 The seminar series on ethical issues and organ transplantation, we're so delighted today that Dr. Enrico Benedetti has come to join us for a talk. Dr. Benedetti is the professor of surgery, the chair of the department of surgery, and the director of the transplant center at the University of Illinois at Chicago. After earning his MD degree from the University of Florence, he completed his residency at the University of Florence and also at the University of Illinois Medical Center. He did his fellowship at the University of Minnesota and has become an expert in kidney and liver donor transplantation, research interests including hepatocyte transplants, pancreatic islet isolation, and transplantation of the islets for diabetes treatment. Dr. Benedetti and I have shared a few patients over the years and I can speak from experience that in addition to his administrative and surgical skills, he's a wonderful doctor for his patients. So it's a pleasure to welcome Enrico here today. His topic is the following. Should morbidly obese patients be denied kidney transplants and also deny the chance to be living donors? Controversial topic Enrico. Welcome. Thank you, Professor Siegler. Michael, it's a pleasure to be here. This is an impressive turnout. I thought there would be few in the room, but this is a full house. And the topic that I've been asked to address is pretty interesting. I'll give you some details regarding the rational that has brought us to adopt a certain tactic, strategy to take care of this patient. As you are all aware, there is an epidemic of obesity in the United States of America. If you look at the obesity trend, you can see that there was a lot of white and light blue in the 90s with a less than 10% prevalence of obesity defined as a BMI greater than 30%. 1999 was worse. 2008 we are in the middle of a tremendous epidemic. Illinois has in 2008 prevalence of BMI above 30 between 25-29%. I've been told that the latest data show a 32% rate. So one in three of Illinois citizens is obese. Interestingly enough, you would expect sick patients in renal failure being sick that don't eat much and they're less obese. They mirror the general population. This is the so-called NANES study, which base the information of U.S. RDS. So all the patients covered by Medicare in this country, it's a court of 580,000 patients currently. As you can see, if you take all the male, this is BMI over 30. This BMI over 40. 30% of the male and almost 40% of the female in the last time they checked in 2006 was morbidly obese. A good number with a BMI greater than 40. We don't have information about Latino, but in African American, mirroring again the general population, the rate of obesity is even greater. It's about 40% in male, 50% in female, and almost 20% of African American female at the BMI over 40. That is important implication in their destiny because majority of center in the country refuse BMI over 35. A recent review from ASTS showed that only one-third of the center accept BMI over 35. Almost no one accept BMI over 40. And we are talking about a lot of patients, probably estimated about 110,000 in the U.S., which at least 40,000 have BMI greater than 40. Now, most of these patients being obese also have diabetes. Diabetes is the leading cause to renalpharia in this country, and of course it's very prevalent in obese population. And the five-year survival and dialysis, excluding the first 90 days mortality, it's about 23 to 25%. So being on dialysis for this patient equal as death sentence most of the time. So three-quarter of them will not be alive in five years, which by the way is the waiting time in Illinois. So when we talk with our patient, we break all these good news. You have a 25% chance of being alive in five years, and by the way, you're going to wait five years. It's a tragic but true, unfortunately. Interestingly enough, even patient listed, and that's data from Doris Segev from John Hopkins, they wait longer than a patient with normal BMI. Of course, there is no rule against obese in Unos. And this reflect not the legislation or rule, reflect attitude of the center. So even if they are listed, obese are transplanted with a longer waiting time and a lower percentage. So there is an ethical issue. Should they be punished because they're obese? In many other situations we have choose not to discriminate. I was attracted in 2009 by the publication of this paper from the University of Michigan that has a good tradition in analyzing large database. One of the reason why obese are not considered prime candidate for transplantation is because as a group they do worse than general population of normal weight individual. And of course, transplant center are under some pressure to optimize their outcomes. Turn to be that obesity itself, it is not a condition that impact graph survival. You can tell that this being that zero, of course, delayed graph function as an important impact that we all know about. Of course, BMI less than 20 reflecting malnutrition as a bad impact on the graph survival. But surgical site infections, surprisingly, are very important. Risk factor for poor graph survival. Of course, a wound infection are more common with the BMI going up. And this paper in the Annals of Surgery, you can see the wound infection is about 5% for normal weight, but goes up to 25% for BMI over 40. And in the experience at University of Michigan, you can see that regardless the presence of obesity, people with wound infection at the worst three years graph survival 50% versus over 80% obese or non obese that did not develop wound infection. So most likely it's not the obesity on its own that cause the inferior survival of the graph in obese. It's the fact that they are more likely to get the wound infection. And based on this, we tried to improve the outcome of obese patient by using robotic technology. We thought if we could avoid the wound infection, we may get better results in the long term. As you know, the use of robotic technology is very controversial. In some cases being just maybe a marketing tool. In some cases it may make a difference. I believe this is a good demonstration that the technology can be helpful in some selected setting. We did publish in 2010 the first successful case. And the operation work in the following way. We have an incision in the upper abdomen about 2.5 inch. And then we do the dissection of the vessel using the robotic technology. So it's intraperitoneal kidney transplant in analogy of what we do for simultaneous kidney pancreas. So the iliac vessel are this setting. And then through this end port, we actually introduced the kidney. In this case it's a life donor kidney ready to be transplanted. It goes through the end port to reach the vessel where we normally transplant the kidney. At this point, instead of using open technique, we use robotic instrument to do in this case the venatomy of the iliac vein. And then using a sutured of Goretex that is a little more resistant than traditional problem. We do the anastomosis the same way we would do in open surgery. And the advantage of the technology is that the tip of the instrument moves like a human wrist. Therefore it's very easy to suture. Universal Chicago is the leader in the most common application of robotic surgery which is radical prostatectomy for cancer. So you are all familiar with this technology. This is one of the center that has high volume. We tend to use robotic for other indication in addition to prostatectomy including liver resection, lung, and in this case the kidney transplant in obese. This is the anastomosis of the artery. Again, same suture, six of problem we use in the open case. Same precision because you have a magnification that go up to 20, 30 times depending on how close you zoom to the target. So we can do the operation quite proficiently. And now we have three surgeon trained to do it. That's the final part where the urethane is implanting of the bladder. Again, we are satisfied with the technique. We pay a little bit of price on the learning curve at the beginning where we took longer. But I show you that now the time came down to a decent amount. That's the final result. Actually we move the incision a little bit higher and we make it a little smaller. But the advantage is instead of having a lung incision in the lower abdomen where the panacea is thicker and is closer to the perineum so more likely to infect, we have a small incision here that is not used for anything but to put the kidney inside. So there is no retraction. Of course you should do this transplant in such a large individual. You need to retract a lot. And the retraction itself will cause fat necrosis which in turn may predispose to a wound infection. So in this case we retract nothing, we just use it to put the kidney in. So we thought maybe we have a better chance to avoid wound infection. So we actually have down to data 80 cases. And I have a study that includes patients that have at least six months follow up. Now we have two years follow up on the same group. As a control group we use obese patients that had open kidney transplant done between 2004 and 2009. We always did obese patients in our center. We're just doing more now I guess. Now comparing the two groups that were sort of matched by the various characteristics, cross-match positive diabetes, nephropathy, living donor, everything was matched. Of course we had actually bigger patients with the robotic because we didn't dare to do BMI up to 50-55 open. Everything else was similar so they were comparable group. And the outcome is interesting. First of all we thought we were very fast in suturing but actually we took the same time with the robot that is open. We do use 25-30 minutes in somebody with normal weight in open surgery, but obese patients are more complex. And to our surprise we noticed that the warm ischemia time which reflect the time of the anestomosis was similar. The creatinine at six months was similar, the wound infection was different. In fact we had one in Matoma on a patient on kumadin but now wound infection versus what you expect about 18% on the open case. So we had now wound infection and today in 80 cases still now wound infection. So the strategy work in preventing the wound infection. Now we have now data of a three years follow-up where in the open group we start having loss of graft. And it's not occurring on the robotic case so we'll see if that data will hold true over the years. But we are seeing a trend that is quite interesting. For sure we did not lose graft to technical complications such as vascular thrombosis. We had one ureteral complication on a patient with double ureter which require robotic re-intervention. We had one of the ureter ischemic so we resect and re-plant again with the robot. So we believe that is an effective approach to reduce wound complication of this recipient. I don't know if it's going to make a difference in long term outcome. Sure make a difference in the short term because the wound infection of obese individual is a big deal. Beside of course decreasing the chance of success we'll impose on the patient a very complex wound care. When they open up it's a huge open wound that last month cost a lot of money to the society and a lot of discomfort for the patient. And somehow influence the outcome. The colleague from Michigan could not figure out why. But has been reported over and over the wound infection decrease patient and graft survival. Maybe it's a marker of something deeper that we do not understand. And I think the issue is should obese patient be transplanted. Of course you know my answer and I'm curious to know the opinion of the group. Dr. Siegler asked me to address an additional topic and maybe I'll address that quickly and then we can open for discussion. But first I want to point out that we believe that we need to do more for this patient. Transplanting is not enough. We need to work to try to go back to ideal weight. So we routinely offer bariatric surgery right after the operation. To date six did it with good success. As you know bariatric surgery before kidney transplant is not commonly employed and had mixed results. Surely the incidence of complication is greater because of the presence of the uremia. But we do also have another option. We talked about the three main operation available for bariatric surgery. And this hospital is one of the three approved bariatric center in Chicago with us in Northwestern. So you are familiar. But for the information of non-doctor we do either gastric bypass where small stomach pouch is actually stapler to allow the patient to have early satiety by having a small reservoir. So this is a restrictive procedure which is mimicked by the lab band which does the same with this implantable device with less morbidity. But we were curious about the sleeve gastrectomy which turned to be a quite efficient way for weight loss and is not a restrictive procedure. You just reset most of the stomach and you make from a pouch a tube. We thought that would be good because our patients are asked to take 30 to 40 pills for various reasons and with this particular operation they cannot do it. But we thought they could do it thus. So we have an IRB approved protocol whereby we are offering the patient to have either the robotic kidney transplant alone or the robotic kidney transplant simultaneously to a sleeve gastrectomy. We have done three cases of which one was randomized to have the operation which is again sleeve gastrectomy and robotic kidney transplant in the same setting. The IRB asked us to stop the study for two months to see what happened to the first case. They were scared as much as we were. But what's happened is that from a BMI of 47 she dropped actually significantly down with very good creatinine clearance which actually improved as she lost weight. So it's the first time of course it's controversial because if you have a complication of the sleeve in the presence of massive immune suppression it may be in trouble. We have a sort of comfortable with robotic sleeve gastrectomy. We have a good track record that we are considering this option. Time will tell if we are on the right track. Now I would like to move to the second topic that Professor Sigler proposed to me. And I will not be long because I can't abuse of your patients. Can obese individuals serve safely as a donor for kidney transplant? Well this is an important question in Illinois where one third of the population is morbidly obese. And it's controversial because you are asking the donor to take a risk maybe increased to benefit somebody else. The ethics of donation especially regarding liver were developed in this university by the people that sit in the room with me. Surely Mike did a lot, surely Professor Sigler did a lot. So it's a good seat to discuss. And I'm sure the discussion will be maybe more interesting this way than the other way. I cannot provide a final answer. I can just provide some technical contribution. Of course there are concerns regarding the fact that obese patients having higher rate of comorbid conditions such as hypertension and diabetes may be at higher risk for long term renal failure after donation. We did interrogate some international registry for example in Switzerland that failed to show an effect of being obese in the long term outcome in term of proteinuria and midford dialysis. We do know that in this country the registry has never worked out well. It's very difficult to keep healthy individual to come back to your center. We always try as much as you do but we both know that it's difficult. So while the transplant ISTS, ATC have been able to produce a lot of information and a number of other issues. In this issue we do not have a lot of information except for center data that is usually not very good in the long term. For the simple reason that these people disappear and refuse to come back. So I cannot comment much about that and it's still an open topic. I can comment about the technical part. As you probably know we do robotic donor nephrectomy. That has been our training ground to do the robotic kidney transplant. We start in 2000, actually it was in September 2000. We did the first one and as December 2011 we had done 700. And we actually studied this donor, my junior partner did study dividing the cohort in four groups based on the BMI. So the LT weight, BMI 20 to 25, overweight 25, 30 obese, 30 to 35, morbid obese over 35. And we had a good number of all of them that has shown in a second. And as you can see they were pretty similar except for the ethnicity where no doubt the African-American had a little higher incidence of obese. Same for the Hispanic. Interestingly enough the hour time was exactly the same regardless the weight. The length of stay was exactly the same regarding the weight. The blood loss was exactly the same. So I can tell you that in our cohort we did not find technically different. So we cannot say I will not do the obese patient because we have more complication or because we take longer. Or because we have higher rate of transfusion. So total surgical time, ABL, length of stay is similar. In the morbidly obese group there was the smallest one. We had only 30 patients with BMI greater than 35. We had more wound complication. 10% versus 4% in the other groups. So, I'm sorry. What I can tell you is that from a technical standpoint is feasible. The price that you pay for this patient, the morbidly obese is increased rate of wound complication. Everything else was within the same range regardless the BMI. And that address of course just half of the problem, the technical half. The functional problem is more difficult to answer for the reason that I stated at the beginning. But I think I'm done with my presentation. Thank you very much for the attention. Thank you, Enrico, for a terrific and very controversial talk. I'm sure we'll have a lot of questions. Just a couple to start off with for me. Do you think that the robotic aspect is significantly better in these types of patients than just a laparoscopic, obviously from the donor side? Are you referring to the donor or the recipient of the operation? The donor operation, it's hard to show a difference. Experienced laparoscopic surgeon can surely have the same result in terms of length of surgery, EBL, length of stay. I believe the merit is subtle in the obese individual. In the obese individual, you have no doubt that robotic technology is going to tell. For example, there is an interesting study from Texas whereby they compare prostatetum, either open laparoscopic or robotically. You don't see any difference at the first side, but then if you divide it in core based on BMI, the cost of the procedure stays steady for robotic and grows in the other two groups with the growing BMI. So I think in obese, you have an advantage with robotic. In the recipient, I think the advantage is more dramatic because you need to suture. Yeah, you got to suture, etc. So have you had any early graft or patient losses in either group with the robotic surgeries? In the recipient group? Yeah. We had one patient dying of MI on post-up day 10 with the functioning grafts. I don't think that can be ascribed. That's right. And conversions from robotic to open? Yeah. We had a total of three conversions. In these three cases, two cases we found the atherosclerotic vessel, so we abort the laparoscopic component the moment we felt the vessel and did the standard open. In the third case, we had the clamp injury, so we had to re-explant the kidney, reconstruct the iliac artery, and then re-plant the kidney in open fashion. And the kidney graft was saved that way. Great presentation, Eric. I know that in looking at taking obese patients to surgery, we worry about increased risk of perioperative pulmonary complications. It's nice to see the very small incision that's made for the robotic. Did you look at differences in terms of perioperative pulmonary complications, length of stay on the ventilator, in the open surgery group versus the robotic, instead of just the wound infection, because that would be very informative. So, in terms of length of ventilation, of course, we extubate in the unit, so it's measuring hours. We extubate three or four hours in the unit. That's our policy. We didn't see any difference. Pneumonia, we had 8% incidence in the same lady with the hematoma in this particular group. She had also a hospital acquired Pneumonia. That was the only case in 80. I would say that from the standpoint of pain control and ability to take deep breath, well, minimally invasive works, and that has been shown in many settings because it eliminates the postoperative pain and improves the ability of the patient to take deep breath and so forth. So respiratory, we have been very happy. Lady? Hi. Thank you very much. So my question is about the living donors and what long-term type of follow-up are you going to do, and are you concerned of any long-term increased risk of kidney failure, for example, in these donors? We are very concerned. And thank you for the question. As you probably know, UNOS mandate center to follow up the donor for two years. We are more than happy to follow for more. The problem is that donors do not come back. Maybe a third of them will be actually able to come to a year. Almost nobody come at two years, not because we fail to call them or we are not ready to see them. They just feel good that they don't want to be bothered. That's a problem that has been universal. Anytime UNOS has tried to do something about donors, the compliance in the follow-up has been a big problem. Being aware of the fact that obese may be at higher risk due to comorbidity for kidney dysfunction, we have a special protocol for workup. So we do not rely simply on creatinine and nuclear scan. We use IOX cell that is the best way to predict GFR in obese individual. Anybody with a BMI greater than 30, we send to Minnesota IOX cell to have a very precise picture of the GFR. And if the GFR is not well above the median for that age, we do not do it. I have a couple of questions in terms of supply and demand and the ethics of opening the lists up. As you noted, several centers in the United States. We go up to a BMI of 40, but not beyond. Most centers in the United States don't go beyond a BMI of 40 for our recipients. We have 95,000 patients on the list as when I checked a couple of days ago for a different talk that I'm giving. You clearly noted that obesity is an epidemic. We've got a huge supply, demand, inequity already. We have a patient population that's challenged. I also know that you have a very experienced robotic team in a room that's dedicated to, you know, PRO, yourself, and the robotic system. So there's an incredible number of resources put for just the robotic team, notwithstanding the transplant itself. And then we're going to increase demand even more than 95,000 transplants and 18,000 being completed every year. So I'm just interested to hear your comments about the resource allocation and the supply-demand issue because if we all open up to BMI's of greater than 40, obviously we're going to have a huge inequity. I think that's the point of this meeting. Is it ethical to deny them access to transplants? I must say that the most relevant precedent would be alcoholic cirrhosis and liver transplant. And of course a lot of people thought that since they brought on themselves the illness, why should they have access to the transplant pool? The answer of the transplant community has been once it was clear that alcoholic cirrhosis was not a risk factor for inferior outcome. In fact, alcoholic cirrhosis do better than hepatitis that we normally do. The alcoholic cirrhosis patient provided they have the six months of abstinence and so forth and so on. So I believe that the precedent and my personal opinion is that you cannot discriminate people because they are obese. I think if you have evidence that using a scarce resource in obese would decrease the chance of success, that's a strong point. But most of these cases are living donors so that is not a public share resource, it's their own resource. And I personally also believe that as a doctor, and I've been in this situation with Dr. Siegler discussing for example, living donor liver bowel in infants, whereby in one small infant you throw two, three million dollar resource. Should we do it? I think as a doctor my imperative would be to save my patient the day that he come to me. And then of course I will listen to policy that are dictated by general interest and public service and public interest. But I think when you confront your patient my reaction is try to do everything I can to make him better. Have you considered offering sleeve gastrectomy to your obese living donors? You might in fact want to wait until there is data to prove that they have a worse outcome but that could take a long time. And it might be something that would be reasonable to think about prophylactically. But I haven't thought about it. What do you do? I have to be a proof study where we do either the sleeve plus the robotic kidney or the kidney transplant alone. The donor. Oh I'm sorry, I misunderstood you. I thought you were came late. We actually had several situations where the donor himself request my response has been let's not mix it. We'll be more than happy to. I mean I don't want the event where we do the donor and a threat which is the most controversial medical act you can do. Be mixed to another operation that can be source of morbidity. Except for the liver or donor. Except. But I'm not saying. I'm not saying that is wrong. I'm saying that maybe actually would justify ethically including even morbidly obese donor. So we didn't do it because we don't want to have a complication in the setting of living donation that may kill my career as much as the program. But if he has more widespread support I think it's a good idea. And the general anesthesia it's the risk that the donor go through that most of the deaths are not technical due to PE. So why not since you are taking that risk anyway do something for the donor. I love the idea. I just didn't have the courage to do it. I'm not shy. You're doing it in the same operation. In the same operation. Same procedure. In the era of shared decision making when the patient has no say in it and certain makes a unilateral rule that at this day they will not get the surgery is it ethical. So I think the issue is basically paternalism making the decision of morbidly obese patients cannot either be a donor or a recipient. Right. So the issue is you know if you're just being paternalistic is that ethical. I think I've been accused of the opposite. I'm probably the least paternalistic doctor in this room. I actually the test being paternalistic. These people are confronted with information and the information that are provided to them are pretty accurate. We use the same style that this university has started for information in living donor liver. We provide word literature our own result and all the possible downside. And then we have an actual ethical committee member when the case is more controversial to talk with them. So I don't think they go into a situation without understanding and the issue are not difficult to understand. If you are an obese recipient and nobody wants to transplant you your alternatives die on the dialysis or being done. And most people will choose to have the operation and the donor same the donor even more so the donor has no need to have an operation. And only if he really wants to help that particular recipient we come forward and again through three layers of control that are independent from the physician. We model our program to yours that is arguably the best developed in the world. So I think that the addition of the bariatric surgery is a very interesting intervention on top of the kidney. But your presentation went from the meta level obesity epidemic in the whole country down to an individual level intervention. And we now have I think pretty compelling data that suggests obesity is something that is a social family and community effect. That obese individuals tend to be in networks with other obese individuals. So have you considered adding that form of intervention in terms of prevention and sort of education on to your program which would then extend potentially extend the effect that you're having on this one individual into the family and into the community from which this individual came. Yeah it's a great question I'll answer in two way. Of course any time there is a bariatric surgery you need to have all the infrastructure that make a center of excellence like this one or ours. Meaning you need to have intervention from dietician from social worker psychologist that work with the patient and the family to make sure that you are a good candidate for bariatric surgery. They have ruled that in a way are similar to transplant including six months period where they need to go through a supervised diet in the attempt to lose weight. Unfortunately we all know that the ability to lose weight would be my over forty three percent in the long term. So majority of obese fail in the attempt of losing weight. The second thing that we do we are painfully aware of the fact that our patient until after the trans may have a normal creatinine are in a terrible state of fitness because complex problem that center in loss of lean mass. And we have actually a study ongoing where we put them through an interesting lifestyle modification plus exercise program that is very promising and I hope to be able to report in the future about it. But we are thinking about the person not just do the operation disappear. I'd like Dan's idea of offering the sleeve gastrectomy to donors because then maybe you'd get more donors. I think again as I told our colleague I love the idea. It's not like I thought about many times I've been and you can tell I'm not a particularly risk averse individual. But this one I never had like the courage to do it. This is something that maybe we need to do as a group and not just as an individual initiative. I don't think you can defend yourself if you have a bad outcome. Let's say you leak a sleeve gastrectomy and the donor died. To strengthen your argument had you considered doing a prospective study with a intent to treat as the starting point for obese patients who are on dialysis and showing that those obese patients with DMIs of greater than 35 for whom a kidney becomes available to a living donor or otherwise and compare them to the dialysis population going forward. Well the number is already available through indirect source. So we know number one that they wait longer as door is show. We know their mortality on dialysis which is available through the U.S. RDS which is approximately 75 percent in five years. So and we know the cost the cost for Medicare is $82,000 a year for emo dialysis $73,000 a year for PD. So we know that kidney trans will become cost effective at 14 to 16 months including the cost of surgery. And after that you have the 10 to 15,000 for maintenance immunosuppression. So we know that this cost effective save life and of course is beneficial to the individual patient. It's hard to argue against. So I just have another comment about the donor getting the lap band or what have you prior to or at the same time of donating. There's so many issues about us coercing people to be a donor. So with the patients if we offer them that are they doing it because they want to lose weight or because they want to give a kidney. And then are the recipients insurance going to pay for that. So that's I think that's a bigger issue. Inducement. I think that's for another day discussion. No pay off donor and inducement. I guess if you could if you could differentiate the cost of the lap band versus the donor nephrectomy then the donor's insurance should pay for the sleeve. And the recipients should pay for the donation part if you can differentiate that. Very nice talk. You mentioned that there's a variability in the practice patterns across the country with respect to obesity. There are some centers that won't consider patients that are obese and it makes me and the reason is because of the higher mortality and that makes that's an issue for patients. And so I think that's where the ethical issue with regard to obesity comes comes you know into play in the U.S. Well my personal opinion is that the daughter or the group of the team should be of course free to choose the case that they intend to tackle or not. On that one I have no objection. If you do not want to do obese over 35 BMI is in your right to do that. What I think is analytical is to accept patient that you will not transplant. If you say yes to BMI 44 knowing that you will not do it that's an ethical. It's not an ethical to say no as long as it's clear at the beginning. But if you then say oh I'll accept you on the list but now you need to lose weight. You're asking them the impossible because as I told you only 3 percent of them will successfully lose weight with diet alone. So you got to be ethical in the sense clear yes clear no. If he's now is now if he's yes you do it. I don't agree with that. Any other questions if not. Enrico thank you very much it was a great talk.