Differences in Yeast Intolerance Between Patients with Crohn’s Disease and Ulcerative Colitis

Purpose Alimentary factors, especially those modifying the intestinal flora, may influence the course of inflammatory bowel disease. It is known that T and B cells of patients with Crohn’s disease can be stimulated with the yeast antigen, mannan. We evaluated the impact of eating habits with special respect to food containing yeast on the course of inflammatory bowel disease. Methods Questionnaires were sent to 180 German-speaking patients of the Inflammatory Bowel Disease Outpatient Clinic at the University Hospital Bern, Switzerland. The following information was obtained by the questionnaires: (1) course of disease, (2) eating habits, (3) environmental data, and (4) inflammatory bowel disease questionnaire. The survey was anonymous. Results A total of 145 patients (80.5 percent 95 with Crohn’s disease, and 50 with ulcerative colitis) responded. Food items containing yeast were better tolerated by patients with ulcerative colitis than by patients with Crohn’s disease. A significant difference between the two groups was observed concerning food containing raw yeast (dough, P = 0.04; and pastry, P = 0.001). Conclusions Food items containing raw yeast led to more frequent problems for patients with Crohn’s disease than for patients with ulcerative colitis. This observation supports our previous data, which showed the stimulatory effect of the yeast antigen, mannan, on B and T cells of patients with Crohn’s disease but not of controls. Poster presentation at Digestive Disease Week (DDW), organized by the American Gastrointestinal Association, Chicago, Illinois, May 14 to 19, 2005.     

Optical Coherence Tomography in Inflammatory Bowel Disease: Prospective Evaluation of 35 Patients

Purpose  Optical coherence tomography is a technique using infrared light in tissues of the gastrointestinal tract and human colon affected by inflammatory diseases. We evaluated whether there are specific patterns of optical coherence tomography for inflammatory bowel disease and compared the technique performance to the histology. Methods  Optical coherence tomography was performed in 35 patients (18 men; 31 ulcerative colitis, 4 Crohn’s disease). The images were obtained from affected and normal colon at endoscopy. Two biopsies of the sites visualized were taken. Two endoscopists scored the images, and two pathologists, blind to the endoscopy and optical coherence tomography, performed the histologic evaluation. Results  Three optical coherence tomography patterns were identified: 1) mucosal backscattering alteration, 2) delimited dark areas, and 3) layered colonic wall. Compared with the histology, mucosal backscattering alteration was the most effective in recognizing the disease in patients (P = 0.007 in colon segments affected, and P < 0.001 in normal segments). The sensitivity and specificity have been 100 and 78 percent, respectively. Conclusions  The in vivo optical coherence tomography correctly detected inflammatory bowel disease features in affected and apparently normal colon, and allowed to discriminate patterns for active ulcerative colitis and Crohn’s disease.     

Association of <Emphasis Type="Italic">SLC22A4/5</Emphasis> Polymorphisms with Steroid Responsiveness of Inflammatory Bowel Disease in Japan

Purpose We investigated the association between steroid responsiveness and single nucleotide polymorphisms of SLC22A4/A5 located within inflammatory bowel disease 5 locus. Our goal is personalized steroid therapy adjusted to match individual variations in drug responsiveness in each inflammatory bowel disease patient. Methods Unrelated Japanese cohorts of 94 patients with Crohn’s, 94 patients with ulcerative colitis, and 257 healthy control subjects were consecutively enrolled in this study. Genotyping and haplotype analysis focusing on steroid responsiveness was performed by using 15 single nucleotide polymorphisms. Results The G allele of −368T > G in SLC22A5, in which strong linkage disequilibrium was observed and the limited diversity of three haplotypes was estimated, was significantly associated with steroid resistance in Japanese patients with Crohn’s disease (P = 0.016). Haplotype analysis between −446C > T and −368T > G in the SLC22A5 promoter region showed that the CG allele appeared to be a risk haplotype for steroid resistance (CG: odds ratio, 4.13; 95 percent confidence interval, 1.41–12.1; P = 0.016). Conclusions This extensive linkage disequilibrium may form a general risk haplotype for steroid resistance in Crohn’s disease in Japanese. Further analyses of the pharmacogenomics of steroid responsiveness are warranted to achieve the goal of individualized steroid therapy against inflammatory bowel disease. Supported by a grant-in-aid from the Ministry of Health, Labour and Welfare (K.I.), Japan. Address of correspondence: Yoshiaki Arimura, M.D., First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan. E-mail: arimura@sapmed.ac.jp     

Clinical Features and Quality of Life in Patients with Different Phenotypes of Crohn’s Disease of the Ileal Pouch

Purpose Crohn’s disease of the pouch can occur in patients with colectomy and ileal pouch-anal anastomosis performed for ulcerative colitis. The clinical features of inflammatory, fibrostenotic, and fistulizing Crohn’s disease have not been characterized. Methods A total of 73 eligible patients with Crohn’s disease of the pouch, who were seen in the Pouchitis Clinic, were enrolled: 25 with inflammatory Crohn’s disease, 17 with fibrostenotic Crohn’s disease, and 31 with fistulizing Crohn’s disease. The clinical phenotypes of Crohn’s disease were based on a combined assessment of clinical, endoscopic, radiographic, and histologic features. Clinical symptoms, endoscopic and histologic features, and health-related quality-of-life scores were assessed. Results Demographic and clinical features, including preoperative and postoperative parameters, were similar between the three phenotypes of Crohn’s disease of the pouch. The use of nonsteroidal anti-inflammatory drugs, neuropsychiatric drugs, antidiarrheal agents, and Crohn’s disease medicines was not different between the three groups. Predominant symptoms, as expected, were significantly different between the three phenotypes: diarrhea and/or pain in 92 percent of patients with inflammatory Crohn’s disease, obstructive symptoms in 64.7 percent of patients with fibrostenotic Crohn’s disease, and fistular drainage in 51.6 percent of those with fistulizing Crohn’s disease (P < 0.0001). There was no statistical difference in quality-of-life scores between the three phenotypes, adjusted for disease activity. There was no significant correlation between quality-of-life and symptom scores in any of the three groups. Although not statistically significant, patients with fistulizing Crohn’s disease (16.1 percent) tended to have an increased risk for pouch failure compared with inflammatory (8 percent) or fibrostenotic (5.9 percent) Crohn’s disease. Conclusions Predominant symptoms were different in clinical phenotypes of Crohn’s disease. Each of the three phenotypes of Crohn’s disease similarly affected quality-of-life. Fistulizing Crohn’s disease may be associated with a higher risk for pouch failure. Supported by NIH R03 DK 067275 and an American College of Gastroenterology Clinical Research Award. Reprints are not available.     

Long-Term Quality of Life in Patients with Crohn’s Disease and Perianal Fistulas: Influence of Fecal Diversion

Purpose Symptomatic perianal fistulas impair quality of life in patients with Crohn’s disease. Fecal diversion improves symptoms but may impair quality of life. This study was designed to compare long-term quality of life in patients with Crohn’s disease with symptomatic perianal fistulas who were treated with or without fecal diversion. Methods From 1996 to 2002, perianal fistulas were treated in 116 patients with Crohn’s disease. A questionnaire, including four quality of life instruments, was mailed to each patient (Short-Form General Health Survey, Gastrointestinal Quality of Life Index, Cleveland Global Quality of Life Score, Short Inflammatory Bowel Disease Questionnaire). Results Questionnaires were returned by 77 of 116 patients (66 percent). Thirty-four of these patients had undergone fecal diversion, whereas 43 had not. Median follow-up was 49 (range, 18–97) months in diverted and 44 (range, 14–98) months in undiverted patients (not significant). In the diverted group, 44 percent complained of Crohn’s disease-related symptoms, which was less compared with 79 percent in undiverted patients (P < 0.05). Diverted patients achieved 68 ± 1 percent of the maximum possible score on the Gastrointestinal Quality of Life Index compared with 60 ± 2 percent in undiverted patients (mean ± standard error of the mean; P < 0.001); diverted patients scored better on the subscale “gastrointestinal symptoms” of the Gastrointestinal Quality of Life Index (81 ± 1 percent vs. 67 ± 2 percent; P < 0.001). There was no difference in the Short Inflammatory Bowel Disease Questionnaire between diverted and undiverted patients except for the subscale “bowel function” (91 ± 2 percent vs. 76 ± 2 percent; P < 0.0001). No difference in quality of life was detected by the Short-Form General Health Survey and Cleveland Global Quality of Life Score. Conclusions In the investigated population of patients with Crohn’s disease, quality of life seems to be similar or potentially superior in diverted patients suffering from perianal fistulas compared with undiverted patients. A diverting stoma, therefore, may improve quality of life in patients with severe perianal Crohn’s disease. Presented at the meeting of the American Gastroenterological Association, Digestive Diseases Week, Los Angeles, California, May 20 to 25, 2006, and published in abstract form Gastroenterology 2006;130(Suppl 2):A620.     

Certolizumab pegol,a monthly subcutaneously administered Fc-free anti-TNFα, improves health-related quality of life in patients with moderate to severe Crohn’s disease

Background and aims Certolizumab pegol, a polyethylene glycolated Fc-free Fab’ was efficacious and well tolerated in patients with moderate-to-severe Crohn’s disease in a previously reported randomized, placebo-controlled study. In this paper, we report the effect of certolizumab pegol on health-related quality of life (HRQoL). Materials and methods Patients with moderate-to-severe active Crohn’s disease (n = 292) received subcutaneous certolizumab pegol 100, 200, or 400 mg or placebo at weeks 0, 4, and 8. A post hoc analysis of the intent-to-treat population (290 patients with HRQoL data) assessed HRQoL by evaluating patients’ responses to the self-administered inflammatory bowel disease questionnaire (IBDQ) at baseline and weeks 2, 4, 6, 8, 10, and 12. Results Patients receiving certolizumab pegol 400 mg at weeks 0, 4, and 8 demonstrated, via their IBDQ total score, significantly (P ≤ 0.05) greater improvement in HRQoL from baseline to week 12 and at all other time points compared with placebo. Moreover, HRQoL improved over time in all certolizumab pegol groups, irrespective of baseline C-reactive protein levels. Emotional well-being (IBDQ Emotional Function domain) improved throughout the study for patients receiving certolizumab pegol 400 mg. This improvement was significantly (P ≤ 0.05) greater than for patients receiving placebo at all time points. In addition, systemic symptoms (IBDQ Systemic Symptoms domain) improved significantly more in patients receiving certolizumab pegol 400 mg than in those receiving placebo at weeks 4, 8, 10, and 12 (P ≤ 0.05) and approached statistical significance at week 2 (P = 0.054). Conclusion This analysis suggests that certolizumab pegol 400 mg improves HRQoL in patients with moderate-to-severe Crohn’s disease.     

Family History and Serology Predict Crohn’s Disease after Ileal Pouch-Anal Anastomosis for Ulcerative Colitis

Purpose Approximately 5 to 10 percent of patients undergoing ileal pouch-anal anastomosis with a diagnosis of ulcerative colitis are subsequently diagnosed with Crohn’s disease. Preoperative predictors for Crohn’s disease post-ileal pouch-anal anastomosis have not been prospectively defined. Methods A total of 238 consecutive patients with ulcerative colitis or indeterminate colitis undergoing ileal pouch-anal anastomosis were prospectively enrolled into a longitudinal database. Clinical factors were assessed perioperatively. Serum drawn preoperatively was assayed for anti-Saccharomyces cerevisiae, antiouter membrane porin-C, anti-CBir1, and perinuclear antineutrophil cytoplasmic antibody using enzyme-linked immunosorbent assay. Crohn’s disease was defined by small bowel inflammation proximal to the ileal pouch or a perianal fistula identified at least three months after ileostomy closure. Predictors were assessed in a multivariate Cox proportional hazards model to predict the rate of Crohn’s disease after ileostomy closure. Results Sixteen patients (7 percent) were diagnosed with Crohn’s disease; median time to Crohn’s disease was 19 (range, 1–41) months. Significant factors for postoperative Crohn’s disease after ileal pouch-anal anastomosis included family history of Crohn’s disease (hazard ratio, 8.4; 95 percent confidence interval, 2.96–24.1; P < 0.0001) and anti-Saccharomyces cerevisiae immunoglobulin-A seropositivity (hazard ratio, 3.14; 95 percent confidence interval, 1.1–9.81; P = 0.04). Crohn’s disease developed in only 8 of 198 patients (4 percent) without these predictors vs. 8 of 40 patients (20 percent) in those with at least one of these factors (P = 0.002). The cumulative risk of Crohn’s disease among patients with two risk factors (67 percent) was higher than in patients with either risk factor (18 percent) or neither risk factor (4 percent, P < 0.001). Conclusions Patients with ulcerative colitis and indeterminate colitis with a family history of Crohn’s disease or preoperative anti-Saccharomyces cerevisiae immunoglobulin-A seropositivity are more likely to be diagnosed with Crohn’s disease after ileal pouch-anal anastomosis. Poster presentation of distinction at Digestive Disease Week, Washington, D.C., May 19 to 24, 2007, and Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 7, 2007. Financial disclosures: Prometheus Laboratories Speakers’ Bureau (Eric A. Vasiliauskas, Konstantinos A. Papadakis, Marla Dubinsky, Andrew Ippoliti), shareholder (Carol Landers, Stephan R. Targan), and cofounder (Stephan R. Targan).     

Fecal Lactoferrin and Calprotectin After Ileocolonic Resection for Crohn’s Disease

Purpose This study was designed to assess the role of fecal lactoferrin and calprotectin as markers of intestinal inflammation in patients with Crohn’s disease who have undergone ileocolonic resection. Methods Sixty-three patients who had undergone ileocolonic resection for Crohn’s disease with a median follow-up of 40.5 (range, 5–102) months were enrolled. Clinical examination and blood test were performed, and fecal lactoferrin and calprotectin levels were dosed. The predictors for fecal lactoferrin and calprotectin levels that resulted to be significant at the univariate analyses were included in two multiple regression analysis models. Results The mean lactoferrin level was 21 ± 3.9 μg/g and the mean calprotectin fecal level was 247 ± 22.7 ng/ml. C-reactive protein levels (P < 0.01), calprotectin levels (P < 0.01), and the presence of clinical recurrence (P = 0.04) resulted to be independent predictors of lactoferrin levels. Only lactoferrin levels resulted to be an independent predictor for calprotectin fecal levels (P < 0.01). Conclusions Crohn’s disease patients maintain high fecal levels of lactoferrin and calprotectin at long-term follow-up after resection of the diseased bowel even in case of clinical remission. The significant correlation between the two fecal markers may be the expression of the ongoing intestinal inflammation. Only lactoferrin significantly correlated with C-reactive protein and showed a reliable threshold value for systemic inflammation. Lactoferrin fecal levels may be a reliable indicator for intestinal inflammation influencing the systemic inflammatory status. The third predictor of lactoferrin fecal level was the presence of episodes of clinical recurrence during the postoperative follow-up. Supported in part by the MIUR grant ex 60%.     

Therapeutic Efficacy of Infliximab on Patients with Short Duration of Crohn’s Disease: A Japanese Multicenter Survey

Purpose  This study was designed to evaluate the efficacy of infliximab in patients with Crohn’s disease of durations less than one year. Methods  Two nationwide surveys of 35 Japanese institutions majoring in inflammatory bowel disease identified 41 patients with active Crohn’s disease who were treated by infliximab within 12 months after the diagnosis (E-group) and 97 patients treated later during their clinical course (L-group). Clinical features, responses to infliximab, and accompanying medications were compared between the two groups. A decrease in Crohn’s disease activity index ≥70 or the index <150 two weeks after infliximab was regarded to be efficacious. Results  The age was younger (24 vs. 33 years, median, P < 0.0001) and intestinal stricture (12 vs. 49 percent, P < 0.0001), internal fistula (0 vs. 26 percent, P = 0.0003), and previous intestinal resection (7 vs. 57 percent, P < 0.0001) were less frequent in the E-group than in the L-group. The efficacy of infliximab was different between the two groups with a significantly higher value in the E-group than in the L-group (90 vs. 61 percent, P = 0.0012). A multivariate logistic regression analysis revealed nonstricturing intestinal lesion to be a significant factor related to the efficacy of infliximab. Conclusion  Infliximab is more efficacious in Crohn’s disease with short duration, probably because of less frequent stenosis. Supported by a grant of Research Committee of Inflammatory Bowel Disease, Japanese Ministry of Labour and Welfare. Presented at the meeting of the Japanese Society of Coloproctology, Tokyo, Japan, November 2 to 3, 2007.     

CT Enterography for Crohn’s Disease: Accurate Preoperative Diagnostic Imaging

Purpose CT enterography (CTE) is a technique that provides detailed images of the small bowel by using a low Hounsfield unit oral contrast media. This study was designed to correlate CTE findings with operative findings in patients with Crohn’s disease. Methods We performed a retrospective study of all patients with Crohn’s disease of the small bowel or colon, who had CTE and subsequent small bowel or colon surgery within three months after the CT examination. CTE findings of stricture, fistula, inflammatory mass, abscess, and combinations of these abnormalities were compared with operative findings. Specialist radiologists and fellowship-trained colorectal surgeons participated in the study. The Fisher’s exact test or chi-squared tests were used with respect to categorical data, and the Wilcoxon’s rank-sum test was used for quantitative data. Results In 36 patients, the presence or absence of stricture, fistula, abscess, or inflammatory mass was correctly determined by CTE in 100, 94, 100, and 97 percent, respectively. The accuracy for stricture or fistula number was 83 and 86 percent, respectively. There were nine patients with multiple disease phenotypes identified on CTE of which eight were confirmed at surgery. CTE overestimated or underestimated the extent of disease in 11 patients (31 percent). Conclusions CTE is an accurate preoperative diagnostic imaging study for small-bowel Crohn’s disease. The ability of this imaging study to detect both luminal and extraluminal pathology is a distinct advantage of CTE compared with small-bowel contrast studies. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

Expression of p53, VEGF, Microvessel Density, and Cyclin-D1 in Noncancerous Tissue of Inflammatory Bowel Disease

We aimed to evaluate the carcinogenesis risk in inflammatory bowel disease via p53 mutation and its relation with hyperproliferation (cyclin-D1) and angiogenesis (with vascular endothelial growth factor [VEGF] and microvessel density) and whether these events play important roles in pathogenesis of inflammatory bowel disease. Colonic tissue samples of 26 ulcerative colitis, 6 Crohn’s disease, and 8 amoebic colitis patients as well as samples of 10 healthy controls were stained with p53, cyclin-D1, CD34, and VEGF monoclonal antibodies by immunohistochemistry and evaluated semiquantitatively. Expression of p53 was higher in ulcerative colitis than in the healthy control and amoebic colitis groups (4.15 ± 2.07, 1.4 ± 1.5, 1.3 ± 1.5; P < 0.001). The Crohn’s disease group had the highest p53 expression (4.6 ± 1.6). The Crohn’s disease, ulcerative colitis, and amoebic colitis groups all had higher VEGF expression than did the healthy controls (respectively, 4.3 ± 1.2, 2.92 ± 2.0, 2.3 ± 1.5, 0.6 ± 0.97; P < 0.001). Also, microvessel density was statistically higher in all three colitis groups than in healthy controls. Cyclin-D1 expression in all four groups was similar. The study showed that p53 mutation was present in nonneoplastic mucosa of inflammatory bowel disease patients. Detecting strong p53 overexpression with VEGF overexpression may help in differentiating inflammatory bowel disease from other colitis.     

Fecal Calprotectin as a Predictor of Abnormal Colonic Histology

Purpose Gastroenterologists have been seeking reliable noninvasive indices of inflammatory and malignant bowel disease. This prospective study was to assess the value of fecal calprotectin in predicting abnormal histologic findings in patients undergoing colonoscopy. Methods Stool specimens supplied before colonoscopy by 72 consecutive patients were measured for calprotectin levels, and the findings correlated with the colonoscopy results and other fecal and blood parameters. Receiver operating characteristics curve analysis was used to determine the predictive value of fecal calprotectin for abnormal colonic histology. Results Patients with abnormal histologic findings had significantly higher calprotectin levels (218 ± 125 mg percent) than patients with normal colonoscopy (77 ± 100 mg percent). There was a highly significant correlation between calprotectin levels and erythrocyte sedimentation rate (r = 0.45, P = 0.008), positive fecal occult blood test (r = 0.57, P = 0.0001), and abnormal colonic histology (r = 0.54, P = 0.0001). Patients with active inflammatory bowel disease had higher calprotectin levels than the rest of the study patients (r = 0.3; P = 0.01). On multivariate analysis, calprotectin was a significant predictor of abnormal colonic histology (P = 0.005; odds ratio, 1.007; 95 percent confidence interval, 1.002–1.012). The area under the receiver operating characteristics curve was 0.79. A fecal calprotectin concentration of 150 μg/ml had a sensitivity of 75 percent, specificity of 84 percent, positive predictive value of 80 percent, and negative predictive value of 75 percent in predicting abnormal colonic histology. Conclusions Fecal calprotectin may serve as a simple, noninvasive surrogate marker of abnormal histologic findings in patients scheduled for colonoscopy. Presented at Digestive Disease Week, Los Angeles, California, May 21 to 24, 2006.     

1007fs, G908R, R702W Mutations and P268S, IVS8+158 Polymorphisms of the CARD15 Gene in Turkish Inflammatory Bowel Disease Patients and Their Relationship with Disease-Related Surgery

Introduction CARD15 gene mutations may present different frequencies in populations and sometimes surgical interventions may become a necessary therapy for inflammatory bowel disease patients. Mutations of 1007fs, G908R, R702W and polymorphisms of P268S, IVS8⁺¹⁵⁸ of the CARD15 gene and their relation with disease-related surgery were investigated in Turkish inflammatory bowel disease patients in this study. Material and Method 1007fs, G908R, R702W mutations and P268S, IVS8⁺¹⁵⁸ polymorphisms of CARD15 gene were analyzed in 130 inflammatory bowel disease patients (67 Crohn’s disease, 63 ulcerative colitis) and 87 healthy controls. After obtaining DNA samples, genotyping was performed by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) analysis. Results were evaluated by statistical analysis and accepted as significant if P < 0.05. Results R702W gene mutation was significantly lower in the inflammatory bowel disease group (1.5%) than the controls (4.8%) (P < 0.05). The overall allele frequency of mutations in the inflammatory bowel disease group (2.7%) was lower than in controls (6.6%) (P < 0.05). Disease-related surgery history was present in 20 Crohn’s and 25 ulcerative colitis patients; familial history was present in four Crohn’s and five ulcerative colitis patients. Statistically, no relationship was detected between disease-related surgeries and the investigated genetic tests. Conclusion In Turkish patients, no important relationship was detected between the investigated allele frequencies of the CARD15 gene and inflammatory bowel disease nor between disease-related surgeries and inflammatory bowel disease. Dedicated to the memory of the Turkish scientist Turgut Tukel MD. Thanks for his contributions and supports.     

Crohn’s Colitis: The Incidence of Dysplasia and Adenocarcinoma in Surgical Patients

Purpose Data supporting an increased risk of colorectal cancer in patients with Crohn’s colitis are inconsistent. Despite this, clinical recommendations regarding colonoscopic screening and surveillance for patients with Crohn’s colitis are extrapolated from chronic ulcerative colitis protocols. The primary aim of our study was to determine the incidence of dysplasia and carcinoma in pathology specimens of patients undergoing segmental or total colectomy for Crohn’s disease of the large bowel. In addition, we sought to identify risk factors associated with the development of dysplasia and carcinoma. Methods We performed a retrospective review of all patients operated on at our institution for Crohn’s colitis between January 1992 and May 2004. Data were retrieved from patient charts, operative notes, and pathology reports. Logistic regression was used to model the probability of having dysplasia or adenocarcinoma. Results Two hundred twenty-two patients (138 females) who underwent surgical resection for the treatment of Crohn’s colitis were included in the study. Mean age at surgery was 41 (range, 15–82) years and the mean duration of disease was 10 (range, 0–53) years. There were five cases of dysplasia (2.3 percent) and six cases of adenocarcinoma (2.7 percent). Three patients with dysplasia and one with adenocarcinoma were diagnosed on preoperative colonoscopy; while the other cases were discovered incidentally on pathologic examination of resected specimens. Factors associated with the presence of dysplasia or adenocarcinoma included older age at diagnosis (38.2 vs. 30.3 years, P = 0.02), longer disease duration (16.0 vs. 10.1 years, P = 0.05), and disease extent (90 percent extensive vs. 59 percent limited, P = 0.05). Conclusions Patients with severe Crohn’s colitis requiring surgery are at significant risk for developing dysplasia and adenocarcinoma, particularly when diagnosed at an older age, after longer disease duration, and with more extensive colon involvement. Presented at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, April 30 to May 5, 2005. Reprints are not available     

Interleukin-18 is increased only in a minority of patients with active Crohn’s disease

Background and aims It has been suggested that Crohn’s Disease (CD) is associated with an elevated T helper 1 response as manifested by increased production of interleukin-18 (IL-18). Local concentrations of neutralizing IL-18 binding proteins (IL-18bp) may counteract biological functions of mature IL-18 in mucosal inflammation. Therefore, we investigated the IL-18/IL-18bp system in a large group of patients with active inflammatory bowel disease (IBD) to identify patients that could respond theoretically to IL-18 neutralizing treatment strategies. Patient/methods IL-18 and IL-18bp messenger RNA (mRNA) expression in colonic mucosa from patients with active CD (n = 72), active ulcerative colitis (UC; n = 32), and non-IBD controls (infectious colitis or diverticulitis; n = 19) and normal, non-diseased controls (n = 20) were measured by reverse-transcribed real-time polymerase chain reaction. Mature IL-18 protein and IL-18bp expression in inflamed mucosa were assessed by Western blotting. Results/findings Although IL-18 mRNA was increased in some patients with CD, the increase was not statistically significant. Densitometric evaluation of IL-18/α-actin ratio in patients with active CD (n = 20) and patients with UC (n = 10) demonstrated an increased ratio of IL-18 protein in CD when compared to UC (1.04 vs 0.72 [median]). On closer inspections, only 7/20 CD patients had an increased IL-18 protein expression in inflamed areas compared to noninflamed mucosa. Interpretation/conclusion IL-18 expression in active CD is heterogeneous, only a minority of patients expresses elevated levels. Further treatment strategies targeting IL-18 expression in active CD should be concentrated on this subgroup of patients.     

Incidence and Risk of Intestinal and Extra-intestinal Complications in Medicaid Patients with Inflammatory Bowel Disease: A 5-Year Population-Based Study

Background and Aim  

Intestinal and extra-intestinal complications are associated with inflammatory bowel disease (IBD) but their exact incidence is not well known. In order to improve our understanding of their incidence and impact, we assessed the complications associated with ulcerative colitis (UC) and Crohn’s disease (CD) in a population-based study in Medicaid patients.     

Colonic Ornithine Decarboxylase in Inflammatory Bowel Disease: Ileorectal Activity Gradient,Guanosine Triphosphate Stimulation,and Association with Epithelial Regeneration but Not the Degree of Inflammation and Clinical Features

The role of colonic mucosal ornithine decarboxylase (ODC) in inflammatory bowel disease (IBD) remains controversial. This study assessed mucosal ODC activity in IBD patients segment by segment with regard to patient characteristics, disease activity/duration, medication, degree of mucosal inflammation, and presence/absence of epithelial regeneration and guanosine triphosphate (GTP) stimulation. Mucosal ODC activity was determined in biopsy specimens from the terminal ileum, cecum/ascending, transverse, and descending colon, and the sigmoid/rectum of 35 patients with IBD (18 with Crohn’s disease, 17 with ulcerative colitis) and 29 controls, using the amount of ¹⁴CO₂ liberated from (carboxyl-¹⁴C)ornithine hydrochloride. GTP-stimulatable activity was expressed as the ratio of ODC activity in the presence and absence of GTP (70 μmol/L). Mucosal inflammation was assessed endoscopically/microscopically with previously described criteria. Presence/absence of mucosal regeneration also was determined by predefined criteria. Mucosal ODC-activity did not significantly differ in IBD patients and controls. There was a 4.4-fold activity gradient from the ileum to the rectum. Mucosal ODC activity was significantly higher in areas with epithelial regeneration compared to those without regeneration, and was stimulated by GTP by a factor of 1.42 in Crohn’s disease and 1.19 in ulcerative colitis patients compared to controls (p < 0.004). On the other hand, there was no significant association/relationship of mucosal ODC activity with disease activity/duration and the endoscopic/histologic degree of mucosal inflammation. The observation of unchanged mucosal ODC activity in patients with IBD and the absence of a significant relationship with clinical and endoscopic/histologic disease characteristics speaks against a major role of ODC in IBD as a major disease marker. The role of the ileorectal gradient, the enhanced activity in areas with epithelial regeneration, and the GTP-stimulatable form, however, need further investigation with regard to a possible involvement in carcinogenesis in IBD.     

Risk Factors for Intra-Abdominal Septic Complications After a First Ileocecal Resection for Crohn’s Disease: A Multivariate Analysis in 161 Consecutive Patients

Purpose This study was designed to assess predictive factors of postoperative intra-abdominal septic complication in a homogenous group of patients undergoing ileocecal resection for Crohn’s disease. Methods From 1984 to 2004, 161 consecutive patients with Crohn’s disease (81 males; mean age, 33 ± 10 years) underwent, as a first operation, an elective ileocecal resection without temporary stoma. Postoperatively, 15 patients (9 percent) developed abdominal septic complications, including abscess and anastomotic leaks. Possible factors for postoperative intra-abdominal septic complication were analyzed by both univariate and multivariate analyses. Results There was no postoperative death. Multivariate analysis found only four independent factors associated with a higher risk of postoperative intra-abdominal septic complication: poor nutritional status (odds ratio, 6.23 (1.75–22.52)), intra-abdominal abscess discovered during surgery (odds ratio, 7.47 (1.5–37.69)), preoperative steroids use more than three months (odds ratio, 5.95 (1.04–34.1)), and recurrent clinical episode of Crohn’s disease (odds ratio (per episode), 1.38 (1.03–1.9)). Conclusions Recurrent clinical episode of Crohn’s disease, preoperative steroids use, poor nutritional status, and the presence of abscess at the time of surgery significantly increased the risk of septic abdominal complications after first ileocecal resection for Crohn’s disease. Knowledge of these risk factors could permit to propose a temporary stoma in very high-risk patients (i.e., with 3 or more risk factors). Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, April 30 to May 5, 2005.     

Activation and Perceived Expectancies: Correlations with Health Outcomes Among Veterans with Inflammatory Bowel Disease

Objective  Inflammatory bowel disease imposes psychosocial stress on the patient. Patients′ adaptive capacities may predict quality of life. We examined two adaptive capacity measures and their association with quality of life. Design  Cross-sectional mail survey of patients with inflammatory bowel disease. The Patient Activation Measure (PAM) assesses knowledge, skill, and confidence in self-health management. The Perceived Expectancies Index (PEI) measures perceived competence and dispositional optimism. Setting/Patients  Four hundred and seventy-seven veterans at VA-Tennessee Valley Healthcare System. Main Outcome Measure  Primary outcome was health-related quality of life (measured by the Short Inflammatory Bowel Disease Questionnaire). Bivariate analysis assessed unadjusted correlations. Sequential multivariate linear regression tested theoretical model relationships by calculating the variation in each dependent variable accounted for by independent variables (R-squared statistic). Results  Two hundred and sixty surveys were returned with usable data (54.5%). Median age was 63 years (range 19–91); 90.8% were men and 86.9% self-identified as white. Fifty percent reported having ulcerative colitis, 36.5% Crohn’s disease, and 12.3% uncertain type. Unadjusted bivariate analysis revealed positive correlations between the PAM and PEI and the Short Inflammatory Bowel Disease Questionnaire (correlation coefficient = 0.35 and 0.60, respectively; p < 0.0001). Multivariate model including the PAM accounted for 26% of the variation in Short Inflammatory Bowel Disease Questionnaire scores, while the model including the PEI accounted for 50% (p < 0.0001). Conclusions  There are positive, highly significant correlations between adaptive capacities and health-related quality of life in patients with inflammatory bowel disease. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.