The diagnostic value of abbreviated MRI protocol in the surveillance of Branch-Duct intraductal papillary mucinous neoplasm.

PURPOSE: To assess the diagnostic value of abbreviated protocol (AP) MRI to detect the degeneration signs in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) in patients undergoing a routine MRI follow-up. METHODS: This dual-center retrospective study include patients with BD-IPMN diagnosed on initial comprehensive protocol (CP) MRI who underwent routine MRI follow-up. CP included axial and coronal T2-weighted images (T2WI), axial T1-weighted images (T1WI) before and after contrast administration, 3D MR cholangiopancreatography (MRCP) and diffusion-weighted images (DWI). Two APs, eliminating dynamic sequences ± DWI, were extracted from CP. Two radiologists evaluated the APs separately for IPMN degeneration signs according to Fukuoka criteria and compared the results to the follow-up CP. In patients who underwent EUS, imaging findings were correlated with pathological results. Per-patient and per-lesion sensitivity, specificity, PPV, NPV, and accuracy of APs were calculated. Additionally, the acquisition time for different protocols was calculated. RESULTS: One hundred-fourteen patients (56.1 % women, median age: 71 years) with 256 lesions were included. Degeneration signs were observed in 24.6 % and 12.1 % per-patient and per-lesion, respectively. Regarding APs, the per patient sensitivity, specificity, PPV, NPV, and accuracy in the detection of the degeneration signs were 100 %, 93.5 %, 83.3 %, 100 %, and 95.1 %, respectively. No additional role for DWI was detected. AP without DWI economized nearly half of CP acquisition time (388 versus 663 s, respectively). CONCLUSION: AP can confidently replace CP for BD-IPMN follow-up with high sensitivity and PPV while offering benefits such as patient comfort, improved MRI accessibility, and reduced dedicated time for image analysis. DWI necessitates special consideration. CLINICAL RELEVANCE STATEMENT: Our data suggest that APs safely detect all degeneration signs of IPMN. While there is an overestimation of mural nodules due to the lack of contrast injection, this occurs in a negligible number of patients.

Risk of Vaccine-Preventable Infections in Swiss Adults with Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a higher risk of infection and are frequently not up to date with their immunizations. OBJECTIVES: This study aims to review vaccination status and evaluate whether age, disease type, or treatment regimen could predict the absence of seroprotection against selected vaccine-preventable infection in adults with IBD. METHODS: Cross-sectional study using questionnaire, immunization records review, and assessment of tetanus-specific, varicella-specific, and measles-specific immunoglobulin G concentrations. ClinicalTrials.gov: NCT01908283. RESULTS: Among the 306 adults assessed (median age 42.7 years old, 70% with Crohn's disease, 78% receiving immunosuppressive treatment), only 33% had an immunization record available. Absence of seroprotection against tetanus (6%) was associated with increasing age and absence of booster dose; absence of seroprotection against varicella (1%) or measles (3%) was exclusively observed in younger patients with Crohn's disease. There was no statistically significant difference in immunoglobulin concentrations among treatment groups. Although vaccinations are strongly recommended in IBD patients, the frequencies of participants with at least 1 dose of vaccine recorded were low for nearly all antigens: tetanus 94%, diphtheria 87%, pertussis 54%, poliovirus 22%, measles-mumps-rubella 47%, varicella-zoster 0%, Streptococcus pneumoniae 5%, Neisseria meningitidis 12%, hepatitis A 41%, hepatitis B 48%, human papillomavirus 5%, and tick-borne encephalitis 6%. CONCLUSIONS: Although many guidelines recommend the vaccination of IBD patients, disease prevention through immunization is still often overlooked, including in Switzerland, increasing their risk of vaccine-preventable diseases. Serological testing should be standardized to monitor patients' protection during follow-up as immunity may wane faster in this population.

TNF-Alpha Blockers in Inflammatory Bowel Diseases: Practical Recommendations and a User's Guide: An Update.

BACKGROUND: Anti-tumour necrosis factor-alpha (anti-TNF) antagonists have been the mainstay in the treatment of inflammatory bowel diseases (IBDs) for over 20 years. SUMMARY: This review article aimed to provide an update on recent advances in TNF antagonist therapy for IBDs. Key Messages: Their position in the treatment algorithm has evolved to "rapid step-up therapy" or "top-down therapy" according to disease severity and patients' characteristics. Limitations of anti-TNF antagonists include loss of response in up to 30-50% of patients with or without the development of antibodies. Therapeutic drug monitoring should provide a tailored, personalized approach to this scenario. Recently, biosimilar agents have been approved for IBDs and are considered equivalent in efficacy to the originator.

Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus.

BACKGROUND: Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. METHODS: To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. RESULTS: The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn's disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 µg/mL, adalimumab 8 µg/mL, certolizumab pegol 10 µg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. CONCLUSION: A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics.

High Immunogenicity of the Pneumococcal Conjugated Vaccine in Immunocompromised Adults With Inflammatory Bowel Disease.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are predisposed to pneumococcal infections due to their underlying disease and iatrogenic immunosuppression. Vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) is recommended, but with poor take-up and few data available. We performed an open-label, phase IV, multicenter study to evaluate the safety and immunogenicity of PCV13 in adults with IBD and to analyze the influence of immunomodulating treatments on anti-pneumococcal seroresponses. METHODS: We enrolled 306 patients with IBD from March 2014 through February 2016, with the following exclusion criteria: current IBD flare, pregnancy, pneumococcal immunization in the previous 5 years, and influenza immunization in the previous 4 weeks. PCV13 was administered intramuscularly. Serotype-specific vaccine responses were evaluated using an opsonophagocytic assay. Adverse events were monitored by diary cards and standardized phone interviews. RESULTS: The median seroprotection rate increased significantly from 43.9% (95% confidence interval [CI], 42.3-45.5) at inclusion to 90.4% (95% CI, 89.5-91.3%; P < 0.001) after vaccination. Patients receiving anti-tumor necrosis factor agents achieved a slightly lower seroprotection rate (from 44.5% [95% CI, 42.3%-46.8%] to 86.6% [95% CI, 84.9%-88.1%]) than patients treated with other types of immunosuppressive regimens (thiopurine, methotrexate, oral corticosteroids; from 44.7% [95% CI, 41.7%-47.7%] to 93.8% [95% CI, 92.1%-95.2%]) or nonimmunosuppressive treatment (5-aminosalicylate, topical corticosteroids, vedolizumab; from 41.3% [95% CI, 37.9%-44.8%] to 95.2% [95% CI, 93.4%-96.6%]). There were no safety issues. DISCUSSION: Overall, the administration of PCV13 was highly immunogenic and well tolerated, irrespective of the baseline treatment, and should be encouraged in all adults with IBD.

Experts Opinion on the Practical Use of Azathioprine and 6-Mercaptopurine in Inflammatory Bowel Disease.

The relevance of azathioprine and 6-mercaptopurine therapy in inflammatory bowel disease, Crohn's disease, and ulcerative colitis, has been challenged in recent publications. In this article, a panel of experts gives advice, based on the relevant literature, on indications and practical use of azathioprine/6-mercaptopurine, prevention, and management of drug adverse reactions and special situations such as vaccination, pregnancy, and lactation.

Characteristics of non-responders to self-reported questionnaires in a large inflammatory bowel disease cohort study.

BACKGROUND: A major threat to the validity of longitudinal cohort studies is non-response to follow-up, which can lead to erroneous conclusions. The objective of this study was to evaluate the profile of non-responders to self-reported questionnaires in the Swiss inflammatory bowel disease (IBD) Cohort. METHODS: We used data from adult patients enrolled between November 2006 and June 2011. Responders versus non-responders were compared according to socio-demographic, clinical and psychosocial characteristics. Odds ratio for non-response to initial patient questionnaire (IPQ) compared to 1-year follow-up questionnaire (FPQ) were calculated. RESULTS: A total of 1943 patients received IPQ, in which 331 (17%) did not respond. Factors inversely associated with non-response to IPQ were age >50 and female gender (OR = 0.37; p < 0.001 respectively OR = 0.63; p = 0.003) among Crohn's disease (CD) patients, and disease duration >16 years (OR = 0.48; p = 0.025) among patients with ulcerative colitis (UC). FPQ was sent to 1586 patients who had completed the IPQ; 263 (17%) did not respond. Risk factors of non-response to FPQ were mild depression (OR = 2.17; p = 0.003) for CD, and mild anxiety (OR = 1.83; p = 0.024) for UC. Factors inversely associated with non-response to FPQ were: age >30 years, colonic only disease location, higher education and higher IBD-related quality of life for CD, and age >50 years or having a positive social support for UC. CONCLUSIONS: Characteristics of non-responders differed between UC and CD. The risk of non-response to repetitive solicitations (longitudinal versus transversal study) seemed to decrease with age. Assessing non-respondents' characteristics is important to document potential bias in longitudinal studies.

Appropriateness and long-term discontinuation rate of biological therapies in ulcerative colitis.

BACKGROUND: Anti-TNFα agents are commonly used for ulcerative colitis (UC) therapy in the event of non-response to conventional strategies or as colon-salvaging therapy. The objectives were to assess the appropriateness of biological therapies for UC patients and to study treatment discontinuation over time, according to appropriateness of treatment, as a measure of outcome. METHODS: We selected adult ulcerative colitis patients from the Swiss IBD cohort who had been treated with anti-TNFα agents. Appropriateness of the first-line anti-TNFα treatment was assessed using detailed criteria developed during the European Panel on the Appropriateness of Therapy for UC. Treatment discontinuation as an outcome was assessed for categories of appropriateness. RESULTS: Appropriateness of the first-line biological treatment was determined in 186 UC patients. For 64% of them, this treatment was considered appropriate. During follow-up, 37% of all patients discontinued biological treatment, 17% specifically because of failure. Time-to-failure of treatment was significantly different among patients on an appropriate biological treatment compared to those for whom the treatment was considered not appropriate (p=0.0007). Discontinuation rate after 2years was 26% compared to 54% between those two groups. Patients on inappropriate biological treatment were more likely to have severe disease, concomitant steroids and/or immunomodulators. They were also consistently more likely to suffer a failure of efficacy and to stop therapy during follow-up. CONCLUSION: Appropriateness of first-line anti-TNFα therapy results in a greater likelihood of continuing with the therapy. In situations where biological treatment is uncertain or inappropriate, physicians should consider other options instead of prescribing anti-TNFα agents.

Penetrating or stricturing diseases are the major determinants of time to first and repeat resection surgery in Crohn's disease.

BACKGROUND: About 80% of patients with Crohn's disease (CD) require bowel resection and up to 65% will undergo a second resection within 10 years. This study reports clinical risk factors for resection surgery (RS) and repeat RS. METHODS: Retrospective cohort study, using data from patients included in the Swiss Inflammatory Bowel Disease Cohort. Cox regression analyses were performed to estimate rates of initial and repeated RS. RESULTS: Out of 1,138 CD cohort patients, 417 (36.6%) had already undergone RS at the time of inclusion. Kaplan-Meier curves showed that the probability of being free of RS was 65% after 10 years, 42% after 20 years, and 23% after 40 years. Perianal involvement (PA) did not modify this probability to a significant extent. The main adjusted risk factors for RS were smoking at diagnosis (hazard ratio (HR) = 1.33; p = 0.006), stricturing with vs. without PA (HR = 4.91 vs. 4.11; p < 0.001) or penetrating disease with vs. without PA (HR = 3.53 vs. 4.58; p < 0.001). The risk factor for repeat RS was penetrating disease with vs. without PA (HR = 3.17 vs. 2.24; p < 0.05). CONCLUSION: The risk of RS was confirmed to be very high for CD in our cohort. Smoking status at diagnosis, but mostly penetrating and stricturing diseases increase the risk of RS.

When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel.

BACKGROUND: Safety and economic issues have increasingly raised concerns about the long term use of immunomodulators or biologics as maintenance therapies for Crohn's disease (CD). Despite emerging evidence suggesting that stopping therapy might be an option for low risk patients, criteria identifying target groups for this strategy are missing, and there is a lack of recommendations regarding this question. METHODS: Multidisciplinary European expert panel (EPACT-II Update) rated the appropriateness of stopping therapy in CD patients in remission. We used the RAND/UCLA Appropriateness Method, and included the following variables: presence of clinical and/or endoscopic remission, CRP level, fecal calprotectin level, prior surgery for CD, and duration of remission (1, 2 or 4 years). RESULTS: Before considering withdrawing therapy, the prerequisites of a C-reactive protein (CRP) and fecal calprotectin measurement were rated as "appropriate" by the panellists, whereas a radiological evaluation was considered as being of "uncertain" appropriateness. Ileo-colonoscopy was considered appropriate 1 year after surgery or after 4 years in the absence of prior surgery. Stopping azathioprine, 6-mercaptopurine or methotrexate mono-therapy was judged appropriate after 4 years of clinical remission. Withdrawing anti-TNF mono-therapy was judged appropriate after 2 years in case of clinical and endoscopic remission, and after 4 years of clinical remission. In case of combined therapy, anti-TNF withdrawal, while continuing the immunomodulator, was considered appropriate after two years of clinical remission. CONCLUSION: A multidisciplinary European expert panel proposed for the first time treatment stopping rules for patients in clinical and/or endoscopic remission, with normal CRP and fecal calprotectin levels.

First-line therapies in inflammatory bowel disease.

BACKGROUND AND AIMS: Medical therapy of inflammatory bowel disease (IBD) is becoming more complex, given the increasing choice of drugs to treat Crohn's disease (CD) and ulcerative colitis (UC). We aimed to summarize the current guidelines for first-line treatments in IBD. METHODS: An extensive literature search with focus on the guidelines of the European Crohn's and Colitis Organisation for the diagnosis and treatment of CD and UC was performed. First-line treatments were defined as the following drug categories: 5-aminosalicylates, budesonide, systemic steroids, azathioprine, 6-mercaptopurine, methotrexate, infliximab, adalimumab and certolizumab pegol. The following drug categories were not included: cyclosporine and tacrolimus (not yet approved by Swissmedic for IBD treatment). RESULTS: Treatment recommendations for the following clinically frequent situations are presented according to disease severity: ileocecal CD, colonic CD, proximal small bowel CD and perianal CD. For UC the following situations are presented: ulcerative proctitis, left-sided colitis and pancolitis. CONCLUSIONS: We provide a summary on the use of first-line therapies for clinically frequent situations in patients with CD and UC.

Treatment of fibrostenotic and fistulizing Crohn's disease.

The majority of Crohn's disease patients will develop a complicated disease course over time which is characterized by the occurrence of stricturing and penetrating disease. Penetrating disease comprises internal fistulas (e.g. enteroenteric) and perianal disease. A complicated disease course may be associated with considerable morbidity and professional and personal disabilities. Treatment options for fibrostenotic Crohn's disease comprise endoscopic balloon dilation, stricturoplasties and surgical resection. Treatment of symptomatic perianal fistulizing disease is based on antibiotics, immunomodulators and anti-TNF drugs. Surgical measures include fistula drainage by means of setons, temporary ileostomy or a proctectomy. The presence of internal fistulas often necessitates surgical measures. A close collaboration between the gastroenterologist and the surgeon is mandatory to solve these interdisciplinary challenges.

Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease.

BACKGROUND: The diagnosis of inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), continues to present difficulties due to unspecific symptoms and limited test accuracies. We aimed to determine the diagnostic delay (time from first symptoms to IBD diagnosis) and to identify associated risk factors. METHODS: A total of 1591 IBD patients (932 CD, 625 UC, 34 indeterminate colitis) from the Swiss IBD cohort study (SIBDCS) were evaluated. The SIBDCS collects data on a large sample of IBD patients from hospitals and private practice across Switzerland through physician and patient questionnaires. The primary outcome measure was diagnostic delay. RESULTS: Diagnostic delay in CD patients was significantly longer compared to UC patients (median 9 versus 4 months, P < 0.001). Seventy-five percent of CD patients were diagnosed within 24 months compared to 12 months for UC and 6 months for IC patients. Multivariate logistic regression identified age <40 years at diagnosis (odds ratio [OR] 2.15, P = 0.010) and ileal disease (OR 1.69, P = 0.025) as independent risk factors for long diagnostic delay in CD (>24 months). In UC patients, nonsteroidal antiinflammatory drug (NSAID intake (OR 1.75, P = 0.093) and male gender (OR 0.59, P = 0.079) were associated with long diagnostic delay (>12 months). CONCLUSIONS: Whereas the median delay for diagnosing CD, UC, and IC seems to be acceptable, there exists a long delay in a considerable proportion of CD patients. More public awareness work needs to be done in order to reduce patient and doctor delays in this target population.

Report of the ECCO workshop on anti-TNF therapy failures in inflammatory bowel diseases: biological roles and effects of TNF and TNF antagonists.

This second section of the first ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases addresses the biological roles of TNFα and the effects and mechanisms of action of TNFα antagonists. Mechanisms underlying their failure, including induction of TNF-independent inflammatory pathways and phenomena of paradoxical inflammation are discussed.

Infliximab for Crohn's disease in the Swiss IBD Cohort Study: clinical management and appropriateness.

OBJECTIVE: Antitumor necrosis factor a agents have significantly improved the management of Crohn's disease (CD), but not all patients benefit from this therapy. We used data from the Swiss Inflammatory Bowel Disease Cohort Study and predefined appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients. METHODS: EPACT II (European Panel on the Appropriateness of CD Therapy, 2007; www.epact.ch) appropriateness criteria have been developed using a formal explicit panel process combining evidence from the published literature and expert opinion. Questionnaires relating to EPACT II criteria were used at enrollment and follow-up of all Swiss Inflammatory Bowel Disease Cohort Study patients. A step-by-step analysis of all possible indications for IFX therapy in a given patient allowed identification of the most appropriate indication and final classification in a single appropriateness category (appropriate, uncertain, inappropriate). RESULTS: Eight hundred and twenty-one CD patients were prospectively enrolled between November 2006 and March 2009. IFX was administered to 146 patients (18%) at enrollment and was most frequently used for complex fistulizing disease and for the maintenance of remission induced by biological therapy. IFX therapy was considered appropriate in 44%, uncertain in 44%, and inappropriate in 10% of patients. CONCLUSION: In this cohort, 9 out of 10 indications for IFX therapy were clinically generally acceptable (appropriate or uncertain) according to EPACT II criteria. Uncertain indications resulted mainly from the current more liberal use of IFX in clinical practice as compared with the EPACT II criteria.

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

OBJECTIVE: The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). MATERIAL AND METHODS: A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. RESULTS: Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. CONCLUSION: Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

Appropriateness of therapy for active Crohn's disease: Results of a multidisciplinary international expert panel-EPACT II.

UNLABELLED: The increasing number of trials testing management strategies for luminal Crohn's disease (CD) has not filled all the gaps in our knowledge and thus, in clinical practice, many decisions for CD patients have to be taken without the benefit of high-quality evidence. METHODS: A multidisciplinary European expert panel used the RAND Appropriateness Method to develop and rate explicit criteria for the management of individual patients with active, steroid-dependent (ST-D) and steroid-refractory (ST-R) CD. RESULTS: Overall, 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD were rated. In anti-TNF naïve patients, budesonide and prednisone were found to be appropriate for mild-moderate CD, and infliximab (IFX) was appropriate when these had previously failed or had not been tolerated. In patients with a prior successful treatment by IFX, this drug, with or without co-administration of a thiopurine analog, was favoured. Other anti-TNFs were appropriate in the presence of intolerance or resistance to IFX. High-dose steroids, IFX or adalimumab were appropriate in severe active CD. For the 105 indications for ST-D or ST-R disease, the panel considered the thiopurine analogs, methotrexate, IFX, adalimumab, and surgery for limited resection, to be appropriate, depending on the outcome of prior therapies. Anti-TNFs were generally considered appropriate in ST-R. CONCLUSION: Steroids, including budesonide for mild-to-moderate CD, remain the first-line therapy for active luminal CD. Anti-TNFs, in particular IFX as shown by the amount of available evidence, remain the second-line therapy for most indications. Thiopurine analogs, methotrexate and anti-TNFs are favoured in ST-D patients and ST-R patients.

Appropriate therapy for fistulizing and fibrostenotic Crohn's disease: Results of a multidisciplinary expert panel - EPACT II.

INTRODUCTION: Many therapeutic decisions in the management of fistulizing and fibrostenotic Crohn's disease (CD) have to be taken without the benefit of strong scientific evidence. For this reason, explicit appropriateness criteria for CD fistula and stenosis treatment were developed by a multidisciplinary European expert panel in 2004 with the aim of making them easily available on the Internet and thus allowing individual case scenario evaluation; these criteria were updated in 2007. METHODS: Twelve international experts convened in Geneva, Switzerland in December 2007. Explicit clinical scenarios, corresponding to real daily practice, were rated on a 9-point scale based on evidence from the published literature and panelists' own expertise. Median ratings were stratified into three categories: appropriate (7-9), uncertain (4-6) and inappropriate (1-3). RESULTS: Overall, panelists rated 60 indications pertaining to fistulas. Antibiotics, azathioprine/6-mercaptopurine and conservative surgery are the mainstay of therapy for simple and complex fistulas. In the event of previous failure of azathioprine/6-mercaptopurine therapy, methotrexate and infliximab were considered appropriate for complex fistulas. The panel also rated 72 indications related to the management of fibrostenotic CD. The experts considered balloon dilation, if the stricture was endoscopically accessible, stricturoplasty and bowel resection to be appropriate for small bowel fibrostenotic Crohn's disease, and balloon dilation and bowel resection appropriate for fibrostenotic colonic disease. In the presence of an ileocolonic or ileorectal anastomotic stricture of <7 cm, endoscopic balloon dilation, and bowel resection were considered appropriate. CONCLUSION: Antibiotics, azathioprine/6-mercaptopurine, and conservative surgery are the mainstay of therapy for fistulizing Crohn's disease. Infliximab is a therapeutic option in patients without prior response to immunosuppressant therapy. In fibrostenotic Crohn's disease, endoscopic balloon dilation, if feasible, or surgical therapy should be considered. These expert recommendations are available online (www.epact.ch). Prospective evaluation is now needed to test the validity of these appropriateness criteria in clinical practice.

Appropriate management of special situations in Crohn's disease (upper gastro-intestinal; extra-intestinal manifestations; drug safety during pregnancy and breastfeeding): Results of a multidisciplinary international expert panel-EPACT II.

INTRODUCTION: High-grade evidence is lacking for most therapeutic decisions in Crohn's disease. Appropriateness criteria were developed for upper gastro-intestinal, extra-intestinal manifestations and drug safety during conception, pregnancy and breastfeeding in patients with Crohn's disease, to assist the physician in clinical decision making. METHODS: The European Panel on the Appropriateness of Crohn's Disease Therapy (EPACT II), a multidisciplinary international European expert panel, rated clinical scenarios based on evidence from the published literature and panelists' own clinical expertise. Median ratings (on a 9-point scale) were stratified into three categories: appropriate (7-9), uncertain (4-6 with or without disagreement) and inappropriate (1-3). Experts were also asked to rank appropriate medications by priority. RESULTS: Proton pump inhibitors, steroids, azathioprine/6-mercaptopurine and infliximab are appropriate for upper gastro-duodenal Crohn's disease; for stenosis, endoscopic balloon dilation is the first-line therapy, although surgery is also appropriate. Ursodeoxycholic acid is the only appropriate treatment for primary sclerosing cholangitis. Infliximab is appropriate for Pyoderma gangrenosum, ankylosing spondylitis and uveitis, steroids for Pyoderma gangrenosum and ankylosing spondylitis, adalimumab for Pyoderma gangrenosum and ankylosing spondylitis, cyclosporine-A/tacrolimus for Pyoderma gangrenosum. Mesalamine, sulfasalazine, prednisone, azathioprine/6-mercaptopurine, ciprofloxacin, and probiotics, may be administered safely during pregnancy or for patients wishing to conceive, with the exception that male patients considering conception should avoid sulfasalazine. Metronidazol is considered safe in the 2nd and 3rd trimesters whereas infliximab is rated safe in the 1st trimester but uncertain in the 2nd and 3rd trimesters. Methotrexate is always contraindicated at conception, during pregnancy or during breastfeeding, due to its known teratogenicity. Mesalamine, prednisone, probiotics and infliximab are considered safe during breastfeeding. CONCLUSION: EPACT II recommendations are freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation.