Post-polypectomy complications: high risk in the cecum

Colorectal cancer (CRC) is the third most frequently occurring cancer in the world [1]. Several randomized trials have shown that screening significantly reduces CRC incidence and mortality [2] [3] [4] The benefit of screening strategies is largely dependent on the effectiveness of colonoscopy, the procedure onto which all screening strategies converge. Colonoscopy allows the detection and removal of advanced adenomas, the precancerous lesions responsible for most CRCs. Endoscopic polypectomy is generally considered a safe procedure, and complications are frequently mild. However, the risk of life-threatening complications does exist, and the likelihood of serious adverse events associated with colonoscopy with polypectomy is almost nine times that of colonoscopy without polypectomy [5]. The most severe post-polypectomy complications are bleeding and perforation. Research on predictive factors for major post-polypectomy complications is of the utmost importance for the development of specific management strategies

Several studies have focused on identifying predictive factors for major post-polypectomy complications, particularly for bleeding and perforation. In general, predictive factors may be categorized as: (a) patient characteristics, including demographic features (older age, female gender) [6] [7], comorbidity (hypertension, cardiovascular comorbidity, chronic renal disease, coagulopathies) [8] [9] and treatment with antiplatelets or anticoagulants [10] [11]; (b) polyp characteristics (size, morphology, histology, and location) [6] [11] [12] [13]; and (c) technical issues (endoscopist experience, use of preventive measures, method of resection and cautery) [14] [15].

Polyp size has been reported in most studies as the most important predictor of endoscopic post-polypectomy complications [8] [9] [11] [13] [16] [17]. Watabe et al. [9] showed that post-polypectomy bleeding is associated with polyp size (0.4 % with small polyps to 5.3 % with those larger than 30 mm). In some studies the risk of bleeding was found to increase by 5 % – 13 % for every additional millimeter in size [6] [11] [17]. In fact, a cutoff polyp size ranging from 14 mm to 17 mm has been suggested as the most important predictor of post-polypectomy bleeding [11] [17]. However, previous studies are not large enough to provide definitive conclusions.

In this issue of Endoscopy, Rutter et al. report the largest observational study to date focusing on post-polypectomy complications [18]. The study is nested in the population-based NHS Bowel Cancer Screening Programme (NHSBCSP) in England which involves guaiac fecal occult blood tests self-administered by average-risk participants aged at least 60 years.

The large sample size allowed the authors to assess the incidence of major complications as well as to separately assess independent predictive factors for delayed bleeding in general, severe delayed bleeding (needing blood transfusion) and perforation. Information about possible complications was collected up to 30 days after the procedure and prospectively included in a national database. The authors concluded that cecal location and large size of polyps are the most important predictors of major post-polypectomy complications.

The main strength of this study is that the sample size was large enough to precisely analyze the risk of delayed bleeding and perforation for specific locations. For large cecal polyps compared with those located in other colonic segments, sequential multivariate analysis showed higher risk for delayed bleeding (odds ratio [OR] 2.49, 95 % confidence interval [95 %CI] 1.54 – 4.03) and for perforation (OR 5.60, 95 %CI 1.37 – 22.83), especially for perforation in sessile polyps (OR 12.19, 95 %CI 1.24 – 119.5). Cecal risk was independently related to polyp size and was even higher for the most severe complications (bleeding needing blood transfusion, OR 13.50, 95 %CI 3.93 – 46.42). The authors conclude that awareness of such high risk might be useful for planning specific prophylactic therapy before resecting large polyps in the cecum. Furthermore, they recommend specific cecal polypectomy training as well as improvement in therapeutic technique in this location. In agreement with Rutter et al., we believe that polypectomies of large sessile and nonprotruded polyps in the cecum should be performed or at least supervised by expert endoscopists.

The precise mechanism by which cecal location is associated with bleeding is still unknown. Several tentative hypotheses have been proposed: first that decreased wall thickness of the proximal colon might increase exposure of the submucosal vessels after polypectomy, as well as making the cecum wall more vulnerable to perforation [19]. Although this is a plausible explanation for immediate bleeding episodes, it is unlikely to explain delayed post-polypectomy bleeding. Furthermore, no differences in wall thickness have been found between the cecum and the ascending colon or the transverse colon [20]. Secondly, it has been proposed that a higher concentration of digestive enzymes and bile acids in bowel fluids might dissolve the clot after polypectomy, thereby increasing the risk of bleeding [6].

Regarding colonic perforation, based on Laplace’s law, it has been suggested that air insufflation during colonoscopy generates a higher pressure in the cecum than in the rest of the colon, increasing vulnerability to injury. This hypothesis is supported by a large study addressing major post-polypectomy complications that reported nine barotraumatic perforations, all of them by cecal blow-out [21]. In addition, Rutter et al. also hypothesized that the more perpendicular approach of polypectomy in the cecum may increase the risk of complications. Scientific evidence in support of these theories is lacking.

The large sample size and the systematic collection of adverse events in the study by Rutter at al. make their conclusions reliable. However, the authors include only a few potential risk factors for post-polypectomy complications. Although some may be confounders (especially patient comorbidity) [11], others such as coagulation status, consumption of thienopyridines (especially in addition to acetylsalicylic acid) or anticoagulants, and timing of resumption may certainly be important. In fact, recent studies have found a higher rate of severe bleeding associated with the combination of thienopyridines and acetylsalicylic acid treatment [10] and the consumption of warfarin is a well-known risk factor [11].

Finally, prophylaxis against bleeding might be another factor to take into account. Although post-polypectomy methods seem to be more effective for the prevention of immediate bleeding, as reported in a meta-analysis [22], a recent controlled study suggests that prophylactic clipping after resection of large flat and sessile polyps (≥ 2 cm) might prevent delayed bleeding also [23].

In conclusion, this study confirms that cecal location per se confers a high risk of major complications, especially following endoscopic polypectomy of large and sessile polyps.

• References

• 1 Ferlay J, Shin HR, Bray F et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-2917
• 2 Shaukat A, Mongin SJ, Geisser MS et al. Long-term mortality after screening for colorectal cancer. N Engl J Med 2013; 369: 1106-1114
• 3 Atkin WS, Edwards R, Kralj-Hans I et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 375: 1624-1633
• 4 Segnan N, Armaroli P, Bonelli L et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial--SCORE. J Natl Cancer Inst 2011; 103: 1310-1322
• 5 Angelini G, Bernardoni L. Management and treatment of complications in diagnostic and therapeutic lower gastrointestinal tract endoscopy. In: Gaetano DelainiGG, Skricka T, Colucci G, eds. Intestinal polyps and polyposis: from genetics to treatment. Milan: Springer-Verlag Italia; 2009: 149-159
• 6 Buddingh KT, Herngreen T, Haringsma J et al. Location in the right hemi-colon is an independent risk factor for delayed post-polypectomy hemorrhage: a multi-center case-control study. Am J Gastroenterol 2011; 106: 1119-1124
• 7 DiPrima RE, Barkin JS, Blinder M et al. Age as a risk factor in colonoscopy: fact versus fiction. Am J Gastroenterol 1988; 83: 123-125
• 8 Kim HS, Kim TI, Kim WH et al. Risk factors for immediate postpolypectomy bleeding of the colon: a multicenter study. Am J Gastroenterol 2006; 101: 1333-1341
• 9 Watabe H, Yamaji Y, Okamoto M et al. Risk assessment for delayed hemorrhagic complication of colonic polypectomy: polyp-related factors and patient-related factors. Gastrointest Endosc 2006; 64: 73-78
• 10 Feagins LA, Iqbal R, Harford WV et al. Low rate of postpolypectomy bleeding among patients who continue thienopyridine therapy during colonoscopy. Clin Gastroenterol Hepatol 2013; 11: 1325-1332
• 11 Sawhney MS, Salfiti N, Nelson DB et al. Risk factors for severe delayed postpolypectomy bleeding. Endoscopy 2008; 40: 115-119
• 12 Dobrowolski S, Dobosz M, Babicki A et al. Blood supply of colorectal polyps correlates with risk of bleeding after colonoscopic polypectomy. Gastrointest Endosc 2006; 63: 1004-1009
• 13 Heldwein W, Dollhopf M, Rösch T et al. The Munich Polypectomy Study (MUPS): prospective analysis of complications and risk factors in 4000 colonic snare polypectomies. Endoscopy 2005; 37: 1116-1122
• 14 Di Giorgio P, De Luca L, Calcagno G et al. Detachable snare versus epinephrine injection in the prevention of postpolypectomy bleeding: a randomized and controlled study. Endoscopy 2004; 36: 860-863
• 15 Van Gossum A, Cozzoli A, Adler M et al. Colonoscopic snare polypectomy: analysis of 1485 resections comparing two types of current. Gastrointest Endosc 1992; 38: 472-475
• 16 Consolo P, Luigiano C, Strangio G et al. Efficacy, risk factors and complications of endoscopic polypectomy: ten year experience at a single center. World J Gastroenterol 2008; 14: 2364-2369
• 17 Gimeno-Garcia AZ, de Ganzo ZA, Sosa AJ et al. Incidence and predictors of postpolypectomy bleeding in colorectal polyps larger than 10 mm. Eur J Gastroenterol Hepatol 2012; 24: 520-526
• 18 Rutter MD, Nickerson C, Rees CJ et al. Risk factors for adverse events related to polypectomy in the English Bowel Cancer Screening Programme. Endoscopy 2013; 46
• 19 Sorbi D, Norton I, Conio M et al. Postpolypectomy lower GI bleeding: descriptive analysis. Gastrointest Endosc 2000; 51: 690-696
• 20 Fisher JK. Normal colon wall thickness on CT. Radiology 1982; 145: 415-418
• 21 Loffeld RJ, Engel A, Dekkers PE. Incidence and causes of colonoscopic perforations: a single-center case series. Endoscopy 2011; 43: 240-242
• 22 Li LY, Liu QS, Li L et al. A meta-analysis and systematic review of prophylactic endoscopic treatments for postpolypectomy bleeding. Int J Cancer 2011; 26: 709-719
• 23 Liaquat H, Rohn E, Rex DK. Prophylactic clip closure reduced the risk of delayed postpolypectomy hemorrhage: experience in 277 clipped large sessile or flat colorectal lesions and 247 control lesions. Gastrointestinal endoscopy 2013; 77: 401-407