It was at these national meetings that ideas were shared and, slowly but surely, Thomas Starzl gained recognition as the central force in efforts at liver transplantation. Indeed, it was at the ASA meeting that Starzl first heard about ongoing experiments (both at Richmond with David Hume and at the Brigham) using chemical immunosuppression with a new drug called 6-Mercaptopurine. It became clear to him that chemical immunosuppression was the next step in transplant, and that in order to make liver transplant a reality in humans, he would first need to master kidney transplant and move forward with chemical immunosuppression.
In December 1961, Starzl moved out to Denver, where he was appointed chief of surgery at the Denver Veterans Affairs Medical Center. Within three months of his arrival, he performed his first kidney transplant. Given the generally bad outcomes that were the norm during this period, he was smart enough to start with a pair of identical twins: he felt he had to prove his worth to the local physicians and medical community with at least one good outcome before diving into the insane world of immunosuppression in the 1960s.
By the time Starzl got into the kidney business in 1962, Joseph Murray at the Brigham had already reported his successful case with nonidentical twins and had just introduced the immunosuppressant azathioprine to human transplantation. It would be this same year that he would have his first graft survival with a deceased-donor transplant.
Although Murray was proceeding as quickly as he could, and Hume and Roy Calne were performing transplants at their centers, Starzl jumped in like a freight train. Calne and Murray had identified that azathioprine would be useful in kidney transplantation, but it was Starzl who realized that combining it with high doses of steroids was a better strategy than using azathioprine alone. Many investigators contributed during these early years of transplant, but Starzl, with his large surgical volumes, his ability to push new protocols through uninhibited, and his obsession with writing up his results, played an outsize role.
After his successes in the kidney world, Starzl knew it was time to try his hand at clinical liver transplantation.
Prometheus Rising
I love that feeling when you pop through the peritoneum, encounter liters of beer-colored ascites, and first lay eyes on a shrunken liver. You never know what a transplant is going to be like until you get in there, but the second you see the shrunken, mobile liver floating in ascites, you know you’re in for a treat.
“Okay, guys, crank the Pitbull. If I don’t screw this up, we should be done in four hours, maximum.”
Liver transplants used to be like this ten years ago, back when it was so much easier for our patients to get one. Nowadays, thanks to changes in allocation that have increased the sharing of livers around the region, our patients have to be so much sicker to get these precious organs. I suppose that’s fair, but it sure has made my job harder.
“C’mon, Elliot,” I said—Elliot was in the second year of his fellowship, having already completed his surgery residency—“let’s move this along. I really want to get out of here today.”
We had the liver out in just over an hour. “Open the new liver,” Elliot said as we switched sides. Elliot is a lefty, so we had to switch in order for him to sew the upper caval anastomosis.
We pulled up the new liver, glistening and perfect—such a contrast from the knobby, shrunken liver we’d just passed off the table to be sent to Pathology. I held it out of the way while Elliot began to sew in the upper cuff. At this point we didn’t really need to say anything about the case. Elliot knew every step and exactly how I wanted it done. This one went perfectly. He sewed the back wall first, and then the front, throwing each stitch while I “followed” him, holding on to the suture to make sure it didn’t get tangled. Once he reached the end, he tied the two ends up, and we moved on to the portal vein. Again, I assisted him as he sewed that end to end with three 6–0 Prolene sutures. It took us about thirty-five minutes to sew this new liver in, and then we removed our clamps and reperfused. The liver pinked up beautifully, and the patient tolerated it without turning a hair. We then turned our attention to the hepatic artery, which again lined up nicely and seemed almost too easy. I looked up at the clock and smiled. It was only 6:30 p.m. I should be able to make it home before my kids went to bed (my daily goal).
“What’s so hard about liver transplant?” I said to Elliot. “I wonder why Starzl had so much trouble?” We both laughed, thinking about the last one we did, which took twelve hours. You just never know.
ON MARCH 1, 1963, Thomas Starzl attempted to perform the first liver transplant in a human. The recipient was Bennie Solis, a three-year-old boy who was unlucky enough to have been born with a disease called biliary atresia, in which the ducts that normally coalesce to form the common bile duct, allowing drainage of bile out of the liver and into the intestine, never form. Perhaps the worst part of this disease for the parents is that those beautiful babies suffering from biliary atresia appear normal when they are born—with the exception of neonatal jaundice either at birth or developing after a couple of weeks. Since half of all children develop neonatal jaundice that eventually resolves, Bennie’s parents were likely told not to worry. Eventually it must have become obvious that something was wrong—maybe he had some white stool or dark urine; maybe he became inconsolable because of persistent itching; or maybe the yellow color just wouldn’t go away. Lab tests would confirm everyone’s worst fears.
Back then, a diagnosis of biliary atresia was essentially a death sentence. By the time Starzl met young Bennie, he was three years old, yellow, swollen with ascites, and filled with thin-walled nests of varices, resulting from the inability of portal blood to flow through the cirrhotic liver. As if that weren’t enough, Bennie’s liver dysfunction was so severe that his blood contained none of the clotting factors we normally rely on to stop bleeding during surgery.
At the time he met Bennie, Starzl had performed two hundred liver transplants in dogs using prednisone and azathioprine, with reasonable short-term survival rates. He had also performed four nonidentical kidney transplants in humans while using this same immunosuppression, all of which were still functioning for at least four months by 1963. Bennie seemed to be an appropriate liver transplant candidate. In Starzl’s own words:
[W]e viewed the principal hurdle to be the operation itself, which would be vastly more difficult than kidney transplantation. However, nothing we had done in advance could have prepared us for the enormity of the task. Several hours were required just to make the incision and enter the abdomen. Every piece of tissue that was cut contained the small veins under high pressure that had resulted from obstruction of the portal vein by the diseased liver. Inside the abdomen, Bennie’s liver was encased in scar tissue left over from operations performed shortly after his birth. His intestine and stomach were stuck to the liver in this mass of bloody scar. To make things worse, Bennie’s blood would not clot. Several of the chemical and other factors necessary for this process were barely detectable. He bled to death as we worked desperately to stop the hemorrhage. The operation could not be completed. Bennie was only three years old and had not enjoyed a trouble-free day in his life. Now, his wound was closed and he was wrapped in a plain white sheet after being washed off by a weeping nurse. They took him away from this place of sanitized hope to the cold and unhygienic morgue, where an autopsy did not add to our understanding of our failure. The surgeons stayed in the operating room for a long time after, sitting on the low stools around the periphery, looking at the ground and saying nothing. The orderlies came and began to mop the floor. It was necessary to prepare for the next case.
“THIS IS NOT good. This is definitely not good.” I uttered this quietly, but I’m pretty sure everyone in the room heard me. When things get really bad in the OR, I tend to speak more quietly. I never yell, but everyone in the room knows things are serious when the jokes stop. They turn the loud music down and try to listen to what I’m mumbling.
It was about two in the morning, and Paul (a
second-year transplant fellow) and I had just reperfused the liver. And that’s when the shit truly hit the fan.
We had found out about the liver earlier in the day. It was from an older donor, a man in his early seventies whose liver had been biopsied and looked fine. Older livers can work well, but the transplant operation needs to go smoothly—old livers don’t like to sit out in the cold a long time and would like their blood flow back as soon as possible.
The recipient, Tito, had been admitted to the unit the night before, and I thought I would swing by and check him out prior to accepting the liver for him. He was sitting in a chair, an oxygen mask on and a catheter coming out of his bladder. His daughter was giving him an extremely worried and caring look. Tito appeared feeble, fragile, exhausted, but he wasn’t on a respirator, he was sitting up on his own, and he was able to smile when Paul and I walked in. After a few pleasantries, I told him we had just accepted a liver for him.
The room erupted in cheers. Everyone knew this meant life for Tito, and not a moment too soon. I mentioned that it was a big surgery, that there was a lot of risk, that he could die—the talk I’d given so many times before.
THE HEPATECTOMY WENT pretty well. The portal dissection went smoothly—we divided the artery, portal vein, and bile duct without too much trouble. Then we freed the liver off the cava, gaining control around the cava up high above the liver near the diaphragm and down low below the liver near the kidneys. We were ready to cut it out.
I noticed that the bowels had become considerably swollen, because their venous drainage, which goes through the portal vein, had been clamped off. I knew that might make it harder to sew the new liver in, since there wouldn’t be a lot of space to work in, but nothing I could do about it now. I put the clamps on the cava and we proceeded to cut the liver out. Then we opened the new liver (meaning our circulating nurse removed it from the cooler, opened the outer bag, and let our scrub tech pull the inner sterile bag out on the field; we package every organ in three sterile bags for protection).
It was a lot bigger than I was expecting. We pulled it up to the field and started to sew it in. I was concerned with how little room we had to work in, what with the big liver, the swollen bowels, and the diaphragm bowing into our field from the fluid our patient had accumulated in his right chest (a common occurrence in cirrhosis). Damn, I thought this was going to be easier. I wondered if we should stop and make our incision bigger, or just go for it. While I held the liver down as hard as I could, Paul sewed the donor and recipient cavas together. Once we finished the anastomosis, I placed a clamp on the liver side of the donor cava and released the cava from my clamp. There was a bit of bleeding, which we easily controlled, but it seemed okay. The patient was more stable now, with his cava unclamped. We turned the music back up, sewed the portal end to end between the donor and recipient vein, and got ready for reperfusion. The anesthesia and nursing teams were ready. We flushed the liver out with saline and then blood, and then released the clamps.
Everything was okay, and then—he started exsanguinating. It was massive. Paul and I put our suckers by the caval anastomosis, but the bleeding was so intense that we couldn’t see anything. Hence my quiet statement “This is not good. This is definitely not good.”
I quietly told anesthesia we were in serious trouble, and asked the nurses to call in one of my partners. Somehow, we were able to get our clamps back on the cava and the portal vein. Now the donated liver was getting no blood flow.
Once everything was clamped, and the bleeding had stopped, what we saw was . . . well, not good. The entire upper cuff of the cava of the donor liver had become shredded. There were multiple linear tears (meaning the sutures had pulled through all the way around, causing long straight tears in the cava), with more air between the sutures than tissue. We were fucked. I probably needed to take the liver out and try to fix it on the back table, perhaps by getting some vessels from the vessel bank and then trying to sew the liver back in. But as I was considering this, Sergei, the anesthesiologist, told me that we were in serious shit. Tito, our patient, was going to code at any minute. I started to picture Tito’s daughter. She had been so happy when I told her we had a liver for her father.
By now my partner Dave had joined me, appropriately impressed with the situation. We racked our brains over what we could do, other than just stand there and watch Tito die. And somehow, we came up with an idea, one that seemed so crazy it just might work, although we had never done it before.
I placed a side-biter clamp on Tito’s cava down below the liver. I cut a hole in his cava above my clamp and proceeded to sew the donor infrahepatic cava to the recipient cava. This took about ten minutes. We opened the clamps and there was flow through it. Then I grabbed a vascular stapler and fired it across the upper cuff. Most of the surgical bleeding from the cava stopped. Success. We basically rerouted blood, so that rather than flow through the donor liver and out the top, the blood flowed through the liver and went out the bottom, still into the recipient cava.
Except . . . we were still swimming in blood. It was now about five in the morning. We had been working all night, and the patient had been tanking for two hours.
“This is not working,” Sergei said, stating the obvious.
The donor liver looked like dogshit—it was mottled, swollen, and pale, and Tito’s labs were abysmal, making it unlikely that he would survive no matter what we did. This new liver was not functioning at all. I told the nurses to find out where his family was; I wanted to tell them he wasn’t going to make it out of the OR. Somehow it seemed important to tell them this before it was over. At least he was still alive now.
It is a helpless feeling walking out of an operating room knowing your patient is going to die. I couldn’t stop thinking that maybe if someone else had performed the surgery—maybe Tony, or Dave—this wouldn’t have happened. I walked toward the surgical waiting room; I could see Tito’s daughter, Orinda, in the distance. I was so tired I could barely walk, but I was acutely aware that she was staring intently at my face, trying hard to catch some clue as to what I was about to say.
I sat down next to her. “Things are not going well. We initially got the liver in, but then we had a tear in the blood vessels. Your father has lost a lot of blood, and he is very unstable. I really don’t think he is going to make it out of the operating room.”
There it was. I’d gotten it out. I could see tears in her eyes, but she held it together.
“Is he still alive?”
“Yes,” I told her. “But he is very sick. I don’t know if his brain is okay. The liver is not working. I think you should call your family to come in now.”
She thanked me profusely for having done everything we could, but then she said, “I know you will do everything you can to try and save my dad.”
Those words were ringing in my ears when I got back to the OR. Maybe we could at least make some progress, I figured; get Tito to the ICU, get him to a point where we could at least entertain the idea of a new liver.
I asked for a stitch, and aggressively threw it in a small hole in the cava. I asked for another. And another. Fuck it. Let’s do this.
Dave, Paul, and I spent the next three hours throwing stitches, burning tissue into bloodless submission with the heat of the argon beam, and intermittently packing Tito’s belly. The energy in the room started to change. We started to think that maybe there was a chance. It still seemed like a one-in-a-million chance, but it was a chance. Tito had lost close to a hundred liters of blood, which, while not a record, is astronomical. There was still a lot of work to do, but I told the nurses to get Tito’s family into a meeting room. I wanted to give them another update.
“Okay, here is the deal,” I told them when I found them later. “We have definitely made some progress. But Tito is very sick. I still think it is likely he won’t make it through this. I have no idea if his brain is okay. We won’t be able to close his belly for now, and he will definitely need to come back to the OR. Honestly, th
e absolute best-case scenario is that we make it to a point where we can list him urgently for another liver. But even that is a long shot.”
At this point, there were about twenty family members there with Orinda. They seemed understanding, and said they were very thankful. They said Tito was a fighter. I felt so glad that at least they’d be able to say good-bye to him.
I went back to the OR. By this point, Tony and Luis had scrubbed in, replacing Dave and joining Paul, who was now only barely awake. (He was in for the long haul. Such is the life of a fellow.) Tito was in good hands.
I walked to the locker room, sat on a bench and looked down at my scrubs. They were covered in blood. I peeled them off and threw them in a hamper. I barely remember driving home. Once there, I stumbled up to my bedroom. My dog, Phoebe, seemed confused. She ran behind me, no doubt hoping I would take her out. I envied her. She has a pretty good life: she sleeps all she wants, and she doesn’t kill anyone . . . except maybe a squirrel or a rabbit.
I lay in bed, my head spinning. I could still see all that blood welling up in Tito’s belly as I fell into a dead sleep. Two hours later, there was a text on my phone telling me I had a patient to see in the clinic.
I SAW TITO in my office recently with his daughter, Orinda. After the transplant, he was extremely ill in the ICU. His kidneys failed, he was on a ventilator, and the liver we had put in was barely keeping him alive. After a week or so, we got him a new liver. That transplant went better. He spent about a week in the ICU and another few weeks in the hospital. Then he went to rehab, and now he was home. His new liver was perfect; his kidneys recovered, and he was back with his family, looking great. (Thinking back on the operation, I couldn’t believe this was the same man sitting in front of me.) He told me about his childhood in Puerto Rico, his current life in Wisconsin. He told me about his big family, how much he loved them. Orinda was sitting next to him beaming, his guardian angel.
How Death Becomes Life Page 18
