Welcome to First Incision, the podcast about preparing for the General Surgery Fellowship exam. I'm your host, Amanda Nikolic. Hello. Thanks for joining me today for another episode of First Incision. Let's get straight into it with our team timeout. Our patient today is the colorectal module from the general surgical curriculum.
And today our patient or the topic we're going to be talking about is an introduction to colorectal cancer. This is quite a large topic, so I've decided just to do... everything up until treatment for now and we will go into treatment in another episode. So a bit of background. Colorectal cancer is a very common malignancy. In Australia, there's over 15,000 new diagnoses each year. And the risk of being diagnosed with a colorectal cancer by the age of 85 is 1 in 11 for men and 1 in 16 for women.
The five-year survival is 57%, but this obviously depends on the stage of diagnosis, with earlier stage cancers having a better prognosis. The majority of colorectal cancers are found in the left side or in the rectum. So 50 to 70% of cancers are found in the left colon or in the rectum. And it's the second most common cause of cancer deaths each year. In terms of definitions or cutoffs, colon cancer can be considered a tumour anywhere proximal to the rectum.
But rectal cancer and where the rectum starts is sometimes a little bit difficult to determine clinically. And there's various definitions, whether that's the end of the sigmoid mesocolon. or at the point that the tinea coli become circumferential longitudinal muscle layer around the bowel again. And this is thought to be around 12 to 15 centimetres from the anorectal verge, depending on what text you look at. Another couple of definitions, so a synchronous.
Metastases is a metastases within six months of the diagnosis of colorectal cancer, and metanchronous metastases are more than six months from the diagnosis of colorectal cancer. And the same definition applies to a synchronous tumour, which is one found within six months of another tumour being diagnosed. And a metachronous colorectal cancer is another colorectal tumor being found more than six months after the first cancer was diagnosed.
The etiology or risk factors for the development of colorectal cancer can be spread up into genetic, modifiable and unmodifiable risk factors. So the genetic risk factors are all of those conditions that I discussed on our recent episode on colorectal cancer syndromes. So these are polyposis syndromes, including FAP, MAP, Piotrziagas. juvenile familial polyposis and serrated polyposis syndrome, and non-polyposis syndromes including HNPCC and Lynch syndrome. Modifiable risk factors include diet,
So there was a large World Cancer Research Fund report in 2007 that talked about foods and activities that could be associated with development of different cancers. And for colorectal cancer, there was an increased risk with red meats. processed meats, alcohol, animal fats, sugar, and obviously patients who are obese and also who smoke.
Unmodifiable risk factors for the development of colorectal cancer includes ulcerative colitis and Crohn's disease, which do increase your risk of development of colorectal cancer, being of the male sex and having diabetes. So I'm going to talk a little bit about the different presentations of colorectal cancer, as well as screening and workup of colorectal cancer.
So patients can present in a variety of ways, depending on the location of the tumor and the size of the tumor and whether or not there's any metastatic disease. So patients may present with abdominal pain or bloating, PR bleeding. anemia, weight loss, change in bowel habit, an abdominal mass or tenesmus if they have erectile cancer.
They may also have evidence of complications, local complications such as pneumaturia if there's a tumour invading into the bladder or faecal vomiting and diarrhoea if there's a gastrocolic fistula. Patients can also present in an emergency setting with obstruction or perforation. And they can also present after an asymptomatic or screening investigation. So in Australia, we do a...
Immunochemical Fecal Occult Blood Test. And this is part of our National Bowel Cancer Screening Program. And this is offered to patients every two years between the ages of 50 and 74. If fecal occult blood is detected, then these patients are referred for a colonoscopy. And just to take a totally random segue into screening tests, there's the 10 WHO principles for screening.
I know this has previously come up before in the exam. And these principles are that you have a cancer that is an important health problem that has a recognizable latent or early symptomatic. that the biology is well understood, which we know it is for colorectal cancer because we've talked about the pathways, that there should be an accepted treatment for patients diagnosed with a recognised premalignant disease, in which case there's polypectomy.
That there is an effective and accurate screening test available, which is the fecal occult blood test, followed by colonoscopy if it's positive. That there's agreement on who should be screened, so the evidence is those patients. between 50 and 74, unless you're in one of three higher risk categories, that there are facilities for diagnosis and treatments available, which there is in Australia.
That there is an economic balance case for screening in relation to healthcare expenditure, which obviously removing a polyp before it becomes a cancer has been proven economically to be better than treating established malignant disease. and that screening can be performed as a continuous process. And colorectal cancer screening, along with breast and cervical cancer screening, are the only cancers that actually meet all of these 10 WHO principles, and that's why we have this established.
screening program in Australia. And the aim of this program is obviously to reduce the morbidity and mortality of colorectal cancer by early detection and also preventing it by removing pre-malignant adenomas. So getting back to colorectal cancer screening, it's worth having a look at the wiki cancer guidelines because there are three...
groups that are considered to be higher risk of colorectal cancer that are suggested to have a different screening program. And this is separate from those patients who have an established high risk familial. cancer syndrome, which have their own screening guidelines. So these three...
categories include category one, which is a low risk, which has a five to 10% lifetime risk of the development of colorectal cancer. And these patients are offered a fecal local blood test slightly earlier, so from 45 years instead of 50 years. is. Category 2 is a moderate risk category. So this is 15% to 30% lifetime risk of colorectal cancer. These patients are offered a fig local blood test from age 40 and also a colonoscopy every five years and also low-dose aspirin.
and prophylaxis should be considered. The third group is category three, and these are high risk patients with a 30 to 40% lifetime risk of development of colorectal cancer. And they get a fecal occult blood test every two years from 35 years old.
a colonoscopy every five years from 45 years old, as well as low-dose aspirin prophylaxis. And the different risk categories are determined based on the family history. So category one is one... a first degree or second degree relative with a colorectal cancer diagnosed at more than 55 years old. Category two is one first degree relative that was less than 55 years of diagnosis or two first degree relatives with colorectal cancer at any age or...
one first degree relative and more than two second degree relatives diagnosed with colorectal cancer at any age. And category three is more than three first degree relatives or second degree relatives with colorectal cancer diagnosed at any age. So when seeing a patient who's presenting with...
red flag symptoms and you're suspicious for a colorectal cancer or they have a positive fecal occult blood test, the next step is a colonoscopy. Firstly, to diagnose whether there is a tumor there and secondly, in order to obtain a tissue diagnosis. So a colonoscopy, as we all know, is an endoscopic examination of the colon from the rectum to the ileocecal valve.
And this is the gold standard investigation that all patients who are suspected of having a colorectal cancer should undergo. And it's important to remember that approximately 3% to 5% of patients will have a synchronous. cancer. So a full colonoscopy should be performed to rule out other cancers. So once you've taken a biopsy of a
colorectal mass, you then need to determine what it is exactly. And this is done by histopathological examination. So there are different types of cancers that can form in the gastrointestinal tract and in the colon. The one that I'm going to talk about today is adenocarcinoma, which is the most common. More than 90% of cancers of the colon are adenocarcinomas. Other less common forms of cancers found in the gastrointestinal tract include
neuroendocrine tumors, squamous cell cancers, spindle cell and undifferentiated carcinomas. But talking about adenocarcinoma, the majority of these are just a conventional adenocarcinoma. And under the microscope, these are characterized by gland formation. And the amount of gland formation or differentiation of the tumor is what determines whether it's well differentiated or poorly differentiated. So within this umbrella of adenocarcinomas, there's different histological variants.
And these include mucinous, signet ring cell, and medullary, which are the three more common. And there's some others that are mentioned in the WHO classification that include micropapillary, serrated. cribriform, comedo, adenosquamous, spindle cell, and undifferentiated. But I'm only going to go into those first three because they're the most common and the sort of most well-known, I would say.
So the first is the mucinous adenocarcinoma, and this makes up about 10% of adenocarcinomas. And this is classified as more than 50% of the tumor volume is composed of extracellular mucin. The second is signet ring cell adenocarcinoma, and this is less than 1% of adenocarcinomas. And the diagnosis histopathologically...
requires at least 50% of tumour cells to show signet ring cell features. And it's worth looking at a photo of what that actually looks like. Once you see it once, you'll remember it. And these are often very poorly differentiated high-grade tumours. And then medullary carcinoma is the last one. And this is where you get sheets of epithelioid neoplastic.
cells, and they often have a pushing border and tumor infiltrating lymphocytes. And this is one of those ones that I mentioned in the familial cancer syndromes to be associated with Lynch syndrome and same for the signet ring cell adenocarcinoma. Basically, the signet ring cell has a very poor prognosis and so does the mucinous adenocarcinoma, but medullary can have a good prognosis compared to the conventional adenocarcinoma.
So I briefly mentioned the grade of a tumor, whether it's well differentiated or poorly differentiated. And this is important. feature that you'll note on a pathological report about a colorectal cancer and can help aid decision making. So basically, this is determined.
by looking at the tumor under the microscope and saying how many glands are present in the tumor. The glands being a normal part of mucosa of the gastrointestinal tract showing a well differentiated tumor. And if there's not many glands, It means that it's lost its differentiation and therefore those tumours are considered to be poorly differentiated. The well differentiated has more than 95% of the tumour being comprised of glandular structures.
Moderately differentiated is 50 to 90% and poorly differentiated is 0 to 50% glandular. structures and that is also correlated with the grading you might see grade one grade two grade three with grade one being well differentiated grade two being moderately differentiated and grade three being poorly differentiated And then the TNM classification also has a grade four, which is undifferentiated, which I assume means no glands. Some other features that you may...
read about in the pathology report that are important is to note whether there is any lymphatic or vascular invasion, which is a poor prognostic feature. Also to know how far the tumor has invaded through the wall of the bowel and we'll go into this a bit more with the TNM staging and there are other features which haven't been
as well proven to be associated to prognosis that include perineural invasion, tumor budding, and if there's any discontinuous extra mural tumor deposits which aren't associated with lymph nodes. The other thing you might find in your pathology report are some additional tests. And these correspond again to the first two episodes we've done on colorectal, which are the...
colorectal polyps and talking about the genetic changes that happen in the polyp to carcinoma pathway, as well as with the familial cancer syndromes. So the first thing that you'll get is... about the mismatch repair enzymes. So this is immunohistochemistry staining for the MLH1, MSH2, MSH6, and PMS2 enzymes or proteins. And this is... basically done for all colorectal cancers in Australia, especially in patients who are under the age of 70. And if any of these
proteins are missing or if any of the staining for any of these mismatch repair enzymes is missing, then microsatellite instability testing should be done, which is a PCR test. And this is looking for the genetic change associated with Lynch syndrome. The other thing you may get or maybe ask for is whether there's a BRAF or a KRAS mutation. The BRAF mutation can help you distinguish between a familial Lynch syndrome cancer and between a sporadic.
So often in Lynch syndrome, the BRAF is not mutated, but in sporadic cancers with hypermethylation of the MLH1, and this is that serrated pathway that we talked about in the first colorectal episode. then the BRAF is often mutated. The KRAS gene mutation may be looked for, and this is not necessarily associated with which pathway the tumor has formed, but it's important because we have a... antibody directed against EGFR, the epidermal growth factor receptor, which the KRAS...
gene basically encodes. And this can be used in these tumours, especially in metastatic disease, to treat them and is associated with a better prognosis. Colorectal cancers on immunohistochemistry will often stay in positive for CK20, CK7, and CDX2. So once a colorectal cancer has been diagnosed, the workup of these patients should include a completed colonoscopy. So that's really important if a patient's only had a flexible sigmoidoscopy or a DRE.
Patients should also have a CEA blood test taken, which is carcinogenic embryonic antigen. This is not a specific marker for colorectal cancer and is not a diagnostic. but it can be useful in monitoring treatment response and also for surveillance. So it's worth having a baseline CEA level. A CEA can also be elevated in other cancers, including gastric, pancreatic, lung. breast and thyroid, and also can be elevated in non-cancer.
situations such as with ulcerative colitis, pancreatitis, cirrhosis, patients with COPD, hypothyroidism, and also in smokers, which is good to be aware of. These patients should also be staged with a CT chest, abdomen and pelvis with oral and IV contrast. And the report should include...
the location, size, and local extent of the primary tumor, noting any invasion of surrounding structures and any complications such as obstruction. And it's really important if there is obstruction there that you... determine whether or not that patient has a competent or incompetent ileocecal valve as if they have a competent valve and an obstructing cancer you have an effective closed loop obstruction and that makes this an emergent situation.
I should also comment on the evidence of any local regional lymph node involvement, as well as any metastatic disease, which commonly is found in the liver and in the lungs. sites for spread of colorectal cancers include direct, lymphatic, blood-borne and transcelemic. So direct.
Spread can include tumor spread through the wall of the bowel and into surrounding structures, which can include pretty much anything in the abdomen, depending on the location of the tumor, but often involves the duodenum. the ureters, the posterior abdominal wall and also other abdominal organs such as small bowel, stomach or pelvic organs including the bladder and vagina.
Patients can have lymphatic spread, which often goes from the bowel wall into the mesenteric nodes and then up to the para-aortic glands. But if you have a very low rectal anal cancer, these can spread to the... internal iliac vessels or iliac lymph nodes as well as the inguinal lymph nodes.
Spread can be via the blood, which is part of how you get liver mets via the portal system. And patients have about a 30% chance of having liver mets at the time of operation after being diagnosed with a colorectal cancer and about a 50%. lifetime risk of developing liver metastases. The next common spot, like I mentioned, is the lung, but patients can also get spread to the ovaries, adrenal glands, bone, brain, and kidney.
And then transcelomic spread is throughout the peritoneum, either through the subperitoneal lymphatics or if there is a perforated tumor or a tumor that's T4 and invading. through the serosal surface of the bowel, then this can shed cells into the peritoneal cavity and cause peritoneal carcinomatosis.
In Australia, PET scans are not funded by the MBS for preoperative staging of colorectal cancer, but it is funded if active therapy is being considered for a patient with a suspected metastatic colorectal cancer. suspected recurrent or suspected residual colorectal cancer. And if a patient's being considered for resection of liver or lung metastases, then a PET scan is really important to make sure there are no additional metastases.
The other imaging study that is routine for rectal cancers only is an MRI of the pelvis. And this is a gold standard investigation, which is really important for the T and the N staging of. rectal cancers.
This is a high-resolution MRI covering the L5-S1 junction all the way down to the anal verge. And some really important features to note on an MRI report for rectal cancer is the distance of the tumor from the... anal verge as well as the distance of the tumor to the puborectalis sling and if there's any involvement of the sphincter muscles. as well as the relationship to the peritoneal reflection, especially the anterior peritoneal reflection.
because rectal cancers are treated different from colon cancers. And whether or not you treat a rectal cancer with neoadjuvant chemoradiotherapy is determined by whether or not it is below the anterior peritoneal reflection. High rectal tumours above this point are managed as colon cancers and often with primary resection.
It's also important to note the T stage of the tumour, which can be given to you from the MRI imaging, which gives you the distance that the tumour appears to have spread through the wall of the bowel, and also if there is any involvement of any adjacent organs. They'll also comment on whether there are any suspicious...
mesocolic lymph nodes and the presence of any extramural venous invasion and whether it's contiguous or non-contiguous. And this is something that in the last few years has been noted and is associated with prognosis. Another really important thing is whether or not the tumor is involving the potential circumferential resection margin. We talk about the total mesorectal excision in...
Rectal cancer as being a really important factor to reduce local recurrence and distance recurrence of rectal cancers. And so if you have a tumor that's involving your TME plane or your circumferential resection margin, then you would probably consider... to try to downstage that patient with neoadjuvant treatment first and you need to be really aware of that when you're doing the operation to make sure that you are getting the entire tumour.
Also, they may be able to note presence of involved pelvic sidewall lymph nodes, which are outside of the mesorectum, which obviously has important prognostic information for a patient about whether or not you're going to be able to completely remove. their cancer. I'm not really clear on whether or not post neoadjuvant treatment imaging is done. I've seen it done for some patients, but not all patients. And this will be something that I ask my special guest when I get them on the program.
There used to be some comment about doing endoscopic ultrasound or endoanal ultrasounds to try to look at the T stage of tumors, but this has really been superseded by MRI. So this takes us into the staging of colorectal cancers. And the staging classification system that I've seen most commonly used is the TNM staging system from the 8th edition of the AJCC guidelines.
So first talking about the T-staging, tumor in situ is carcinoma in situ, TIS, and this is where you have a tumor that only involves the mucosa with no extension through the muscularis mucosa. T1 invades through the submucosa. T2 invades into the muscularis propria. T3 invades through the subserosa. and T4 invades the visceral peritoneum or other organs or structures.
AT4A being tumor penetrating the surface of a visceral peritoneum. And this includes gross perforation of the bowel through an area of the tumor or inflammation. and T4B is where the tumour directly invades other organs or structures. Looking at the N status now, there's N1 and N2. So N1 is where there is one to three regional lymph nodes involved. And this is macrometastases only. So more than...
a 0.2 millimetre deposit of tumour. So if there's isolated tumour cells which are less than 0.2 millimetre deposits, the same as for breast cancer, then these are considered an N0 disease. N1 can be split into N1A, B, and C. N1A is one regional lymph node. N1b is two to three regional lymph nodes. And N1c is where there's no lymph nodes, but there is tumor deposits in the subserosa, in the mesenteric fat, or in non-pericolic or perirectal.
tissues. N2 disease is where there's greater than or equal to four positive lymph nodes and that's also divided up into N2A which is four to six and N2B which is more than six lymph nodes. And M1 is distant metastases. Again, this is split up into M1A, B, and C. M1A is where there's one site or organ with METs. M1b is where there's two or more sites or organs with METs. And M1c is where there's peritoneal disease. The staging of colorectal cancer then is...
classified as zero to stage four, zero being TIS. Stage one is when you have a T1 or 2 tumor, but no lymph nodes involved. Stage two is a T3, T4 with no lymph nodes involved. Stage three is T1 to 4 and any nodal involvement, N1 or 2, but no distant metastases. And stage four is any T or N but metastatic disease. The other staging system which I'll touch on is the Dukes.
staging system which is not really used anymore but sometimes patients will come to you having had a cancer diagnosed in the past and we'll have this classification system assigned to them so it's good to know and it is also mentioned in our curriculum. So this is based on the extent of the tumor spread through the bowel wall and whether there's lymph node metastases. So a dukes A cancer is not breaching the muscularis propria.
Adukes B is breaching the muscularis propria but not involving regional lymph nodes. Duke's C is involving regional lymph nodes and there's a C1 which is where the apical node of the resection is negative and C2 where the apical node is positive. And I think this differentiation was added because it was found that the apical node being...
positive was a poorer prognostic sign and dukes d has been updated to involve distant metastases that wasn't in the original staging classification so that's good to know but really we use the tnm staging system now So that's all for this first episode on... colorectal cancer. I just wanted to do a bit of an introduction and some of those sort of interesting points and this will really be the
diving board for us to go into a bit more depth about treatment. And for treatment, I'm going to split it up into colon cancer and rectal cancer because they are very different. So stick with me in the coming episodes and we'll see how we go. Thanks so much for listening and remember 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!