Lily Mandel Allen was one of the earliest patients to receive a liver transplant at UCLA 25 years ago. Today she is thriving, and so is the program that saved her life. By David Greenwald
THE PHOTOGRAPH OF LILY MANDEL in her hospital bed at age 14 months is shocking. Twig-thin arms and legs stick out from her swollen torso. Her belly is a taut vein-streaked balloon bulging with her bloated liver that has been invaded by tumors. The baby’s dark eyes are huge and startled. Her condition, a non-malignant hemangioendothelioma, is very rare; only about a dozen cases have been reported worldwide. Lily’s doctors at the University of Arizona in Tucson have tried to stop the progression of the disease with drugs and chemoembolization, but nothing has worked. Surgical removal is not possible – her liver is so filled with tumors, it would be like trying to cut holes out of Swiss cheese. As the tumors continue to grow, they will suffocate Lily’s other organs. There is nothing more that can be done, the doctors tell her parents. Begin to prepare for the inevitable.
“There comes a point, they said to us, when all we can do is try to keep her comfortable and to let her go when it’s time,” says Lily’s mother, Lydia Moon, her voice cracking.
A few days after what Moon refers to as “the death talk,” one of Lily’s doctors calls with news. About 500 miles away, in Los Angeles, a young vascular surgeon named Ronald W. Busuttil, M.D., Ph.D., and a group of his colleagues at UCLA have launched a liver-transplant program. It is very new, just a few months old, and Dr. Busuttil and his team have done only a handful of cases. Transplantation is a long shot, but for Lily there are no other options. Arrangements are made, and she is brought to UCLA Medical Center for evaluation. The year is 1984.
TEARS POOL IN DR. BUSUTTIL'S EYES when Lily Mandel – now Lily Mandel Allen – walks through the glass doors of Mattel Children’s Hospital UCLA. It is December 2008. She is 25 years old, a lively, brown-haired newlywed with bright eyes and a wide, engaging smile. It is difficult upon seeing her to reconcile the healthy young woman framed in the doorway with the stark picture of her as a baby. Lily stops for a moment when she catches sight of Dr. Busuttil – she was a toddler when he operated on her, and she has no conscious memory of him – and then walks quickly toward him to embrace.
“It was,” she says later, “one of the very best hugs of my life.”
Lily visited with Dr. Busuttil for the first time in so many years after traveling to Los Angeles from Syracuse, N.Y., where she lives with her husband, Brian, to help decorate and ride on the 2009 Rose Parade float of the Donate Life transplantation-support organization.
“After all these years, this feels so beautiful to be able to say to him ‘thank you for giving me my life,’” Lily says. “It is an amazing gift.”
On February 1, 2009, the 25th anniversary of the first successful human-liver transplant at UCLA, there was another reunion: Some 1,800 transplant recipients and their families gathered with members of the transplant team to commemorate the milestone, an event that Dr. Busuttil says was “emotionally overwhelming.”
UCLA’s program has done close to 5,000 liver transplants since its inception – roughly the equivalent of performing one transplant every two days for 25 years – making it the largest and most-active program in the country. Lily’s operation, on August 8, 1984, was the ninth transplant Dr. Busuttil performed. “When you think that three-quarters or more of our patients are still alive, it’s an amazing thing to comprehend,” Dr. Busuttil says.
GETTING THE PROGRAM STARTED HERE was no easy feat. Liver transplantation was in its infancy 25 years ago. Only the University of Pittsburgh had established a significant program, under the leadership of the pioneering transplant surgeon Thomas E. Starzl, M.D., Ph.D., and there were a few other smaller centers elsewhere, but the operation still was considered by most to be experimental. Many were skeptical of the procedure, and some even questioned its morality.
But Dr. Busuttil was determined that UCLA would establish the first successful program west of the Mississippi River. Other institutions in the West had tried to start centers but with sometimes disastrous results. One hospital had to use so much blood product during an operation that its blood bank was forced to shut down for elective surgeries for three days. UCLA also made an early attempt to establish a liver-transplant program, but it was suspended in 1968 after four surgeries.
This time, UCLA would succeed. Frustration was the impetus for wanting to launch a program, Dr. Busuttil says. As a vascular surgeon, he could successfully manage a patient’s bleeding from such conditions as varices in the stomach or esophagus that developed from liver disease. But too often these patients subsequently went into liver failure and died.
“If a patient is in kidney failure, there’s a machine that can keep him or her alive for years. If a patient is in liver failure, there is no such support device,” says UCLA adult-liver specialist Leonard Goldstein, M.D. “The only hope for patients in that situation is a transplant. A liver transplant can restore them to life.”
The death of one young man struck particularly hard. Dr. Busuttil had successfully performed a distal splenorenal shunt to control the young man’s bleeding from congenital hepatic fibrosis, but the patient went into liver failure a day or two later. Though Dr. Starzl in Pittsburgh had agreed to accept the patient for transplantation, the young man died before he could be transferred.
“It was absolutely devastating to us,” Dr. Busuttil says. That led to what he calls “the stairwell conversation.” He and Dr. Goldstein were walking from the sixth-floor Intensive Care Unit to the seventh floor when Dr. Busuttil turned to his friend and said, “Leonard, we need to start doing liver transplantation here at UCLA.” To which Dr. Goldstein replied, “Yeah, bubby. Sure.” And that, Dr. Busuttil says, “is exactly how the whole thing started.”
In late 1982, he pitched the idea to William P Longmire Jr., M.D., the founding chair of surgery, who was himself a pioneer in liver surgery and immunosuppression research. “He asked me, ‘Have you ever done any?’ No. ‘Have you ever seen any?’ No.” Dr. Longmire provided a small training grant and told Dr. Busuttil to go to the lab and see if he could learn how to do them.
After assembling a multidisciplinary team of world-class specialists in surgery, medicine, anesthesia and nursing – “This is absolutely a team of equals whose dedication and collegiality are the true recipe for our success,” Dr. Busuttil asserts – he spent close to a year working out the operation on pigs and the procedures for postoperative care. He notes that many of those early team members are still at UCLA, including Dr. Goldstein; general surgeon Jonathan Hiatt, M.D.; vascular surgeon William J. Quiñones-Baldrich, M.D.; pediatrician Judith Brill, M.D.; and pediatric gastroenterologists Marvin Ament, M.D., and Jorge Vargas, M.D. Later, he spent several weeks in Pittsburgh to train with Dr. Starzl – “He was a triple threat,” the older surgeon says of Dr. Busuttil, “one of the smartest and most skillful people that we ever had around here” – and participate in a half-dozen cases.
When Dr. Busuttil returned to Los Angeles, he felt ready to begin. Many among the university’s powers-that-be, however, weren’t as sure. While Dr. Longmire and Sherman Mellinkoff, M.D., dean of the School of Medicine, and Chair of Surgery Eugene Stern, M.D., were supportive, others were less so. “I didn’t get a whole lot of enthusiasm from some of the people in the hospital administration,” Dr. Busuttil says.
He prepared a grand rounds to present his proposal. “There were a lot of people there – department chairs and faculty and administration – and I brought in a couple of pigs that I had transplanted, and I explained the program to everyone and what it was we wanted to do,” he says.
The response, Dr. Busuttil recalls, was decidedly chilly. “There was an extraordinary amount of skepticism,” he says. “They feared it would be very unsuccessful” – like many of the programs that had been tried elsewhere – “and that it would cost a lot of money and drain the hospital’s resources.”
Ultimately, Dr. Busuttil’s request was approved, but with restrictions on the number of cases he could perform, and the implication was clear that he must succeed from the outset or his program would be cancelled. “They told us we could do only six cases in six months – one a month – and then they would re-evaluate and decide if we could continue,” he says. “I had to do an enormous amount of cajoling and using my best persuasive abilities to work around that. If a patient needs a liver transplant and I’ve already done my one for the month, and we have a donor, am I supposed to say to that patient, no, I can’t do it?” In the end, Dr. Busuttil and his team ended up doing 22 transplants in the program’s first year, with a survival rate of close to 80 percent.
“Liver transplantation at UCLA was a fantastic adventure from the very beginning,” Dr. Hiatt says. “Ron Busuttil built the program against the odds. He’s like a guy who put together a go-kart in his garage and ended up winning the Indy 500.”
ON FEBRUARY 1, 1984, A WEDNESDAY, at around 2 p.m., Dr. Busuttil was in his accountant’s office in Palos Verdes, preparing his taxes, when he received a phone call. “‘You’ve got a donor,’ I was told. ‘Where?’ ‘At Saint Joe’s in Burbank, and you’ve got to be there by 6 o’clock.’”
At this point in transplantation’s incipient history, there wasn’t much protocol for collecting organs. Dr. Busuttil rushed back to Westwood, called two colleagues to accompany him and stopped at a convenience store at the corner of Gayley and Le Conte avenues to buy an Igloo cooler and four bags of ice, which he stashed in the trunk of his car. He and the two other doctors raced the 17 miles to Saint Joseph’s Medical Center to harvest the donor organ, put it on ice in the cooler, and then headed back to UCLA.
The operation began at about 9 p.m. in OR 1 of UCLA Medical Center. The patient, Dal Caudill, was a 44-year-old drugstore manager with liver cancer for which other treatments had been unsuccessful. “I told him before we started, ‘You know, I’ve never done one of these and you are going be my very first.’ But he was an extraordinarily religious man, and he had a lot of faith. And he said to me, ‘Doc, I don’t have any other choice because there’s nothing else that can be done for me. It’s in your and God’s hands.'''
The experience of doing that first transplant was exhilarating – and also filled with trepidation, knowing all that was at stake. “Failure was not an option,” Dr. Busuttil says. “With the prevailing skepticism regarding liver transplantation, our first case might have been our last.” By 5 a.m., it was finished. “When it was all over and he was off the table, I breathed a huge sigh of relief,” Dr. Busuttil says. The patient had received just 17 units of blood, and 17 days later, Caudill, his wife, Pat, and Dr. Busuttil walked together out of UCLA Medical Center, an image captured in a photograph that ran in the Santa Monica Evening Outlook over the headline, “UCLA liver transplant program chalks up its first success story.”
So the program indeed started off with a triumph and has been on a steep upward trajectory ever since. Twenty-five years after that first operation, about 60 percent of the program’s early patients are still alive. Unfortunately, Caudill’s malignancy did recur, and he died from cancer about nine months after the transplant. “But if it weren’t for Mr. Caudill and the success we had with him, this program would have not gotten off the ground,” Dr. Busuttil says.
THERE WAS SOMETHING OF a wild-wild West aspect to those early years of the program. For one thing, there was no Organ Procurement and Transplantation Network (OPTN) – that didn’t come online until 1986 – to match potential donors with recipients, so the physicians in the program were pretty much on their own when it came to finding suitable organs. That led to what Dr. Busuttil and others allow were some decidedly ghoulish moments.
“One of the jobs that I had was to call Intensive Care Units up and down the West Coast and as far east as the Mississippi River to ask if they had any potential donors,” recalls Dr. Ament. “There was no OPTN, so if we had a sick child or infant, we just had to pick up the phone and ask, ‘Do you have anybody who potentially is going to be declared brain dead?’ It sounds pretty awful, but there was no other way to do it at that time.”
Adds Dr. Vargas, “This was completely unknown territory for us. But it was also very exciting and very rewarding.”
They have come a long way since then. Today, OR 16 in the new Ronald Reagan UCLA Medical Center is dedicated to the liver service, and there is a separate ICU just for transplantation patients. Instead of taking eight or 10 or 12 hours, the procedure now takes about four or five. Dr. Busuttil is now the chair of surgery at UCLA and the Dumont Professor of Transplantation Surgery, and he is co-editor of the definitive text in the field, Transplantation of the Liver (Saunders, second edition, 2005). In 1994 – only 10 years after it started – the UCLA Liver Transplant Program surpassed the University of Pittsburgh to become the busiest liver-transplant center in the country. Its fellowship program has trained more than 50 liver-transplant surgeons, many of whom have gone on to head their own programs, including at such major centers as the University of Chicago, Massachusetts General Hospital, University of Arizona, Montefiore Hospital in New York, the Johns Hopkins University in Baltimore, University of Texas, University of Cincinnati and the University of Pennsylvania. And about 150 foreign fellows have come to Westwood to observe and study liver transplantation, and bring their new knowledge back to their home countries.
The program also has been at the forefront of advancements in new surgical techniques that utilize the limited resource of donor organs more effectively. UCLA is a leader in living-donor transplantation, and also in-situ split-liver transplantation in which a single donor organ is divided and transplanted into two patients. And the UCLA program is in the vanguard of clinical research, offering patients access to the latest innovations in immunosuppressive therapy and treatment for transplantation-related complications such as rejection and infection.
“We have grown up a lot since that first patient in 1984, but the fundamental mission, saving lives, has not changed,” Dr. Busuttil says.
A LITTLE WHILE AFTER LILY'S SURGERY, her mother walked into the child’s room in the pediatric ICU and found Dr. Busuttil sitting in a chair by the bedside. He was still wearing his blue surgical booties. Another doctor stopped by and asked if he wanted to get something to eat. “No,” Lydia Moon recalls Dr. Busuttil responding, putting his feet up. “I’ll stay right here for now. I just want to baby-sit for a while.”
For more information about the UCLA Liver Transplant Program, as well as other transplant programs at UCLA, go to https://www.uclahealth.org/transplants.