively reviewed. Bowel function, including stool frequency, stool consistency, and degree of nighttime soiling, was correlated with age at the time of surgery, time after ileostomy closure, mean resting anal pressure, longitudinal length of ileal J pouch, and duration of fecal diversion by using univariate and multivariate analyses. Stool frequency decreased significantly with time after ileostomy closure in both univariate and multivariate analyses. Stool frequency tended to be less in patients having a long J pouch, but the correlation was not significant (P = 0.071) in univariate analysis. Nighttime soiling ameliorated with time after ileostomy closure in multivariate, but not univariate, analysis. Deterioration of nighttime soiling was seen in patients whose duration for fecal diversion was long, both in univariate (P = 0.068) and multivariate (P = 0.052) analyses. Stool consistency was related to none of the five factors investigated. These results indicate that as the time after surgery increases, stool frequency decreases and nighttime soiling ameliorates. Delaying ileostomy closure because of anticipated postoperative incontinence does not significantly alter postoperative continence.

Haneda S, Fukushima K, Funayama Y, Shibata C, Takahashi K, Ogawa H, Nagao M, Watanabe K, Sasaki I. · Department of Surgery, Tohoku University, Graduate School of Medicine, Sendai, Japan. · J Gastrointest Surg. · Pubmed #16843877 No free full text.

Abstract: Our previous studies demonstrated that sodium glucose cotransporter 1 (SGLT-1) was induced in the remnant ileum of total colectomized rats via the action of factors other than hyperaldosteronism. The aim of the present study was to clarify whether fecal stream is required for the enhancement of SGLT-1-mediated sodium transport. Twenty-seven pairs of ileal tissues were obtained from the proximal and distal side, respectively, of loop ileostomy after total proctocolectomy. Mucosae were mounted in an Ussing chamber to evaluate glucose-coupled sodium transport. Levels of SGLT-1 mRNA in proximal and distal mucosae were compared by Northern blotting. Villous height and crypt depth were measured to test for correlations between mucosal structure and SGLT-1-mediated sodium transport or mRNA expression levels. Both glucose-coupled sodium transport and expression of SGLT-1 mRNA were significantly lower in distal mucosae relative to proximal mucosae. In distal mucosae, villous height, but not crypt depth, was significantly lower than in proximal mucosae, demonstrating a positive correlation between villous height and SGLT-1 function and expression. Comparative studies of proximal and distal mucosae demonstrated that in addition to hormonal changes, fecal stream is required for full induction of the sodium transport system (which includes SGLT-1-mediated transport) in the remnant ileum following total proctocolectomy.

Yamauchi K, Takeda H, Kobayashi K, Watanabe K, Machida Y, Suzuki H. · Saiseikai Yamagata Saisei Hospital, Internal Medicine. · Nihon Kokyuki Gakkai Zasshi. · Pubmed #16218420 No free full text.

Abstract: A 25-year-old woman who had been receiving mesalazine for 2 weeks for ulcerative colitis presented with a nonproductive cough, high fever, and exertional dyspnea. Her chest radiograph showed bilateral pleural effusion. At first, infectious pleuritis was suspected and antibiotics were administered, but the pleural effusion increased and high fever continued. Because clinical and radiographic abnormalities markedly improved with discontinuation of mesalazine and treatment with corticosteroid, mesalazine was thought to be the cause of pleural effusion in this case. This case was thought to be of interest when we consider the onset mechanism of pleurisy by mesalazine. Mesalazine-induced pleuritis must be considered in patients who develop unexplained respiratory symptoms while taking this agent.

Kawashima D, Oshitani N, Jinno Y, Watanabe K, Nakamura S, Higuchi K, Arakawa T. · Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. · J Clin Pathol. · Pubmed #16189151 links to  free full text

Abstract: 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.

Kawachiya T, Oshitani N, Jinno Y, Watanabe K, Nakamura S, Fujiwara Y, Higuchi K, Maeda K, Nishiguchi Y, Hirakawa K, Matsumoto T, Arakawa T. · Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan. · Int J Mol Med. · Pubmed #15702231 No free full text.

Abstract: The etiology of ulcerative colitis (UC) is not known. Recent studies support a primary role of the appendix in the pathogenesis of UC, however phenotypical studies of proliferating cells in the appendix have not been reported. We report phenotypical studies of lymphocytes and of proliferating subpopulations in the appendix of patients with inflammatory bowel disease and of controls. Surgical samples of the appendix were obtained from 5 patients with colon cancer, 5 with acute appendicitis, 12 with UC and 7 with Crohn's disease (CD). Frozen sections were cut from fixed samples, and immunostained with lymphocyte markers and anti-Ki-67 antibodies. The number of Ki-67(+) proliferating cells, CD19, and CD138 cells was significantly higher in the appendix of patients with UC than in controls, patients with acute appendicitis, and patients with CD. Immunohistological double staining revealed significant proliferation of CD3, CD19, and CD138 cells in the appendix of patients with UC. The proportions of Ki-67(+) cells in CD3, CD19, and CD138 cells were significantly higher in both total UC patients and patients in remission-stage UC, than in controls, patients with acute appendicitis, and patients with CD. Lamina propria cells in the appendix of patients with UC showed augmented proliferation with increased numbers of CD19 and CD138 cells. The number of CD3 cells was not significantly increased, but the proportion of proliferating CD3 cells was increased. An increased proportion of Ki-67(+) cells in CD19 and CD138 cells represents proliferation of immature plasma cells in the appendix of patients with UC, and proliferation of such immature plasma cells was seen in both active- and remission-stage UC. Proliferation of immature plasma cells in the appendix of patients with UC suggests a primary role of humoral immune responses in the pathogenesis of UC.

Oshitani N, Watanabe K, Nakamura S, Fujiwara Y, Higuchi K, Arakawa T. · Third Department of Internal Medicine, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan. · Int J Mol Med. · Pubmed #15702229 No free full text.

Abstract: Crohn's disease is associated with increased permeability of the intestinal barrier even in quiescent patients. Increased intestinal permeability may cause dysregulated immunological responses in the intestinal mucosa that leads to chronic intestinal inflammation. We have studied the expression of tight junction proteins (occludin and zonula occludens), alpha2-smooth muscle actin, TGF-beta with a cytoskeletal protein (F-actin) in the intestinal epithelium of patients with inflammatory bowel disease. Surgical samples were obtained from 6 controls (individuals without inflammatory bowel disease), 8 patients with ulcerative colitis and 7 patients with Crohn's disease. F-actin was visualized with fluorescein phalloidin. Tight junction proteins, alpha2 smooth muscle actin, and TGFbeta were visualized by the immunofluorescent method. Occludin and zonula occludens found in apical tight junctions in normal epithelium were dislocated to the basolateral position and in the lamina propria extracellular matrix in patients with Crohn's disease, while the structure of F-actin was maintained in inactive or minimally inflamed mucosa. TGF-beta positive inflammatory cells were increased in ulcerative colitis and Crohn's disease mucosa. Subepithelial myofibroblasts were constitutively found in controls, ulcerative colitis, and Crohn's disease mucosa. Latent dislocation of tight junction proteins, without disturbance of the cytoskeleton in the inactive mucosa of patients with Crohn's disease, may permit the invasion of gut antigens because the functional disruption of tight junctions could initiate an altered immune response.

Shibata C, Jin XL, Funayama Y, Fukushima K, Takahashi K, Hashimoto A, Nagao M, Haneda S, Watanabe K, Matsuno S, Sasaki I, Naito H. · Division of Biological Regulation and Oncology, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. · Tohoku J Exp Med. · Pubmed #14738325 links to  free full text

Abstract: We report a patient with synchronous multiple liver metastases from rectal cancer associated with ulcerative colitis. Because the liver tumors were unresectable, we performed total proctocolectomy and hepatic intra-arterial cisplatin infusion with systemic oral administration of fluorouracil. A complete response was obtained. The patient is alive without sign of recurrence 5 years postoperatively. Hepatic intra-arterial administration of cisplatin should be considered in the treatment of unresectable liver metastases from colorectal cancer.

Oshitani N, Watanabe K, Maeda K, Fujiwara Y, Higuchi K, Matsumoto T, Arakawa T. · Department of Gastroenterology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan. · Int J Mol Med. · Pubmed #14532999 No free full text.

Abstract: Intraepithelial lymphocytes play an important role in mucosal immunology, and are involved in the pathogenesis of inflammatory bowel disease. We studied expression of CD103 on mucosal lymphocytes with epithelial adhesion molecules in patients with inflammatory bowel disease. Surgical specimens of human colon were obtained from 12 patients with ulcerative colitis, 12 patients with Crohn's disease, and 5 controls. Frozen sections were cut and expression of CD103 on lymphocytes, E-cadherin, CD44V3, and CD44v6 on intestinal epithelium was studied. Frequency of CD103-positive intraepithelial lymphocytes did not differ among controls, patients with ulcerative colitis, and patients with Crohn's disease. The frequency of CD103-positive lamina propria lymphocytes was significantly higher in patients with Crohn's disease than in controls and patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with that of lamina propria lymphocytes in patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with epithelial E-cadherin expression but that of lamina propria lymphocytes was not. Differential up-regulation of CD103 expression on lamina propria lymphocytes in Crohn's disease may indicate differential humoral or cellular regulation in inducing CD103 molecules on lymphocytes in patients with this disease.