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Right in the Gut

By Ault

Organ transplants, once-exotic procedures carried out at the edge of medicine,

have become almost commonplace. Surgeons have succeeded with, and in some cases

nearly perfected, the harvest and implanting of kidneys, hearts, livers,

pancreases, corneas, bone marrow, even skin and lungs.

But one of the most difficult challenges in transplant science is in the gut.

More specifically, the small intestine.

Every known pathogen " lives in a big cesspool in your intestinal tract, " said

Fishbein, 41, of town University Hospital, one of the few surgeons

who perform transplants of the small intestine, also known as the small bowel.

" On top of that, what's in your bowel? "

When transplant patients receive this highly infectious organ, they are also

taking powerful immune-suppressing drugs to prevent organ rejection. In other

words: Insert dirty organ, turn off immune system.

" That is a very deadly combination, " Fishbein said.

Though experimental small bowel transplants were done as early as the 1960s,

until the last few years the operation was reserved for patients near death,

surviving on intravenous nutrition and out of other options. But rejection rates

are down and the survival rate is improving. About 150 bowel transplants are now

done worldwide each year.

In a paper he published last year in the journal Transplantation, Fishbein

estimated that 90 percent of his patients were alive three years after

transplant surgery, about the same percentage as for kidney transplants. Based

on a review of the most recent government data, he said, about 60 percent of

patients are still alive after five years.

Because the procedure is so new, long-term survival rates are not available.

The longest-surviving bowel recipient, a French girl who received her organ when

she was 5 months old, has lived for 15 years, according to the girl's surgeon,

Olivier Goulet of the Necker Hospital in Paris.

Fishbein said he believes small intestine transplant is in transition from a

frontier technology designed to rescue the dying to an accepted primary

treatment for a variety of serious bowel conditions, including Crohn's disease,

tumors, blood clots and traumatic injuries from gunshots or car accidents.

" It's just starting to work well enough to consider that maybe we shouldn't

reserve it for patients who are about to die, " Fishbein said.

Quality of Life

In January 2003, Mohammed Javed, a New Jersey father of five daughters, was

fighting for his life at New York's Mount Sinai Hospital. He thrashed through

three weeks of semi-consciousness, delirious and convinced that his doctors were

trying to kill him.

A few years earlier, a blood clot had developed in his small intestine. It

gradually strangled the organ's blood supply, and a serious infection raged

throughout his body. After three fruitless operations, surgeons removed almost

all of his intestine.

The small intestine, which is usually around 20 feet long in adults, is largely

responsible for digestion, absorbing nutrients and flushing waste into the

colon. When the organ is harmed or diseased, it starts dying and leaks its

infection-causing contents into the body cavity. At this point it is usually

removed.

As Javed's infection continued unabated after the January surgery, he went into

that altered mental state, the memory of which still gives him nightmares.

When he regained his faculties and was released from the hospital, he carried

88 pounds on his 5-foot, 6-inch frame.

Like most patients without an intestine, Javed chose to be fitted with a

colostomy bag that captures his waste. (The alternative: running to the bathroom

every time food or water passes their lips, up to 15 times a day.)

He also was started on total parenteral nutrition, or TPN, which delivers a

slurry of fats, proteins and other nutrients through an intravenous tube. Many

people can live years, if not decades, on TPN. But it is not a good quality of

life. Catheter-related infections are common, and eventually the liver fails

though researchers don't know why.

Despite his predicament, Javed was lucky. His surgeon was Fishbein, who was

then working at Mount Sinai and told Javed that a transplant could be the best

option for returning to a normal life.

Any transplant carries serious risks. With the small intestine, 40 to 60

percent of recipients reject the organ to some degree in the first few months.

But most eventually keep them, thanks to immune-suppressing drugs.

For Javed, 44, the decision was easy. " I wanted to go through the transplant

because I didn't want to live a life dependent on TPN, " he said. He dreaded

inconvenient and embarrassing leaks from his waste bag, and he had grown weary

of hospitalizations for infections.

Fishbein, a Rockville native, moved his surgical team and his highly

specialized expertise to town University Hospital in September. Javed

followed, temporarily moving his family from New Jersey to Vienna.

On Jan. 15, town called to say an organ was available, from the body of a

23-year-old man who had died of a brain hemmorhage. Javed did not hesitate.

" Mentally, I was ready for anything, " he said. He'd already expected to die

several times.

Four hours after surgery, Javed was well enough to call his wife. But he

started to reject his organ a short time later and had to spend another two

months at town. Last month, Fishbein operated again to connect Javed's new

small intestine to his colon, the final step in the surgical procedure.

Javed returned to New Jersey with his family, without a waste bag. He began

eating solid food, but he suffered serious bouts of diarrhea. To keep the organ

from being rejected, he had to take 60 pills a day, which together caused high

blood pressure, diabetes and high cholesterol.

While his life is not normal yet, " at least I have the hope, " Javed said. " But

if you don't do the transplant, you don't have the hope. "

History in the Making

Surgeons who pioneered small intestine transplant pushed the boundaries of

medicine with the goal of helping thousands of people who would otherwise be

left for dead.

Before TPN was developed in the 1970s, babies born with such defects as short

intestines -- a condition that deprives them of some important means of getting

nutrition -- were simply put on a morphine drip to ease them into death. The

same was true for adults who lost part or all of the organ due to disease or

trauma.

Initially TPN was administered only in hospitals. Technology eventually allowed

people to receive the intravenous feedings at home. But the 40,000 to 60,000

people on TPN in the United States at any given time still faced a life of

infections, colostomy bags, liver failure and the eventual need for a liver

transplant -- which carries its own set of risks, organ shortages and chance for

rejection.

Fishbein chose transplantation, and small intestine as his niche, because he

wanted to make a mark. He did his first bowel transplant in 1995.

" I felt like I was going to work tremendously hard at my life, " he said. " And

if I was going to do that and sacrifice much of my personal life for my work, I

wanted to leave a legacy behind. "

He believes he will do that. But for now, even many specialists don't know it's

possible to transplant the small bowel.

Success, Survival Up

According to the United Network for Organ Sharing in Richmond, about 200 people

in the United States are waiting for a small intestine -- a tiny number compared

with the 58,934 waiting for a kidney.

Kareem Abu-Elmagd, director of the University of Pittsburgh Medical Center's

Intestinal Rehabilitation and Transplant Center and a pioneer in the field, said

that 3,000 to 4,000 Americans could use a new intestine. But they are unlikely

to get one due to most physicians' lack of knowledge about the procedure, or to

persistent beliefs that it's failure-prone.

Elmagd's center performs approximately 50 of the transplants each year.

After the small intestine is harvested from a donor who has just died, the

entire organ is transplanted and the top end is attached to any remaining

intestine the patient has near the stomach. The bottom end is poked out through

the lower abdomen, leaving a small hole called a stoma, which allows for

biopsies to check for rejection. Surgeons create new inflow and outflow arteries

using blood vessels from the donor's legs.

Patients may begin to eat solid food again, but for the first three months they

still use a bag to collect waste via the stoma. Once the rejection danger is

past, the stoma is closed and the end of the intestine is reconnected to the

colon in a second procedure.

Often patients with diseased intestines also need a pancreas, stomach and

liver. That multi-visceral procedure can take up to 18 hours.

When he does one of these operations, physicians from all over the hospital

come to observe, Fishbein said. They can't believe that a patient can undergo

such a radical and dramatic transformation: receiving another human's guts.

Although a small bowel transplant costs $250,000 on average, it is considered

more cost-effective than TPN, which requires about $150,000 per year just for

the liquid nutrition; physician and nurse fees are additional.

Elmagd was instrumental in persuading Medicare in 2001 to cover small bowel

transplants, although the federal health program still covers it only for

patients with life-threatening complications from TPN. And it covers surgery

only at centers that perform more than 10 transplants a year. town is one

of those centers.

Private insurers also tend to cover the procedure.

Small bowel transplant has also provided hope for Capricuso of East

Rutherford, N.J. He found out three years ago that he had familial adenomal

polyposis, a rare inherited disease that causes polyp overgrowth in the colon.

His doctors decided to remove his colon to cut his cancer risk. During surgery

they found a huge, non-malignant tumor growing near his small intestine. The

surgeons could not cut it out.

The tumor's stranglehold on his intestine caused blockages and leaks of

infectious pathogens, leading to months of vomiting and raging fevers.

Capricuso's weight dropped from 230 pounds to 160, and he spent more time in the

hospital than out. Luckily his surgeon had heard about small intestine

transplant and referred him to Fishbein, who removed his intestine in January

2003 and transplanted a new one in November.

Nine months later, Capricuso, 32, is starting to regain some normalcy. He

hasn't gone back to his job as an art store manager, but he is pursuing

publication of a comic book he wrote. He plans to marry the woman who stuck with

him through his illness.

" You break it down to basic concepts -- you're either going to live or you're

going to die, " Capricuso said. " If you're going to live, you have to take

everything that comes your way and try.

" They say I can live a nice, long, happy life. " •

Ault is a regular contributor to the Health section.

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