Episode 192 - Introduction to Colon Polyps with Dr Ali Eqbal
Colon polyps develop on the inner lining of the large intestine or rectum and are medically significant, as a small percentage may subsequently develop into colon cancer.
They affect roughly 15% to 40% of all adults and become increasingly frequent with age. Whilst we are now observing an increasing prevalence of polyps and colon cancer in young adults, they are still relatively uncommon before the age of 40 years.
Colorectal polyps are found in about 25% of adults aged 45 years. By age 50 years, approximately 40% to 50% of people will develop at least one polyp, slightly more in men than women.
Polyps generally fall into two main categories: non-neoplastic, including hyperplastic polyps, inflammatory polyps and hamartomas; and potentially neoplastic polyps, which include adenomas and sessile serrated polyps. Distinct molecular pathways underlie the development of each polyp subtype. While harmless initially, adenomas and sessile serrated polyps are considered precancerous and may develop into invasive cancer over time. Fortunately, only a small minority, approximately 5% to 10% of conventional adenomas and an estimated 2% to 6% of isolated non-dysplastic sessile serrated polyps (SSPs), will ever progress to malignancy.
Conventional adenomas progress to cancer via a traditional adenoma-to-carcinoma pathway, a relatively slow process that may take 10 to 15 years. The risk of malignancy depends highly on the microscopic growth pattern of each adenoma. In this genetic sequence, APC gene mutation activates, in turn, the Wnt/β-catenin pathway, which promotes dysplasia development in daughter cells arising from colonic crypts. Additional mutations, including KRAS activation and TP53 loss, result in progressive accumulation of mutations, changing the polyp from harbouring low-grade dysplasia to one with invasive carcinoma.
Tubular pattern adenomas are the most common subtype (representing ~80% of adenomas) and carry the lowest risk of transformation, with fewer than 5% becoming malignant. Tubulovillous adenomas have a mixture of growth patterns and carry an intermediate risk of 10% to 20%. Villous adenomas are less common and are characterised histologically by finger-like projections of tissue. These adenoma types carry the highest risk of malignant progression, with 20% to 25% potentially developing into cancer, with the risk increasing as they grow above 2 cm in diameter.
By contrast, sessile serrated polyps (SSPs) develop through an alternative biological pathway characterised by specific genetic mutations (including BRAF). They are flat, often hidden under a mucus cap, tend to be more right-sided in location, and are historically difficult to spot during a colonoscopy.
For an isolated non-dysplastic SSP, the 10-year cumulative risk of becoming cancerous is relatively low, at around 2% to 6%. When dysplasia is present, however, the malignant potential is much higher. Such polyps may progress to cancer much more rapidly. Studies show dysplastic SSRAs may be harbouring invasive carcinoma in 12% to 23% of cases.
For all potentially fatal neoplastic polyps, key risk multipliers for malignancy include size greater than 10 mm, the presence of high-grade dysplasia, and multiplicity (three or more), which indicates more aggressive genetics or colonic environment.
By contrast to the adenoma-carcinoma sequence driving traditional adenoma development, sessile serrated polyps develop through the so-called serrated neoplasia pathway, which is commonly associated with BRAF mutations that keep intracellular signalling constitutionally active. This is often coupled with CpG island methylation (CIMP), which is a process that silences mismatch repair genes, especially MLH1, leading to microsatellite instability (MSI) and aberrant cell division.
There is a lot of information that we have just discussed in relation to polyps. The bottom line is that colorectal surveillance by colonoscopy is essential. Colon cancer surveillance and screening have been shown to reduce colorectal cancer (CRC) incidence by approximately 50% to 90%. This dramatic reduction is achieved primarily because colonoscopy allows direct detection and removal of precancerous polyps before cancer development.
To discuss this important topic in more detail, particularly focussing on large colonic polyp management, we are joined by Dr Ali Eqbal. Ali has expertise in advanced colonic interventional endoscopy and inflammatory bowel disease. He completed a two-year advanced endoscopy fellowship at King's College Hospital, London, where he developed expertise in the diagnosis and management of complex colonic polyps using techniques including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). He also undertook a clinical research fellowship in complex IBD at the Austin Hospital in Melbourne. He is widely respected and recognised for his advanced technical skills and commitment to minimally invasive treatment options. He has published and presented both nationally and internationally.
Please welcome Ali to the podcast.
References
National Center for Biotechnology Information (NCBI). Colonic Polyps. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK430761/