New Layout-Dt 14-2-2009 - final.pmd 1 2/14/2009, 5:16 PM FROM THE EDITOR’S DESK / CONTENTS
2 From the Editor’s Desk Dr. Reeta J. Dalal
3 Guest Editorial Dr. Sudeep Shah
4 Cadaver Transplantation Dr. Rasika Sirsat
8 Corneal Transplant Dr. Nisheeta Agarwala & Dr. Pradyna
12 Heart Transplant Dr. Kaushal Pandey
16 Frontiers of Immunosuppression in Renal Transplant Dr. Jatin Kothari
20 Liver Transplant Dr. Sudeep Shah From the 24 Live Related Renal Transplant Dr. Alan Almeida Editor’s Desk 30 Stem Cell Transplant (SCT) Dr. Asha Kapadia
Worldwide tens of 32 Lung Transplant - thousands of lives are Where does it stand today? transformed by the miracle Dr. Manoj Agni of organ donation. Tissue 36 Short History of Organ Transplant transplants e.g. skin, Dr. R. A. Bhalerao
cornea, bone-marrow, 38 Hinduja News vessels are invaluable. In 40 Welcome the last half century transplant surgery has transformed from research to life-saving surgery.
For every successful transplant there are Editorial Board thousands who are on the waiting list and Dr. Philip Abraham Dr. Tester Ashavaid probably die waiting to receive the graft. Organ Dr. C. Balakrishnan transplants are complicated by scarcity of organ Dr. Sudeep Shah Dr. Gauri Mankekar donors, various ethical and social issues. Editor In this issue Dr. Sudeep Shah, Liver Transplant Dr. Reeta J. Dalal Surgeon at Hinduja Hospital has put together Editor Emeritus articles from various specialities to give you an Dr. V. R. Joshi ‘Update on organ transplants’. Guest Editor Dr. Sudeep Shah
Photography Pramod Tandel Dr. Reeta J. Dalal Consultant Physician
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Dr. Sudeep Shah Introduction to Organ Transplantation
ORGAN TRANSPLANTATION IS one of the miracles of modern medicine. The ability to replace failed organs has been dreamt about since the beginning of the last century. However, with the greater understanding of the immune system and technical advances in surgery, this became a reality in the 6th and 7th decades of the last century. The arrival of more effective immunosuppression in the form of Cyclosporine radically improved the results and in the eighties this treatment became established as the standard of care for organ failure. In this issue of the Newsletter, we highlight the indications and outcome for major organ transplantation and also outline the procedure for cadaver organ donation. Transplant is a reality now in tertiary care centers such as ours and we need to go forward and build further. This is possible with greater awareness about organ donation. The gift of life is the greatest that can be given as seen in the case study and we hope this issue will serve to reinforce this.
DR. SUDEEP SHAH
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New Layout-Dt 14-2-2009 - final.pmd 3 2/14/2009, 5:16 PM Cadaver Transplantation Despite the immense benefits of successful organ transplant, the full development of the transplant program is hindered by organ shortage. By Dr. Rasika Sirsat
TRANSPLANTATION IS CURRENTLY considered skin and cornea can be transplanted. This is due to an accepted treatment modality for patients with end important break throughs in immunosuppressant drugs stage organ failure where therapy with drugs or and tissue typing. More than 1 million people world wide restorative surgery is not feasible. Approximately, 25 have benefitted from successful organ transplantation. different organs and tissues including kidney, heart, Of these, kidney transplant results have been the most lung, liver, pancreas, bone, cartilage, bone marrow, gratifying. With improvement in results, the demand for
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NEUROLOGICAL EXAMINATION TO human organs for transplantation has following the second set of test to confirm DEMONSTRATE
increased. The source of donor organs are Brain Death. BRAIN DEATH living related donors (LRD), living un- The Zonal Transplant Co- ARE related donors (LURD), cadaver – non ordinating Center (ZTCC) is informed
heart beating donors (NHBD) and about a potential Cadaver donor. The Absence of oculomotor/ cadaver – heart beating donors ZTCC is a city based organisation who co- photomotor “ reflex
Absence of MORE THAN 1 MILLION PEOPLE WORLD corneal reflex WIDE HAVE BENEFITTED FROM Absence of facial SUCCESSFUL ORGANTRANSPLANTATION. movements “ Absence of spontaneous muscle (HBD). Most of cadaver transplanted ordinate all activities for organ procurement, movements kidneys are obtained from brain dead donors maintainenance of a computerized central with functional circulation. Brain death can registry of potential recipients and allocates Absence of oculo-vesitibular occur due to spontaneous intracranial organs as per the criteria laid down. The reflex hemorrhage, head trauma, cerebral aim of ZTCC is to provide impartial and ischemia or primary cerebral tumours. effective organ distribution. The prospective Absence of gag reflex Brain death can be diagnosed at the 2 recipients for kidney transplant are called bedside by performing various tests in as per criteria laid down by ZTCC. It is Absence of patients in whom the cause of coma is known essential that a person who registers for a cough reflex and those who do not have severe cadaver transplant keeps some funds aside Absence of hypothermia (< 35oC) and have not in the eventuality of being called for a spontaneous received neurodepressor drugs, transplant surgery. The recipient should also breathing neuromuscular blockers and anti-cholinergic follow up regularly, at the center where he is determined by Apnea test. drugs. registered so that the nephrologist is aware The transplant co-ordinator can then of his/her medical fitness for surgery. counsel the close relatives regarding organ The suitability of donor organ is checked
donation. Once close relatives give written by performing a Lymphocyte cross match. If
consent for organ donation, organs can be negative the recipient can proceed for retrieved after declaration of brain death Transplant. If the lymphocyte cross match is BRAIN STEM DEATH IS IRREVERSIBLE AND “ “HAS BEEN RECOGNISED BY LAW SINCE 1995. 2008 Vol 23 Vol No. 1 5
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positive the recipient next on professionals and lack of the list is considered for the Apnea test organ sharing agencies.
transplant, provided Patient is put on FiO2 of 100% for 20 India spends 1.5% of GNP lymphocyte cross match is minutes while still on the ventilator. on health care. End stage negative. The shortage of Thereafter ventilator is disconnected and kidney disease (ESKD) organs can be expanded by patient is put on 6L/minute of O2. Serial treatment has extremely low including non-heart beating arterial blood gas are checked until priority as compared to donors (NHBD) i.e. organs PCO2 > 60mm Hg with PO2 around population control, are retrieved only after heart 100 mm/Hg. Watch for movements of eradication of stops functioning. The main diaphragm if there is no spontaneous communicable disease, issue with NHBD is higher nutritional program, etc. respiration that indicates an absence of rate of delayed graft function hence government funding brain stem respiratory centre function. compared with that for renal replacement These tests are repeated and confirmed associated with heart beating treatment is a miniscule after 6 hours. Only then the patient can brain dead donors. However amount. Very few ESKD at 3 months graft function is be declared as Brain dead. These tests patients are reimbursed by not significantly different are to be performed by 4 medical their employers, while others between the two. practitioners (Neurosurgeon, Physician, rely on their family and Most of the kidney Neurologist, Intensivist) as per charitable organizations for transplants performed in Transplantation of Human Organs Act funds. Public unawareness, India are from live donors. (TOHA) 1994. Brain death is explained religious sentiments, family For those patients who do to relatives by the treating physician after pressures all contribute to not have an option of related the first set of tests are performed. bringing down the number of kidney transplantation, the actual organ retrieval from only option is to wait for a potential cadaver donors. cadaver kidney. The Human Organ Transplantation Act In Spain organ procurement system has been
was passed in 1994 following which cadaver transplants professionalized. The organ procurement team is
have been carried out all over India. In Maharashtra, the responsible for the whole organ donation process from first cadaver transplantation after the act was performed donor identification to organ retrieval and they are LACK OF PUBLIC AWARENESS, MISPLACED RELIGIOUS “ SENTIMENTS, FAMILY PRESSURES ALL CONTRIBUTE TO BRINGING “DOWN THE NUMBER OF POTENTIAL CADAVER DONORS.
on the 27th of March 1997, thereafter about a hundred accountable for their performance, there are 127 such and fifty more have been performed up to date. So far, teams. Their organ donation rate has more than doubled about 1200 cadaver transplants have been carried out in over the last one decade and the percentage of multi- India, far short of what is required. This is in spite of 8500 organ retrieval has soared from 35 to 83% enabling a 3- fatal road traffic accidents per year. Per city about 8 to 10 fold rise of possible solid organ transplant. brain dead patients would be there at a time, however, Currently, organ shortage is the main obstacle to the the conversion rate is less than 19%. This is due to multiple full development of the transplant programme. It is possible factors like poor infrastructure for quick and safe to increase the cadaveric organ donation rate and also transportation of accident victims, lack of ventilatory promote living donation. It is still possible to further facilities, ignorance, failure to convince the near relatives improve graft survival rates and thus reduce the need for to donate organs, indifferent attitude of health care re-transplantation.
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Case Study By Dr. G. B. Daver
A 34 YEAR old lady- in the prime of her life struck down Mr D, an engineer in the prime of his life, struck down by a stroke leading to brain stem death leaving behind a by liver cirrhosis. He was unable to work and worried about grieving husband and child would in ordinary the future of his sons, aged 16 and 10. His wife was the circumstances be nothing more than a terrible tragedy. wrong blood group and he had no other relatives to donate However, the extraordinary act of generosity by the family a part of their liver. He was on our waiting list for over a in intense grief transformed the lives of three unrelated year for a suitable liver donor. A liver from a cadaver individuals. donor was his only hope. Miss C was a young lady with kidney failure. She had On the day before Dassera 2007, the family of the had so many dialysis that there was no further access to lady with severe brain damage leading to brain stem death her blood vessels to remove blood for purification. No consented to donate her liver, kidneys and corneas after suitable relative was available to give her a kidney and realizing that she was lost to them forever. These organs doctors were wondering what to do when her last open were useless to her but could transform three lives. access point would block. A kidney from a cadaver donor A team of surgeons commenced the procedure at 5 was her only hope. AM and surgeries carried on through the day and late Mr P was a young man tired of life. Struck down by into the night. The recipients of the liver and two kidneys kidney disease in his teens, he had already had a failed were home 14 days after the operation. transplant. Now, he was tethered to a dialysis machine Today all three recipients are back to a normal, productive three times a week and unable to do anything productive; life, the nightmare years of their illnesses are behind them. his blood pressure swingig dangerously due to kidney They realize that they are amongst the lucky few recipients damage. A kidney from a cadaver donor was his only of a cadaver organ donation. Many more patients with end hope. stage organ failure wait for such a gift of life.
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New Layout-Dt 14-2-2009 - final.pmd 7 2/14/2009, 5:16 PM CORNEAL TRANSPLANT The cornea is the clear tissue covering the front of the eye. If the cornea becomes cloudy or scarred, vision is markedly reduced or lost. By Dr. Nisheeta Agarwala & Dr. Pradyna
FORTUNATELY, THROUGH THE medical miracle transplantation process depends upon the priceless gift of of Corneal Transplants, sight restoration is possible. eye donation after death. To meet the requirements, eye More than 2 million Indians, a majority of them donation has to be increased several times and this is children, suffer from corneal blindness and another possible only when the concept becomes a movement 25,000 are added to that number every year. Since and spreads to all families. there is no substitute for human tissue, the The decision to donate eyes is made by the family
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FACTS ABOUT EYE DONATION
Donated eyes of all ages can be members when a death occurs. The desire CORNEAL TRANSPLANTATION used to donate your eyes, should be conveyed to The cornea is made up of 5 layers. the immediate family, during one’s It can get opaque due to infections,injury, Spectacle
wearers, and lifetime.Our eyes, can be recycled into the following eye surgery, ageing and people suffering priceless gift of vision for millions of our degenerative changes. Conventionally, the from even
corneally blind citizens instead of being entire diseased central cornea is removed diabetes, hypertension or asthma can “ donate eyes.
MORE THAN 2 MILLION INDIANS, A MAJORITY Patients who have OF THE CHILDREN, SUFFER FROM CORNEAL undergone BLINDNESS AND ANOTHER 25,000 ARE ADDED TO cataract surgery “ THAT NUMBER EVERY YEAR. can donate eyes. Eyes can be donated even if they have not buried or burnt. In the past people were not and replaced with high quality transparent been pledged aware of blood donation. They were corneal tissue from a donated eye. This is earlier. gradually educated and started donating called Penetrating Keratoplasty. Eye donation voluntarily. There is no shortage of potential gives sight to two donors. All that is needed is the desire to corneally blind donate and a timely request so that the persons. Eyes are never closest eye collection services can be removed from a contacted. living person.
The process of removing the eyes from the body of the deceased is called ENUCLEATION.
Image is taken from Google
If only superficial layers are opaque, then those are replaced by Lamellar Keratoplasty procedures and if the deep Corneal opacity due to infection layer is diseased then that is replaced by
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endothetial Keratoplasty procedures. At our hospital What Needs To Be Done? we have a 24 hour cornea • If there is a death in your family or friend circle, motivate the family retrieval team – which will and call the nearest Eye Bank or dial 1919 (National & Local eye conduct an enucleation donation helpline) within the shortest period, for • Eyes are best removed within 6 hours of death any patient who passes away • The death certificate should be available. in the hospital. • Switch off fans and place wet cotton / cloth over the close eyelids, FOR REST OF to keep eyeballs moist. BOMBAY • Raise head with a pillow Contact nearest Eye Bank or • Most eye banks have a 24 hours response service, which receives Dial 1919 for prompt calls and sends a medical practitioner for the enucleation. response from an Eye • The Eye Bank team will enucleate the eyes wherever the donor is, Donation Cell at no cost • The Eyes are removed without disfiguring the face • Although it is only the corneas that are finally used, the entire eye is removed and transported in special containers to the Eye Bank. 10 cc of blood sample is collected from the donor’s body for testing. • The eyes will be evaluated and processed by trained Eye Bank staff according to International standards. • Eye Banks are non-profit organizations and the processed cornea is supplied to qualified corneal surgeons. • If the patients are identified with HIV infection, hepatitis B, C, rabies, septicaemia or active leukemia, their corneas cannot be used for transplantation.
NATIONAL & LOCAL EYE DONATION HELPLINE 1919
Donate Organs, Save Lives! After your life time, wouldn’t it make you happy to know that you can give a new lease of life to many other people?? One life can give hope to many. But that’s only if you give the NOD to pledge your organs. Organs Donation 1. What is organ Donation? Organ donation is the gift an organ to a person who needs a transplant. It’s a procedure in which a healthy organ is taken from an individual who has died and transplanted into a person whose own organ is not functioning properly. Donated organs give the recipients the opportunity of a longer and better quality of life 2. Why is Organ Donation required? Sometimes people suffer for irreversible organ failure and the only way they can recover or lead a normal life is to receive an organ transplant. 3 . Is it legal ? Yes it is legal. In India it is governed by the Transplantation of Human Organs Act (HOTA), 1994. This Act makes it mandatory for institutions conducting transplants to register with an authority appointed by the state government. Many safeguards against misuse have been built in the rules.
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4. Which organs and tissues can be donated? Organs that can be transplanted are Kidneys, Heart, Liver, Lungs, Pancreas, Small Bowel, Cornea. Tissues like Heart Valves, Bone and skin can also be donated. 5. Do I need to be dead to donate an organ or tissue? No, Blood and Bone marrow may be donated by live donors. Partial Liver & Kidney donation is allowed by law for blood relatives of the recipient. For other organ donation, the person has to pronounced ‘brain dead’ 6. Are you sure I will be dead when they transplant my organs? The Transplantation of Human Organs Act lays down criteria for determining brain steam death. The brain stem death tests must be performed by four Doctors together, none of whom has anything to do with the transplant, and this must be done twice, with a minimum gap of six hours. Such brain death can be declared only in institutions recognized by state appropriate authority. 7. Will the doctors just let me die if they know I will be donating my organs? No. Your doctors will take the utmost efforts to save your life. This is their first duty. If despite their efforts, the patient dies, only then will the organs / tissues will be considered for donation. These doctors will not be involved with the organ transplantation, a completer different set of doctors will take over for the further procedures. 8. Can I donate if I die in an accident? Yes if you are taken to the hospital in time and that hospital has capability for organ transplantation and is registered with the state authority. 9. Who will get my organs? The recipient has to be on state waiting list for receiving organs and has to be compatible for that organ. If not, the next person in waiting will be considered. 10. Will the Rich get priority in waiting list ? No, the recipient has to be on state waiting list for receiving organs. Clinical criteria like blood group, immunological status, and medical urgency are considered for the transplantation. There is no discrimination based on money colour, race and religion. 11. Will my family know who gets my organs? No, the details of the recipient are not revealed to the donor family. 12. Will the recipient know my name and details? No, the details of the donors are not revealed to the recipient. 13. Are there any religious objections to organ transplants? All religions in India consider organ donation as an Act of Charity, Support it. 14. Can I specify to donate any specific organ and not any others? Yes you can specify the same on your organ donation card. 15. Can I agree to donate to specific person and not to anyone else? No. The recipient has to be on state waiting list for receiving organs. Organ donation is not accepted if it is conditional. 16. Is there any cost of donation to my family? No, the cost is borne by the recipient’s family 17. How can I become a donor? You simply have to fill up and sign the Organ Donor card that is attached. Please carry this card with you at all times. 18. Do I need to inform my family about my decision? If you discuss you wish with your family they will be ready for the donation when the time comes and will be able to process the donation faster. 19. Does organ donation cause any delay in funeral arrangement? No, if consent for organ / tissue donation is given, the surgery is done immediately and there is no interference with the customary funeral arrangement 20. Can I change my mind about organ donation? Yes, simply tear your organ donation card. 21. Will I be paid for donating an organ? No, the law does not permit commercial dealing in human organs. 22. Can I donate if have a medical condition? The medical condition of the donor will be assessed at the time of organ donation. HIV and Cancer are specific conditions which excludes people from donating. 23. Would there be an additional expense for donating organs? No. 24. How can I be sure that the donated organs are safe and diseases free? All potential donors’ blood is screened for ruling out transmitted dieses such as HIV and Hepatitis. The family of the potential donor is kept informed of this requisite procedure. 25. Who can be a life organ donor? Anyone 18 year of age and above can be a donor. Parents or Guardians consent will be required for any individual below 18 year wishing to donate an organ.
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New Layout-Dt 14-2-2009 - final.pmd 11 2/14/2009, 5:16 PM Heart Transplant Heart transplant surgery has come a long way in the last 40 years. However, due to newer technology, the number of transplants performed each year is actually falling. By Dr. Kaushal Pandey
HEART TRANSPLANTATION IS the most functioning heart. For the surgical team it is just another satisfying surgical procedure for a Cardiac day at the office, but for this patient, it is new life. From Surgeon. A sick patient with a failing heart (not the epoch-making, first heart transplant in December expected to survive more than a few months) gets 1967, heart transplant surgery has come a long way in wheeled into the operating room; three hours later last 40 years. These forty years of heart transplant surgery comes out into the ICCU with a new normal have been indeed tumultuous. There have been many
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RECIPIENT SELECTION:
highs, but numerous lows. Surgery now is Terminal Heart Disease standard; but the yearly numbers are actually falling. With newer technology impacting our lives in more ways than one, surgery of heart transplant has an uncertain future. Sooner but not later, totally implantable artificial heart (or assist device) will make heart transplant surgery obsolete. First successful heart transplant surgery was performed on 3rd December 1967 by Dr. Christan Bernard. However the true pioneer of Heart Transplant Surgery has been Dr. Norman Shumway from Stanford Brain death declared Age: New bornCHECK – 60 yrs, Irremediable cardiac disease NYHA LISTClass IV, Medical Centre, U.S.A. His persistent and Pulmonary Vascular Resistance < 6-8 Wood units untiring work on heart transplantation over or pharmacologically reversible the decades has firmly established heart Reasonable physiological - normal function or transplant as a standard operation with a reversible dysfunction of kidneys, liver, lungs, CNS significantly low peri-operative mortality Psychosocial stability and satisfactory long-term results. Well over No alcohol, tobacco or drug abuse 60,000 heart transplant procedures have Absence of been performed worldwide so far. At • Active malignancy or infection present, less than 2700 heart transplants • Recent pulmonary Infarction are performed each year in the world and • Severe peripheral or cerebro vascular disease these numbers are falling. The surgical Contraindications technique of this operation and the Fixed pulmonary vascular resistance associated problems have not changed Peripheral vascular disease much with time. Problems of rejection Acute malignancy (both acute and chronic), susceptibility to
COPD /chronic bronchitis infection and long-term problems with the Morbid obesity
transplanted heart have remained same ABO incompatibility over the decades. The longest survivor of THE FIRST SUCCESSFUL HEART TRANSPLANT “ SURGERY WAS PERFORMED ON 3RD DECEMBER “ 1967 BY DR. CHRISTAN BERNARD.
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heart transplant has now • Hyperacute • Acute lived for over 28 years. Tony • Chronic (ACAD) Haesman from Washington Donor Selection: • Cellular • V a s c u l a r has worked as a salesman for • Only 10-20% of brain dead patients (Humoral) 28 years. He had Heart with suitable hearts become donors; Diagnosis Transplantation at Stanford cardiac transplantation is currently • Endomyocardial and continues to lead an limited by donor availability biopsy • Non-invasive active life. • Age <45 (special exceptions) • Clinical SURGERY • No pre-existent heart disease, Treatment Orthotopic normal ECG, normal ECHO ALLOGRAFT CORONARY Hetrotopic (piggyback) • Few CAD risk factors ARTERY DISEASE POST TRANSPLANT • No untreated acute infections Leading cause of death CONCERNS • Negative T cell cross match if panel > 1 year after Immunosuppression reactive antibodies 10% or greater transplantation As in other solid organ • Negative HIV. HbsAg, HCV Equivalent to: transplants • No systemic malignancy • “Chronic rejection” in Transvenous myocardial • No cardiac trauma renal allografts biopsy • “Vanishing bile • Minimal pressure support • Internal jugular ducts” in hepatic • ABO compatibility approach allografts • Size within 20%-50% of recipient • 3-5 specimens • “Bronchiolitis • weekly for the first 4 obliterans” in weeks pulmonary allografts • grading system developed by Billingham Prevalence of angiographically detectable disease
Coronary graft vasculopathy • 1 year: 10-2O% Infection as in other solid organ transplants • 5 years: 30-50%
MEDICAL COMPLICATIONS OF CARDIAC TRANSPLANT Cardiac “ THE LONGEST Ventricular dysfunction SURVIVOR OF HEART Sinus node dysfunction TRANSPLANT HAS NOW Tricuspid regurgitation LIVED FOR OVER Allograft rejection “ 28 YEARS. Allograft coronary artery disease Decreased exercise tolerance Non-cardiac, Non-infectious Renal insufficiency Hypertension Osteoporosis Hyperlipidemia Malignancy Psychologic/behavioral/societal Glucose intolerance Pancreaticobiliary disease Obesity
CARDIAC ALLOGRAFT REJECTION Propensity decreases with time Types
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Functional Status Following Heart Transplant Post Transplant Functional Status • 1 year follow up: 90% - no activity limitation, 8.5% -performs with assistance, 1.4% total assistance • 3 year follow up: 93.5% no activity limitation, 5.8% performs with assistance, 0.8% total assistance Post Transplant Work Status • 1 year follow up: 29.2% working full time, 8.1% working part time, 47.7% not working, 15.0% retired • 3 year follow up: 32.5% working full time, 8.5% working part time, 39.8% not working, 19.1% retired Post Transplant Rehospitalization • 1 year follow up: 57.5% no hospitalization, 9.2% hospitalization (not rejection not infection), 11.4% (rejection), 14.8% (Infection), 7.1% (rejection + Infection)
(Diagrams by Dr. Balkrishna) Causes of Death after Transplantation Rejection Surgery now is standard; but the yearly numbers are Infection actually falling. With newer technology impacting our lives Technical in more ways than one, surgery of heart transplant has an CNS uncertain future. Sooner but not later, totally implantable Malignancy artificial heart (or assist device) will make heart transplant After First year surgery obsolete. • Graft Atherosclerosis • Infection • Malignancy- Lymphoma • Rejection
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Maintenance immunosuppressive therapy is administered to all transplant recipients to prevent acute rejection and loss of allograft. By Dr. Jatin Kothari
Induction immunosuppressive strategies in renal transplantation
High dose conventional agents Antibody induction
Calcineurin inhibitor: Cyclosporine or tacrolimus Calcineurin inhibitor: Cyclosporine or tacrolimus (lower doses than conventional agent strategy)
Corticosteroid Corticosteroid
Antimetabolite: Mycophenolate mofetil or Antimetabolite: Mycophenolate mofetil or azathioprine azathioprine (lower doses than conventional agent strategy)
Plus one of the following: . ALG ATG OKT3 Anti-TAC: Daclizumab or basiliximab
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EVALUATION OF INDUCTION ALTHOUGH AGGRESSIVE the renal allograft. Although an PROTOCOL
INDUCTION therapy offers clinical adequate level of immunosuppression is REQUIRES advantages even in low-risk groups, such required to dampen the immune response CONSIDERATION
a regimen produces the greatest benefits to the allograft, the level of chronic OF THE in groups at high-risk for allograft immunosuppression is slowly decreased FOLLOWING rejection which include pediatric patients, over time (as the risk of acute rejection FACTORS: “ Incidence and severity of delayed allograft function or THE LEVEL OF CHRONIC IMMUNOSUPPRESSION primary IS SLOWLY DECREASED OVER TIME nonfunction including the requirement for “ and duration of dialysis following transplantation. African-Americans, recipients of kidneys decreases) to help lower the overall risk Incidence of with prolonged cold ischemia time, and of infection and malignancy; these risks acute rejection those at high immunologic risk, directly correlate with the degree of Incidence, type, particularly individuals who are overall immunosuppression. The type of and severity of presensitized. The sequential induction immunosuppression may also be varied associated regimen of thymoglobulin (or OKT3) to decrease the risk of developing infections followed by cyclosporine or tacrolimus is chronic allograft nephropathy, the most Long-term recommended in these high-risk groups. common underlying long-term cause of allograft survival allograft loss. Conventional and function MAINTENANCE maintenance regimens consist of a Mortality and IMMUNOSUPPRESSIVE combination of immunosuppressive morbidity, THERAPY IN RENAL agents that differ by mechanism of Incidence and TRANSPLANTATION IN ADULTS action. This strategy minimizes morbidity type of Maintenance immunosuppressive and mortality associated with each class malignancy during long-term
therapy is administered to almost all of agent while maximizing overall follow-up renal transplant recipients to help effectiveness. Such regimens may vary by
prevent acute rejection and the loss of transplant center and geographic Cost including length of hospitalization THE INTRODUCTION OF CYCLOSPORINE IN THE “ EARLY 1980S IMPROVED RENAL ALLOGRAFT SURVIVAL BY APPROXIMATELY 15 PERCENT AT “ ONE YEAR POST-TRANSPLANT.
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area.The major immunosuppressive agents that are frequency as with OKT3 . currently being used in various combination regimens Anti-ICAM-1 antibodies — Several adhesion are corticosteroids (primarily oral prednisone), molecules contribute to the interaction between T cells azathioprine, mycophenolate mofetil (MMF), and antigen presenting or target cells. One critical mycophenolate sodium (myfortic), Cyclosporine , adhesive receptor-counterreceptor combination is Tacrolimus, Everolimus, and Rapamycin (sirolimus) leukocyte function-associated molecule-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) . INVESTIGATIONAL IMMUNOSUPPRESSIVE Anti-LFA-1 antibodies — phase I/II trials DRUGS IN CLINICAL RENAL evaluated two doses of efalizumab, a humanized anti- TRANSPLANTATION LFA-1 antibody, plus maintenance therapy with either The introduction of Cyclosporine in the early 1980s full dose cyclosporine, mycophenolate and steroids or improved renal allograft survival by approximately 15 half dose cyclosporine, sirolimus and prednisone . At percent at one year posttransplant. However, Cyclosporine six months, patient and allograft survival were 97 and failed to enhance long-term graft survival because of the 95 percent, respectively. inability to suppress the chronic and progressive loss of Anti-B7 antibody — Of the numerous functioning renal tissue arising from antigen dependent costimulatory pathways for T cell activation identified and independent immunologic factors .The administration thus far, that provided by the interaction of CD28 on of cyclosporine or tacrolimus may also exacerbate this the T cell surface with its antigen presenting cell surface process because of direct nephrotoxicity . In addition, ligands, B7-1 or B7-2 (CD80 and CD86, respectively), renal transplant recipients are at risk for significant side has been most studied. T cell anergy and apoptosis effects due to immunosuppression, including infection, induced by T cell receptor signaling alone is prevented cardiovascular disease, hypertension, and malignancy. by signaling through CD28.Phase III trials are currently These limitations constitute the rationale for the continued underway, which is evaluating Belatacept in a calcineurin development of new immunosuppressive agents. inhibitor free maintenance immunosuppressive regimen. MONOCLONAL ANTIBODIES — OKT3 EVEROLIMUS — The efficacy and adverse effects remains the only non-humanized mouse antibody of Everolimus an immunosuppressive agent that is a licensed for the therapy of allograft rejection . However, structural analogue of sirolimus, has been evaluated in the administration of OKT3 is associated with frequent multiple studies . Dose levels up to 5 mg/day were well and occasionally serious adverse effects.Since OKT3 is tolerated; an increased incidence and severity of adverse a T cell mitogen, most of these symptoms are thought events, particularly thrombocytopenia and reversible to be mediated by T cell release of cytokines via CD3 cholesterol elevations, were observed at a dose of 10 binding. Other serious complications, arising from the mg/day. more intense immunosuppression, include infection and FINGOLIMOD (FTY720) — Fingolimod an increased incidence of lymphoproliferative disease (FTY720) is a sphingosine analogue that functions as Humanized OKT 3 — To reduce the side an immunosuppressant by altering normal lymphocyte effects and the antigenicity of murine OKT3, a non- homing patterns . This agent interferes with the exit of mitogenic “humanized” variant has been lymphocytes from the thymus into the blood and from developed . The humanized hybrid molecule the tissue of secondary lymphoid organs into the efferent was engineered by transferring the lymphatics. It may also reduce the risk of malignancy complimentary determining regions of OKT3 after transplantation . onto a human IgG framework and then PHOTOPHERESIS — Photopheresis is a form of mutating single amino acids to reduce the extracorporeal photochemotherapy in which peripheral affinity of the “humanized” anti-CD3 lymphocytes are collected via apheresis and treated with monoclonal antibodies. 8-methoxypsoralen and ultraviolet light . The process T10B9.1A monoclonal antibody — T10B9.1A appears to downregulate activated T cell is a murine monoclonal antibody directed against an clones.Preliminary evidence suggests that photopheresis epitope of the T cell receptor alpha/beta heterodimer . may decrease the frequency of rejection in both cardiac Unfortunately, the development of human antimouse and renal transplant recipients. antibodies with T10B9.1A occurs with the same
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Research
Patents: ‘Method and research tool for identification of mycobacterium along with detection of drug resistance in mycobacterium tuberculosis complex’. Has been filed for patency to Indian National Patent’s Office. The study was carried out by Shubadha Shenai under the guidance of Dr Camilla Rodrigues and Dr Ajita Mehta.
Awards: Shubadha Shenai won
– (i) Gold medal 2007 for best paper [Title : Development of a Reverse line blot hybridization (RLBH) assay for species identification of mycobacteria and drug resistant testing in M. tuberculosis complex. ] presented at the XXXIst at the Indian Association of Medical Microbiologist.
– (ii) Best paper award in PhD category 2007 from the ‘Dhala’s Felicitation Fund’.
Dr Hari Talreja won the Burgis N. Khushetji Award in the Indian society of Nephrology , Western chapter held at Raipur in sept 2007 for his paper; ‘Assesment of currently available methods of GFR, need for a new marker (Cystatin C)? ’.
Annual Research Day was held on 12th April 2008. Best paper awards were given to following papers:
– First prize: To Dr Dipika Agarwal for her paper ‘Prevalence of sleep disordered breathing in patients with heart failure’
– Second prize: To Shubadha Shenai for her paper ‘Comparison of phenotypic& genotypic methods of pyrazinamide susceptibility testing’ & to Rani Raghavan for her paper For her paper ‘Genetic screening of cystic fibrosis gene in Indian patients’.
Mid Annual Research Day was held on 3rd November 2007. Best paper awards were given to following:
– First prize: To Apurva Sawant for her paper ‘Prevalence of dyslipidemia in young adult Indian population’.
– Second prize: To Jency Courien for her paper ‘Kikuchi-fujimoto disease : A study of 25 patients.
2008 Vol 23 Vol No. 1 19
New Layout-Dt 14-2-2009 - final.pmd 19 2/14/2009, 5:16 PM Liver Transplant Liver Transplantation has been gaining popularity due to its high success rate and the fact that it is currently the only cure for end-stage liver disease. By Dr. Sudeep R Shah
LIVER TRANSPLANTATION IS, today, the only anesthesia, intensive care and refining of surgical curative option for end-stage liver disease. Dr techniques, survival of more than 80% have been Thomas Starzl in the USA and Sir Roy Calne in the achieved. UK who pioneered these surgeries in the 1960s initially had success rates of 30%. However, CONTRAINDICATIONS paralleling advances in immunosuppression, Systemic illnesses precluding anesthesia, untreated
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INDICATIONS FOR LIVER TRANSPLANTATION
Hepatitis C cirrhosis Hepatitis B cirrhosis Alcoholic liver disease sepsis, AIDS and extrahepatic malignancy, Cholestatic liver disease non neuroendocrine liver metastases, liver • Primary sclerosing cholangiitis angiosarcoma and cholangiocarcinoma • Biliary cirrhosis- primary and secondary are considered absolute contraindications. Autoimmune liver disease Hepatocellular Carinoma (HCC) beyond Budd-Chiari syndrome the Milan criteria (> 5 cm tumour, >3 Metabolic disorders: tumours each < 3cm), have survival • Wilsons disease reduced by tumor reccurrence. HCC with • Haemochromatosis tumour thrombus in the portal vein. HBV DNA positive patients have high graft loss. • Oxalosis Severe porto-pulmonary hypertension, • Alpha 1 antitrypsin deficiency non-compliers with treatment and active • Erythropoetic porphyria substance abusers are not considered. • Hypercholesterolemia • Familial amyloid polyneuropathy IMMUNOSUPPRESSION AND Liver space occupying lesions: REJECTION • Polycystic disease Only blood group matching is required • Multiple adenomatosis for liver transplantation. Though acute • Caroli’s disease rejection may occur in up to 50% of cases, chronic rejection leading to graft loss takes Fulminant liver failure place in < 5% of transplants. Diagnosis • Viral hepatitits (B, A, E) is suspected on altered liver function and • Drug toxicity established by biopsy. • Paracetamol overdose Lifelong immunosuppression is required. • Halothane Modern immunosuppression centers on • Wilson’s disease the use of calcineurin inhibitors- In children: Tacrolimus (FK 506) or microemulsified • Biliary atresia Cyclosporine A Levels are closely • Progressive familial intrahepatic cholestasis monitored to limit toxicity. Steroids are • Metabolic disorders Criggler Najjar syndrome, Urea started in high doses and rapidly tapered. cycle disorders In the majority of cases these can be stopped by 3 months post operatively. • Unresectable hepatoblastoma Episodes of acute rejection are treated by pulsed steroids for 3 days. In rare cases, severe rejection requires treatment with dysfunction.. Recently induction agents antilymphocytic globulin or OKT3. such as anti IL2 receptor antibodies- Mycophenolate moefetil is used as an basiliximab and daclizumab and new adjunct, especially to reduce calcineurin drugs rapamycin and sirolimus are also inhibitor dose in case of renal being used.
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POST OPERATIVE nosocomial organisms, COMPLICATIONS opportunistic infections of Primary failure of graft note are cytomegalovirus function is most feared- Donor Selection and (CMV) which occurs as occurring in 5% of cases. Procedure fever, leucopenia and The causes include poor The donor may be a brain-stem dead colitis, hepatitis, pneumonia donor liver quality- cadaver from whom the whole liver or meningitis after the third especially steatohepatitis., may be retrieved, or a relative who is week. Prophylaxis is preservation injury and fit, free of liver pathology and willing instituted especially if the hepatic artery thrombosis to donate part of the liver. An donor has previous (HAT), which almost anatomical lobe or sector may be exposure and recipient does invariably requires removed amounting to 0.8 to 1% of not. Viral and fungal retransplantation. HAT recipient body weight. Living donor risk infections too are common. occurs in 5% of adult and to life is estimated at <0.5% , with a Live vaccines should be 15% of pediatric 10% risk of major morbidity. The donor avoided post transplant. transplants. Portal vein liver regenerates to near normal Drug toxicity is a major thrombosis is rarer, volume. morbidity. Calcineurin occurring in 2%. Biliary Brain stem dead cadavers may not inhibitors cause complications have been provide a good quality liver if they have hypertension, called the Achilles’ heel of poor hemodynamic stability, are on high hyperlipidemia and liver transplantation and pressor doses, have fatty change, long diabetes. High levels are occur in 12-30% of cases. ICU stay or prolonged starvation. nephrotoxic and may lead HAT may be associated Potential brain dead organ donors to tremors, neuropsychiatric with this as the artery is the require careful maintainance in ICU. changes and rarely, main supply to the bile Cadaver livers may be divided along convulsions. Cyclosporin duct. Corrective surgery is anatomical planes to reduce size for leads to hirsuitism and often required. children or alternately split to provide gingival hypertrophy. Liver dysfunction due to two grafts- a smaller left lobe for children Mycophenolate causes a small graft is a particular and right lobe for small adults, either in leucopenia and diarrhoea. problem of living related situ or on the bench after retrieval. Rapamycin leads to retarded transplant in case of small The liver is perfused with University of wound healing. Drug donor graft. Failure to Wisconsin (UW) solution or Histidine- interactions are common establish adequate venous tryptophan-ketoglutarate (HTK) and complex, requiring outflow especially from solution. The liver may preserve for upto physicians to be careful middle hepatic vein 24 hours in UW and 15 hours in HTK while adding new drugs. branches of a right lobe solution. Post transplant graft may lead to graft lymphoproliferative
congestion . disorders and skin cancers
Infections owing to immunosuppression are the occur in up to 7% of immunosuppressed patients. common cause of morbidity and mortality. Besides Disease recurrence is a major issue, especially in PARALLELING ADVANCES IN IMMUNOSUPPRESSION, ANESTHESIA, “ INTENSIVE CARE AND REFINING OF SURGICAL TECHNIQUES, “ SURVIVAL OF MORE THAN 80% HAVE BEEN ACHIEVED.
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The Recipient Procedure The native liver is removed, a step that is difficult because of portal hypertension collaterals and coagulopathy, and replaced by the donor liver, joining the vena cava, portal vein, hepatic artery and bile duct. T-tubes or stents are occasionally employed across the biliary anastomosis. In case of bile duct disease such as biliary atresia, a Roux loop of jejunum is used. longer considered essential. The native vena cava is left in place in all living related transplants and also in select cadaveric transplants.
Hepatitis C, where accelerated cirrhosis may occur in INDIAN SCENARIO up to 25% cases. Autoimmune hepatitis, primary Cadaver liver transplantation has been legally possible sclerosing cholangiitis and tumours may recur. since the Human Organ Transplant Act of 1994. Recidivism causes graft loss in alcoholics. However, numbers have been limited. Various agencies such as the Mohan Foundation (Chennai, Hyderabad), PROGNOSIS Organ retrival banking organization (ORBO) (Delhi) Modern transplant techniques offer a one year survival and Zonal Transplant Co-ordinating Center (ZTCC) of 80-90% and 5 year survival of 70-80% for (Maharashtra) are involved in increasing awareness appropriately selected patients with chronic liver disease for cadaver organ donation amongst physicians and undergoing timely transplants. The survival for fulminant lay people. Living related liver transplant is offered in liver failure is marginally lesser. Living related and some centers for those patients with suitable related cadaver transplant have similar survival rates. donors, with good results.
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New Layout-Dt 14-2-2009 - final.pmd 23 2/14/2009, 5:16 PM Live Related Renal Transplant Renal transplantation is the best form of renal replacement therapy with live related donor transplant being the solution of choice in End Stage Renal Disease patients. By Dr. Alan Almeida & Dr. Ashwinikumar Khandekar
RENAL TRANSPLANTATION REMAINS the dialysis. Contrary to common perception, best form of renal replacement therapy providing transplantation, in the long run, is a less expensive better quality of life and survival compared to option than dialysis, giving better rehabilitation. Live
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WHO CANNOT related donor transplant still remains the soon became the standard DONATE A solution of choice in End Stage Renal immunosuppressant regimen for KIDNEY? Disease patients with the promise of transplants. Cyclosporine became Following is a list of deceased donor (cadaver donor) available in the mid-80s, dramatically conditions which preclude renal transplantation still not fulfilling its reducing the incidence of acute rejection donation. promised growth. and improving overall graft survival. ABSOLUTE Psychiatric disease interfering with Percent survival after living-related/cadaveric donor transplant and dialysis ability to consent Treatment 1 yr 2 yr 5 yr 10 yr Active drug or Type survival survival survival survival alcohol abuse Evidence of renal Living-related donor disease (low GFR, renal transplant 97.79 95.82 90.21 74.84 urinary abnormalities)
Cadaveric donor transplant 94.68 91.96 78.93 55.07 Recurrent or bilateral Dialysis 77.96 62.39 27.96 8.49
kidney stones Collagen vascular disease “ Diabetes with CONTRARY TO COMMON PERCEPTION, kidney RENAL TRANSPLANTATION, IN THE LONG involvement Severe RUN, IS A LESS EXPENSIVE OPTION THAN Hypertension “DIALYSIS, GIVING BETTER REHABILITATION. Malignancy Active infection Chronic active viral infection HISTORY Mycophenolate mofetil (and (hepatitis B or C, HIV) The first successful renal transplantation mycophenolic acid), tacrolimus, Significant chronic was performed between identical twins sirolimus / everolimus and other agents liver disease by Joseph Murray in 1954. No were added over the ensuing years. Not Current pregnancy immunosuppression was used because only were newer drugs added but RELATIVE the donor was genetically identical to the biological agents to prevent or treat Age <18 or >65
recipient. Transplantation grew with the rejection have evolved. The current day years advent of newer immunosuppressive standard triple regime includes Obesity (especially
agents such as azathioprine (1960). A Mycophenolate, Tacrolimus or BMI >35) combination of steroids and azathioprine Cyclosporine and steroids. Mild or easily treated hypertension “ Single prior episode of nephrolithiasis THE FIRST SUCCESSFUL RENAL Borderline urinary TRANSPLANTATION WAS PERFORMED BETWEEN abnormalities IDENTICAL“ TWINS BY JOSEPH MURRAY IN 1954.
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OPTIONS FOR PATIENTS WITH END STAGE Contraindications to Renal Transplantation RENAL DISEASE (ESRD) Contraindication Absolute Relative Uremic symptoms arise in renal failure patients with a creatinine clearance ≤ 10 mL/min with symptoms of Cancer X anorexia, nausea, weight loss, breathlessness, anemia HIV positive/AIDS X and sometimes reduced urine output being HCV infection X HBV infection X predominant. Toxins, otherwise thrown out in the urine Morbid obesity X by better functioning kidneys, accumulate in the Atherosclerosis X circulation in uremic patients,. This is the time that Cardiac Disease X the excretory function of the kidney need to be replaced Uncontrolled hypertension X by the process of dialysis, either hemodialysis or Smoking X peritoneal dialysis. The synthetic functions viz. Unresolved psychosocial issues X production of vitamin D and the hormone erythropoietin Active UTI X still need an external supplement in the form of Active tuberculosis X injections or tablets. Renal Transplant is a more Irreversible heart failure, X complete solution since a normal functioning kidney Irreversible lung failure X Irreversible liver failure X is placed inside the recipient which carries out both Active systemic disease the excretory as well as the synthetic functions. (ie, lupus, sickle cell Sometimes, it may be prudent to do a transplant even disease, Wegener’s disease) X before the patient requires institution of dialysis and is called a pre-emptive transplant (pre-empt the need WHO CAN DONATE A KIDNEY? for dialysis). As per the existing Human Organ Transplant Act 1994, any first degree relatives of the recipient ( parents, WHO CANNOT HAVE A KIDNEY siblings, children) or the spouse can be an organ donor TRANSPLANT? provided they are blood group compatible. Blood group Treatment options for patients with ESRD include [ABO] compatibility is the same as that in relation to palliative care, hemodialysis, peritoneal dialysis, and blood transfusion except that the Rh compatibility is not kidney transplantation. During the pretransplant required for renal transplant. Blood group ‘AB’ is a evaluation, patients are categorized as low, moderate, universal recipient while ‘O’ is a universal donor. A or high risk based on surgical risk factors and comorbid donor between 18 and 55 years of age would be medical conditions. Absolute and relative preferred, though at times, donors of older age may contraindications to kidney transplantation are listed in also be accepted (biological age vs chronological age). the table. Absolute contraindications include some types It is understandable that a kidney from an elderly donor of neoplastic disease, HIV infection, AIDS, some would have lower GFR (commensurate with the age- infectious processes, some systemic diseases, and related decline) and other associated co-morbidities. irreversible vital organ failure. However, due to special
expertise and/or research protocols at individual centers, WORK UP OF A DONOR patients with these contraindications may be A donor is identified at a family conference and
transplanted, but this is not reflective of current practice undergoes detailed evaluation starting off with a detailed standards. history to rule out medical disorders that would preclude AS PER THE EXISTING HUMAN ORGAN TRANSPLANT ACT 1994, “ ANY FIRST DEGREE RELATIVES OF THE RECIPIENT ( PARENTS, SIBLINGS, CHILDREN) OR THE SPOUSE CAN BE AN ORGAN “ DONOR PROVIDED THEY ARE BLOOD GROUP COMPATIBLE.
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organ donation. After conventional renal an in-depth clinical angiogram or Digital examination, the donor is Common side effects of Subtraction Angiogram subjected to laboratory Immunosuppressives: (DSA) or Computerized workup. • Cyclosporine can cause excessive Tomography (CT) The first step is the facial hair growth, gum hypertrophy, Angiogram depending on demonstration of blood hypertension, lipid abnormalities and availability. group compatibility (ABO). the drug itself is toxic to the kidneys If the blood group is if the blood levels are high. It can HLA TEST AND compatible, the donor is also affect the endocrine functions LYMPHOCYTE tested for renal functions of pancreas and lead to diabetes CROSSMATCH and any systemic condition mellitus. Human Leukocyte Antigen which might interfere with • Azathioprine can cause bone (HLA) is a set of antigens organ donation or surgical marrow suppression encoded by Major fitness. If the renal functions • Mycophenolate causes selective Histocompatibility Complex are good and there is no suppression of WBC production. on chromosome 6. There risk other than that Loose motions are a common side are two classes, class I and associated with an elective effect. class II. Class I includes surgery, only then the • Steroids side effects include truncal subgroups A, B and C and prospective donor is obesity, hypertension, lipid class II includes subgroups considered fit to donate. abnormalities, cataracts, avascular DR, DQ and others. Each The possibility of necrosis of femur head, muscle subgroup expresses two transmitting an infection weakness, osteoporosis and glucose alleles. Hundreds of such should be ruled out by intolerance. alleles have been identified performance of serological • Sirolimus and Everolimus can affect and more are added every tests. HIV seropositivity is a wound healing, cause proteinuria few months. For Renal contra-indication to renal and in combination with Transplantation, the donation. Similarly, Cyclosporine or Tacrolimus affect subgroups A, B and DR are Hepatitis B or Hepatitis C the kidney function. considered important. seropositive individuals Identical twins will have cannot donate to respective seronegative recipients. Any 100% matching in these alleles. The other siblings can active infection, especially urinary tract infection should have a 100% match (HLA identical), a 50% match be completely treated prior to kidney donation. Specific (haplo-identical) or a zero match between them. Parents viral illnesses which are quiescent in a normal individual, have a 50% match with their offsprings. Better the HLA can become life threatening in an immunosuppressed match, lesser is the immunosuppression required and individual and need to be ruled out prior to donation. longer is the graft survival. Even though the HLA match These includes Cytomegalovirus (CMV) and Epstein - may be 100%, there are several other antigenic stimuli Barr virus (EBV). An active infection can be ruled out which can incite an immunological response by the serologically by measuring IgM antibodies against these recipient precipitating a graft rejection. This can be viruses. tested by doing a lymphocyte crossmatch test where To quantify the donor’s renal functions, a 24 hr urinary donor lymphocytes are incubated with recipient serum creatinine clearance is done or similar information may and if more than 10% of donor lymphocytes are destroyed be obtained by measuring the level of kidney function by recipient serum, it is designated as positive and a on a nuclear medicine study (DTPA GFR). Surgical fitness transplant precluded at that stage and a search for is largely decided by cardiovascular fitness followed by alternative donor initiated. This situation arises after the hepatic functions and respiratory illnesses multiple pregnancies or donor specific transfusions. compromising lung functions. Finally the surgical anatomy of blood supply to the kidneys needs to be clearly WORKUP OF THE RECIPIENT delineated prior to surgery. This is done by either a The workup is largely directed towards surgical fitness
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LIVE RELATED RENAL TRANPLANT THE OLD KIDNEYS ARE USUALLY PRESERVED SINCE “ THEY ARE HARMLESS AND CAN ACTUALLY CONTRIBUTE “ SOME FUNCTION EVEN AFTER TRANSPLANT.
and the viral illnesses mentioned above and have similar surgery and after a fixed interval thereafter depending implications as in the donor. Active infections including on the drug used. The immunosuppression needs to UTI, dental abscesses, dental caries need to be ruled be continued life-long. These drugs need to be out. In children, a common cause of renal failure is monitored since the ‘therapeutic index’ is quite narrow. abnormal bladder function. Bladder function needs to Blood levels of cyclosporine and Tacrolimus are checked be tested for its ability to accommodate and hold the routinely till the desirable level is achieved and thereafter increased urine after transplant. If abnormal, a corrective whenever the need is felt. Levels are also monitored for bladder surgery may be required. Sirolimus and Everolimus. With the current day potent immunosuppressants, graft life has increased at the cost TRANSPLANT SURGERY of increased risk of infections. Urinary Tract Infection Two surgical teams operate simultaneously on the donor still remains the commonest infection followed by and the recipient. The donor kidney is placed in the bacterial pneumonia, viral illnesses like CMV and fungal recipient’s iliac fossa outside the peritoneal sac. The infections. Tuberculosis still remains a potent threat in renal blood vessels are joined to the iliac blood vessels transplant recipients . A polyoma virus called BK virus and the ureter is joined to the bladder with a technique is becoming increasingly more recognized as a cause designed to prevent reflux from the bladder into the renal for steady decline in graft function. graft. The old kidneys are usually preserved since they are harmless and can actually contribute some function POST TRANSPLANT PERIOD even after transplant. The additional surgery of removing The transplant recipient requires close follow-up in the old kidneys can be avoided unless they are severely post transplant period. The initial year is the most infected or are too large and occupying the whole of important but the surveillance should continue lifelong abdomen. to ensure a long survival.
IMMUNOSUPPRESSION OUTCOMES OF RENAL TRANSPLANT Except in an identical twin, immunosuppression is With potent immunosuppressive options available required to prevent rejection. This includes the today, graft survival has significantly improved. The medications like cyclosporine or Tacrolimus, graft ‘half-life’ has increased to 12 to 15 years from a Mycophenolate (MMF) or Azathioprine along with previous 5 to 10 years. The outcomes are better with glucocorticoids. Newer, more potent drugs include complete HLA match (100%) compared to haplo- Sirolimus and Everolimus. If the HLA match is poor, an identical (50% match) which in turn has better survival ‘induction’ agent is used in the form of monoclonal or than zero match. However, the outcomes are affected
polyclonal antibodies against lymphocytes. These by acute rejection episodes, severe infections,
medications are started a day or two prior to the surgery recurrence of the native kidney disease in the graft and the antibodies are usually given just prior to the and cardiovascular diseases. THE GRAFT ‘HALF-LIFE’ HAS INCREASED TO 12 TO 15 “ “ YEARS FROM A PREVIOUS 5 TO 10 YEARS.
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New State-of-the-Art Operation Theatres
To commemorate the 75th Birth Anniversary of Smt. Lalita Girdhar Hinduja on 1st November 2007, Hinduja Hospital took another step forward in the hi-tech world of modern medicate to uphold the strong organization values of to improve patient safety and comfort, inaugurated 8 new state-of-the-art operation theatres.
The new digitalized Operation Theatre complex is the first in many aspects in the country and can match the best in the world. These theatres have been designed , keeping in mind the surgeon, anesthetist, nurses and other OT personnel working requirements.
Highlights of this new OT complex:
• Guided Airflow Ventilation System (GAF): a patent technology for keeping surgical site free of contamination.
• The Heat Ventilation and Air Conditioning Systems (HVAC): Each OT has it’s individual Air Handling Unit (AHU) with independent temperature and humidity controls. The first hospital to install the Digital Direct Control (DDC) for management of pressurization of the complex, cleanliness of the various filtration process based on room zoning, will greatly enhance the management of the air quality with in the complex.
• Operating Lights: Light Emitting Diodes (LED) provides shadowless operating light, excellent visualization, minimum heat generation and proper dissipation with high light intensity.
• Integrated camera with LED lamps to capture crystal clear live images
• Simultaneous web telecasting of procedures.
CONFERENCE AND SEMINAR
PLEASE VISIT www.hindujahospital.com/registration to register online OR VIEW PAST & FUTURE EVENTS.
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New Layout-Dt 14-2-2009 - final.pmd 29 2/14/2009, 5:16 PM Stem Cell Transplant (SCT) While Stem Cell Transplant has vast benefits, it is associated with a number of complications, some of which may be life threatening. By Dr. Asha Kapadia, Dr. Sachin V. Almel & Dr.Uma Dangi
THE IDEA OF rebuilding a bone marrow INDICATIONS destroyed by radiation was born in the aftermath The rationale for SCT differs for different diseases. Mainly, it serves as: of World War II and the subsequent nuclear arms. • A rescue procedure after treatment with high dose First modern transplants started in 1957 in patients chemotherapy in certain malignancies with end stage leukemia. • As replacement therapy in patients with marrow
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DONOR SELECTION The choice of the source of stem cells depends on many failure or autoimmune disorders • Thrombocytopenia factors, importantly • As a vehicle for gene therapy • Infections the patient’s disease. • Possible strategy to establish tolerance • Mucositis Depending upon the for solid organ transplants • Venoocclusive disease source, transplant • Acute GVHD can be – TRANSPLANT PROCEDURE • Graft failure Autologous - In preparation for SCT, it is necessary to Late effects: source are “condition” the patient. The conditioning • Chronic GVHD
patient’s own regimens vary with the type of disease and • Growth failure cells can be high dose chemotherapy, biologic • Infertility
Syngeneic – donor is an identical twin “ Allogeneic – POST TRANSPLANT, THE ENGRAFTMENT • HLA identical DEPENDS ON THE SOURCE OF THE STEM donor (related CELLS AND THE USE OF G-CSF, USUALLY / unrelated) OCCURRING AT DAY 10 – 21. • HLA non “ identical donor (related / unrelated) Xenogeneic – therapy and radiation. The stem cells are • Cataracts different species infused through a large bore central • Second malignancies The stem cells are venous catheter. Post transplant, the Transplant program at Hinduja Hospital either collected engraftment depends on the source of the We have been doing Autologous from the bone stem cells and the use of G-CSF, usually peripheral blood stem cell transplants’s marrow; or the occurring at day 10 – 21. here at Hinduja Hospital for last 6 years, peripheral blood mostly for malignant conditions viz. after treating with COMPLICATIONS multiple myeloma and relapsed / growth factors. SCT is associated with a lot of refractory lymphomas. We have done complications, some of which may be life around 13 transplants so far, with good threatening. results. We also plan to start Allogeneic Early Toxicities: transplant at our centre in a short • Neutropenia while.
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New Layout-Dt 14-2-2009 - final.pmd 31 2/14/2009, 5:16 PM Lung transplant – Where does it stand today ? With refinement of surgical techniques and a greater understanding of immunology and microbiology, the success of lung transplantation has increased manifold. By Dr. Manoj Agni
INTRODUCTION: This has essentially been due to the amazing advances TWENTY FIVE YEARS AGO the first successful that have been made in the field through refinement of clinical lung transplant was performed and since surgical techniques and improved understanding of then lung transplantation has become the modality transplant immunology and microbiology. of choice for a variety of end-stage lung diseases. Approximately 1,400 transplants are performed
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SINGLE OR DOUBLE LUNG TRANSPLANT ? ON OR OFF BYPASS ? worldwide each year. The operative 25% predicted. General guidelines for mortality rates are less than 10% and one • Resting Hypoxia – PaO2 < 60 mm the selection of the
year survival is greater than 80% for most Hg. procedure are based
diagnoses. Functional results are excellent • Hypercapnia – PaCO2 > 50 mm on the nature of the
and durable. Post-transplant quality-of-life Hg. original disease and are as follows: Double-lung “ transplantation • Cystic fibrosis • Generalized DONOR SHORTAGES CONTINUE TO LIMIT bronchiectasis THE MORE WIDESPREAD APPLICATION OF LUNG TRANSPLANTATION. • Some patients with COPD “ Single-lung transplantation • Restrictive fibrotic lung studies demonstrate significant DONOR LUNGS ISSUES disease improvement in the majority of patients. Ideal donors are ones with a • Eisenmenger
Unfortunately, donor shortages continue nonsmoking history, clear chest syndrome with to limit the more widespread application radiograph, negative bronchoscopy and reparable of lung transplantation. In order to address good gas exchange (PaO2)/ (FIO2) cardiac this issue, marginal donors, living lobar >300). Unfortunately, only 5–10% of anomaly and split lung donor techniques have been multiorgan donors have lungs that meet • Some patients used clinically to increase the number of these criteria with COPD donor lungs available. Donors aged less than 60 yrs are • Primary preferable. pulmonary hypertension FOR WHOM AND WHEN ? Contraindications: ABO Heart-lung • Emphysema due to chronic incompatibility between donor and transplantation obstructive pulmonary disease recipient, human immunodeficiency virus • Eisenmenger or -1-antitrypsin deficiency positivity, active malignancies (outside the α syndrome with • Cystic fibrosis and central nervous system), and active irreparable
• Pulmonary fibrosis. hepatitis infections remain absolute cardiac defect • In the paediatric population, contraindications to donor lung • Pulmonary cystic fibrosis and pulmonary procurement. hypertension vascular disease are the prime Most adult lung transplants can with cor indications. be conducted without the requirement pulmonale Referral guidelines: for cardiopulmonary bypass. Patients • End-stage • Endstage lung disease with life with severe primary or secondary pulmonary lung disease expectancy less than 1 - 2 yrs. hypertension and paediatric patients need, with concurrent severe cardiac • Postbrochodilator FEV1 less than cardiopulmonary bypass. disease
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AFTER ALL THIS, months. Mobility, energy,
HOW WELL DO THE What to watch out for sleep, activities of daily RECIPIENTS DO ? living dependency level postoperatively – early Operative mortality and and late ? and dyspnoea were reported long-term survival vary by to be improved following diagnosis, with emphysema Reperfusion injury - Early lung lung transplantation. providing results somewhat allograft dysfunction occurs in 15–20% Pretransplant psychological superior to more of cases. status appears to affect challenging conditions Airway complications post-transplant quality of life such as pulmonary fibrosis Infections and adjustment. and pulmonary Rejection - Most recipients experience hypertension. The operative at least one episode of acute rejection BILATERAL mortality is usually around within the first year following the LIVING-DONOR 5 - 10%. transplant. Calcineurin inhibitors are LOBAR LUNG Postoperative functional used in virtually all patients TRANSPLANTATION results are excellent. Bilateral living-donor lobar Bronchiolitis obliterans syndrome - Following bilateral lung transplantation is a BOS transplantation for procedure for patients emphysema, the mean considered too ill to await
FEV1 increases from a preoperative level of 16% of the cadaveric transplantation. In this procedure, right and predicted value to 84% at 3 months. This improvement left lower lobes from two healthy donors are implanted in pulmonary function is maintained at 1 yr with a mean in the recipient in place of the whole right and left lungs,
FEV1 of 75% predicted. Among cystic fibrosis patients, respectively.
results are similar, with a preoperative FEV1 of 22% Because only two lobes are transplanted, it seems to predicted increasing to 68% predicted early be best suited for children and small adults Furthermore, postoperatively and 70% predicted at 2 yrs. since paediatric patients receiving living lobar Among more than 14,500 lung transplant recipients transplants experienced less BOS and better pulmonary on the ISHLT ( International Society of Heart Lung function than paediatric recipients receiving cadaveric Transplantation) Registry, overall 1-, 3- and 5-yr survival donor lungs, living lobar transplantation may be the is 76, 57 and 43% respectively. Among single lung preferred method for children. recipients, FEV at 5, 6 and 7 yrs after transplantation 1 Dramatic improvement of was 75, 73 and 68% predicted respectively. Experience pulmonary hemodynamics is with pulmonary hypertension has also been gratifying. confirmed by chest X-ray and These patients have experienced immediate restoration echocardiogram. The mean of normal right heart function and pulmonary pulmonary artery pressures can haemodynamics which persists over a 4-yr follow-up decrease from 72 mmHg to 11
period. Actuarial survival of paediatric recipients is mmHg. A year postoperatively, the patient is in 77% at 1 yr, 62% at 3 yrs and 55% at 5 yrs.
excellent physical condition with a forced vital capacity Improvement in quality of life is seen after the and FEV1 close to 90% of predicted. transplant and usually becomes evident after 3–6 IN BILATERAL LIVING-DONOR LOBAR LUNG TRANSPLANTATION, “ RIGHT AND LEFT LOWER LOBES FROM TWO HEALTHY DONORS ARE IMPLANTED IN THE RECIPIENT IN PLACE OF THE WHOLE “ RIGHT AND LEFT LUNGS, RESPECTIVELY.
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Chest X-rays before (A) and after (B) receiving LDLLT. (A) Before operation. Marked cardiomegaly was present. (B) Three months after receiving Survival after living-donor lobar lung LDLLT. Well-expanded lobes filled the chest cavity, transplantation. After receiving a living-donor leaving no detectable dead space without lobar lung transplantation, 31 of 33 recipients cardiomegaly. (94%) are currently alive for as long as 77 months.
TYPES OF TRANSPLANTS Auto graft - Xeno graft - Transplant of tissue to the same person e.g. Skin Transplant from one species to another e.g. porcine grafts, vessel grafts for CABG heart valve transplant
Allo graft - Split Transplants - Transplant from a genetically non-identical member Donor organ (e.g. liver) may be divided between of same species e.g. human organ/ tissue two recipients. transplants. Domino Transplants - Iso graft - This operation is performed for cystic fibrosis as both Transplant to a genetically identical recipient e.g. lungs and heart are easier to transplant enbloc, identical twins recipients healthy heart is transplanted into someone else.
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AUTO SKIN GRAFTS have been in Mumbai since Solid organ transplant of kidney first took place in 1950 progress happened in improved knife blades, around 1965 – 66. It was performed by Dr. Pardanani, electronic dermatome and meshing. Heterogenous under leadership of Dr. P. K. Sen in K.E.M. Hospital. grafting did not succeed, as was expected. Skin However organ performed for a few days, as powerful banking and culture are for the future. immuno-suppressives were not available. Donation of
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AWARDS
1. Dr. Ashwini Gandhi Bhalerao was awarded the “Dr. Suresh Nadkarni Mitramandal Award for the year 2006-2007” by the Indian Medical Association, Maharashtra State for her activities in the field of health education through mass media, books on health related topics and conducting lectures for public health organ from cadaver was obtained by education. obtaining affidavit from “cadaver” patient’s 2. Dr. Shusheel Kharbanda, resident relative, in presence of a Magistrate or JP. (urology) won the first prize in paper Same process was used for cadaveric presentation for a paper “PROLONGED donations of two livers and two hearts. Liver ILEUS POST RADICAL CYSTECTOMY: transplantation was carried out by Dr. R. A. CONSIDER TOBACCO”. The paper was Bhalerao and cardiac transplant by Dr. P. K. presented in Mumbai Urology Society – Sen. The retrieval team was headed by Annual Meeting 2008, held at Lonavala between 4th – 7th July Dr. R. A. Bhalerao. However these efforts 2008. were mainly supplemented by first successful 3. Dr. Lancelot Mark Pinto, 3rd year Dip. N.B. cardiac transplant in South Africa by in Respiratory Medicine, won the second Christian Bernard. The liver transplants were prize for the South Asian Cochrane mainly technical success, cardiac transplants Network Essay competition for Post – worked for few hours. Further efforts got graduate students in the health sciences dwarfed by some legal technical objections on the topic “BARRIERS TO EVIDENCE pointed out by Dr. T. H. Ridani, the then INFORMED PRACTICE IN SOUTH ASIA Dean of K.E.M. Hospital. One additional AND POSSIBLE SOLUTIONS” at the 2nd South Asian Regional cardiac transplant was done by Dr. K. F. Symposium on Evidence Informed Health Care at the Christian Dastur in Nair Hospital. Further cadaveric Medical College, Vellore on April 9th 2008. transplants, had to wait till Human Organ Transplantation Act, 1994. The first long term successful cadaveric kidney transplant ‘morality’ block by different segments was performed by Dr. Vatsala Trivedi, of society including press, police, Urologist from Sion Hospital, and since then, judiciary, doctors. Government being L.T.M.G., K.E.M. Hospital and corporate involved in more ‘urgent’ national problems hospitals Jaslok and Hinduja Hospital are the future looks unclear. The same happened in forefront of kidney and liver transplant in ‘blood transfusion’ programme operations, with both cadaveric and live where now voluntary donor programme is related donor programme. ‘Selling’ of replacing professional donor programme. kidneys, prosecutions, and public debates In Asian countries cadaveric donations have now brought the organ donations share additional social and religious programme to a new crisis with shrinking inhibitions, hence this slow progress appears cadaver organs rising demands and inevitable.
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PET SCAN camp for the juvenile diabetes on Children’s Day. More P.D.Hinduja Hospital and MRC recently installed the than 60 diabetic children with their families joined in this second generation PET/CT in September 2007, an celebration. The chief guest for the day was Abhijeet TM advanced version of Discovery Ste from GE Sawant, India’s very first Indian Idol. The programme Healthcare for the first time in India. The advantages of this PET/CT scanner gives images that help doctors to diagnose patients in early stages of cancer and increase the prospect of preventive cure. It enables the radiation oncologist to focalize the beam of
Interactive Session by Dr. Phulrenu Chauhan
included an electrifying tabla performance by the young tabla artists, the Khan Brothers. Magic show performance by Mr. Ashraf Khan and active participation from the radiation to the active part of the tumor. This helps the risk of radiation exposure to the neighboring normal tissue. The machine has been used to perform a whole body scan on a seven year-old patient.
CAMPS 12 Medical Camp were organised commemorating the 75th anniversary year of L. G.H.
WORLD JUVENILE DIABETES DAY & CHILDREN’S DAY On 14th November, Hinduja Hospital organized a Abhijeet Sawant with his young fans
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Dr. Kirtane felicitating Mrs. Vakil at the 2nd Cochlear Demonstration of Intubation Implant Workshop
children during the brief interactive session conducted by Cornell, USA. A team of outstanding faculty members from Dr. Phulrenu Chauhan which included a quiz on juvenile both the institutions provided an integrated view of diabetes for educating and raising awareness among the Emergency Medicine. audience. The highlights of this conference were hands-on – experience with mannequins which is first of its kind in WORKSHOP India, especially flown in from USA. These mannequin The P D Hinduja Hospital organized the 2nd Cochlear simulators helped develop an increasingly realistic physical Implant Update from 22 – 23 December, 07. The and procedural components to complement an already Workshop was aimed at ENT surgeons, audiologists and high level of situational realism. The objective of this educators for the hearing impaired, keen to start their conference was to establish a residency programme in EMS own Cochlear Implant Programmes. Recognizing the need for a wider awareness on Cochlear Implants and the need for professionals to understand the team approach required to make Cochlear Implants a success, P D Hinduja National Hospital, through this workshop, aimed to provide basic information and training to the participants. The workshop also felicitated Mrs. Meher K Vakeel, a pioneer in the field of education for the hearing impaired in India. Mrs. Vakeel, who has dedicated over forty years of her life, to the education of the hearing impaired is credited with establishing The Education Emergency procedure – Drawing of Femoral blood Audiology and Research Society, the first teacher training course for the hearing impaired in India, an infant centre by sensitizing the medical fraternity to the nuances of EMS for early diagnosis and parent guidance, and the as a practice in the developing countries. introduction of neonatal hearing screening To take the EMS dream further, P.D. Hinduja National programmes. Among other accolades she is the recipient Hospital & MRC has taken a step towards developing of the prestigious ‘International Meritorious Service Emergency Medicine as an independent specialty in India. Award” by the Alexander Graham Bell Association for Hinduja hospital has always been at the vanguard of the Deaf, UK.’ pre-hospital care development. A Policy program is being developed for recommendation to the National CONFERENCE ON EMERGENCY Knowledge Commission a high level advisory body, during MEDICINE the meeting of the Dean and Heads of major institutions On 14th & 15th November, Hinduja Hospital conducted a from Mumbai apart from senior faculty on Emergency workshop on Emergency Medical Services, in collaboration Medicine from New York Presbyterian – The University with the Division of Emergency Medicine – New York of Columbia and Cornell was held on the 13th of Presbyterian - The University Hospital of Columbia and November 2007.
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WELCOME
Dr. (Mrs.) Chitra Madiwala has joined as the Consultant Histopathologist in the department of Laboratory Medicine. Dr. Madiwale completed her MD (Pathology) in 1988 from the University of Mumbai and fellowship in Nephropathology from USA. She has over 22 years of experience having worked at G.S.Medical College & KEM hospital - Mumbai and as an associate Professor at G.S. Medical College & KEM Hospital. Her areas of interest include nephropathology, gynecologic - pathology and orthopedic - pathology. Dr. Sudhir Warrier has joined as a Consultant in Hand & Reconstructive Surgery, section of Orthopedics. Dr. Warrier did his MS (Orthopedics) in 1987 from Grant Medical College, University of Mumbai. He has done fellowships from Gyeongsang National University, Korea; Okayama University, Japan & Government Stanley Hospital, Chennai. He was awarded the Best Discourse Award at the XIIth International Orthopedic Congress, Pakistan in the year 1997 and the Scholarship of Asia Pacific Societies for Surgery of the Hand, Hong Kong in the year 2002. Dr. Warrier is attached to Laud Clinic, Shushrusha Citizen Co-op Hospital & Jaslok Hospital. He is regularly involved in training programmes across the country for the post-graduate students & practicing orthopedic surgeons through workshops on Hand Surgery & External Fixation.
Dr. Pankaj Deshpande has joined as Consultant in Pediatric Nephrology, section of Pediatric Medicine. After completing his MD in pediatrics and 2 years in Pediatric Nephrology from Bai Jerbai Wadia hospital for Children, Dr. Deshpande went to UK in 1996. He pursued his MRCP in Pediatrics in 1997 and post MRCP he specialized in Pediatric Nephrology in various centers' of excellence in UK. He has worked as a Pediatric Nephrology Consultant at Southampton General Hospital, UK from 2001 to 2005. He returned to Mumbai in 2005 and ever since then has been practicing as a pediatric nephrology consultant at MGM Hospital, Lok Hospital, Kidney Speciality Group and Sai Child Care Centre.
Dr. Sharmila Ghosh has joined as the Consultant Haematologist in the Dept of Laboratory Medicine Dr. Ghosh completed her MD in Pathology in 1995 from Kasturba Medical College. She was trained in Hematology from St. Jude Hospital - US, in January 2008 and did advanced training in Bone Marrow reporting, Flow Cytometry and FISH at the Royal Free Hospital - London in 2004. She has also received training in Quality Systems e.g. ISO - 13000 from Tata Business Excellence. Dr. Ghosh has expertise in Phase I to Phase IV Clinical Trials, entailing planning, resource utilization and manpower management. She is skilled in planning and scheduling work, establishing systems, setting goals and standards. Dr.Ghosh has worked at Asian Institute of Oncology, Raheja Hospital and Tata Memorial Hospital in Mumbai and Jamshedpur. Prior to joining us she had worked at SRL Ranbaxy Ltd. as a Consultant Hematologist. Her area of interest is Hemato-Oncology.
Dr. Uday Limaye has joined as the Consultant in Interventional Neuroradiology, section of Interventional Radiology (DSA) in the department of Imaging. He completed his DNB from Grant Medical College and Sir JJ Group of Hospitals, Mumbai in 1995 and underwent specialty training from world renowned Interventional Neuroradiology centres like Foundation Rothshield Hospital,(France); Royal Perth Hospital, Australia and Haciteppe University, Turkey. Dr. Limaye is the Associate Professor& Chief of Interventional Neuroradiology at Seth G.S.Medical College & KEM Hospital; Mumbai .He has done pioneering work on Dural Venous Sinus thrombolysis, which was adjudged as the best paper at the Eastern Neuroradiology Meeting, Toronto in 2005. His areas of interest & expertise include intracranial stenting for Brain Aneurysms & Intracranial Artherosclerosis, Acute Stroke Therapy & Endovascular management of Craniofacial Vascular Malformations.
Printed and Published by Marketing Department, P. D. Hinduja National Hospital & Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai - 400 016 at SYNERGY CREATIONS, for free and private circulation. Editor : Dr. Reeta Dalal. Registered. (The Publisher cannot be held responsible for errors or for any consequences arising from the use of the information contained in this newsletter.)
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