Welcome to First Incision, the podcast about preparing for the General Surgery Fellowship exam. I'm your host, Amanda Nikolic. Let's get straight into our team timeout. Our patient today is the colorectal module from the general surgical curriculum and the operation we're performing or the topics we're going to be covering today is all you need to know about colorectal polyps.
So getting straight into it, a colorectal polyp is a circumscribed mass which projects above the epithelial surface of the mucosa of the colon. The risk factors for development of colorectal polyps cover both genetic and environmental factors. So genetic factors include a personal family history of polyps or colorectal cancer, as well as genetic colorectal cancer.
polyposis syndromes, which we will talk about on another episode. Environmental factors include a low fiber diet, smoking, alcohol excess, and other factors include inflammatory bowel disease and age. Most polyps are found asymptomatically on screening colonoscopies. Large polyps can present with symptoms. They may partially obstruct the lumen of the bowel and cause pain. They may cause a change in bowel habits. They may secrete mucus.
And they may also be detected with a fecal occult blood test leading to a screening colonoscopy. Cholorectal polyps can be classified in a couple of ways. One way is based on their appearance. So talking about whether a polyp is sessile or pedunculated. A sessile polyp is like a flat polyp that arises from the mucosa and doesn't have a stalk.
versus a pedunculated polyp, which is one that extends up from mucosa with a fibrovascular stalk. And there's also other classifications like the Paris classification that goes into more detail into protruded lesion. flat elevated, flat depressed lesions, etc. But I think the sessile pedunculated are the most common ways of classifying polyps based on their appearance. In terms of another way to classify colorectal polyps, they can be classified...
depending on whether they are neoplastic or non-neoplastic. And this has to do with the histological examination of the polyp. So some neoplastic types of polyps include adenomatous polyps. Serrated polyps and non-neoplastic polyps include juvenile polyps, hematomas, and inflammatory pseudopolyps. Going into a little bit more detail about some of these types.
We'll start with adenomatous polyps, which are the most common type of colorectal polyp. They form two-thirds of all colonic polyps that are found and occur in 20% to 40% of the population. and they can occur anywhere throughout the colon. They arise from the mucus secreting colonic epithelial cells and are considered to be a pre-malignant lesion.
And I recently heard one of the fellows say not all polyps become a cancer, but all cancers were once a polyp, which is a nice way of thinking about it. In terms of the risk of progression to a cancer, the risk increases with a number of factors in the polyp. So the increasing size of the polyp, so if it's more than 10 millimeters, it's more likely to progress or already contain.
and adenocarcinoma. The different types of adenomatous polyps are more likely to turn into cancer. So a villus type has a higher likelihood than a tubulovillus than a tubula, which I'll talk about in a minute. If they have dysplasia within the polyp, then it's more likely that they will turn into or already harbour adenocarcinoma. And if they are friable and ulcerated, they're also at a higher risk.
So talking about those different pathological subtypes of adenomatous polyps, there's tubular villus and tubulobilus. Tubular is the most... Common tubular adenomas make up 65 to 80% of all adenomatous polyps. And under the microscope, they're often seen as a network of branching epithelium. And these are often the pedunculated polyps. Villis are pretty rare, about 5% to 10% of polyps, adenomatous polyps are villis.
adenomas and under the microscope you'll see long glands that extend from the surface to the center of the polyp and they're like finger-like projections is the buzzwords for a villus adenoma and these are more likely to have a sessile macroscopic appearance and are more likely to have atibia or dysplasia and they're the type that has a higher risk of progressing to an adenocarcinoma. And tubulobulus basically means that under the microscope there's a component of both of those patterns.
of the tubular and the villus, and these have an intermediate risk out of the two of developing into adenocarcinoma. Moving on now to serrated polyps. These polyps under the microscope exhibit sawtooth appearance, which is why they're called serrated polyps. And there's three different types of serrated polyps. This includes hyperplastic polyps. These are technically not... Neoplastic polyp, there's technically a non-neoplastic polyp. They are not considered to have malignant.
They're usually very small and often seen in the distal colon and rectum. It's pretty common to see lots of these little hyperplastic polyps in the distal colon and rectum. and they usually, like I said, are benign, and often you just take a small sample of a couple of these to prove that that's what they were. The other types are traditional serrated adenomas and sessile serrated adenomas.
So the traditional serrated adenomas have variable malignant potential. They're more common in the rectosigmoid and distal colon, and they can have... sort of mild cytologic dysplasia and they may look and behave like a conventional adenoma and be pedunculated and are usually around five or six millimeters in size. Under the microscope, they will have that serrated appearance, but they will have crypts with columnar cells lining those crypts and often eosinophilic cytoplasm of those cells.
Sessile serrated polyps are more concerning. They are more prominent in the right. colon or the proximal colon and the typical macroscopic appearance of these is a sort of difficult to discern polyp with a cap of mucus which can obscure your ability to see these polyps so they're difficult to find and they do have a malignant potential.
They are associated with high rates of synchronous or metancronous cancers and have a high prevalence of high-grade dysplasia. Up to 15% of them will have high-grade dysplasia.
So these are pretty important to know about and pretty important to pick up. And these two main types of polyps, the adenomatous polyps, and the serrated polyps are important to know because they are considered the pre-malignant lesions and they have different pathways to turning into cancer, which we will go into in another episode. So the other polyps just to mention, these are mostly important when talking about familial cancer syndromes. So the hematomatous polyps or juvenile polyps.
These are relatively uncommon and usually, like I said, associated with familial polyposis syndromes, including Piotr's-Yager's disease. familial juvenile polyposis, and Cowden syndrome or P10 hematomatous tumor syndromes, which again we will talk about later. So these are... macroscopically quite rounded or spherical. You should look up a photo of these. They have a very characteristic appearance. They're often pedunculated and usually have an abnormal color, sort of cherry red color.
And under the microscope, they contain mostly connective tissue, so smooth muscle, lamina propria, and also can contain inflammatory cells. And these usually don't have a malignant. and they can occur anywhere throughout the gastrointestinal tract. And with these syndromes, I guess they usually present with small bowel interception at a young age. That's the kind of characteristic presenting feature.
The last group of non-neoplastic colorectal polyps are inflammatory polyps or inflammatory pseudopolyps. And these are mostly seen in inflammatory bowel disease and can also be seen in infectious pathologies or ischemic colitis. And they're not true polyps but inflammatory infiltrates that cause a... protrusion or visible protrusion and these also do not have a malignant potential. So what should you do if you find a colorectal polyp?
Well, firstly, you're probably doing the colonoscopy because you want to find them, because we know that if we remove them, especially if they're a pre-malignant or a... neoplastic polyp that you are going to stop the ability for that polyp to progress into a colorectal cancer and this is why we have the screening programs that we do because we know that we can reduce the incidence of colorectal cancer by removing these
pre-malignant lesions. So usually you would remove it and this can be done in a variety of ways and really does depend on a thorough assessment of the polyp and an assessment of the whole colon so that you know how many polyps there are, their distribution throughout the colon and how large they are and you can make a plan to remove them. So a good polyp that would be suitable for an endoscopic resection is a polyp that has a good stalk or is pedunculated and also small sessile polyps.
If a polyp is sessile and has a wide base, especially if it looks like it's more than three centimeters in size, more than a third of the circumference of the bowel, or if it's crossing two haustral folds, then... This can be difficult to remove endoscopically with a normal polypectomy procedure. And also polyps that are close to the appendiceal orifice can also be difficult to remove with polypectomy.
Options we have for a polypectomy include cold and hot biopsy forceps, as well as cold and hot snares. So the biopsy forceps would be useful for a polyp that was very small, like one to three millimeters in size that fits into the jaws of the biopsy forcep. And the forceps are used to grab and pull the polyp tissue away from the mucosa and then the area is inspected to make sure that any residual fragments are also removed.
For a slightly larger polyp, you know, five to eight millimeters, you could also use electrocautery to help. I guess remove the polyp as well as stop any potential bleeding from the site but this increases the risk of perforation and also disrupts the tissue that you're removing which makes it difficult to then subsequently analyze that histologically. So that's something to think about in terms of smaller polyps. For larger polyps we can use cold and hot snares.
These are appropriate for larger lesions and especially for pedunculated polyps. And it's basically a wire loop that comes out of the end of the instrument. And you can put that around the base of the polyp and then pull it through to cut the polyp mechanically or use electrocautery through the loop. help you cut through the base of the polyp. We would usually use a cold snare for smaller peniculated polyps and a hot snare for larger polyps especially if they have a
thick stalk because it's likely they'll have a feeding vessel in there. But it's really important that you're careful not to snare a deep fold or a layer underneath the mucosa as this can cause transmural injury, especially if you're using electrocautery. and perforation. Some other options if you have a polyp that isn't really suitable for endoscopic polypectomy, such as those larger polyps, sessile polyps, or those that are close to the appendiceal orifice, is that you can
either refer the patient to a gastroenterologist or a surgeon with appropriate skill to do an endoscopic mucosal resection. And this is basically an adaptation of that snare polypectomy technique where an injection of... gel effusion and usually with a blue dye in there is injected into the submucosa to lift the polyp and this is important so that you know that there is an invasion deep to the submucosa that polyp should lift nicely with this injection.
And then following that, the specimen is removed in a piecemeal fashion using that wire loop to take systematic pieces of the polyp and also often uses electrocautery as well with the resection. This procedure can be quite effective. It's worth looking up some videos if you've never seen it before and can achieve good resection of the polyp.
But it may require additional procedures to completely remove the polyp, especially if it's very large, and obviously needs close surveillance of the area. And some downsides are obviously that it is removed piecemeal and that electrocordia is used. larger polyp which has a higher risk of harboring malignancy it can be more difficult to evaluate whether the tumor has been completely removed how deep the polyp is or the abnormal tissue is extending and therefore ruling out any invasive component.
And also requires someone who's very experienced at this procedure so that they can identify concerning features such as they're not lifting properly or abnormalities on the narrowband imaging that would make you more suspicious of an invasive component. and therefore early recognition that that's not a lesion that's appropriate for AMR. Another procedure that can be used for endoscopic resection of polyps is endoscopic submucosal dissection.
which is something that I've seen used a lot in esophageal and gastric polyps or malignancies. But from what I can glean, this isn't something that's used as commonly in colorectal because of the risk of perforation. When talking about colorectal polyps, I cannot not mention the clinical practice guidelines on the Cancer Council Australia website.
This website is wiki.cancer.org.au and it's got a number of guidelines that are really handy for... colorectal polyps and colorectal cancer and pretty easy to navigate sidebar with you know different advances and clinical tools and especially surveillance after polypectomy.
So I won't go into this in too much detail because it is quite complex depending on... how many polyps are removed where they're removed from whether they're adenomas or serrated polyps etc etc as well as considering family history previous history of bowel cancer, but in general, I'll run through a couple of different follow-up guidelines. So for a patient who has an adenoma removed,
It depends on the number of adenomas. So there's a little table saying that if there's only one to two adenomas removed and there's no high-grade dysplasia and there's no villus. so it's not a villous adenoma, then these patients could have another colonoscopy in...
10 years, as long as they don't have metabolic syndrome, a family history, and also you could consider doing fecal occult blood tests for these patients after four years from the colonoscopy. If a patient has... three to four polyps removed and again no high-grade dysplasia or villus changes then you would repeat that colonoscopy in five years and then if there's five to nine adenomas removed you would do a colonoscopy in three years and if there's more than 10 then in one year.
And this interval changes. So if there's any high grade changes or vealus changes, then the screening interval would be reduced in time. And then if the polyps that you remove are over 10 millimeters in size, and again, if there's any high grade. changes or villus changes then those intervals are shortened again. So it's worth having a look at there's some nice sort of summary tables on the clinical practice guidelines.
And then for serrated polyps, it again depends. So if there's one to two polyps removed and they're all serratus polyps, but they're less than 10 millimeters in size, there's no dysplasia or... traditional serrated adenoma, they're sessile serrated adenomas, then If there's one to two, you would repeat the scope in five years. If there's three to four in three years, and if there's more than five in one year, and if there's any dysplasia.
If it's a traditional serrated adenoma or if it's more than a centimeter in size, again, you would repeat the colonoscopy earlier. Again, there's a lot of variations in these guidelines depending on individual factors. So it's good to have an idea about the sort of common presentations, but also to have a look and see all the different things that may change your surveillance interval. So although I wish I didn't have to go into this, I think I can't not
talk about malignant polyps and also the polyp to colorectal cancer pathways when talking about colorectal polyps. So first thing to talk about is malignant polyps. So this is where you get a polyp that when you excise it, you find that there is a malignant or invasive component. So reminding ourselves of the layers of the bowel wall, there is the mucosa and the mucosa is comprised of the epithelium and then the lamina propria and then under that, the muscularis mucosae.
Underneath that layer is the submucosa and underneath that is the muscularis propria, followed by the subserosa and then the serosa. So an in situ... malignancy or in situ cancer is placed in the mucosal layer, not invading through the lamina propria. Intramucosal carcinoma is characterized by invasion into the lamina propria.
And once the carcinoma spreads into the submucosa, that is when the polyp is considered to have become malignant. And that is when it gains the ability to spread to lymph nodes or to distant sites. When considering malignant polyps, there are two classification systems we need to be aware of. The first is the Haggett classification, and this is talking about malignant pedunculated polyps.
The second is the Kikuchi classification, K-I-K-U-C-H-I, which is talking about malignant sessile polyps. So the Haggett classification... basically divides the depth of invasion of the invasive cancer component of the polyp into one, two, three, or four. 1 is where the carcinoma is invading into the submucosa but only in the head of the polyp. Level 2 Haggert classification is where the carcinoma is invading into the submucosa in the neck of the polyp.
Level three is where the carcinoma is invading submucosa into the stalk of the polyp. And level four is where it's invading below the stalk of the polyp. And it's worth looking at a picture of this. so that you can get a better idea about what this exactly looks like. The next one, the Kikuchi classification, is for sessile polyps, so for those flat polyps that don't have a stalk.
These are divided into SM1, SM2, and SM3. And these split the submucosa up into thirds. So SM1 is the carcinoma invading into the top one third of the submucosa. SM2 is carcinoma invading into the middle third of the submucosa and SM3 is carcinoma invading into the deepest third of the submucosa. And the reason we have these different classification systems is because the different levels or depth of invasion correspond to the likelihood of...
that malignant polyp having lymph node metastases. And this is really important when we're talking about how to counsel that patient about their future risk and whether or not you should be suggesting a... formal resection to try to minimize their risk and to remove those draining lymph nodes. So for the Haggett classification, Invasion level one, two, or three is associated with a very low risk of having any lymph node metastases versus invasion into the submucosa below the...
neck of the polyps, a level four, is associated with a lymph node metastasis rate that's between 12 and 25%. So that's significantly high enough that you would suggest a resection for those patients. For the Kikuchi classification, SM1 and SM2 have a low risk of lymph node metastases. So an SM1 is 0% to 3% risk, and an SM2 is up to sort of an 8% or 10% risk, which balanced against the risk.
surgery could be considered, depending on other factors, to be a reason to or a reason not to do any further surgery. But SM3 is associated with a 25% risk of lymph node metastases. So again, that risk is high enough that you would be suggesting a formal oncological resection for that patient.
There are some other things that are also considered though that make the patient higher risk of having lymph node metastases and will add to your decision making about whether to or not to suggest a resection. So some high risk... Features that would make you more concerned about lymph node metastases and more likely to suggest surgery are if the tumor is poorly differentiated, if the margin of resection is less than one millimeter.
And this can be particularly difficult to determine, especially if there's been a hot snare removal because that margin has been diathermied and can be difficult to interpret pathologically. pallet was removed piecemeal, then again, that makes it more difficult to know whether or not you've definitely got a clear margin. So that may influence your decision-making.
if there's presence of lymphovascular invasion, and also if there's evidence of tumor budding. So these are all high-risk features. And in these situations, you would be more likely to suggest that you do a formal resection because the risk of that patient having lymph... node metastases is higher. So on the flip rise of that, if you have a pedunculated polyp that's Haggart level 1 to 3 or a sessile polyp that's SM1 or 2, that's well differentiated.
that you've got a one or two millimetre resection margin. that it's been removed on block and there's no evidence of lymphovascular invasion, then you would be more likely to say, look, the risk is very low of any lymph node metastases and you would just surveil that patient. So these are all things to consider.
There's also a risk prediction score that you can use, which the St. Mark's lymph node positivity model can be done online. And this helps you balance the number or estimated risk of lymph node metastases against the risk of surgery. to determine the treatment choice for that patient. And it's important to remember that even though
these patients are at high risk, that still a significant proportion of them will not have any residual disease when you do do their resection. So if their risk of lymph node metastases is 20 or 30%, then that means that 70 to 80% of patients will undergo. a colectomy and not have any residual disease. And this is really important when you're counselling the patients about what to do to discuss with them.
So on to the last piece of today's podcast. We're going to talk about the pathways in colorectal cancer. Oh, I really don't want to do this. But at least my notes will be there for me to listen back to and cram before the exam as well. So let's do it. So the adenoma to carcinoma.
sequence. So this is looking at the adenomatous polyps. This is the most common and sort of well-researched pathway of development of colorectal cancer. And I'm just going to give you the summary version of this pathway. This is also known as the conventional pathway and also the CIN or chromosomal instability pathway. And this is the pathway that happens in most sporadic.
colorectal cancers, as well as in FAP associated cancers. And I suppose I'll have to do another podcast about familial cancer syndromes, but basically same pathway. The adenoma to carcinoma sequence is a pathway where multiple cumulative genetic changes happen that progresses the adenoma into a... early adenoma, intermediate, late adenoma, and then into carcinoma and subsequently into metastatic cancer. This begins with an inactivation mutation in the APC gene.
And this is what causes an early adenoma. The next genetic abnormality is the KRAS mutation. And the KRAS gene is involved in the EGFR signaling. which is important in proliferation. And 50% of colorectal cancers have this mutation. And this is what progresses an early adenoma into an intermediate adenoma. The next mutation is the SMAD4 mutation or also the deleted in colorectal cancer mutation can also be mutated here. And this changes an intermediate adenoma into a late.
And the last hit that changes a late adenoma into carcinoma is a TP53 mutation. The important things to remember from that particular pathway... is that the KRAS mutation, which I said 50% of colorectal cancers will have, is important to know because we have a targeted monoclonal antibody therapy to the EGFR receptor, which can help improve. improve survival in these patients. The next pathway to talk about is the serrated pathways. This is the pathway where we have the serrated polyps.
And this is how they turn into colorectal cancers. And it was more recently discovered that this was a separate pathway. This is also known as the hypermethylation pathway and about 30% of colorectal cancers are thought to be formed through this pathway. So the key genetic mutations that are involved in this pathway The first one is a BRAF mutation. And this is the key initiating event that changes normal mucosa into a serrated polyp.
BRAF is an oncogene and it's in the same sort of pathway or group as KRAS. The next abnormality that happens is how the pathway gets its name, the hypermethylation component. And this is where you get inactivation of MLH1, which is one of the mismatch repair genes. And this is inactivated due to hypermethylation of the promoter region of the gene, so not actually through a genetic mutation in the MLH1 gene.
And this basically changes a hyperplastic polyp or a serrated anenoma into a dysplastic polyp and then into a carcinoma. So some interesting facts about this pathway is that these sorts of tumors are more common in women and also more common in the right colon, as are the sessile serrated adenomas that we talked about earlier. They have a slightly better prognosis than the adenoma to colorectal cancer pathway. And a key thing here is that they don't respond as well to 5-FU-based chemotherapies.
These tumours will have a BRAF mutation, not a KRAS mutation like the conventional pathway has. So that's one test that can differentiate between the two. The last pathway to talk about is the microsatellite instability pathway. And microsatellites are short tandem repeats in DNA. Accumulation of DNA mistakes or tandem repeat mistakes is called microsatellite instability. And this pathway is associated with Lynch syndrome or HNPCC, hereditary non-polyposis colorectal cancer, which are...
Very similar things. And again, I will talk about in our familial colorectal cancer syndrome talk. But basically, these begin with a germline mutation because they're inherited syndromes in the mismatch repair genes. And these genes are MLH1. MSH2 and MSH6 and PMS2. And these mutations basically mean that there's accumulation of DNA mistakes or issues with mismatch repair leading to DNA mistakes and microsatellite instability, which then leads to carcinoma. So those...
Mismatch repair genes, the MLH1, MSH2 and 6 and PMS2 can be stained for on the tumour with immunohistochemistry to show whether or not the normal expression of those genes is present or not. And if any of those genes or the immunohistochemistry for those genes shows that it's not present, then...
PCR testing for microsatellite instability can then be performed to determine whether or not there is actually a mutation in those genes. Because remember, with the serrated pathway we talked about, there's inactivation of the MLH1, so it will stain. as not present in the sess ulcerated pathway as well. But that doesn't mean that they have a germline mutation in one of those genes. It's just that that gene has been inactivated through hypermethylation. So it's important to test for that.
you find that the staining is abnormal. And the other thing is that the microsatellite instability pathway should not have a BRAF mutation, which is that first step in the serrated pathway. So those are ways that you can tell those apart. And also usually the microsatellite instability pathway won't have abnormalities in KRAS, but it can have KRAS abnormalities.
There's definitely a lot more to talk about in regards to these different genetic pathways and their links to those familial cancer syndromes, but we might save that for another day. Thanks for bearing with me, even though I had a good old whinge about doing genetic pathways in colorectal cancer. Definitely wasn't as painful as I had been expecting, which just goes to show how much all of this study stuff is actually in our heads.
Until next time, happy studying and don't forget to rate, review and subscribe so that other people can find this podcast. It's time to close up. Thanks for listening to First Incision. If you have any comments or feedback, send us a message at firstincisionpodcast at gmail.com or follow us on Instagram at firstincision. Happy studying!