Benefits of Complete Mesocolic Excision (CME) for Colon Cancer Patients

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals. Exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepherd, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase 1 and Sarcoma Programs. Today I'm happy to be joined by Dr. Hermann Kessler, a senior colorectal surgeon focusing on laparoscopic surgery here at Cleveland Clinic. He's here today to discuss the benefits of complete mesocolic excision for patients with colon cancer. So welcome.

Hermann Kessler, MD, PhD: Thank you. Thanks for the invitation and thanks for having me.

Dale Shepard, MD, PhD: Absolutely. So maybe to start off, give us a little bit about your background and your role here at Cleveland Clinic.

Hermann Kessler, MD, PhD: I am a senior surgeon now at the Department of Colorectal Surgery, which is part of the larger Digestive Disease and Surgery Institute. And I'm focusing on Laparoscopy. That's right. But nowadays, I'm also a member of the Cancer Team, the IBD team, and doing cases like diverticulitis, endometriosis, and basically all types of diseases of colorectal surgery and try to stay laparoscopic. For open surgery, I was trained in Germany at the University of Erlangen in Nuremberg and Northern Bavaria. And this university had been very renowned for colorectal surgery all over Europe.

And from there I was sent to Cleveland Clinic for the first time in '97 for a year of clinical and research fellowship. And I went along with Dr. Milson who was leading the program at that time to the Mount Sinai, a hospital in New York City where I spent another year before I went back to Germany and set up the laparoscopic program at my home university. But I'm also fully trained for robotic surgery, so I'm really focusing on the minimally invasive techniques nowadays.

Dale Shepard, MD, PhD: Excellent. And so, we're going to focus on a particular aspect of colorectal surgery, this complete mesocolic excision. But we have a lot of different people that would be listening in. Give us just a broad overview. When we think about surgery for colon cancer, what are the big options? How do we approach this?

Hermann Kessler, MD, PhD: Still, it's a surgical domain, so it's priority surgery. So, the vast majority of cases are treated with surgery and adjuvant chemotherapy plays a role. And in a few cases, also neoadjuvant therapy, which is mostly chemotherapy, sometimes immunotherapy. But we have learned from rectal cancer surgery that in many developed countries, nowadays, colon cancer has worse survival rates than rectal cancer. And this is due to the fact that the international community of researchers focused on rectal cancer. And we nowadays have preoperative neoadjuvant chemotherapy compared with post-operative ones. There are many studies.

We have different types of access. We have the TATE approach like from below. We know that the mesorectum has to be removed and we know how pathology has to look. We can do robotic surgery on the pelvis very well. It's all well established. And colon cancer was kind of neglected and this is why colon cancer didn't get the attention, which is probably necessary. So nowadays you should focus on colon cancer to improve the results also there, with a goal that nobody should die anymore of colon cancer.

And for the anatomy it would be important to say that the colon is suspended on the so-called mesentery, or mesocolon in the case of the colon, and we note that the local spread with lymph nodes or tumor deposits around the primary colon cancer goes into this mesentery, into this mesocolon, and normally follows the arteries towards centrally. So, what complete mesocolic excision means is that we must consider the mesocolon for each segment of the colon and check where the lymph flow goes or the potential lymph node involvement goes along the arteries, and then take these areas out as well, completely.

Dale Shepard, MD, PhD: And so, when we think about the difference, and this is actually, like you say, much more common in the results, research, and effort in rectum. Was this because it was kind of considered that we knew what we were doing for lack of a better way to put it, in colon and there were problems in rectum. So, there's all this focus and there was just a lack of attention or were people truly satisfied with the outcomes in colon? What led to that?

Hermann Kessler, MD, PhD: That is right. Colon cancer was looked upon to be an easy case because the rectum is located in the pelvis, which is more difficult to access. Also think about obese people and it's suspended on the mesorectum and partially located retroperitoneal, even two thirds of this. And this made it traditionally more difficult to access. This is why most of the focus went down tractile cancer and they said colon cancer can be done any way, just cut it out. But this is not true. You have to check exactly how to cut it out.

Dale Shepard, MD, PhD: And I guess from that standpoint, the how to cut it out, tell us a little bit about advances between open surgeries and laparoscopic, robotic assisted, those sorts of things. How has the field changed in that regard?

Hermann Kessler, MD, PhD: Well, it started out with open surgery first because this is the traditional surgery, and this is the established surgery. And here, data were compared, colon cancer and rectal cancer results as a big German study group of colorectal cancer, which the Erlangen Hospital was a crucial part of. And there was one hospital, an outlier which had 38 percent local recurrence rates in colon cancer. And nobody believed these figures.

And this was the reason to go into the details. And this study was very precious. It has been published multiply, and it could be found out that it's technical reasons which caused the recurrences to happen. So, the more mesocolon you take out and the less you injure the surface of the mesentery. So, the fascias on top, in front, and behind the mesocolon need to be preserved because otherwise tumor cells which are located in the mesocolon can be spread. So, they need to stay intact, the surfaces, and you have to do high vascular tie. So, the arteries which are feeding this part of colon and where the lymph nodes are potentially involved have to be taken down at their origins at the large vessel, which is the SMA, the superior mesenteric artery, or the aorta on the left side. And then you take out the tumor with the complete mesentery as a package. And this is the optimum you can achieve on the surgical basis when technique plays a role.

Dale Shepard, MD, PhD: And from a technique standpoint, traditionally there's always been consideration in making sure there is adequate lymph node sampling and things like that. But that's not maintaining the mesentery, is that correct?

Hermann Kessler, MD, PhD: Yeah, well they're still teaching books from the 1940s. We had just cut out the tumor with a little bit of mesentery and then just sewed both ends together. And we must think that surgeons were reading this who would still work 40 years in practice, so until the 1980s. So, it takes time to teach the surgeons to do it differently.

But many have come back to Cleveland Clinic with this aspect because Rupert Turnbull was a very renowned chairman of our department of colorectal surgery, and he developed the so-called no-touch isolation technique. So, he believed that the tumor has to be left alone initially. You mobilize medially first along the mesocolon, take a good part of mesocolon, and then mobilize the tumor. And he compared his technique with colleagues of his, which he called traditional technique. And it's illustrated in the publication from 1967. And if you see the difference between traditional and Dr. Turnbull's technique is that he took out a lot of mesocolon, approaching complete mesocolic excision. And we believe that his results, which are double as good as the results of his colleagues, are due to this very good surgical aspect he did at that time already.

Dale Shepard, MD, PhD: When we think about outcomes that would be local recurrence and distance spread?

Hermann Kessler, MD, PhD: This is what we have to distinguish. So, the surgeon can avoid local region recurrence. It's difficult to avoid distal spread. For this, we need oncology to help with chemotherapy. But most important would be to diagnose colon cancer at an early stage where no metastasis has been set to the liver or to the lungs or to the bone or to the mesentery, or to the peritoneum. Because then it's ideal to treat the patient surgically. So, screening programs are crucial.

Dale Shepard, MD, PhD: And so, when we think about, and we'll come back to screening in a little bit, we'll talk about the chemo parts here in a little bit as well, when we think about the technique itself, doing this complete mesocolic excision, how much better are outcomes?

Hermann Kessler, MD, PhD: Well, it was published from the Erlangen University Hospital because we compared our results at that time in Germany in like eight-year ranges, from the early 1980s to about 2010. And we could gradually increase the survival rate and lower the local recurrence rate to less than 5 percent, which was initially more than 10 percent. And this was by teaching the younger surgeons how to do the technique and by limiting the number of surgeons doing these procedures. We all had numbers and our results were compared in an anonymous way. And so, we could get a kind of feedback as well, how we did regarding our long-term results personally as individual surgeons.

Dale Shepard, MD, PhD: I guess when we think about the fact that you can get better outcomes with this type of surgery, how common is this surgical technique being adapted?

Hermann Kessler, MD, PhD: It is adapted in the major centers. Interestingly also in Japan, because Japan has a different type of nomenclature. They call it D2 and D3 dissection. So complete mesocolic excision would correspond to D3 dissection, which is taking the lymph nodes down to the origin of the arteries and even along the feeding larger arteries. And they take out shorter lengths of bowel, because they say that the spread along the colon reaches out only about 10 centimeters.

In the western world, we take longer segments out because we focus on the neighboring two named arteries where lymph nodes can spread along and the results in Japan are still good. So that has been an established technique with their special nomenclature. And in the western world, in the major centers it's being established. All the major American centers deal with this. And in Europe as well. At Erlangen University Hospital, we did colorectal courses, so surgeons came from all over Europe and also from other continents to watch how we do this, mainly in open surgery.

Dale Shepard, MD, PhD: So, a question is from open versus laparoscopic, is this a technique that can be done in either open or laparoscopic? And how has progress in robotics and changes in techniques, how has it changed our ability to do these surgeries?

Hermann Kessler, MD, PhD: Yeah, this is a very interesting question, because for the Hohenberger, who called it complete mesocolic excision, he was the chairman of Erlangen University Hospital, and I was his private attending at that time. So, I helped him over more than 10 years in countless cases, doing this type of surgery. So, he didn't believe that it could be done laparoscopically.

So, when I moved to Cleveland Clinic, which was a great opportunity because we always had support by our chairman, Dr. Fasio, now Dr. Steele, they always supported the minimally invasive approach. And I started out doing these surgeries in the cadaver lab. So, I'm happy the Cleveland Clinic offers this. So, I set up the surgery and with some assistance, I tried out how to do this in a cadaver laparoscopically. And then I tried stepwise this approach to how it works in patients, and it works well.

You still can't apply it to all patients. I would say obesity plays a role. Also, previous diseases like pancreatitis play a role where the mesentery is more fused and there, I would favor an open approach, because safety for the patient is absolutely first. But you can do it laparoscopically very well now and it's my routine nowadays. And I published videos about this. I was invited to ASCRS for this, so the American Society of Colorectal Surgeon Congress. And so, it's getting established too, and surgeons come here to see it too. And they learn from the videos and it's spreading to the United States as well.

Dale Shepard, MD, PhD: And so, you've mentioned a couple times that this is something being done at major centers, perhaps not at some of the more community settings of things. You talked about laparoscopic versus open and patient selection. Are there particular patients, or tumor characteristics, that make this technique, this complete mesocolic excision better or worse?

Hermann Kessler, MD, PhD: Yes, of course. Anatomy plays a role because the mesocolon is based on anatomy. Anatomic studies, which mainly were done at Keele University by Professor Vale. He could show how the mesocolon turns around during embryologic development and these planes where the colon turns, we know these cases from non-rotation, malrotation where the cecum doesn't reach the right lower quadrant. This plays a role because the planes where the mesocolon moves along are aralia planes.

So, we have to teach the surgeons, stay in these aralia planes. We have learned this from rectal cancer because behind the so-called holy plane, which is the mesorectal fascia, there's this aralia or looks like spider web tissue area where you can dissect along where there are no vessels. So, it's a bleeding less surgery. So, you can really operate without much blood loss. A few CCs.

If you stick to these planes and we could prove now that the same is true for the colon, not only for the rectum, which could be kind of natural because rectum and colon derive from the same string in embryology. If you look at an embryo, it's fourth week of development, it's one string where all the organs are suspended and then twisting and folding occurs. So, if you reverse the embryological development during your surgery, you can have a very good result because this means automatically preserving the surfaces of the mesocolon as well.

So, patients who have had no surgeries before that have best conditions for this type of surgery and obesity, not necessarily. You can also do it in obese patients. But previous diseases played a role. As I said, pancreatitis plays a role or if any disease in an organ around there has been present or sepsis, sepsis of the abdominal cavity, then it may make it more difficult because of adhesions being around. And then I would favor an open approach. I've also done hybrid approaches where I mobilize the colon at least laterally to a mini laparotomy and do the central part of dissection in an open fashion to achieve the best result for the patient.

Dale Shepard, MD, PhD: And are there differences in outcomes or ability to do this technique based on where the tumor is located, left side or right side?

Hermann Kessler, MD, PhD: Yes, that's right. The left side is easier to operate, normally because there's only one major artery, the inferior mesenteric artery, which has to be taken down centrally. And then you do the central mesocolic dissection. On the right side there are vascular variations. This affects the arteries, like a right colic artery being present only in about 11 percent of cases. So, this can be different, but it's even more specific in the different variations of the venous flow because there's a so-called gastrocolic trunk of henle, which is having its mouth towards the SMV, the superior mesenteric vein. And this has variations, many variations which have been examined already. So, the gastroepiploic veins can come in there, the right colic vein, the superior right colic vein, or even the middle colic vein can have its mouth together in a common trunk. And you don't know ahead of time.

So, during the surgery, use the SMV as your landmark and dissect upwards and then you encounter these vessels. But you have to act carefully. Because if you have not been trained, the risk is that you injure a vessel, then you have bleeding, and this needs to be avoided. So, this is why some learning, and some teaching is necessary and this I think should be done at the major centers, but basically every good correct surgeon can learn this technique.

Dale Shepard, MD, PhD: Excellent. Thinking back to sort of that tie in with what we do in rectal on how that might teach us a little bit more about how to improve colon surgeries. What are your thoughts in terms of, you talked before about chemotherapy and neoadjuvant chemotherapy, and should we be doing more in that area? What are your thoughts about how we incorporate different modalities into surgical procedures?

Hermann Kessler, MD, PhD: Well, chemo radiotherapy has been traditionally developed for rectal cancer and there was a big study comparing it done postoperatively versus preoperatively. And now we know if we do it preoperatively, even completely, TNT, total neoadjuvant therapy, then we may achieve the best result regarding shrinkage of the tumor.

We may encounter similar situations nowadays in large colon cancers. And there are studies, like the FOxTROT study, which check if preoperative chemotherapy can make these large colon cancers shrink too. And there's a minority of tumors which have a genetic predisposition, and you can check the genetic markers which are susceptible to immunotherapy. I have an example. I operated on a heavy patient of 47 years of age who had a large transverse colon cancer, which was invading the pancreas, the lesser sac, the duodenum, the first lower jejunum. And when we did an exploratory laparotomy first, we couldn't resect it and then it turned out by biopsy that this is a cancer has genetic features which allow us to do preoperative immunotherapy.

So, this took a long time, many months, and we checked the patient and checked the progress of the tumor, of shrinkage of the tumor in CT scans and when the tumor had shrunk to a certain limit, we talked to our oncologist. So, the corporation is really crucial in the tumor board where all specialties are coming together and talking about these cases. So, we defined a certain time where we said now, we should check again and do another exploration. And the tumor had shrunk down to zero. It was a complete remission.

So, these are amazing cases, and these cases should guide us into the future. But as I said, immunotherapy is indicated in the minority of tumors, so still chemotherapy is there, and I've applied it in some patients too. There was a not genetically related cancer, and I achieved tumor shrinkage so the tumor could be operated on later with much better chances of not having to remove neighboring organs or other adjacent organs and avoid local regional recurrence.

Regarding this, the metastasis, we still need the help of oncology because the oncologists have to help us to avoid distal metastases. If we have a case where distal metastases are present from the beginning, which is still more than 10 percent of cases like mainly liver metastases, then the liver surgeon is on board from the beginning as well. And then we discuss the situation where the oncologist and often choose a so-called liver first therapy, which means we give the patient chemotherapy. We talked to the oncologist; he takes care of this. And then we make and try to make also the liver mets shrink and often leave the primary inside her because it's not obstructing. If it's obstructing, the primary tumor has to be operated on earlier, but otherwise we can do chemotherapy first and shrink everything and then get better chances of removal of liver mets with a liver surgeon and the primary with a colorectal surgeon.

Dale Shepard, MD, PhD: Which is great, that whole multidisciplinary approach, because too often I've seen patients come into clinic and they've just been on a long string of chemotherapy without consideration of going back to take care of the colon primary.

Hermann Kessler, MD, PhD: That's right.

Dale Shepard, MD, PhD: Tell us a little bit about, I know with your interest in laparoscopic surgeries, what are the exciting things coming in terms of laparoscopic surgery for colon cancers?

Hermann Kessler, MD, PhD: I think in laparoscopy in general, it's about refinement of the therapies nowadays because we have shown in these more than 30 years, laparoscopy has been on the market since the beginning of the nineties that many cases and diseases can be treated laparoscopically. But now it's about the refinement of the technique.

And this laparoscopic CME is one of these examples. It's a demanding procedure. You have to be trained in oncological surgery. So doing colon cancers. Also, they should be able to do them open of course, which is crucial for the younger fellows. They have to learn open technique as well. And then at the same time learn how to manage these cases laparoscopically and learn a good technique from the beginning. So, this is very crucial, but this is true also for other diseases. It's true for rectal cancer where the robot has a major role because it's elegant with the three-dimensional movements in the pelvis. You can dissect the mesorectum very well in many cases.

But it also has its role in benign diseases. Laparoscopy has been applied in endometriosis for instance. Another pioneer is Dr. Falcone, who has been here for such a long time, and I am happy to say that I learned managing laparoscopic endometriosis cases with him as a fellow already in '97, '98. And now when I came in 10 years ago on staff, he invited me for grand rounds in gynecology and we've done many cases together until he moved to London. But he will come back, and he has many well-trained laparoscopic surgeons in gynecology as well.

Dale Shepard, MD, PhD: I guess just something I hadn't asked about before. From this standpoint of taking the mesentery, doing this type of surgery, what does it look like for a patient standpoint, for length of stay, recovery, operative times, things like that? What's the difference?

Hermann Kessler, MD, PhD: Operative time may be a little longer. Operative time has been longer traditionally in laparoscopic surgery than in open surgery. If you use refined techniques, it takes longer, but the stay in the hospital is not prolonged normally. It's the same as an open surgery and many publications mainly from Asia, have checked on potential complications. Could be like for instance, but they are rare, around or below 5 percent. And in Germany, in Erlangen with Hohenberger himself are seeing them in less than 2 percent of cases and they're treated like by waiting, watch and wait.

Other inter-operative complications are careful dissection, don't injure the vessels when you do central dissection. So, you have to learn this, but the complication rate in the Erlangen database has not been larger for CME than without CME. In doing laparoscopically, it's just a little bit more demanding, but it does not affect the length of the stay of the patient. In general, of course, laparoscopic surgery reduces the stay in the hospital, reducing the need for pain medication. You can eat earlier; you can go on a fast track earlier and with little incisions. There's also normally the observation that you have less adhesion formation and less hernia formation.

Dale Shepard, MD, PhD: That's fantastic. You've given us some great insights today and appreciate you being with us.

Hermann Kessler, MD, PhD: Thank you. Thank you for your invitation.

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled.

This concludes this episode of Cancer Advances. You'll find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget, you can access real time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website, at consultqd.clevelandclinic.org/cancer.

Thank you for listening. Please join us again soon.