by using objective and clinical biological outcome measures and the subsequent adjustment of treatments (78). Therapeutic targets have been recommended for UC, as part of the Selecting Therapeutic Targets in Inflammatory Bowel Diseases (STRIDE) consensus statement, which was based on a systematic literature review and expert opinion of 28 IBD specialists. The targets for UC were composite end points that include resolution of rectal bleeding, normalization of bowel habits, and a Mayo endoscopic subscore of 0 or 1. STRIDE proposed that these end points should be assessed at a minimum every 3 months during the active phase of disease (79). The STRIDE recommendations to set endoscopic remission as a primary target were based on evidence that supports that the degree of mucosal healing is correlated with clinical outcomes, including avoiding colectomy (57,58,80). It is acknowledged that endoscopic improvement (Mayo endoscopic subscore of 0 or 1) rather than complete healing (Mayo endoscopic subscore of 0) may be sufficient and associated with similar outcomes (58). At the time of the 2015 STRIDE statement, histology was not identified as a target for treatment, but the research and understanding of this biomarker has evolved. Recent studies and critical reviews of histology as a marker of disease activity and potential end point of therapy demonstrate that the presence of active microscopic inflammation (defined by the presence of mucosal neutrophils) is predictive of clinical relapse, hospitalization, and steroid use (81). In addition, there are several significant studies, which demonstrate that the increased degree of histological inflammation is associated with dysplasia and colorectal cancer (also discussed below) (8–10). Although a specific index for clinical use has not been clarified, it is anticipated that further work will clarify the value of this end point as a separate target for management and prognosis. However, at this time, based on the lack of clinical trial data and current levels of evidence, histologic healing is not a recommended management end point. There is a need for less invasive markers of inflammation. Such markers can be used to assess for subclinical detection of disease relapse, response to therapy, and distinction between inflammatory and noninflammatory causes of symptoms. There are studies exploring fecal lactoferrin, FC, and, more recently, fecal immunohistochemical tests of hemoglobin (82). In general, these fecal markers are better tools in UC than in CD, and the attractiveness of them is that they offer less invasive and less resource-intense ways to serially assess disease activity. The most data exist for FC. Calprotectin is an antimicrobial manganese sequestration protein complex, which comprises 60% of the soluble proteins in the cytosol of neutrophils (83). It is secreted by an unknown mechanism during inflammation, is a stable protein in stool, and quantification of it is possible with commercially available laboratory assays. FC levels correlate with degrees of endoscopic and histologic inflammation in UC and therefore have been proposed as a marker of disease activity to guide treatment (83,84). FC levels are more sensitive and specific than serum inflammatory markers and obviously also less invasive than endoscopy or mucosal biopsies, so this assessment has become routine for many clinicians who are managing patients with UC (35,85). FC therefore has been proposed as a monitoring tool to assess response to therapy or