Recent advances in colonoscopy

Colorectal cancer screening

Colorectal cancer is the second most common cancer worldwide¹. There is variation in screening practices globally². Most screening programs employ a non-invasive test such as fecal occult blood testing to identify higher risk patients needing to undergo colonoscopy. Many screening programs are now using or moving towards using newer non-invasive tests, such as fecal immunochemical testing (FIT) or fecal DNA tests, which are associated with greater uptake and detection rates for adenomas and colorectal cancer^3,4. In higher income settings, colonoscopy may be offered as the screening test. In the USA, a national survey estimated 65% of adults to be engaged with colorectal cancer screening, with colonoscopy being the most commonly used test⁵. Such widespread colonoscopy screening appears to be reducing colorectal cancer incidence in the USA⁶.

Sedation

Current UK practice in colonoscopy is to use light conscious sedation or an unsedated approach. Maximum recommended doses of commonly used agents include midazolam (up to 5 mg) and fentanyl (up to 100 mcg) or pethidine (up to 50 mg). Unsedated colonoscopy, often using Entonox, is increasingly prevalent owing to improvements in technique. In the English Bowel Cancer Screening Program in 2014, 29.4% of colonoscopies were performed unsedated (personal correspondence, Professor M.D. Rutter). No difference in adenoma detection was observed in the unsedated group¹⁵.

In some areas of the world, deeper sedation with propofol or general anesthesia is the preferred approach, although this may not be associated with improved adenoma detection, patient experience, or cost effectiveness, and has been shown to be associated with increased risk of complications^16,17.

Improving adenoma detection

An important objective of screening and surveillance colonoscopy is adenoma detection. Decreased incidence of post-colonoscopy colorectal cancer has been observed among colonoscopists with higher ADRs¹⁸. An important paper by Corley et al. has also demonstrated an inverse relationship between ADR and interval cancer incidence and mortality from colorectal cancer. Based on 314,872 colonoscopies performed by 136 gastroenterologists, each 1.0% increase in ADR was associated with a 3.0% decrease in the risk of colorectal cancer (hazard ratio, 0.97; 95% confidence interval, 0.96–0.98)¹⁹. The progress in understanding the importance and relevance of ADR has led to its recognition as the key performance indicator of colonoscopy and a useful tool for quality improvement, as discussed later in this paper.

A number of recent advances have sought to overcome some of the barriers to adenoma detection. Regular feedback of performance indicators to colonoscopists, ideally with peer comparators, has been shown to positively affect adenoma detection²⁰. The introduction of a simple training package and a bundle of simple maneuvers (withdrawal time >6 minutes, rectal retroversion, Buscopan use, and right lateral positioning on withdrawal) led to an increase in adenoma detection among a group of colonoscopists in the Quality Improvement in Colonoscopy (QIC) study²¹.

New technologies to facilitate examination of difficult-to-access mucosa are currently being evaluated, although not all studies of quality improvement have been successful. These aim to increase the exposure of mucosa behind haustral folds, rectal valves, the ileocecal valve, and at flexures. Innovations included cap-assisted colonoscopy²², the Third Eye® Retroscope®²³, wider-angle colonoscopes²⁴, and the Endocuff® device²⁵. Improving the definition of the colonoscopy image has been shown to increase adenoma detection, particularly small and flat lesions²⁶.

Chromoendoscopy is the technique of enhancing mucosal inspection using a dye applied to the mucosa. Commonly used dyes include indigo carmine and methylene blue. Dye spray chromoendoscopy has become the standard technique for colonoscopic surveillance for dysplasia in inflammatory bowel disease, increasing pathology detection and reducing unnecessary biopsies when compared to random biopsy protocols²⁷.

Dye spray colonoscopy may also increase adenoma detection in routine colonoscopy, but the incremental gain in detection of diminutive lesions is offset by increased procedure time²⁸.

Electronic image processing allows “virtual chromoendoscopy” with mucosal enhancement without physical dye application. Systems such as Narrow Band Imaging (Olympus), FICE (Fujinon), and i-scan (Pentax) have made such technology widely available. These techniques are particularly useful for lesion classification but have not consistently been shown to improve adenoma detection. The NICE system and Kudo’s pit pattern can help differentiate hyperplastic lesions from neoplastic lesions and identify higher grades of dysplasia that may be associated with submucosal invasion. This has become an important tool in planning management of lesions and deciding whether a lesion is resectable endoscopically or may require a surgical approach.

Improved lesion interrogation using electronic image enhancement has been proposed as an alternative to conventional polypectomy and histology. The American Society of Gastrointestinal Endoscopy (ASGE) has proposed a Preservation and Integration of Valuable endoscopic Innovations (PIVI) statement identifying criteria that a resect and discard strategy would have to meet to be acceptable for widespread use. An important driver for this strategy is the cost associated with pathological examination of small polyps which have an extremely low risk of containing advanced dysplasia. The DISCARD study demonstrated that in a single center with expert endoscopists, a resect and discard strategy accurately recognized adenomas with a sensitivity of 94% and accurately predicted appropriate surveillance strategy in 98%²⁹.

Management of large colonic polyps

Endoscopic removal of large pre-malignant or suspected early malignant gastrointestinal (GI) lesions poses a challenge in that a complete resection that allows for staging and appropriate further management is warranted in these cases.

Traditionally, EMR, a technique that comprises submucosal injection of lifting solution followed by snare excision, has been used for such lesions. However, EMR is considered suboptimal for large lesions where there is an increased risk of submucosal invasion and therefore a need for a more oncologically sound, en-bloc resection that allows adequate staging. With piecemeal EMR, recurrence rates are significant (16% in a large Australian series), but recurrence is manageable endoscopically in the majority of cases³⁸ for colorectal lesions larger than 10 mm³⁹. The obvious need for a technique that allows for en-bloc removal of large, advanced esophagogastric and colorectal lesions recently led Japanese endoscopists to develop endoscopic submucosal dissection (ESD) as a more efficient alternative. This technique is based on the use of endoscopic knives to achieve a deep submucosal, en-bloc excision that allows for accurate histopathologic staging⁴⁰. Excellent pre-excision lesion assessment is warranted based on size, morphology, and surface pattern. To justify an attempt of endoscopic resection, advanced imaging modalities, mainly high-definition and chromoendoscopy, are utilized to achieve a meticulous lesion assessment.

Therapeutic indications of ESD in the colorectum include polyps that are suspicious of early neoplastic submucosal involvement as defined by endoscopic appearance (lesions with focal depression, irregular surface patterns, or poor submucosal lift), polyps larger than 2 cm, and polyps that pose difficulties to conventional EMR, such as areas of recurrence after previous polypectomy^23,34.

Accurate recognition of colonic lesions with submucosal invasion can be challenging, and considerable variation in proficiency has been demonstrated among western endoscopists⁴¹.

It should be stressed that ESD is a highly demanding modality in terms of endoscopist skill and requires specialized training and a certain volume of procedures to ensure competency⁴². Perforation is a potentially severe complication of the technique, with a risk of 6–20% in colorectal lesions^43,44. Surgery is still considered the gold standard for the treatment of most lesions that also fulfill criteria for ESD, although the latter appears to be superior in terms of periprocedural morbidity and mortality when performed by experienced endoscopists^23,34.

Discussion of the management options for large colonic polyps by a multidisciplinary team is recommended, as regional variation in surgical management rates has been observed in England⁴⁵. Recent consensus guidelines on the management of large non-pedunculated colonic polyps have suggested a range of key performance indicators that aim to measure and improve standards of management of large polyps⁴⁶. There is likely to be a variation in performance of advanced polypectomy techniques and a subsequent variation in recurrence rates (which may be associated with risk of interval cancer)⁴⁷.

Serrated lesions

Previously, the majority of colorectal cancers were thought to arise from the “adenoma-carcinoma” sequence as a result of an accumulation of genetic mutations⁴⁸. This process is slow, taking 10–15 years for normal mucosa to progress to malignancy, thus offering the opportunity of a long latent phase in which to detect and remove the malignant precursor (adenoma).

Recent years have seen the increasing recognition and understanding of an alternative pathway for the development of colorectal cancer. This arose from the appreciation of the hyperplastic polyposis syndrome, in which multiple hyperplastic polyps are present in the colon and associated with an increased lifetime risk of colorectal cancer of 20–50%⁴⁹.

Serrated lesions are now thought to represent an alternative pathway to colorectal cancer through mutations in BRAF, CpG island methylation, and subsequently methylation of MLH1⁵⁰. Hyperplastic polyps, which are very common and occur in up to 95% of individuals, progress to sessile serrated adenomas (SSAs), of which a proportion may have cytological dysplasia. A separate, morphologically and histologically different polyp called a traditional serrated adenoma (TSA) is recognized. SSAs or TSAs can be challenging to detect at colonoscopy due to their flat appearance and relative lack of differentiation from the background mucosa. They tend to occur in the proximal colon where lesion detection is impaired by prominent haustral folds⁵¹.

Serrated lesions are thought to be clinically important due to their association with the presence of synchronous advanced neoplasia⁵². They may also be a significant cause of advanced neoplasia or cancer detected following colonoscopy, presumably due to the increased likelihood of not being detected and subsequent rapid progression⁵³.

Increased awareness of serrated lesions and appreciation of their subtle appearance may aid detection⁵⁴. They commonly have an adherent mucosal cap, which obscures detection. Recently, an open shape pit pattern (type II-O) has been described to aid differentiation of dysplastic SSA from hyperplastic polyps; however, the clinical applicability of this is limited⁵⁵.

Complications

Recognized important or commonly occurring complications of colonoscopy include bleeding, colonic perforation, and those related to sedation or anesthetic use. Current estimates of the frequency of such events depend on the indication for the colonoscopy, relevant patient factors, such as comorbidity, and whether endoscopic therapy is delivered during the procedure.

In the English NHS Bowel Cancer Screening Program, the overall rate of bleeding following colonoscopy is 0.65%, bleeding requiring transfusion 0.04%, and colonic perforation 0.06%. Risk of adverse events increases if polypectomy is performed. Factors relating to the polyp, including cecal location and increasing size, are associated with increasing risk of bleeding or perforation⁵⁶.

Endoscopic management of bleeding and perforation, including clip placement, over-the-scope closure devices, and endoscopic suturing techniques, may reduce the need for surgical intervention following such complications^57,58.