Colonoscopy, the most sensitive test used to detect advanced adenoma and cancer, has been shown to prevent colorectal cancer (CRC) when combined with polypectomy. CRC remains the third most commonly diagnosed cancer and the second leading cause of cancer death in men and women in the United States. In 2009, approximately 100,610 colon and 40,870 rectal cancer cases were diagnosed in the United States. In the same year, approximately 49,920 CRC deaths were projected. Regrettably, some newly diagnosed patients with cancer had a clearing colonoscopy before their diagnosis. Rex and colleagues have estimated that approximately 1 in 130 patients who undergo colon cancer screening colonoscopy will develop an interval CRC within 3 years of their clearing colonoscopy, thought mainly to be because of missed or incompletely treated lesions ( Fig. 1 ). In the authors’ experience, proven fast-growing CRC are thought to be less common ( Fig. 2 ).

An interval colon cancer was diagnosed at the hepatic flexure ( A ) during an evaluation for weight loss and iron-deficiency anemia. The patient had a clearing colonoscopy approximately 3 years earlier elsewhere, which was reported to be with good preparation quality. Multiple other, large ( B ) and small ( arrow ) ( C ), superficial elevated (flat) neoplasms were detected. A subtle fourth interval neoplasm—a subcentimeter superficial elevated/flat neoplasm—and its enhanced image using narrow-band imaging and diluted indigo carmine is shown ( D , E , and F , respectively).

A case of fast-growing rectal cancer. A colonoscopy performed for average-risk CRC screening 2 years earlier showed the rectum to be normal ( A , B ). A subsequent colonoscopy, performed to evaluate symptoms of tenesmus and pain on sitting, showed a large circumferential mass in the distal rectum ( C , D ). On endoscopic ultrasound, the lesion was consistent with T3N1. The pathologic condition was signet cell adenocarcinoma. This case also highlights the importance of picture documentation. A picture is worth a thousand words. The lesion was clearly not visible during the examination 2 years previously.

The knowledge, techniques, and technologies are available today to optimize the colonoscopic detection and diagnosis of pre- or early CRCs, and ultimately, improve advanced CRC prevention. The inconspicuously flat or depressed shape of non-polypoid colorectal neoplasms (NP-CRN), which can cause their detection to be a challenge, may contribute to interval CRC. Thus, familiarity with subtle mucosal changes in wall contour, color, and vascularity of normal and abnormal mucosa is critical to their successful detection ( Fig. 3 ), and a step forward in quality colonoscopy. Image-enhanced endoscopy (IEE) is a useful technique that can be used for detailed inspection and diagnosis of NP-CRN, once an abnormal patch of mucosa has been detected using standard white light colonoscopy. This article reviews the use of IEE in the detection, diagnosis, and treatment of the flat and depressed colorectal neoplasms.

Images from a colonoscopy of a patient who self-referred for evaluation of a reddish fold (biopsy was adenoma) in the cecum and a large flat adenoma in the transverse colon ( A ). A large flat adenoma in the cecum ( B ) that extended into the ileocecal valve ( C , D ) was diagnosed. The lesion was sprayed with diluted indigo carmine to further delineate its large size, which precluded endoscopic mucosal resection ( E ). Target biopsies were obtained from the area suspected of containing the most advanced pathologic condition ( F ) at the ileocecal valve, and showed adenoma. The patient had multiple other flat adenomas throughout the colon, shown using white light ( G , I , J , K ), NBI ( H ) and indigo carmine ( L ). Note on careful inspection of the still images of these lesions that the lesions seem more reddish compared with the surrounding normal mucosa, have disrupted vascularity, and deformity of the fold contour of the colon wall. Similar to the case shown in Fig. 1 , these multiple-interval neoplasms suggest that the prior examination was inadequate.

Techniques of image-enhanced endoscopy

IEE can be readily accomplished using dyes or features of the endoscope equipment. In the colon and rectum, dye-based IEE includes the use of indigo carmine and crystal violet, although crystal violet is used primarily in Japan. Endoscope equipment–based IEE is now available through all major gastrointestinal endoscopy manufacturers, with each manufacturer offering a proprietary technique and technology.

Dye-Based IEE Techniques

In the colon and rectum, dye-based IEE includes the use of diluted indigo carmine and crystal violet solutions. These dyes significantly differ in their properties and methods of actions.

Indigo carmine dye

Indigo carmine is a contrast dye, that is, it is not absorbed into the cells. It functions by pooling into the mucosal pits, grooves, erosions, and depressions. Its deep blue color enhances visualization of these structures and allows the endoscopist to characterize the lesions by enabling them to better visualize the border, depth, and surface topography of the lesion. Diluted indigo carmine is usually made by mixing 5 mL of 0.8% solution of indigo carmine (American Reagent Laboratories Inc, Shirley, NY, USA) with 15 mL of water using a 60-mL syringe. The solution is sprayed directly through the accessory channel of the colonoscope ( Table 1 ) ( Fig. 4 ).

Table 1

Preparations of indigo carmine for the detection, diagnosis, and treatment of NP-CRN

1. Solution for image enhancement endoscopy 4–5 mL of 0.8% indigo carmine mixed with 20 cc water

2. Solution for submucosal injection Need: indigo carmine, 19-gauge filter needle, sterile cup (100-mL specimen cup), and 10 mL normal saline flush syringe For EMR : Mix 20 drops of indigo carmine using 19-gauge filter needle in 100 mL of sterile normal saline For ESD : Mix 1 cc of indigo carmine with 30 cc sterile normal saline Mix 1 mL of 1:10,000 Epinephrine in 10 cc of sterile normal saline

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