TransplantUpdate. A Report from the Annette C. and Harold C. Simmons Transplant Institute Volume 3 Number 2

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1 TransplantUpdate A Report from the Annette C. and Harold C. Simmons Transplant Institute Volume 3 Number 2 Recurrence of Hepatocellular Carcinoma Decreases in Last Decade 2 The recurrence of hepatocellular carcinoma has decreased significantly over the last 10 years, from 30 percent to 6.2 percent. At Baylor University Medical Center at Dallas, 353 patients with liver cancer have received a liver transplant for hepatocellular carcinoma, and only 18 percent have developed a tumor recurrence. Laparascropic Nephrectomy Eases Burden of Living Donation 3 Patients who receive a kidney from a living donor experience much better outcomes than with one from a deceased donor. Graft survival at one, five and 10 years is significantly better. In living donation, the organ is procured and transplanted quickly so the kidney is not out of the body very long, which enhances its viability. Baylor Offers Comprehensive Care for Complex Pancreatic Disease 4 Patients with complex pancreatic diseases have access to comprehensive treatment options at Baylor University Medical Center at Dallas and Baylor All Saints Medical Center at Fort Worth, primarily within the umbrella of transplant and surgical oncology. Recent Progress in Islet Cell Transplantation 5 In patients severely affected by type 1 diabetes, maintenance of normal blood glucose levels is often difficult to achieve. Hypoglycemic unawareness can lead to life- threatening complications. The past decade has seen tremendous progress in pancreatic islet transplantation, still considered an investigational procedure in the United States, as a treatment for patients severely affected with type 1 diabetes. HeartWare Ventricular Assist System to be Studied as Destination Therapy 6 Baylor University Medical Center at Dallas has begun a clinical trial of the HeartWare Ventricular Assist System as destination therapy for advanced heart failure patients. Baylor Dallas is one of only two medical centers in North Texas participating in the national, multicenter trial. Treatment Alternatives for Chronic Obstructive Pulmonary Disease 7 Chronic obstructive pulmonary disease (COPD) remains the fourth-leading cause of death. Although medical therapies may improve symptoms, they have not had a major impact on improving lung function.

2 2 Recurrence of Hepatocellular Carcinoma Decreases in Last Decade The recurrence of hepatocellular carcinoma has decreased significantly over the last 10 years, from 30 percent to 6.2 percent. At Baylor University Medical Center at Dallas, 353 patients with liver cancer have received a liver transplant for hepatocellular carcinoma, and only 18 percent have developed a tumor recurrence. According to Nicholas Onaca, M.D., a transplant surgeon on the medical staff of Baylor University Medical Center at Dallas, a combination of factors is responsible for this improvement, including more accurate imaging, reduced waiting times for transplant, pre-transplant therapy and specific immunosuppressive regimens. The inclusion criteria for transplant include the size and number of tumors a patient has, said Dr. Onaca. In the past, a patient may be diagnosed with two tumors in his or her liver when in fact there were four. With improvements in imaging quality and accuracy, we have fewer tumors that are found only after we remove the patient s liver. Today we do not transplant patients who would not benefit because the tumors are too large or numerous. A second factor that has played a part in the reduced recurrence of hepatocellular carcinoma is the decreased waiting time for a transplant that resulted from changes in the allocation system. Since the implementation of the MELD score in 2002, patients with liver cancer have better access to transplantation before their disease progresses. Pre-transplant therapy also plays a role, Dr. Onaca said. Most of our patients with significant tumors above 2 centimeters in size receive pre-transplant therapy based on a multidisciplinary approach, including oncology, hepatobiliary surgery and radiology. We decide which treatment modality is best suited for the particular tumor size and location inside the liver. As a result, there has been a decrease in the number of patients on the waiting list who drop off because there is too much progression of their cancer. Dr. Onaca emphasized that no single pretransplant treatment modality alone, such as radiofrequncy ablation or emobolization, has been shown to significantly decrease tumor recurrence after transplant. The final factor in the reduced recurrence of hepatocellular carcinoma, which has been demonstrated statistically, Dr. Onaca said, is the use of sirolimus as part of the posttransplant immunosuppressive regimen. This medication was initially used in oncology as an anti-tumor medication, he said. Through research, we realized that it also is effective as an immunosuppressive agent. According to Dr. Onaca, physicians on the medical staff at Baylor performed a casecontrol review of prospectively collected data that compared two groups of patients according to the type of immunosuppression after liver transplantation for hepatocellular carcinoma. One hundred six patients received tacrolimus and mycophenolate mofetil, and 121 received sirolimus. Patients in the sirolimus group had significantly higher recurrencefree survival rates than patients in the tacrolimus group. The sirolimus group also had significantly higher patient survival rates than the tacrolimus group at 1 year (94% versus 79%), 3 years (85% versus 66%), and 5 years (80% versus 59%; P = 0.001). Sirolimus was well tolerated, and the patients in this study did not have the increase in surgical complications noted by other investigators. iver Over 25 years ago, Baylor pioneered the first liver transplant program in the Southwest. One of three programs in the nation to perform more than 3,300 liver transplants. * Baylor s expertise in the areas of hepatitis B and C is internationally renowned. * Volumes based on liver transplants at Baylor University Medical Center and Baylor All Saints Medical Center

3 Laparascropic Nephrectomy Eases Burden of Living Donation Patients who receive a kidney from a living donor experience much better outcomes than with one from a deceased donor. Graft survival at one, five and 10 years is significantly better. In living donation, the organ is procured and transplanted quickly so the kidney is not out of the body very long, which enhances its viability. For approximately a decade, the vast majority of living donations are performed laparoscopically. Baylor University Medical Center at Dallas has performed between 600 and 700 such procedures. Compared to traditional open procedures, laparoscopic nephrectomy results in better outcomes for the donor. In a laparoscopic nephrectomy, small incisions are made to dissect the kidney. An incision about the size of the donor s fist, which is equivalent to the size of the donor s kidney, is made in the abdominal wall to allow the kidney to be removed undamaged. This incision is much smaller than the flank incision used in the traditional nephrectomy and heals more quickly, said Jeffrey Campsen, M.D., a transplant surgeon on the medical staff of Baylor Dallas. Cosmetically, the size of the incision is better. Patients generally recover faster, with most leaving the hospital in two to four days and returning to work in two weeks. Dr. Campsen said an open nephrectomy, which entails a large incision through the back muscle to reach the retroperitoneal space, may have to be considered if an otherwise healthy donor has had several open abdominal surgeries, resulting in the build-up of scar tissue. This procedure has excellent results in terms of viability of the donated kidney, but the donor experiences more pain, and his or her recovery time is significant, he said. At Baylor Dallas, transplant surgeons on the medical staff perform two types of minimally invasive nephrectomies: completely laparoscopic or hand-assisted. In a handassisted procedure, the surgeon places his or her hand in the abdomen and uses one hand as a dissecting tool. Some surgeons prefer the dexterity and feel of the hand-assisted procedure, but there is no difference in outcome. Laparoscopic nephrectomy also is an important factor in paired kidney donation, which Baylor Dallas and Baylor All Saints Medical Center at Fort Worth now offer. Approximately one-third of all willing living kidney donors have an incompatible blood type with their intended recipient. Others may have a positive cross-match against the recipient. Patients are then faced with finding someone else who is a suitable donor or waiting on the transplant list until an organ from a deceased donor becomes available. Paired kidney transplantation allows incompatible living donor/recipient pairs to still donate and receive kidney transplants despite the original incompatibility. A patient should never be ruled out because of an incompatibility with his or her willing donor, Dr. Campsen said. Each patient should be evaluated at a transplant center that offers paired kidney donation. Kidney With more than 3,100 kidney transplants performed, our kidney and kidney/pancreas program is one of the largest in Texas. * According to the United Network for Organ Sharing (UNOS), survival rates for Baylor kidney recipients exceed the national and state averages. * Volumes based on kidney transplants at Baylor University Medical Center and Baylor All Saints Medical Center. 3

4 4 Baylor Offers Comprehensive Care for Complex Pancreatic Disease Patients with complex pancreatic diseases have access to comprehensive treatment options at Baylor University Medical Center at Dallas and Baylor All Saints Medical Center at Fort Worth, primarily within the umbrella of transplant and surgical oncology. In a patient-centered model of care, a full range of medical, surgical and endoscopic services is available to patients with pancreatic disease all in one location. We work closely with our colleagues in the gastroenterology area in caring for patients with pancreatic disease, including some gastroenterologists on the medical staff at Baylor who specialize exclusively in the care of the pancreas, said Marlon Levy, M.D., surgical director of transplantation at Baylor Fort Worth and physician on the medical staff at Baylor Fort Worth and Baylor Dallas. Patients with malignancies within the head of the pancreas may undergo a pancreaticoduodenectomy, commonly referred to as the Whipple procedure. In this surgical procedure, the head of the pancreas, first portion of the small intestine, gallbladder, a portion of the bile duct and sometimes a small portion of the stomach is removed with the goal of removing all tumors. After resection, the gastrointestinal tract is reconstructed. For patients with tumors in the body or tail of the pancreas, a distal pancreatectomy may be performed. In this procedure, the left half of the pancreas is surgically removed. In addition to procedures for pancreatic cancer, Baylor offers a broad range of surgeries, including total pancreatectomy with or without islet cell transplant and the Puestow procedure for chronic pancreatitis and pancreatic drainage for chronic pancreatic stricture. Diseases of the pancreas can be extremely complex. Their treatment requires a multidisciplinary team approach that customizes solutions and calls on the skills and expertise of many different practitioners, such as are found at Baylor. Pancreas First facility in the Southwest to be approved by the American Society of Transplant Surgeons as a surgical training program in pancreas transplantation. Pancreas patient survival rates at Baylor University Medical Center and Baylor All Saints Medical Center exceeded the national average for one year survival.

5 5 Recent Progress in Islet Cell Transplantation In patients severely affected by type 1 diabetes, maintenance of normal blood glucose levels is often difficult to achieve. Hypoglycemic unawareness can lead to life-threatening complications. The past decade has seen tremendous progress in pancreatic islet transplantation, still considered an investigational procedure in the United States, as a treatment for patients severely affected with type 1 diabetes. The potential advantage of islet cell transplantation over administration of exogenous insulin is that the transplanted islets would maintain normal glucose levels preventing hypoglycemic episodes and could also minimize the long-term complications of diabetes. Overall, the short-term results in terms of achieving insulin independence after islet cell transplantation have been impressive whereas the long-term outcomes have been poor. Isolation of transplantable quality islets from a donor pancreas requires adherence to a series of technically demanding steps. Preservation of the organ under cold conditions and minimization of cold ischemia time prior to isolation has been shown to be critical for successful isolation. Our research also has shown that preservation of the pancreatic duct prior to isolation can significantly improve islet yield and quality, said Bashoo Naziruddin, Ph.D., director of the Islet Cell Laboratory at Baylor University Medical Center at Dallas. We have made significant improvements in several technical steps involved in isolation that have resulted in consecutive transplants from seven clinical islet isolations. In the majority of patients, the function of the transplanted islets deteriorates over time, requiring them to go back to exogenous insulin administration. Several events could be responsible for the poor long-term survival of islets, including allogenic and autologous immune responses, toxicity of immunosuppressive drugs and lack of beta cell regeneration. Current issues hampering further progress of islet transplantation include a need to improve the quality and quantity of islets isolated from deceased donor pancreata, minimizing the loss of transplanted islets during the peritransplant period caused by an inflammatory reaction and development of an immunosuppressive regimen that effectively controls development of autoimmune and/or alloimmune responses without causing beta cell toxicity and allowing beta cell regeneration. Before allogeneic islet cell transplantation can be considered as a standard therapy for type 1 diabetes, there are challenges to overcome. These include the necessity for immunosuppressive drugs that put recipients at risk for infections and certain cancers. Furthermore, the immunosuppressive drugs have side effects that range from mild to severe. In addition, most recipients require two or more islet infusions to attain insulin independence, which adds to the cost for this treatment. Allogenic islet transplantation is a complex immunological state involving constant interaction between the graft and the recipient s immune system, Dr. Naziruddin said. Multiple interrelated immune pathways operative in autoimmunity and allogenic response could be responsible for the loss of islet function over the long term. As we increase our understanding of the mechanisms involved in acute and chronic rejection and the effects of immunosuppressive drugs following islet transplantation, we will achieve improvements in clinical outcomes. North Texas first islet cell transplant. Baylor s islet cell laboratory is one of only a few in the country to process cells for transplantation. Baylor achieves 100 islet cell isolations.

6 6 HeartWare Ventricular Assist System to be Studied as Destination Therapy The VAD program at Baylor Dallas was the nation s first to receive the Gold Seal of Approval from the Joint Commission. The Baylor/UTSW heart transplant program ranks above the national average for one year and three year patient survival statistics. L Baylor University Medical Center at Dallas has begun a clinical trial of the HeartWare Ventricular Assist System as destination therapy for advanced heart failure patients. Baylor Dallas is one of only two medical centers in North Texas participating in the national, multicenter trial. Somewhat smaller than the HeartMate II, the HeartWare Ventricular Assist System features the HVAD pump, a small fulloutput circulatory support device (up to 10L/min flow) designed to be implanted next to the heart in the pericardial space, avoiding the abdominal surgery generally required to implant similar devices. Implantation above the diaphragm is expected to lead to relatively short surgery time and quicker recovery. Designed to enroll up to 450 patients at 50 U.S. hospitals, the ENDURANCE study is a randomized, controlled, unblinded, multicenter clinical trial to evaluate the use of the HeartWare Ventricular Assist System as a destination therapy in advanced heart failure patients. The study population will be selected from patients with end-stage heart failure who have not responded to standard medical management and who are ineligible for cardiac transplantation. The HeartWare device has the potential to last longer than the currently available pumps, said Dan Meyer, M.D., surgical director of the heart and lung transplantation program at Baylor University Medical Center at Dallas, a collaboration with the University of Texas Southwestern Medical Center. The data from the trial studying the device as a bridge to transplant look very favorable. Depending on the results of this trial, we believe the HeartWare LVAD s improved durability and smaller size will offer an excellent option for patients as an alternative to transplant. Patients in the study will be randomly selected to receive either the HeartWare Ventricular Assist System or, as part of a control group, they will be implanted with any alternative LVAD approved by the FDA for destination therapy in a 2:1 ratio. Each patient receiving the HeartWare Ventricular Assist System or control LVAD will be followed to the primary endpoint at two years, with a subsequent follow-up period extending to five years post implant. eart

7 ung 7 Treatment Alternatives for Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease (COPD) remains the fourth-leading cause of death. Although medical therapies may improve symptoms, they have not had a major impact on improving lung function. The prevalence of COPD is 12 to 24 million individuals, resulting in approximately 2 million emergency department visits, 661,000 hospitalizations and approximately 125,000 deaths per year. The standard therapy for COPD is dependent on the severity of the disease as judged by measurements in airway function. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has classified COPD into four stages. I. Mild FEV 1 /FVC < 70 % FEV 1 > 80% predicted II. Moderate FEV 1 /FVC < 70 % FEV % predicted III. Severe FEV 1 /FVC < 70% FEV % predicted IV. Very Severe FEV 1 /FVC, 70% FEV 1 < 30% predicted or < 50% plus chronic respiratory failure Recommendations for therapy include the use of short-acting bronchodilators on an as-needed basis for all patients, the use of long-acting bronchodilators in patients with at least moderate disease, and the addition of inhaled steroids in those patients with severe disease. Rehabilitation is considered an adjunct to medical therapy, and surgical therapy is recommended only in those patients with a FEV 1 < 30% or in patients with chronic respiratory failure. This year, the FDA approved a new drug, phosphodiesterase 4 inhibitor, for patients with chronic bronchitis. The drug is a selective PDE-4 inhibitor, which targets pro inflammatory mediators underlying the pathogenesis of COPD. Its impact on reducing the number of exacerbations and improving lung function have been similar to the other agents, such as anticholinergic agents, inhaled steroids and sympathiometic agents, used singularly or in combination. The medication has been associated with weight loss and a higher rate of neuropsychiatric events. Lung transplantation, which is reserved for those patients with COPD in the very severe classification, results in a significant improvement in functional capacity, although the evidence for an improvement in survival is less clear. This is in contrast to the survival advantage seen in patients with cystic fibrosis and interstitial lung disease. Consequently, lung transplantation is presently recommended for those patients with COPD if their BODE score is 7 or above, their FEV 1 is < 20% predicted, the diffusing capacity is less than 20% predicted, or there is an increased number of exacerbations despite adequate therapy. Most transplant centers prefer that patients be referred earlier in the course of the disease. The guideline for referral is a BODE score is >5, the FEV 1 is < 25% or the presence of hypoxemia, hypercapnea or pulmonary hypertension. Patients with emphysema may benefit from lung volume reduction surgery. The removal of non-functioning lung tissue is thought to improve the elastic recoil of the remaining lung and the mechanics of the respiratory system. The National Emphysema Treatment Trial (NETT) identified a group of Dallas first single and double lung transplant. Dedicated nurses on call 24 hours a day, seven days a week for the management of an advanced lung disease patient. patients who clearly benefited from the surgery in terms of survival, exercise capacity and health-related quality of life. These patients had more disease in the upper lobes and poor exercise tolerance, whereas those patients with a homogeneous distribution of disease or good exercise tolerance had poorer or equal survival to those completing medical therapy. It should be noted, however, that the improvement in functional status was not equivalent to lung transplantation. Because of the mortality seen with volume reduction surgery (8% overall but only 2% in those patients with upper lobe predominance and poor exercise tolerance), endobronchial one-valves have been developed to collapse the part of the lung that essentially is non-functional in an attempt to improve the elastic recoil of the respiratory system. These studies have revealed a 4.3% increase in the FEV 1 at six months compared to a (Continued on back cover)

8 Annette C. and Harold C. Simmons Transplant Institute 3410 Worth Street, 9th Floor Dallas, Texas NONPROFIT ORG US POSTAGE PAID DALLAS, TX PERMIT #777 (Continued from page 7) Treatment Alternatives for Chronic Obstructive Pulmonary Disease decrease in FEV 1 of 2.5% in the medically treated group. The six-minute walk test revealed a similar improvement in comparison to a decrease in the medical therapy. However, these improvements in lung function and exercise tolerance were counterbalanced by a increased rate of exacerbation of COPD requiring hospitalization (7.5% vs. 1.1%), hemoptysis (6.1% vs. 0%) and pneumonia (4.2%) Thus the complication rate has dampened the enthusiasm for valve therapy. A CONTINUING MEDICAL EDUCATION EVENT EXPLORING NEW APPROACHES TO THE DIAGNOSIS AND MANAGEMENT Of GASTROINTESTINAL & LIVER DISEASES SEPTEMBER 24, 2011 THE RITZ-CARLTON DALLAS, TX FOR INFORMATION & REGISTRATION VISIT OR CALL Gastroenterology and Hepatology Round-Up 2011, the seventh annual, is designed to update providers in gastroenterology and hepatology on new approaches to the diagnosis and management of gastrointestinal and liver diseases. This course is specifically targeted toward gastroenterologists, hepatologists, family practitioners, nurse practitioners, internists, surgeons, physician assistants, registered nurses and clinical transplant nurses and coordinators. Thus, medical treatments for COPD may decrease exacerbations and improve symptoms, whereas surgical treatments, in a selected population, also improve lung function and functional status. For More Information, Call With one phone call, a physician can request additional information, an appointment for a patient, or a consult. Call and a representative will assist you. If you wish to be taken off this mailing list please call BAYLOR. Physicians are members of the medical staff at one of Baylor Health Care System s subsidiary, community or affiliated medical centers and are neither employees nor agents of those medical centers, Baylor University Medical Center at Dallas, Baylor All Saints Medical Center at Fort Worth or Baylor Health Care System Baylor Health Care System. DH_ACHC_284_ Worth Street, 9th Floor Dallas, Texas BaylorHealth.com/Transplant 1400 Eighth Avenue Fort Worth, Texas BaylorHealth.com/Transplant