1. Organ Transplantation Dr. Nelson L. Rhodus Director of Oral Medicine University of Minnesota

2. Organ Transplantation n Bone Marrow ( stem cell) n Solid organs –Heart –Lung –Liver –Kidney –Pancreas –Small intestine

3. Organ Transplantation n Heart transplants n First performed in 1967; first year only 1:5 survived n 2000= 3500 performed n Total= 53,000 n Present survival rate >70%

4. Organ Transplantation n Kidney n First solid organ transplant ( 1954) performed n Since then >490,000 kidney transplants n Presently 581 centers perform >10,000 kidney transplants per year: 1-year survival rate >90%( cadaver~80%) n Presently 581 centers perform >10,000 kidney transplants per year: 1-year survival rate >90%( cadaver~80%) ( 5 yr. ~70%)

5. Organ Transplantation n Liver transplants n First liver transplant in 1967 n >90,000 liver transplants n > 8,000 liver transplants per year1-year survival rate >90% n > 8,000 liver transplants per year1-year survival rate >90% ( 5 yr. ~70%)

6. Organ Transplantation n Pancreas transplants n n first pancreas transplant was performed in 1966, by Kelly and Lillehei at the University of Minnesota n n 2000 >3500 transplants performed n n >2000 at the U of M ! n n 1 year survival rate >85% ( 5 yr. ~70%) n n survival rate w/o pancreas transplant = about the same ! ( JAMA- Dec. ‘03)

7. Organ Transplantation n Heart - lung transplants n ~ 800 performed as of 2000 n 1 year survival ~ 60 %

8. Organ Transplantation n Small intestine transplants n n less than 50 performed (some combined with liver transplants) n n four transplant centers (Cambridge; London, Ontario; Pittsburgh, and Omaha). n n current 1-year survival rate at 70%. 1

9. Bone marrow transplantation n First performed in 1958 n Early = very poor prognosis n Immunosuppression, GVHD, rejection n 2000 > 100,000 n Today = successful ( 50-80% survival rate-1 year)

10. Organ Transplantation n HEART TRANSPLANTS n Reasons; cardiomyopathy, congenital heart disease, atherosclerotic coronary artery disease n Terminal heart disease (6-12 months) n Age <50-55 years

11. Organ Transplantation n HEART TRANSPLANTS n Good renal and hepatic function n No infections n No diabetes n Family support

12. Organ Transplantation n HEART TRANSPLANTS n Causes of death: n Infection40% n Acute graft rejection25% n Chronic graft rejection10 % n Cardiac disease25%

13. Organ Transplantation n HEART TRANSPLANTS n Endocarditis prevention n Pacemakers-arrhythmias n Medications- drugs n Avoid epinephrine n Anticoagulation

14. Organ Transplantation n HEART TRANSPLANTS n Immunosuppression n Adrenal suppression n Bleeding n Infection (IE)

15. Organ Transplantation n HEART TRANSPLANTS n ACCELERATED GRAFT ATHEROSCLEROSIS(AGAS) n ~ 50 % of post-transplant patients have AGAS ( same degree as pre-transplant)

16. Organ Transplantation n HEART TRANSPLANTS n Transplanted heart has no nerve supply n Therefore with AGAS there is NO ANGINA. MI will cause sudden death.

18. Organ Transplantation n LIVER TRANSPLANTATION n Indications: n Chronic active hepatitis n Extrahepatic biliary atresia n Primary biliary cirrhosis n Budd-Chiari syndrome (hepatic vein thrombosis) n Sclerosing cholangitis n Hepatocellular carcinoma

19. Organ Transplantation n LIVER TRANSPLANTATION n Primary organ disease problems n Excessive bleeding n Infection n Altered drug metabolism n Hypertension

21. Organ Transplantation n RENAL TRANSPLANTATION n ESRD management n Endocarditis, endarteritis n Same as other organ transplants n Aggessive prevention-treatment of infections n Viral infections( CMV, HBV,HCV, HIV)

23. Organ Transplantation n RENAL TRANSPLANTATION n Avoid certain drugs( acetaminophen, phenacetin, tetracycline, aminoglycosides, ASA, K+, PCN, Magnesium-antacids, etc.) n Laboratory tests: urinalysis( BUN, creatinine, protein, electrolytes)

24. Bone marrow transplantation n conditionsuccess rate n ALL20-25% n AML40-60% n CML60% n Aplastic anemia20-25% n Lymphoma25-40% n Neuroblastoma20-30%

25. Bone marrow transplantation n HISTOCOMPATABILITY n Autologousself30-50% n Allogeneicsibling15-25% n Syngeneicident. twin< 5% n Haploidenticalparent< 5% n Unrelatedany donor25-30%

26. Bone marrow transplantation n Stages: n Medical evaluation1 week n Histocompatibility matching1 day n BM procurement (iliac crest)1-2 weeks n Immunosuppressive Tx (TBI)1-2 weeks n Pancytopenic phase4-6 weeks n Immune recovery phase1 year n Long-term recovery1-4 years

27. Bone marrow transplantation n Three phases of immunosuppressive Tx n 1.) pre-transplant n Cyclophosphimide or methotrexate ± TBI ( single or fractionated) n 2.) transplant( pancytopenic phase) n 3.) cyclosporine, methotrexate, IFN-a to prevent GVHD

28. Bone marrow transplantation n Phases 2-3 pancytopenic phase n ANC<500: severe susceptibility to infection : 4-6 weeks post-transplant n Immunosuppression ( long-term) n Recurrence of leukemia n GVHD n encephalitis

30. Bone marrow transplantation n ORAL COMPLICATIONS n Peak 2-3 weeks post BMT n ( pancytopenic phase: ANC<500) n Mucositis, xerostomia, GVHD, viral infections (HSV,HIV), ELP-like, erythema, Candidiasis

34. Dental management of the Organ Transplant patient Dr. Nelson L. Rhodus Director of Oral Medicine University of Minnesota

35. Organ Transplantation n Before transplant n MEDICAL CONSULTATION n Establish patient status n primary organ failure-complications n Current treatment-drugs, etc. n Antibiotic prophylaxis

36. Organ Transplantation n LABORATORY TESTS n CBC n differential white count n platelets n PT, PTT, BT

37. Organ Transplantation n COMPLICATIONS n Over-immunosuppression n Side-effects of drugs n Rejection of transplant –Acute –Chronic

38. Organ Transplantation n DENTAL EVALUATION n Aggressive treatment prior to immunosuppression n Extract teeth with poor prognosis n Advanced perio, endo, questionable n Aggressive oral hygiene: maintenance

39. Organ Transplantation n IMMUNOSUPPRESSION n Prednisone n Aziothioprine(Immuran)33%* n Cyclosporine72%* n Antilymphocyte globulin (ALG)84%* n * 1 year survival rate

40. Organ Transplantation n IMMUNOSUPPRESSION n Infection n Delayed wound healing n Bleeding n Hypertension n Heart failure n Diabetes mellitus

41. Organ Transplantation n IMMUNOSUPPRESSION n Tumors ( lip cancer, lymphoma) n Adrenal crisis n Anemia n Osteoporosis n GI problems

42. Organ Transplantation n DENTAL MANAGEMENT n MEDICAL CONSULTATION n Minimize stress, short appointments n Monitor vitals ( HTN) n Infections( endocarditis, endarteritis) n Pneumonia, encephalitis n Aggessive prevention & Tx of infection

43. Organ Transplantation n DENTAL MANAGEMENT n Bleeding n GI problems n IMMUNOSUPPRESSION n Consider steroid supplementation n Personal Oral hygiene

44. Transplantation n ORAL COMPLICATIONS n Bleeding, infections, poor wound healing n Pain n Mucositis, ulcers, xerostomia, dysguesia, dysphagia

45. Organ Transplantation n Tumors n Lip carcinoma8-10% n Kaposi’s6-7 % n Lymphoma20 % n Kidney Ca 5 %

51. Organ Transplantation n IMMUNOSUPPRESSION n Minor complications n Gingival hyperplasia n Hirsutism n Gynecomastia n Depression

52. Organ Transplantation n Graft rejection n Heart- death, retransplant( unlikely) n Kidney- death, Hemodialysis, re-Tx n Pancreas- death, insulin, re-Tx

53. Organ Transplantation n IMMEDIATE POST-TRANSPLANT n No routine dental treatment ~ 6 mos. n POH n Emergency( conservative) treatment n MEDICAL CONSULTATION

54. Organ Transplantation n Stable graft period ( >6 months) n Most dental treatment can be performed with adequate management n OVER-IMMUNOSUPPRESSION n GVHD n HTN, BLEEDING, DRUGS, etc. n OTHER INFECTIONS

55. Organ Transplantation n CHRONIC REJECTION PERIOD n No routine dental treatment n POH n Emergency( conservative) treatment n MEDICAL CONSULTATION

56. Organ Transplantation n Salivary gland dysfunction n Very aggressive oral hygiene program n POH: plaque control : toothbrushing, flossing, fluorides n Dietary counseling n Perio treatment n Chlorohexidine gluconate