The thing that blows me away about Tito’s case is how close I came to giving up on him. I remembered the thoughts that went through my head in the OR:
I can’t save him.
He doesn’t have a chance.
It would be better for his family if we called it and moved on.
They could grieve and then go on with their lives.
But then something changed my mind. I attribute it mostly to Orinda’s expression of her trust in me. This is the crux of being a surgeon: Patients and their families trust you to do the best thing for them, for their loved ones. They take you at your word. You bring people to the OR, you open up their bellies or their chests, their heads, their limbs, you put their lives into your hands, and your judgment becomes everything. This is both the beauty and the challenge of surgery. This is why we train so hard and help one another and push ourselves to be perfect even when we can’t be. This is why surgery can be so wonderful, but also so humbling. It is also why we need to call for help, own our mistakes, always try to be better.
These organs we transplant—the livers, the kidneys, the hearts—they are the ultimate gift, the gift of life, the last thing the dead can bestow upon the living. We, as surgeons, simply transfer them from one person to another. We are the stewards, and it is our job to make sure the gift is given. Yet I am blown away by how hard we need to fight for it sometimes, how often we must remind ourselves about the pioneers in transplant: They never gave up. It would never have crossed their minds.
THOMAS STARZL WAS not deterred by the surgical challenge presented by the case of Bennie Solis, the three-year-old who died on the table. He recruited a clotting expert onto his team and came up with a game plan that involved infusing human clotting factors during surgery. With this technique, Starzl performed his next transplant in May 1963, on a forty-eight-year-old male with a primary liver cancer. The surgery was successful, and the patient awoke by the next day with a functioning liver and beautiful golden bile coming out of the tube left in his bile duct during the surgery. Unfortunately, twenty-two days later he died when blood clots, which had formed in the plastic tubing bypassing blood around the liver while the portal vein was clamped, entered his lungs. Starzl would perform three more technically successful liver transplants in 1963, but all these patients would die from clotting problems.
In September 1963, Franny Moore and his team jumped into the fray, performing the first liver transplant at the Brigham, on a fifty-eight-year-old patient with metastatic colon cancer. While the patient made it through the operation, he died on post-op day eleven from pneumonia and infection in the liver. An attempt was also made in Paris, in January 1964, but this failed due to hemorrhage. Moore and his team completed four cases, two adults and two children, between 1963 and 1965. None survived. Soon clinical trials were halted all over the world due to a self-imposed moratorium on the procedure.
Starzl was certainly disappointed with these early failures, but in no way did they shake his belief in liver transplant becoming a reality. He was a man on a mission, and he was going to take this all the way. He knew there would be heartbreak, complications, and resistance from colleagues. None of that deterred him. By this point he had done hundreds, maybe thousands, of transplants in dogs and knew the operation on a healthy animal inside and out. He also knew that things such as coagulopathy and infection would need to be sorted out in humans as well. His lab work became very focused.
Three months before he resumed liver transplantation, he decided to focus only on children. The pediatric department at Denver supported his efforts, but the adult medical team did not. This was not the first time Starzl proceeded without support, and it wouldn’t be the last.
On July 23, 1967, he transplanted Julie Rodriguez, a nineteen-month-old with an unresectable cancer in her liver. The surgery went beautifully, and Starzl thought he had cured her—until new spots were noticed on her chest X-ray three months later. He returned Julie to the OR at three and a half months and again at seven months, to take out new tumors, but they kept recurring. She lived for four hundred days. Starzl would keep a painting of her over his bed for the rest of his life.
On April 17, 1968, Starzl presented data on his first seven transplants since the moratorium had ended. Four patients had died in less than six months, but three were still living. One was Julie; a second was Terry, a sixteen-year-old who lived for more than a year and actually returned to high school until her tumor recurred. The last, Randy, was a two-year-old with biliary atresia. After suffering chronic rejection, he died at the age of four and a half during an attempt at retransplantation. In 1969, Starzl finally had a long-term success. Kimberly, another child with biliary atresia, was still alive twenty-two years later.
Starzl put it bluntly: “A grim conclusion was unavoidable. Liver transplantation was a feasible but impractical way to treat end-stage liver disease.” The bad outcomes continued to weigh heavily on him:
The mortality from the failed early trials and that which occurred later did not mean that liver transplantation was causing deaths. These patients were under a death sentence already because of the diseases that had brought them to us. Even now, I continue to receive letters from parents or family members. These always start by saying that they know I won’t remember Jimmie or whatever was the patient’s name. Then they express thanks for the fact that we had made an effort instead of letting their children die, off in a back room without hope. Those opposed to trying always claimed that these little creatures had been denied the dignity of dying. Their parents believed that they had been given the glory of striving.
They were wrong about one thing. That I would not remember.
He remembered every single one of them.
Enter Roy Calne, Again
If Starzl came to the discipline of liver transplantation because he was fascinated by the organ and the complexity of the operation (and was looking for a mission), Calne came to it because of his love of immunology. He began experimenting with liver transplantation in pigs and was surprised to see that rejection was much less likely with this organ than with kidneys, and in some animals, he could even achieve long-term graft survival. Finally, in 1968, he announced to his colleagues at Addenbrooke’s Hospital, in Cam-bridge, England, that he was ready to perform a liver transplant in a human. His first case would be a woman with a tumor in her liver.
On May 2, a child was admitted with viral meningitis and was deemed to have an irreversible brain injury. The ventilator was to be turned off, and the family consented to organ donation. Calne knew that he was alone in his desire to proceed, and called a meeting with his colleagues to try to win them over. In yet another stroke of luck, on top of having a donor and a recipient available at the same time, he received a call from none other than Franny Moore, his old mentor. He was in town visiting his son, a graduate student at Cambridge, and agreed to come to the meeting to discuss whether Calne could proceed with the surgery.
The meeting convened a few hours later. Calne presented his plan, and then went around the room asking for opinions. Every last person voted no; they deemed the surgery too dangerous. Then Calne turned to the visitor sitting quietly at the back of the room, unnoticed but listening intently. “After listening to this litany of pessimism, I introduced Dr. Moore, world-famous (even in Cambridge), and together with Starzl, one of the pioneers of liver grafting. Moore’s response was short and typical of him. ‘Roy, you have to do it.’ The opposition collapsed, and we made immediate plans for the surgery.”
Moore assisted Calne on this first liver transplant in England. The case was complex, but ultimately went well. Calne was concerned that the small size of the cava would be too small to replace the recipient’s adult-size cava, so he performed the world’s first piggy back transplant, leaving the recipient IVC intact and sewing the end of the donor IVC to the side of the recipient IVC. The recipient woke up postoperatively with immediate liver function. Sadly, she died of infection over two months later.
Fou
r of Calne’s first five patients never left the hospital. But one, a forty-eight-year-old woman named Winnie Smith, survived for five years (before succumbing to infection after a blockage of her bile duct). She did so well that, in 1972, Calne brought her with him to the International Transplant Society meeting in San Francisco. After her case was presented, she took the stage and answered questions.
In a recurring theme, if the 1960s were full of promise, accomplishment, and hope, the ’70s were generally a period of carnage interrupted by the occasional bright moment. Although a few other transplant teams popped up and then folded over this decade, a large majority of the liver transplants were performed by Starzl’s and Calne’s teams, with Starzl’s bearing the biggest load. By 1975, few other liver transplant programs existed. Starzl and Calne, along with kidney transplant surgeons scattered around the world, were using the triple drug therapy of azathioprine, steroids, and an antibody to immune cells that had recently been developed (antithymocyte globulin, or ATG). Still, they lost their patients due to either rejection or, more often, infection. The spark that was needed to truly start the fire was a novel immunosuppressant.
When Calne finally introduced cyclosporine to kidney transplant, Starzl jumped on board to see if this was the spark they’d been looking for. As soon as he had some experience with cyclosporine in kidney transplants, he quickly moved on to liver transplant. This was no easy task. By this point, he was on his way out at Denver—when it came to Starzl and his insane quest to make liver transplantation work, the leadership and most of the faculty there had lost their nerve and weren’t interested in supporting another expensive trial that was sure to fail. Starzl hammered through anyway, beginning a liver trial in March 1980. He performed twelve liver transplants between March and September 1980. Eleven of the twelve lived for a year or longer.
In 1981, Starzl published his one-year follow-up on the cyclosporine livers in The New England Journal of Medicine. He was at Pittsburgh now, finally starting to believe that liver transplantation might be more than an experimental therapy. But his first four liver transplant patients at Pittsburgh died within four to twenty-two days. Then Starzl’s luck—and that of his patients—turned around. Of the next twenty-two liver transplants, nineteen had long-term survival, and that number would keep doubling. By 1983, cyclosporine would finally get FDA approval, and the world of transplantation would explode. That same year, with some help from the US surgeon general C. Everett Koop, liver transplantation was deemed a service rather than an experimental therapy, which led to insurance companies finally covering those undergoing the procedure.
If this were a movie, Starzl would now walk off into the sunset as the credits rolled. But he wasn’t done yet. He wanted to train the next generation of transplant surgeons, and he had plenty of organs to work with. As there were still few transplant centers to compete with, the volume at Starzl’s hospital skyrocketed—one year, he transplanted more than five hundred livers—and fellows flocked to Pittsburgh to spend two years with the master. It’s shocking to think about all the people Starzl trained. Virtually every liver transplant center in this country can trace its origins to Starzl within one or two generations, and to this day, many of the leaders in our field are Starzl disciples. He is like a god to so many, the most important mentor in their professional lives—although more than a few have some PTSD from the experience, the demands and intensity were so high.
Starzl hung up his scalpel in 1991, at the age of sixty-five. Some of his colleagues and trainees were shocked and disappointed, but for Starzl, it was perhaps the easiest decision he had made in years. “I was wiped out, ” he said. He had accomplished everything he had set out to do, including championing a new immunosuppressive drug, FK506, which would go on to replace cyclosporine as the primary immunosuppressant and is still used today in solid organ transplantation. Starzl lived an additional twenty-five years, and for that time, he came into work every day to continue his research on transplant immunology. He died on March 4, 2017, just a week before his ninety-first birthday. As Münci Kalayoğlu, a Turkish-born surgeon who trained with the “maestro,” once said, “Watching Dr. Starzl was . . . was not surgery, but art.”
Part IV
The Patients
If the history of medicine is told through the stories of doctors, it is because their contributions stand in place of the more substantive heroism of their patients.
— SIDDHARTHA MUKHERJEE, THE EMPEROR OF ALL MALADIES
10
Jason
The Secret Is to Live in the Present
We cannot change the cards we are dealt, just how we play the game.
— RANDY PAUSCH, PROFESSOR OF COMPUTER SCIENCE AT CARNEGIE MELLON UNIVERSITY; AUTHOR OF THE LAST LECTURE; DIED OF PANCREATIC CANCER ON JULY 5, 2008, AT THE AGE OF FORTY-SEVEN
You must live in the present, launch yourself on every wave, find your eternity in each moment. Fools stand on their island of opportunities and look toward another land. There is no other land; there is no other life but this.
— HENRY DAVID THOREAU
A friend once told me, “You are only as happy as your unhappiest child.” True. And as a surgeon, I am only as happy as my sickest patient. I worry about my patients before and after surgery, expecting something to go wrong even when I’m sure everything has gone perfectly. After some years of being a surgeon, I assumed that this nervousness would go away, but there is rarely a time when my patients are not in the back of my mind. I scour their charts every morning and night, looking at every vital sign, nursing note, lab value. I text my fellows to get updates, particularly when I notice they’ve ordered an X-ray or CT scan—and I always notice. The details are critical. A single overlooked lab or test result can lead to a disaster that could have been averted.
There are only two times when I don’t worry about my patients. One is when I am in the operating room with them. I’m not cavalier about surgery. I am acutely aware that it is critical to stay focused, keep your mind clear, and not get frustrated. Good surgery is so much about mental toughness and intestinal fortitude in the face of stress and exhaustion and interruptions such as phone calls and pages. And yet the operating room is not a stressful place for me. I am there with my team, my music (generally Tupac on Pandora), and my jokes (which everyone always laughs at, funny or not). I am focused on operating, teaching, and keeping the room light and positive. I love getting to know my patients preoperatively and postoperatively, but none of that plays any role in the OR. It doesn’t matter if the patient is nice or a jerk, rich or poor, loving of mankind or a complete racist (like the guy with the swastika tattoo I recently put a kidney into). Most of the patients I evaluate for liver transplants have led difficult lives and made poor choices with regard to their health. I don’t judge them for it, though, and I certainly don’t claim to understand what their lives were like.
The other time I don’t worry about my patients is when they are dead. I feel terrible that they died, and guilty for my role in that, but I have developed a strong coping mechanism that somehow allows me to move on.
I remember most of the patients I’ve transplanted over the last decade incredibly well, and the details of their operations almost to the last stitch. Sometimes I can’t picture their faces or their families, but when I review the operative note, I remember every aspect of the case—how the liver sat, how I struggled on the upper cuff, how I encountered bleeding on the cava. I remember best the ones who had problems—difficult recoveries, lengthy postoperative courses, and returns to the operating room.
This is a sad thing about surgery. Most of our patients do really well, but we spend all our time working on and thinking about the ones who do poorly. One of the things that attracted me to the field of transplantation, other than my love of immunology and my (mistaken) belief that it would impress women at parties, was that it is one of the few remaining areas of surgery where we develop lifelong relationships with our patients. We see them when they are being considered for the trans
plant waiting list, during their hospital stay, and forever thereafter. This is partially because patients don’t want anyone to make decisions about their health other than the doctors who put in their new organs, and also because they are on immunosuppressive medication, which makes them much more complicated to care for than other patients. With medication suppressing their immune systems, simple illnesses can explode into life-threatening conditions, minor outpatient surgeries become disasters, wounds don’t heal, bowel anastomoses fall apart. It is an honor to be a part of their recovery, but also a burden.
Every now and then, I have run across a patient who leaves an indelible impression on me. Jason was one of those people. I first met him in the transplant clinic in 2011. It was a Thursday, and his visit was scheduled for 10:30 a.m. I was running late doing a donor nephrectomy (removal of a kidney from a donor) and had to run to the appointment with Jason still wearing scrubs and a white coat.
Jason was sitting by the door watching me approach. I remember being surprised at how young he looked. (He was thirty at the time.) His parents, sister, and brother were there, too, looking nervous, respectful, and supportive all at the same time. I was struck by the scene because I was so used to seeing older patients, many of them ravaged by alcohol addiction or hepatitis C, and often from troubled families and therefore with little familial support. Overall, with the exception of the unmistakable yellow tinge to the whites of his eyes, Jason looked pretty healthy to me.
We began talking, and I learned that he was a history teacher at a high school in Wisconsin. He particularly loved teaching European history, and had a strong devotion to Scotland, where he had first gone as a college student. In fact, his illness—or, at least, the part of his illness that included his liver—had begun during that summer trip to Scotland. It started with itching, which at first seemed to be no big deal but soon became harder and harder to ignore. He then found himself extremely lethargic, to the point where he had to drag himself out of bed in the morning. Years before (at the tender age of fifteen), he had been diagnosed with Crohn’s disease, but that was under control. Something different was going on now.
How Death Becomes Life Page 19