Breathing Easier
By Kim M. Norton
For The Record
Vol. 19 No. 8 P. 30

Lung transplantation boosts survival rates and, just as importantly, improves the patient’s quality of life

Before the onslaught of media attention about stem cell research, organ transplants were the darling of the fourth estate. Today, as science evolves and surgical methods improve, just about any person can become a lifesaver by donating blood, organs, tissues, tendons, valves, bones, cells, or eyes.

Of the organs that can be donated, the lungs remain the most difficult to transplant because of their delicate architecture. The lungs are also the only organ constantly exposed to elements outside the body, making transplantation even more difficult.

Patients recommended for lung transplantation generally meet specific criteria. The patient is usually dependent on an oxygen tank or has an overall lower quality of life because of decreased lung capacity. Typical diagnoses warranting transplantation, if all other treatment regimens fail, are emphysema, pulmonary fibrosis, cystic fibrosis, idiopathic pulmonary fibrosis, pulmonary hypertension, or chronic bronchitis. The patient would have to be in reasonable health, a nonsmoker for at least six months, and not be expected to survive more than two years without a transplant.

The main motivating factor behind transplantation is to dramatically improve the patient’s quality of life, says Mark K. Robbins, MD, medical director of the Lung Transplant Program at the University of Virginia (UVa) Health System in Charlottesville. “Following transplantation, these patients can enjoy their lives to the full extent, because prior to the transplant, some were only functioning with 30% or less lung capacity. Most of these patients became too winded just moving around their homes and were completely reliant on an oxygen tank,” he says.

Lung transplants, while capable of dramatically improving the patient’s life, are relatively uncommon when you consider that there were approximately 27,000 transplants nationwide last year (of all organs), and only 1,319 were lung transplants, according to the Organ Procurement and Transplantation Network (OPTN) in Richmond, Va.

Although the ratio between lung transplants and overall transplants is rather disproportionate, what is more unbalanced is that, as of late February, there were 95,177 people waiting for an organ transplant, and of those, 2,826 were waiting for a lung or lungs, according to the OPTN. The disparity in the number of donations is driven by the availability of donors as well as the viability of the lung or lungs to be transplanted, says Robbins.

Waiting for Relief
Because of the limited number of lungs available for donation, the selection process is rigorous to ensure the greatest success. Until last year, once a patient was determined to be a candidate for a lung transplant, he or she was placed on a waiting list. The person with seniority on the list had the highest priority. There was no preferential treatment for the gravely ill patient who would not survive six months without a transplant; it was all a matter of where the patient fell on the list.

In March 2005, the lung transplant waiting list was changed to incorporate two important goals: to minimize the mortality rate while on the list and to mandate an equitable way to distribute the organs, otherwise known as the final rule. “The outcome has been that a score is assigned to transplant patients, which takes into account the likelihood of the patient dying on the list within a year and the chance of survival following the transplant,” explains Kenneth R. McCurry, MD, director of the University of Pittsburgh Medical Center (UPMC) Lung and Heart-Lung Transplantation Program.

Once patients are assigned a score, they are entered into the United Network for Organ Sharing (UNOS) database, which is a national allocation system that works with 11 Organ Procurement Organization (OPO) regions across the country to distribute organs in an equitable manner. For instance—when a patient is registered with UNOS and given a score—when an organ becomes available in a particular region, the local OPO will run the specifics of the donor against the list until a match is found. “Taking into account the donor’s blood type and type of organ to be donated, the computer will deduce who is to receive the organ,” explains McCurry.

Once a match has been made, the patient scheduled to receive the organ is contacted and prepared for surgery. Meanwhile, the transplant team will travel to the hospital to procure the organ, which will be transferred back to their home hospital and transplanted into the recipient. Time is of the essence when it comes to organ transplantation, especially with the lungs. Because of the delicate nature of the lungs, there is a limited time frame in which the surgeons can work. “Typically, we prefer the organ be preserved for less than six or seven hours, although there are some larger programs out there that have newer preservation systems that can extend that time by two to three hours,” says McCurry.

UVa Health System
To ensure the redesigned scoring system’s success, patient selection and evaluation are important first steps. “Our patients undergo an extensive battery of tests to determine if they are both physically and emotionally capable of undergoing the procedure. Patient compliance is a substantial part of the scoring process, because after the transplant, the patient will be taking myriad medications to combat infection and rejection,” says Robbins.

If it is determined that the patient is in acceptable shape with good heart and kidney function, has a good social support system, and has end-stage lung disease with a prognosis of less than two years to live, he or she will be recommended for a transplant.

Since its inception in 1990, UVa has performed more than 300 transplants and boasts a survival rate of 100% after the first year; 98.08% after the second year; and 81.4% after the third year—all of which are higher than the national average, according to data from the Scientific Registry of Transplant Recipients. “Our numbers are higher than the national average, and we attribute this to good patient selection, donor management, and consistent patient protocol,” says Robbins.

As of February, UVa had 56 patients on its lung transplant waiting list with a typical wait time for the most needy patients of three to six months, says Robbins. But he has seen transplants occur anywhere from one week to one year after a patient is placed on the list.

UPMC
Established in 1983, UPMC’s lung transplant program is one of the country’s oldest. To date, the center has performed more than 900 transplants, and each year it sees a steady increase in the numbers. “In 2004, the center performed between 61 and 65 transplants; in 2005, the number rose to 91, and last year, there were 93 isolated lung transplants and eight heart/lung transplants,” says McCurry. Currently, 109 patients are waiting for a lung or lungs and 10 others are waiting for a heart/lung transplant with an estimated wait time of 30 days to nearly five years, depending on organ compatibility and the scoring scale, according to OPTN data.

UPMC, which has consistently had survival rates above the national average, recently took steps to reduce rejection events and the patient’s reliance on one of the required immunosuppressants. “In our liver and kidney program, we aggressively wean our patients off of immunosuppressants, and we have been seeing good results. Although taking lung transplant recipients off of immunosuppressants is never going to be entirely possible, we have had success with administering alemtuzumab intravenously at the time of transplant,” says McCurry.

One dose of alemtuzumab at the time of transplant has been “shown effective in depleting immune cells that would otherwise react against the lung transplant and enables the patient to not be on the maintenance immunosuppressant drug prednisone,” says McCurry. By administering alemtuzumab, surgeons at UPMC are modifying the rejection rates following the transplant and avoiding a number of toxicities that occur from rejection. “Without prednisone, we are seeing reduced numbers of steroid-induced hypertension and immunosuppressant hypertension,” McCurry adds.

Overall Outcomes
The delicate, spongelike lung is a complex network of blood vessels, cells, air sacks, and bronchial tubes that is easily susceptible to injury. Even the heart, which most people assume is delicate, is really just a muscle that beats, explains McCurry.

Despite both UPMC’s and UVa’s programs having surpassed the national average for survival rates, long-term survival rates decrease with each passing year. “Overall, in the United States, about 60% of lung recipients will have at least one episode of rejection,” McCurry says. The reason? Lungs are more susceptible to outside pollutants, bacteria, and allergens.

The national average for one-year, postlung transplant survival is approximately 80%. However, the five-year survival rate drops to 55% because of the continued exposure to outside elements, susceptibility to infection, and recurrent rejections that could lead to chronic rejection, which is the most common cause of death in the two- to three-year posttransplant population, according to McCurry.

Compared with the survival rates of kidney (81% after five years) and heart (74% after five years) transplants, the lungs lag behind. However, the main goal of transplanting the lungs is to improve the quality of life. Although these statistics are the national norm, it is important to recognize that patients do survive longer. “There are some patients who are still doing well 10 to 15 years later, and until very recently, a patient who had a transplant in 1983 was still alive,” says McCurry.

Importance of Donation
It can be a frustrating experience for those waiting for an organ; there is a critical shortage of the number of organs donated compared with the number of people waiting to receive one. Most donations come from deceased donors either following either brain or clinical death. Patients’ religious or cultural beliefs may dictate whether they are organ donors, but for some, it is a matter of never considering it, says McCurry.

Potential organ donors should discuss their wishes with family members so it does not lead to an uncomfortable discussion at an already difficult time, says UNOS. “Depending on the state the patient is in, they can notate on their driver’s license if they are an organ donor and which organs they would like to donate. The patient can also consider carrying a donor card,” says McCurry.

For more information on organ donation, visit the UNOS Web site at www.unos.org/helpSaveALife.

— Kim M. Norton is a New Jersey-based freelance writer specializing in healthcare related topics for various trade and consumer publications.

Resources

The Organ Procurement and Transplantation Network, www.optn.org

Scientific Registry of Transplant Recipients, www.ustransplant.org

United Network for Organ Sharing, www.unos.gov

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A Recipient’s Journey

Dallas Weston, 49, knew he was foolish. He picked up his first cigarette at the age of 15 and put down his last at the age of 48. This was not before he developed emphysema, chronic obstructive pulmonary disease, and asthma, resulting in negligible lung capacity. “One year ago, I could not walk three feet without my oxygen tank. I was only capable of sitting in front of the TV connected to that tank,” he says.

This small-town newspaper reporter decided to do some research into possible treatments to help improve his life. His wife, a nurse, knew her husband was not doing well, and at one doctor’s appointment, she noticed, “His blood gases were not compatible with human life.”

His general practitioner shot down all of Weston’s suggestions, but his doctor felt transplantation could be a viable option. Weston was referred to the University of Virginia (UVa) Health System’s Lung Transplant Program to meet with program director Mark K. Robbins, MD.

In February 2006, Weston began to undergo the evaluation process, which included an extensive psychiatric evaluation, to ensure that he would be capable of complying with the medications he would need to take after surgery. “They [the doctors] wanted to make real sure that they got the most bang for their buck. They wanted someone who could survive the surgery and that first step was the lengthy, total-body evaluation process,” he says.

Five months later, Weston was placed on the national waiting list for a bilateral lung transplant. Twenty-two days later, he got the call to come to the hospital for his transplant.

“I apparently was a lot worse off than I originally thought, since I spent less than three weeks on the waiting list,” he says. Following the five-hour surgery that opened him “from armpit to armpit,” he spent two weeks in the hospital recuperating. “Dr. Robbins came in to check on me the day after surgery, and I was sitting up in bed working on my laptop and I had no oxygen line attached to me,” Weston recalls. “I expected to be laid up for weeks in intense pain, but at the most, I had mild discomfort. This procedure is amazing; that the technology is available to give me back my quality of life is wonderful.”

Today, Weston cannot say enough about Robbins, UVa, and the importance of organ donation. He has become an outspoken advocate of organ donation and says he wishes he could thank his donor. “They don’t know that the last thing they did in their life was to help a stranger, and for that, I cannot thank them enough,” he says.

— KMN

Minimally Invasive Procedure Effectively Detects, Evaluates Lung Cancer

Endoscopic ultrasound, a minimally invasive procedure in which a camera-tipped scope is inserted down the esophagus, can safely and effectively determine whether masses in or around the lungs are cancerous or benign.

Duke University Medical Center gastroenterologists who analyzed the results of 18 clinical trials have concluded that the procedure should be used routinely to evaluate, or stage, possible malignant masses. The researchers say that if the procedure were universally adopted, nearly one third of possible lung cancer patients would not need additional, more invasive staging procedures.

The key to successfully treating lung cancer is determining the type of cells that comprise the mass and whether they have spread. With the endoscopic ultrasound procedure, physicians can sometimes visualize the mass, but more importantly, they can determine whether it has spread to adjacent tissues or lymph nodes by inserting a slender needle through the endoscope that “sucks” out a sample from the mass. A pathologist in the procedure room can quickly determine whether malignancy is present.

“The results of this analysis should change the way we stage some types of lung cancers,” says Frank Gress, MD, senior member of the research team whose analysis was published in the February issue of Chest. The analysis was supported by Duke’s division of gastroenterology and Center for Clinical Health Policy Research.

“The procedure is safe, improves our ability to evaluate and stage certain lung masses and cancers, and may even improve the quality of life for these patients,” Gress says. “We are hopeful that more centers will adopt this approach as a routine part of lung cancer staging.”

The endoscopic technology used for lung cancer staging is the same used for 20 years by gastroenterologists to view the lining of the esophagus, stomach, and small and large intestines during an endoscopy procedure. With the added use of ultrasound, gastroenterologists can look at structures beyond the wall of the intestine, such as the pancreas, gall bladder, and bile duct. In the mid-1990s, gastroenterologists began to use the same approach to view structures beyond the walls of the esophagus, such as lymph nodes located near the lungs, and combined that with tissue sampling techniques to make a definitive diagnosis.

Lymph nodes are filters within the lymphatic system, which carries immune system cells that fight off infections. Cancer cells often break off from tumors, travel through the lymphatic system, and collect in the nodes, where they can start forming new tumors. The degree of this spread, or metastasis, determines the prognosis of the cancer.
For their study, the Duke researchers combined the data from 18 small clinical trials evaluating the procedure’s diagnostic accuracy in detecting the spread of non–small-cell lung cancer in 1,201 patients. Non–small-cell lung cancer, which represents about 80% of all lung cancers, is a fast-growing form of the disease.

The researchers found that the procedure—known technically as endoscopic ultrasound with fine needle aspiration—correctly excluded involvement of chest lymph nodes with cancer 83% of the time. The procedure also identified 97% of the patients whose lymph nodes contained cancer. There were no major complications in any cases, the researchers say.

Gress says that wide adoption of the procedure would mean that, probably, approximately 30% of lung cancer patients would avoid the need for more invasive approaches for staging of their disease. In one of these procedures, surgeons take samples through slits in the chests of patients, who must receive general anesthesia. The endoscopic ultrasound procedure takes roughly 20 minutes and requires the same mild sedation used during a colonoscopy procedure.

“This study demonstrates the important role for endoscopic ultrasound with fine needle aspiration to stage patients with lung cancer,” Gress says. “The procedure is widely available in academic medical centers and has begun to branch out to other community referral centers over the past five years. What has held back the wider use of the procedure is the lack of available training opportunities for gastroenterologists interested in learning this procedure. This is an advanced procedure requiring an additional year of training to become proficient.”

The researchers are currently conducting an analysis to evaluate the procedure’s cost-effectiveness.

— Source: Duke University Medical Center