Association of extraintestinal manifestations of inflammatory bowel disease in a province of western Hungary with disease phenotype:Results of a 25-year follow-up study

AIM:IBD is a systemic disease associated with a large number of extraintestinal manifestations (EIMs).Our aim was to determine the prevalence of EIMs in a large IBD cohort in Veszprem Province in a 25-year follow-up study. METHODS:Eight hundred and seventy-three IBD patients were enrolled (ulcerative colitis/UC/:619,m/f:317/302, mean age at presentation:38.3 years,average disease duration:11.2 years;Crohn's disease/CD/:254,m/f:125/129, mean age at presentation:32.5 years,average disease duration:9.2 years).Intestinal,extraintestinal signs and laboratory tests were monitored regularly.Any alteration suggesting an EIMs was investigated by a specialist. RESULTS:A total of 21.3% of patients with IBD had EIM (UC:15.0%,CD:36.6%).Age at presentation did not affect the likelihood of EIM.Prevalence of EIMs was higher in women and in CD,ocular complications and primary sclerosing cholangitis (PSC) were more frequent in UC.In UC there was an increased tendency of EIM in patients with a more extensive disease.Joint complications were more frequent in CD (22.4% vsUC 10.2%,P<0.01).In UC positive family history increased the risk of joint complications (OR:3.63).In CD the frequency of type-1 peripheral arthritis was increased in patients with penetrating disease (P=0.028).PSC was present in 1.6% in UC and 0.8% in CD.Dermatological complications were present in 3.8% in UC and 10.2% in CD,the rate of ocular complications was around 3% in both diseases.Rare complications were glomerulonephritis,autoimmune hemolytic anaemia and celiac disease. CONCLUSION:Prevalence of EIM in Hungarian IBD patients is in concordance with data from Western countries.The high number of EIM supports a role for complex follow-up in these patients.

Risk for colorectal cancer in ulcerative colitis:Changes,causes and management strategies

The risk of colorectal cancer for any patient with ulcer-ative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer in-clude extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflam-mation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epide-miological trends and causes for the observed chang-es. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this change is unknown; it may partly be explained by the more widespread use of maintenance therapy and surveillance colonoscopy.

Recent trends in the epidemiology of inflammatory bowel diseases:Up or down?

Inflammatory bowel disease (IBD) is traditionally con- sidered to be common in the Western world, and its incidence has sharply increased since the early 1950s. In contrast, until the last decade, low prevalence and incidence rates have been reported from other parts of the world including Eastern Europe, South America, Asia and the Pacific region. Recent trends indicate a change in the epidemiology of IBD with previously low incidence areas now reporting a progressive rise in the incidence, while in West European and North American countries the figures have stabilized or slightly increased, with decreasing incidence rates for ulcerative colitis. Some of these changes may represent differences in diagnostic practices and increasing awareness of the disease. The quality of studies is also variable. Additional epidemio- logic studies are needed to better define the burden of illness, explore the mechanism of association with envi- ronmental factors, and identify new risk factors.

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.

Striking elevation in incidence and prevalence of inflammatory bowel disease in a province of western Hungary between 1977-2001

AIM:An investigation into inflammatory bowel disease and colorectal cancer in Veszprem Province was conducted from 1977 to 2001.METHODS: Both hospital and outpatient records were collected and reviewed comprehensively. The majority of patients were followed up regularly.RESULTS:The population of the province was decreased from 386000 to 376000 during the period. Five hundred sixty new cases of ulcerative colitis (UC), 212 of Crohn's disease (CD), and 40 of indeterminate colitis (IC) were diagnosed. The incidence rates increased from 1.66 to 11.01 cases per 100 000 persons for UC, from 0.41 to 4.68 for CD and from 0.26 to 0.74 for IC. The prevalence rate at the end of 2001 was 142.6 for UC and 52.9 cases per 100 000 persons for CD. The peak onset age in UC patients was between 30 and 40 years, in CD between 20 and 30 years. A family history of IBD was present in 3.4% in UC and 9.9% in CD patients.Smoking increased the risk for CD (OR=1.94) while it decreased the risk for UC (OR=0.25). Twelve colorectal carcinomas were observed in this cohort, the cumulative colorectal cancer risk after 10 years in UC was 2%, after 20 years 8.8%, after 30 years 13.3%.CONCLUSION:The incidence and prevalence rates of IBD have increased steadily in Veszprem Province, now equivalent to that in Western European countries. Rapid increase in incidence rates supports a probable role for environmental factors. The rate of colorectal cancers in IBD is similar to that observed in Western countries.

Current concept on the pathogenesis of inflammatory bowel disease-crosstalk between genetic and microbial factors:Pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take"toll"?

The pathogenesis of inflammatory bowel disease （IBD） is only partially understood. Various environmental and host （e.g. genetic-, epithelial-, immune and nonimmune） factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity. Some genes are associated with IBD itself, while others increase the risk of ulcerative colitis （UC） or Crohn＇ s disease （CD） or are associated with disease location and/or behaviour. This review addresses recent advances in the genetics of IBD. The article discusses the current information on the crosstalk between microbial and genetic factors （e.g. NOD2/CARD15, SLC22A46A5 and DLG5）. The genetic data acquired in recent years help in understanding the pathogenesis of IBD and can identify a number of potential targets for therapeutic intervention. In the future, genetics may help more accurately diagnose and predict disease course in IBD.

Perianal disease,small bowel disease,smoking,prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease

AIM:To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine(AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn's disease(CD).METHODS:Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed(M/F:155/185, duration:9.4 ± 7.5 years) with a complete clinical follow-up.Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively.Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits.RESULTS:A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean diseaseduration of 9.0 ± 7.2 years.In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/ biological therapy use were independent predictors of disease behavior change.In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location(P = 0.001), presence of perianal disease(P < 0.001), prior steroid use(P = 0.006), early AZA(P = 0.005) or AZA/biological therapy(P = 0.002), or smoking(P = 0.032) were independent predictors of disease behavior change.CONCLUSION:Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.

Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy and endoscopic treatment of bile duct stones:Results of a retrospective,single center study between 1996-2002

AIM: The optimal treatment for bile duct stones (in terms of cost, complications and accuracy) is unclear. The aim of our study was to determine the predictive factors for preoperative endoscopic retrograde cholangiopancreatography (ERCP).METHODS: Patients undergoing preoperative ERCP (≤90 d before laparoscopic cholecystectomy) were evaluated in this retrospective study from the 1^st of January 1996 to the 31^st of December 2002. The indications for ERCP were elevated serum bilirubin, elevated liver function tests (LFT), dilated bile duct (≥8 mm) and/or stone at US examination, coexisting acute pancreatitis and/or acute pancreatitis or jaundice in patient's history. Suspected prognostic factors and the combination of factors were compared to the result of ERCRRESULTS: Two hundred and six preoperative ERCPs were performed during the observed period. The rate of successful cannulation for ERC was (97.1%). Bile duct stones were detected in 81 patients (39.3%), and successfully removed in 79 (97.5%). The number of prognostic factors correlated with the presence of bile duct stones. The positive predictive value for one prognostic factor was 1.2%, for two 43%,for three 72.5%, for four or more 91.4%.CONCLUSION: Based on our data preoperative ERCP is highly recommended in patients with three or more positive factors (high risk patients). In contrast, ERCP is not indicated in patients with zero or one factor (low risk patients).Preoperative ERCP should be offered to patients with two positive factors (moderate risk patients), however the practice should also be based on the local conditions (e.g.skill of the endoscopist, other diagnostic tools).

Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

Smoking in inflammatory bowel diseases:Good,bad or ugly?

Smoking is an important environmental factor in inflammatory bowel disease （IBD）, having different effects in ulcerative colitis （UC） and Crohn＇s disease （CD）. A recent meta-analysis partially confirmed previous findings that smoking was found to be protective against ulcerative colitis and, after onset of the disease, might improve its course, decreasing the need for colectomy. However, smoking increases the risk of developing Crohn＇s disease and worsens its course, increasing the need for steroids, immunosuppressants and re-operations. Smoking cessation aggravates ulcerative colitis and improves Crohn＇s disease. Data are however, largely conflictive as well as the potential mechanisms involved in this dual relationship are still unknown. In this review article, the authors review the role of smoking in inflammatory bowel diseases.

Disease monitoring strategies in inflammatory bowel diseases: What do we mean by “tight control”?

In recent years,there has been a critical change in treatment paradigms in inflammatory bowel diseases(IBD)triggered by the arrival of new effective treatments aiming to prevent disease progression,bowel damage and disability.The insufficiency of symptomatic disease control and the well-known discordance between symptoms and objective measures of disease activity lead to the need of reviewing conventional treatment algorithms and developing new concepts of optimal therapeutic strategy.The treat-to-target strategies,defined by the selecting therapeutic targets in inflammatory bowel disease consensus recommendation,move away from only symptomatic disease control and support targeting composite therapeutic endpoints(clinical and endoscopical remission)and timely assessment.Emerging data suggest that early therapy using a treat-to-target approach and an algorithmic therapy escalation using regular disease monitoring by clinical and biochemical markers(fecal calprotectin and C-reactive protein)leads to improved outcomes.This review aims to present the emerging strategies and supporting evidence in the current therapeutic paradigm of IBD including the concepts of“early intervention”,“treat-to-target”and“tight control”strategies.We also discuss the real-word experience and applicability of these new strategies and give an overview on the future perspectives and areas in need of further research and potential improvement regarding treatment targets and(“tight”)disease monitoring strategies.

Prevalence,predictors,and clinical consequences of medical adherence in IBD:How to improve it?

Inflammatory bowel diseases(IBD)are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment.However,non-adherence has been reported in over 40%of patients,especially those in remission taking maintenance therapies for IBD. The economical impact of non-adherence to medical therapy including absenteeism,hospitalization risk, and the health care costs in chronic conditions,is enormous.The causes of medication non-adherence are complex,where the patient-doctor relationship, treatment regimen,and other disease-related factors play key roles.Moreover,subjective assessment might underestimate adherence.Poor adherence may result in more frequent relapses,a disabling disease course, in ulcerative colitis,and an increased risk for colorectal cancer.Improving medication adherence in patients is an important challenge for physicians.Understanding the different patient types,the reasons given by patients for non-adherence,simpler and more convenient dosage regimens,dynamic communication within the health care team,a self-management package incorporating enhanced patient education and physician-patient interaction,and identifying the predictors of nonadherence will help devise suitable plans to optimize patient adherence.This editorial summarizes the available literature on frequency,predictors,clinical consequences,and strategies for improving medical adherence in patients with IBD.

Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis

To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. METHODSSera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various anti-microbial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. RESULTSA total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of anti-microbial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA posvsneg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. CONCLUSIONPresence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.

Is early limited surgery associated with a more benign disease course in Crohn's disease?

AIM:To analyze the difference in disease course and need for surgery in patients with Crohn’s disease(CD).METHODS:Data of 506 patients with incident CD were analyzed(age at diagnosis:31.5±13.8 years).Both hospital and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database,which includes incident CD patients diagnosed between January 1,1977 and December 31,2008.Follow-up data were collected until December 31,2009.All patients included had at least 1year of follow-up available.Patients with indeterminate colitis at diagnosis were excluded from the analysis.RESULTS:Overall,73 patients(14.4%)required resective surgery within 1 year of diagnosis.Steroid exposure and need for biological therapy were lower in patients with early limited surgery(P<0.001 and P=0.09).In addition,surgery rates during follow-up in patients with and without early surgery differed significantly after matching on propensity scores(P<0.001,HR=0.23).The need for reoperation was also lower in patients with early limited resective surgery(P=0.038,HR=0.42)in a Kaplan-Meier and multivariate Cox regression(P=0.04)analysis.However,this advantage was not observed after matching on propensity scores(PLogrank=0.656,PBreslow=0.498).CONCLUSION:Long-term surgery rates and overall exposure to steroids and biological agents were lower in patients with early limited resective surgery,but reoperation rates did not differ.

Use of new once-daily 5-aminosalicylic acid preparations in the treatment of ulcerative colitis:Is there anything new under the sun?

5-aminosalicylate(5-ASA)agents remain the mainstay treatment in ulcerative colitis(UC).A number of oral 5-ASA agents are commercially available,including azobond pro-drugs,as well as delayed-and controlledrelease forms of mesalazine.However,poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC.Recently, new,once-daily formulations of mesalazine,including the unique multi-matrix delivery system and mesalazine granules,were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC,with a good safety profile comparable to that of other oral mesalazine formulations.In addition,they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice.This editorial summarizes the available literature on the short-and medium-term efficacy and safety of the new once-daily mesalazine formulations.

Mucocele of the appendix: An unusual cause of lower abdominal pain in a patient with ulcerative colitis-. A case report and review of literature

The authors report the case of a 60-year-old male patient. In November 2001 he developed intestinal symptoms of bloody diarrhea and abdominal pain. Colononoscopy and biopsy established the diagnosis of ulcerative colitis (proctosigmoiditis). The disease activity was moderate at the beginning. No significant laboratory alterations were found (including CEA, CA19-9), and mesalazine was started orally. He was in remission until November 2003, when he was admitted to our Outpatient Clinic for upper and right lower abdominal pain and bloody diarrhea. Colonoscopy found proctosigmoiditis with a moderate activity, gastroscopy revealed chronic gastritis, laboratory data was normal. Treatment was amended with mesalazine clysma and methylprednisolone (16 mg) orally. Symptoms ameliorated; however, right lower abdominal pain persisted. US and CT examinat'on demonstrated a pericecal cystic mass (11 cm×3.5 cm). At first pericecal abscess was suspected, as the previous US examination (6 mo earlier) had revealed normal findings. Fine needie aspiration was performed. Cytology confirmed the diagnosis of mucocele. The patientunderwent partial cecum resection and extirpation of the mucocele. He recovered well and the final histology revealed a cystadenoma of the appendix. Follow up was started. The pati雗t is now free of symptoms. Although primary adenocarcinoma of the appendix is uncommon, the authors emphasize that preoperative diagnosis of an underlying malignancy in a mucocele is important for pati雗t management; however, it is difficult on imaging studies.

Prediction of disease course in inflammatory bowel diseases

Clinical presentation at diagnosis and disease course of both Crohn's disease(CD) and ulcerative colitis are heterogeneous and variable over time.Since most patients have a relapsing course and most CD patients develop complications(e.g.stricture and/or perforation),much emphasis has been placed in the recent years on the determination of important predictive factors.The identification of these factors may eventually lead to a more personalized,tailored therapy.In this TOPIC HIGHLIGHT series,we provide an update on the available literature regarding important clinical,endoscopic,fecal,serological/routine laboratory and genetic factors.Our aim is to assist clinicians in the everyday practical decisionmaking when choosing the treatment strategy for their patients suffering from inflammatory bowel diseases.

NKX2-3 and IRGM variants are associated with diseasesu sceptibility to IBD in Eastern European patients

AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.

Evolution of disease phenotype in adult and pediatric onset Crohn's disease in a population-based cohort

AIM:To investigate the evolution of disease phenotypein adult and pediatric onset Crohn's disease(CD) populations,diagnosed between 1977 and 2008.METHODS:Data of 506 incident CD patients were analyzed(age at diagnosis:28.5 years,interquartile range:22-38 years).Both in-and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database,which included incident patients diagnosed between January 1,1977 and December 31,2008 in adult and pediatric onset CD populations.Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis.RESULTS:Among this population-based cohort,seventy-four(12.8%) pediatric-onset CD patients were identified(diagnosed ≤ 17 years of age).There was no significant difference in the distribution of disease behavior between pediatric(B1:62%,B2:15%,B3:23%) and adult-onset CD patients(B1:56%,B2:21%,B3:23%) at diagnosis,or during follow-up.Overall,the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5-and 10-years of follow-up.Similarly,time to change in disease behaviour from non stricturing,non penetrating(B1) to complicated,stricturing or penetrating(B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis.Calendar year of diagnosis(P = 0.04),ileal location(P < 0.001),perianal disease(P < 0.001),smoking(P = 0.038) and need for steroids(P < 0.001) were associated with presence of,or progression to,complicated disease behavior at diagnosis and during follow-up.A change in disease location was observed in 8.9% of patients and it was associated with smoking status(P = 0.01),but not with age at diagnosis.CONCLUSION:Long-term evolution of disease behavior was not different in pediatric-and adult-onset CD patients in this population-based cohort but was associated to location,perianal disease and smoking status.

Double balloon enteroscopy examinations in general anesthesia

AIM:To demonstrate that the double balloon enteroscopy(DBE) can be safely performed in general anesthesia with intubation.METHODS:We performed a retrospective examination between August 2005 and November 2008 amongpatients receiving intubation narcosis due to DBE examination.The patients were grouped based on sex,age and physical status.Anesthesia records includedduration of anesthesia,quantity of medication usedand anesthesia-related complications.We determinedthe frequency of complications in the different groupsand their relation with the quantity of medication usedand the duration of anesthesia.RESULTS:We compiled data for 108 cases of general anesthesia with intubation.We did not observeany permanent anesthesia-related complications;themost frequent side effects of anesthesia were hypo-tension(30.55%),desaturation(21.29%),and apnea(17.59%).These complications were significantly more frequent among patients with multiple additional diseases [hypotension(23.1% vs 76.9%,P = 0.005),desaturation(12.3% vs 69.2%,P < 0.001) and apnea(7.7% vs 53.8%,P = 0.001)],however,their incidence was not proportional to the quantity of medication used or the duration of anesthesia.CONCLUSION:General anesthesia with intubation is definitely a viable option among DBE methods.It is highly recommended in patients with multiple additional diseases.