Will such dose or class escalation result in more adverse events than benefits? Will it result, as the available GSK1120212 evidence thus far suggests, in most patients “burning” through all of the available therapies and never achieving this level of inflammation control? How will the loss of this level of control and so-called disease drift be monitored? How often, and how invasive will repeated assessments be needed? Obviously there remain many unanswered questions before a disease-wide modification in treatment goals can be applied. Nonetheless, there are ongoing efforts to apply a treat-to-target approach used in other chronic diseases to IBD.14 Such paradigm

shifts in management will answer these questions and guide future therapies. Being Ibrutinib cost able to accurately detect precancerous lesions in patients with colonic IBD is requisite for screening colonoscopy and subsequent interval surveillance examinations. IBD-associated colorectal neoplasia may be a challenge to detect endoscopically because it may be multifocal, broadly infiltrating, and arising from flat mucosa, and therefore endoscopically indistinct

from the surrounding tissue. Therefore, to adequately sample representative mucosa and identify dysplasia histologically, historical (and current) guidelines endorsed by multiple societies suggest 4-quadrant random biopsy specimens obtained every 10 cm throughout the colon, aiming to obtain at minimum 32 biopsy samples.15 However, this approach is limited in that it samples less than 1% of colonic surface area and at the same time is subject to poor patient compliance with surveillance, lack of gastroenterologist knowledge, and compliant practice patterns, in addition to poor pathologist interobserver agreement for dysplasia diagnoses.16 and 17 Furthermore, retrospective studies evaluating the visibility of dysplasia

and CRC in patients with IBD have found that most dysplastic lesions are endoscopically visible. In a 14-year, retrospective review of 2204 surveillance Glutathione peroxidase colonoscopies, Rutter and colleagues18 found the neoplastic per-lesion and per-patient sensitivity to be 77.3% and 89.3%, respectively. A total of 22.7% of lesions were macroscopically invisible on colonoscopy. A 10-year, single-institution, retrospective study by Rubin and colleagues19 in the United States similarly found dysplasia or cancer had per-lesion and per-patient endoscopic visibility of 61.3% and 76.1%, respectively. In this series, 38 of 65 dysplastic lesions (58.5%) and 8 of 10 cancers (80.0%) were visible to the endoscopist as 23 polyps and masses, 1 stricture, and 22 areas of irregular mucosa. In this series 38.7% of lesions were endoscopically invisible, detected only by random biopsy.