Ulcerative Colitis: Takahashi K

Masutani M, Takahashi K, Matsuda T, Ohira K, Nomura A, Sadaoka K, Douchin A, Suzuki J, Kawakami Y. · First Department of Medicine, Hokkaido University, School of Medicine. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #10368996 No free full text.

This publication has no abstract.

Kohyama A, Funayama Y, Fukushima K, Shibata C, Miura K, Takahashi K, Ogawa H, Ueno T, Sasaki I, Hiwatashi N. · Division of Biological Regulation and Oncology, Department of Surgery, Tohoku University Postgraduate School of Medicine. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19498314 No free full text.

Abstract: We encountered a rare operative case of hyperthyroidism followed by ulcerative colitis (UC). A 26-year-old mam was referred to our department to undergo an operation. We suspected the possible complication of adrenal insufficiency, since he suffered from severe weight loss, a high fever and palpitation on admission. We diagnosed hyperthyroidism, however, based on the presence of high serum free T3 and T4 levels and a decreased TSH level. After improving the symptoms and the thyroid function by administering thiamazole, we then performed a total proctocolectomy. Although a high rate of association of autoimmune thyroid diseases with UC has been suggested, only 9 cases of hyperthyroidism coexisting with UC have so far been reported in Japan. A common immunological process has been suggested to be implicated in the pathogenesis of this association, however, the exact mechanism needs to be elucidated in the future.

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.

Kohyama A, Ogawa H, Funayama Y, Takahashi K, Benno Y, Nagasawa K, Tomita S, Sasaki I, Fukushima K. · Department of Surgery, Tohoku University, Sendai, Japan. · Surgery. · Pubmed #19303993 No free full text.

Abstract: BACKGROUND: Colonic transformation is defined by phenotypic alterations in the ileum after total proctocolectomy. Changes in microbiota of the ileal pouch and the roles of these microbes in colonic transformation, however, have not been addressed. METHODS: A total of 151 stool samples were collected from patients with ulcerative colitis patients and an ileostomy, those with an ileal pouch, and healthy control volunteers. Bacterial DNA was extracted from stool, and the diversity of complex bacteria was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, a novel DNA-based approach that enables us to investigate the presence of nonculturable bacteria. To determine whether ileal pouch bacterial communities shift to a more colon-like distribution, the relative abundance of terminal restriction fragments that could be classified as "colonic," "ileal," or "common" was investigated. RESULTS: Cluster analysis demonstrated that most of the ileostomy samples were categorized into Cluster I or II and that less than 10% of ileostomy samples were classified into Cluster IV. In contrast, more than 90% of control samples were grouped in Cluster IV. In further analyses, the median lifetimes of pouches in Clusters I, II, III, and IV were significantly different at 11, 56, 265, and 310 days, respectively. T-RFLP patterns of the ileal pouch were characterized by a time-dependent decrease in "ileal" and increase in a part of "colonic" fragments, which represented mainly nonculturable bacteria such as the Clostridium coccoides group. CONCLUSION: T-RFLP analysis demonstrated that a time-dependent shift to a "colon-like" bacterial community, including nonculturable bacteria, in the ileal pouch after total proctocolectomy.

Funayama Y, Kumagai E, Takahashi K, Fukushima K, Sasaki I. · Department of Colorectal Surgery, Tohoku Rosai Hospital, Sendai, Japan. · Dis Colon Rectum. · Pubmed #19279428 No free full text.

Abstract: PURPOSE: To evaluate the efficacy of early diagnosis and early administration of corticosteroid for peristomal pyoderma gangrenosum, a prospective study was carried out. METHODS: In April 1998, we began studying a new treatment regimen of peristomal pyoderma gangrenosum in which prednisone at a dose of 20 to 40 mg was administered systemically immediately after diagnosis. Early-stage peristomal pyoderma gangrenosum was treated concurrently with topical cadexomer iodine, and at the granulation stage, treatment with clobetasol ointment was started. Healing of peristomal pyoderma gangrenosum was determined by complete epithelialization of ulcer without pain or exudates. Patients were assigned to group A (n = 7) before April 1998 and group B (n = 10) after April 1998, and historical comparison was done between the 2 groups. RESULTS: In group A, all patients had ulcerative colitis, and in group B, 7 patients had ulcerative colitis, 2 had Crohn's disease, and one had indeterminate colitis. In group B, significantly earlier diagnosis (P = 0.0093), earlier start of treatment (P = 0.0057), higher initial dose of corticosteroid (P = 0.0052), and earlier healing of peristomal pyoderma gangrenosum (P = 0.0023) were observed. CONCLUSIONS: Early diagnosis and early corticosteroid administration appeared to be effective for promoting healing of peristomal pyoderma gangrenosum.

Takahashi K, Funayama Y, Fukushima K, Shibata C, Ogawa H, Kumagai E, Sasaki I. · Department of Surgery, Division of Gastrointestinal and Colorectal Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. · Dig Surg. · Pubmed #18292656 No free full text.

Abstract: BACKGROUND: This study was designed to evaluate the incidence and details of stoma-related complications in patients with ulcerative colitis and Crohn's disease who underwent permanent enterostomas, and to analyze the specific problems in these diseases. METHODS: Permanent enterostomas constructed for ulcerative colitis and Crohn's disease between 1984 and 2004 in our institution were included. The incidence and details of stoma-related complications were investigated retrospectively. The cumulative probability of complications and stoma reconstruction was also estimated by the Kaplan-Meier life-table analysis. RESULTS: 43 patients with ulcerative colitis and 59 patients with Crohn's disease underwent 46 and 76 stoma constructions, respectively. Stoma-related complications, including fistula, retraction and stenosis, were significantly more frequent in patients with Crohn's disease (36.8%) than ulcerative colitis (17.4%) (p < 0.05). The cumulative risk of complications and the necessity for stoma reconstruction was significantly higher in patients with Crohn's disease (p < 0.05). Among the patients with Crohn's disease, colostomies were likely to receive revisional surgery earlier than ileostomies (p < 0.05). CONCLUSION: In the surgical therapy of inflammatory bowel disease, special attention should be paid in the high incidence of stoma-related complications in patients with Crohn's disease, which needs revisional surgery more frequently.

Fukushima K, Fujii H, Yamamura T, Sugita A, Kameoka S, Nagawa H, Futami K, Watanabe T, Hatakeyama K, Sawada T, Yoshioka K, Kusunoki M, Konishi F, Watanabe M, Takahashi K, Ogawa H, Funayama Y, Hibi T, Sasaki I, Anonymous00291. · Department of Surgery, Tohoku University, Graduate School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan. · J Gastroenterol. · Pubmed #17940832 No free full text.

Abstract: "Pouchitis" is a term for nonspecific mucosal inflammation of the pouch after total proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis. Pouchitis is the most frequent complication of the pelvic pouch at the late stage. To improve the accuracy of the pouchitis diagnosis, sets of clinical symptoms and endoscopic findings (with or without histology of biopsy samples) have previously been evaluated. Endoscopic findings are central to the diagnosis, and a universal consensus of various endoscopic findings must be the initial step toward an objective diagnosis of pouchitis. Since a proper signpost for the endoscopic evaluation of pouchitis has been absent, we developed this pouchitis atlas to minimize the diagnostic variation inherent among individual endoscopists. We also propose new criteria for the diagnosis of pouchitis: the Japanese criteria for diagnosis of pouchitis. These criteria are based on clinical symptoms and endoscopic findings that are clearly categorized in the atlas, and exclude infectious enteritis, anastomotic insufficiency, pelvic infection, anal dysfunction, and Crohn's disease. Advantages of the new criteria include ease of bedside diagnosis, without the calculation of points required by the other criteria for pouchitis. This pouchitis atlas, together with our new criteria, should contribute to the establishment of a clear-cut diagnosis for pouchitis and promote better evaluation and treatment of this novel intestinal inflammation.

Lin X, Zamora PO, Takahashi K, Lui Y. · BioSurface Engineering Technologies, Inc., 9430 Key West Avenue, Suite 220, Rockville, Maryland 20850, USA. · Dig Dis Sci. · Pubmed #17404850 No free full text.

Abstract: Recombinant fibroblast growth factors (FGFs) maintain the integrity of the gut epithelium and reduce mucosal injury in experimental inflammatory bowel disease (IBD). Chemically synthesized FGF mimetics could potentially extend the utility of FGFs by tailoring them for optimal bioactivity and oral administration, for example. Here, F2A4-K-NS (Fibratide), a synthetic FGF mimetic peptide, alleviated dextran sulfate sodium (DSS)-induced ulcerative colitis in mice when delivered systemically and, to a lesser extent, orally. Intraperitoneal injection of Fibratide (1 or 5 mg/kg/day) ameliorated DSS-induced ulcerative colitis, resulting in reduced weight loss, decreased colon wall thickening, and increased colon length. Fibratide also improved epithelial integrity by reducing histological-detectable crypt damage and inflammation. Orally administered Fibratide (1 mg/kg/day) was also effective in ameliorating symptoms with effects generally similar to those of intraperitoneal injection. In vitro studies were conducted to help clarify how Fibratide might act in vivo. Fibratide exhibited a modest enhancement of epithelial cell proliferation. On the other hand, Fibratide doubled the rate of epithelial cells migration and restitution in a cell culture model of wound repair. Collectively, the results indicate that Fibratide reduced the severity of experimental ulcerative colitis and may be potentially useful in the treatment of IBD.

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.

Kato K, Ishii Y, Mizuno S, Sugitani M, Asai S, Kohno T, Takahashi K, Komuro S, Iwamoto M, Miyamoto S, Takayama T, Arakawa Y. · Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, 173-8610, Japan. · Scand J Gastroenterol. · Pubmed #17327940 No free full text.

Abstract: OBJECTIVE: Impaired butyrate metabolism plays a part in ulcerative colitis (UC). To assess the usefulness of measuring butyrate metabolism as an indication of inflammatory activity, we investigated the rate of butyrate metabolism by breath test after administering [1-(13)C]-butyrate rectally to patients with UC. MATERIAL AND METHODS: Thirty-eight UC patients (22 active, 16 quiescent) and 15 healthy controls were given [1-(13)C]-butyrate enemas. The (13)CO2 production rate was measured by breath test using an infrared spectrometric analyzer. RESULTS: The quantity of expired (13)CO2 was significantly lower in the active than in the quiescent UC and control groups. Cumulative (13)CO2 production at 240 min showed significant negative correlations with the clinical activity index (r=-0.65, p<0.0001), endoscopic activity index (r=-0.63, p=0.0001) and histology (r=-0.71, p<0.0001) in the active UC group. The (13)CO2 production rate was significantly increased in the quiescent stage as compared with the active stage in six UC patients, in whom clinical remission was achieved, in accordance with improvements in the clinical activity index, the endoscopic activity index, histology and fecal butyrate concentrations. Significant inverse correlations between the cumulative (13)CO2 production rate and these three parameters were seen in these six UC patients assessed in both the active and quiescent stages. CONCLUSIONS: Measurement of expired (13)CO2 after rectally administering [1-(13)C]-butyrate in active and quiescent UC appears to be a promising and reliable method for evaluating disease activity and metabolic changes associated with amelioration of inflammation.

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.

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.

Tosa M, Negoro K, Kinouchi Y, Abe H, Nomura E, Takagi S, Aihara H, Oomori S, Sugimura M, Takahashi K, Hiwatashi N, Takahashi S, Shimosegawa T. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Scand J Gastroenterol. · Pubmed #16373276 No free full text.

Abstract: OBJECTIVE: Population-specific differences in the genetic susceptibility to inflammatory bowel disease (IBD) are indicated by the fact that Crohn's disease (CD) in Japanese patients does not have any of the common CARD15 variants that are associated with CD in Caucasians. Recently, the disease-causing mutation in the IBD5 haplotype was identified. The TC haplotype, composed of L503F in SLC22A4 and -207G/C in SLC22A5 promoters, was reported to alter the function of the organic cation transporter and to be associated with CD in Caucasians. To determine whether the TC haplotype is also associated with IBD in a Japanese population, we genotyped L503F and -207G/C variants in Japanese subjects. Furthermore, we also performed a case-control association study with all representative single nucleotide polymorphisms (SNPs) in IBD5 using previous information of linkage disequilibrium extension reported in Japanese patients to determine whether there were variants in IBD5 specifically associated with IBD in Japanese patients. MATERIAL AND METHODS: A total of 758 Japanese individuals, 241 patients with CD, 247 patients with ulcerative colitis (UC) and 270 healthy controls, were analyzed in this study. Genotyping for SNPs was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: We found L503F and -207G/C to be very rare (<1% frequency) in CD, UC and HC in the Japanese population. Furthermore, we also found that none of the representative SNPs in IBD5 was associated with CD or UC in the Japanese subjects. CONCLUSIONS: In contrast to Caucasians, IBD5 is not a major component of the susceptibility to IBD in the Japanese population.

Andoh A, Hirashima M, Maeda H, Hata K, Inatomi O, Tsujikawa T, Sasaki M, Takahashi K, Fujiyama Y. · Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan. · Nutrition. · Pubmed #15850963 No free full text.

Abstract: OBJECTIVE: Selenoprotein-P is a selenium-rich serum protein that carries more than 50% of serum selenium. We evaluated changes in serum selenoprotein-P levels in patients with inflammatory bowel disease. METHODS: Serum selenoprotein-P levels were measured by enzyme-linked immunosorbent assay. Twenty healthy individuals (controls), 34 patients with ulcerative colitis, and 37 patients with Crohn's disease (CD) were studied. RESULTS: A highly significant correlation was found between the serum selenium and selenoprotein-P levels. There was no significant difference in serum selenoprotein-P levels between healthy controls (average 3.4+/-0.8 microg/mL, n=20) and patients with ulcerative colitis (3.0+/-1.0 microg/mL, n=34). Serum selenoprotein-P levels were significantly lower in patients with CD (average 1.8+/-0.5 microg/mL, n=37). Serum selenoprotein-P levels were significantly lower in the elemental diet group of patients who had CD (average 1.4+/-0.4 microg/mL, n=17) than in the non-elemental diet group of patients who had CD (average 2.1+/-0.3 microg/mL, n=20). CONCLUSION: We found that the serum selenoprotein-P level is decreased in patients with CD. It may be a useful marker to monitor the systemic selenium status in various disorders.

Kitayama T, Funayama Y, Fukushima K, Shibata C, Takahashi K, Ogawa H, Ueno T, Hashimoto A, Sasaki I. · Department of Surgery, Division of Gastrointestinal and Colorectal Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. · Surg Today. · Pubmed #15772791 No free full text.

Abstract: PURPOSE: Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is now a common procedure for ulcerative colitis (UC). Moreover, it has been reported that fertility is preserved in women who undergo this procedure, many of whom can experience normal delivery. METHODS: We assessed the perinatal outcomes and changes in anal function in four women, aged from 27 to 35 years, who gave birth after undergoing IPAA for UC. Pregnancies were confirmed 15-111 months after IPAA, three women had full-term pregnancies, and one gave birth after 31 weeks' gestation. RESULTS: Cephalic delivery with a vacuum extractor was used for one patient, and another underwent cesarean section. The other two patients experienced normal delivery. None of the patients needed artificial insemination and none had any symptoms of intestinal obstruction during their pregnancy. After delivery, two patients suffered a transient increase in bowel frequency and soiling, which gradually resolved. CONCLUSIONS: Although transient anal dysfunction occurred in the puerperal period, there were no changes in anal function during pregnancy. Therefore, there are no factors directly prohibiting pregnancy and vaginal delivery in women who undergo IPAA for UC.

Saruta M, Takahashi K, Suzuki T, Torii A, Kawakami M, Sasano H. · Department of Pathology, Tohoku University School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. · J Clin Endocrinol Metab. · Pubmed #15531481 links to  free full text

Abstract: Ulcerative colitis (UC) is characterized by a long-standing chronic inflammation of the bowel with intermittent periods of exacerbation and remission. Its acute exacerbation appears to be related to various stresses. Urocortin 1 (Ucn1) may play important roles in integrated local responses to stress. We therefore examined local production of Ucn1 in patients with UC by immunohistochemistry and mRNA in situ hybridization. Ucn1 immunoreactivity was predominantly detected in lamina propria plasma cells and enterochromaffin cells. In UC patients without glucocorticoid treatment, Ucn1-positive cells and plasma cells increased in proportion to the severity of inflammation (P < 0.0001). Ucn1-positive cells significantly increased in UC patients with advanced inflammatory grades, compared with a control group (P < 0.0001) and nonspecific colitis group (P < 0.0001). In glucocorticoid-treated patients, Ucn1-positive cells were significantly lower in number, compared with the nonglucocorticoid-treated group. Ucn1 mRNA was expressed in lamina propria plasma cells, and both corticotropin-releasing factor(1) and corticotropin-releasing factor(2(a)) mRNAs were also partially coexpressed in these cells and macrophages. The present study showed that Ucn1-positive cells were correlated with the severity of inflammation in colonic mucosa with UC, and glucocorticoid treatment decreased these cells. Ucn1 therefore may act as a possible local immune-inflammatory mediator in UC.

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.

Ogawa H, Fukushima K, Naito H, Funayama Y, Unno M, Takahashi K, Kitayama T, Matsuno S, Ohtani H, Takasawa S, Okamoto H, Sasaki I. · Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. · Inflamm Bowel Dis. · Pubmed #12792221 No free full text.

Abstract: Although microorganisms play a role in gut inflammation, it remains uncertain which epithelial genes are expressed in response to luminal flora and whether these molecules are also involved in pathologic mucosal inflammation. Germ-free mice were orally challenged with a bacterial suspension prepared from conventionally housed mice (bacterial reconstitution). Thereafter, the differential gene expression in gut epithelial cells was identified by differential display. The expression of the identified genes was also examined in dextran sulfate sodium (DSS)-induced colitis and human inflammatory bowel disease (IBD) epithelial cells. Regenerating gene III (Reg III) was strongly induced in gut epithelial cells following bacterial reconstitution, as well as in the colitis initiated by DSS. The mRNA expression of hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP), a human counterpart of Reg III, was enhanced in colonic epithelial cells of patients with IBD. Reg III mRNA expression was localized in the epithelial cells including goblet cells and columnar cells in mice; on the other hand, HIP/PAP-expressing cells were correlated with Paneth cell metaplasia in human colon. Epithelial expression of Reg III or HIP/PAP was induced under mucosal inflammation initiated by exposure to commensal bacteria or DSS as well as inflamed IBD colon.

Hashimoto A, Funayama Y, Naito H, Fukushima K, Shibata C, Naitoh T, Shibuya K, Koyama K, Takahashi K, Ogawa H, Satoh S, Ueno T, Kitayama T, Matsuno S, Sasaki I. · First Department of Surgery, Tohoku University School of Medicine, Sendai, Miyagi, Japan. · Surg Today. · Pubmed #11318122 No free full text.

Abstract: To assess the advantages of a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis compared with conventional procedures, we retrospectively analyzed the results of the two procedures as follows: Eleven patients including five patients with familial adenomatous polyposis (FAP) and six with ulcerative colitis (UC) underwent a laparoscope-assisted proctocolectomy and hand-sewn ileal J-pouch anal anastomosis at our department from June 1997 to November 1999. This laparoscope-assisted colectomy (LAC) group was then compared with a group of 13 patients who had undergone conventional ileal pouch anal anastomosis using a standard laparotomy from 1986 to 1997. The median operative time of the LAC group was 8h 23min, which was 81 min longer than that of the standard colectomy (SC) group. The number of days during which eating was prohibited were similar in the two groups but the median postoperative hospital stay was significantly shorter in the LAC group (24.1 days). In the LAC group, the small incisions showed better cosmetic results and there was also a remarkable reduction in the degree of postoperative pain. In conclusion, a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis can be employed widely in patients with FAP and also in selected patients with UC.

Fukushima K, Sasaki I, Takahashi K, Naito H, Funayama Y, Matsuno S. · The First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan. · Tohoku J Exp Med. · Pubmed #10458490 links to  free full text

Abstract: Because the beginning of extraction of lamina propria mononuclear cells is to obtain mucosal tissues that are exposed to luminal bacteria, the contaminated endotoxin in this step and/or the enzymes for mucosal digestion may activate mucosal macrophages and other cells. To address this issue, endotoxin levels in isolation solutions were evaluated during the extraction of lamina propria mononuclear cells from 8 control, 7 Crohn's disease and 8 ulcerative colitis specimens. Endotoxin levels were measured using Toxicolor system based on the limulus tests. Endotoxin levels were consistently below 500 pg/ml, and more importantly, these in enzyme digestion solutions were comparable among control, Crohn's disease, and ulcerative colitis. Therefore, comparative experiments using lamina propria mononuclear cells from these mucosae can be appropriately carried out, at least as far as in a comparable amount of contaminated endotoxin. However, careful consideration is required for the comparative and functional study using peripheral blood and lamina propria mononuclear cells.

Fukushima K, Sasaki I, Takahashi K, Naito H, Matsuno S. · First Dept. of Surgery, Tohoku University, School of Medicine, Sendai, Japan. · Scand J Gastroenterol. · Pubmed #10232875 No free full text.

Abstract: BACKGROUND: Although epithelial cells in ulcerative colitis may be metabolically deficient, it remains unknown whether epithelial cells modulate energy metabolism in inflamed mucosa. The purpose of the present study is to investigate whether inflammatory mediators such as lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) alter energy metabolism in epithelial cells. METHODS: Adenosine 5'-triphosphate (ATP) levels in HT29 cells cultured with LPS, IL-1beta, IL-6, or TNF-alpha were measured with high-performance liquid chromatography, using a reversed-phase chromatography column. Cellular and mitochondrial (antimycin A-sensitive) respiration rates were determined polarographically, using a Clark-type oxygen electrode. RESULTS: When the cells were cultured with LPS, IL-6, and TNF-alpha but not IL-1beta, ATP levels increased significantly at 6 h, followed by a decrease at 24 h. Enhancement of oxygen consumption, which was completely blocked by antimycin A, was also shown at 3 h by the exposure to these substrates. CONCLUSION: LPS and proinflammatory cytokines induced cellular ATP generated by mitochondrial phosphorylation. An active energy production in epithelial cells on the exposure to inflammatory mediators may be critical for escape from chronic mucosal inflammation.

Funayama Y, Fukushima K, Shibata C, Koyama K, Miura K, Takahashi K, Hashimoto A, Sasaki I, Kinouchi Y, Hiwatashi N, Takeda K, Matsuno S. · No affiliation provided · J Gastroenterol. · Pubmed #15235881 No free full text.

This publication has no abstract.