Michael S. Verhille

Improving the quality of bowel preparation: one step closer to the holy grail?

Colonoscopy is associated with a reduction in colorectal cancer (CRC) incidence and mortality [1], although this association may be limited to cancers arising in the distal colon [2]. Recently, a prospective randomized controlled trial showed that flexible sigmoidoscopy reduces CRC mortality [3], but a comparable prospective randomized trial for colonoscopy is currently in phase III and will not be completed until 2036 [4]. Nevertheless, the American Cancer Society and the US Preventive Services Task Force recommend screening colonoscopy every 10 years starting at age 50 for patients with average risk of CRC. Likewise, Medicare has covered a majority of the costs of this screening procedure since 2001 for patients at average risk. The molecular basis for the adenoma–carcinoma sequence in CRC is well described [5]. More recently it was proposed that a genetic pathway characterized by microsatellite instability (MSI) accounts for a number of sporadic CRC [6]. Many of these lesions arise from nonpolypoid lesions in the proximal colon [7]. Although proximal cancers occur less frequently than distal ones, they may more frequently result from a missed precursor lesion at colonoscopy, as an association between interval cancers and both the presence of MSI and proximal location has been reported [8]. This evidence represents a significant challenge to colonoscopists. Distal CRC represents the low-hanging fruit, so to speak, in that its precursor lesions are more numerous, more polypoid and reachable with a shorter, cheaper and safer procedure. Removal of a sufficient number of precursor lesions to significantly reduce mortality from proximal CRC may require a more consistent level of training and expertise than is currently reported in the literature. In some of the retrospective trials that failed to show a reduction in CRC mortality from proximal lesions removed at colonoscopy, gastroenterologists comprised a minority of the colonoscopists [2]. In an effort to further lower CRC mortality, many approaches to quality improvement in colonoscopy have been proposed including standards for withdrawal time, withdrawal technique, operator experience, optical enhancement and measurement of adenoma detection rate. However, none of these quality standards will succeed if the colonoscopist cannot consistently visualize an adequate amount of the colonic mucosa. In the end, the quality of the bowel preparation may determine whether screening colonoscopy, rather than flexible sigmoidoscopy, continues to be so universally recommended and reimbursed. It remains to be seen how to best administer bowel preparation before colonoscopy so that the colonoscopist has greatest opportunity to reduce CRC mortality. We have known for decades that both polyethylene glycol (PEG) and bile take approximately 1 h to reach the cecum [9, 10]. It is the goal of a bowel preparation, then, to deliver a sufficient quantity of fluid to the cecum to cleanse the entire colon, allow enough time for the cleansing agent to pass completely through the colon, but not wait so long that the proximal colon is again coated in a film of bilious secretions. With respect to the latter two goals, timing is everything. There have been a number of recent studies, including the present one, which investigated the relationship between timing and quality of bowel preparation [11–18]. In this issue of Digestive Diseases and Sciences, Eun et al. [11] draw an association between the quality of bowel preparation and the interval between the time of last PEG intake and the start of colonoscopy. In this single-center E. W. Holt (&) M. S. Verhille California Pacific Medical Center, San Francisco, CA, USA e-mail: edholt@gmail.com

Su1046 Early-Onset Colorectal Cancer Is Independently Associated With Shorter Overall Survival

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer, as well as the third most common cause of cancer deaths in the United States. Bisphosphonates are antiresorptive agents widely used in treating and preventing osteoporosis. Several large studies have recently reported a reduced risk of CRC with bisphosphonate use, however no meta-analysis on the subject exists. AIM: We aimed to conduct a meta-analysis of existing observational studies and thus provide a quantitative estimate of the association between bisphosphonate use and the risk of CRC. METHODS: We followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines in performing our systematic review. A search was conducted through Medline, PubMed, Embase, and Current