Colonoscopy: basic principles and novel techniques

REVIEWS

Colonoscopy: basic principles and novel techniques Yark Hazewinkel and Evelien Dekker Abstract | Colonoscopy is considered the ‘gold standard’ for detection and removal of premalignant lesions in the colon. However, studies suggest that colonoscopy is less protective for right-sided than for left-sided colorectal cancer. Optimizing the effectiveness of colonoscopy is a continuous process, and during the past decade several important quality indicators have been defined that can be used to measure the performance of colonoscopy and to identify areas for quality improvement. The quality of bowel preparation can be enhanced by split-dose regimens, which are superior to single-dose regimens. Cecal intubation rates should approximate 95% and can be optimized by good technique. In selected patients, specific devices can be used to facilitate cecal intubation. Adenoma detection rates should be monitored and exceed a minimum of 25% in men and 15% in women. To this aim, optimal withdrawal technique and adequate time for inspection are of utmost importance. Of all advanced imaging techniques, chromoendoscopy is the only technique with proven benefit for adenoma detection. Finally, the technique of polypectomy affects the number of complications as well as the success of completely removing a lesion. In this Review, we provide an overview of both standard and novel colonoscopy techniques and their impact on quality indicators. Hazewinkel, Y. & Dekker, E. Nat. Rev. Gastroenterol. Hepatol. 8, 554–564 (2011); published online 6 September 2011; doi:10.1038/nrgastro.2011.141

Introduction Colonoscopy is an endoscopic procedure pioneered in Japan in the late 1950s that allows visualization of the entire mucosa of the large intestine and distal terminal ileum. Furthermore, it enables tissue sampling for histopathology as well as an opportunity for therapeutic procedures such as polypectomy or dilatation of a stenosis. Among other indications, colonoscopy is considered as the ‘gold standard’ for early detection and removal of colorectal cancer (CRC) and its precursors. However, colonoscopy is not perfect. Accumulating evidence suggests that colonoscopy is not fully protective for right-sided colon cancer. To enhance the diagnostic and therapeutic yield of colonoscopy, definition and measure ment of quality parameters are essential to identify areas for improvement. In this Review, we discuss the basic principles and new techniques of colonoscopy and its relation to various important quality parameters. Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, PO Box 22700, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands (Y. Hazewinkel, E. Dekker). Correspondence to: E. Dekker [email protected]

General aspects Informed consent Colonoscopy is an invasive procedure with a potential risk of complications, such as perforation or bleeding (Box 1).1–7 Every patient should receive verbal and written information about the procedure, the risk of complications and possible alternatives. That the patient understands the Competing interests E. Dekker declares an association with the following companies: Olympus, Pentax. See the article online for full details of the relationships. Y. Hazewinkel declares no competing interests.

554 | OCTOBER 2011 | VOLUME 8

importance of a successful bowel preparation is essential. Patient understanding enhances compliance and improves the quality of bowel preparation, as highlighted by a 2011 study that demonstrated that provision of a simple educational booklet aimed at addressing patients’ knowledge of, attitude and belief barriers to bowel preparation markedly improved the quality of the preparation.8

Bowel preparation Inspection of the colon requires a clean colon without any residual stool or liquid that could mask a suspicious area. Inadequate bowel preparation is associated with reduced adenoma detection rates, incomplete colonoscopy and increased costs.9–11 The quality of preparation should be assessed during endoscopy and documented in the procedure report. The UK National Health Service (NHS) Bowel Cancer Screening Program (BCSP) Endoscopy Quality Assurance group recommends using the descriptors ‘excellent’ (no or minimal solid stool and only clear fluid requiring suction), ‘adequate’ (collections of semisolid debris that are cleared with washing or suction) and ‘inadequate’ (solid or semi-solid debris that cannot be cleared effectively) to pragmatically report bowel preparation quality (Table 1).12 In daily practice, however, these descriptors are also frequently used without standardized definitions. To assess the preparation quality in a validated and standardized format, several bowel preparat ion scales (such as the Ottawa, Boston and Aronchick scales) are available.13–15 Although these scales have been shown to be a reliable tool for assessing the www.nature.com/nrgastro

© 2011 Macmillan Publishers Limited. All rights reserved

FOCUS ON ENDOSCOPY quality of preparation, their use in clinical practice is not yet recommended by formal guidelines. The quality of the preparation depends on the compli ance of the patient, as well as on the chosen pharma ceutical lavage agent and the timing of ingestion. Polyethylene glycol (PEG) solutions are widely used because they are safe and effective.16 Nevertheless, the high volume of PEG solutions (usually 3–4 l) is challenging for the patient to consume and is often poorly tolerated. This downside is partially solved by the addition of ascorbic acid to the PEG solution, which in excessive amounts will not be absorbed in the gut and function as an osmotic laxative, thereby reducing the required PEG volume to 2 l. These low-volume PEG regimens are generally better tolerated than the high-volume PEG regimens, with comparable cleansing results.17–19 Another frequently used preparation agent is sodium phosphate.16 A systematic review comparing sodium phosphate and PEG reported no differences concerning colon cleansing results, but sodium phosphate was better tolerated.16 A 2011 randomized study compared three bowel cleansing agents—sodium phosphate, sodium picosulfate and PEG—and showed preparation quality with sodium phosphate was worst for morning procedures, while all agents were equally effective for afternoon procedures.20 Concerning the timing of preparation, a meta-analysis of five randomized controlled trials demonstrated that split-dose regimens, in which half the volume is administered on the day before and the other half on the day of colonoscopy, is superior to single-dose preparation on the day before by improving both quality and tolerability.21 In conclusion, none of the available bowel preparation agents have been shown to be consistently superior over another in terms of adverse events, but split-dose regimens do markedly improve the quality of bowel preparation. Finally, we believe it is preferable to systematically document the quality of preparation by using either standardized descriptors or one of the available validated bowel preparation scores.

Sedation and discomfort during colonoscopy The use of sedation during colonoscopy varies between countries and clinical practices. Three main options are available: no sedation, conscious sedation (combination of benzodiazepines and opiates) or deep sedation with propofol. The choice of method depends on factors such as the personal preference of the endoscopist, the indication for the procedure, the patient’s preference, the availability of anesthesiology personnel and financial considerations. A meta-analysis showed that, when compared with traditional sedation, propofol leads to increased patient satisfaction and faster discharge times without an increase in adverse effects.22 No differences were observed in other clinically important outcomes, such as cecal intubation rates and procedure times. However, because of the assumed increased risk of respiratory depression, propofol is often administered by an anesthetist or dedicated nurse resulting in substantially higher treatment costs.23 In addition, little or

Key points ■■ Quality assurance using a minimal set of indicators is essential to continuously improve the effectiveness of colonoscopy ■■ Split-dose preparation is superior to single-dose preparation for both the quality of preparation and the tolerability ■■ The use of variable stiffness colonoscopes is associated with a higher cecal intubation rate than are standard colonoscopes ■■ Of all advanced imaging techniques, panchromoendoscopy is the only one proven to improve adenoma detection ■■ Cold biopsy polypectomy seems to be associated with a high incomplete resection rate

Box 1 | Incidence of serious complications during colonoscopy Estimated incidence per 1,000 procedures ■■ Bleeding: 0.01–3.21–7 ■■ Perforation: 0.05–1.21–7 ■■ Postpolypectomy syndrome*: 0.1–0.51,4 ■■ Cardiorespiratory events: 0.1–0.23,6 *Refers to the symptoms of abdominal pain, fever and peritoneal inflammation in the absence of a frank perforation (absence of free air on plain abdominal radiography).

no sedation only has two other considerable advantages in comparison with deep sedation. First, dynamic position changes are an important technique during colono scopy and sometimes the key to cecal intubation, and is much easier to achieve with a conscious and cooperating patient.24 Second, conscious patients report pain, which can indicate loop formation. This feedback is important for endoscopists, and especially trainees, because it forces them to practice good and safe endoscopic techniques. In our opinion, sedation should be offered to all patients, whereas deep sedation should be reserved for specific indications (such as severe discomfort or anxiety during colonoscopy). The patients’ burden during colonoscopy should be measured and documented. The modified Gloucester comfort score descriptors (ranging from no discomfort to severe discomfort) can be used to quantify the discomfort experienced by patients (Table 1).12 Discomfort experienced during and after colonoscopy can be caused by retained gas in the colon. To reduce the accumulation of gas, carbon dioxide can be used instead of oxygen, as carbon dioxide is absorbed much faster from the colon than oxygen. Several randomized trials have shown that using carbon dioxide instead of oxygen for insufflation substantially reduces abdominal pain and discomfort in patients undergoing colonoscopy.25–27 We believe, use of carbon dioxide insufflation is, therefore, recommended for daily colonoscopic practice.

Complication registration Complications occur in approximately 2 per 1,000 colonoscopies and this risk increases when a biopsy or polypectomy is performed during the procedure (Box 1).1–7 Complications can occur either immediately during the procedure or several days later. To monitor the safety of colonoscopy programs, every institution should

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY © 2011 Macmillan Publishers Limited. All rights reserved

VOLUME 8 | OCTOBER 2011 | 555

REVIEWS Table 1 | Minimal set of quality indicators, auditable outcome measures and accepted standards in colonoscopy Quality indicator

Outcome measure

Standard

Bowel preparation

Quality of bowel preparation

≥90% described as ‘excellent’ or ‘adequate’,12 preferably assessed with a validated bowel preparation scale

Cecal intubation

Cecal intubation rate with photodocumentation of cecal landmarks

≥90% unadjusted (intention to scope)12 ≥90% in all colonoscopies and ≥95% in screening colonoscopies48

Adenoma detection

Adenoma detection rate (number of patients with a least 1 adenoma/total number of patients)

≥25% in men and ≥15% in women during screening colonoscopies48 ≥20% during screening colonoscopy47

Withdrawal time

Time in minutes from cecal pole to anus

≥6 min inspection time in an intact colon12,48

Polyp retrieval

Polyp retrieval rate

≥90% of polypectomy specimens12,48

Burden

Gloucester comfort score

Not established

Complications

Incidence of perforation

≤1:1,000 colonoscopies (diagnostic or therapeutic)12 ≤1:500 colonoscopies with polypectomy12

Incidence of postpolypectomy bleeding

≤1:100 colonoscopies with polypectomy12

systematically register the incidence of complications and mortality up to 30 days after the procedure (Table 1).12

Cecal intubation Accumulating evidence suggests that colonoscopy is more protective for left-sided than for right-sided cancer.28–30 Among others, a possible explanation for this finding is that polyps in the right colon are not visualized, either because they are nonpolypoid, because of inadequate bowel preperation or because this part of the colon is not visualized at all. In a population-based cohort study of patients who underwent a previously incomplete colonoscopy, advanced neoplasia was detected in the nonvisualized part of the colon during follow-up examination in 4.3% of patients.31 Worryingly, studies have demonstrated that only the minority of patients with an incomplete colonoscopy do undergo a complete colonic evaluation within 12–18 months after the initial colonoscopy.31,32 Completeness of a colonoscopy is confirmed when the ileocecal valve and appendiceal orifice are visualized, which should be documented in the procedure report. An unadjusted cecal intubation rate of ≥90% is recommended by the NHS BCSP Endoscopy Quality Assurance group12 (Table 1). Variable cecal intubation rates are reported in the literature, ranging from 75.4% to 97.7%, depending on the clinical setting and the indication for colonoscopy.33,34 Reasons for incomplete colonoscopy are a dolichocolon, discomfort of the patient, obstructing tumors, insufficient bowel preparation, diverticulosis, stenosis and severe inflammation.31 In addition, a large population-based study demonstrated that advanced age, female sex and prior abdominal or pelvic surgery were statistically significant independent predictive factors associated with an incomplete colonoscopy.33 Several techniques are available that can facilitate cecal intubation and these are discussed below.

Abdominal pressure and position changes Exertion of external abdominal pressure and position changes of the patient are frequently used during advancement of the colonoscope. Abdominal pressure 556 | OCTOBER 2011 | VOLUME 8

is commonly applied to reduce loop formation in the sigmoid and transverse colon and is effective in helping the tip of the colonoscope pass the hepatic flexure.24 Rex et al.35 demonstrated that applying abdominal pressure was the most important noninstrumental technique in achieving cecal intubation in patients referred because of prior incomplete colonoscopy. Another option is changing the position of the patient, which is particularly used when difficulties are encountered in the sigmoid, descending and transverse part of the colon. In a study by Shah and colleagues,24 position changes were effective 66% of the time (95 of 144 maneuvers), which was defined as improvement of the luminal view or a definite advancement of the colonoscope.24 Nevertheless, no randomized studies have been performed to determine the exact role of external abdominal pressure and position changes on cecal intubation rates.

Pediatric and variable stiffness colonoscopes Pediatric colonoscopes have a smaller diameter (11 mm versus 12.5 mm for standard colonoscopes) and are more flexible than standard adult colonoscopes, which makes passage of a fixed or narrowed colon easier, but might also allow more loop formation owing to the increased flexibility of the scope. Concerning cecal intubation rates and procedure times, two randomized studies in non selected patients failed to show any advantage of pediatric colonoscope use in adults in comparison with standard adult colonoscope.36,37 However, in women with previous hysterectomy, higher cecal intubation rates were obtained with a pediatric colonoscope (96.1% versus 71.4%, P 10 mm, 13% for polyps 5–10 mm and 26% for polyps 2 cm that a combination of epinephrine and a detachable snare versus epinephrine alone significantly reduced the number of early bleeding episodes (1.2% versus 9.3%, P = 0.02). However, because technical failures are often reported, intention-to-treat studies are needed to evaluate the feasibility and safety of using detachable snares.96 Nonpedunculated lesions Flat and sessile lesions have a high risk (approximately 7%) of containing submucosal invasive cancer.85,97 To avoid noncurative EMR procedures, these lesions should be identified beforehand. Lesions with a depressed component, with a nongranular surface, or with an advanced pit pattern have a markedly increased risk of containing adenocarcinoma.85,98,99 EMR involves lifting of flat or sessile polyps by injecting a liquid substance beneath the lesion into the submucosa, followed by snare polypectomy (Figure 5). The injected fluid elevates the mucosa, thereby increasing the distance between the base of the polyp and the muscle www.nature.com/nrgastro

© 2011 Macmillan Publishers Limited. All rights reserved

FOCUS ON ENDOSCOPY layer of the gut wall. This step allows the snare to enclose a large piece of the polyp, including the base of the lesion, which might result in a more-radical polypectomy and might reduce perforation risk. Furthermore, in our experience, when a few drops of methylene blue are added to the injection solution, delineation of the lesion from normal mucosa is easier, potentially facilitating radical polypectomy. The most frequently used substance for EMR is normal saline, which dissipates rather quickly, often requiring multiple injections to maintain an adequate submucosal fluid cushion. To this aim, succinylated gelatin was compared with normal saline for sessile lesions >20 mm.100 Succinylated gelatin markedly reduced the number of resections and injections, lowered the injected volume and shortened the procedural time with no harmful adverse effects reported. Taken together with the wide availability and low costs of this substance, succinylated gelatin is a promising new injection fluid for EMR of large colonic lesions. EMR allows en bloc (one piece) resection of polyps as large as 15–20 mm.101 Larger resections are generally performed in a piecemeal fashion, but this procedure is associated with increased recurrence rates. 102 The application of argon plasma coagulation to the margins of the polypectomy reduces adenoma recurrence and is, therefore, recommended for routine use after piecemeal EMR.103 Moss et al.85 published the first prospective, multicenter, intention-to-treat study evaluating the safety, efficacy and success predictors for EMR of large sessile colorectal polyps in 2011. In this study, 479 patients with 514 lesions were included with a median lesion size of 30 mm. The intention-to-treat analysis showed a successful EMR procedure rate of 84%. Independent predictors for EMR failure were: previous attempt by the referring endoscopist, involvement of the ileocecal valve, and a difficult polyp position. The polyp size (>40 mm) and use of argon plasma coagulation were independent predictors of recurrence after an effective EMR. Complications requiring hospitalization occurred in 7.7% of patients, including 14 bleedings (2.9%) and 6 perforations (1.3%). Endoscopic submucosal dissection (ESD) was developed in Japan and was initially used to treat patients with early upper gastrointestinal tract cancers,104,105 and was later also applied to large lesions in the colon.106 The technique involves removal of a lesion with an electros urgical knife, enabling en bloc resection of polyps >20 mm. In Japan, ESD is accepted as a therapeutic treatment for large colonic lesions in specialized institutions, whereas in Western countries the technique is still not widely practiced, with high perforation rate, long procedure time and extensive learning curve as the most important barriers for widespread implementation. In 2010, a panel of European experts recommended a step-up approach for anatomic location and defined minimum training requirement for ESD.107 In Japan, several studies demonstrate high en bloc and curative resection rates with ESD.86,108 In a prospective

a

b

c

d

e

f

Figure 5 | Endoscopic mucosal resection. a,b | Normal saline with a drop of methylene blue is injected beneath the lesion creating a submucosal fluid cushion. c | The added methylene blue in the injection solution clearly demarcates the borders of the polyp. d–f | Snare polypectomy enables removal of the polyp.

study including 1,111 colorectal tumors (with a mean size of 35 mm) in 1,090 patients, en bloc and curative resection rates were 88% and 89%, respectively.86 The mean procedure time was 116 min and perforations occurred in almost 5% of the cases. A perforation rate of 5% is notable in comparison with EMR (1.3%), but new endoscopic closure techniques could make ESD a more attractive procedure.109 Regarding long-term outcomes after ESD, a Japanese study showed a promising recurrence rate of only 2% during a follow-up time of 30 months.108 Interestingly, all recurrent tumors were initially treated in a piecemeal fashion, which highlights the importance of en bloc resections.

Conclusions Quality assurance using a minimal set of indicators is essential to continuously improve the effectiveness of colonoscopy. The quality of bowel preparation should be documented and can be enhanced by providing information brochures and prescription of split-dose regimens. Performing a total colonoscopy is essential and is confirmed when the ileocecal valve and appendiceal orifice are visualized. Cecal intubation rates should approximate 95% and specific devices, such as a variable stiffness or pediatric colonoscope, can aide the endoscopist in achieving this goal. The adenoma detection rate is an independent predictor of the risk of interval cancer after a screening colonoscopy and should exceed a minimum of 25% in men and 15% in



REVIEWS women. Careful inspection, longer withdrawal time and an optimal withdrawal technique can enhance adenoma detection. To date, chromoe ndoscopy is the only advanced imaging technique with proven benefit in adenoma detection. Finally, in the past few years, several informative studies have been published showing that the technique of polypectomy can affect the number of complications and the completeness of a resection. Although this information provides a basis for deciding on the optimal polypectomy technique, more data from randomized controlled trials on this important issue for clinical gastrointestinal practice are warranted in the future. 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13. 14.

Ko, C. W. et al. Serious complications within 30 days of screening and surveillance colonoscopy are uncommon. Clin. Gastroenterol. Hepatol. 8, 166–173 (2010). Rabeneck, L. et al. Bleeding and perforation after outpatient colonoscopy and their risk factors in usual clinical practice. Gastroenterology 135, 1899–1906 (2008). Singh, H. et al. Colonoscopy and its complications across a Canadian regional health authority. Gastrointest. Endosc. 69, 665–671 (2009). Levin, T. R. et al. Complications of colonoscopy in an integrated health care delivery system. Ann. Intern. Med. 145, 880–886 (2006). Regula, J. et al. Colonoscopy in colorectal-cancer screening for detection of advanced neoplasia. N. Engl. J. Med. 355, 1863–1872 (2006). Sieg, A., Hachmoeller-Eisenbach, U. & Eisenbach, T. Prospective evaluation of complications in outpatient GI endoscopy: a survey among German gastroenterologists. Gastrointest. Endosc. 53, 620–627 (2001). Viiala, C. H., Zimmerman, M., Cullen, D. J. & Hoffman, N. E. Complication rates of colonoscopy in an Australian teaching hospital environment. Intern. Med. J. 33, 355–359 (2003). Spiegel, B. M. et al. Development and validation of a novel patient educational booklet to enhance colonoscopy preparation. Am. J. Gastroenterol. 106, 875–883 (2011). Froehlich, F., Wietlisbach, V., Gonvers, J. J., Burnand, B. & Vader, J. P. Impact of colonic cleansing on quality and diagnostic yield of colonoscopy: the European Panel of Appropriateness of Gastrointestinal Endoscopy European multicenter study. Gastrointest. Endosc. 61, 378–384 (2005). Harewood, G. C., Sharma, V. K. & de Garmo, P. Impact of colonoscopy preparation quality on detection of suspected colonic neoplasia. Gastrointest. Endosc. 58, 76–79 (2003). Rex, D. K., Imperiale, T. F., Latinovich, D. R. & Bratcher, L. L. Impact of bowel preparation on efficiency and cost of colonoscopy. Am. J. Gastroenterol. 97, 1696–1700 (2002). National Health Service Bowel Cancer Screening Programme Endoscopy Quality Assurance Group. Quality assurance guidelines for colonoscopy publication no.6. National Health Service [online], http://www.cancerscreening. nhs.uk/bowel/publications/nhsbcsp06.pdf (2011). Aronchick, C. A. Bowel preparation scale. Gastrointest. Endosc. 60, 1037–1038 (2004). Lai, E. J., Calderwood, A. H., Doros, G., Fix, O. K. & Jacobson, B. C. The Boston bowel preparation scale: a valid and reliable instrument for


15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

Review criteria The PubMed database was searched for full-text articles written in English using the term “colonoscopy” together with the following terms: “quality indicators”, “bowel preparation”, “sedation”, “cecal intubation”, “magnetic endoscopic imaging”, “chromoendoscopy”, “narrow band imaging”, “i-scan”, “FICE”, “autofluorescence imaging”, “third eye retroscope”, “cap-assisted colonoscopy”, “polypectomy“, “endoscopic mucosal resection” and “endoscopic submucosal dissection. The majority of the articles selected were published in the past 10 years. Furthermore, we used the reference list of identified articles to select other relevant papers.

colonoscopy-oriented research. Gastrointest. Endosc. 69, 620–625 (2009). Rostom, A. & Jolicoeur, E. Validation of a new scale for the assessment of bowel preparation quality. Gastrointest. Endosc. 59, 482–486 (2004). Belsey, J., Epstein, O. & Heresbach, D. Systematic review: oral bowel preparation for colonoscopy. Aliment. Pharmacol. Ther. 25, 373–384 (2007). Corporaal, S., Kleibeuker, J. H. & Koornstra, J. J. Low-volume PEG plus ascorbic acid versus highvolume PEG as bowel preparation for colonoscopy. Scand. J. Gastroenterol. 45, 1380–1386 (2010). Marmo, R. et al. Effective bowel cleansing before colonoscopy: a randomized study of split-dosage versus non-split dosage regimens of high-volume versus low-volume polyethylene glycol solutions. Gastrointest. Endosc. 72, 313–320 (2010). Ell, C. et al. Randomized trial of low-volume PEG solution versus standard PEG + electrolytes for bowel cleansing before colonoscopy. Am. J. Gastroenterol. 103, 883–893 (2008). Lawrance, I. C., Willert, R. P. & Murray, K. Bowel cleansing for colonoscopy: prospective randomized assessment of efficacy and of induced mucosal abnormality with three preparation agents. Endoscopy 43, 412–418 (2011). Kilgore, T. W. et al. Bowel preparation with splitdose polyethylene glycol before colonoscopy: a meta-analysis of randomized controlled trials. Gastrointest. Endosc. 73, 1240–1245 (2011). Singh, H. et al. Propofol for sedation during colonoscopy. Cochrane Database Syst. Rev. 2008, Issue 4. Art. No.: CD006268. doi:10.1002/14651858.CD006268.pub2 (2008). Rex, D. K. et al. Endoscopist-directed administration of propofol: a worldwide safety experience. Gastroenterology 137, 1229–1237 (2009). Shah, S. G., Saunders, B. P., Brooker, J. C. & Williams, C. B. Magnetic imaging of colonoscopy: an audit of looping, accuracy and ancillary maneuvers. Gastrointest. Endosc. 52, 1–8 (2000). Bretthauer, M. et al. NORCCAP (Norwegian colorectal cancer prevention): a randomised trial to assess the safety and efficacy of carbon dioxide versus air insufflation in colonoscopy. Gut 50, 604–607 (2002). Sumanac, K. et al. Minimizing postcolonoscopy abdominal pain by using CO2 insufflation: a prospective, randomized, double blind, controlled trial evaluating a new commercially available CO2 delivery system. Gastrointest. Endosc. 56, 190–194 (2002).

27. Church, J. & Delaney, C. Randomized, controlled trial of carbon dioxide insufflation during colonoscopy. Dis. Colon Rectum 46, 322–326 (2003). 28. Baxter, N. N. et al. Association of colonoscopy and death from colorectal cancer. Ann. Intern. Med. 150, 1–8 (2009). 29. Brenner, H. et al. Protection from right- and leftsided colorectal neoplasms after colonoscopy: population-based study. J. Natl Cancer Inst. 102, 89–95 (2010). 30. Singh, H. et al. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Gastroenterology 139, 1128–1137 (2010). 31. Neerincx, M. et al. Colonic work-up after incomplete colonoscopy: significant new findings during follow-up. Endoscopy 42, 730–735 (2010). 32. Rizek, R. et al. Rates of complete colonic evaluation after incomplete colonoscopy and their associated factors: a population-based study. Med. Care 47, 48–52 (2009). 33. Shah, H. A., Paszat, L. F., Saskin, R., Stukel, T. A. & Rabeneck, L. Factors associated with incomplete colonoscopy: a population-based study. Gastroenterology 132, 2297–2303 (2007). 34. Lieberman, D. A. et al. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N. Engl. J. Med. 343, 162–168 (2000). 35. Rex, D. K., Chen, S. C. & Overhiser, A. J. Colonoscopy technique in consecutive patients referred for prior incomplete colonoscopy. Clin. Gastroenterol. Hepatol. 5, 879–883 (2007). 36. Shumaker, D. A., Zaman, A. & Katon, R. M. A randomized controlled trial in a training institution comparing a pediatric variable stiffness colonoscope, a pediatric colonoscope, and an adult colonoscope. Gastrointest. Endosc. 55, 172–179 (2002). 37. Saifuddin, T., Trivedi, M., King, P. D., Madsen, R. & Marshall, J. B. Usefulness of a pediatric colonoscope for colonoscopy in adults. Gastrointest. Endosc. 51, 314–317 (2000). 38. Marshall, J. B., Perez, R. A. & Madsen, R. W. Usefulness of a pediatric colonoscope for routine colonoscopy in women who have undergone hysterectomy. Gastrointest. Endosc. 55, 838–841 (2002). 39. Othman, M. O., Bradley, A. G., Choudhary, A., Hoffman, R. M. & Roy, P. K. Variable stiffness colonoscope versus regular adult colonoscope: meta-analysis of randomized controlled trials. Endoscopy 41, 17–24 (2009). 40. Shah, S. G., Brooker, J. C., Williams, C. B., Thapar, C. & Saunders, B. P. Effect of magnetic

www.nature.com/nrgastro © 2011 Macmillan Publishers Limited. All rights reserved

FOCUS ON ENDOSCOPY

41.

42.

43.

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

56.

57.

58.

endoscope imaging on colonoscopy performance: a randomised controlled trial. Lancet 356, 1718–1722 (2000). Shah, S. G. et al. Effect of magnetic endoscope imaging on patient tolerance and sedation requirements during colonoscopy: a randomized controlled trial. Gastrointest. Endosc. 55, 832–837 (2002). Wehrmann, T., Lechowicz, I., Martchenko, K. & Riphaus, A. Routine colonoscopy with a standard gastroscope. A randomized comparative trial in a western population. Int. J. Colorectal Dis. 23, 443–446 (2008). Park, C. H. et al. Sedation-free colonoscopy using an upper endoscope is tolerable and effective in patients with low body mass index: a prospective randomized study. Am. J. Gastroenterol. 101, 2504–2510 (2006). Keswani, R. N. Single-balloon colonoscopy versus repeat standard colonoscopy for previous incomplete colonoscopy: a randomized, controlled trial. Gastrointest. Endosc. 73, 507–512 (2011). Rex, D. K., Khashab, M., Raju, G. S., Pasricha, J. & Kozarek, R. Insertability and safety of a shapelocking device for colonoscopy. Am. J. Gastroenterol. 100, 817–820 (2005). Van Rijn, J. C. et al. Polyp miss rate determined by tandem colonoscopy: a systematic review. Am. J. Gastroenterol. 101, 343–350 (2010). Kaminski, M. F. et al. Quality indicators for colonoscopy and the risk of interval cancer. N. Engl. J. Med. 362, 1795–1803 (2010). Rex, D. K. et al. Quality indicators for colonoscopy. Gastrointest. Endosc. 63, S16–S28 (2006). Lee, R. H. et al. Quality of colonoscopy withdrawal technique and variability in adenoma detection rates (with videos). Gastrointest. Endosc. 74, 128–134 (2011). East, J. E. et al. Dynamic patient position changes during colonoscope withdrawal increase adenoma detection: a randomized, crossover trial. Gastrointest. Endosc. 73, 456–463 (2011). Lee, J. M. et al. Effects of hyosine N.‑butyl bromide on the detection of polyps during colonoscopy. Hepatogastroenterology 57, 90–94 (2010). East, J. E. et al. A comparative study of standard vs. high definition colonoscopy for adenoma and hyperplastic polyp detection with optimized withdrawal technique. Aliment. Pharmacol. Ther. 28, 768–776 (2008). Pellise, M. et al. Impact of wide-angle, highdefinition endoscopy in the diagnosis of colorectal neoplasia: a randomized controlled trial. Gastroenterology 135, 1062–1068 (2008). Burke, C. A., Choure, A. G., Sanaka, M. R. & Lopez, R. A comparison of high-definition versus conventional colonoscopes for polyp detection. Dig. Dis. Sci. 55, 1716–1720 (2010). Tribonias, G. et al. Comparison of standard vs high-definition, wide-angle colonoscopy for polyp detection: a randomized controlled trial. Colorectal Dis. 12, e260–e266 (2010). Buchner, A. M. et al. High-definition colonoscopy detects colorectal polyps at a higher rate than standard white-light colonoscopy. Clin. Gastroenterol. Hepatol. 8, 364–370 (2010). Ignjatovic, A. et al. What is the most reliable imaging modality for small colonic polyp characterization? Study of white-light, autofluorescence, and narrow-band imaging. Endoscopy 43, 94–99 (2011). van den Broek, F. J. et al. Combining autofluorescence imaging and narrow-band imaging for the differentiation of adenomas from

59.

60.

61.

62.

63.

64.

65.

66.

67.

68.

69.

70.

71.

72.

73.

non-neoplastic colonic polyps among experienced and non-experienced endoscopists. Am. J. Gastroenterol. 104, 1498–1507 (2009). Kiesslich, R., von, B. M., Hahn, M., Hermann, G. & Jung, M. Chromoendoscopy with indigocarmine improves the detection of adenomatous and nonadenomatous lesions in the colon. Endoscopy 33, 1001–1006 (2001). Pohl, J. et al. Pancolonic chromoendoscopy with indigo carmine versus standard colonoscopy for detection of neoplastic lesions: a randomised two-centre trial. Gut 60, 485–490 (2011). Lecomte, T. et al. Chromoendoscopic colonoscopy for detecting preneoplastic lesions in hereditary nonpolyposis colorectal cancer syndrome. Clin. Gastroenterol. Hepatol. 3, 897–902 (2005). East, J. E. et al. Narrow band imaging for colonoscopic surveillance in hereditary nonpolyposis colorectal cancer. Gut 57, 65–70 (2008). van den Broek, F. J., Reitsma, J. B., Curvers, W. L., Fockens, P. & Dekker, E. Systematic review of narrow-band imaging for the detection and differentiation of neoplastic and nonneoplastic lesions in the colon (with videos). Gastrointest. Endosc. 69, 124–135 (2009). Hoffman, A. et al. High definition colonoscopy combined with i‑Scan is superior in the detection of colorectal neoplasias compared with standard video colonoscopy: a prospective randomized controlled trial. Endoscopy 42, 827–833 (2010). Aminalai, A. et al. Live image processing does not increase adenoma detection rate during colonoscopy: a randomized comparison between FICE and conventional imaging (Berlin Colonoscopy Project 5, BECOP‑5). Am. J. Gastroenterol. 105, 2383–2388 (2010). Chung, S. J. et al. Efficacy of computed virtual chromoendoscopy on colorectal cancer screening: a prospective, randomized, back‑to‑back trial of Fuji Intelligent Color Enhancement versus conventional colonoscopy to compare adenoma miss rates. Gastrointest. Endosc. 72, 136–142 (2010). Pohl, J. et al. Computed virtual chromoendoscopy versus standard colonoscopy with targeted indigocarmine chromoscopy: a randomised multicentre trial. Gut 58, 73–78 (2009). Ramsoekh, D. et al. A back‑to‑back comparison of white light video endoscopy with autofluorescence endoscopy for adenoma detection in high-risk subjects. Gut 59, 785–793 (2010). van den Broek, F. J. et al. Clinical evaluation of endoscopic trimodal imaging for the detection and differentiation of colonic polyps. Clin. Gastroenterol. Hepatol. 7, 288–295 (2009). Kondo, S. et al. A randomized controlled trial evaluating the usefulness of a transparent hood attached to the tip of the colonoscope. Am. J. Gastroenterol. 102, 75–81 (2007). Lee, Y. T. et al. Efficacy of cap-assisted colonoscopy in comparison with regular colonoscopy: a randomized controlled trial. Am. J. Gastroenterol. 104, 41–46 (2009). Morgan, J., Thomas, K., Lee-Robichaud, H. & Nelson, R. L. Transparent cap colonoscopy versus standard colonoscopy for investigation of gastrointestinal tract conditions. Cochrane Database Syst. Rev. Issue 2. Art. No.: CD008211. doi:10.1002/14651858. CD008211.pub2. (2011). Hewett, D. G. & Rex, D. K. Cap-fitted colonoscopy: a randomized, tandem


74.

75.

76.

77.

78.

79.

80.

81.

82.

83.

84.

85.

86.

87.

88.

89.

90.

91.

colonoscopy study of adenoma miss rates. Gastrointest. Endosc. 72, 775–781 (2010). Tee, H. P. et al. Prospective randomized controlled trial evaluating cap-assisted colonoscopy vs standard colonoscopy. World J. Gastroenterol. 16, 3905–3910 (2010). DeMarco, D. C. et al. Impact of experience with a retrograde-viewing device on adenoma detection rates and withdrawal times during colonoscopy: the Third Eye Retroscope study group. Gastrointest. Endosc. 71, 542–550 (2010). Waye, J. D. et al. A retrograde-viewing device improves detection of adenomas in the colon: a prospective efficacy evaluation (with videos). Gastrointest. Endosc. 71, 551–556 (2010). Leufkens, A. M. et al. Effect of a retrogradeviewing device on adenoma detection rate during colonoscopy: the TERRACE study. Gastrointest. Endosc. 73, 480–489 (2011). Endoscopy Classification Review Group. Update on the Paris classification of superficial neoplastic lesions in the digestive tract. Endoscopy 37, 570–578 (2005). Winawer, S. J. et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N. Engl. J. Med. 329, 1977–1981 (1993). Iqbal, C. W. et al. Surgical management and outcomes of 165 colonoscopic perforations from a single institution. Arch. Surg. 143, 701–706 (2008). Pabby, A. et al. Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial. Gastrointest. Endosc. 61, 385–391 (2005). Farrar, W. D., Sawhney, M. S., Nelson, D. B., Lederle, F. A. & Bond, J. H. Colorectal cancers found after a complete colonoscopy. Clin. Gastroenterol. Hepatol. 4, 1259–1264 (2006). Ignjatovic, A. et al. Optical diagnosis of small colorectal polyps at routine colonoscopy (Detect InSpect ChAracterise Resect and Discard; DISCARD trial): a prospective cohort study. Lancet Oncol. 10, 1171–1178 (2009). Efthymiou, M., Taylor, A. C., Desmond, P. V., Allen, P. B. & Chen, R. Y. Biopsy forceps is inadequate for the resection of diminutive polyps. Endoscopy 43, 312–316 (2011). Moss, A. et al. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology 140, 1909–1918 (2011). Saito, Y. et al. A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video). Gastrointest. Endosc. 72, 1217–1225 (2010). Singh, N., Harrison, M. & Rex, D. K. A survey of colonoscopic polypectomy practices among clinical gastroenterologists. Gastrointest. Endosc. 60, 414–418 (2004). Hewett, D. G. & Rex, D. K. Colonoscopy and diminutive polyps: hot or cold biopsy or snare? Do I send to pathology? Clin. Gastroenterol. Hepatol. 9, 102–105 (2011). Woods, A., Sanowski, R. A., Wadas, D. D., Manne, R. K. & Friess, S. W. Eradication of diminutive polyps: a prospective evaluation of bipolar coagulation versus conventional biopsy removal. Gastrointest. Endosc. 35, 536–540 (1989). Yoo, T. W. et al. Clinical significance of small colorectal adenoma less than 10 mm: the KASID study. Hepatogastroenterology 54, 418–421 (2007). Lieberman, D., Moravec, M., Holub, J., Michaels, L. & Eisen, G. Polyp size and advanced histology in patients undergoing


REVIEWS

92.

93.

94.

95.

96.

97.

98.

colonoscopy screening: implications for CT colonography. Gastroenterology 135, 1100–1105 (2008). Wadas, D. D. & Sanowski, R. A. Complications of the hot biopsy forceps technique. Gastrointest. Endosc. 34, 32–37 (1988). Nelson, A. M. Delayed hemorrhage following “hot biopsy” of a diminutive colonic polyp. Gastrointest. Endosc. 36, 418 (1990). Di Giorgio, P. et al. Detachable snare versus epinephrine injection in the prevention of postpolypectomy bleeding: a randomized and controlled study. Endoscopy 36, 860–863 (2004). Paspatis, G. A. et al. A prospective, randomized comparison of adrenaline injection in combination with detachable snare versus adrenaline injection alone in the prevention of postpolypectomy bleeding in large colonic polyps. Am. J. Gastroenterol. 101, 2805 (2006). Matsushita, M. et al. Ineffective use of a detachable snare for colonoscopic polypectomy of large polyps. Gastrointest. Endosc. 47, 496–499 (1998). Heresbach, D. et al. A national survey of endoscopic mucosal resection for superficial gastrointestinal neoplasia. Endoscopy 42, 806–813 (2010). Tanaka, S. et al. Clinicopathologic features and endoscopic treatment of superficially spreading


colorectal neoplasms larger than 20 mm. Gastrointest. Endosc. 54, 62–66 (2001). 99. Uraoka, T. et al. Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum. Gut 55, 1592–1597 (2006). 100. Moss, A., Bourke, M. J. & Metz, A. J. A randomized, double-blind trial of succinylated gelatin submucosal injection for endoscopic resection of large sessile polyps of the colon. Am. J. Gastroenterol. 105, 2375–2382 (2010). 101. Swan, M. P., Bourke, M. J., Alexander, S., Moss, A. & Williams, S. J. Large refractory colonic polyps: is it time to change our practice? A prospective study of the clinical and economic impact of a tertiary referral colonic mucosal resection and polypectomy service (with videos). Gastrointest. Endosc. 70, 1128–1136 (2009). 102. Mannath, J., Subramanian, V., Singh, R., Telakis, E. & Ragunath, K. Polyp recurrence after endoscopic mucosal resection of sessile and flat colonic adenomas. Dig. Dis. Sci. 56, 2389–2395 (2011). 103. Brooker, J. C. et al. Treatment with argon plasma coagulation reduces recurrence after piecemeal resection of large sessile colonic polyps: a randomized trial and recommendations. Gastrointest. Endosc. 55, 371–375 (2002). 104. Onozato, Y. et al. Endoscopic submucosal dissection for early gastric cancers and large

flat adenomas. Endoscopy 38, 980–986 (2006). 105. Imagawa, A. et al. Endoscopic submucosal dissection for early gastric cancer: results and degrees of technical difficulty as well as success. Endoscopy 38, 987–990 (2006). 106. Saito, Y. et al. Endoscopic treatment of large superficial colorectal tumors: a case series of 200 endoscopic submucosal dissections (with video). Gastrointest. Endosc. 66, 966–973 (2007). 107. Deprez, P. H. et al. Current practice with endoscopic submucosal dissection in Europe: position statement from a panel of experts. Endoscopy 42, 853–858 (2010). 108. Niimi, K. et al. Long-term outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms. Endoscopy 42, 723–729 (2010). 109. Voermans, R. P., Vergouwe, F., Breedveld, P., Fockens, P. & van Berge Henegouwen, M. I. Comparison of endoscopic closure modalities for standardized colonic perforations in a porcine colon model. Endoscopy 43, 217–222 (2011). Author contributions Both authors contributed equally to researching, discussing, writing, reviewing and/or editing this manusript.

www.nature.com/nrgastro © 2011 Macmillan Publishers Limited. All rights reserved