Search

Background: The noninferiority of pH-dependent release mesalamine (Asacol) once daily (QD) to 3 times daily (TID) administration was investigated., Methods: This was a phase 3, multicenter, randomized, double-blind, parallel-group, active-control study, with dynamic and stochastic allocation using central registration. Patients with ulcerative colitis in remission (a bloody stool score of 0, and an ulcerative colitis disease activity index of ≤2), received the study drug (Asacol 2.4 g/d) for 48 weeks. The primary efficacy endpoint of the nonrecurrence rate was assessed on the full analysis set. The noninferiority margin was 10%., Results: Six hundred and four subjects were eligible and were allocated; 603 subjects received the study drug. The full analysis set comprised 602 subjects (QD: 301, TID: 301). Nonrecurrence rates were 88.4% in the QD and 89.6% in the TID. The difference between nonrecurrence rates was -1.3% (95% confidence interval: -6.2, 3.7), confirming noninferiority. No differences in the safety profile were observed between the two treatment groups. On post hoc analysis by integrating the QD and the TID, nonrecurrence rate with a mucosal appearance score of 0 at determination of eligibility was significantly higher than the score of 1. The mean compliance rates were 97.7% in the QD and 98.1% in the TID., Conclusions: QD dosing with Asacol is as effective and safe as TID for maintenance of remission in patients with ulcerative colitis. Additionally, this study indicated that maintaining a good mucosal state is the key for longer maintenance of remission.

An 80-year-old Japanese woman suffered multiple brain infarctions of unknown etiology during maintenance therapy of prednisolone and azathioprine for ulcerative colitis. Although a small cavity in the left lung spontaneously regressed, the patient suddenly died of massive brain hemorrhage due to disseminated aspergillosis, which was not identified until autopsy.

Background: Both ulcerative colitis (UC) and Crohn's disease (CD) have a complex etiology involving multiple genetic and environmental factors. Many genome-wide association studies (GWAS) and subsequent replication studies revealed that both diseases share some of the susceptibility loci; however, common genetic factors for both diseases are not fully elucidated. This study is aimed to identify the common genetic factors for CD and UC by a meta-analysis of published studies., Methods: We first reviewed the 10 GWAS for CD to select candidate single nucleotide polymorphisms (SNPs). Next, we performed a PubMed literature search up to June 30, 2010 and carried out a systemic review of published studies that examined the association of CD susceptibility loci in UC patients. Meta-analysis was carried out using the inverse variance-weighted method or the DerSimonian-Laird method after estimating the heterogeneity among the studies. The data for highly linked SNPs were combined. Finally, we performed a meta-analysis of 43 published studies in 45 SNPs located at 33 loci by using a total of 4852 to 31,125 subjects., Results: We confirmed the association of 17 reported common susceptibility loci. Moreover, we found associations at eight additional loci: GCKR, ATG16L1, CDKAL1, ZNF365, LRRK2-MUC19, C13orf31, PTPN2, and SBNO2. The genetic risk of each locus was modest (odds ratios ranged from 1.05-1.22) except IL23R., Conclusions: These results indicate that CD and UC share many susceptibility loci with small genetic effect. Our data provide further understanding of the common pathogenesis between CD and UC., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Aims: Activation-induced cytidine deaminase (AID) is a DNA/RNA-editing enzyme that is essential for hypermutation and class-switch recombination in immunoglobulin genes. The aim of this study was to investigate the expression of AID and its association with p53 mutation in ulcerative colitis (UC)-associated carcinogenesis., Methods and Results: The expression of AID was examined in 25 patients with UC-associated neoplasia, 20 UC patients without neoplasia, 18 patients with non-inflamed colorectal mucosa unaffected by UC, and 19 patients with sporadic colorectal cancer, by immunohistochemistry and quantitative reverse transcription polymerase chain reaction analysis. Mutational analysis and immunohistochemistry for p53 were also performed. The degree of AID expression was not different between UC-associated neoplasia and sporadic colorectal cancer. However, AID was expressed in both UC-associated neoplasia and UC without neoplasia. Whereas AID expression in UC-associated neoplasia was not correlated with the grade of dysplasia, expression in non-neoplastic mucosa of UC was correlated with the histological grade of inflammation. In UC-associated neoplasia, there was no significant correlation between AID expression and p53 mutation., Conclusions: AID is associated with inflammation in UC, whereas it may not specifically contribute to carcinogenesis in UC., (© 2011 Blackwell Publishing Limited.)

Aim: Autofluorescence imaging (AFI) is a novel technology for endoscopy, which enhances neoplastic lesions of the gastrointestinal tract. The aim of this investigation was to examine whether AFI colonoscopy can identify dysplasia in ulcerative colitis., Method: We examined 48 patients with ulcerative colitis by AFI colonoscopy. Apparently flat, coarse granular mucosa and visible protruding lesions under conventional colonoscopy were observed by AFI. Those target areas were classified into low AF and high AF according to the colour under AFI colonoscopy. The grade of dysplasia was determined in the specimens obtained from the target areas., Results: About 126 sites (35 protruding lesions and 91 flat areas) were examined by AFI colonoscopy. AF was determined to be high in 42 areas and to be low in 84 areas. The positive rate of dysplasia was higher in protrusions (31%) than in flat mucosa (3.3%, P < 0.0001). The rate of positive dysplasia was not statistically different between lesions determined to be low AF (14%) and those to be high AF (5%, P = 0.09). The positive rate of dysplasia in protruding lesions was significantly higher in low AF than in high AF (45.0%vs 13.3%, P = 0.043), while the value in flat lesions was not different between low AF and high AF (8.2%vs 0%, P = 0.3)., Conclusions: Autofluorescence imaging colonoscopy seems to have a role for the detection of dysplaia in ulcerative colitis., (© 2010 The Authors. Colorectal Disease © 2010 The Association of Coloproctology of Great Britain and Ireland.)

Background: Mesalamine has been used as the first-line medication for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two different mesalamine formulations in the maintenance of remission in patients with UC., Methods: In a multicenter, double-blind, randomized study, 131 patients with quiescent UC were assigned to two groups: 65 to receive a pH-dependent release formulation of mesalamine at 2.4 g/day (pH-2.4 g) and 66 to receive a time-dependent release formulation of mesalamine at 2.25 g/day (Time-2.25 g). Both formulations were administered three times daily for 48 weeks. The primary endpoint was the proportion of patients without bloody stools., Results: In the full analysis set (n = 130), the proportion of patients without bloody stools was 76.9% in the pH-2.4 g and 69.2% in the Time-2.25 g, demonstrating the noninferiority of pH-2.4 g to Time-2.25 g. No statistically significant difference in time to bloody stools was found between the two formulations (P = 0.27, log-rank test), but the time to bloody stools tended to be longer in pH-2.4 g compared to Time-2.25 g, and a similar trend was observed with regard to the time to relapse. No differences were observed between the safety profiles of the two formulations., Conclusions: The pH- and time-dependent release of mesalamine formulations were similarly safe and effective. Interestingly, the remission phase tended to be longer in the group that received the pH-dependent formulation compared to the group that received the time-dependent formulation (UMIN Clinical Trials Registry, no. C000000289).

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC., Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI)., Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles., Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288).

Ulcerative colitis is one of the principal forms of inflammatory bowel disease with complex manifestations. Although previous studies have indicated that there is a genetic contribution to the pathogenesis of ulcerative colitis, the genes influencing susceptibility to the disease have not been fully determined. To identify genetic factors conferring risk of ulcerative colitis, here we conducted a two-stage genome-wide association study and subsequent replication study using 1,384 Japanese individuals with ulcerative colitis and 3,057 control subjects. In addition to the expected strong association with the major histocompatibility complex (MHC) region, we identified three new susceptibility loci: the immunoglobulin receptor gene FCGR2A (rs1801274, P = 1.56 x 10(-12)), a locus on chromosome 13q12 (rs17085007, P = 6.64 x 10(-8)) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 x 10(-8)). rs1801274 is a nonsynonymous SNP of FCGR2A that is reported to have a critical effect on receptor binding affinity for IgG and to be associated with other autoimmune diseases. Our findings provide insight into the molecular pathogenesis of ulcerative colitis.

We describe a case of a 47-year old Japanese man with steroid-dependent, refractory ulcerative colitis complicated by non-tuberculous mycobacterial skin infection. The patient remained in remission by combination therapy of 100mg azathioprine and 27.5mg prednisolone (total dose over 25g for three years), but developed a deep genital ulcer. Mycobacterium szulgai was confirmed by skin culture, and the ulcer became turned into a scar after oral administration of isoniazid, rifampicin, and ethanbutol.

8-Hydroxy-guanine (8-OH-G) mismatches readily with adenine residues, leading to a G : C to T : A transversion mutation. The human mutY homologue (MUTYH) excises adenine misincorporated opposite 8-OH-G during replication and suppresses mutations caused by reactive oxygen species. We defined the expression of 8-hydroxydeoxyguanosine (8-OHdG) and MUTYH in ulcerative colitis (UC)-associated neoplasia by immunohistochemistry and compared this with expression in UC patients without neoplasia and patients unaffected by UC. We also performed mutation analyses for MUTYH and K-ras. 8-OHdG was expressed more intensely in the mucosa of UC-associated neoplasia and UC without neoplasm than in the mucosa unaffected by UC. Immunohistochemistry with two different types of MUTYH antibody showed that UC-associated neoplasia and UC without neoplasia exhibited strong cytoplasmic expression and attenuated nuclear expression of MUTYH when compared with patients unaffected by UC. No pathological MUTYH mutations were detected in any of the UC-associated neoplasia cases. However, K-ras mutation was detected in two cases, one of which showed G : C to T : A transversion mutation and attenuated nuclear staining of MUTYH. In conclusion, inflamed mucosa of UC is exposed to oxidative damage. An increase in cytoplasmic MUTYH, rather than its mutation, may contribute to the promotion of carcinogenesis in UC.

Background and Aim: Narrow band imaging (NBI) is a novel endoscopy system, which enables a clear visualization of the mucosal vasculature of the gastrointestinal tract. The aim of this study is to determine whether this system may be of value for assessing the disease severity in ulcerative colitis (UC)., Materials and Methods: We observed the mucosal vascular pattern (MVP) in 157 colorectal segments of 30 patients with UC using both conventional and NBI colonoscopy. The MVP was determined to be normal or distorted under conventional colonoscopy and, subsequently, to be clear or obscure under NBI colonoscopy. The histologic variables in each segment were assessed in biopsy specimen. The possible correlation between MVP and the histologic grade of inflammation was evaluated., Results: The MVP under conventional colonoscopy was normal in 60 segments while it was distorted in 97 segments. In all of the former 60 segments, their MVP was clear under NBI colonoscopy. The MVP in the latter 97 segments were determined to be clear (n = 44) or obscure (n = 53) under NBI colonoscopy. Acute inflammatory cell infiltrates (26% vs. 0%, p = 0.0001), goblet cell depletion (32% vs. 5%, p = 0.0006), and basal plasmacytosis (2% vs. 21%, p = 0.006) were more frequently observed in segments with an obscure MVP than in those with a clear MVP., Conclusion: NBI colonoscopy may be of value for determining the grade of inflammation in patients with quiescent UC.

Background: Narrow-band imaging (NBI) is a novel illumination technology for endoscopy that enhances vasculature of the GI tract., Objective: The aim was to elucidate whether NBI colonoscopy can identify dysplasia in patients with ulcerative colitis (UC)., Design: Cross-sectional study of eligible patients., Setting: Single center., Patients: 46 patients with UC., Interventions: Apparently flat mucosa at each segment and visible protruding lesions were observed by magnifying NBI colonoscopy. The surface structure was classified into honeycomb-like, villous, or tortuous pattern. The grade of dysplasia was determined in the specimens obtained from protrusions and from flat mucosa., Main Outcome Measurements: The positive predictive value of conventional and NBI colonoscopy for the diagnosis of dysplasia., Results: A total of 296 sites (20 protruding lesions and 276 flat areas) were examined by NBI colonoscopy. The surface pattern was determined to be honeycomb like in 161 sites, villous in 85 sites, and tortuous in 50 sites. Five dysplastic lesions were detected in 3 patients. A patient had 3 dysplastic lesions and the other 2 had a dysplastic lesion each. The positive rate of dysplasia was higher in protrusions (2/20 sites, 10%) than in flat mucosa (3/276 sites, 1.1%, P = .038; however, correction for the multiple testing of data removes this significance). When the surface pattern was taken into account, the rate of positive dysplasia was higher in the tortuous pattern (4/50 sites, 8%) than in the honeycomb-like or villous patterns (1/246 sites, 0.4%, P = .003)., Limitations: Uncontrolled study., Conclusions: The tortuous pattern determined by NBI colonoscopy may be a clue for the identification of dysplasia during surveillance for UC.

Purpose: The microsatellite instability and CpG island hypermethylation of p14 ( ARF ) and p16 ( INK4a ) are related to the pathogenesis of neoplasia in ulcerative colitis. This study was designed to assess the significance of those genetic or epigenetic alterations for cancer surveillance in ulcerative colitis., Methods: During surveillance colonoscopy in 39 patients with ulcerative colitis, biopsy specimens were obtained from the cecum and the rectum as well as from any other areas suspected of being neoplasia by chromoscopy. Using DNA extracts, the methylation status of p14 ( ARF ) and p16 ( INK4a ) and the microsatellite status were determined., Results: Microsatellite instability was positive in one of five dysplasias, but it was negative in the cecum and the rectum. The incidence of hypermethylation of p14 ( ARF ) was 0 percent in the cecum, 26 percent in the rectum, and 100 percent in dysplasia, whereas that of p16 ( INK4a ) was 10, 10, and 0 percent, respectively. Patients who were positive for the hypermethylation of p14 ( ARF )in the rectum had a longer duration of ulcerative colitis than those who were negative for such hypermethylation. Two of 10 patients who were positive for p14 ( ARF ) hypermethylation in the rectum and 1 of 29 patients who were negative for the hypermethylation had dysplasia. During the subsequent surveillance of 36 patients, dysplasia was detected in 2 of 8 patients with p14 ( ARF ) hypermethylation and in none of 28 patients without hypermethylation (P = 0.044)., Conclusions: In patients with ulcerative colitis, hypermethylation of p14 ( ARF ) seems to be associated with an early stage of dysplasia. The hypermethylation may be one of candidates for potential biomarker to identify patients at a high risk of dysplasia.

Background and Aims: Immunosuppressive therapy with intravenous ciclosporin is an alternative treatment option to total colectomy for patients with ulcerative colitis (UC), while the benefits of oral administration of tacrolimus are not well defined and are based on reports of several uncontrolled studies., Methods: Patients with refractory active UC were randomly assigned to a high trough concentration (10-15 ng/ml) group (HT group) (n = 21), low trough concentration (5-10 ng/ml) group (LT group) (n = 22), or placebo group (n = 20). Patients received an initial oral dose of 0.025 [DOSAGE ERROR CORRECTED] mg/kg tacrolimus or placebo twice daily. Efficacy was evaluated in 60 patients based on a disease activity index (DAI) score. Fifty eight patients had additional treatment with tacrolimus and were evaluated for efficacy in a 10 week open label extension., Results: An improvement in DAI score (>or=4 points, all categories improved) was observed for 68.4% of cases in the HT group compared with 10.0% in the placebo group (p<0.001). In the HT group, 20.0% of patients had clinical remission and 78.9% had mucosal healing. In the open label extension, 55.2% of all patients had an improved DAI score at week 10. Mean dose of prednisolone was reduced from 19.7 mg/day at study entry to 7.8 mg/day at week 10. The incidence of side effects in the HT group was significantly higher than that of the placebo group (p = 0.043). The most common event was mild finger tremor., Conclusions: Our findings demonstrate dose dependent efficacy and safety of oral tacrolimus for remission-induction therapy of refractory UC. The optimal target range appears to be 10-15 ng/ml in terms of efficacy with two week therapy.

Aminosalicylates have a wide range of anti-inflammatory and immunomodulatory effects. Oral salazosulfapyridine (SASP) and 5-aminosalicylic acid (5-ASA) are the 'first-line' therapy for induction of remission in mild to moderate active ulcerative colitis (UC). SASP, which is consisted of 5-ASA and sulfapyridine, has greater incidence of side effects. 5-ASA is a therapeutically active compound, while sulfapyridine is related to adverse effects. For this reason, 5-ASA formulas exclusive of sulfapyridine were developed and they enabled higher dose of 5-ASA administration without adverse effects. Topical treatment by 5-ASA enema or SASP suppository should be considered for the treatment of proctitis or distal type of UC. Oral aminosalicylate therapy is also effective for the maintenance of remission in UC. Therefore, aminosalicylates are key drugs for the treatment of UC.

A 32-year-old Japanese woman with a 14-month history of ulcerative colitis (UC), pancolitis type, was referred to our institution, because of abdominal distention. Plain abdominal X-ray and computed tomography (CT) showed marked dilatation of the right side of the colon. The patient was treated by immediate total colectomy, with the diagnosis of toxic megacolon. Macroscopically, there was a constricting lesion with giant polyposis in the middle part of the transverse colon. Histologically, there was transmural inflammation with a thickened proper muscular layer overlaid by inflammatory polyposis. This case suggests that giant polyposis in UC patients may result in severe stenosis and that such a condition should not be misinterpreted as toxic megacolon or as colitic cancer.

A male patient with a 17 year history of intractable ulcerative colitis of the entire type was treated by total proctocolectomy. Colonoscopy before surgery did not identify dysplasia. Histological examination of the resected colorectum revealed that, in addition to chronic inflammatory infiltrates, there were 21 areas of microcarcinoids located in the muscularis propria and in the superficial layer of the submucosa. Carcinoids may be more common than previously thought, and they may be a reactive phenomenon to a variety of factors in ulcerative colitis.

Purpose: In Japan, leukocytapheresis has become an accepted therapy for ulcerative colitis. The purpose of this retrospective study was to determine the efficacy of additional leukocytapheresis in patients with moderate-to-severe recurrence of ulcerative colitis., Methods: From 1998 to 2002, 35 patients with moderate-to-severe recurrence of ulcerative colitis were treated by intravenous prednisolone only or prednisolone plus leukocytapheresis once per week. Previous clinical features of ulcerative colitis, activity index at four weeks, and subsequent course were compared between patients with leukocytapheresis and those without., Results: Sixteen patients were treated with prednisolone only (prednisolone group), and 19 patients were treated with prednisolone plus leukocytapheresis (leukocytapheresis group). Previous prednisolone dose (13.6 +/- 10.4 g vs. 7.9 +/- 9.8 g; P < 0.05) was higher in the leukocytapheresis group than the prednisolone group. Clinical response rate at four weeks was not different between the two groups (leukocytapheresis group, 68.4 percent vs. prednisolone group, 75 percent). However, ulcerative colitis activity index at four weeks was significantly higher in the leukocytapheresis group than the prednisolone group (180.5 +/- 44.2 vs. 142.5 +/- 45.3; P < 0.05). During the subsequent clinical course, 15 of 35 patients required proctocolectomy (leukocytapheresis group, 11 patients vs. prednisolone group, 4 patients). Proctocolectomy rate was significantly different when patients were divided by previous prednisolone dose (P = 0.0029) and ulcerative colitis activity index at four weeks (P = 0.002), but it was not different according to the application of leukocytapheresis. Cox proportional hazards model revealed previous prednisolone dose to be the only independent risk factor for proctocolectomy., Conclusions: Addition of leukocytapheresis to prednisolone therapy does not seem beneficial in ulcerative colitis patients with moderate-to-severe recurrence.

Objectives: Multiple biopsy has been a recommended procedure for cancer surveillance in patients with ulcerative colitis (UC). The aim of this study was to investigate the accuracy of chromoscopic findings in surveillance for patients with UC., Methods: During the period 1995-2002, we performed 117 surveillance colonoscopies in 57 patients with pancolitis for more than 5 yr. Multiple biopsy specimens were uniformly obtained from flat mucosa in each segment of the colorectum, and, when necessary, from areas specified by chromoscopy. The specified area was classified as polypoid lesion or visible flat lesion. In each specimen, histology was graded according to the classification of dysplasia., Results: Among 818 specimens, 28 (3.4%) were positive for dysplasia. There were 20 low grade dysplasias and eight high grade dysplasias. Dysplasia was more frequently positive in visible flat lesions (37.1%, p < 0001) and in polypoid lesions (16.9%, p < 0.0001) than in flat mucosa (0.4%, p < 0.0001). Furthermore, it was more frequently positive in visible flat lesions than in polypoid lesions (p < 0.05). High-grade dysplasia was found in 4.4% of polypoid lesions and in 14.8% of visible flat lesions, but it was not detected in flat mucosa. Overall, dysplasia was detected in 12 patients. Positive dysplasia was confined to visible flat lesions in four patients and to flat mucosa in one patient., Conclusions: Our results suggest that biopsy from flat visible lesions under chromoscopy might improve the accuracy of cancer surveillance in UC.

Patients with ulcerative colitis (UC) have a less frequent prior history of appendectomy than the general population. The aim of the present investigation was to elucidate histological and immunological characteristics of the appendix in UC and to assess the effect of appendectomy on the disease. Nine subjects with mildly active UC were treated by surgical appendectomy. In four subjects, the histological findings of the appendix were compatible with ulcerative appendicitis. CD3+CD4+CD25+, CD3+CD4+CD45RO+, and CD3+CD8+CD45RO+ appendiceal mononuclear cells were significantly higher in UC than in acute appendicitis and in normal appendix. There was a trend towards higher mRNA transcripts of IFN-gamma in the appendix of UC than those in other two groups. Clinical activity index decreased significantly four weeks after the appendectomy, although the effect was transient. The appendix is a site of involvement in UC, where mononuclear cells are presumed to be at a state of basal activation.

A case of ulcerative colitis complicated by Wilson's disease is described. In this case, ulcerative colitis occurred 12 years after the diagnosis of Wilson's disease, and the colitis was intractable to prednisolone and salazosulfapyridine. Because copper is one of the trace elements necessary for antioxidant defenses during inflammatory process, altered copper metabolism may have contributed to the intractability of the ulcerative colitis in this case.

Background: The appendix is occasionally involved in patients with distal ulcerative colitis. This study investigated the clinical significance of patchy involvement at the appendiceal orifice in ulcerative colitis., Methods: Colonoscopy was performed in 40 patients with active distal ulcerative colitis of mild to moderate severity. Patients were divided into 2 groups based on the presence or absence (positive or negative) of involvement at the appendiceal orifice at colonoscopy. Clinical activity, histologic grade of inflammation, and subsequent clinical course were compared between patients who were positive (appe(+)) and negative (appe(-))., Results: Twenty-three patients had involvement at the appendiceal orifice (reddish mucosa with mucinous exudate). The proximal-most extent of involvement by ulcerative colitis, the endoscopic grade, and clinical activity were not different between appe(+) and appe(-) groups. However, histologic grade of inflammation in the ascending colon was higher in the appe(+) group than in the appe(-) group. The endoscopic remission rate at 12 months was higher in the appe(+) group than in the appe(-) group (84% vs. 40%, p < 0.05)., Conclusions: In patients with distal ulcerative colitis, involvement at the appendiceal orifice may be indicative of histologically active disease, which responds reasonably well to pharmacotherapy.

A rare case of concurrent primary biliary cirrhosis and ulcerative colitis is described in a 61 year-old Japanese male. Primary biliary cirrhosis was diagnosed on the basis of characteristic histologic findings and a positive serum mitochondrial antibody test. Ulcerative colitis was diagnosed from typical findings on colonoscopy and the histologic features of a sigmoid colon biopsy specimen. This is the 12th report of a patient presenting with the combination of primary biliary cirrhosis and ulcerative colitis. The potential autoimmune relationships on the basis of these conditions are discussed.

Objective: Mucosal inflammation in ulcerative colitis (UC) is presumed to be regulated by Th2-like cytokines. The aim of this study was to characterize local expression of various cytokines mRNA., Methods: Total RNA was extracted from rectal biopsy specimens in 61 patients with UC, 18 inflammatory controls, and 16 noninflammatory controls. Reverse-transcription polymerase chain reaction (RT-PCR) was used to determine mRNA expression of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-10, IL-13, and IL-15., Results: Expression of IL-10 was more frequent in UC (75.4%) than in noninflammatory controls (37.5%, p < 0.01). IL-4 was more frequently positive in UC (41%) than in inflammatory controls (5.6%, p < 0.01) and in noninflammatory controls (6.3%, p < 0.01). Positive expressions of IL-4 (66.7% vs 20.6%, p < 0.01) and IL-13 (63.0% vs 29.4%, p < 0.01) were higher in active UC than in inactive UC. The positive rate of IL-2, interferon (IFN)-gamma, and IL-15 expression showed no difference among the groups divided by clinical, endoscopic, and histological grade of inflammation., Conclusions: These findings suggest that in active UC, IL-4 is pivotal, in combination with other Th2-like cytokines. In contrast, Th1-like cytokines and IL-15 bear no definite relation to local inflammation of UC.

Background: A magnifying colonoscope that enables high-power observation of the colorectal mucosa has been recently developed. The aim of this study was to investigate the value of the magnifying instrument in determining the severity of ulcerative colitis., Methods: Magnifying colonoscopy was performed in 41 patients with ulcerative colitis, and the findings in the rectum were graded according to network pattern and cryptal openings. These findings were correlated with endoscopic, clinical, and histologic severity of the disease., Results: Magnifying colonoscopy did not detect network pattern in 37% and cryptal opening in 24% of the subjects. The clinical, endoscopic, and histologic grades of activity were not different between groups divided by the presence or absence of each finding. However, when the two features were coupled, patients with visible network pattern and cryptal opening had a lower clinical activity index and lower grade of histologic inflammation than those in whom both findings could not be visualized., Conclusions: Observation under magnifying colonoscopy can be another clue to determining the severity of disease in patients with ulcerative colitis.

Purpose: To determine to usefulness of barium enema examination in detecting dysplasia in patients with ulcerative colitis., Materials and Methods: Radiographic findings of 22 areas of dysplasia in 10 patients (seven men, three women; aged 34-81 years at diagnosis) were reviewed. Serial changes in radiographic features of four areas of dysplasia in three patients were retrospectively investigated., Results: Fourteen of 22 areas of dysplasia were shown on radiographs. Dysplasia in the rectum or sigmoid colon was depicted less frequently than that in other segments of the colon. Radiographic features were classified as obvious nodular protrusions (seven lesions), irregular mucosa (five lesions), or nodular protrusions with irregular mucosa (two lesions). Six of the seven areas of dysplasia shown as irregular mucosa were accompanied by minute spiculations in the margin of the colonic lumen. There was no correlation between radiologic features and histologic grade of dysplasia., Conclusion: Barium enema examination may be used as a complementary method of cancer surveillance with endoscopy. These methods show about two-thirds of lesions associated with dysplasia.

We describe a very rare case in which macroamylasemia was associated with ulcerative colitis of total colitis type. The patient's serum amylase isozyme pattern by electrophoresis showed a broad abnormal peak toward the side of the positive pole compared with regular salivary and pancreatic fractions. Sephadex G-200 column chromatography showed a sedimentation coefficient of 6.6 S. Amylase activity was bound to IgG. Double diffusion experiments demonstrated that amylase activity could be precipitated in gel by an antibody to the lambda chain. Although inflammatory bowel disease is occasionally associated with hyperamylasemia due to pancreatitis, we emphasize that, when hyperamylasemia is recognized in patients with inflammatory bowel disease, macroamylasemia also should be considered.

To elucidate the long-term outcome of the ulcerative colitis we analyzed 124 patients suffering for more than 10 years concerning the long-term prognosis, cumulative rate of colectomy, cumulative risk of cancer development and cumulative survival rate. Long-term prognosis were divided to three categories as good, fair and poor, according to present disease activities, social availability and subjective judgement. One hundred and twenty four patients were divided to 66 patients with good prognosis, 27 fair and 31 poor (2:1:1). The rate of patients having active disease at each year were followed-up annually for 10 years according to final three categories of the prognosis. The serial curve of annual rate of having active disease of the patients with poor prognosis was the highest, fair prognosis the second, good prognosis the lowest. The factors affecting the final prognosis were the period before initiation of proper treatment, the severity of the first attack or the elder age (> 40 year old) at the first attack. Twenty six patients were undergone colectomy in relation to ulcerative colitis. The cumulative colectomy rate was 16.5% at 10 years and 38.5% at 15 years after the onset. Malignant disease or severe dysplasia of the colon developed in 4 patients 10 to 14 years after the onset. Cumulative survival rate was equal to the expected survival curve during 16 years. The main causes of death were intracranial hemorrhage and colorectal malignant disease.

During the past 10 years, 122 patients with ulcerative colitis were diagnosed by double-contrast barium enema and colonofiberscopy with endoscopic biopsy. Among them, five patients (4%) had longitudinal ulcers and eccentric deformities in the colon. Other radiologic findings included thumbprinting (two cases), sacculations (two cases), and inflammatory polyps (four cases). The possibility of the concomitance of ischemic colitis in cases of ulcerative colitis is discussed, due to their radiographic similarities.

We reported a case of 21 years old male with ulcerative colitis in whom barium-enema follow-up study demonstrated two localized narrowing areas with clustered inflammatory polyps in the transverse colon although there was no severe attack during the 3-year observation period. In this case, the possibility of malignant changes was considered radiographically, but denied endoscopically and histologically by examining the nature of the polyps.

The long chain fatty acid composition of phospholipids in colonic mucosa was determined by high performance liquid chromatography in nine patients with active ulcerative colitis and eight healthy controls. The arachidonic acid composition was 12.5 +/- 1.4 mol % (mean +/- 2 SEM) in the inflamed colonic mucosa from the patients with active ulcerative colitis and 6.8 +/- 1.2 mol % in the intact mucosa from healthy controls (p less than 0.001). In the inflamed colonic mucosa, oleic acid and palmitoleic acid were concomitantly decreased (p less than 0.001 and p less than 0.02, respectively), while docosahexaenoic acid was increased (p less than 0.05). Histopathological examination showed that there was a three fold increase in the cell density of inflammatory infiltrate in the lamina propria of the inflamed colonic mucosa (p less than 0.001). The cell density of inflammatory infiltrate correlated with the arachidonic acid composition of phospholipids in colonic mucosa (r = 0.89, p less than 0.005). These findings indicate that inflammation alters the long chain fatty acid composition of phospholipids in colonic mucosa. The observed increase in the arachidonic acid composition of phospholipids in inflamed colonic mucosa may contribute to the enhanced arachidonic acid metabolism in patients with active ulcerative colitis.