S100A Expression and Interleukin-10 Polymorphisms Are Associated with Ulcerative Colitis and Diarrhea Predominant Irritable Bowel Syndrome

Background

Both ulcerative colitis (UC) and diarrhea-predominant irritable bowel syndrome (IBS-D) are associated with alterations in enteric serotonin (5-HT) signaling.

Aims

The purpose of this study was to compare the rectal and sigmoid colonic mucosal expression of S100A proteins and functional polymorphisms of the 5-HT transporter (5HTT) and interleukin-10 genes in patients with IBS-D or UC with healthy controls.

Methods

mRNA expression of S100 proteins was measured in sigmoid and rectal biopsies and in rectal epithelium isolated by laser-captured microdissection. Leucocyte DNA was analyzed by PCR-based reaction fragment length polymorphisms and direct sequencing. Clinical symptoms were assessed by the self-rating depression scale and by the gastrointestinal symptom rating scale.

Results

Fifty patients with IBS-D, 56 with UC and 50 healthy controls were studied. Colonic mucosal expression of S100A8 and S100A9 in UC was significantly higher than in IBS or controls and correlated with the UC disease activity index (r = 0.65, p < 0.001). S100A10 expression in the rectal epithelium of the IBS patients was significantly higher (0.643 vs. 0.402, p = 0.01) than in controls and correlated with the SDS scores (r = 0.41, p = 0.002). The frequency of IL10-819 CC genotype was significantly higher in IBS-D (10.7 vs. 0 %, p = 0.047) and UC (16 vs. 0 %, p = 0.007) than that in controls.

Conclusion

Overexpression of S100A10 in the rectum may play a role in IBS as it is involved in modulating 5-HT1B receptors. The IL10-819 CC is a candidate genotype for both IBS and UC in Japanese.     

Severe Disease Activity and Cytomegalovirus Colitis Are Predictive of a Nonresponse to Infliximab in Patients with Ulcerative Colitis

Background and Aims

The role of infliximab in the treatment of patients with ulcerative colitis (UC) in Asia is still unclear. The aim of this study was to evaluate the clinical outcomes of infliximab therapy in Korean UC patients, including efficacy and predictors of response.

Methods

Patients who received infliximab induction therapy for moderate to severe UC at Asan Medical Center were retrospectively analyzed. The demographic characteristics of these patients and their clinical outcomes following infliximab therapy were evaluated.

Results

Of the 89 UC patients receiving infliximab induction therapy, 53 (59.6 %) were steroid-refractory and 36 (40.4 %) were steroid-dependent. At the initiation of infliximab, the median Mayo score was 9 (range 7–12). After the induction therapy of infliximab, 59 patients (66.3 %) demonstrated a clinical response at week 8, of which 29 (32.6 %) were determined to be in clinical remission. A colectomy was performed within 1 year after infliximab initiation in 11 (36.7 %) of 30 patients who displayed no clinical response to infliximab therapy, but in none of the 59 patients who showed a response to this drug (p < 0.001). Multivariate regression analysis identified severe disease (Mayo score ≥ 11) at the initiation of infliximab (p = 0.007) and history of cytomegalovirus colitis within 3 months prior to infliximab treatment (p = 0.001) as independent positive predictors of nonresponse to infliximab.

Conclusions

The efficacy of infliximab in Korean UC patients seems to be similar to that of previously published Western reports. Severe disease and a history of cytomegalovirus colitis are predictors of a nonresponse to infliximab.     

Increased Pulse Wave Velocity and Carotid Intima-Media Thickness in Patients with Ulcerative Colitis

Background

Ulcerative colitis (UC) is characterized with chronic, progressive inflammation of the gastrointestinal tract. The association of UC with cardiovascular disease is still a matter of debate.

Aim

The aim of this study was to investigate whether carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cf-PWV) as surrogates of atherosclerosis and arterial stiffness are increased in patients with UC.

Methods

Our study was cross-sectional and observational in design. Baseline characteristics were recorded during interview with the patient. Patients with previous cardiovascular disease, rheumatoid arthritis, chronic renal failure, and infectious and inflammatory disorders other than UC were excluded. Thirty-seven consecutive patients with UC and 30 control participants underwent cf-PWV assessment and CIMT measurement. The diagnosis of UC was based on clinical, radiologic, endoscopic, and histological findings.

Results

CIMT, cf-PWV, and C reactive protein were significantly higher in patients with UC. Although linear regression analyses identified UC as an independent predictor of CIMT (β ± SE, 0.39 ± 0.08; p < 0.001), only age independently predicted cf-PWV (β ± SE, 0.08 ± 0.03; p = 0.003) in our study population. Moreover, we revealed higher CIMT and PWV values in patients with higher disease activity and more extensive involvement, compared to patients with mild activity and limited disease.

Conclusion

We revealed increased pulse wave velocity and CIMT in patients with UC. UC appears to be associated with arterial stiffness and atherosclerotic burden, but the underlying mechanisms require further studies to be identified.     

Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis

Purpose/Aim

Colon cancer risk is high in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid has been shown to have some promise as a chemopreventive agent. A meta-analysis was performed to compare the efficacy of ursodeoxycholic acid in the prevention of colonic neoplasia in patients with UC and PSC.

Methods

Multiple databases were searched (January 2011). Studies examining the use of ursodeoxycholic acid vs. no ursodeoxycholic acid or placebo in adult patients with UC and PSC were included. Data were extracted in standard forms by two independent reviewers. Meta-analysis for the effect of ursodeoxycholic acid was performed by calculating pooled estimates of adenoma or colon cancer formation by odds ratio (OR) with random effects model. Heterogeneity was assessed by calculating the I ² measure of inconsistency. RevMan 5 was utilized for statistical analysis.

Results

Four studies (n?=?281) met the inclusion criteria. The studies were of adequate quality. Ursodeoxycholic acid demonstrated no overall improvement in adenoma (OR 0.53; 95?% CI: 0.19?1.48, p?=?0.23) or colon cancer occurrence (OR 0.50; 95?% CI: 0.18?1.43, p?=?0.20) as compared to no ursodeoxycholic acid or placebo in patients with UC and PSC.

Conclusion

Ursodeoxycholic acid use in patients with UC and PSC does not appear to decrease the risk of adenomas or colon cancer.     

Clinical Presentation and Disease Course of Inflammatory Bowel Disease Differs by Race in a Large Tertiary Care Hospital

Background

While the incidence of inflammatory bowel disease (IBD) among African-Americans (AAs) is increasing, there is limited understanding of phenotypic differences and outcomes by race.

Aim

To describe disease characteristics of AA patients compared to Caucasian (Ca) patients in a tertiary care population.

Methods

We performed a cross-sectional review of the IBD registry at the University of Chicago from January 2008 to January 2013. Data regarding race, phenotype, disease onset, disease duration, medical therapy, and surgical treatment were abstracted from the database, then compared via Pearson’s chi-square analysis, Kruskal–Wallis analysis, and logistic regression with a significance level of p < 0.05.

Results

A total of 1,235 patients with Crohn’s disease (CD) and 541 patients with ulcerative colitis (UC) included 108 AA CD patients and 28 AA UC patients. AA CD patients had an increased rate of IBD-related arthralgias (36.5 vs. 23.9 %, p < 0.01) and surgery (p < 0.01), less ileal involvement (57.8 vs. 71.0 %, p < 0.01), and no differences for other extraintestinal manifestations or disease locations compared to Ca CD patients. AA UC patients were older at diagnosis, had an increased rate of arthralgias (28.6 vs. 14.6 %, p = 0.047) and ankylosing spondylitis/sacroiliitis (7.1 vs. 1.6 %, p = 0.035), with no differences for disease extent or rate of IBD-related surgeries compared to Ca UC patients. There were no differences in medication usage by race for CD and UC patients.

Conclusion

We identified significant differences in disease characteristics and extraintestinal manifestations between AA and Ca IBD patients in a large tertiary care population. These results have implications for future genotype-phenotype studies.     

Assessing Health Status in Inflammatory Bowel Disease Using a Novel Single-Item Numeric Rating Scale

Background

Current instruments used to measure disease activity and health-related quality of life in patients with Crohn’s disease (CD) and ulcerative colitis (UC) are often cumbersome, time-consuming, and expensive; although used in clinical trials, they are not convenient for clinical practice. A numeric rating scale (NRS) is a quick, inexpensive, and convenient patient-reported outcome that can capture the patient’s overall perception of health.

Aims

The aim of this study was to assess the validity, reliability, and responsiveness of an NRS and evaluate its use in clinical practice in patients with CD and UC.

Methods

We prospectively evaluated patient-reported NRS scores and measured correlations between NRS and a range of severity measures, including physician-reported NRS, Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), inflammatory bowel disease questionnaire (IBDQ), and C-reactive protein (CRP) in patients with CD. Subsequently, we evaluated the correlation between the NRS and standard measures of health status (HBI or simple colitis clinical activity index [SCCAI]) and laboratory tests (sedimentation rate [ESR], CRP, and fecal calprotectin) in patients with CD and UC.

Results

The patient-reported NRS showed excellent correlation with CDAI (R ² = 0.59, p < 0.0001), IBDQ (R ² = 0.66, p < 0.0001), and HBI (R ² = 0.32, p < 0.0001) in patients with CD. The NRS showed poor, but statistically significant correlation with SCCAI (R ² = 0.25, p < 0.0001) in patients with UC. The NRS did not correlate with CRP, ESR, or calprotectin. The NRS was reliable and responsive to change.

Conclusions

The NRS is a valid, reliable, and responsive measure that may be useful to evaluate patients with CD and possibly UC.     

Effect of Follow-Up Endoscopy on the Outcomes of Patients with Inflammatory Bowel Disease

Background

Little is known about the role of follow-up endoscopy in patients with inflammatory bowel disease (IBD).

Aim

The present study aimed to evaluate whether repeated endoscopies would be beneficial in improving outcomes of patients with IBD.

Methods

Patients who had been initially confirmed to have IBD at two tertiary hospitals in Korea were regularly followed and included in this study. The clinical impact as assessed by the presence or absence of a change in management after endoscopy and cumulative hospitalization rate was compared between two groups classified according to the presence or absence of indications.

Results

A total of 188 patients with IBD were enrolled [69 patients with Crohn’s disease (CD) and 119 with ulcerative colitis (UC)]. Of these patients, 130 underwent follow-up endoscopy (48 with CD and 82 with UC). The rate of management change was significantly higher in the group with indications for follow-up endoscopy (p = 0.001 in CD and <0.001 in UC). The presence of any indications for follow-up endoscopy was found to be a significant predictor of hospitalization risk in patients with UC (p = 0.015), but not in those with CD. However, there was no significant difference in cumulative hospitalization hazard with respect to treatment change in patients without any endoscopic indications (p = 0.561 in CD and 0.423 in UC).

Conclusions

Follow-up endoscopy might not have a significant impact on the overall clinical course and outcomes in patients with IBD. However, the presence of endoscopic indications predicts a poor clinical outcome in UC.     

Sporadic Duodenal Adenoma and Association with Colorectal Neoplasia: A Case–Control Study

Background

Sporadic duodenal adenomas are uncommon. Prior studies show that patients with sporadic duodenal adenoma have increased risk of colorectal neoplasia and should undergo colorectal screening. However, the nature of the risk, location, and type of colorectal neoplasia are not well studied.

Aim

We aimed to identify the risk of colorectal neoplasia in patients who have duodenal adenomas.

Methods

A retrospective case–control study was conducted to identify sporadic duodenal adenoma patients using the databases at one academic center. Colonoscopic findings including histology and location of colorectal cancer neoplasia in sporadic duodenal adenoma patients were compared with a control group of patients without duodenal adenomas who underwent both gastroduodenoscopy and colonoscopy.

Results

Hundred and two patients with sporadic duodenal adenomas or adenocarcinomas were identified. Colonoscopy was performed in 47 patients (46 %), and colorectal neoplasia was present in 22 (46 %). There was a significantly higher rate of colorectal neoplasia in patients with sporadic duodenal adenoma (43 %) compared to the control group (24 %) odds ratio 4.8, 95 % confidence interval (1.7–7.4), but not for advanced colorectal adenoma (9 vs. 26 %, p = 0.17). Case patients had significantly more right-sided lesions than matched controls (p = 0.02).

Limitations

Single-center, retrospective study.

Conclusions

Individuals with sporadic duodenal adenomas have a significantly higher risk of colorectal neoplasia and proximal location of neoplasia. Therefore, these patients should undergo colonoscopy with particular attention to the right colon.     

Relationship Between Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels and Inflammatory Bowel Disease Type and Activity

Background and Aim

Neutrophil gelatinase associated lipocalin (NGAL) is a recently identified molecule, which is bacteriostatic, has tissue destructive effects and is pro-inflammatory with chemoattractant molecule binding properties. Our aim was to investigate the relationship between serum NGAL levels and the type and level of disease activity of IBD.

Methods

A total of 92 patients [43 with Crohn’s disease (CD) and 49 with ulcerative colitis (UC)], and 30 age- and sex-matched healthy controls (HC) were included in this study. Serum NGAL levels were measured using ELISA.

Results

Serum NGAL levels were elevated in the IBD group [median 171, range (57–312) ng/mL] compared to the HC group [107 (45–234) ng/mL] (p < 0.0001) and were elevated in UC patients [188 (74–312) ng/mL] compared to CD patients [168 (57–279) ng/mL] (p = 0.006). When NGAL levels were further analysed based on localization of the CD and UC, the levels in ulcerative pancolitis [233 (144–312) ng/mL] were significantly higher (p = 0.004) than the left-sided colitis [156 (103–309) ng/mL]. Similarly, NGAL levels were significantly higher in colonic CD [207 (125–249) ng/mL] than ileal CD [114 (78–210) ng/mL], and also in ileocolonic CD [198 (57–279) ng/mL] than ileal CD (p = 0.033). When CD and UC groups were further categorized as active and inactive according to clinical and endoscopic activity indices, serum NGAL concentrations did not differ between inquiescent versus active stages. When a cut-off level of 129 ng/mL was used to distinguish IBD from HC, a sensitivity of 76.1 % and a specificity of 60.9 % was reached.

Conclusions

The serum NGAL levels in the IBD group was significantly higher than the HC group. Serum NGAL levels were higher in more extensive colonic involvement.     

Randomized clinical trial: Atorvastatin versus placebo in patients with acute exacerbation of mild to moderate ulcerative colitis

Background

Statins are known to possess pleiotropic anti-inflammatory properties which have been evaluated for clinical benefits in a number of disorders. Studies have demonstrated beneficial actions of statins in experimental models of colitis. Clinical evidence in acute exacerbation of ulcerative colitis (UC) is lacking.

Aim

This study aims to assess the efficacy and safety of add-on atorvastatin in mild to moderately severe acute exacerbation of UC.

Methods

Patients with acute exacerbation of UC were randomized to receive either atorvastatin (20 mg) or matching placebo once daily orally for 8 weeks in addition to the standard therapy. Clinical efficacy was assessed by using partial Mayo score (PMS).

Results

Previously diagnosed 64 cases of UC presenting with mild to moderately severe acute exacerbation were randomized to receive either atorvastatin of 20 mg or placebo. Mean PMS increased by 1.5 points and decreased by 0.31 points in atorvastatin and placebo groups, respectively, at 8 weeks compared to the baseline values (p?=?0.04). Eight (25 %) and 13 (40.6 %) patients attained the primary outcome criteria for clinical improvement in the atorvastatin and placebo arms, respectively (p?=?0.18). Fifteen (46.8 %) patients in the atorvastatin group and no patient in the placebo group had ≥2 point increase in PMS after 8 weeks (p?<?0.001).

Conclusion

Atorvastatin therapy in acute exacerbation of UC may not be associated with beneficial effects. Paradoxical increase in disease activity may be seen in some patients. However, these findings need to be substantiated in larger studies.     

Colon capsule endoscopy versus standard colonoscopy in assessing disease activity of ulcerative colitis: a prospective trial

Background

The aim of our study was to compare colon capsule endoscopy (CCE) with standard colonoscopy (SC) in the assessment of mucosal disease activity and localization of inflammatory colonic mucosa in patients with known ulcerative colitis (UC).

Methods

Thirteen symptomatic patients (8 males, 5 females, mean age 38.5 ± 12.0 years) with known UC (mean duration of colitis: 9.7 ± 8.1 years) and indication for endoscopy due to suspected disease activity were included. All patients underwent CCE (first generation capsule, Given Imaging Ltd., Yokneam, Israel) on day 1 followed by SC on day 2 in a single center non-randomized, non-placebo-controlled diagnostic study (NCT00837304). SC and CCE were video recorded, and analysis was independently performed by 6 experienced endoscopists. The modified Rachmilewitz score was calculated, and Wilcoxon signed-rank test was used for analysis. Difference in recognition of disease activity by the endoscopists was assessed by application of the Kruskal–Wallis test.

Results

Assessment of disease activity revealed a significantly higher Rachmilewitz score of 7.3 ± 2.9 in the SC group compared to 4.8 ± 3.4 in the CCE group. Significantly, more detection of vessel vulnerability, granulated mucosa and mucosal damage was seen by SC. Disease extension was underestimated by CCE compared to SC. Disease activity assessment by means of SC or CCE did not differ statistically between the investigators (p = 0.26 and p = 0.1, respectively). After CCE, the capsule egestion rate was 77 %. The overall acceptance of both procedures was similar.

Conclusion

Considering the significantly different assessment of disease activity and significantly more appropriate assignment of the horizontal spread of inflammation by SC versus CCE, we recommend the preferential use of SC in the assessment of inflammation in UC patients.     

Is Pyloric Gland Metaplasia in Ileal Pouch Biopsies a Marker for Crohn’s Disease?

Background

Approximately 5–10 % of ulcerative colitis (UC) patients who undergo ileal pouch-anal anastomosis (IPAA) will develop postoperative complications such as refractory pouchitis or a change in diagnosis to Crohn’s disease (CD). Serological markers and histologic aspects of the pouch such as pyloric gland metaplasia (PGM) have been associated with a risk for these complications.

Methods

Twenty-eight IPAA patients with either CD of the pouch or chronic pouchitis (cases) and 36 IPAA controls who experienced a normal postoperative course were originally consented. Of these 64 subjects, 22 cases and 17 controls had histopathologic and serologic data available and were subsequently enrolled. Demographic and clinical data were entered into a database, blood analyzed for serological markers (Prometheus Labs, San Diego, CA) and biopsies of the pouch and the afferent limb reviewed by two GI pathologists.

Results

Of the cases, 55 % (12/22) had evidence of PGM in their pouch and/or small bowel biopsies, as compared to 12 % (2/17) of the controls (p = 0.006). Of 13 subjects with CD, 77 % (10/13) were found to have PGM versus subjects with chronic pouchitis in which 22 % (2/9) were found to have PGM (p = 0.03). There was a trend of ASCA positivity (both IgG and IgA, p = 0.20) and of higher ASCA titer levels (p = 0.07) with postoperative complications.

Conclusion

This study suggests that the presence of ileal pouch PGM is associated with postoperative complications and favors a diagnosis of CD over UC with chronic pouchitis.     

Vitamin D Deficiency and Corticosteroid Use Are Risk Factors for Low Bone Mineral Density in Inflammatory Bowel Disease Patients

Background

As several factors can contribute to low bone mineral density (BMD), we investigated the role of vitamin D in low BMD while controlling for other risk factors in inflammatory bowel diseases (IBD) patients.

Methods

We conducted a prospective cross-sectional study between 2008 and 2012 in adult IBD patients. Demographic data including age, gender, ethnicity, BMI, along with disease type and location, vitamin D levels, prior corticosteroid use, and anti-TNF use were recorded and evaluated with DEXA results.

Results

A total of 166 patients [105 Crohn’s disease (CD), 61 ulcerative colitis (UC)] qualified for the study. Low BMD was found in 40 %, twice as frequently in CD than in UC (p = 0.048). Higher prevalence of low BMD was associated with those of male gender (p = 0.05), Asian ethnicity (p = 0.02), and history of corticosteroid use (p = 0.001). Age, body mass index, or disease location did not increase the risk of low BMD. The overall prevalence of low vitamin D was 60 %, with insufficiency (25-hydroxy levels between 20 and 30 ng/mL) found in 37 % and deficiency (levels <20 ng/mL) found in 23 % of the patients. Vitamin D insufficient and deficient patients were two times (p = 0.049) and almost 3 times (p = 0.02) as likely to have low BMD, respectively.

Conclusions

Low vitamin D, male gender, Asian ethnicity, CD, and corticosteroid use significantly increased the risk of having low BMD, while age and disease location did not affect BMD in our IBD population. It remains important to evaluate for vitamin D nutritional deficiency and limit corticosteroid use to help prevent low BMD in IBD patients.     

Association of PTPN22 gene (rs2488457) polymorphism with ulcerative colitis and high levels of PTPN22 mRNA in ulcerative colitis

Purpose

Our aims were to evaluate protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene polymorphisms in ulcerative colitis (UC) and explore PTPN22 mRNA levels in colonic biopsies of UC patients in central China.

Methods

A total of 165 Chinese UC patients and 300 healthy controls were enrolled in this study. PTPN22 ?1123G/C, +1858C/T, and +788G/A polymorphisms were genotyped by PCR-restriction fragment length polymorphism method. PTPN22 mRNA expressions in colonic biopsies and serum C-reactive protein (CRP) levels were determined by quantitative PCR and immunonephelometry, respectively.

Results

The frequency of C carrier was higher in UC patients than in healthy controls (66.7 vs. 53.3 %, P?=?0.005, odds ratios?=?1.75, 95 % CI 1.18–2.60) and associated with extensive colitis (P?=?0.029). PTPN22 mRNA levels were elevated in UC patients than in healthy controls (P?<?0.001). Among UC patients, PTPN22 mRNA expression levels were higher in biopsies of inflamed colonic tissue compared with noninflamed tissue (P?<?0.001) and were correlated with CRP levels (r?=?0.578, P?<?0.001). PTPN22 mRNA expression levels were elevated in extensive colitis compared to proctitis (P?=?0.008) and to left-sided colitis (P?=?0.029) and were higher in moderate and severe disease than in mild disease (P?=?0.005).

Conclusions

Our study showed the potential association between PTPN22 ?1123G/C polymorphism and UC in central China. PTPN22 mRNA levels were highly expressed in UC, especially in active disease, and were correlated with CRP levels, disease location, and disease severity in UC patients.     

PTGER4 modulating variants in Crohn’s disease

Purpose

Variants modulating expression of the prostaglandin receptor 4 (PTGER4) have been reported to be associated with Cohn’s disease (CD), but the clinical impact remains to be elucidated. We analyzed these variants in a large German inflammatory bowel disease (IBD) cohort and searched for a potential phenotype association.

Methods

The variants rs4495224 and rs7720838 were studied in adult German IBD patients (CD, n?=?475; ulcerative colitis (UC), n?=?293) and healthy controls (HC, n?=?467). Data were correlated to results from NOD2 genotyping and to clinical characteristics.

Results

We found a significant association for the rs7720838 variant with overrepresentation of the T allele to CD (p?=?0.0058; OR 0.7703, 95 % CI 0.641–0.926) but not to UC. Furthermore, logistic regression analysis revealed that the presence of the T allele was associated with stricturing disease behavior in CD patients (p?=?0.03; OR 1.84, 95 % CI 1.07–3.16). Interestingly, the chance for developing stricturing disease behavior was enhanced if mutant alleles in both rs7720838 and NOD2 were present (OR 2.87, 95 % CI 1.42–5.81; p?=?0.003). No overall association to CD or UC was found for the rs4495224 variant.

Conclusions

The PTGER4 modulating variant rs7720838 increases susceptibility for CD and might resemble a risk factor for stricturing disease behavior.     

Grape Seed Extract Reduces the Severity of Selected Disease Markers in the Proximal Colon of Dextran Sulphate Sodium-Induced Colitis in Rats

Background

Grape seed extract (GSE) constitutes a rich source of procyanidins. GSE has been demonstrated to exert encouraging anti-inflammatory and anti-ulcer properties in experimental settings, although its effects on inflammation of the colon remain undefined.

Aim

To determine the effects of GSE in a rat model of dextran sulphate sodium (DSS) for ulcerative colitis.

Methods

Male Sprague–Dawley rats were gavaged daily (days 0–10) with GSE (400 mg/kg). Ulcerative colitis was induced by substituting DSS (2 % w/v) for drinking water from days 5–10. A sucrose breath test was performed on day 11 to determine small bowel function and intestinal tissues were collected for histological analyses. Statistical analysis was by one-way or repeated-measures ANOVA and p < 0.05 was considered significant.

Results

Compared to DSS-treated controls, GSE significantly decreased ileal villus height (14 %; p < 0.01) and mucosal thickness (13 %; p < 0.01) towards the values of normal controls. GSE reduced qualitative histological severity score (p < 0.05) in the proximal colon, although no significant effect was evident in the distal colon. However, GSE failed to prevent DSS-induced damage to the crypts of both colonic regions. Administration of GSE did not negatively impact metabolic parameters, nor did it induce any deleterious gastrointestinal side effects in healthy animals.

Conclusions

GSE decreased the severity of selected markers of DSS-induced colitis in the distal ileum and proximal colon, suggesting the potential as an adjuvant therapy for the treatment of ulcerative colitis. Future studies of GSE should investigate alternative delivery methods and treatment regimens, further seeking to identify the individual bioactive factors.     

Increase in the Tight Junction Protein Claudin-1 in Intestinal Inflammation

Background and Aims

Studies have shown a decrease in key tight junction (TJ) proteins such as ZO-1 and occludin in both inflammatory bowel disease (IBD) and experimental models of inflammation. Our group has also shown an increase in claudin-1 in experimental colitis.

Methods

IEC-18 cells were treated with increasing doses of tumor necrosis factor alpha (TNF??). The TJ was assessed by transepithelial resistance (TER), permeability, Western blot, PCR, and immunofluorescence. Mucosal samples from patients with ulcerative colitis (UC), Crohn??s disease (CD), and without IBD (normal) were assayed for TJ proteins occludin and claudin-1 by Western blot and a ratio of claudin-1 to occludin (C:O) was calculated.

Results

IEC-18 cells had increased permeability, decreased TER and an increase in claudin-1 with TNF?? treatment. In human specimens, there was a decrease in occludin and an increase in claudin-1 leading to a significant increase in the C:O ratio in diseased UC colon compared to non-diseased UC colon (P < 0.001) and normal colon (P < 0.01). In CD, the C:O ratio was similar in all CD tissue irrespective of disease status.

Conclusions

Treatment of IEC-18 cells with TNF??, a key inflammatory cytokine in IBD, led to a significant increase in claudin-1 expression. There was a significant increase in the C:O ratio in diseased colon in UC compared to the healthy appearing UC colon and normal controls. The C:O ratio was unchanged in CD despite presence or abscence of gross disease. This suggests that there may be an underlying difference in the TJ between UC and CD.     

Management of colorectal cancer in patients with inflammatory bowel disease

Background

This study evaluated the clinicopathological features and survival rates of patients with inflammatory bowel disease who developed colorectal cancer (CRC).

Methods

A retrospective review was performed on a prospectively maintained institutional database (1981–2011) to identify patients with inflammatory bowel disease who developed CRC. Clinicopathological parameters, management and outcomes were analysed.

Results

A total of 2,843 patients with inflammatory bowel disease were identified. One thousand six hundred and forty-two had ulcerative colitis (UC) and 1,201 had Crohn’s disease (CD). Following exclusion criteria, there were 29 patients with biopsy-proven colorectal carcinoma, 22 of whom had UC and 7 had CD. Twenty-six patients had a preoperative diagnosis of malignancy/dysplasia; 16 of these were diagnosed at surveillance endoscopy. Nodal/distant metastasis was identified at presentation in 47 and 71 % of the UC and CD group, respectively. Operative morbidity for UC and CD was 33 and 17 %, respectively. Despite the less favourable operative outcomes following surgery management of UC-related CRC, overall 5-year survival was significantly better in the UC group compared to the CD group (41 vs. 29 %; p = 0.04) reflecting the difference in stage at presentation between the two groups.

Conclusions

Patients who undergo surgery for UC-related CRC have less favourable short-term outcomes but present at a less advanced stage and have a more favourable long-term prognosis than similar patients with CRC and CD.     

Prevalence of Colorectal Neoplasia Among Young African Americans and Hispanic Americans

Background

The disproportionately higher incidence of and mortality from colorectal cancer (CRC) among African Americans (AA) led the American College of Gastroenterology to recommend screening starting at age 45 in 2005.

Aim

The purpose of this study was to determine the prevalence of colorectal neoplasia among 40–49-year-old inner city AA and Hispanic Americans (HA).

Methods

We reviewed the medical records of 2,435 inner city AA and HA who underwent colonoscopy regardless of indication and compared the prevalence of colorectal neoplasia between AA and HA patients. We used logistic regression models to calculate odds ratios (OR) and 95 % confidence intervals (CI).

Results

There were 2,163 AAs and 272 HA. There were 57 % women in both groups. A total of 158 (7 %) AA and 9 (3 %) HA (P = 0.014) underwent the procedures for CRC screening. When compared to HAs, AAs had higher prevalence of any polyp (35 vs. 18 %, OR = 2.53; 95 % CI 1.82–3.52). Overall, AA had higher prevalence of colorectal neoplasia (adenoma and cancer) when compared to HAs (16 vs. 10 %; OR = 1.68; 95 % CI 1.10–2.56).

Conclusion

We observed a higher frequency of colorectal neoplasia among 40–49-year-old AAs as compared to HAs suggesting an increased susceptibility to CRC risk in this population.     

Association of common gene variants in vitamin D modulating genes and colon cancer recurrence

Purpose

Low concentrations of 25-hydroxyvitamin D3 (25(OH)D) have been associated with increased risk and poor prognosis of various cancer types, including colon cancer. Common genetic variants in genes that influence circulating 25(OH)D levels may affect vitamin D concentrations and risk of vitamin D insufficiency. In the present study, we investigated the association of three functional gene variants in GC (rs2282679 T>G), DHCR7 (rs12785878 G>T) and CYP2R1 (rs10741657 A>G) with time to recurrence (TTR) in patients with stages II and III colon cancer.

Methods

Two hundred and sixty-four patients were included in this retrospective study. Genomic DNA was genotyped for GC rs2282679 T>G, DHCR7 rs12785878 G>T and CYP2R1 rs10741657 A>G by 5′-exonuclease (TaqMan?) technology.

Results

In the univariate analysis, GC rs2282679 GG was significantly associated with decreased TTR (HR = 3.30, 95 % CI 1.09–9.97, p = 0.034) in patients with surgery alone and remained significantly associated in multivariate analysis including lymph node involvement and clinical stage (HR = 3.64, 95 % CI 1.16–11.46, p = 0.027). In patients with adjuvant chemotherapy, GC rs2282679 T>G was not significantly associated with TTR (HR = 1.02, 95 % CI 0.44–2.37, p = 0.964). Furthermore, we observed a trend toward decreased TTR in patients harboring the CYP2R1 rs10741657 A>G gene variant including all patients (HR = 1.50, 95 % CI 0.98–2.28, p = 0.060). No association was found between DHCR7 rs12785878 G>T and TTR in our study cohort.

Conclusion

In conclusion, our results may indicate a prognostic effect of GC rs2282679 in stages II and III colon cancer patients with surgery alone. Larger studies have to be performed to validate our findings.