Summer 2006

Department of Surgery healthpoints NewYork-Presbyterian ALL THE POSSIBILITIES OF M O D E R N M E D I C I N E

Jean C. Emond, MD Vice Chairman and Transplantation: Chief of Transplantation at NewYork-Presbyterian/ Columbia University Where we've been, where we're going Medical Center

When Dr. Emond When he transplanted a chimpanzee kidney into a human patient in the late joined the faculty in 1960’s, the late Keith Reemtsma, MD, then Department of Surgery Chairman at 1997, he applied a Tulane University, revolutionized treatment of end-stage organ failure and initiated an multidisciplinary era of unprecedented exploration into organ transplantation that would affect the lives model to the liver transplant program, and established a joint collaboration of patients around the world. between hepatology and surgery. In the Transferring to Columbia-Presbyterian Medical Center in 1971, Dr. Reemtsma decade since then, the program has recruited Mark A. Hardy, MD, who laid another cornerstone of organ transplant transformed into one of the largest and medicine by founding the program for dialysis and kidney transplantation. Dr. Hardy most innovative in the country. His based the new program on the principle of collaborative clinical care between dedication to finding new and better surgeons and nephrologists. During a time when renal transplant programs were solutions for transplant patients continues to raise the bar of excellence managed by one or the other discipline but never by both simultaneously, the medical and inspire creative advances throughout the transplantation programs at Columbia University Medical Center.

INNOVATIONS IN TIME 1969 Joseph Buda, MD, performs the first kidney transplant at Columbia- Presbyterian Medical Center.* Kidney Transplantation, page 3

1977 First heart transplant at at Columbia-Presbyterian Medical Center. Heart Transplantation, page 10

1986 Lung transplantation begins at Columbia-Presbyterian Medical Center. Eric A. Rose, MD, left center (current Chairman, Department of Surgery), performing the first Lung Transplantation, page 5 successful pediatric heart transplant in 1984. This special issue of healthpoints is dedicated to transplant pioneer Keith Reemtsma, MD, who is overseeing the operating field (top of photo).

INNOVATIONS IN TIME 1997 community regarded the concept as folly. organs, performs transplants among National search assembles team to Yet the program grew steadily, as did the incompatible donors, and is a leader in establish Center for Liver Disease program’s immune tolerance research initia- coordinating “donor swaps” to maximize and Transplantation, for adults tives to induce the transplant recipient’s availability of compatible donor organs. and children. body to accept a donor organ. This multi- Since Dr. Ratner’s arrival, this program has Liver transplantation, page 8 disciplinary cooperation also led to major doubled its volume, performing over 300 contributions in immunogenetics, kidney transplants per year. immunosuppression, and treatment of Under the leadership of Dr. Hardy and autoimmune diseases and lymphoma — Kevan Herold, MD, Columbia has been and it ultimately became the overarching designated one of ten regional islet resource principle for all the NewYork-Presbyterian centers in the U.S. that isolate and trans- Hospital transplant services. plant pancreatic cells to treat type 1 Colleagues universally give credit to Eric diabetes as part of a limited protocol 2004 A. Rose, MD, who co-founded the heart controlled by the FDA. Recent progress in Intestinal Rehabilitation and Transplantation program opens at transplantation program with Dr. visualization of pancreatic islets using PET NewYork-Presbyterian/Columbia. Reemtsma, for his successful transformation technology, under the guidance of Paul Pediatric intestinal and of the program into the outstanding center Harris, PhD, has been recognized by the liver transplantation, page 5 it is today. A parade of achievements marks scientific community as a milestone in this the history of the heart transplant program, developing field. including the first mechanical bridge-to- While the transplantation program as a transplantation using intra-aortic balloon whole forecasts over 600 solid organ trans- pumps in the 1970’s, and the first successful plants this year, transplantation of cells, pediatric heart transplant, performed by Dr. rather than organs, is emerging as a therapy Rose in 1984. Under the guidance of Dr. with enormous potential. Transplantation 2004 Rose and his successors, the program has of either a patient’s own or a foreign First pancreatic islet cell pioneered research in immunosuppressant donor’s bone marrow cells, for example, transplantation at Columbia. medications, mechanical assist devices, and offers hope of regenerating the heart so that minimally invasive surgical procedures. It patients with heart failure may be able to currently performs over 100 heart trans- avoid heart transplantation. The SCCOR plants yearly, with among the highest trial, a pivotal NIH-funded study including success rates in the nation. cell transplantation in patients with heart In 2004, Dominique M. Jan, MD, created failure, is enrolling patients now. a new rehabilitation and transplant service In introducing the transplantation 2005 for children with liver and small bowel programs, it would be remiss to neglect NewYork-Presbyterian Hospital sets U.S. diseases, also in a fully interdisciplinary mention of the yet another dimension in record for number of heart transplants fashion. Its team approach is unique in the which they excel – education. “Because this is performed in one year, at 119. U.S., combining the efforts of pediatricians, an academic medical center, physician train- hepatologists, and liver transplant surgeons. ing is a top priority along with patient care 2006 “Every problem is discussed by both and research,” says Dr. Rose. “We have First 3-way kidney swap at NewYork- pediatric specialists and surgeons, and this trained many of the greatest transplant Presbyterian/Columbia. gives patients the best results,” says Dr. Jan. surgeons over the last 20 years, including Also in 2004, Lloyd E. Ratner, MD, many of the leaders of transplant programs succeeded Dr. Hardy as director of the renal throughout the U.S.” and pancreas transplant program. One of the first to perform laparoscopic donor This special issue highlights just a few recent operations, Dr. Ratner has found creative exciting developments in transplantation solutions to overcome immune barriers to research and patient care. Readers can learn kidney transplantation. The program now more by visiting www.columbiatransplant.org * In 1998, Columbia-Presbyterian Medical Center and New York Hospital merged routinely uses extended-criteria donor or by calling the department. to form NewYork-Presbyterian Hospital.

2 healthpoints • summer 2006

Kidney Transplantation: Thinking Outside the Box

Kidney transplantation has come a area, the program has developed new ns io long way since the first successful ways to safely use more organs than unicat mm transplant between identical twins in ever for transplantation. First, it has o

1954. Since then, improvements in implemented new protocols for using dical C me io B

surgical technique, medical manage- extended criteria organs that may not f esy o ment, and immunosuppressive therapy meet the usual criteria for transplan- t our have facilitated transplants from family tation, but are healthy enough for a C members, genetically unrelated living successful transplant. Donor kidneys In many cases of living donor trans- plantation, family members donate donors, and deceased donors. In 2005, that might go unused in regions with organs to their loved ones. In the case over 16,400 kidney transplants were fewer people on the organ waiting list of the rare three-way kidney swap per- performed in the U.S., approximately can be matched with appropriate formed May 30, 2006, altruistic donor 60% from deceased donors and the candidates in areas with greater John McGuinness did not know any of remainder from living donors. Success demand, according to Dr. Ratner. the recipients, but just wanted to help. rates have increased steadily, and now Organs in this category include Public service is a way of life for exceed 90% at one year and 50% at ten those from donors who are older, have John, who came from a family with a years. Despite this extraordinary hypertension or diabetes, or who at the strong background in volunteer work. success, however, many challenges time of their death suffered mild Today he volunteers as a firefighter and remain. kidney injury. As is the case with heart, as a wrestling coach, serves in his Topping the list is the chronic short- liver, and lung transplantation, the use church, and regularly donates blood. age of organs, which creates dilemmas of extended criteria kidneys is proving Yet he wanted to do even more, and about fairly allocating kidneys to highly successful, especially among after a fellow firefighter and friend of ten years died in Iraq, John decided to patients with varying degrees of need, older recipients and those doing poorly give someone else the gift of a new life. risk, and potential benefit. Another on hemodialysis. He contacted the living donor major challenge is medical in nature – Second, the program has developed kidney transplant program at Columbia finding safe and effective ways of over- strategies to address immunologic in February 2006. By April, there was a coming the body’s natural tendency to issues that, until recently, were match. The recipient was so ill that reject the new kidney. At NewYork- thought to preclude transplantation. dialysis no longer worked, and there Presbyterian Hospital/Columbia Using new methods to “clean” were no other options left. John gave University Medical Center, the Renal mismatched antibodies from the his left kidney, and in so doing, facili- and Pancreatic Transplantation recipient’s blood, the program now tated the swap that enabled three Program is leading the nation in performs incompatible donor trans- recipients to be matched with three addressing both of these critical areas. plantation of kidneys into recipients compatible donors. “Our goal is to successfully transplant whose immunologic makeup would For John, donating his kidney was as many patients as possible so they normally result in rapid rejection of not too much to do for a stranger. “There are thousands of people on the can return to normal, productive lives,” the new organ. The long-term survival waiting list, but very few receive a says Lloyd E. Ratner, MD, Director. rate for incompatible transplants is deceased-donor kidney each year,” he “We are not content to accept the exactly the same as for compatible says. “These are average people who status quo.” transplants at NewYork- will die if they don't get the organ Presbyterian/Columbia, one of of the they need. So why not give someone a Meeting the challenge of few institutions in the world offering whole new way of life? If other people organ shortage this option today. knew they could step up to the plate To meet the high demand for donor To further maximize transplant and do living donor transplantation, so organs in the New York metropolitan continued on page 9 many other people could be helped too.” referrals • 1.800.227.2762 healthpoints • summer 2006 3

Transplantation for Short Bowel Babies

When Kyle was 14 months old, he had no way the program defies the odds on a Intestinal rehabilitation functional intestine. His duodenum was so regular basis, performing heroics in a Most children with Short Bowel short it did not reach the skin, and had to field not always known for great Syndrome (little or no functional intes- be surgically vented through the stomach. optimism. Under the direction of tine) have to be nourished by total The parents had sought multiple opinions Dominique M. Jan, MD, Professor of parenteral nutrition (TPN, or nutrition at other centers, and were advised he Clinical Surgery, the program offers a through an intravenous line), which can needed both an intestinal and a liver unique method of independent manage- contribute to the development of liver transplant. ment of children with intestinal failure failure. The center has special expertise and liver disease. Its strength lies in a in minimizing this risk, says Dr. Despite assertions by Kyle’s previous comprehensive team approach: a multi- Lobritto. “Proper management of the physicians that he would not survive disciplinary group including a pediatric nutritional balance in TPN is one of the without both intestinal and liver trans- surgeon, a transplant surgeon, gastroen- most important keys in preventing liver plants, the team at the Pediatric terologists, hepatologists, nutritionists, damage. With proper balance of nutri- ents, it is often possible to avoid both liver and intestinal transplantation, and to even encourage oral feeding.” “We make every effort to use the intestine that a patient has left, and give the patient a chance to adapt,” explains Robert A. Cowles, MD, Assistant Profes- sor of Surgery. When nutritional rehabilitation is not sufficient, however, the program provides the full spectrum of surgical options. Some children may be candidates for the Serial Transverse Enteroplasty procedure (STEP), an operation to lengthen and reshape a segment of intestine into a longer, thinner intestine. Dr. Jan, who has performed many intestinal transplants worldwide, emphasizes that “if patients with short bowel syndrome receive

Kyle Cramer (center) received an intestinal transplant at age 14 months in October 2005 proper treatment early on, many and no longer needs TPN (total parenteral nutrition). Kyle is flanked by surgeon complications — and potentially the Dominique Jan, MD (far left), Kara Ventura, NP, and his parents, Cara and Ben Cramer. need for intestinal or liver transplanta- tion — can be avoided.” Intestinal Rehabilitation and Transplant and nurse practitioners, works together program was able to complete an isolated to determine the best course of treat- Biliary atresia intestinal transplant while saving his ment for each child. According to Dr. In children with biliary atresia (a liver. “Today he is doing very well,” Jan, “This team approach results in far congenital defect of the bile duct that reports Steven J. Lobritto, MD, Interim superior care than is available at centers prevents the liver from excreting bile), Chief of Pediatric Gastroenterology. that rely on a surgical or medical emergency surgery called porto-enteros- This scenario is emblematic of the approach alone.” continued on page 12

4 healthpoints • summer 2006

Lung Transplant Surgery

Combating organ rejection GER (the passage of fluid Highly effective treatments can success- from the stomach upward fully protect patients against the threat of into the esophagus), some

the acute form of rejection that occurs also aspirate the refluxed ez r e

fluid into the lungs. né P immediately after transplant surgery. Yet e R even the best medical therapies are Although not all lung Since Drs. Selim M. Arcasoy and Joshua R. Sonett were recruited to powerless against the tide of chronic transplant patients with lead the Lung Transplant program five years ago, success rates have rejection, which slowly and steadily GER aspirate, those who soared dramatically. Survival rates for lung transplant patients at undermines the health of over half of do usually remain Columbia are 93% after one year, and 78% after three years, which lung transplant patients during the first unaware of this danger far surpass the national average of 79% and 62% respectively. three to five years after transplantation. because it occurs in small Since chronic rejection may lead to the quantities and causes no could contribute to chronic lung rejec- demise of transplanted lungs in five to ten unique symptoms. Chronic micro-aspira- tion. In fact it provides evidence that GER years, and is the leading cause of death tion of gastric content as bile acid is toxic is truly a problem for some lung trans- among lung transplant recipients, it is to lung tissue, creating an inflammatory plant recipients,” explains Dr. D’Ovidio. “the major Achilles heel in lung trans- process and possibly disrupting the innate Moreover, Dr. D’Ovidio’s research has plantation,” according to Joshua R. immune system (which normally provided a potentially far more useful Sonett, MD, Surgical Director of the Lung responds to the presence of infectious diagnostic test in the lung transplant Transplant program. agents, dusts, and allergens in the context than has been available to date. Frank D’Ovidio, MD, PhD, Assistant environment). “The ongoing inflamma- Until now, tests to detect reflux have relied Professor of Surgery in the Section of tory state induced by chronic on pH-testing methods. These detect Thoracic Surgery and the Lung Trans- micro-aspiration is likely to cause an stomach acid reflux, but miss the non-acid plant program, has shed light on the role earlier development of chronic rejection,” type of reflux that can occur with bile of gastro-esophageal reflux (GER) as one says Dr. D’Ovidio. acid. Most importantly, pH testing misses of the causes of chronic lung transplant By testing samples of patients’ the most dangerous aspect of reflux for dysfunction, and/or chronic rejection. broncho-alveolar lavage fluid collected lung transplant recipients – the aspira- Many people think of “reflux” as an during bronchoscopies after transplanta- tion. “Not all patients with reflux end up annoying condition that can be treated tion, Dr. D’Ovidio is the first researcher to aspirating,” says Dr. D’Ovidio. with anti-acid medications. But for confirm an association between the Various lung transplant centers have patients who undergo lung transplanta- presence of bile acid in the airways as a been performing Nissen fundoplication, a tion, reflux may be a far more serious marker of and toxic agent in GER, and relatively safe, laparoscopic anti-reflux problem because it can expedite the clinical outcomes among lung transplant surgical procedure, in the majority of body’s rejection of the transplanted lung. patients. He found micro-aspiration of their lung transplant patients with GER. It has been recognized since the 1990’s bile acid to be a predictor of early chronic This treatment has likely helped to curtail that GER contributes to the deterioration lung transplant dysfunction. Also known chronic rejection in some patients, says of lung tissue among lung transplant as bronchiolitis obliterans syndrome, Dr. D’Ovidio, but “not every lung trans- recipients. Until recently, however, no chronic lung dysfunction has been plant patient with GER needs to have sur- studies defined the way in which GER considered a clinical indicator of chronic gery.” The lung transplant program is now might actually lead to chronic lung rejec- rejection. developing protocols to routinely test tion, or established which patients would “The documentation of the relation- patients for aspiration about three truly benefit from anti-reflux surgery ship between aspirated bile acid and months post-transplant. Testing is done (known as gastric fundoplication). bronchiolitis obliterans syndrome via broncho-alveolar lavage during rou- Among those patients who experience validated previous observations that GER continued on page 11 www.columbiasurgery.org healthpoints • summer 2006 5

Columbia Kreitchman PET Center

PET at the Click of a Mouse

While patients used to arrive at their doctor’s office For doctors, the system has markedly improved the way holding large envelopes of films and pictures, today they can they can view PET or PET/CT images, translating to vastly come with a CD of digital images. But as is the case with much improved accessibility, readability and flexibility. For patients, computer technology, standardization is lacking among the Stentor means better treatment. For example, using a laptop systems used to create the data, so that in some cases, doctors with Internet access, physicians can import scans during may not be able to view test results taken at another facility. conferences about patient treatment and progress. “Impor- “Many programs out there are very difficult to use,” says Paul tant treatment decisions are made in these conferences, so it’s F. Simonelli, MD, PhD, FCCP, a pulmonologist and Assistant ideal to have everyone — the oncologist, the radiation oncol- Professor of Clinical Medicine in the Division of Pulmonary, ogist, the surgeon, and the pulmonologist — viewing the Allergy & Critical Care at the Columbia University College of image at the same time,” says Dr. Simonelli. Physicians and Surgeons. Dr. Simonelli uses Stentor to view his lung cancer patients’ But for physicians referring patients to Columbia for PET PET/CT scans. PET (positron emission tomography) visual- or PET/CT, this is not a problem. As of 2005, the Columbia izes chemical activity, which is elevated in the presence of any Kreitchman PET Center has adopted an advanced system for cancer, and CT (or CAT) scans visualize the body’s anatomi- cal structures. PET/CT fuses these images into a single, overlapping picture that shows precisely where the cancer is located. PET and PET/CT capture three-dimensional pictures that are viewed in cross sections known as “slices.” Previously, hard copies of selected slices were delivered to the physician a few days after the patient’s scan. If the physician wanted to view all of the scan slices, he was compelled to visit the scanning facility. Stentor now provides all slices as soon as the scan is complete. Accessing them on his computer, the referring physician is able to easily navigate through these images and compare them. “You’re in essence creating a 3-D picture that you can scroll through and manipulate,” says Dr. Simonelli. When patients come to the Kreitchman PET Center for a scan, the technician saves the images to a server under the referring physician’s name. At that point, they become

Using the Kreitchman PET Center’s iSite Stentor system, Dr. Paul immediately available for the Columbia or outside referring Simonelli can access all of the slices of his patients’ PET/CT scans physician to access by logging on to the Center’s iSite Stentor from his desk. server with a password. No special software beyond a browser is required, and physicians can access the system in the office, viewing PET and PET/CT scans. Because the Philips iSite in a conference room, or at home. Navigation buttons and Stentor system is web-based, physicians can access it anywhere, tools to manipulate and store copies of the scan appear when anytime, and from any computer, via the Internet. the program is opened in the browser. “Stentor has revolutionized how we communicate with “When people talk about 21st century medicine, this is it,” referring physicians and how these same physicians communi- says Dr. Simonelli. cate visually and verbally with their patients,” says Ronald L.Van Heertum, MD, Professor of Radiology, Columbia If you are a physician and would like to set up a Stentor University College of Physicians and Surgeons, and Director, account with the Columbia Kreitchman PET Center, please Columbia Kreitchman PET Center. contact Judy Parenta at 973.650.2133.

6 healthpoints • summer 2006 www.columbiapet.org

212-923-1555 • [email protected]

A Second Chance for the Ailing Heart

A dvances in biomedical technology are making organ trans- plantation safer and more effective. For some, it is even helping to avoid the need for transplantation altogether. Patients with severe coronary artery disease may become candidates for heart transplant when prolonged nutrient and oxygen deprivation due to blocked arteries has killed portions of their heart muscle. But using PET (positron emission tomography) imaging to detect cardiac viability can offer these hearts a second chance. When an area of the heart is starved of blood by a blocked artery, the heart muscle (or myocardium) in that area dies and forms scars. If enough of the heart muscle has been compromised in this way, the organ can no longer do its job of pumping blood through the body. Decreased blood flow doesn’t always kill myocardium, however. It can also simply render portions of the heart muscle dormant. Often referred to as “hibernating ns io t myocardium,” such living muscle is under-active, but can be u ol revived by procedures to restore blood flow (revascularize) such as dical S e

coronary artery bypass or angioplasty and stenting. ns M me ie But first, hibernating myocardium must be properly detected. S f esy o Routine tests that measure the amount of blood flow (perfusion) t our to the heart, such as the thallium test, can underestimate the C amount of hibernating myocardium that is present. PET, with its HIBERNATING HEART MUSCLE ability to detect cell metabolism, can distinguish the faint activity An FDG PET scan (top) indicates there is living muscle in a place of dormant heart muscle. For this purpose, PET is recognized as where a blood flow scan (bottom) shows there is little circulation. offering the highest accuracy level of any non-invasive cardiac test. “In analyzing a given area of the myocardium, a PET scan will lived (or have a short half-life), remaining in the body for a much reveal living cells in 40% of patients whose thallium test showed briefer amount of time. no living tissue,” Says Sabahat Bokhari, MD, Assistant Professor of Before undergoing a PET scan for myocardial viability, patients Medicine, and Director of Cardiac PET at the Columbia Univer- receive an injection of a radio-labeled glucose compound called sity Kreitchman PET Center. In addition to being more precise, FDG that can be tracked by the PET scanner. Glucose (a form of PET is safer than other nuclear cardiac scans because the radioac- sugar) is required by the body’s cells for nutrition, and the FDG tive “tracer” compounds administered during PET scans are short taken up by the tissues appears on the PET scan as areas of increased brightness. Scar tissue in the myocardium, where there is no living activity, appears dark. Hibernating myocardium, meanwhile, appears brighter. With such a picture, the cardiologist The Centers for Medicare and Medicaid Services (CMS) currently is in a position to make an informed decision about whether the has approved reimbursement for cardiac PET scans in patients patient requires heart transplant, or whether they would benefit with cardiovascular disease. Some private insurers also cover from a revascularization procedure. Furthermore, the scan can cardiac PET on a case-by-case basis. Cardiac PET is used to: assist the physician in deciding which type of treatment will be ‰ Delineate blood-flow patterns right for the patient. ‰ Assess the viability of heart muscle ‰ Determine the optimal treatment path — identifying For a PET cardiac viability referral, please contact your cardiolo- whether a patient is a candidate for coronary angioplasty, gist. For more information, call the Columbia Kreitchman PET coronary artery bypass graft surgery, or heart transplanta- tion. Center at 212.923.1555.

healthpoints • summer 2006 7

Living Donor Liver Transplantation Saves Lives

Because of the manner in which the to wait on the list for a donor. note that at this center, living donor national organ donation system is Although some potential donors are transplantation is “facilitated, but never organized, some regions, such as the reluctant to take the risks associated with pushed.”An Independent Donor Assess- New York tri-state area, have longer donation, the risks are low, according to ment Team (IDAT) performs medical waiting lists than others. As a result, Jean C. Emond, MD, Chief of Transplan- evaluations of every potential donor, patients in New York face longer waiting tation. The donor’s liver regenerates to educates them about the procedure, and times for deceased-donor organs, and its original size in several weeks, and serves as a dedicated donor advocate. consequently, a higher risk of dying donors are able to return to normal Even when a parent is considering while on the waiting list. At this time activity in about a month. Dr. Emond, a donation to a child, a separate doctor there are eight patients on the waiting member of the team that performed the assesses the parent in order to protect his list for every available liver – and many first living donor liver transplant in the or her best interests. “We are especially patients are considered too sick or too United States, in 1989, brings the vigilant about ensuring that there is no old to even get a place on the list. To perspective of nearly 20 years of experi- coercion involved in the donor’s address this serious shortage, the Center ence with living donation to the center. decision,” he adds. The recipients’ insur- for Liver Disease and Transplantation CLDT is a lead center among the nine ance pays the costs involved with (CLDT) is pioneering methods of participating in the Adult to Adult evaluation, education, and donation. increasing access to liver transplantation. Living-donor Liver Transplant (A2ALL) To provide yet another method of Living donor liver transplantation study, a seven-year trial funded by the increasing access to liver transplantation, offers one solution. In this procedure, a NIH to investigate the outcomes of John F. Renz, MD, PhD, Surgical Director healthy adult undergoes a surgical proce- living donor liver transplantation. “Data of CLDT, specializes in “extended crite- dure to remove part of his or her liver. indicate that by using living donor liver ria” transplantation, or the use of organs The donated portion is then trans- transplantation, centers may reduce that don’t meet the usual criteria for planted into a blood-type compatible patients’ risk of dying by 20-40%,” says transplantation due to various health adult or child with end-stage liver Robert S. Brown, Jr., MD, MPH, Chief of problems, but are still healthy enough disease. For an adult transplant, up to the Center for Liver Disease and Trans- for a successful transplant. Dr. Renz 60% of a donor’s organ may be plantation. “It is not that living donor explains that “EDC recipients accept a removed, while a child’s transplant may transplantation is a better operation, but slightly higher risk of a donor-transmit- require 20-25% of a donor’s liver tissue. it improves access to transplantation.” ted disease, but EDC livers are used in In some cases, family members or Milan Kinkhabwala, MD, FACS, patients who are not as sick as those who friends choose to donate a portion of a Surgical Director of the Living Donor receive optimal organs.” Regular and liver, which saves a patient from having Liver Transplant Program, is careful to EDC liver recipients have equivalent survival rates. In a living donor liver transplant, the donor gives up only a portion of his liver. Within several In addition to the A2ALL study, weeks, the organ will regenerate until it reaches full-size in both the donor and recipient. about 40 other studies related to liver function are underway at this center. A number of these address hepatitis C, which is the leading indication for trans- plantation and a major cause of organ failure after transplantation.

To learn more about the Center for Liver Disease and Transplantation, please visit www.livermd.org.

8 healthpoints • summer 2006

Kidney Transplantation “There is an urgent need for donors,” accord- continued from page 3 ing to Joan Kelly, RN, Renal Transplant Coordinator. “We hear from 50 people every opportunities, the program has instituted an month who need transplants. Often family aggressive approach to its waiting list. Its Top 40 members would be willing to donate, but don’t List identifies the ten patients from each of the realize they can be donors.” To provide the best WARM WELCOME four blood groups who are most likely to receive care possible for those considering donating a TO NEW SURGEONS a kidney transplant in the near future. These kidney, the program has established an IN THE CENTER patients are specially evaluated so that any extremely thorough and exemplary system of FOR LIVER DISEASE AND medical or psychosocial problems, or new finan- living donor evaluation and advocacy. TRANSPLANTATION cial or insurance issues that would affect transplantation, can be addressed. Patients unfit Preventing rejection after transplant Investigators in the Departments of Surgery Sarah Bellemare, MD for transplantation are placed on the inactive list Assistant Professor of while these issues are resolved. This process is and Medicine are now testing new immuno- Surgery repeated every two to four weeks, ensuring that suppressant drugs with fewer uncomfortable Dr. Bellemare specializes all patients on the list are “optimized” — side effects. “It is critical to develop new and in laparoscopic liver healthy, ready, and available to undergo trans- better ways to prevent rejection,” says Mark A. surgery, living donor liver plant when a kidney becomes available. A study Hardy, MD, Director Emeritus and founder of transplantation, and by nurse coordinator Johanna Camacho-Rivera, the Renal and Islet Transplantation program. hepatobiliary and RN, which won the Quality Assurance/Improve- Dr. Hardy is Principal Investigator of a multi- pancreatic surgery. ment prize at the UNOS Transplant Manage- center clinical trial exploring a combination of ment Forum in April 2006, found that during two immunosuppressant drugs, sirolimus and James V. Guarrera, MD the strategy’s first year, waiting time for trans- tacrolimus. “Both of these drugs prevent the Assistant Professor of plantation at Columbia was better than halved, activation of T-cells,” says Dr. Hardy. He and Surgery from about six to two or three years. colleague David J. Cohen, MD, Medical Director Dr. Guarrera brings of Renal Transplantation, hope this combined expertise in liver and Dr. Ratner has pioneered still other creative kidney transplantation strategies to make use of a potentially viable medical therapy will reduce rejection episodes and hepatobiliary donor organ. He is the first physician to perform and lead to improved kidney function in the surgery. His research dual renal transplantation, the transplant of two long term. In another study, they are evaluat- interests are in organ adult kidneys into a single recipient. “If one sub- ing new classes of immunosuppressive preservation, ischemia, optimal kidney would not provide sufficient medications which hold great promise in and reperfusion injury. function, two may give excellent renal function,” avoiding many of the side effects of currently says Dr. Ratner. used drugs. They are also investigating methods Benjamin Samstein, MD In another first, Dr. Ratner performed the of induction therapy, which promotes tolerance Assistant Professor of first paired kidney exchange (“swap”) in New to the foreign kidney, including Campath 1-H, Surgery York City in 2004. Kidney swaps entail trading thymoglobulin and monoclonal antibodies for Dr. Samstein's expertise the healthy and willing, but incompatible, Il2R, and HLA allopeptides. includes kidney, liver, and donors of two patients, enabling both patients to pancreatic transplan- tation, and advanced receive compatible kidneys. A unique procedure, laparoscopic liver surgery. kidney swapping requires four simultaneous A new program with the Department of His research endeavors operations (the two donations and two trans- Obstetrics and Gynecology provides women focus on immunology plants). Moving from a double to a triple swap, undergoing renal transplantation with special- and prevention of organ the team performed the region’s first three-way ized care in fertility and pregnancy. Another rejection. kidney exchange, which required six concurrent program, with the Department of Dermatology, operations, on May 30, 2006. treats skin cancer and other dermatologic “The beauty of this approach is that by diseases in transplant patients. For information simply working out the logistics, we can give about these programs or about becoming a living people straightforward transplants, with excel- donor, please visit www.columbiatransplant.org lent results,” explains Dr. Ratner. or call 201.342.7001.

www.columbiasurgery.org healthpoints • summer 2006 9

Blood Test Replaces Heart Biopsy

Since the 1970’s, heart transplant sion variations that correspond to patients have had to regularly undergo immune activity during rejection. If so, an invasive, uncomfortable, and poten- these changes could be identified by tially risky test for signs of rejection, a testing a regular blood sample,” explains So-called “heat maps” like the one above leading cause of death among heart Mario C. Deng, MD, Director of Cardiac show which genes are upregulated (red) transplant recipients. The test, endomy- Transplantation Research at Columbia and downregulated (green) during ocardial biopsy, or EMB, involves University, Department of Medicine, rejection of a transplanted heart. inserting a catheter into a vein in the Division of Cardiology, and Co-Princi- tion to determine their levels of activ- neck and threading it into the heart, so pal Investigator of the Cardiac Allograft ity. From there, further analysis that a tiny amount of the heart muscle Rejection Gene Expression Observa- produced an 11-gene set of the most can be sampled for analysis. Now, a tional study (CARGO). significant genes associated with the quick, easy-to-administer blood test is CARGO proceeded in three phases, immune changes in organ rejection. rapidly replacing EMB as the gold and involved testing of over 600 patients Using these 11 genes and another 9 for standard for diagnosing rejection of in eight U.S. centers. control, the company developed the the donor heart. AlloMap™ molecular expression test – The test, a product of a five-year, PHASE 1: GENE DISCOVERY a tiny chip with 20 genes used to evalu- multicenter study conducted with During the first phase of the study, the ate a cardiac patient’s blood sample. biomedical company XDx, was based on researchers determined the genetic the hypothesis that a genetic test could changes associated with the immune PHASE 3: VALIDATION detect the absence of rejection in heart process involved in rejection after heart During this phase, a prospective, transplant recipients. “We believed that transplantation. They constructed blinded study of post-transplant using the knowledge gained by the DNA microarrays and analyzed over patients was conducted to verify mapping of the human genome, it 7000 genes identified in medical litera- whether the 20-gene test could might be possible to detect gene expres- ture as involved in immune activation accurately detect the absence of organ by cells known as leukocytes. In rejection. contrast to older methods of studying Results: The test was able to consis- GENOMICS AT the activity of single genes, powerful tently detect the absence of rejection. NEWYORK-PRESBYTERIAN HOSPITAL/ DNA microarrays arrange the entire Patients with low scores had a very low COLUMBIA UNIVERSITY genome on a single chip, and can MEDICAL CENTER risk of rejection, while those with higher provide a picture of the activation scores were more likely to experience Human genomics, or the study of the status of thousands of genes at once. moderate to severe rejection. 20,000-25,000 genes in the human Screening of more than 7000 genes As a result of this clinical trial, body, has been made possible during during Phase 1 refined the researchers’ AlloMap™ testing for rejection after the last decade by advances in key gene selection to 252 candidate genes. heart transplantation has been certified technologies such as DNA microar- in all 50 states and is now covered by rays, sophisticated data analysis tools, imaging equipment, robotics, and PHASE 2: DEVELOPMENT insurance. “This represents a paradigm other developments. The NIH has OF A DIAGNOSTIC TOOL change in how transplant rejection will recently awarded the Columbia Further analysis of the 252 candidate be monitored,” Dr. Deng states. “For Genome Center over $50 million in genes then narrowed the pool to a set many patients, this simple blood test can grants for genomic work, capitalizing of 62. During this phase, Dr. Deng and now be used instead of invasive biopsy.” on the university’s diverse strengths the study team worked with XDx to Results of the CARGO study were in these areas. analyze each of these genes in patients published in 2006 in the American who did and did not experience rejec- Journal of Transplantation.

10 healthpoints • summer 2006 referrals • 1.800.227.2762

IMPLICATIONS FOR LUNG Lung Transplant program, and co-inves- Lung Transplant Surgery TRANSPLANTATION AND BEYOND tigator in LARGO. With a simple blood continued from page 5 While the CARGO study is already test to detect rejection, lung transplant tine bronchoscopy, so that patients need benefiting heart transplant patients, the patients could avoid the need for contin- not come in for extra appointments. success of its approach holds tremen- uous bronchoscopies, which are invasive, Those found positive for aspiration of dous potential for applications uncomfortable, and potentially risky. bile acid are then considered for treat- throughout clinical medicine. Moreover, a blood test for rejection ment by Nissen fundoplication. Researchers in the Lung Allograft Rejec- may enable physicians to detect subtle “With early testing now available, we tion Gene expression Observational forms of rejection before symptoms may be able to block or prevent this study (LARGO) are already applying develop, according to Dr. Arcasoy. “Most relentless inflammatory agent in the lessons of CARGO to help detect diagnostic tools identify a problem only patients with proven reflux,” says Dr. rejection after lung transplantation. after it has progressed to a point where Sonett. At this time, LARGO is in the first treatment is difficult and there is risk of In addition to providing key phase, and second year of progress, in ten permanent damage to the involved evidence about aspiration and a new U.S. centers. “Once we pinpoint which organ. The genetic test has the potential diagnostic tool to detect it, Dr. genes are over- or under-expressed to identify subtle rejection long before D’Ovidio’s work has opened the door to during lung rejection, we will be able to the patient notices any symptoms,” he understanding how the lung’s specific develop a diagnostic molecular expres- explains. “This could make it possible to innate immune system may influence sion test to detect them,” says Selim M. prevent symptomatic rejection or combat chronic lung rejection. As he studied the Arcasoy, MD, Medical Director of the it earlier and more successfully.” way in which bile acid disrupted his patients’ lung innate immunity and in Learn more about the CARGO: http://cardiactransplantresearch.cumc.columbia.edu particular the lung surfactant system, or by calling 212.305.0200. Dr. D’Ovidio discovered that genetic variations of certain proteins, called surfactant proteins, were associated with LEFT VENTRICULAR ASSIST DEVICES earlier dysfunction of the transplanted lung. This suggests that the ability of The expertise of the heart transplantation some transplanted lungs to be more or program is complemented by an equally less able to withstand injury, infection, strong program in cardiac assist devices, and other assaults, may be determined which provide mechanical support to failing n

io at a genetic level. “Further study in this at r hearts. The most common type of cardiac o p r area may help explain why certain o assist device is a Left Ventricular Assist Device, c C e

at lungs, despite our best selection criteria, r or LVAD. Although they were originally intend- ho T f ed to serve as a “bridge to transplantation” for fare worse than others after transplanta- esy o t patients with heart failure, LVADs are also tion.” In time, he suggests, genetic tests our C approved as “destination,” or permanent ther- might be used to better modulate apy, in patients who are not eligible for transplantation. medical therapy or even match organs Approval for the use of LVADs as destination therapy was based on the landmark with recipients. For this outstanding REMATCH trial (Randomized Evaluation of Mechanical Assistance for the Treatment of contribution, Dr. D’Ovidio was awarded Congestive Heart Failure), which was led by Eric A. Rose, MD, Chairman of the Depart- the 2005 Philip K. Caves Award by the ment of Surgery. This trial found that end-stage heart failure patients who received an International Society for Heart and LVAD device were twice as likely to survive at one year compared to patients who Lung Transplantation. More about this received medical treatment. genetic work will be published in scien- Columbia University Medical Center is now participating in an important clinical tific journals later in 2006. trial of the HeartMate® II Left Ventricular Assist System (LVAS). In another study, funded by the NIH for $17 million, the center is investigating ways of stimulating For more information about lung recovery of the native heart, combating infection, and improving outcomes overall for transplantation, please visit patients with ventricular assist devices. www.columbiatransplant.org. More about mechanical cardiac assist devices is available at www.columbiaLVAD.org.

healthpoints • summer 2006 11

healthpoints • summer 2006 Transplantation for Short Bowel Babies advantages, including the ability to choose a continued from page 4 healthy donor and to plan the transplant in healthpoints is published by tomy, or the Kasai procedure, is essential. “If advance, so that the child’s medical team can Columbia University this is done early enough, the injured bile duct ensure he or she is fully optimized for the Department of Surgery as a can be reconnected with the small bowel before operation. service to our patients. the liver is destroyed,” says Dr. Jan. Although a Surgeons at this center regularly perform You may contact External Affairs number of U.S. institutions perform the Kasai operations that many centers won’t consider, in for additional information, to be procedure for biliary atresia, their survival rates children of every age. “Our knowledge of the added to our mailing list, and fall short of the 98% survival rate achieved by liver gives us the ability to do things that other to request additional copies. R. Peter Altman, MD, Surgeon-in-Chief at centers simply don’t do,” states Dr. Lobritto. In Please call 201.346.7001. Morgan Stanley Children’s Hospital of NewYork- this past year, Dr. Jan performed a successful For physician referrals, please call Presbyterian, and his colleagues. “Our surgeons living-related liver transplant in a premature, perform reconstructions of the biliary system failure-to-thrive newborn who weighed only five 1.800.227.2762 with incredible expertise,” says Dr. Jan. pounds, and in a five-day old baby with Deborah Schwarz-McGregor, PA Dr. Altman, who is world-renowned among the metabolic liver disease. Executive Director, External Affairs best pediatric surgeons for this procedure, is “We are not doing transplants to give our M. El-Tamer, MD currently training other surgeons at Columbia patients an extra six months,” says Dr. Lobritto. Medical Editor University Medical Center in the procedure. “That would be a failed transplant. We do them Sherry Knecht Managing Editor to help them grow normally and have normal Tanya Krawciw Liver failure lives. That is what we look forward to.” Creative Director When a child requires a liver transplant, a family member will frequently volunteer to donate a For further information, please contact the portion of their liver, according to Dr. Lobritto. Intestinal Rehabilitation and Transplantation Using tissue from living donors has several team at 212.305.5300.

Affairs of the Heart™ The Cardiovascular Health Education Center of NewYork-Presbyterian/Columbia Univer- sity Medical Center held its first free cardiovascular health fair, sponsored by Affairs of the Heart™, on Saturday, May 20th. Over 150 participants from the tri-state area received massages, peripheral vascular and blood pressure screenings, and more. Presentations on prevention and risk factors for cardiovascular disease, nutrition, diabetes, Medicare part D, and other topics were given in both English and Spanish by the Integrative Medicine Department, the Naomi Berry Diabetes Center, and other volunteers. E N I Department of Surgery External Affairs

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