Ioannis A. Mouzas

European evidence based consensus on the diagnosis and management of Crohn’s disease: special situations

This third section of the European Crohn’s and Colitis Organisation (ECCO) Consensus on the management of Crohn’s disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn’s disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn’s disease.

Does pregnancy change the disease course? A study in a European cohort of patients with inflammatory bowel disease

BACKGROUND AND AIMS:Inflammatory bowel disease (IBD) often affects patients in their fertile age. The aim of this study was to describe pregnancy outcome in a European cohort of IBD patients. As data are limited regarding the effect of pregnancy on disease course, our second objective was to investigate whether pregnancy influences disease course and phenotype in IBD patients.METHODS:In a European cohort of IBD patients, a 10-yr follow-up was performed by scrutinizing patient files and approaching the patients with a questionnaire. The cohort comprised 1,125 patients, of whom 543 were women. Data from 173 female ulcerative colitis (UC) and 93 Crohns disease (CD) patients form the basis for the present study.RESULTS:In all, 580 pregnancies, 403 occurring before and 177 after IBD was diagnosed, were reported. The rate of spontaneous abortion increased after IBD was diagnosed (6.5% vs. 13%, p = 0.005), whereas elective abortion was not significantly different. 48.6% of the patients took medication at the time of conception and 46.9% during pregnancy. The use of cesarean section increased after IBD diagnosis (8.1% vs 28.7% of pregnancies). CD patients pregnant during the disease course, did not differ from patients who were not pregnant during the disease course regarding the development of stenosis (37% vs 52% p = 0.13) and resection rates (mean number of resections 0.52 vs 0.66, p = 0.37). The rate of relapse decreased in the years following pregnancy in both UC (0.34 vs 0.18 flares/yr, p = 0.008) and CD patients (0.76 vs 0.12 flares/yr, p = 0.004).CONCLUSIONS:Pregnancy did not influence disease phenotype or surgery rates, but was associated with a reduced number of flares in the following years.

Crohn’s disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort

Background: No previous correlation between phenotype at diagnosis of Crohn’s disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. Methods: Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. Results: Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30–2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10–3.14)) and males (SMR 1.79 (95% CI 1.11–2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32–3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80–2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. Conclusions: This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.

Anti–saccharomyces cerevisiae mannan antibodies and antineutrophil cytoplasmic autoantibodies in Greek patients with inflammatory bowel disease

OBJECTIVES:The combined measurement of perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) and anti–Saccharomyces cerevisiae mannan antibodies (ASCA) has recently been suggested as a valuable diagnostic approach in inflammatory bowel disease (IBD). The aim of this study was to assess the value of detecting pANCA and ASCA in the differentiation between ulcerative colitis (UC) and Crohns disease (CD) in a Greek population with IBD.METHODS:Sera were collected from 157 patients with IBD (97 with UC, 56 with CD, and four with indeterminate colitis) and 150 healthy controls. Determination of pANCA was performed by a standard indirect immunofluorescence technique on ethanol-fixed granulocytes and ASCA by an ELISA assay.RESULTS:In patients with UC, sensitivity, specificity, positive predictive value, and negative predictive value of the pANCA test was 67%, 84%, 93%, and 46% respectively. These values did not change significantly when the combination of positive pANCA and negative ASCA was used. ASCA test in diagnosing CD yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 54%, and 81%. The combination of pANCA negative and ASCA positive increased the positive predictive value to 77% and it was associated with small bowel disease.CONCLUSIONS:A positive pANCA test in Greek patients has a diagnostic value in confirming a diagnosis of UC. Measurement of pANCA and ASCA together has a rather limited value in the differential diagnosis between UC and CD but may be of help in studying disease heterogeneity.

Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease

OBJECTIVE:Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. A recently identified mechanism for thrombophilia, the poor anticoagulant response to activated protein C, has been suggested as one of the leading risk factors for thrombosis. The aim of this study was to evaluate the frequency of thrombophilic abnormalities, including activated protein C-resistance (APCR), in Greek patients with ulcerative colitis (UC) and Crohns disease (CD).METHODS:Forty-eight patients with UC, 36 with CD, and 61 matched healthy controls (HC) were studied. Cases with presence of lupus anticoagulant, use of anticoagulants or heparin, and pregnancy were excluded. Disease activity in CD was evaluated by use of the Crohns Disease Activity Index (CDAI) score and in UC by the Truelove-Witts grading system. Plasma levels of protein C, free protein S, antithrombin III (AT-III), activated protein C resistance (APCR), and fibrinogen were determined in IBD patients, as well as in HC. All the cases and controls with abnormal APCR were further studied by genetic testing for the factor V Leiden mutation.RESULTS:Mean fibrinogen levels in UC and CD patients were significantly elevated (p < 0.0001), compared with HC. The mean values of free protein S, as well as mean APCR, were significantly lower in UC and CD patients than in the HC (p < 0.0001). Seven (five UC and two CD) of 84 IBD patients (8.3%) and three of the HC (4.9%) had the factor V Leiden mutation. No significant difference was observed for the other thrombophilic parameters. Fibrinogen levels and profound free protein S deficiency were found related to disease activity.CONCLUSIONS:Thrombophilic defects are common in Greek patients with IBD and they could interfere either in the disease manifestation or in the thrombotic complications.

The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients

Background and Aim: The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north–south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti‐Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population‐based IBD cohort. Methods: Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files. Results: Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north–south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype. Conclusion: The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.

Is endosonography an effective method for detection and local staging of the ampullary carcinoma? A prospective study

BackgroundThe relatively rare carcinoma of the ampulla of Vater is a neoplasia with a good prognosis compared to pancreatic cancer. Preoperative staging is important in planning the most suitable surgical intervention.AimTo prospectively evaluate the diagnostic accuracy of Endoscopic Ultrasonography (EUS) in comparison with conventional US and CT scan, in staging of patients with ampullary carcinoma.Patients and Methods20 patients (7 women and 13 men) with histologically proven carcinoma of the ampulla of Vater were assessed by EUS, CT scan and US. Results were compared to surgical findings.ResultsEndoscopic biopsies were diagnostic in 76% of the patients. Detection of ampullary cancer with US and CT scan was 15% and 20% respectively. Only indirect signs of the disease were identified in the majority of cases using these methods. Overall accuracy of EUS in detection of ampullary tumours was 100%. The EUS was significantly (p < 0.001) superior than US and CT scan in ampullary carcinoma detection. Tumour size, tumour extension and the existence of metastatic lymph nodes were also identified and EUS proved to be very useful for the preoperative classification both for the T and the N components of the TNM staging of this neoplasia. The diagnostic accuracy for tumour extension (T) was 82% and for detection of metastatic lymph nodes (N) was 71%.ConclusionEUS is more accurate in detecting ampullary cancer than US and CT scan. Tumor extension and locally metastatic lymph nodes are more accurately assessed by means of EUS than with other imaging methods.

Ulcerative colitis: no rise in mortality in a European-wide population based cohort 10 years after diagnosis

Background: Population based studies have revealed varying mortality for patients with ulcerative colitis but most have described patients from limited geographical areas who were diagnosed before 1990. Aims: To assess overall mortality in a European cohort of patients with ulcerative colitis, 10 years after diagnosis, and to investigate national ulcerative colitis related mortality across Europe. Methods: Mortality 10 years after diagnosis was recorded in a prospective European-wide population based cohort of patients with ulcerative colitis diagnosed in 1991–1993 from nine centres in seven European countries. Expected mortality was calculated from the sex, age and country specific mortality in the WHO Mortality Database for 1995–1998. Standardised mortality ratios (SMR) and 95% confidence intervals (CI) were calculated. Results: At follow-up, 661 of 775 patients were alive with a median follow-up duration of 123 months (107–144). A total of 73 deaths (median follow-up time 61 months (1–133)) occurred compared with an expected 67. The overall mortality risk was no higher: SMR 1.09 (95% CI 0.86 to 1.37). Mortality by sex was SMR 0.92 (95% CI 0.65 to 1.26) for males and SMR 1.39 (95% CI 0.97 to 1.93) for females. There was a slightly higher risk in older age groups. For disease specific mortality, a higher SMR was found only for pulmonary disease. Mortality by European region was SMR 1.19 (95% CI 0.91 to 1.53) for the north and SMR 0.82 (95% CI 0.45–1.37) for the south. Conclusions: Higher mortality was not found in patients with ulcerative colitis 10 years after disease onset. However, a significant rise in SMR for pulmonary disease, and a trend towards an age related rise in SMR, was observed.

Comparison of Ranson, APACHE II and APACHE III Scoring Systems in Acute Pancreatitis

Introduction Acute pancreatitis runs an unpredictable course. The early prediction of the severity of an acute attack has important implications for management and timely intervention. Aim To assess the prognostic accuracy of Ranson and APACHE II and III scoring systems in predicting the severity of acute pancreatitis. Methods One hundred fifty-three patients with acute pancreatitis (67.3% gallstone-related, 9.2% alcoholic, 17% idiopathic, and 6.5% of miscellaneous causes) were studied prospectively. Data conforming to the scoring systems were recorded 24 (the APACHE scores) and 48 hours (the Ranson score) after admission. Analysis was performed by using receiver operating characteristic curves (ROC), area under a curve (AUC), and by comparing likelihood ratios of positive test (LRPT). Results One hundred nineteen cases of pancreatitis were classified as mild, and 34 were classified as severe. The mortality rate was 3.2%. All three scores correlated with length of stay and disease severity. AUC for Ranson was found to be significantly larger than AUC for APACHE II and APACHE III score (0.817, cut-off ≥3; 0.618, cut-off, ≥10; and 0,676, cut-off ≥42 respectively). The Ranson score achieved the highest sensitivity and the lowest false-negative rate, but the positive and negative predictive values and LRPT were of similar extent for all three scores. Conclusion The APACHE III offers little, if any, advantage over the APACHE II score. Ranson criteria proved to be as powerful a prognostic model as the more complicated APACHE II and III scoring systems, but with the disadvantage of a 24-hour delay.

Disease outcome in inflammatory bowel disease: mortality, morbidity and therapeutic management of a 796-person inception cohort in the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD).

BACKGROUND The course of inflammatory bowel diseases (IBD) has mainly been studied using different methods in single patient cohorts. The aim of the present study was to assess clinical aspects of disease outcome in a population-based cohort of IBD patients over a 4-year period in multiple centres across Europe. METHODS A total of 796 patients with IBD diagnosed in 10 centres between October 1991 and October 1993, registered at the EC IBD study centre (98% of the original cohort), participated in the study. Investigators filled out a standard follow-up form containing questions on the method of follow-up, vital status of the patient, change in diagnosis, extraintestinal manifestations, medical and surgical treatment, and physicians global assessment of disease activity. RESULTS Complete relief of the complaints was reported in 255 (48%) patients with ulcerative colitis (UC), 9 (50%) with indeterminate colitis (IC), but only in 87 (35%) of patients with Crohn disease (CD). Improvement was reported in 195 (37%) patients with UC, 113 (45%) with CD and 6 (33%) with IC. During the 4-year follow-up period, 23 patients died (14 UC, 8 CD. and 1 IC). The mean age at death was 69.3 years (s, 14.9 years). The deaths of three patients were recorded as directly due to IBD. CONCLUSIONS With the present approach to therapeutic management the short-term outcome of patients with IBD seems to be favourable in 10 medical centres in the north and south of Europe. However, more detailed studies including both objective and subjective measures are necessary.Background: The course of inflammatory bowel diseases (IBD) has mainly been studied using different methods in single patient cohorts. The aim of the present study was to assess clinical aspects of disease outcome in a population-based cohort of IBD patients over a 4-year period in multiple centres across Europe. Methods: A total of 796 patients with IBD diagnosed in 10 centres between October 1991 and October 1993, registered at the EC IBD study centre (98% of the original cohort), participated in the study. Investigators filled out a standard follow-up form containing questions on the method of follow-up, vital status of the patient, change in diagnosis, extraintestinal manifestations, medical and surgical treatment, and physicians global assessment of disease activity. Results: Complete relief of the complaints was reported in 255 (48%) patients with ulcerative colitis (UC), 9 (50%) with indeterminate colitis (IC), but only in 87 (35%) of patients with Crohn disease (CD). Improvement was reported in 195 (37%) patients with UC, 113 (45%) with CD and 6 (33%) with IC. During the 4-year follow-up period, 23 patients died (14 UC, 8 CD, and 1 IC). The mean age at death was 69.3 years (s, 14.9 years). The deaths of three patients were recorded as directly due to IBD. Conclusions: With the present approach to therapeutic management the short-term outcome of patients with IBD seems to be favourable in 10 medical centres in the north and south of Europe. However, more detailed studies including both objective and subjective measures are necessary.