Rolf N. Barth, M.D. Department of Surgery University of Maryland School of Medicine

1. Innovations in Transplantation:Single-Port Donor Nephrectomy for Living-Donor Kidney TransplantationFace Transplantation: Preclinical and Clinical Trials Rolf N. Barth, M.D. Department of Surgery University of Maryland School of Medicine AHRQ 2011 Annual Conference September 19, 2011

2. Single-Port Donor Nephrectomy for Living-Donor Kidney Transplantation

3. Renal Transplantation as Therapy for End Stage Renal Disease2000 - 2009 The Organ Procurement and Transplantation Network (OPTN). www.optn.org. 2009.

4. Rationale for Single-Port Donor Nephrectomy Program Advanced laparoscopic approach achieved with existing instrumentation and techniques Improved cosmetic appearance Potential for improved post-operative recovery Motivate recipient/donor combinations Encourage living kidney donation

5. University of Maryland Experience • Performed 1300 laparoscopic donor nephrectomies • Preparation for single-port • Minimized ports on standard donor • Observed procedures • Animal lab • April 2009 initiated single-port donor nephrectomy as routine approach • Currently performed over 140 single-port donor nephrectomies

6. Access Devices SILS Port Device (Covidien) Gelport/Gelpoint Device (Applied Medical)

8. Transumbilical Renal ExtractionMinimizes apparent length of incision

9. BMI 30 Healing POD 0 POD 15 POD 22

10. 6 Months Post-Op

11. 2 Years Post-Op

12. Anatomical Variants 2 Arteries Lumbar Vein 2 Arteries

13. Single vs. Multi-port

14. Operative Time Learning Curve Single Port Donor Nephrectomy Trendline Average Multiple Port Donor Nephrectomy (2.6 hr)

15. SF=36 and Survey Responses

16. Conclusions • Single port donor nephrectromy is safe and may be accomplished in broad spectrum of donors with experienced team. • Patients report improved satisfaction with cosmesis and donation process with single port compared to multiple port technique. • No definite evidence regarding recovery time or pain. • Further investigation of implications: • Willingness of recipients to ask potential donors • Additional kidney donors to alleviate organ shortage

17. Face Transplantation: Preclinical and Clinical Trials

18. Incidence of Facial Trauma • Incidence of facial injury among soldiers in Iraq=30% (Colonel Mark Bagg MD, ASRM, Arizona, January 2006) • Incidence of facial injury at University of Maryland Shock Trauma Center= 15% (unreported data: ~ 7,000-10,000 admissions per year)

20. Vascularized Composite Allograft (VCA) Composite tissue defined to elements of skin, muscle, bone Applications include: Limb transplantation Transplantation for soft tissue defects Facial transplantation for devastating burn/blast injuries Results are life-saving, limb-saving, allow for avoidance of permanent disability

21. Barth et al, Plast. Reconstr. Surg. 123: 493, 2009.

22. Prolonged Survival of Composite Facial Allografts in Non-Human Primates Associated With PosttransplantLymphoproliferative Disorder Donor Recipient Tumor= 87% Donor Barth et al, Trans. 2009, 88: 1242

23. Vascularized Bone Marrow-Based Immunosuppression Inhibits Rejection of Vascularized Composite Allografts in Nonhuman Primates

24. Vascularized Bone Marrow-Based Immunosuppression Inhibits Rejection of Vascularized Composite Allografts in Nonhuman Primates MRI of Vascularized Bone Marrow Histology of Vascularized Bone Marrow

25. Facial CTA Summary

26. Non-Human Primate Model of Fibula Vascularized Composite Tissue Allotransplantation Demonstrates Donor-recipient Bony Union Plastic Reconstructive Surgery, 2011

27. Clinical CTA Strategies • Co-transplanted vascularized bone marrow may be permissive towards the development of prolonged graft survival. • CTA were rejected at early timepoints without calcineurin-based immunosuppression. • ‘Prope’ tolerance or minimal immunosuppression are the most attainable goals for widespread application of clinical CTA.

28. Craniofacial Composite Tissue Allotransplantation 2009 2010 2011 2012 Phase 1 (Active): Research and Preclinical Model Phase 2 (Active): Clinical program development: IRB approved, DOD approval Phase 3 (Active): Active Clinical Center: Patient Listed for Transplant

29. Minimizing Chronic Immunosuppression • Lymphocyte-depleting induction therapies • Lowest rates of acute cellular rejection • Steroid Avoidance or Weaning • Nearly all kidney, pancreas, and liver transplant patients have steroids eliminated between 3 and 21 days • Permissive of chronic therapy with 1 or 2 drugs • Future – costimulatory blockade reagents requiring once monthly treatment

30. Immunosuppression Induction Humanized CAMPATH Antibody (Alemtuzumab) CD4 T cells depleted 99.7% 2 wks, 85% at 1 year, 69% at 2 years, and 63% at 3 years TxInt 19 (2006): 885-892

31. CTA Immunosuppressive Regimen Day 0 C1H POD 21 Tacrolimus MMF Prednisone

32. Instruments Multi-Organ Recovery Team Scrub Nurse Thoracic Team Abdominal Team CTA Team Mayo Stand CTA Team Thoracic Team Abdominal Team Anesthesia - Tracheostomy & Circuit