Transplant Immunology: The Science Behind Organ TransplantationThe Columbia Center for TranslationalImmunology leads research usinghematopoietic cell transplantation forinduction of tolerancePatients receiving treatment at the renowned organtransplant programs at NewYork-Presbyterian Hospital/Columbia University Medical Center may be unaware that justbeyond their treatment rooms, a one-of-a-kind research power-house is quietly at work conducting some of the most vitalstudies underway in transplant immunology today.

The multidisciplinary Columbia Center for TranslationalImmunology (CCTI), established in 2010 under the leadershipof Megan Sykes, MD, Director, is performing a host of cutting-edge studies. The work aims to increase understanding ofimmunologic diseases and directly translate that knowledge tothe development of new or improved clinical therapies fortransplant patients at NYP/Columbia and beyond.

Of these areas of study, one area holds particular impor-tance for patients undergoing organ transplantation:hematopoietic cell transplantation (HCT). Hematopoieticcells are cells (including bone marrow cells) that developinto blood cells; transplantation of these cells from ahealthy donor, the most widely used form of cellulartherapy today, is the only known cure for certain bloodcancers (leukemia, lymphoma, myeloma) and is performedin approximately 60,000 patients each year for thatpurpose. But HCT also has the potential to reverse theautoimmune process responsible f or diseases such as type 1diabetes–and to induce tolerance in patients who receiveorgan transplants.

To begin, I am pleased that so manyof our readers were able to glimpsehappenings in the Department ofSurgery during the very popular ABC series, NY Med, which featureda disproportionately high number of

our faculty members. The television series may be over,but the advent of fall coincides with an exciting newacademic year in the department. The past year has seengrowth in many clinical areas, with an astonishing increase incardiothoracic surgery that is once again straining our infra-structure and leading to further expansion of services. Thisyear the forecast at the Department of Surgery includesimportant new recruitments in several areas, including theColumbia Center for Transplant Immunology, which iscollaborating with the Department of Surgery in vital initia-tives, including the studies on hematopoeitic celltransplantation discussed in this issue of healthpoints. Thedepartment has reinvested in key junior faculty researchprojects, providing funding for innovative research inpediatric surgery and plastic & reconstructive surgery. A new weekly departmental chairman's morbidity & mortalityconference is now underway, enhancing residents' educa-tion and providing an essential forum for quality of careassessment and evidence-based review of cases. Another ofour department's educational efforts, the COACH OnlineMedical Education Training Paradigm, has seen tremen-dous success and growth. This educational program, whichwas developed by our Chief of Endocrine Surgery, Dr.James Lee, is now being used in 95% of general surgerytraining programs in the US.

I extend a warm welcome to our new faculty members andto the patients and family members who have become partof the Department of Surgery family this year. n

Craig R. Smith, MD, Chairman, Department of Surgery

Pediatric Heart SurgeryLatest outcomes data for Morgan Stanley Children's Hospital of New York

Fall 2012

p.1 p.3 p.4

IN THIS ISSUE

GreetingsMessage from the chairman

A L L T H E P O S S I B I L I T I E S O F M O D E R N M E D I C I N E

Transplant ImmunologyAdvances in hematopoietic cell transplantation and induction of tolerance

Intraductal PapillomectomyScarless endoscopic procedure to detect causes of nipple discharge

Continued on page 2

healthpoints is published by the ColumbiaUniversity Department of Surgery as a service to our patients.You may contact the Office of External Affairs for additional information and to request additional copies.Please call: 1-855-CU.SURGE.

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Deborah Schwarz, RPA, CIBEExecutive Director, Office of External Affairs

Jada FabrizioDesign and Photography

Sherry KnechtManaging Editor

What is “Tolerance”?When a patient receives a heart, lung, liver, kidney, orpancreas from an organ donor (living or deceased), thepatient's immune system will recognize the foreign tissueand mobilize to reject the organ unless he or she takesmedications that suppress the immune system's naturalprocesses. These medications, known as immunosuppres-sants, are a lifelong requirement after organ transplantation.While these drugs allow people to tolerate the presence offoreign organs, they also increase patients' risk of contract-ing infections, and infections and are associated with otherundesirable side effects. The ability to induce tolerance toa transplanted organ, allowing it to thrive in the bodywithout requiring these life-long immunosuppresssants,would signify a dramatic improvement in quality of life forpatients undergoing organ transplantation. For many in thefield, induction is considered the “holy grail.”

During the last decade, Dr. Sykes' research in HCT (begunwhile she was Associate Director of the TransplantationBiology Research Center at Massachusetts General Hospital)has produced notable results toward that goal. In one proto-col, out of ten patients studied, seven have achieved longterm tolerance, so far lasting three to ten years. Althoughseveral other U.S. hospitals have subsequently attemptedsimilar protocols, this has been the most successful and long-lasting tolerance demonstrated to date.

To achieve these results, Dr. Sykes' team first administereddrugs known as a “conditioning regimen” to reduce boththe immune function and the numbers of the patients' own

bone marrow cells. Next, they performed bone marrow andkidney transplants from living unrelated donors. A shortcourse of immunosuppressant medications was adminis-tered immediately after transplantation, and then tapereddown and stopped altogether.

According to Dr. Sykes, it was remarkable that tolerance wassuccessful even when the donor's most potent transplanta-tion antigens were mismatched to the recipient's. Most bonemarrow transplants normally require a match between thedonor's and recipient's human leukocyte antigen (HLA)system, part of the immune system which encodes the mostpotent antigens. Performing bone marrow transplants acrossthe HLA barrier usually results in serious, systemic rejectionknown as graft versus host disease (GVHD). Using the proto-col mentioned above, however, they achieved significantsuccess without GVHD even across HLA barriers. “These areexciting results showing that we can achieve robust toler-ance,” says Dr. Sykes.

Dr. Sykes' team continues to test multiple protocols in aneffort to strengthen tolerance even further, first in animalmodels to evaluate safety and efficacy. These protocols aimto achieve the following goals in stages:

• inducing tolerance with HLA-identical patients with kidneyfailure due to malignant disease (such as multiple myeloma);

• reliably performing transplants without GVHD in HLA-mismatched patients;

• using a large animal model to achieve more durable bonemarrow engraftment and hence more reliable tolerance;

• achieving tolerance of pancreatic islet cells–to be studiedin animal models and eventually in patients withcombined islet and bone marrow transplants;

• achieving tolerance of liver transplants by combining liverand bone marrow transplantation;

• eventually, expanding tolerance studies to lung and hearttransplantation.

Markus Mapara, MD, PhD, Director of the Blood and MarrowTransplantation (BMT) Program at Columbia UniversityMedical Center, will collaborate with CCTI to develop novelhematopoietic cell transplant protocols beginning in 2013.According to Dr. Sykes, “The establishment of the BMTprogram is a key step in allowing NYP/Columbia to take aleadership role in these promising new applications ofhematopoietic cell transplantation.” CCTI and the BMTprogram will further collaborate with leaders of theNYP/Columbia kidney and liver transplant programs,including Drs. Lloyd Ratner, David Cohen, Waichi Wong,Jean Emond and Tomoaki Kato. n

To learn more about CCTI, please visit:www.cumc.columbia.edu/ccti

Megan Sykes, MD, Director, Columbia Center for TranslationalImmunology, and Director of Research, Transplant Initiative, NewYork-Presbyterian Hospital

Continued from page 1

2 healthpoints • 855.CUSURGE • Fall 2012

Patients at NewYork-Presbyterian Hospital/Columbia University Medical Center willsoon benefit from yet another in a longstring of advances: intraductal diagnosis,and eventually, treatment of breast papillo-mas. Intraductal papillomas are benignlesions within the milk ducts that account for40% of cases of pathologic nipple dischargein women aged 20-40.

The development of intraductal approachesto diagnosis and treatment represents oneof the most important advances in breastdisease treatment in the past decade.Intraductal techniques allow surgeons toperform evaluations through the nippleusing very fine micro-endoscopes withoutsurgery and without general anesthesia.This minimally invasive approach has beenproven highly successful in the detectionof papillomas. Sheldon M. Feldman, MD,Chief, Breast Surgery Section, is consid-ered the most experienced breastendoscopist in the U.S., having researchedand used minimally invasive techniques forten years.

Now, NYP/Columbia is poised to becomethe only facility in the U.S. to offer scarlessendoscopic papillomectomy for diagnosisof pathologic nipple discharge. Thisunprecedented advance will be madepossible in large part by the presence ofFatih Levent Balci, MD, a postdoctoralresearch scientist who also has extensiveexpertise in endoscopic ductoscopy. In hisnative Turkey, Dr. Balci and colleaguesdetermined that the intraductal approachcould be successfully used not only for thediagnosis of intraductal lesions, but also to remove single papillomas. In his 2009paper published in Onkologie, “ScarlessEndoscopic Papillomectomy of the Breast,”Dr. Balci’s team found that the techniquehad 95% therapeutic efficacy in patientswith pathologic nipple discharge due topapillomas. “Using this procedure, we canremove single papillomas in an office with alocal anesthetic cream,” Dr. Balci says.

Despite its value in treating papillomas,endoscopic papillomectomy is currentlyrestricted to diagnostic purposes in theU.S., as the super-fine micro-endoscopeneeded for removal of papillomas has notyet received FDA approval in this country.That technology is currently available inTurkey, permitting endoscopic removal ofpapillomas in patients there. Dr. Balci andDr. Feldman have submitted applicationsfor approval of the necessary catheter sothat NYP/Columbia can begin using intra-ductal ductoscopy for both detection andremoval of breast papillomas at this hospi-tal. That process is likely to take severalmonths, according to Dr. Balci.

In addition to its role in detecting andremoving papillomas, Dr. Balci points to yetanother potentially groundbreaking role ofintraductal endoscopy: Detection of ductalcarcinoma in situ (DCIS), a non-invasiveform of breast cancer in the milk ducts.Although studies have yet to confirm hisgroup's early findings, Dr. Balci's team hasbeen able to detect DCIS using intraductalendoscopy during its research in Okmey-dani Teaching and Research Hospital,Istanbul, Turkey, from 2004 to 2009. “DCISdoes not always appear on conventionalimaging such as MRI or mammography, butearly results of our study indicate that DCIScan be detected during ductoscopy. Theability to detect breast cancer before ourconventional imaging models find it wouldbe an enormously valuable advance.”Moreover, Dr. Balci explains it would bepossible to easily extract just the isolatedduct using ductoscopy and microductec-tomy. “Extracting just the isolated ductshould give women the best cosmetic result,with no deformity of the breast,” he says.

Dr. Feldman concludes, “By assemblinga robust team with expertise in mammaryductoscopy and ductscopic minimallyinvasive procedures, we are well poisedto advance diagnosis and treatment ofbreast cancer.” n

To learn more, visit: breastmd.org

ductoscopic vision of a papilloma that causes bloody nipple discharge

basket inside the duct

basket while extracting the papilloma

macroscopic vision of papillomaextracted by ductoscopic basket

3 healthpoints • 855.CUSURGE • Fall 2012

Advances in Breast Surgery: Intraductal PapillomectomyDivision of Breast Surgery to offer scarless, endoscopic procedure to detect intraductal papillomas

Outcomes in Pediatric Cardiac Surgery January 2008 – December 2011

Most Frequent Procedures (Neonates)

Norwood Procedure 85 12.9% 16.7%

Arterial Switch or Arterial Switch/Ventricular Septal Defect Repair 76 0% 3%

Coarctation Repair 38 2.6% 2.2%

Aortopulmonary Shunt 33 0% 6.7%

Aortic Arch Repair 31 0% 4.4%

TAPVC Repair 26 3.8% 14.1%

Interrupted Aortic Arch Repair 14 0% 5.4%

Ventricular Septal Defect Repair 97 0% 0.6%

Tetralogy of Fallot Repair 92 0% 1%

Bidirectional Glenn 75 4% 1.7%

Complete Atrioventricular Canal 55 0% 2.2%

Heart Transplant 87 0% 3.1%

Number of Procedures

Mortality at NYPH

STS Mortality (National)

Most Frequent Procedures (Infants)

Number of Procedures

Mortality at NYPH

STS Mortality (National)

Pediatric Cardiac SurgerySTS report confirms hospital's outstanding surgical outcomes About one in 125 newborns is affected by a heart defect atbirth, making congenital heart defects a leading cause ofdeath in infancy. Over 35 identified defects span the rangefrom mild and treatable to complex and life-threatening. Yettoday, the vast majority of infants born with heart defects –even those with severe disease–are successfully treated andcan expect to live healthy and active lives, thanks to theexpertise of programs such as NewYork-PresbyterianMorgan Stanley Children's Hospital of New York(MSCHONY) and Komansky Children's Center.

Of all the centers that treat children with heart disease inNew York State, MSCHONY far surpasses all others in termsof patient volume. The most recent national evaluation alsoconfirms the program's performance not just in terms ofvolume, but in clinical excellence: despite treating manypatients with the most severe and complex conditions, thepediatric cardiac surgery program at NYP/Columbia hasachieved outcomes superior to every other New York hospi-tal performing the same surgeries. In addition to its topposition in New York, MSCHONY's outcomes also surpassthe national rates in virtually every procedure. Overall. thecenter continues to rank in the top four centers nationally.

The most recent report, the Congenital Heart SurgeryDatabase of the Society of Thoracic Surgeons (STS), lists themost frequent procedures performed in newborns andinfants, and compares NYPH's results against nationaloutcomes from January 2008 to December 2011 (four fullyears). The STS database is considered the gold standard interms of quality assessment in Congenital Heart Surgery. Inall but two procedures, NYPH's outcomes are significantlybetter than the national average, as measured by mortality.

For example, the national mortality rate for newborns under-going the Norwood procedure (for hypoplastic left heartsyndrome or other single ventricle disorders) is 16.7%, while

at NYP/Columbia, the mortality rate is 12.9%. The mortalityrates for arterial switch or arterial switch with ventricularseptal defect (VSD) repair, and surgeries for aorto-pulmonary shunt, aortic arch repair, and interrupted aorticarch repair, are 3%, 6.7%, 4.4%, and 5.4% respectivelyacross the nation. In comparison, the mortality rates for eachof those procedures at NYPH is 0. For totally anomalouspulmonary venous connection (TAPVC) repair, the hospital'smortality rate is just 3.8%, compared to 14.1% nationally.Overall, the non-risk adjusted mortality rate for all proce-dures is 2.4% at NYP compared to 3.3% nationally–butwhen adjusted for the higher risk of many of its patients,NYPH's mortality rate improves even further. n

To learn more about the Pediatric Surgery Program,please visit : www.childrensnyp.org

4 healthpoints • 855.CUSURGE • Fall 2012 www.facebook.com/columbiasurgery

Bridging the Gap:Enhancing Breast Cancer Prevention, Screening & Wellness

November 17, 20128:30am to 2:30pm

This annual breast cancer symposium will include discussion of disparities in health care, genetics, holistic wellness, Q&A sessions,

and much more. Breakfast and lunch will be served.

Annual Pancreatic Cancer Awareness DaySaturday, November 3, 2012

1:00 to 3:00pm

Topics of discussion will include risks, screening, early detection, and treatments of cancer of the pancreas.This year each lecture topic will be augmented with

in-depth patient testimonials.

THESE EVENTS ARE FREE AND OPEN TO THE PUBLIC, BUT RESERVATIONS ARE REQUIRED.

For information and reservations please contact: Christine ReinTel: 201.346.7014 • Fax: 201.346.7011 • E-mail: cmr2146@columbia.edu

Register online: www.columbiasurgery.org/events

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