Oriented to Thoracic Transplant Recipients -- January 1998

The UPBEAT! Archive

CAUSES OF LATE FAILURE AFTER HEART TRANSPLANTATION: A TEN-YEAR SURVEY

Pietro Gallo et al, Cardiac transplant Units of Italy

The continuous improvement in heart transplantation outcome over the past 20 years has assessed orthotopic heart transplantation as an efficient therapy. Nevertheless, a significant amount of death could still be avoided if the causes were better understood. The distribution of the causes of death of heart transplant recipients varies substantially according to the survival interval; accordingly, short-term and long-term survivors deserve separate consideration.

Data from the Registry of the International Society for Heart and Lung Transplantation about the causes of death of long-term survivors are largely incomplete and presently not usable. On the contrary, the Italian Cardiac Transplantation Program is particularly!suitable for performing a multicenter mortality study because it permits the collection of data from a homogeneous population, Which undergoes the same monitoring procedures. The aim of this study was to gain an insight into the late failures of heart transplant recipients during the first decade of heart transplantation in Italy (1985 to 1995).

PATIENTS AND METHODS

Patient Population
We studied all the recipients who died or underwent retransplantation at least 2 years after the grafting procedure. The patients underwent surgery in the 12 heart transplantation units that have been functioning in Italy for a period long enough to meet the follow-up requirements of the present study. All the recipients were treated with a similar immunosuppressive procedure (induction therapy followed by triple therapy with cyclosporine, prednisone, and azathioprine) and monitored with the same schedule of endomyocardial biopsy.

Study Design
The study was set up by the first author by sending to the pathologist in charge of all the Sections of Cardiovascular Pathology a questionnaire for each patient who had either died or undergone retransplantation a minimum of 2 years after surgery. Data about the 97 recipients who died and the 12 who underwent retransplantation were collected and subsequently analyzed. Deaths and retransplantations of long-term survivors were subdivided by time intervals as follows: late (>2 years, <5 years) and belated (>5 years).

Data about patients who had died or had undergone retransplantation within 2 years after surgery, which ~ been used for comparison purposes, have been derived from previous surveys on the same patient population. Deaths and retransplantation of short-term survivors had been subdivided by time intervals as follows: preoperative (within 1 month after surgery), early (>1 month, <3 months), and intermediate (>3 months, <2 years).

Because of the shortage of donors, retransplantation could be equated to a death in terms of denying another patient the opportunity of undergoing transplantation. Moreover, because late retransplantation is usually reserved for patients with graff vascular disease, the only way to estimate the real impact of this transplant-associated condition is to include deaths and retransplantations under the common heading of "failures," as was done in this study. Depending on the circumstances, data are accordingly given in the text as percentages of either deaths or failures.

RESULTS

Source of Data
This analysis of late and belated failures deals with the records of 12 patients who underwent retransplantation and 97 patients who died. The data from the former group were derived from the pathologic examination of the explanted heart; the information about the latter came mainly from the postmortem examinations, which were performed in 56 of 97 patients (58%). In the remaining cases autopsy was impossible because the patient died at home (usually suddenly) or in peripheral hospitals. The primary cause of death could be assessed on pathologic or clinical grounds in 85 of 97 cases. The statistical analysis of these data will accordingly refer to the 85 known deaths and to the 12 explanted hearts (97 transplant failures in total).
Analysis of the Causes of Death and Organ Loss in Long-term Survivors
Data are summarized in Figure 1. The single most common cause of late graft failure (47.4%) was graft vasculopathy, which was responsible for 34 of 85 deaths and for all the retransplantations.

Tumors caused, respectively, 20.6% and 23.5% of late failures and deaths. The most common neoplasia was lung cancer, which was the definite cause of death in seven recipients and the putative cause of an additional patient dying of a disseminated malignancy. The histologic typing of the neoplasia could be ascertained (at surgery, biopsy, or autopsy) in five of seven cases and proved to be adenocarcinoma in four and a squamous cell carcinoma in one. Second in frequency were non-Hodgkin lymphomas (6.2%), followed by tumors of the central nervous system (2.1%), Kaposi's sarcoma, carcinoma of the tongue, gastric cancer, and cholangiocarcinoma of liver (1.0% each).

The third most common cause of late failure was represented by the emergence or recurrence of retransplantation diseases such as systemic atherosclerosis (6.2%), diabetes (1.0%), and amyloidosis (1.0%). Fatal infections accounted for 4.7% of deaths only and were represented by bacterial pneumonia in all the cases. Another 4.7% of deaths was caused by the development of "iatrogenic" transmissible diseases such as viral hepatitis, leading to posthepatitic liver cirrhosis (3.5%), or acquired immunodeficiency syndrome (1.2%). Late acute rejection was held as the cause of death in 2.3% of patients.

A 54 year-old man underwent transplantation for dilated cardiomyopathy. As a result of a postoperative aortic dissection, his aorta was replaced with a prosthesis. Ninety-two months later an anastomotic pseudoaneurysm and rupture ensued, and the patient died of hemorrhagic shock. Because of this chain of events, the death has been ascribed to the original postoperative complication.

Finally, miscellaneous conditions such as chronic kidney failure (two cases), necrotizing pancreatitis, sclerosing cholangitis, Creutzfeldt-Jakob disease, and a car accident (one case each) were grouped under the "others" heading.
Distribution of the Causes of Late Failure by Survival Intervals
The occurrence of graft vasculopathy as a cause of graft failure rose only slightly from the late (>2 years, <5 years) to the belated (>5 years, <10 years) periods, accounting for 46.1% and 48.9 % of failures, respectively. However, if death and organ loss are considered separately, the trend in long-term survivors is inversed, with the number of deaths consistently falling from the late (40.4%) to the belated period (28.9%), and the retransplantation frequency conversely rising from the late (5.8%) to the belated period (20.0%).

Tumors were more frequent in the late period (28.6% of deaths) than in the belated period (16.7%). Tumors such as Kaposi's sarcoma, carcinoma of the tongue, gastric cancer, and cholangiocarcinoma of liver were exclusively observed as a cause of death in the late period.

Apart from recurrent amyloidosis, the other pretransplantation diseases were exclusively represented or more frequent in the belated period. Fatal infections and transmissible diseases showed the same prevalence in the two considered time intervals, and acute rejection was never registered as a cause of death in the belated period.
Distribution of the Causes of Late Failure by Reason for Transplant
Graft vasculopathy was more frequent among patients undergoing transplantation for ischemic heart disease (54.3%) than for any other reason (40.4%), but the difference did not attain statistical significance. Conversely, tumors as a whole were rarer among the patients undergoing transplantation for ischemic heart disease (10.9% vs 30.6%), and this difference attained statistical significance. It is meaningful and statistically significant that conditions such as sudden death, systemic atherosclerosis, and diabetes were more frequent among the recipients undergoing transplantation for ischemic heart disease (21.7% vs 6.1%).

DISCUSSION

Source of Data
The postmortem examination rate observed in this study is substantially lower than the one (86%) registered in a previous survey of short-term survivors performed on the same study population. This can be attributed to the fact that short-term survivors are mostly inpatients and are accordingly more likely to undergo an autopsy than long-term survivors.

Analysis of the Causes of Death and Organ Loss in Long-term Survivors
It is common knowledge that graft vasculopathy is the most frequent single cause of death in long-term survivors. In the Italian experience the graft vascular disease has been the leading cause of death since the intermediate period, and it has resulted in most of the retransplantations, confirming that it represents the major hazard for long-term surviving heart transplant recipients, out of proportion to kidney and liver transplant recipients.

Sudden death at home is a common occurrence in long-term survivors. Hearts with graft vasculopathy very often display features such as hypertrophy and disarray of myocytes and substitution scarring that can account for electrical instability. Accordingly, late sudden death in recipients known to be affected by chronic rejection was considered a putative consequence of graft vascular disease from a statistical standpoint.

Tumors were the second most common cause of death in this series of long-term survivors (23.5% of deaths). In addition to the 20 patients who died of a malignancy, four patients, who died of unrelated causes (mainly of graft vascular disease), were found to have cancer (renal cell carcinoma, urinary bladder carcinoma, Kaposi's sarcoma, and lung cancer.)

Tumors such as non-Hodgkin' s lymphomas and Kaposi's sarcoma have been definitively connected with the effects of the immunosuppressive therapy, but they represented only a minority of the neoplasms appearing in our series (6.9% and 1.1% of deaths, respectively). Lung cancer seemingly should not bear any relationship with transplantation, but its actual frequency, especially the high prevalence of a specific histologic type (such as adenocarcinoma), in heart transplant recipients is too high to be merely coincidental, All eight patients who either died of lung cancer or were found to be affected by this tumor (an eighth patient who died of graft vascular disease) were men, with a mean age of 52.9 years (range 46 to 60 years). They had undergone transplantation for either dilated cardiomyopathy (5 of 8) or ischemic heart disease (3 of 8) and died after a mean follow-up period of 4.9 years. Two patients underwent operation, and three died with a widely disseminated pattern of metastases. Another patient died of a malignancy infiltrating pleural serous membrane, mediastinum, and retroperitoneum, but a primary site in the lungs could not be ascertained. Patients who died of non-Hodgkin's lymphomas were conversely younger (40 to 50 years, mean 46.4), one of them was female, none of them had undergone transplantation for ischemic heart disease (dilated cardiomyopathy in two, valvular heart disease in two, and restrictive cardiomyopathy and arrhythmogenic cardiomyopathy in one), and they had died after a slightly longer follow-up period (5 .5 years on average). Patients who died of or were found to be affected by "other" malignancies were mainly male (9/10), had an intermediate mean age (50.1 years, range 3 to 66), had undergone transplantation for different reasons (dilated cardiomyopathy in six, ischemic heart disease in three, and a cardiac fibroma in one), and had died after the shortest follow-up period (4.4 years on average).

The spectrum of diseases resulting in death in short-term recipients is relatively limited. For this reason, and for the sake of comparison, studies on long-term survivors tend to list a considerable number of different causes of death as "other," that is, ascribed to a composite group of diseases that are seemingly non-related to the transplantation itself. Actually, only a minority of them are really coincidental: several other deaths are due to the emergence or recurrence of pretransplantation diseases (such as systemic atherosclerosis, diabetes, or recurrent amyloidosis); other causes of death, as the development of either a posthepatitic cirrhosis or acquired immunodeficiency syndrome, are probably due to some kind of transmission and could be considered as "iatrogenic" diseases. These conditions were related to transplantation but could have been connected with any other form of major surgery.

Fatal infections are infrequent occurrences in late survivors. In our series, all of the infections were bacterial and, in keeping with other authors' observations, they affected the respiratory tract.

Untreatable acute rejection is no longer frequent in the late period. In one of our cases, acute rejection was the consequence of voluntary withdrawal of the immunosuppressive therapy. Before a diagnosis of late acute rejection is made, attention must be paid to discern it from the effects of graft vasculopathy, such as the concurrence of ischemic myocyte necrosis with lymphocytic infiltration, the so-called "aggressive fibrosis that can mimic the features of acute rejection.
Distribution of the Causes of Late Failure by Survival Intervals
Given the limited life expectancy of patients after heart transplantation, determination of the causes of late failure, that is that these events can potentially be modified, is an important issue. However, the comparison among published data is hindered by the different definitions of long-term survivors used in the literature. They have been defined as patients surviving for more than 2 years, 1 year, 3 months, 2 months, or even 1 month after transplantation. In addition to this, most studies limit themselves to a 5 year follow-up period, and little is known of patients who die after longer time intervals. They supposedly die of the same causes, but this has not been truly ascertained. This is why this study makes a difference between late and belated failures. The major dissimilarities between the two time intervals regarded graft vascular disease (responsible for more deaths and fewer retransplantations in the late than in the belated period), acute rejection (absent in the belated period), tumors (less frequent in the belated period), and the emergence of pretransplantation disease that prevails in the belated period (13.9% vs 6.1% of deaths): death was due to diabetes in one case (a 50-year-old male patient who underwent transplantation for ischemic heart disease and died 6 years after transplantation of diabetic nephropathy) and systemic atherosclerosis in six. These patients died of either a ruptured atherosclerotic aneurysm of the abdominal aorta (two men, 54 and 60 years old, respectively, who underwent transplantation for ischemic heart disease and dilated cardiomyopathy, died after more than 5 years) or stroke (four men, 5 1 to 60 years old, three of four of whom underwent transplantation for ischemic heart disease, died after 3, 4, 6, and 9 years). It is worth noting that these patients were all men in their fifties and, as will be underlined later, five of seven of them had undergone transplantation for ischemic heart disease.

Expanding the comparison between survival intervals to the entire follow-up period, several noteworthy observations can be made. Graft vasculopathy may be evident as early as 3 months after transplantation, and, conversely, it may cause the recipient's death 22 years later. In the Italian experience, the frequency of graft vasculopathy as a cause of graft failure has progressively risen from 6% of the early period to 42% (intermediate), 46% (late), and 49% (belated), and, if sudden death at home were considered along with graft vasculopathy, the number of failures directly or indirectly attributable to a graft coronary disease would further rise from 9% (early period) to 43% (intermediate), 50% (late), and 58% (belated). The inverse trend of retransplantation and deaths from the late to the belated time interval underlines an attitude to giving a second chance to patients who have survived for more than 5 years but opens the ethical problem of priorities in organ assignment that is made harder to solve by the shortage of donors.

In the Italian experience, tumors (Figure 3) have been a cause of death since the early period (3%), and their frequency has progressively risen in the intermediate and late periods (17% and 29%, respectively), being almost halved (17%) in the belated span of time. Lung cancer caused a fairly constant rate of deaths: 7% in the intermediate period, 10% in the late, and 5% in the belated period. Also non-Hodgkin's lymphomas displayed a relatively uniform frequency: they already represented a cause of death in the early period (3%) and were subsequently responsible for 3%, 6%, and 8% of deaths, respectively, in the intermediate, late, and belated periods. As previously observed, Kaposi's sarcoma occurred only in the intermediate period, even if one patient in this series died of this neoplasia in the late period 2 years after the onset of the tumor.

In the Italian experience, the overall percentage of deaths for infections fell from the early (31%) to the late period (4%) because of the disappearance as a cause of death of the viral fungal, and protozoal diseases. On the contrary the rate of fatal bacterial infections remained almost unchanged in the various time intervals (8% in the perioperative period; 6%. early; 7% intermediate 4% late; 4% belated). In the late periods, indeed, all the fatal infections were represented by bacterial pneumonia.

Acute rejection represents a life-threatening hazard in the first 6 months after surgery. In the Italian experience, it caused 9% of the perioperative deaths and 19% of the early deaths. Subsequently, the percentage of deaths resulting from acute rejection fell to 5 % and 4% in the intermediate and late periods, respectively, and no additional deaths were attributed to an acute rejection in the belated period.
Distribution of the Causes of Late Failure by Reason for Transplant
The assessment of risk factors for graft vasculopathy has drawn conflicting results, even if undergoing transplantation for ischemic heart disease has been frequently associated with the development of this condition. Also in our series, the patients who had undergone transplantation for ischemic heart disease and subsequently had development of a graft vasculopathy were more numerous than those who underwent transplantation for any other cause, especially dilated cardiomyopathy, but the difference did not attain statistical significance. It was to be expected that dying as a result of systemic atherosclerosis and diabetes was much more common among patients who underwent transplantation for ischemic heart disease, which reopens the discussion about the opportunity of giving priority to patients with cardiomyopathy as heart transplant recipients. On the contrary, the observation that tumors develop more rarely among patients who undergo transplantation for ischemic heart disease, although confirmed by other investigations, remains difficult to explain.

CONCLUSIONS

This study has confirmed that the distribution of the causes of death of heart transplant recipients substantially varies according to the survival interval, and that there is a difference, too, between the late (>2 years, <5 years after surgery) and belated (>5 years) periods. Graft vasculopathy is the most frequent single cause of transplant failure in both the late and belated periods; in the latter, the organ loss (need for retransplantation) becomes almost as significant as death. A sudden death at home is a frequent occurrence in long-term survivors and could be tentatively attributed to the myocardial disarray and scarring that is often observed in graft vascular disease.

The mortality rate for tumors is highest in the late period, with non-Hodgkin's lymphomas showing a fairly constant prevalence in the different periods. Kaposi's sarcoma does not seem to develop in the late period, but its effects can last until this period. In addition to these tumors, which are commonly associated with an immunosuppressive therapy, an unexpected and unexplained high number of lung cancers, especially metastasizing adenocarcinomas, have been noticed in this series. In the belated period, and especially in patients not undergoing. tranplantation for cardiomyopathy, death is frequently due to the emergence or recurrence of pretransplantation diseases.

Long-term survivors of heart transplantation can also die of complications such as a transmissible disease, which can be connected to any kind of major surgery. Fatal infections are limited to bacterial and are infrequent in long-term survivors. Finally, acute rejection is no longer a cause of death in late survivors, unless the patient voluntarily discontinues the immunosuppressive therapy.

J. of Heart & Lung Transplantation
Vol. 16, No. 11,Nov '97 pp. 1113-21

SHALALA WANTS ORGAN DEATH ANSWERS

By Laura Meckler - Associated Press Writer

WASHINGTON (AP 12/17/97) -Concerned about lower-than-expected survival rates at some organ transplant centers, the secretary of Health and Human Services is asking for an explanation.

Forty-three programs that transplant hearts, livers or kidneys had low survival rates between 1988 and 1994, including 29 whose low rates continued through 1994, the Department of Health and Human Services said.

"I know you share my concern," HHS Secretary Donna Shalala wrote to the director of the United Network for Organ Sharing, which runs the nation's transplant program.

UNOS plans to review the 29 programs whose low rates extended through 1994.

Shalala asked the organ sharing network to explain, within 30 days, whether any of these programs have been reviewed before and if not, why not. She also asked whether these programs shared any characteristics and asked UNOS to explain how it planned to assist them.

Releasing the list, officials warned it was only one piece of information patients should consider when choosing an organ transplant center. And they cautioned that some excellent programs may show up on the list.

"This is another tool available to patients that we hope will be helpful," said Mary Ann Wirtz, spokeswoman for the organ network.

The report, produced every three years, offers a wealth of information about every transplant program in the country. Overall, it showed patient survival rates improving for every type of transplant.

The list includes a few very large programs, such as University of Alabama, which performed 1,652 kidney transplants between 1988 and 1994. Its survival rate was just barely below expected, and government officials said it illustrated why patients should not take this list as gospel.

"You'd never say the University of Alabama is anything but a quality center," said Charlotte Mehuron, an HHS spokeswoman.

To compile the list, United Network tracked the percentage of organs that are still functioning a year after being transplanted. It then calculated each program's expected survival rate, taking into consideration a variety of factors such as age and health of the patients.
The 43 programs identified Tuesday had one-year survival rates that were below the expected rate between 1988 and 1994. In each case, the difference was statistically significant.

Five of them had closed by 1992, and others may have closed since then. Nine programs improved their survival rates during 1992-94 and were performing at least as well as would be expected.

That left 29 programs that merited further review, HHS said.

Following a similar report in 1994, analysts identified 15 programs that warranted further study. Of those, four stopped performing transplants, 10 programs showed improvement and one program remained under review.

Hospitals on the list contacted Tuesday generally said they had instituted improvements to their programs since 1994, the last year covered by the report. Sacred Heart Medical Center in Spokane, Wash., determined it needed to modify its post-transplant drug program, said Dr. Robert Golden, director of kidney transplant program. Its statistics then improved, he said.
"I think its a good tool for hospitals to look at how they're doing," he said. "Patients will use this as a starting point when they evaluate a center to ask more questions and become more fully informed."

Organ Transplant Centers Below Standards-List

By The Associated Press
Transplant programs whose one-year graft survival rates are below expected, given a variety of factors. The rate indicates what percent of transplanted organs were still working a year later.

The first column of numbers is the transplants performed by each center between 1988 and 1994. The second column is the actual survival rate. The third column is the expected survival rates.

Programs designated with an "x" had survival rates in 1992-94 that still were below expected and are subject to review.

The source is the 1997 Report of Center Specific Graft and Patient Survival Rates, produced by the United Network for Organ Sharing under a contract from the Department of Health and Human Services.

KIDNEY PROGRAMS
xUniversity of Alabama Ho1652 80.4 83.5
xGood Samaritan Regional,528 81.0 86.3
xMemorial Medical Center, 78 78.2 85.9
xBrigham and Women's Hosp369 74.5 81.8
xBorgess Medical Center, 152 76.7 86.8
Grace Hospital, Detroit 61 52.0 77.6
St. Luke's Hospital, Kans223 78.5 83.3
Pitt County Mem Hospital,147 76.4 84.3
xNew York Hospital, New Y356 78.6 84.1
xSt. Anthony's Hospital, 136 66.6 83.0
xGeisinger Medical Center227 76.1 81.3
xHermann Hospital, Housto627 77.6 82.5
xLatter-Day Saints, Salt 463 79.4 84.4
xSacred Heart Medical Cen180 77.2 84.3
Swedish Medical Center, S288 78.5 84.4

HEART PROGRAMS
xColumbia Presbyterian, D49 69.4 82.4
xHines VA Hospital, Hines38 60.5 82.6
xKosair Children's Hospit22 36.4 67.5
xHarper Hospital, Detroit14 55.1 81.8
Depaul Medical Center, Br2 0.0 85.8
MenDrab Medical Center, K5 20.0 77.3
North Carolina Baptist, Wll 63.6 84.9
xBuffalo General Hospital63 60.3 85.1
xPresbyterian Hospital, N502 75.9 81.1
xUniversity Hospitals, Cl23 65.2 83.2
Children's Hospital, Oklal5 40.0 66.6
xSt. Christopher's Hospit36 44.4 72.7
The Methodist Hospital, H200 72.5 80.8
Baylor University Medical123 74.8 81.7
xJohn L. Doyne Hospital, 40 70.0 82.2

LIVER TRANSPLANT PROGRAMS
xGood Samaritan Regional,65 55.6 77.4
xYale New Haven Hospital,35 54.3 71.4
xJackson Memorial Hospital63 56.2 68.4
xTampa General Hospital, 10 30.0 78.0
University of Chicago 496 55.4 62.4
xRush Presbyterian, Chica318 57.9 63.5
Presbyterian Hospital, Ne6 7.7 72.5
xDuke University Medical 163 56.4 73.0
xUniversity of Pennsylvan152 58.8 71.6
Children's Hospital, Phil78 51.3 61.5
xThe Methodist Hospital, 42 45.0 69.5
xWilford Hall, Lackland A59 59.3 75.0
Columbia Henrico Doctor's5 20.0 77.3
PVCS
Open Letters to UpBeat Readers:
#1
Dear Friends,
I greatly regret to inform you that as is not unusual for long term heart transplants,
I have developed cancer. In my case it is located in the throat. A great many wonderful
and very professional people have helped me try and grasp this ugly situation and
make a decision as to what treatment course to follow. I have selected a program that
begins 1/19.

Just what effect this treatment may have on me, and my ability to keep UpBeat
on a schedule with quality content is yet to be learned - I shall try very hard, first to
get well, and also to keep the newsletter going. Should the situation turn even nastier
than it already is, give me a bit of a break on the schedule over the next 3 or 4 months.

One more thing - this event has proved to me one more time that the field of
transplantation has the friendliest, most professional, and most caring individuals in
the world.
Stay well,
Don S. Marshall, Tx 1/8/88, Loma Linda U.M.C.



#2

DON MARSHALL

P.O. Box 482

Mathews, Virginia 23109


January 15, 1998

Ms. Susan Hirsch, Public Relations
Continental Airlines
2929 Allen Parkway, Suite 1109
Houston, TX 77019

Dear Ms. Hirsch:

I received a heart transplant at Loma Linda in California ten years ago this month. It has been a wonderful event that has allowed me to take part of many events in my family as a basically normal person.

Just recently, as is not unexpected in patients who have been immunosuppressed over a relatively long period, I developed cancer of the larynx. We now live in Virginia as an expense expedient, yet it became an obvious medical conclusion that I should return quickly to Loma Linda for a consult as to the best possible treatment of this disease.

As we live on disability income, the fares quoted for an immediate departure were just not within our reasonable means. However, I remembered that I had heard of a connection between the American Organ Transplant Association and Continental Airlines. My wife made a call to them, as I can no longer talk well, and within 36 hours we had a ticket voucher for the entire trip!

This program to service people in legitimate health need is simply outstanding. I put together a newsletter for thoracic transplant recipients with a small but widely distributed mailing list in all 50 states and 4 foreign countries. I can assure you that in a future issue (as soon as I get some chemotherapy behind me) Continental Airline' s "heart" will be brought to the fore.

Again sincere thanks.

Sincerely,

Don S. Marshall

MAN REGAINS VOICE AFTER TRANSPLANT

By John Affleck - Associated Press Writer

CLEVELAND (AP 1/9/98) -- A man who lost his voice in a motorcycle accident 19 years ago rasped "Hello" and "Hi Mom" just three days after the first larynx transplant since 1969.
Timothy Heidler, 40, could be speaking in a normal voice in five months or less, doctors at the Cleveland Clinic said Friday.

In a 12-hour surgery on Sunday, Heidler received the larynx, part of the trachea and 70 percent of the throat of an unidentified donor.

The surgery, last performed in 1969 in Belgium, is causing some controversy in the medical community over the risks vs. the benefits of transplanting a non-vital organ. Undergoing major surgery is always risky, and the body could later reject the transplanted organ, requiring more surgery to have it removed.

"I think there will be some folks that will perhaps say we shouldn't do it, but I'm not one that ascribes to that," said Dr. Marshall Strome, leader of Heidler's surgical team.
"I think that if people want to be normal, or as normal as they can be, and are willing to make the sacrifices to make it happen, we're here to serve the population," Strome said.
Heidler's larynx was destroyed when he crashed his motorcycle on the way to firefighter training school. He spent years recovering from his injuries and currently is unemployed. The clinic on the way to firefighter training school. He spent year on the way to firefighter training school. He spent years recovering f on the way to firefighter training school. He spent years recovering from his injuries and currently is unemployed. The clinic on the way to firefighter training school. He s on the way to firefighter training school. He spent years recovering from his i on the way to firefighter training school. He spent years recovering from his injuries and currently on the way to firefighterrg, Pa., volunteered for the surgery last year after being informed of the risks of infection and organ rejection.

"Tim is very verbal, very bright; very motivated," Strome said. "He clearly understood what he wanted to have done."

Heidler is taking anti-rejection medicine, but he'll live with the risk of rejection for at least another five years. Strome believes there is a 70 percent chance the larynx will still be functioning by then.

Strome and other experts in head and neck surgery said the last larynx transplant was performed on a cancer patient who died not long afterward. Strome said articles written about that transplant indicate the operation failed to re-establish the patient's voice.

Strome said Heidler's operation may open the door for other accident victims, people with large benign growths on the larynx and long-term cancer survivors whose larynxes were destroyed by the disease.

But other doctors reserved judgment, saying that the success of the operation won't be known for years.

If there are serious complications or rejection, doctors will question the value of replacing an organ that people can live without; said Dr. Michael Johns, editor of the professional journal, "The Archives of Otolaryngology-Head and Neck Surgery."

If not, the operation could be a valuable new procedure.

"School will be out until the long-term report on this," Johns said.

In my present condition, l'm real partial to this guy. DM\


TRANSPLANT SURVIVAL RATE UP - U.S. GOVERNMENT

WASHINGTON (Reuters 12/12/97) More people are surviving organ transplants and living longer after transplant surgery thanks to better care, the U.S. Health and Human Services (HHS) department said Friday.

Once an organ recipient survives the first year after the dangerous transplant surgery, the patient is more likely to remain alive longer.

For example, the HHS said that 94.3 percent of kidney recipients -- an all-time high -- and 91 percent of pancreas transplant patients now survive their organ transplant surgeries.

The HHS' s three-year survey of more than 97,000 transplant patients showed "excellent" survival rates for those who lived a year past their transplants.

"For this group, three-year patient survivals range from 75.9 percent for lung recipients to 81.2 percent for heart-lung, to more than 90 percent for kidney, liver, heart and pancreas," HHS said in a statement.

"This report with data on nearly 100,000 transplants is a clear indication that transplantation is a lifesaving treatment," said Claude Fox, acting administrator of the department's Human Resources and Services Administration.

"Information like this is important in helping patients make informed medical decisions in consultation with their physicians."

But despite the encouraging figures there are still problems, one being a lack of organs donated for transplant.

"With the success of organ transplantation, the need for organs is growing much faster than the number of donated organs," Fox said. "The waiting list is now more than 55,000."

BETTER TRANSPLANT STANDARDS ADVISED

By Alice Ann Love - Associated Press Writer

WASHINGTON (AP 12/18/98) -Gravely sick people whose hearts have stopped but whose brains are alive could help solve the shortage of transplant organs, but rigid protective standards are needed, medical experts advised the government Thursday.
"If the estimates are accurate, non-heartbeating donors could represent an increase of at least 1,000 organ donors each year," said Dr. John Potts, director of research at Massachusetts General Hospital in Boston. "To ensure that these patients receive proper care, however, it is critical that all transplant organizations adopt a consistent approach that respects the wishes of patients and families."

Potts led a study presented by the Institute of Medicine to the Health and Human Service Department, which requested the research earlier this year.

"This could be a significant source for expanding organ donation, but not unless the public understands it," said HHS spokesman Campbell Gardett.


People whose hearts have stopped -most often because of a traumatic injury from a car accident, homicide or suicide -but whose brains can be kept working by life-support equipment, account for only about 1 percent of all organ donors.

To be successful, organ recovery from such patients must take place quickly, and the opportunity is easily lost if family members can't be reached for consent.

Organ recovery from patients who are brain-dead is far more common, because their beating hearts can continue to preserve other organs indefinitely while complicated emotional and ethical decisions are made.

But with more than 50,000 sick Americans on waiting lists for organ transplants -more than 4,000 of whom died still waiting last year -- federally supervised organ procurement organizations have become increasingly aggressive about pursuing those whose hearts have stopped.

In some cases, hospitals have taken steps to preserve organs in such patients -possibly causing pain or hastening their deaths -- before family members could be found to give consent.

Of 63 federally supervised organ-procurement organizations, researchers found fewer than half have written standards for dealing with such cases -- and even those vary widely and are not well-publicized.

"Everything happens in a mad rush," said Dr. Roger C. Herdman, the Institute of Medicine's senior scholar. "This is a medically and ethically complex situation... you should think about this before you do it."

The institute recommended in its report Thursday that the following national standards be established to ensure ethical practices and public trust in organ donation programs:

--Discussion of organ donation with family members should take place only after the family has made an independent decision to withdraw life support.
--A five-minute wait should be required after life support is withdrawn and before organ recovery begins to ensure a patient's heart would not resume beating on its own.
--The doctor who declares death should not be involved in any way with an organ-procurement organization.
--Families should be allowed to attend the death of organ donors and should not be

required to bear any costs associated with the donation.

The institute also recommended that decisions about whether to use organ-preserving medical procedures on patients who are not brain dead should be made only with family consent, unless non-consensual intervention is specifically allowed by law.

The District of Columbia, Virginia, and Florida have such laws.

FDA PANEL SUPPORTS HEART TRANSPLANT DRUG

GAITHERSBURG, Md. (Reuters 1/15/98) A federal Food and Drug Administration advisory panel has voted unanimously in favor of giving marketing approval for a drug to help prevent rejection of heart transplants.

The agency is not bound by its panels' decisions but it generally follows their advice.

CellCept, made by Swiss firm Roche Holding Ltd. and known generically as mycophenolate mofetil, is already approved for kidney transplants and is already in wide use for heart surgery as well. Once the agency approves a drug for one use, doctors commonly prescribe it for other, non-approved uses.

The panel made the recommendation Wednesday despite some reservations that Roche reconfigured results after a first analysis showed no real difference between CellCept and a comparison drug, azathioprine, which is commonly used but not approved for heart transplants.

Even though Roche's analysis was questioned, many panelists -- including Lawrence Hunsicker of the University of Iowa Hospitals, chairman of the United Network for Organ Sharing -- said there were some kernels of hope in the Roche study.

"It looks as though patients survive better," Hunsicker said.

Roche re-analyzed data to exclude 72 patients who were too sick after transplant to take an oral medication. That might have biased results, said the FDA and some panelists. FDA reviewer Michael Elashoff said:

"Performing several analyses gives multiple chances to win."

MISTAKE STOPS JAPAN HEART DONATION

TOKYO (AP 1/6/98) -- Failure to properly fill out an organ donor card prevented a man from becoming the first person in Japan to donate a heart and liver under a new law designed to make organ donation easier.

In the first test of the law, a man in his 50s who died last month had indicated he wanted to donate his organs, but neglected to specify when, Kazuhiro Shigeto, an official at the Japanese Health Ministry, said today.

Shigeto said the donor card allowed three choices for donation: after brain death, after heart failure, or not at all. He said new, easier-to understand cards were now being issued.

Under the new law, enacted in October, Japan joined the rest of the industrialized world in legally recognizing brain death, making heart, lung and liver transplants much less problematic.

Japan's previous law said a person could be declared dead only at the moment when the heart stopped beating. But in many cases, the vital organs have deteriorated too much by that point to transplant them.

implementation of the controversial law has been hindered by cultural attitudes, a lack of donors and a scarcity of transplant experience among doctors.

Even if the potential donor, whose name has not been released, had properly completed the card, the hospital where he died did not have Health Ministry authorization to handle organ donations from brain dead donors, Shigeto said.

As a result, only his kidneys and corneas were donated after his heart stopped beating.

PIONEERING HEART SURGEON HONORED

By Paul Harris - Associated Press Writer

CAPE TOWN, South Africa (AP 12/3/97) -- Thirty years after performing the world' s first heart transplant, pioneering surgeon Christiaan Barnard says he never expected to be famous.
Since Barnard performed the operation on Dec. 3, 1967, he has been in the media spotlight, the recipient of awards from around the world, able to hobnob with such celebrities as Princess Diana.

"We really did not see it as a big event," Barnard, 75, told The Associated Press on Tuesday. "We did not even take photographs of the operation that night."

A transplant museum opens today at the Groote Schuur Hospital in Cape Town, where Barnard put the heart of road accident victim Denise Darvall into the chest of 55-year-old Louis Washkansky.

Washkansky lived for 18 days before his body rejected the heart. But the operation created instant headlines worldwide and gained Barnard international fame. His one regret is that he did not hire an agent to deal with the publicity.

"That was the most difficult part, trying to handle all the publicity," he said.

Doctors already had transplanted livers and kidneys by the time Barnard and his team attempted their operation. But the heart, with its poetic imagery of life and love, caught the public and scientific imagination.

Dark-haired Barnard, who looks 10 years younger than his age, said he saw it as just another part of the body.

"We didn't see the heart as the seat of the soul. The cessation of the heart did not mean the end of life. We knew that," he said.

After Washkansky died, Barnard and his team persevered with their innovative surgical procedure.

His second transplant patient, Philip Blaiberg, lived for 18 months after the operation and the survival time of patients has increased ever since. Now 90 percent of patients survive the operation with an 85 percent chance of living for a year and a 70 percent to 75 percent chance of lasting five years.

Barnard's longest-surviving patient, Dirk van Zyl, lived with an implanted heart for 23 years before dying last year of diabetes unrelated to his heart condition.

What was pioneering 30 years ago is now commonplace, with more than 40,000 transplants having been performed.

Barnard predicted that someday human hearts will be grown artificially to suit patients, using genetic engineering techniques that already can produce human skin.

"There is now tremendous progress in genetic engineering and it may be possible eventually to grow a human heart," he said.

Barnard, the son of a clergyman, grew up in Beaufort West, a small town in the dusty Karoo semi-desert region of South Africa. Last month, the town opened the Chris Barnard Museum, where his numerous honorary degrees and overseas awards are now displayed.

Last month, he received an honorary doctorate in Ukraine and delivered lectures in Switzerland, France and Italy.

Despite the International recognition, Barnard said that the highlight of his career was performing operations on children with abnormal hearts, with each operation requiring different techniques and skills.

"That was real surgery," he said.

Barnard lives in Cape Town after retiring in 1987. Last year, his third wife, Karin, who at 33 is less than half

her husband's age, gave birth to his sixth child.


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