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

2 Organ TransplantationBone Marrow ( stem cell) Solid organs Heart Lung Liver Kidney Pancreas Small intestine

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

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

5 Organ TransplantationLiver transplants First liver transplant in 1967 >90,000 liver transplants > 8,000 liver transplants per year 1-year survival rate >90% ( 5 yr. ~70%)

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

7 Organ TransplantationHeart - lung transplants ~ 800 performed as of 2000 1 year survival ~ 60 %

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

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

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

11 Organ TransplantationHEART TRANSPLANTS Good renal and hepatic function No infections No diabetes Family support

12 Organ TransplantationHEART TRANSPLANTS Causes of death: Infection 40% Acute graft rejection 25% Chronic graft rejection 10 % Cardiac disease 25%

13 Organ TransplantationHEART TRANSPLANTS Endocarditis prevention Pacemakers-arrhythmias Medications- drugs Avoid epinephrine Anticoagulation

14 Organ TransplantationHEART TRANSPLANTS Immunosuppression Adrenal suppression Bleeding Infection (IE)

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

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

17 Heart - lung transplantsfirst 1981 ( now~800 performed) per year

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

19 Organ TransplantationLIVER TRANSPLANTATION Primary organ disease problems Excessive bleeding Infection Altered drug metabolism Hypertension

20 Liver- small bowel transplant

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

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

24 Bone marrow transplantationcondition success rate ALL % AML % CML 60% Aplastic anemia % Lymphoma % Neuroblastoma %

25 Bone marrow transplantationHISTOCOMPATABILITY Autologous self % Allogeneic sibling % Syngeneic ident. twin < 5% Haploidentical parent < 5% Unrelated any donor %

26 Bone marrow transplantationStages: Medical evaluation 1 week Histocompatibility matching 1 day BM procurement (iliac crest) 1-2 weeks Immunosuppressive Tx (TBI)1-2 weeks Pancytopenic phase 4-6 weeks Immune recovery phase 1 year Long-term recovery 1-4 years

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

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

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

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

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

36 Organ TransplantationLABORATORY TESTS CBC differential white count platelets PT, PTT, BT

37 Organ TransplantationCOMPLICATIONS Over-immunosuppression Side-effects of drugs Rejection of transplant Acute Chronic

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

39 Organ TransplantationIMMUNOSUPPRESSION Prednisone Aziothioprine(Immuran) 33%* Cyclosporine %* Antilymphocyte globulin (ALG) 84%* * 1 year survival rate

40 Organ TransplantationIMMUNOSUPPRESSION Infection Delayed wound healing Bleeding Hypertension Heart failure Diabetes mellitus

41 Organ TransplantationIMMUNOSUPPRESSION Tumors ( lip cancer, lymphoma) Adrenal crisis Anemia Osteoporosis GI problems

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

43 Organ TransplantationDENTAL MANAGEMENT Bleeding GI problems IMMUNOSUPPRESSION Consider steroid supplementation Personal Oral hygiene

44 Transplantation ORAL COMPLICATIONSBleeding, infections, poor wound healing Pain Mucositis, ulcers, xerostomia, dysguesia, dysphagia

45 Organ TransplantationTumors Lip carcinoma 8-10% Kaposi’s 6-7 % Lymphoma 20 % Kidney Ca 5 %

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51 Organ TransplantationIMMUNOSUPPRESSION Minor complications Gingival hyperplasia Hirsutism Gynecomastia Depression

52 Organ TransplantationGraft rejection Heart- death, retransplant( unlikely) Kidney- death, Hemodialysis, re-Tx Pancreas- death, insulin, re-Tx

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

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

55 Organ TransplantationCHRONIC REJECTION PERIOD No routine dental treatment POH Emergency( conservative) treatment MEDICAL CONSULTATION

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