Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

Main Recommendations 1 ESGE recommends that the initial assessment of patients presenting with acute lower gastrointestinal bleeding should include: a history of co-morbidities and medications that promote bleeding; hemodynamic parameters; physical examination (including digital rectal examination); and laboratory markers. A risk score can be used to aid, but should not replace, clinician judgment.Strong recommendation, low quality evidence. 2 ESGE recommends that, in patients presenting with a self-limited bleed and no adverse clinical features, an Oakland score of ≤ 8 points can be used to guide the clinician decision to discharge the patient for outpatient investigation.Strong recommendation, moderate quality evidence. 3 ESGE recommends, in hemodynamically stable patients with acute lower gastrointestinal bleeding and no history of cardiovascular disease, a restrictive red blood cell transfusion strategy, with a hemoglobin threshold of ≤ 7 g/dL prompting red blood cell transfusion. A post-transfusion target hemoglobin concentration of 7–9 g/dL is desirable.Strong recommendation, low quality evidence. 4 ESGE recommends, in hemodynamically stable patients with acute lower gastrointestinal bleeding and a history of acute or chronic cardiovascular disease, a more liberal red blood cell transfusion strategy, with a hemoglobin threshold of ≤ 8 g/dL prompting red blood cell transfusion. A post-transfusion target hemoglobin concentration of ≥ 10 g/dL is desirable.Strong recommendation, low quality evidence. 5 ESGE recommends that, in patients with major acute lower gastrointestinal bleeding, colonoscopy should be performed sometime during their hospital stay because there is no high quality evidence that early colonoscopy influences patient outcomes.Strong recommendation, low quality of evidence. 6 ESGE recommends that patients with hemodynamic instability and suspected ongoing bleeding undergo computed tomography angiography before endoscopic or radiologic treatment to locate the site of bleeding.Strong recommendation, low quality evidence. 7 ESGE recommends withholding vitamin K antagonists in patients with major lower gastrointestinal bleeding and correcting their coagulopathy according to the severity of bleeding and their thrombotic risk. In patients with hemodynamic instability, we recommend administering intravenous vitamin K and four-factor prothrombin complex concentrate (PCC), or fresh frozen plasma if PCC is not available.Strong recommendation, low quality evidence. 8 ESGE recommends temporarily withholding direct oral anticoagulants at presentation in patients with major lower gastrointestinal bleeding.Strong recommendation, low quality evidence. 9 ESGE does not recommend withholding aspirin in patients taking low dose aspirin for secondary cardiovascular prevention. If withheld, low dose aspirin should be resumed, preferably within 5 days or even earlier if hemostasis is achieved or there is no further evidence of bleeding.Strong recommendation, moderate quality evidence. 10 ESGE does not recommend routinely discontinuing dual antiplatelet therapy (low dose aspirin and a P2Y12 receptor antagonist) before cardiology consultation. Continuation of the aspirin is recommended, whereas the P2Y12 receptor antagonist can be continued or temporarily interrupted according to the severity of bleeding and the ischemic risk. If interrupted, the P2Y12 receptor antagonist should be restarted within 5 days, if still indicated.Strong recommendation, low quality evidence.

Background and aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis (UC) in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the five-year outcome and disease course of patients with UC in the Epi-IBD cohort. Methods: In a prospective, population-based inception cohort of unselected patients with UC patients were followed-up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. Results: A total of 717 patients were included in the study. During follow-up, 43 (6%) patients underwent a colectomy, while 163 (23%) patients were hospitalized. Of patients with limited colitis (distal to the left flexure), 90 (21%) progressed to extensive colitis. In addition, 92 (27%) patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalization (HR: 0.5 CI95% 0.3-0.8). Overall, patients were treated similarly in both geographical regions and 80 (11%) patients needed biological therapy while 210 (29%) patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalization (HR: 0.5 CI95% 0.3-0.8). Conclusions: While patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes including colectomy rates were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalization.

Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the genomics of CRC has recently been achieved thanks to the widespread use of next generation sequencing with potential future therapeutic implications. Microsatellite instability (MSI) has been suggested as a predictive marker for response to anti-programmed-cell-death protein 1 (PD-1) therapy in solid tumors, including CRC. It should be noted that not all cancers with MSI phenotype respond to anti-PD-1 immunotherapy, highlighting the urgent need for even better predictive biomarkers. Mitogen-Activated Protein Kinase (MAPK) pathway genes KRAS, NRAS, and BRAF represent important molecular targets and could serve as independent prognostic biomarkers in CRC, and identify those who potentially benefit from anti-epidermal growth factor receptor (EGFR) treatment. Emerging evidence has attributed a significant role to inflammatory markers including blood cell ratios in the prognosis and survival of CRC patients; these biomarkers can be easily assessed in routine blood exams and be used to identify high-risk patients or those more likely to benefit from chemotherapy, targeted therapies and potentially immunotherapy. Analysis of cell-free DNA (cfDNA), circulating tumor cells (CTC) and/or micro RNAs (miRNAs) could provide useful information for the early diagnosis of CRC, the identification of minimal residual disease and, the evaluation of the risk of recurrence in early CRC patients. Even the selection of patients suitable for the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Finally, the development of treatment resistance with the emergence of chemo-resistance clones after treatment remains the most important challenge in the clinical practice. In this context it is crucial to identify potential biomarkers and therapeutic targets which could lead to development of new and more effective treatments.