The Serrated Polyp Pathway: Is It Time to Alter Surveillance Guidelines?

Abstract

Purpose of the review In this manuscript, we review current surveillance guidelines for serrated polyps (SPs) and discuss how recent studies inform the selection of appropriate surveillance intervals for patients with SPs. Recent Findings Large and/or proximal SPs, particularly sessile serrated polyps (SSPs), are associated with increased risk of both synchronous and metachronous neoplasia, including advanced adenomas and colorectal cancer (CRC). Persons harboring multiple SSPs or dysplastic SSPs are at the highest risk. Moreover, a high percentage of large and/or proximal SPs are reclassified as SSPs when read by trained gastrointestinal pathologists, even if they were originally reported as hyperplastic polyps. These findings support the adoption of surveillance guidelines that prescribe closer surveillance of large and/or proximal SPs, regardless of subtype. Summary SSPs remain a challenge to reliably identify, resect, and diagnose via histology. The increased risk of future neoplasia in patients with SSPs is likely driven by a combination of underdetection, inadequate removal, misclassification, and biology. Until further evidence emerges, we support guidelines that recommend close surveillance of patients with a history of large and/or proximal SPs and SSPs specifically in order to mitigate the threat of interval CRC.

Receptor tyrosine kinase fusions act as a significant alternative driver of the serrated pathway in colorectal cancer development

“…An alternative CRC Kinase fusions in colon sessile serrated lesions 81 tumorigenic pathway, known as the serrated pathway, has been proposed recently. SSL has been recognized as an important malignant precursor and implicated in the development of interval cancer [21]. The development of CRC through the serrated pathway is believed to involve BRAF/KRAS mutation, CIMP, and microsatellite instability [6].…”

“…Tumor diameter was measured and documented every 3 days for 2 weeks. To evaluate the effect of RET kinase inhibitors in this model, mice were assigned randomly to different groups (n = 7/group) 2 weeks after inoculation when the tumor sizes reached approximately 50 mm 3 , and given an oral dose of either cabozantinib (30 mg/kg), vandetanib (40 mg/kg), or vehicle for seven consecutive days (Days [16][17][18][19][20][21][22]. At the end of investigation, mice were sacrificed and xenografts were collected for diameter check and weight assessment.…”

Endoscopist factors that influence serrated polyp detection: a multicenter study

“…First, this means that the SPDR metric is somewhat of a misnomer, as technically, hyperplastic polyps are also serrated polyps [35]. Second, some pathologists may misclassify SSPs as hyperplastic polyps [36], which may explain why hyperplastic polyps in the proximal colon are associated with higher risk [37 – 40]. Therefore, some of the variation we observe across endoscopists could be due to differences in pathologist readings, as has been described in other studies [13].…”

Serrated Lesions in Inflammatory Bowel Disease: Genotype-Phenotype Correlation

“…27 In IBD patients, close surveillance of multiple, large, especially proximally located lesions has been recommended. 20,28…”