Driving up the adenoma detection rate: is it time to make a U-turn?

Colon cancer is the second most common cause of cancer-related death for both men and women in the United States [1]. Colonoscopy with polypectomy has been proven to substantially reduce the incidence and mortality associated with the disease [2], but colonoscopy appears to be less effective in preventing right-sided colon cancers [3] [4] [5] [6]. Studies have shown that interval colon cancers are almost twice as likely to occur in the right colon, and may represent a biologically distinct subset with regard to demonstrating higher rates of microsatellite instability and CpG island methylator phenotype [7]. Studies have also suggested that polyps with advanced histology are smaller in size, and more likely to be sessile in the right colon than in the left colon [8] [9]. Furthermore, the right colon is technically more difficult to examine during colonoscopy [10]. Repeat examination of the right colon to improve the detection of polyps is therefore considered. The repeat examination can be done in a standard forward-view manner, or the colonoscope can be retroflexed in the cecum and the right colon examined in a retroflexed manner. Retroflexion has the theoretical advantage of being able to visualize the back-side of haustral folds and flexures, mucosa that can be difficult to examine in the forward-view position. Retroflexion however is not always possible, because of colon anatomy, a looped position of the colonoscope, and operator inexperience; and it is also associated with a small risk of perforation [11].

“A third look in the right colon should be considered by endoscopists with limited experience and with low ADR.”

In this edition of Endoscopy, Hyun Seok Lee and colleagues report on a prospective study assessing the yield of retroflexion in the right colon after two standard forward-view examinations of the right colon had been performed. The study population consisted of 1020 patients who presented for screening or surveillance colonoscopies to an academic medical center in Korea. Colonoscopies were performed by 11 gastroenterologists, of whom only 3 had performed more than 1000 colonoscopies in their career. A hood-cap was used for all procedures. Retroflexion in the right colon was possible in 82.4 % of all cases. The overall adenoma detection rate was 27.5 %. On the first forward-view withdrawal in the right colon, 386 (76.9 %) adenomas were found. On the second forward-view withdrawal in the right colon, another 64 (12.7 %) adenomas were found. On the third examination of the right colon, which was done with the colonoscope in the retroflexed position, an additional 52 (10.4 %) adenomas were found. Of the polyps found on retroflexion, 3/52 (5.8 %) were ≥ 10 mm, and most (84.6 %) were found in the mid and distal ascending colon. The per-adenoma miss rate for 2 forward-view examinations was 10.4 % (52/502), and the per-patient adenoma miss rate was 4.9 % (50/1020). The authors computed that 20.4 retroflexed examinations would have to be performed, to detect 1 additional adenoma. These data suggest that retroflexion identifies polyps in the right colon that were missed by two forward-viewing examinations.

This study adds to what several other publications have shown, in that a repeat examination of the right colon yields additional polyps. A meta-analysis of retroflexion in the right colon compared with conventional forward-view colonoscopy showed a significant increase with retroflexion, identifying a per-adenoma miss rate of 17 % with an overall successful retroflexion rate of 92 % and adverse event rate of 0.03 %, among 3660 patients in 8 studies. [11]. Assuming that the endoscopist did a meticulous exam during the first withdrawal, why does a second look in the right colon yield additional polyps? Variables known to influence polyp detection rates that are endoscopist-associated (e. g. technique, experience) and patient-associated (e. g. age, gender, quality of bowel preparation, indication for colonoscopy, colon anatomy) are obviously unchanged during the second withdrawal. We know that 100 % of the colon mucosa is not visualized during colonoscope withdrawal. During the second withdrawal some mucosal surfaces come into view that may not have been fully visualized on the initial withdrawal and thus more polyps are found. This may be due to the endoscopist’s making a conscious effort to examine different segments of the mucosa, or due to random changes in the colonoscope position and bowel motility. The study by Lee et al. takes this logic one step further, and suggests that a third look in the right colon may yield still more polyps, 10.4 % in the case of their study. Their study does not address whether a third examination in forward view compared with a third examination in retroflexed view would yield different results.

Based upon Lee et al.’s results, should a third examination of the colon now be recommended for all screening and surveillance colonoscopies? In answering this question, it is instructive to compare this study with a carefully executed randomized controled trial by Kushnir et al [13]. These authors randomized 850 patients to a second colonoscope withdrawal performed either with a forward view or in the retroflexed position. No difference between the two groups was found with regard to adenoma detection rate, or number of adenomas per patient. The per-adenoma miss rate for the initial exam in the right colon was 27 % in the forward-view group compared to 20.3 % in the retroflexion group (P = 0.08). There are several pertinent differences between the present study and the study of Kushnir et al. In the study of Kushnir et al., the overall adenoma detection rate was 46.6 %, compared to 27.5 % in the study by Lee et al. In the Kushnir study no endoscopist had an adenoma detection rate less than 25 %, while in the Lee study more than 50 % of endoscopists had an adenoma detection rate less than 25 %. Gastroenterologists in the Kushnir study had been in practice for a median of 12 years (range 1 – 32), while only 3 of 11 gastroenterologists in the Lee study had performed > 1000 colonoscopies in their careers. It is possible that a miss rate of 10.4 % even after 2 examinations of the right colon may be related to the inexperience and low adenoma detection rate characteristics of the endoscopists in this study, and therefore these results might not be generalizable. More studies are needed before a third examination of the right colon can be recommended in routine clinical practice.

However, based upon this study, a third look in the right colon should be considered by endoscopists with limited experience and with low adenoma detection rates. This should be done especially in patients who are at increased risk of adenomas, such as those ≥ 55 years of age, and in those found to have polyps on initial withdrawal. When feasible, the endoscopist should attempt to perform the third examination with the colonoscope in the retroflexed position. Experienced endoscopists and those with a high adenoma detection rate should consider a second look in the right colon either in forward view or with retroflexion. Whether these endoscopists routinely need to perform a third look in the right colon remains to be seen.

• References

• 1 Jemal A, Bray F, Center MM. et al. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90
• 2 Zauber AG, Winawer SJ, O’Brien MJ. et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 2012; 366: 687-696
• 3 Baxter NN, Goldwasser MA, Paszat LF. et al. Association of colonoscopy and death from colorectal cancer. Ann Intern Med 2009; 150: 1-8
• 4 Singh H, Nugent Z, Mahmud SM. et al. Predictors of colorectal cancer after negative colonoscopy: a population-based study. Am J Gastroenterol 2010; 105: 663-673 ; quiz 74
• 5 Mulder SA, van Soest EM, Dieleman JP. et al. Exposure to colorectal examinations before a colorectal cancer diagnosis: a case–control study. Eur J Gastroenterol Hepatol 2010; 22: 437-443
• 6 Brenner H, Chang-Claude J, Seiler CM. et al. Protection from colorectal cancer after colonoscopy: a population-based, case–control study. Ann Intern Med 2011; 154: 22-30
• 7 Sawhney MS, Farrar WD, Gudiseva S. et al. Microsatellite instability in interval colon cancers. Gastroenterology 2006; 131: 1700-1705
• 8 Rondagh EJ, Bouwens MW, Riedl RG. et al. Endoscopic appearance of proximal colorectal neoplasms and potential implications for colonoscopy in cancer prevention. Gastrointest Endosc 2012; 75: 1218-1225
• 9 Gupta S, Balasubramanian BA, Fu T. et al. Polyps with advanced neoplasia are smaller in the right than in the left colon: implications for colorectal cancer screening. Clin Gastroenterol Hepatol 2012; 10: 1395-1401 .e2
• 10 Farrar WD, Sawhney MS, Nelson DB. et al. Colorectal cancers found after a complete colonoscopy. Clin Gastroenterol Hepatol 2006; 4: 1259-1264
• 11 Cohen J, Grunwald D, Grossberg LB. et al. The effect of right colon retroflexion on adenoma detection: a systematic review and meta-analysis. J Clin Gastroenterol; 2016 [Epub ahead of print] PMID: 27683963
• 12 Lee HS, Jeon SW, Park HY. et al. Improved detection of right colon adenomas with additional retroflexion following two forward-view examinations: a prospective study. Endoscopy 2017; 49: 334-341
• 13 Kushnir VM, Oh YS, Hollander T. et al. Impact of retroflexion vs. second forward view examination of the right colon on adenoma detection: a comparison study. Am J Gastroenterol 2015; 110: 415-422