Serrated Lesions Pose Difficulties in Detection, Treatment

Issue: July 2015

ByFarzan Fahrtash Bahin, MBBS (Hons)

ByMichael Bourke, MBBS, FRACP

Q: A 58-Year-Old Female Underwent a Screening Colonoscopy That Showed a 2.5-cm Flat Polyp in the Proximal Ascending Colon. I Tattooed the Area and Biopsied the Polyp, Which Was Initially Reported as Hyperplastic. What Should I Do?

A: Large, flat proximal colonic lesions are usually not hyperplastic. Serrated lesions (SL) are being increasingly recognized as lesions with a significant premalignant potential. Due to their flat and inconspicuous appearance, they can be difficult to detect. We will describe herein the significance of large serrated lesions and an approach to safe and effective endoscopic treatment.

Lesion Detection and Characterization

The polyp described is most likely an SL. Large, flat polyps >10 mm in the proximal colon with histological features suggestive of a hyperplastic polyp (HP) are usually SLs. If a large, proximal colonic lesion is histologically reported as hyperplastic, it is useful to consider having the slides reviewed because a correct diagnosis is important, and there are significant therapeutic and surveillance implications. There are two main subtypes of SLs:

1. Sessile serrated adenomas (SSAs) are the most common, often multiple, and usually found in the proximal colon, particularly in females.

2. Traditional serrated adenomas (TSAs) are <10% of the total, have a greater risk of malignant transformation, and are typically located in the left colon.

Proximal colonic SLs are usually flat and inconspicuous and may be easily overlooked (Figure 1). A mucus cap is a characteristic feature and stool residue may also adhere to the lesion. The endoscopist must be alert to these aspects because they are useful red flags to improve SL detection. As a universal standard, endoscopists should aim for complete mucosal inspection by various techniques, including cleaning by water jet irrigation and aspiration of fluid. This is especially important for the detection of SLs because in sections of clean mucosa, an area of adherent mucus or stool may harbor an SL beneath it. The importance of good-quality bowel preparation and meticulous efforts to identify subtle lesions cannot be overemphasized. These are factors known to influence both adenoma and SL detection.

Figure 1. Barely perceptible flat lesion at the hepatic flexure, seen only on retroflexion.

Lesion Biology and Significance

Twenty percent to 30% of colorectal carcinomas develop through the “serrated pathway,” which is characterized by widespread gene inactivation via hypermethylation of promoter regions (the CpG island methylator phenotype [CIMP]), BRAF mutations, and frequent microsatellite instability (MSI). Phenotypically these lesions arise in the proximal colon and have a greater incidence in smokers and females. Elevated CIMP and MSI lesions such as those found in inconspicuous SLs may have a more rapidly progressive transition to invasive carcinoma, and consequently lead to interval carcinomas. Alternatively, they may be more consistently overlooked at colonoscopy, despite a large size, as they are most often very flat (Paris classification 0-IIB), and thus can be hard to recognize, even at the point of transition to invasive disease.

The detection of this type of polyp may imply the presence of the serrated polyposis syndrome (SPS), formerly known as the hyperplastic polyposis syndrome (HPS). The World Health Organization’s definition of a diagnosis of SPS is fulfilled if any of the following three clinical criteria are met:

1. More than 5 serrated polyps proximal to the sigmoid colon, two of which are greater than 10 mm in size

2. Any number of serrated polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with SPS

3. More than 20 serrated polyps of any size distributed throughout the colon

SPS is underrecognized by endoscopists and confers a greatly increased risk of colorectal carcinoma development of approximately 25% to 50%. When a large SL is found, a very careful interrogation of the colon under optimal conditions is required to examine for synchronous lesions.

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Refer or Resect?

Lesions larger than 20 mm carry different therapeutic implications and risk profiles, particularly in the right colon. Conventional polypectomy has a risk of serious adverse consequences of 1:1000 to 3000 procedures, whereas wide field endoscopic resection carries a perforation rate of 1% and a clinically significant bleeding risk of 5% to 7%. Bleeding is dependent on the site of the lesion, being generally 2% to 3% in the left colon and 10% to 12% in the right colon. Although endoscopic resection has comparable efficacy and the most favorable safety and cost profile in comparison with surgery, the patient needs to be appropriately informed about the potential risks of the procedure. Performing an unexpected endoscopic resection during a busy day of performing routine screening colonoscopy is also unlikely to lead to optimal outcomes.

Competent endoscopists should be comfortable with removing lesions up to 20 mm maximal size in the right colon. Lesions larger than 25 mm require different and more advanced technical skills and are probably best managed in tertiary care centers. Endoscopists routinely employing endoscopic resection require the appropriate resources for optimal patient outcomes, including expert nursing assistance, appropriate equipment, and surgical support.

Tattoo and Biopsy of the Lesion

Because SLs are often difficult to detect and thus potentially hard to identify subsequently, marking the lesion is useful. Marking is also valuable for scar identification at surveillance. However, the approach needs to be standardized for optimal outcomes. A 2-step technique for tattoo is advised. A submucosal injection of saline creates the initial bleb; with the needle tip in the same plane, the solution is changed to a carbon particle suspension and injection of 2 to 3 mL is performed. The sterile carbon is not biologically inert and causes a fibroinflammatory response in the submucosa, which may cause adherence between the mucosa and the muscularis propria, creating difficulty with later endoscopic resection or increased risk of perforation due to adherence between these two layers. Placing the tattoo at least 3 cm distal to the lesion is advised.

For any resectable lesion where biopsy is considered to be necessary, take 1 to 2 biopsies from the edge. Avoid tunneling biopsies or the use of diathermy to minimize the subsequent development of submucosal fibrosis, which may compromise subsequent endoscopic resection.

Figure 2. Lesion seen on narrow band imaging.

Figure 3. Close-up view with narrow band imaging. The margins of the lesion, which were difficult to appreciate with white light endoscopy, are more clearly defined. Note the sessile shape, surface grooves, heterogeneous pit pattern, and low vascular intensity.

Lesion Assessment

The application of standardized lesion assessment tools facilitates optimal lesion assessment and subsequent resection. Imaging enhancement, such as narrow-band imaging, may improve characterization of SLs (Figures 2 and 3). Apply the Paris system of endoscopic classification of superficial neoplastic lesions for standardized description of lesion morphology. Most SLs have IIA or IIB morphology. The Kudo pit pattern and lesion granularity are used mainly for assessment of adenomatous lesions. Photodocumention of the lesion should be performed. Size, location, adjacent landmarks, and other features that may be relevant to endoscopic resection should also be recorded.

Lesion Resection Technique

Injection Solution

Submucosal injection separates the mucosa from the muscularis propria and thus minimizes the likelihood of deep resection or transmural injury that may lead to colonic perforation. Use of a biologically inert dye that is taken up only by the submucosa (eg, indigo carmine) in the injection solution helps to confirm resection is taking place in the right plane and clearly delineates the lesion’s margins and the extent of the submucosal cushion. This is particularly relevant for SLs where margins are hard to discern. Use of a colloidal plasma volume expander solution, such as succinylated gelatin (Gelofusine), in the injection solution creates a sustained and uniform mucosal lift. It has been shown to improve resection size and en bloc resection rate, decrease resection time, and lead to superior clinical outcomes compared with normal saline. Hydroxyl ethyl starch (Voluven) would be an appropriate, readily available, and inexpensive alternative agent to be considered in the United States where Gelofusine is not accessible.

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Resection

The following points pertain to the essentials of endoscopic resection of this lesion (Figure 4):

Start at one edge (generally the most difficult or inaccessible area, as this area will only become more difficult to access later) and work sequentially from the point of first entry to the submucosal plane.
Start the injection before you stab the mucosa with the needle. This technique swiftly identifies the submucosal plane.
Elevate only each segment to be resected (sequential inject and resect approach).
Include a margin of normal tissue (approximately 2 to 3 mm).
Meticulously place the snare at the edge of the advancing defect.
Carefully inspect the post endoscopic resection defect.

Figure 4. After endoscopic resection; note the clear margins. Although initial biopsy histology showed a serrated morphology, final histology after resection was a mixed tubular adenoma and sessile serrated adenoma.

Postresection

Carefully inspect the post endoscopic resection margin and defect for residual lesion or signs of deep injury. The “target sign” represents muscularis propria resection, indicating a deeper resection and, as such, a potential risk for perforation. A similar mirror target sign may be appreciated on the resected specimen. Appropriate recognition of this sign allows for early closure of the defect and may avoid the need for surgery or prolonged hospital admission.

Screening and Surveillance Implications

The timing of endoscopic surveillance intervals after endoscopic resection of colonic laterally spreading tumors is dictated by the completeness of excision, underlying histology, and the patient’s clinical context. If the lesion has been completely removed in one to three pieces, follow-up colonoscopy at 12 months would be appropriate. Photodocumentation and biopsy of the resection scar should be performed. The resection scar requires assessment, and the risk of metachronous lesions is significant, thus a subsequent 12-month surveillance interval is appropriate.

If the patient has SPS, all serrated lesions should be completely excised in due course. In the case of numerous large lesions (>50) the risks and benefits of endoscopic resection and compliance with endoscopic surveillance need to be weighed against surgical intervention and discussed with the patient. In the author’s experience, with diligent endoscopic follow-up, it is possible to completely clear the colon of residual disease. Initially, surveillance colonoscopies should be performed once or twice per year.

Because first-degree relatives of patients with SPS are at an increased risk for the development of colorectal cancer, the screening colonoscopy of this patient group should begin at age 40, or 10 years prior to the age at which any advanced colorectal neoplasia has occurred.

Excerpted from:

References:
Bourke M. Tech Gastrointest Endosc. 2011;13(1):35-49.
Holt BA, et al. Clin Gastroenterol Hepatol. 2012;10(9):969-979.
Kahi CJ, et al. Clin Gastroenterol Hepatol. 2011;9(1):42-46.
Kudo S, et al. J Clin Pathol. 1994;47(10):880-885.
Leggett B, et al. Gastroenterology. 2010;138(6):2088-2100.
Snover DCA, et al. Serrated Polyps of the Colon and Rectum and Serrated (“Hyperplastic”) Polyposis. Berlin: Springer Verlag; 2010.

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