Colorectal Cancer

Stay Current is a multimedia publication designed to keep healthcare professionals up to date with standards of care and new emerging ideas. Stay Current and General Surgery is edited by Jeffrey Ponsky, Mina Boles, and Harveen Lambaugh in partnership with GlobalCastMD and is recorded and produced at Cleveland Clinic in Cleveland, Ohio. So, we're here today with Dr. Conor Delaney, who is the Chairman of the Digestive Disease and Surgery Institute here at the Cleveland Clinic. He's a Professor of Surgery at the Cleveland Clinic Lerner College of Medicine, and I'm Jeffrey Ponsky, who is a Professor of Surgery at the Cleveland Clinic Lerner College of Medicine as well. And today we're going to talk a little bit about colon cancer and how you discover it and how you treat it. So, welcome Conor. Thanks for being with us. Thanks for being here, Jeff. So, the first question, let's just talk a little bit about colon cancer and colonoscopy. Is colonoscopy still believed to be important in the detection of colon cancer? Yeah. Colonoscopy is still very important. It's still the best test that we have. There is no perfect test, and we know that colonoscopy doesn't find every cancer, although it finds the vast majority, every polyp, although it finds the vast majority. But it's certainly the best thing we have. And so, it gives us obviously the ability to diagnose and get people on a treatment course when they have a cancer. But obviously, the whole other side of it is that by taking out polyps we get to prevent cancers from many others. And that's the part we can't see so easily. Right. Harder to measure, but beneficial for many people. So, you know, I'm somebody who does colonoscopy, and when you think you know it all, you start to learn something new. I've been hearing more about serrated polyps recently, and I really don't know what to make of them. Can you tell me anything about them? Sure. Sure. So, you know, I think many of us used to think of hyperplastic polyps, and there are these small hyperplastic polyps that people can get in the rectum, but sometimes on the right colon there will be larger hyperplastic polyps. And over the last five to ten years, particularly, as we've found out more, it's become clear that these weren't actually hyperplastic, and they were really polyps that are better described as serrated adenomas. And the term's important for a couple of reasons. First is, there's good evidence there's a genetic predisposition, and they may tie into many of the family cancer syndromes. Second is, these polyps have a really high risk of cancer, so it's very important to deal with them. But third is that it's very important to be able to tell the patient that they're at higher risk, and to do a family assessment and decide if they do have a family cancer syndrome, and they may need to change the frequency of their colonoscopies, and they may need family members to have colonoscopy or other testing based on finding these. So it's a significant change. If we see these, and when I do a colonoscopy, and I see these little hyperplastic type polyps in the right colon, it's important to biopsy them and take them out, and to assess them. Is that right? Absolutely. And then, colonoscopy should then proceed based, like they would have true adenomas, not just hyperplastic polyps? Correct. Okay, so we've got that straightened out. Let's assume that I have a... And then maybe just to mention, then some of these are flat and are difficult to see. So I think people increasingly now, when they do a colonoscopy, will retroflex in the cecum, because often they're on the inferior or superior side of the valve, or otherwise folds in the colon and they can't be seen. So retroflexion is useful. And then if you can't get it out, just with a simple snare, you know, raise it, do an EMR, and if you're not sure, mark it, and send it to someone who may have more experience in doing a more advanced polypectomy, or even ESD. So some of these are suitable for endoscopic submucosal dissection if you do it. And then, obviously, the biggest, or those otherwise unresectable, or thought of perhaps as cancers, will need a laparoscopic or open resection. Great. So let's just go back to standard happenstance. If I'm doing a colonoscopy and I see a lesion in the rectum, and rectal cancer is a changing field all the time, and I want to try to stay updated in this area. Let's assume that I see a semi-circumferential lesion probably going around 180 degrees of the rectum. It's exophytic. It's clearly friable. I biopsy it, and this is a patient who presented with rectal bleeding. And I do the rest of the colonoscopy, and it's otherwise negative. How do we proceed with rectal cancers at, say, 6 centimeters in today's era? So I'm glad you brought up rectal cancer because it's certainly changed. Standard of care, standard of practice has changed. And it's a bit like property. So the first question is location. So 6 centimeters can be a very different thing in many surgeons' minds or gastroenterologists, and it can also be a very different thing depending on the patient. So first for the patient, 6 centimeters in a 90-pound, 80-year-old female can be almost mid-rectum. 6 centimeters in a guy who's 6'6 and 300 pounds can be the top of the anal canal or even close to the dentate line. So location becomes important. And so that swings to the surgeon's perspective. So when I think of these lower rectal cancers particularly, upper rectal cancer, a little bit more like colon cancer. But when I think of a lower rectal cancer, I'm thinking of what operation am I going to need to remove this? Okay. So let's think of first a transanal resection. Generally only done now for T1s. Many people would argue it's not even the right thing for those. So let's put transanal resection off the table for the moment and think of if you're doing a rectal resection. Well then your distal margin needs to be 5 centimeters if you can get it, 2 centimeters if you can get it, and for the very lowest tumors, perhaps 1 centimeter as long as they're not poorly differentiated. So I want to stop you a moment. I just want to stop you because I don't want to miss this point. We talked about T1 and we don't talk about that. People think about T1 and then T2 in an older fashion. We're now using new technology to develop the concept of T1 and subsections of T1 like T1a and T1b. Can you describe the workup of that rectal cancer once I give it to you? You bet, and I'm going to come to that in a second. Okay. All right. So that's a really critical question, what you're talking about, is how to work up and stage the rectal cancers. But just swinging back to this distal margin. So you know, if it's in the upper third of the rectum, you're going to get a 5 centimeter margin. They likely won't need any preoperative therapy and they likely won't need a stoma. For these middle and lower third rectal cancers, there's a good chance that they may need preoperative neoadjuvant therapy. There's a very good chance they're going to need a temporary stoma or rarely a permanent stoma. But so it comes down to that distal margin. So six centimeters from the surgeon's point of view, people describe six centimeters from the anal verge, from the anal rectal ring, and from the dentate line. And there are three very different things. Because six centimeters from the anal rectal, from the anal verge, may be the anal rectal ring or in a very big person close to the dentate line. And so you may have to do an intersphincteric resection, going in at the dentate line, taking the upper internal sphincter and doing a hand-sewn anastomosis or a stapled coloanal anastomosis to the upper anal canal. So the point I'm just trying to make there is that six centimeters doesn't mean six centimeters. It's not the same to everybody and it's not the same to every patient. And so what you're concentrating on is adequate distal margin and what type of anastomosis you may need to do. So that's kind of the, that's the property and the location. I want to take you back because I'm a simple guy. I'm just a general surgeon. And you're saying words that make me confused, interesting. Derek, let's start back again. I have this patient with a lesion at six centimeters. Let's say he weighs 70 kilograms. He's a normal size person. 70 kilograms, six centimeters. I'm right about at the middle valve sort of position. And I send it to you. Tell me the things that you're thinking about. Does this patient need endoscopic ulcerative sound? Does he need preoperative radiation? Because there's some debate about preoperative radiation. How do you select the correct operation for the correct patient? And what is the timing of that operation? So can you take me through that? He's just appeared in your office. Go ahead. Absolutely. So the other stuff is just the borderline areas where if you're not sure, you may need to seek advice or seek help because there still are options for anastomosis. But so for the more average patient with a rectal cancer, as Dr. Ponsky said, mid rectum or whatever, the next question is going to be after location, meaning this is a patient who we know we can do some kind of anastomosis. So it's someone we're going to hook up. Next question is going to be local and distant staging. So distant staging is still best with CT of the abdomen to look at the liver. And now most people and most guidelines have transitioned over to CT of chest rather than doing a chest x-ray. So patients can have one test. So you'll get a CT of chest, abdomen, pelvis, a CEA. And then really the majority of local staging has transitioned over to MRI. And Bill Heald in the UK and Gina Brown at the Royal Marsden really have done a lot of work over the last 10 or 15 years standardizing the quality and type of MRI that's done. And really with a high resolution, high Tesla magnet standardized protocol. So it's not like an MRI of the knee or something like that, or liver. It's a different protocol. You can get very high resolution images of the tumor. And that becomes important for a couple of reasons. First is T staging. It's not as good at distinguishing T1, 2, but it's particularly good at distinguishing T3, T4, and particularly good at looking at circumferential resection margins. So I talked a little bit earlier about the distal margin that you need. The next most important margin, or many really think probably the more important margin, is the circumferential resection margin. If you look back in the literature for rectal cancer, local recurrence rates in series from good institutions were 20 to 38 percent and some up to 50 percent. Nowadays, really, it should be under 10 percent. And if you look at our last 10 years, Jeff, it was about 3 percent. So if you optimize surgery, imaging, who you treat, you can get these local recurrence rates down to very low levels. And MRI is the best way to assess the circumferential margin. Endoscopic ultrasound can be used selectively for distinguishing between T1s, 2s, who might have a transanal resection, but it doesn't get the distance to look at the circumferential resection margin. And so the circumferential resection margin will allow you determine whether a standard total mesorectal excision is the right operation for the patient, or whether you need to go beyond the TME plane, meaning is this something that's locally invading sacrum, sidewall of pelvis, bladder, prostate, and do an excenteration. So this comes to the next point, which is really important, is that when you do an operation, and we'll come back to the neoadjuvant treatment, but when you do the operation on these patients, you've got to do it in a way that they have a negative pathological margin. If you have a negative pathological margin, the chance of local recurrence is low. An MRI allows one to predict that surgery very well. If you think it's going to be at risk, you're going to give them preoperative neoadjuvant therapy, or you're going to do a more extended resection. So the operation then that you do has to hit the total mesorectal excision plane, meaning you can take out a whole rectum with about 5 mils of blood loss because it's a bloodless plane. And if you've got bleeding, you hopefully are deliberately outside of that plane, but otherwise you're in the wrong plane. So the key becomes the quality of the rectal cancer surgery guided by the preoperative imaging. And so the second side of it then is using the preoperative imaging to guide a use of neoadjuvant therapy. And the most accepted guidelines for use of neoadjuvant therapy are for tumors that are T3, so outside the wall of the rectum, or that are node positive. So node negative on the MR or ultrasound, whichever you choose, if you have node negative, then you can consider omitting radiation preoperatively. Is that correct? If you've node negative and T1 or T2, so a stage one tumor, particularly if it's upper third, you'll omit. Yeah, absolutely. Now you have to remember, you mentioned ultrasound there. So if you think of accuracy of MRI versus ultrasound, because it comes down to accuracy of your testing, right? So MRI is probably 90 to mid 90s accurate at T staging, and it's probably high 80s to 90% accurate for nodal staging. And the ways it can do that are first resolution, second, you can look at characteristics of the node and characteristics of the signal to see if it's homogenous or not. Ultrasound is much more operator dependent, and it's probably only 70% accurate for predicting nodal involvement. So you would say the standard of care today is shifted from ultrasound to MR? Exactly. Okay. Let's assume, and we've taught a lot in the literature lately about the difference between T1A and T1B. Do you make any difference in them if you're just going to do a standard resection, or is that only a predictor for local resection? So it's really, yeah, so there's discussion whether T1A, T1B, or SM1, 2, or 3, but the concept being that the most superficial T1 tumors may have a lower risk of recurrence. So let's briefly talk about transanal resection then, and who's appropriate for transanal resection. And it's generally tumors that are less than a third of the circumference, ideally probably less than two centimeters, that are T1. But even with that, if you look at the historical local recurrence rates for these transanally excised rectal cancers, it was about 18%. And it was remarkably consistent across outcome data from several big centers, about 18%. So now people will often use transanal endoscopic microsurgery. So an operating, a specific operating anoscope with a laparoscopic type platform to do these. And there's suggestions, there's no level one data, but certainly better outcomes. And it's not clear whether it's the technology or just that people are understanding how to do surgery better. But the point I'm trying to make here, I guess, is with a transanal resection, it's not an operation to be underestimated. And generally still, for most people, if they're young and curable, people will tend to favor a radical resection with transanal resection as a general rule, being kept for patients who aren't fit for a rectal resection, or patients whose tumor is so close to the dentate line, you'd have to give them a permanent stoma. And so they may wish to accept a higher risk of local recurrence for the opportunity of avoiding a permanent stoma. So this is an excellent discussion. I want to make a point here to just be clear. We talk about endoscopic submucosal dissection in various parts of the colon for pre-malignant or very early malignant diseases. But in a rectal cancer, would you ever consider ESD, endoscopic submucosal dissection, or would you go to things like transanal microsurgery? I'm glad you mentioned that. So just to clarify, so if it's a rectal cancer, it needs to be a full thickness excision. So you would never do an ESD type procedure. So we commonly do ESD type procedures, or you can actually do an EMR a lot of the time. It doesn't have to be an ESD formally. But that'll be for a benign polyp. You can use a transanal platform to do that same procedure. But if it's a cancer, high risk of cancer or proven cancer, if you're going to do it, even if it's a T1, you're going to do a full thickness resection transanally. Okay. Very good. And then the question, and we won't discuss it more because I know it's a more general audience, but if it's more than a T1, then it becomes complicated. Do you do? So if you think it's T1 and the pathology comes back, T2, T3, do you come back and do a radical operation, or do you give them chemotherapy and radiation afterwards? And for the moment, let's just say it's kind of complicated and it's something you do on a case-by-case basis. So let's talk about the role of radiation in rectal cancers preoperatively. When do you use that? Right. So as we said briefly, it's generally for T3 or node-positive disease. For bulky disease? Not necessarily always bulky because they're not always bulky, but T3 are node-positive. And the other ones to consider for are people who may not have that, but it's so close to the anorectal junction that the mesorectum is tapered away to being something very minimal. So you know you'll have a threatened margin. And so that's the other concept, the threatened margin. So I talked a little earlier on about a circumferential resection margin for a total mesorectal excision. And you want one to two millimeters of a margin. If your margin is threatened, that's certainly another indication. And then your options become short or long course radiation. In Europe, it's very much gone towards five times five gray, given over five days. And then you operate about a week to two weeks later. In Europe, sorry, in the U.S., for a variety of reasons, it's a six-week, 40 to 45 gray, given with chemotherapy, staged over six weeks, and then a six-week to eight-week waiting period. Now the difference between those from a radiotherapeutic perspective is not much because it's the same equivalent dose. 25 gray over a short period is equivalent to 40 to 45 over a longer period. But it can make a big difference for tumor response. So you've mentioned bulky tumors. So if you do have a bulky tumor, it's particularly a patient to go for the longer course chemoradiation because you may be hoping for that physical downstaging of the tumor. I'm going to give you some short vignettes now and just get your quick response on some of these as to therapy. Let's assume that I find a patient with a carcinoma in the sigmoid at 40 centimeters in the sigmoid colon. The colon is otherwise unremarkable. What is your planned therapy for that patient? Any further workup? So workup would be, so you've had the colonoscopy, so it's CT, and CT of chest, abdomen, pelvis, and a laparoscopic sigmoid colectomy. So that's what I wanted to ask you. A sigmoid colectomy as opposed to a left hemicolectomy, is that correct? Correct. So you're looking for two things for colon cancer. So switch into colon cancer. You're looking for two things. Now, actually maybe more than two. So the kind of historical things that you're looking for at least a five centimeter proximal and distal margin, but usually it's determined by blood supply. And second, you're looking for at least 12 lymph nodes. Many of us would hope for at least 16. So you're going to mobilize the inferior misenteric artery. You're going to protect the autonomic nerves to protect sexual function. You're going to go up, and most of us would do a high ligation, meaning above the takeoff of the left colic artery. And then the next, and this is increasingly being realized to be important, the next thing is as you dissect the mesocolon. So I mentioned you can do a total mesorectal excision with five mils of blood loss. You should be able to do a total mesocolic excision with five mils of blood loss. The plane you want to be in is the plane between the embryological peritoneum of the retroperitoneum, or Toltz fascia, and the embryological peritoneum on the mesocolon, which, as you remember, will have rotated and laying back on the abdomen in utero. And you want to be between those planes. And that keeps your mesocolon complete. And the reason that's really important is if you look at the Scandinavian data, I mentioned their local recurrence rates were 27%, high 20s, when they were doing some very good rectal cancer trials. They focused on rectal cancer surgical technique and got the local recurrence rate down to under 10%. While their local recurrence rate for colon cancer was even higher than their rectal cancer local recurrence rate, because they realized they weren't doing adequate colon cancer surgery. Now, many people have been doing adequate colon cancer surgery for years, but the point is you need a complete mesocolic specimen. Do you take the vessels before you take the bowel? Is that still part of the... Yeah, I absolutely do. And then to your point about left colon, most of us would think of a left colectomy as going from mid-transverse colon or left-sided transverse colon down to rectal sigmoid junction. You know, for a mid-sigmoid cancer, so 35, 40 centimeters, what have you, mid-approximal sigmoid, you know, you can end up taking a mid-descending colon down to rectal. Obviously, you need good vascularity, and I would always check that there's pulsatile flow before I do my anastomosis. But you don't necessarily have to take the splenic flexure down. Well, you'd have to take it down to get reach, but you don't need to resect it. So for a sigmoid, it would be, especially a cancer, it would be very unusual not to take the splenic flexure down, particularly in the U.S., even for diverticulitis, frankly, because of body habitus. So most people would take the splenic flexure down. There, because the tumor's in the sigmoid, you can go between the colon and the greater omentum, get into the lesser sac, bring the splenic flexure down. If the tumor's up near the splenic flexure, obviously you want to leave the greater omentum en bloc on the colon, and then you'll do a formal left hemicolectomy. All right. So we see a lot of right colon tumors. We see a lot of right and ileocecal type disease. Let's assume that you have a patient with only a cecal cancer. What's the extent of the resection you do there? So I'm going to start doing a mesocolic excision. So I'll go close to the SMA, open the mesocolon, come up to the origin of the ileocolic, take the ileocolic close to its origin, and then I'm going to lift up laparoscopically, going from medial to lateral, in that same embryological plane between the mesocolon and Toltz fascia, and go laterally, come up, take down the hepatic flexure, so the entire right colon is mobilized. Take the right colic at its origin, and having one piece of mesocolon, so it's an intact mesocolon. And the dissection for a cecal tumor, if it's cecal or near the ileocecal valve, you should take 10 centimeters of small bowel. If it's mid-ascending colon, you should take 5. And then on the colon, it only strictly needs to be about 5 centimeters, but for a cecal lesion, it'll usually end up being close to the hepatic flexure. If it's a hepatic flexure lesion, it's going to be close to mid-transverse colon. And if it's, just to finish, if it's just to the right of the middle colic vessels, so it's kind of transverse colon, but only just there, you may want to think about doing an extended right, taking the middle colics, getting all the nodes around the base of the middle colics, and extending over to the left of the midline. How do you do your anastomosis if you're doing this laparoscopic? Yeah, I do an extracorporeal stapled anastomosis. It's quick. So you bring it out through the same... Bring it out through the extraction site. It's quick, it's easy, it's reproducible. We've reported leak rates of 0.8% over 1,000 cases. It's worked well in our hands. Final question now, because we're just about wrapping up. I think we've underestimated in the past the genetic factors in colon cancer. Particularly, you know, we have a hereditary non-polyposis cancer syndrome, which we're familiar with. But when do you consider a genetic workup of your patients who have colon cancer? So we're lucky to have the Weiss Center for Hereditary Colorectal Cancer here, which David Jagelman started, and then Jim Church, and now Matt Kaledi have run and built into something very special and very big. And they've got the biggest polyposis database in the world, and probably now the biggest HMPCC database as well. So having genetics and coordinators around, we have a very low threshold to asking. So if people have, you know, any risk of Bethesda criteria, first degree relatives, somebody young in the family, I'll just get one of the Weiss Center coordinators to come in and talk to them and do a full family tree. If you don't have that available, if you think somebody is a high risk, you know, cancer under 40, first degree relative, multiple cancers in a family, non-GI cancers in a family, send them to, and you're not sure, send them either to someone who has an interest in this, or send them to somebody who is a genetic specialist at your institution. But you're absolutely right. It's something we really need to be aware of for two reasons. One is for their families, and for their own screening and surveillance recommendations. But the other is for the operation you do. So it may actually change your operation. So if you assess these people, and it's just a right colon cancer, but they also have multiple polyps, or they have a very significant history, you know, maybe they're better with a subtotal colectomy, an iliosigmoid or iliorectal. And if it's familial polyposis, you know, maybe it's a procto-colectomy or what have you. So certainly a lot of complexities and a very important question to have asked. I want to stop here and thank you for helping us again today, and we'll be back with you at another time. Thanks, Connor. Thank you, Jeff. Stay Current is a multimedia publication designed to keep healthcare professionals up to date with standards of care and new emerging ideas. Stay Current and General Surgery is edited by Jeffrey Ponsky, Mina Bolas, and Harveen Lamva in partnership with GlobalCastMD, and is recorded and produced at Cleveland Clinic in Cleveland, Ohio.