A new oral formulation for the release of sodium butyrate in the ileo-cecal region and colon

AIM： To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon. METHODS： One-gram sodium butyrate coated tablets containing ^13C-butyrate were orally administered to 12 healbhy subjects and 12 Crohn＇s disease patients and the rate of ^13C-butyrate absorption was evaluated by t3CO2 breath test analysis for eight hours. Tauroursodeoxycholic acid （500 rag） was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration. RESULTS： The coated formulation delayed the ^13C-butyrate release by 2-3 h with respect to the uncoated tablets. Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn＇s disease patients than in healthy subjects. The variability of the peak ^13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time. However, the coating chosen ensured an efficient release of the active compound even in patients with a short transit time. CONCLUSION： Simultaneous evaluation of breath ^13CO2 and tauroursodeoxycholic acid concentrationtime curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn＇s disease patients with variable intestinal transit time. This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.

Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 =4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desir- able for individuals with such affected genotypes.

Contribution of the IL-17/IL-23 axis to the pathogenesis of inflammatory bowel disease

Inflammatory bowel diseases(IBDs) are chronic disorders of modern society, requiring management strategies aimed at prolonging an active life and establishing the exact etiology and pathogenesis.These idiopathic diseases have environmental, genetic,immunologic, inflammatory, and oxidative stress components. On the one hand, recent advances have shown that abnormal immune reactions against the microorganisms of the intestinal flora are responsible for the inflammation in genetically susceptible individuals. On the other hand, in addition to T helper cell-type(Th) 1 and Th2 immune responses,other subsets of T cells, namely regulatory T cells and Th17 maintained by IL-23 are likely to develop IBD. IL-23 acts on innate immune system members and also facilitates the expansion and maintenance of Th17 cells. The IL-17/IL-23 axis is relevant in IBD pathogenesis both in human and experimental studies. Novel biomarkers of IBD could be calprotectin,microRNAs, and serum proinflammatory cytokines.An efficient strategy for IBD therapy is represented by the combination of IL-17 A and IL-17 F in acute IL-17 A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17 F knockout, DSS-induced colitis have been observed.Studying the correlation between innate and adaptive immune systems, we hope to obtain a focused reviewin order to facilitate future approaches aimed at elucidating the immunological mechanisms that control gut inflammation.

Fecal microbiota transplantation as novel therapy in gastroenterology:A systematic review

AIM:To study the clinical efficacy and safety of Fecal microbiota transplantation(FMT).We systematically reviewed FMT used as clinical therapy.METHODS:We searched MEDLINE,EMBASE,the Cochrane Library and Conference proceedings from inception to July,2013.Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category,on an intention-to-treat basis.RESULTS:We included 45 studies;34 on Clostridium difficile-infection(CDI),7 on inflammatory bowel disease,1 on metabolic syndrome,1 on constipation,1 on pouchitis and 1 on irritable bowel syndrome(IBS).In CDI 90% resolution of diarrhea in 33 case series(n = 867) was reported,and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial(RCT)(n = 16).In ulcerative colitis(UC) remission rates of 0% to 68% were found(n = 106).In Crohn's disease(CD)(n = 6),no benefit was observed.In IBS,70% improvement of symptoms was found(n = 13).100% Reversal of symptoms was observed in constipation(n = 3).In pouchitis,none of the patients(n = 8) achieved remission.One RCT showed significant improvement of insulin sensitivity in metabolic syndrome(n = 10).Serious adverse events were rare.CONCLUSION:FMT is highly effective in CDI,and holds promise in UC.As for CD,chronic constipation,pouchitis and IBS data are too limited to draw conclusions.FMT increases insulin sensitivity in metabolic syndrome.

Role of antibiotics for treatment of inflammatory boweldisease

Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease(CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.

Utility of serological markers in inflammatory bowel diseases: Gadget or magic?

The panel of serologic markers for inflammatory bowel diseases （IBD） is rapidly expanding. Although antiSaccharornyces cerev/siae antibodies （ASCA） and atypical perinuclear antineutrophil cytoplasmic antibodies （P-ANCA） remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. The role of the assessment of various antibodies in the current IBD diagnostic algorithm is often questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is becoming increasingly well-established. An increasing number of observations confirms that patients with Crohn＇s disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease （e.g. stricture and/or perforation） and are at higher risk for surgery than those without, or with low titers of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD.

Importance of nutrition in inflammatory bowel disease

Inflammatory bowel disease （IBD） results from the interaction between an individual＇s immune response and precipitant environmental factors, which generatean anomalous chronic inflammatory response in thosewho are genetically predisposed. Various feeding practices have been implicated in the origin of IBD based on epidemiological observations in developed countries, but we do not have solid evidence for the etiological role played by specific food types. IBD is associated with frequent nutritional deficiencies, thepattern and severity of which depends on the extent,duration and activity of the inflammation. Nutritional support allows these deficiencies in calories, macro and micronutrients to be rectified. Enteral nutrition is also aprimary therapy for IBD, especially for Crohn＇s disease,as it allows the inflammatory activity to be controlled,kept in remission, and Drevents or delays the need forsurgery. Nutritional support is especially important in childhood IBD as an alternative to pharmacological treatment. This report discusses the complex relationship between diet and IBD.

Assessment of disease specific knowledge and health-relatedquality of life among United States military veterans withinflammatory bowel disease

AIM To evaluate the association between patientdisease knowledge of inflammatory bowel disease （IBD）and health related quality of life （HRQoL） and identifypatient and disease related predictors of patientknowledge of IBD.METHODS： We performed a cross-sectional study ofIBD patients with an established diagnosis of IBD longerthan 3 mo prior to enrollment. The Crohn＇s and colitisknowledge score （CCKNOW） and short inflammatorybowel disease questionnaire （SIBDQ） were selfadministeredto assess patient knowledge of IBDand HRQoL, respectively. Demographic and diseasecharacteristics were abstracted from the electronicmedical record. The correlation between CCKNOWand SIBDQ scores was assessed by a linear regressionmodel. Associations of patient knowledge and thevariables of interest were calculated using ANOVA.RESULTS： A total of 101 patients were recruited.Caucasian race, younger age at diagnosis, and having a college or post-graduate degree were significantlyassociated with higher CCKNOW scores. Patients withCD had higher CCKNOW scores compared to patientswith ulcerative colitis and inflammatory bowel diseasetype unclassified, P 〈 0.01. There was no significantcorrelation between overall CCKNOW and SIBDQ scores（r^2 = 0.34, P = 0.13）. The knowledge sub-domain ofdiet in CCKNOW was negatively correlated with HRQoL（r^2 = 0.69, P 〈 0.01）.CONCLUSION： IBD diagnosis at a younger age inaddition to Caucasian race and higher education weresignificantly associated with higher knowledge aboutIBD. However, patient knowledge of IBD was notcorrelated with HRQoL. Further studies are required tostudy the effect of patient knowledge of IBD on otherclinical outcomes.

Chronic fatigue is associated with increased disease-related worries and concerns in inflammatory bowel disease

AIM:To investigate the impact of chronic fatigue on disease-related worries in inflammatory bowel disease (IBD) and the potential multicolinearity between subjective questionnaires.METHODS:Patients in remission or with mild-tomoderate disease activity completed the fatigue questionnaire (FQ),the rating form of IBD patient concerns (RFIPC),the Short-Form 36 (SF-36),and IBD questionnaire (N-IBDQ).In addition,clinical and epidemiological data were obtained.RESULTS:In total,140 patients were included;of which 92 were diagnosed with ulcerative colitis and 48 with Crohn's disease.The mean age of patients with chronic fatigue was 44.2 years (SD=15.8) and for non-fatigued patients was 44.7 years (SD=16.0).Chronic fatigued patients had clinically significantly increased levels of disease-related worries,as measured by Cohen's d effect size.Worries about having an ostomy bag,loss of bowel control,and energy levels were most prominent in both chronic fatigued and non-chronic fatigued IBD patients.Variance inflation factor (VIF) and tolerance indicated that there were no problematic multicolinearity among the FQ,RFIPC,SF-36 and N-IBDQ responses (VIF < 5 and tolerance > 2).CONCLUSION:Chronic fatigue is associated with increased levels of disease-related worries and concerns in IBD.Increased levels of worries were also associated with impaired health-related quality of life.

NOD2: Ethnic and geographic differences

Investigations into the inheritance of the three risk alleles R702W, G908R and 1007 fsInsC in NOD2 associated with susceptibility to Crohn＇s disease have demonstrated a remarkable amount of heterogeneity across ethnicities and populations, with regional variation across Europe for example, suggesting local founder effects. In nonCaucasian populations Crohn＇s disease continues to increase in incidence but this increase appears not to be a consequence of variation in NOD2, further advancing the accumulating evidence for other susceptibility loci. Frequencies of the known alleles are compared across populations in health and disease and evidence for additional alleles in NOD2 is reviewed. Based on its position on chromosome 16 coincident with some other autoimmune disease susceptibility Iocalizations, research has targeted NOD2 variation as the potential cause of other autoimmune disorders. While these investigations have mostly returned negative findings, two diseases, Blau Syndrome and Graft versus Host Disease, have been shown to be caused by risk alleles in NOD2. As is frequent in complex disease investigations, some results await validation, but the identification of NOD2 and the differences within and across population raises intriguing questions about the population genetics of the variation at this locus.

Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: When and how to apply prophylaxis, with a special focus on corticosteroid therapy

Currently immunosuppressive and biological agentsare used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus(HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to preemptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.

Role of soluble factors and three-dimensional culture in in vitro differentiation of intestinal macrophages

AIM: To examine the factor(s) involved in differentiation of intestinal macrophages (IMACs) using a recently established in vitro model. METHODS: To test whether soluble or membrane bound factors induce IMAC-differentiation, freshly elutriated monocytes (MO) were incubated with conditioned media or cell membranes of intestinal epithelial cells (IEC) or cultured with IEC in transwell systems. To determine the importance of an active migration of MO, three- dimensional aggregates from a 1:1-mixture of MO and IEC were examined by immunohistochemistry and flow cytometry. Apoptosis was examined by caspase-3 Western blots. Extracellular matrix production in differentiation models was compared by immunohistochemistry. RESULTS: IMAC differentiation was observed in a complex three-dimensional co-culture model (multicellular spheroid, MCS) with IEC after migration of MO into the spheroids. By co-culture of MO with conditioned media or membrane preparations of IEC no IMAC differentiation was induced. Co-culture of MO with IEC in transwell- cultures, with the two cell populations separated by a membrane also did not result in intestinal-like differentiation of MO. In contrast to IEC-spheroids with immigrating MO in mixed MCS of IEC and MO only a small subpopulation of MO was able to survive the seven day culture period. CONCLUSION: Intestinal-like differentiation of MO in vitro is only induced in the complex three-dimensional MCS model after immigration of MO indicating a roleof cell-matrix and/or cell-cell interactions during the differentiation of IMACs.

PillCam COLON 2~ in Crohn's disease:A new concept of pan-enteric mucosal healing assessment

AIM: To evaluate mucosal healing in patients with small bowel plus colonic Crohn's disease(CD) with a single non-invasive examination, by using PillCam COLON 2.(PCC2).METHODS: Patients with non-stricturing nonpenetrating small bowel plus colonic CD in sustained corticosteroid-free remission were included. At diagnosis,patients had undergone ileocolonoscopy to identify active CD lesions, such as ulcers and erosions, and small bowel capsule endoscopy to assess the Lewis Score(LS). After ≥ 1 year of follow-up, patients underwent entire gastrointestinal tract evaluation with PCC2. The primary endpoint was assessment of CD mucosal healing, defined as no active colonic CD lesions and LS < 135.RESULTS: Twelve patients were included(7 male;mean age: 32 years), and mean follow-up was 38 mo.The majority of patients(83.3%) received immunosuppressive therapy. Three patients(25%) achieved mucosal healing in both the small bowel and the colon,while disease activity was limited to either the small bowel or the colon in 5 patients(42%). It was possible to observe the entire gastrointestinal tract in 10 of the12 patients(83%) who underwent PCC2.CONCLUSION: Only three patients in sustainedcorticosteroid-free clinical remission achieved mucosal healing in both the small bowel and the colon, highlighting the limitations of clinical assessment when stratifying disease activity, and the need for pan-enteric endoscopy to guide therapeutic modification.

High-dose infliximab for treatment of pediatric ulcerative colitis:A survey of clinical practice

AIM:To assess attitudes and trends regarding the use of high-dose infliximab among pediatric gastroenterologists for treatment of pediatric ulcerative colitis(UC).METHODS:A 19-item survey was distributed to subscribers of the pediatric gastroenterology(PEDSGI) listserv.Responses were submitted anonymously and results compiled in a secure website.RESULTS:A total of 113 subscribers(88% based in the United States) responded(101 pediatric gastroenterology attendings and 12 pediatric gastroenterology fellows).There were 46% in academic medical institutions and 39% in hospital-based practices.The majority(91%) were treating >10 patients with UC;13% were treating >100 patients with UC;91% had prescribed infliximab(IFX) 5 mg/kg for UC;72% had prescribed IFX 10 mg/kg for UC.Using a 5-point Likert scale,factors that influenced the decision not to increase IFX dosing in patients with UC included:"improvement on initial dose of IFX"(mean:3.88) and "decision to move to colectomy"(3.69).Lowest mean Likert scores were:"lack of guidelines or literature regarding increased IFX dosing"(1.96) and "insurance authorization or other insurance issues"(2.34)."Insurance authorization or other insurance issues" was identified by 39% as at least somewhat of a factor(Likert score ≥ 3) in their decision not to increase the IFX dose.IFX 10 mg/kg was more commonly used for the treatment of pediatric UC among responders based in the United States(75/100) compared to non-United States responders(6/13,P = 0.047).Induction of remission was reported by 78% of all responders and 81% reported maintenance of remission with IFX 10 mg/kg.One responder reported one death with IFX 10 mg/kg.CONCLUSION:IFX 10 mg/kg is more commonly used in the United States to treat pediatric UC.Efficacy and safety data are required to avoid insurance barriers for its use.

Lymphogranuloma venereum proctosigmoiditis is a mimicker of inflammatory bowel disease

There has been an increasing prevalence of lymphogranuloma venereum(LGV) or Chlamydia trachomatis(C.trachomatis) cases among the men who have sex with men(MSM) population,particularly in Europe and North America.These cases may present with an incomplete or undisclosed history and proctosigmoiditis without characteristic adenopathy syndrome.During the initial evaluation and colonoscopy,there is a strong clinical and endoscopic suspicion of inflammatory bowel disease(IBD) by virtue of presentation and endoscopic and histological findings.The diagnosis of IBD is subsequently modified to LGV proctosigmoiditis when one or more of the following transpire:(1) there is failure of response to IBD therapy;(2) additional components of history(MSM/travel) may be identified;(3) return of initially performed Chlamydia antibody test is positive;and(4) response to antibiotics effective against Chlamydia.We describe three such cases initially suspectedto be an inflammatory bowel disease and subsequently identified as C.trachomatis proctosigmoiditis.

Effect of oral mesalamine on inflammatory response in acute uncomplicated diverticulitis

AIM: To evaluate the impact of mesalamine administration on inflammatory response in acute uncomplicated diverticulitis.METHODS: We conducted a single centre retrospective cohort study on patients admitted to our surgical department between January 2012 and May 2014 with a computed tomography-confirmed diagnosis of acute uncomplicated diverticulitis. A total of 50 patients were included in the analysis, 20(study group) had received 3.2 g/d of mesalamine starting from the day of admission in addition to the usual standard treatment, 30(control group) had received standard therapy alone. Data was retrieved from a prospective database. Our primary study endpoints were: C reactive protein mean levels over time and their variation from baseline(ΔCRP) over the first three days of treatment. Secondary end points included: mean white blood cell and neutrophile count over time, time before regaining of regular bowel movements(passing of stools), time before reintroduction of food intake, intensity of lower abdominal pain over time, analgesic consumption and length of hospital stay.RESULTS: Patients characteristics and inflammatoryparameters were similar at baseline in the two groups. The evaluation of CRP levels over time showed, in treated patients, a distinct trend towards a faster decrease compared to controls. This difference approached statistical significance on day 2(mean CRP 6.0 +/- 4.2 mg/d L and 10.0 +/- 6.7 mg/d L respectively in study group vs controls, P = 0.055). ΔCRP evaluation evidenced a significantly greater increment of this inflammatory marker in the control group on day 1(P = 0.03). A similar trend towards a faster resolution of inflammation was observed evaluating the total white blood cell count. Neutrophile levels were significantly lower in treated patients on day 2 and on day 3(P < 0.05 for both comparisons). Mesalamine administration was also associated with an earlier reintroduction of food intake(median 1.5 d and 3 d, study group vs controls respectively, P < 0.001) and with a shorter hospital stay(median 5 d and 5.5 d, study group vs controls respectively, P = 0.03).CONCLUSION: Despite its limitations, this study suggests that mesalamine may allow for a faster recovery and for a reduction of inflammatory response in acute uncomplicated diverticulitis.

Associations between CD24 gene polymorphisms and inflammatory bowel disease:A meta-analysis

AIM: To evaluate the relationships between CD24 gene polymorphisms and the risk of inflammatory bowel disease(IBD), including ulcerative colitis(UC)and Crohn's disease(CD).METHODS: The PubMed, Web of Science and Cochrane Library databases were searched(up to May30, 2014). The search terms "CD24", "inflammatory bowel disease", "Crohn's disease", "Ulcerative colitis","IBD", "CD" or "UC"; and "polymorphism", "mutation"or "variant" were used. Association studies were limited to the English language, but no limitations in terms of race, ethnicity or geographic area were employed.Stata SE12 software was used to calculate the pooled odds ratios(ORs) with 95% confidence intervals(CIs).P < 0.05 was considered statistically significant. The information was independently extracted from each eligible study by two investigators. Two common polymorphisms, C170T(rs8734) and TG1527del(rs3838646), in the CD24 gene were assessed.RESULTS: A total of three case-control studies including 2342 IBD patients and 1965 healthy controls were involved in this meta-analysis. The patients and controls were from Caucasian cohorts. The three articles included in this meta-analysis all conformed to Hardy-Weinberg equilibrium. This meta-analysis revealed that there were no significant associations between the two CD24 polymorphisms and the risk for IBD(all P > 0.05). However, in a disease subgroup analysis, we found that the CD24 C170 T polymorphism was associated with an increased risk of UC in a dominant model(OR = 1.79, 95%CI: 1.15-2.77, P =0.009) and an additive model(OR = 1.87, 95%CI:1.19-2.93, P = 0.007), but this relationship was not present for CD. The CD24 TG1570 del polymorphism was significantly associated with CD in the additive model(OR = 1.24, 95%CI: 1.01-1.52, P = 0.037).CONCLUSION: Our findings provide evidence that the CD24 C170 T polymorphism might contribute to the susceptibility to UC, and the CD24 TG1527 del polymorphism might be associated with the risk of CD.

Adenocarcinoma arising at ileostomy sites:Two cases and a review of the literature

Total colectomy with ileostomy placement is a treatment for patients with inflammatory bowel disease or familial adenomatous polyposis(FAP). A rare and late complication of this treatment is carcinoma arising at the ileostomy site. We describe two such cases: a 78-year-old male 30 years after subtotal colectomy and ileostomy for FAP, and an 85-year-old male 50 years after colectomy and ileostomy for ulcerative colitis. The long latency period between creation of the ileostomies and development of carcinoma suggests a chronic metaplasia due to an irritating/inflammatory causative factor. Surgical excision of the mass and relocation of the stoma is the mainstay of therapy, with possible benefits from adjuvant chemotherapy. Newly developed lesions at stoma sites should be biopsied to rule out the possibility of this rare ileostomy complication.