Histological Phenotyping in Eosinophilic Esophagitis: Localized Proximal Disease Is Infrequent but Associated with Less Severe Disease and Better Disease Outcome.

INTRODUCTION: It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease. METHODS: We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications. RESULTS: We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p < 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia. CONCLUSION: Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype.

Effectiveness and safety of vedolizumab induction with or without budesonide in patients with moderately to severely active Crohn's disease in Europe: a retrospective observational study.

BACKGROUND: Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking integrin antibody, is effective in treating patients with moderately to severely active Crohn's disease (CD). In this study, we examined the real-world effectiveness and safety of induction therapy using VDZ alone or in combination with budesonide (VDZ + BUD) among patients with CD in Belgium, Israel, and Switzerland. METHODS: This retrospective chart review analysis included adult patients with moderately to severely active CD who started induction treatment with VDZ or VDZ + BUD (January 2015 through January 2019). The primary objective of this study was to assess the effectiveness in terms of clinical remission of VDZ alone or VDZ + BUD using patient-reported outcomes (PRO) of abdominal pain (AP) and/or loose stool frequency (LSF) (PRO-2) at weeks 0, 2, 6, 10, and 14. Regression models were used to assess differences and associations between the treatment groups. RESULTS: Overall, 123 patients were included (VDZ, n = 73; VDZ + BUD, n = 50). Clinical remission rates at week 14 were 71.4% (50/70) and 68.0% (34/50) with VDZ and VDZ + BUD, respectively. Mean percentage change in AP and LSF from baseline to week 14 was comparable between the groups. Median (95% confidence interval [CI]) time to clinical remission was 91 [70.0-98.0] and 95 [70.0-98.0] days, respectively. One patient in each group discontinued VDZ and 68.0% of patients in the VDZ + BUD group discontinued BUD before week 14. The rates of overall adverse events were similar between the groups (VDZ, 23.3%; VDZ + BUD, 26.0%). CONCLUSIONS: In this retrospective study, VDZ alone and VDZ + BUD showed similar high remission rates in patients with moderately to severely active CD. Prospective randomized studies are needed to conclude on the role of combining VDZ with BUD. TRIAL REGISTRATION: Not applicable.

[Extraintestinal manifestations in inflammatory bowel disease].

INTRODUCTION: Chronic inflammatory bowel diseases (IBD) are inflammatory gastrointestinal disorders that are not limited to the gastrointestinal tract. Many different organ systems may be involved, which makes IBD a systemic disease. The most common extraintestinal manifestations (EIM) include musculoskeletal, ophthalmological, dermatological, and hepato-biliary disorders. EIM considerably contribute to the morbidity of patients with IBD, and they limit quality of life of affected patients. Due to the diversity of the organ systems involved, care should be provided by an interdisciplinary team. Early detection of EIM allows targeted therapy and reduces overall morbidity. Of importance is the fact that EIM can occur in up to 25% of all IBD patients before the onset of the first Crohn's episode or ulcerative colitis. Therefore, all doctors, especially dermatologists, ophthalmologists and rheumatologists should be aware of this possible association between EIM and the simultaneous occurrence of intestinal symptoms.

Emerging treatment options for extraintestinal manifestations in IBD.

Extraintestinal manifestations (EIMs) are frequently observed in IBDs and contribute considerably to morbidity and mortality. They have long been considered a difficult to treat entity due to limited therapy options, but the increasing use of anti-tumour necrosis factors has dramatically changed the therapeutic approach to EIM in recent years. Newly emerging therapies such as JAK inhibitors and anti-interleukin 12/23 will further shape the available armamentarium. Clinicians dealing with EIMs in everyday IBD practice may be puzzled by the numerous available biological agents and small molecules, their efficacy for EIMs and their potential off-label indications. Current guidelines on EIMs in IBD do not include treatment algorithms to help practitioners in the treatment decision-making process. Herein, we summarise knowledge on emerging biological treatment options and small molecules for EIMs, highlight current research gaps, provide therapeutic algorithms for EIM management and shed light on future strategies in the context of IBD-related EIMs.

Abdominal pain in patients with inflammatory bowel disease: association with single-nucleotide polymorphisms prevalent in irritable bowel syndrome and clinical management.

BACKGROUND: Abdominal pain is a frequent symptom in patients with inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC). Pain can result from ongoing inflammation or functional disorders imitating irritable bowel syndrome (IBS). Several single-nucleotide polymorphisms (SNPs) have been associated with IBS. However, the impact of IBS genetics on the clinical course of IBD, especially pain levels of patients remains unclear. METHODS: Data of 857 UC and 1206 CD patients from the Swiss IBD Cohort Study were analysed. We tested the association of the maximum of the abdominal pain item of disease activity indices in UC and CD over the study period with 16 IBS-associated SNPs, using multivariate ANOVA models. RESULTS: In UC patients, the SNPs rs1042713 (located on the ADRB2 gene) and rs4663866 (close to the HES6 gene) were associated with higher abdominal pain levels (P = 0.044; P = 0.037, respectively). Abdominal pain was not associated with any markers of patient management in a model adjusted for confounders. In CD patients, higher levels of abdominal pain correlated with the number of physician contacts (P < 10-15), examinations (P < 10-12), medical therapies (P = 0.023) and weeks of hospitalisation (P = 0.0013) in a multivariate model. CONCLUSIONS: We detected an association between maximal abdominal pain in UC patients and two IBS-associated SNPs. Abdominal pain levels had a pronounced impact on diagnostic and therapeutic procedures in CD but not in UC patients.

Evaluation of Acute Mountain Sickness by Unsedated Transnasal Esophagogastroduodenoscopy at High Altitude.

BACKGROUND & AIMS: It is not clear how rapid ascent to a high altitude causes the gastrointestinal symptoms of acute mountain sickness (AMS). We assessed the incidence of endoscopic lesions in the upper gastrointestinal tract in healthy mountaineers after a rapid ascent to high altitude, their association with symptoms, and their pathogenic mechanisms. METHODS: In a prospective study, 25 mountaineers (10 women; mean age, 43.8 ± 9.5 y) underwent unsedated, transnasal esophagogastroduodenoscopy in Zurich (490 m) and then on 2 test days (days 2 and 4) at a high altitude laboratory in the Alps (Capanna Regina Margherita, 4559 m). Symptoms were assessed using validated instruments for AMS (the acute mountain sickness score and the Lake Louise scoring system) and visual analogue scales (scale, 0-100). Levels of messenger RNAs (mRNAs) in duodenal biopsy specimens were measured by quantitative polymerase chain rection. RESULTS: The follow-up endoscopy at high altitude was performed in 19 of 25 patients on day 2 and in 23 of 25 patients on day 4. The frequency of endoscopic lesions increased from 12% at baseline to 26.3% on day 2 and to 60.9% on day 4 (P < .001). The incidence of ulcer disease increased from 0 at baseline to 10.5% on day 2 and to 21.7% on day 4 (P = .014). Mucosal lesions were associated with lower hunger scores (37.3 vs 67.4 in patients without lesions; P = .012). Subjects with peptic lesions had higher levels of HIF2A mRNA, which encodes a hypoxia-induced transcription factor, and ICAM1 mRNA, which encodes an adhesion molecule, compared with subjects without lesions (fold changes, 1.38 vs 0.63; P = .001; and 1.37 vs 0.66; P = .011, respectively). CONCLUSIONS: In a prospective study of 25 mountaineers, fast ascent to a high altitude resulted in rapid onset of clinically meaningful mucosal lesions and ulcer disease. Duodenal biopsy specimens from these subjects had increased levels of HIF2A mRNA and ICAM1 mRNA, which might contribute to the formation of hypoxia-induced peptic lesions. Further studies are needed of the mechanisms of this process.

Improved treatment outcome and lower skin toxicity with intensity-modulated radiotherapy vs. 3D conventional radiotherapy in anal cancer.

PURPOSE: Radiochemotherapy is the standard treatment for anal carcinoma (ACa). Intensity-modulated radiotherapy (IMRT) has been introduced, allowing focused irradiation of the tumor area. Whether physical benefits of IMRT translate to clinical benefits has not been sufficiently demonstrated. METHODS: We retrospectively reviewed data from 82 patients with newly diagnosed ACa. Patients treated with IMRT were compared with previous patients treated with conventional three-dimensional computational radiotherapy (3D-CRT). The influence of IMRT on complete remission and acute and chronic side effects was analyzed in univariate and multivariate analyses. RESULTS: 39/40 patients treated with IMRT were in complete remission after 1 year compared to 31/39 patients treated with 3D-CRT (p = 0.014). Multivariate analysis confirmed tumor T stage as well as lack of IMRT treatment as risk factors for persistent tumor at 6 months. No significant benefits of IMRT were apparent at later timepoints (median follow up 52 months, IQR: 31.5-71.8 months). Patients treated with IMRT had a significantly lower degree of skin toxicity (median 2 vs. 3 in a scale ranging from 0 to 3, p = 0.00092). Rates of hematological toxicity/proctitis were not reduced and rates of acute diarrhea increased (p = 0.034). Median length of hospitalization tended to be shorter in patients treated with IMRT (n. s.). CONCLUSION: We present a real-world experience of shifting radiation technique from conventional 3D-CRT to IMRT. IMRT patients had better tumor control at 1 year and lower degrees of skin toxicity. Our data indicate that IMRT can enable therapies with lower side effects with equal or better oncological results for patients with ACa.

Systematic Assessment of Adult Patients' Satisfaction with Various Eosinophilic Esophagitis Therapies.

BACKGROUND AND AIMS: The treatment options for eosinophilic esophagitis (EoE) patients include drugs (proton pump inhibitors [PPIs], swallowed topical corticosteroids [STCs]), elimination diets, and dilation. Given the lack of data, we aimed to assess adult EoE patients' satisfaction with different EoE-specific treatment modalities. PATIENTS AND METHODS: We evaluated therapy satisfaction recalled over a 12-month period using the validated Treatment Satisfaction Questionnaire for Medication that assesses effectiveness, side effects, convenience, and overall satisfaction. The score for each scale ranges from 0 (dissatisfied) to 100 (satisfied). To evaluate satisfaction with nonpharmacologic therapies, the questionnaire was modified and debriefed into three focus groups. The final questionnaire was sent to 147 patients. RESULTS: The patient response rate was 74%. In the last 12 months, 24, 75, 19, and 9% were treated with PPIs, STCs, elimination diet, and dilation, respectively. Patients identified the following considerations as important for therapy choice: effect on symptoms (89%), effect on esophageal inflammation (76%), side effects (69%), and ease of use (58%). Patients found STCs to be effective (83 points), convenient (83 points), and experienced no side effects when using this therapy. When using STCs alone (43%), overall patient satisfaction was high (86 points). Patients judged PPIs to be most convenient (89 points), STCs to be a bit less convenient (83 points), and diet to be most inconvenient (46 points) of the three therapies examined. CONCLUSIONS: Adult EoE patients consider both therapy effect on symptoms and esophageal inflammation as important criteria when choosing EoE therapy and appear to be satisfied with STC use.

Malignancies in Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to, the gut. Association between IBD and cancer has been clearly established and is uniformly accepted. SUMMARY: IBD patients are at particular risk for intestinal and extraintestinal cancers. There are 2 underlying mechanisms: (1) IBD-related inflammation triggers initiation and progression of tumor formation. This particularly results in the development of colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, anal cancer, and cholangiocarcinoma. (2) Immunosuppressive drugs exhibit carcinogenic properties such as shown for azathioprine and anti-TNF promoting lymphoproliferative malignancies and melanoma and nonmelanoma skin cancer. However, within the last years, IBD-related cancer incidence and prevalence have been decreasing, which might be attributed to better treatment options and surveillance strategies. Moreover, novel biological drugs have been introduced in clinical practice and have dramatically changed long-term IBD management. Therefore, we sought to summarize up-to-date knowledge about (1) overall cancer risk; (2) risk and protective factors for cancer development; and (3) inflammation- and immunosuppression-related malignancies in the current anti-TNF era of IBD. Key Messages: Recent studies and meta-analyses questioned the excess rates of cancer in IBD patients. However, IBD still is associated with cancer development due to ongoing intestinal inflammation and the use of potential carcinogenic drugs. Patients should be educated about the increased risk of cancer with IBD and IBD drugs. However, they should also be informed that most malignancy subtypes are possibly preventable by controlling intestinal inflammation and by using adequate screening strategies.

Gender Differences in Inflammatory Bowel Disease.

Immune-mediated diseases typically show a female preponderance. Looking at all autoimmune diseases combined, 8 of 10 patients are females. Although not as prominent, gender differences in inflammatory bowel disease (IBD) have been reported for epidemiology, disease presentation, disease course and complications, medical and surgical therapies, adherence, psychosocial functioning, and psychiatric co-disorders. While for some factors evidence is rather good, for others data are conflicting. Gastroenterologists dealing with IBD patients in daily clinical practice should be aware of gender-specific issues for the following reasons: (1) misperception of disease presentation potentially delays IBD diagnosis, which has been shown to have deleterious effects, and (2) awareness of gender-specific symptoms and disease severity allows initiation of early and adequately tailored treatment. This might prevent development of complications. And (3) insights into gender-specific differences in terms of treatment and adherence to treatment can improve disease management and foster a more individualized treatment approach. In this review, we summarize current knowledge about gender-specific differences in IBD and highlight the most clinically relevant aspects.

Therapies in Inflammatory Bowel Disease Patients with Extraintestinal Manifestations.

Extraintestinal manifestations (EIM) have become an important source of morbidity and disability as well as an identified risk factor for an unfavorably course of disease in inflammatory bowel diseases (IBD). Therefore, efforts have been put into a more global and interdisciplinary management of IBD patients in collaboration with rheumatologists, dermatologists, and ophthalmologists. A real therapeutic success has also been obtained with a more "systemic" IBD treatment associated with the development of monoclonal antibodies against TNF alpha and biological agents derived from the treatment of rheumatological disease (also called biological Disease-Modifying Antirheumatic Drugs). The prevalence of these EIM remains too low to undergo randomized controlled trials with this specific focus and therefore the evidence relies on case series and experts' opinions, which lowers the level of evidence. After a careful review of the most recent literature, this paper aims to update the reader on the latest therapeutic management of IBD patients with EIM.

Nutrition in Inflammatory Bowel Disease.

BACKGROUND: Westernization, above all associated changes in diet, has been postulated to be one of the most important factors contributing to the increasing incidence in inflammatory bowel disease (IBD), consisting mainly of Crohn's disease and ulcerative colitis. SUMMARY: Diet represents a crucially important and intuitively relevant topic for IBD patients. Although a substantial number of patients are prone to follow dietary advice from a variety of sources, including the lay press, there is intriguingly little scientific evidence for such an incitement. This may result in physicians being insufficiently informed about various aspects of nutrition, precluding adequate guidance of their patients with IBD. Importantly, IBD patients are at risk to develop deficiencies in iron, vitamin B12, folic acid, and several micronutrients, which may even be more pronounced in patients with active disease and those following a restrictive diet. This review aims to summarize the latest data from clinical and epidemiological studies investigating diet and its effect on the course of the disease and to outline the most important nutrient deficiencies in IBD patients. Key Messages: A western diet with an imbalance between omega-6 (n-6)/omega-3 (n-3) polyunsaturated fatty acids (PUFAs), in favor of n-6 PUFAs, may increase the risk of IBD, whereas a diet high in fruits and vegetables may decrease the risk of IBD. Many approaches to influence the course of IBD with dietary intervention exist. However, to induce or maintain remission in IBD with a change of diet is still in its infancy, and more dietary research is needed before we can apply it in daily practice. Patients with IBD, even in remission, have to be screened regularly for malnutrition.

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.

Lower Risk of B1-to-pB3-Stage Migration in Crohn's Disease Upon Immunosuppressive and Anti-TNF Treatment in the Swiss IBD Cohort Study.

BACKGROUND: While the long-term evolution of disease behavior in Crohn's disease has been well described in the pre-anti-TNF era, our knowledge thereon remains scarce after the introduction of anti-TNF. AIMS: Our investigation examined the long-term evolution of disease concerning Montreal classification's B-stages over time in patients enrolled into the Swiss IBD Cohort Study between 2006 and 2017. METHODS: We analyzed prospectively collected SIBDCS data using a Markov model and multivariate testing for effects of treatment and other confounders on B-stage migration over time. The primary outcome was a transition in disease behavior from B1 to either B2 or pB3, or from B2 to pB3, respectively. RESULTS: The 10- and 15-year probability of remaining in B1 was 0.61 and 0.48, as opposed to a probability to migrate to B2 or B3 of 0.25 or 0.14, and 0.32 or 0.2, after 10 and 15 years, respectively. In multivariate testing, the hazard ratio for migrating from B1 to pB3 (HR 0.27) and from B2 to pB3 (HR 0.12) was lower in patients > 40 years compared to patients < 17 years. We found that immunosuppression (HR 0.38) and treatment with anti-TNF for > 1 year (HR 0.30) were associated with a decreased likelihood of transitioning from stage B1 to pB3. CONCLUSIONS: While in the anti-TNF era most patients with Crohn's disease will eventually develop stricturing and/or penetrating complications, our data indicate that immunosuppressive and anti-TNF treatment for more than 1 year reduce the risk of transitioning from stage B1 to pB3 in the long-term run.

ß6 -integrin serves as a novel serum tumor marker for colorectal carcinoma.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify ß6 -integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.

Maintenance Treatment Of Eosinophilic Esophagitis With Swallowed Topical Steroids Alters Disease Course Over A 5-Year Follow-up Period In Adult Patients.

BACKGROUND & AIMS: Although swallowed topical corticosteroids (STCs) are effective in inducing remission of active eosinophilic esophagitis (EoE), there are few data on maintenance of long-term remission. We evaluated the long-term effectiveness of STC therapy for adults with EoE. METHODS: We performed a retrospective study using the Swiss EoE database. We analyzed data on 229 patients with EoE treated with STCs (175 male; mean age at diagnosis, 39±15 years; median time until diagnosis, 6 years) from 2000 through 2014. Patients were followed for a median of 5 years (interquartile range [IQR], 3-7 years). We collected data from 819 follow-up visits on clinical, endoscopic and histological disease characteristics. The primary endpoint was proportions of clinical, endoscopic, and histological remission in all patients and groups, based on the status and duration of STC treatment. RESULTS: Patients were taking STCs at 336 of the follow-up visits (41.0% of visits). The median duration of STC use before a follow-up visit was 347 days (IQR, 90-750 days) corresponding to 677 doses (IQR, 280-1413 doses) of 0.25 mg each. At the visits, higher proportions of patients who were still taking STCs were in clinical remission (31.0%) compared to patients not taking STCs (4.5%) (P <.001), as well as endoscopic remission (48.8% vs 17.8%; P < .001), histologic remission (44.8% vs 10.1%; P < .001), and complete remission (16.1% vs 1.3%; P < .001). Higher cumulative doses of STCs and longer durations of treatment were associated with higher proportions of clinical and complete remission. No dysplasia or mucosal atrophy was detected. Esophageal candidiasis was observed at 2.7% of visits in patients taking STCs. CONCLUSION: In an analysis of data from the Swiss EoE database, we found maintenance therapy with STCs to achieve complete remission at 16.1% of follow-up visits, which was higher than in patients receiving no treatment (1.3%). Given the good safety profile of low-dose STC, we advocate for a prolonged treatment. Dose-finding trials are needed to achieve higher remission rates.

Malignancies in Inflammatory Bowel Disease: Frequency, Incidence and Risk Factors-Results from the Swiss IBD Cohort Study.

BACKGROUND: Malignancy may occur as long-term complication of inflammatory bowel disease (IBD) due to different risk factors. We assessed prevalence and incidence of malignancy, and predictive factors in the Swiss IBD Cohort Study (SIBDCS). METHODS: All IBD patients in the SIBDCS were analyzed from a cross-sectional and longitudinal perspective. Patients with malignancies were compared to controls. Standardized incidence ratios (SIR) were calculated based on age-specific and sex-specific background rates. RESULTS: Malignancies were identified in 122 of 3119 patients (3.9%). In a logistic regression model, age (OR 1.04 per year), intestinal surgery (OR 3.34), and treatment with steroids (OR 2.10) were the main predictors for the presence of malignancy, while treatment with 5-ASA (OR 0.57) and biologics (OR 0.38) were protective. From a longitudinal perspective, 67 out of 2580 patients (2.6%) were newly diagnosed with malignancy during a follow-up of 12,420.8 years (median 4.9 years). While there was no increased risk for malignancy overall (SIR 0.93, 95% CI 0.72-1.18) and colorectal cancer (SIR 1.55, 95% CI 0.71-2.95), IBD patients had an increased risk for lymphoma (SIR 2.98, 95% CI 1.36-5.66) and biliary cancer (SIR 6.3, 95% CI 1.27-18.41). In a Cox regression model, age and recent use of immunomodulators were the main predictors for development of malignancies, while 5-ASA, biologics were protective. CONCLUSIONS: IBD patients showed increased risk for lymphoma and biliary cancer, but not colorectal cancer and cancer overall. Age and recent use of immunomodulators were the main risk factors for malignancy, while aminosalicylates and biologics appear to be protective.

Unmet Medical Needs in Ulcerative Colitis: An Expert Group Consensus.

BACKGROUND: The authors aimed to conduct an extensive literature review and consensus meeting to identify unmet needs in ulcerative colitis (UC) and ways to overcome them. UC is a relapsing and remitting inflammatory bowel disease with varied, and changing, incidence rates worldwide. UC has an unpredictable disease course and is associated with a high health economic burden. During 2016 and 2017, a panel of experts was convened to identify, discuss and address areas of unmet need in UC. METHODS: PubMed and Cochrane Library databases were searched for relevant articles describing studies performed in patients with UC. These findings were used to generate a set of statements relating to unmet needs in UC. Consensus on these statements was then sought from a panel of 9 expert gastroenterologists using a modified Delphi review process that consisted of anonymous surveys followed by live meetings. RESULTS: In 2 literature reviews, over 5,000 unique records were identified and a total of 138 articles were fully reviewed. These were used to consider 26 areas of unmet need, which were explored in 2 face-to-face meetings, in which the statements were debated and amended, resulting in consensus on 30 final statements. The unmet needs identified were categorised into 7 areas: impact of UC on patients' daily life; importance of early diagnosis and treatment; drawbacks of existing treatments; urgent need for new treatments; and disease-, practice- or patient-focused unmet needs. CONCLUSIONS: These expert group meetings found a number of areas of unmet needs in UC, which is an important first step in tackling them in the future. Future research and development should be focused in these areas for the management of patients with UC.

[Extraintestinal manifestations in chronic inflammatory bowel diseases]. / Extraintestinale Manifestationen bei chronisch entzündlichen Darmkrankheiten.

Extraintestinal manifestations in chronic inflammatory bowel diseases Abstract. Chronic inflammatory bowel diseases (IBD) are inflammatory gastrointestinal disorders that are not limited to the gastrointestinal tract. Various organ systems may be involved, making IBD a systemic disease. The most common extraintestinal manifestations (EIMs) include musculoskeletal, ophthalmic, dermatological and hepato-biliary disorders. EIMs considerably contribute to the morbidity of patients with IBD and also limit their quality of life. Due to the diversity of the organ systems involved, care should be provided on an interdisciplinary basis by a medical staff trained in the treatment of IBD. Early detection of EIM allows targeted therapy and reduces the overall morbidity of the affected patients. Of importance is the fact that EIM can occur in up to 25 % of all IBD patients before the onset of the first Crohn's episode or ulcerative colitis. Therefore, dermatologists, ophthalmologists and rheumatologists should beware of this possible association in EIM and the simultaneous occurrence of intestinal symptoms.

Eosinophilic Esophagitis: Relationship of Subepithelial Eosinophilic Inflammation With Epithelial Histology, Endoscopy, Blood Eosinophils, and Symptoms.

OBJECTIVES: For technical reasons, the histologic characterization of eosinophilic esophagitis (EoE)-specific alterations is almost exclusively based on those found in the esophageal epithelium, whereas little is known about subepithelial abnormalities. In this study, we aimed to systematically assess the nature of subepithelial histologic alterations, and analyze their relationship with epithelial histologic findings, endoscopic features, and symptoms. METHODS: Adult patients with established EoE diagnosis were prospectively included during a yearly follow-up visit. Patients underwent assessment of clinical, endoscopic, and histologic disease activity using EoE-specific scores. RESULTS: We included 200 EoE patients (mean age 43.5±15.7 years, 74% males) with a median peak count of 36 intraepithelial eosinophils/hpf (IQR 14-84). The following histologic features were identified in the subepithelial layer: eosinophilic infiltration (median peak count of 20 eosinophils/hpf (IQR 10-51)), eosinophil degranulation (43%), fibrosis (82%), and lymphoid follicles (56%). Peak intraepithelial eosinophil counts were higher, identical, and lower when compared to the subepithelial layer in 62.5%, 7%, and 30.5% of patients, respectively. Anti-eosinophilic treatment at inclusion did not influence the relation between subepithelial and epithelial peak eosinophil counts. Subepithelial histologic activity correlated with epithelial histologic activity (rho 0.331, P<0.001), endoscopic severity (rho 0.208, P=0.003), and symptom severity (rho 0.179, P=0.011). Forty percent (21/52) of patients with <15 intraepithelial eosinophils/hpf had subepithelial peak counts of ≥15/hpf. CONCLUSIONS: There is a significant but modest correlation between subepithelial histologic activity and epithelial histologic activity, endoscopic severity, and symptom severity. The long-term clinical impact of assessing subepithelial alterations in EoE needs to be further elucidated.