Sunday, June 14, 2015

Protecting the public trust--a robotically assisted liver donation case

One common theme of the Lewis Blackman and Michael Skolnik stories is that of a surgeon who neglects to engage in a proper informed consent with a patient about the relative risks and benefits of a new surgical procedure. That both cases end in tragedy is immensely sad, but it would be a mistake to view the cases as isolated examples.  Indeed, they are representative of a broader violation of the public trust.  As I have noted with regard to the Blackman case:

[These are] cases in which an ambitious surgeon with a new technique or using new equipment takes on a case without providing full disclosure to the patient or family about the potential for increased risk compared to proven methods.  Some hospitals are complicit in promoting such "experiments" by not requiring IRB approval (i.e., human subjects review) or approval by some peer ethics committee.  They (surgeon and hospital) do this for business reasons, to offer themselves in a competitive marketplace as having "the latest and the best."  The surgeon then writes an article proclaiming the success of the new procedure, but that article seldom or ever looks at the long-term consequences, and it never indicates why--in terms of risk to the patient--the new procedure went forth in the first place.

Today, I summarize another case that, to me, raises similar concerns.  I offer it so that you can make your own judgment, and I welcome your comments below.

The surgery occurred several years ago.  Of course, I have no access to the detailed patient records.  I only have materials that are in the public domain, but they offer a story worth telling.

There is perhaps no procedure more compelling than a living related liver donation, and I count the surgeons who carry out these procedures as nothing short of heroic.  USCF notes:

In living donor liver transplantation, a piece of liver is removed from a living donor and transplanted into a recipient. The procedure, performed after the diseased liver has been removed, is possible because the liver regenerates or grows. The liver's unique ability to regenerate itself — combined with technological advances — allows more people to be donors.

Regeneration happens over a short period, possibly days to weeks and certainly within eight weeks. When surgeons remove a piece of the donor's liver, the part that remains grows back quickly to its original size.

That simple description belies the complexity and risks of this procedure, not only for the recipient, but also for the donor.  Back in 2010, Dr. William F. Balistreri, Medical Director, Liver Transplantation Program, Cincinnati Children's Hospital Medical Center, noted (cites omitted):

Live donor liver transplantation, specifically, performance of a major hepatectomy on a healthy individual who has no medical indication other than offering an allograft liver for the recipient, has long been viewed with caution and skepticism. Therefore, substantial efforts are expended to ensure the safety and long-term well being of the donor. The best outcomes for both donors and recipients have been maximized via technical refinements, innovative pre- and postoperative management strategies, and careful follow-up.

The estimated risk of mortality is 0.5 to 1%. Overall donor morbidity is high, estimated to be roughly 35%. This is usually related to the surgical incision and the possibility of blood clots; other reported problems include bleeding, infection, bile leaks, damage to the bile tree, or risks from anesthesia. Donors have reported chronic problems, including bile strictures, reoperations, and chronic pain.

In summary, the risk of dying from living liver donor surgery may be as high as 0.5% when donating the right lobe. If all complications are included, 1 of every 3 donors will experience a complication; most are considered minor or have no permanent sequelae. Thus, centers must carefully weigh the risks against the benefits. Likewise, potential living liver donors should balance the decision to donate with the advice of family, friends, an independent donor advocate, and the medical/surgical team. As stated by Marsh and colleagues, "no matter how carefully right lobar living donor transplantation is applied, the historical verdict on the ethics of this procedure may be harsh." 

Dr. Balisteri's remarks relate to the general case. Adding the use of robotic surgery techniques increases that risk, as noted in the textbook Transplantation of the Liver, by Ronald W. Busuttil, Goran B. Klintmalm (page 734):

So, now let's go back to 2008.  What more compelling story can we imagine than a brother donating a portion of his liver to his sibling?  Titled "True Example of Brotherly Love," Channel 13 reported:

Finding the perfect match means accepting that the right person may never come along. But for one Rockford area family the right donor is not only a perfect match, but a testament of brotherly love. The two underwent a first in the medical world. It's called the da Vinci Robotic Surgical System and now the University of Illinois Medical Center in Chicago completed the world's first minimally invasive liver resection.

This is basically bonding two brothers in a very unique way. Gary Tongue needed a living donor. Gary tells 13 News, "One day he showed up and wanted to know about the live donor transplant thing." "He" is Charles Tongue, Gary Tongue's half-brother. Gary had liver cancer which to him was a death sentence until both families started exploring. Charles says, "You have to be pretty much a perfect match. Weight, height, everything has to be about right."

With the most important match being blood-type. Dr. Enrico Benedetti completed the procedure by taking 60% of Charles' liver to replace the diseased liver in Gary. Doctors ended up finding five tumors saying it was worse then they thought. Gary states, "It was rough for awhile. It's one heck of a surgery to go through, but I think it's all going to worth it." Both came home last week and continue to recover together. Charles states, "It's a big weight off his shoulders that you know he's got it and things are working good and I know he's going to live now."

Gary continues on by saying "You really have to love someone to do what he did. By giving me a piece of that. It saved my life is what he did."

The publicity continued on a liver failure support group site, with the following headlines:

Surgeons used the Da Vinci System to perform the first ever robotic liver transplant, done at the UIC Medical Center.

Team performs world's first robotic liver transplant 

The story continues (emphasis not added):

Transplant surgeons performed the world's first minimally-invasive liver resection for living-donor transplantation last week at the University of Illinois Medical Center.

Gary Tongue, a Rockford area man, was the first to receive this transplantation performed by robotic surgical techniques. Charles Tongue, his half-brother, was the donor of the liver. When Charles realized how high his half-brother's risks were, Gary decided he could donate a portion of his liver to him and potentially save his life.

UIC's chief of general surgery, Dr. Pier Cristoforo Giulianotti and his colleague Dr. Fabio Sbrana, used the da Vinci Robotic Surgical System to remove 60 percent of Charles Tongue's liver. Surgeons then placed Charles' liver into his half-brother, Gary. The process would have included a long incision covering the entire upper abdomen that is required to remove the right lobe of the liver. UIC's surgical team, aided by the da Vinci Robotic System, used a different approach. They completed the procedure through four small incisions. They then removed the lobe through a three-inch incision in the lower abdomen to minimize any postoperative pain that patients might experience.

According to Giulianotti, "this transplant could be a turning point event heralding a new era in living-donor liver transplantation. The possibility of offering the donor a perfect minimally-invasive operation, increasing the accuracy of the resection while minimizing operative risk and blood loss, is a major step forward." 

Benedetti further explained transplantations by clarifying the risks involved. "We discuss openly the risk of the donor procedure with prospective donors and we routinely involve an ethical committee representative to ensure that the potential donor has fully understood the risks," said Benedetti. "We quote a risk of mortality of 0.2-0.5 percent, according to the current Literature data. We also quote a risk of about 30 percent of complications, including potential for bleeding, leak of bile, infection etc. Usually after resection the liver will regenerate to full size within five to seven weeks."

"Living donor liver transplantation is a life-saving option, especially for a patient with liver cancer," Benedetti said, "but it's very important that the donor understands the risks and be healthy enough to be a good candidate." He pointed out that in order to do this surgery doctors must operate on a healthy man to remove much of his liver. In the Tongues' case, Charles didn't hesitate to offer his liver to his half-brother, Gary. "I couldn't ask Charles to do this, but he insisted," said Gary. 

The same story showed up on this investor website.

In 2011, the case was summarized by the surgeons and others in an article in Transplant International.  Of relevance to us here, the article stated:

The possibility of using minimally invasive robotic technique for RLDH was discussed during the process of informed consent. All technical aspects and safety issues were explained, emphasizing the fact that the robotic approach had never been used before for RLDH. Subsequently, the ethics committee of the hospital evaluated the donor in accordance with the previously published standard protocol [6]. The donor agreed to proceed with the planned RLDH using robotic technique.

The "previously published standard protocol" is dated 2005. Its focus is on the general ethical standards that apply to liver transplants, well before any application of robotic surgery to this kind of procedure.  And we are left with no information as to how the surgeon explained the risk of the robotic technique to the patient, or how the surgeon explained why use of the robotic technique would be superior to standard procedures.

Of particular note, the authors acknoweldge that "the length of surgery was longer than that normally required for open right donor hepatectomy," but then state that "it must be considered that the complicated venous anatomy prolonged the total operating time."

I can't evaluate the latter clause, but my understanding from experts in the field is that the 8-hour duration of this case was considerably longer than a standard open donor hepatectomy, which is usually 5 to 6 hours.

Years later, the April 2015 Annals of Surgery "Recommendations for Laparoscopic Liver Resection" (Volume 261, Number 4, at page 623) notes that the quality of evidence--which presumably includes the above article--that the outcomes of robotic liver resections "are superior or not inferior to other techniques" is "low" and that the procedure should still be considered in the stage of development that requires institutional ethical approval and detailed reporting of results and maintenance of a registry:

It is hard to go back to 2008 and imagine what was in the mind of the surgical team for this case.  The issue is complicated by the intense desire of this hospital to be known as a center for robotically assisted surgery and the surgical team's long-term relationship with the company manufacturing this equipment.  (Interpretations today are also complicated by their financial relationships with the company.)

In my mind, the team should have been required to get IRB approval (a standard for objective review of human subjects experiments) for this case.  It was a new technology being applied to a live donor who had little to gain and well documented risks of morbidity and mortality.  Approval of the usual ethics committee for live donors was likely inadequate when adding on the unknown risk of robotic surgery.  The biggest risk of doing these cases in a minimally invasive way is that if you get into serious (and often sudden) massive bleeding you won't be able to open and control the bleeding quickly enough. The patient could die or have severe hemorrhage before it is controlled. There is also the additional risk of a longer time under anaesthesia.  An IRB review by uninvolved individuals with a variety of backgrounds would have balanced those potential risks against the additional scientific and clinical knowledge that could result from the experiment.

In summary, new surgical approaches like this--where there will not likely be randomized trials but where the risk is high--suggest that IRB approval should be part of the development of the new technology.  Absent that, the patient is held hostage to the possibility that the surgeon's personal judgment--no matter how well intentioned--might be colored by commercial strategies of that doctor, the hospital, and the equipment supplier.


David States said...

From Facebook:

Important issue. IRB can respond urgently when needed.

Anonymous said...

Sadly that is the truth nowadays.

Neville Sarkari MD, FACP said...

There is much that is wrong with the way that new procedures and new technology are introduced in our healthcare system. The DaVinci and Proton Beam radiation are just two of the more visible examples. There are many others. Until the incentive to make tremendous profit is removed, it will always be this way...

Anonymous said...

Dear Paul, you are spot on.
Another point that I would ask you to ponder is the realization that in this country what is new is always perceived as better even if the evidence is against version 2.0. Of course, Apple may provide you with a better version of its PC all the time, but medicine is different. Version 2.0 might not be better and the history of medicine is full of examples of things who have gone bad. The problem in medicine is that physician self-regulate their practices without any sort of control. Professional Societies only provides guidelines but never address the fundamental problem.
...And patients trust their physicians. Hence the IRB is necessary to protect patients from a healthcare model that so far provides value ($) only to physicians (In most cases, though).