1. Innovations in Transplantation: Single-Port Donor Nephrectomy for Living-Donor Kidney Transplantation Face 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 Disease 2000 - 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 Extraction Minimizes apparent length of incision

9. BMI 30 Healing POD 0POD 15POD 22

10. 6 Months Post-Op

11. 2 Years Post-Op

12. Anatomical Variants 2 Arteries Lumbar Vein

13. Donor DemographicsSILS(n=135)Multiport (n=100)p Age (yrs)44±1343±110.38 Gender (F)73.1%71.0%0.40 Race (Non AA)81.5%81.0%0.53 BMI27±428±40.19 Renal Arteries1.3±0.61.2±0.50.06 Renal Veins1.0±0.2 0.88 Lumbar Veins1.0±0.81.0±1.30.98 Donor Surgical OutcomesSILS(n=135)Multiport (n=100)p Cross Clamp Time (hrs)2.8±0.72.6±0.50.12 Estimated Blood loss (ml)77±64107±1220.019 Length of stay (days)2.6±0.92.3±0.70.009 Recipient Renal FunctionSILS(n=135)Multiport (n=100)p Recipient Post TX eGFR 1 week59±1955±190.23 Recipient Post TX eGFR 1 month60±1852±160.003 Single vs. Multi-port

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

15. Donor SF-36 ResultsSILS(n=52)Multiport (n=39)p Physical Health (Composite)88.3±10.885.8±15.50.36 Mental Health (Composite)85.1±14.184.3±14.10.78 TOTAL SF36 Score88.8±12.187.1±14.10.54 Donor Pain Levels Night of Surgery6.0±2.86.1±2.80.85 Post Op 15.5±2.65.3±2.70.73 Day of Discharge4.1±2.3 0.93 Post Op 72.6±2.02.7±2.40.84 Post Op 300.8±1.21.0±1.60.40 Current0.0±0.10.2±0.70.10 Donor Satisfication Results Donation Decision9.9±0.59.4±1.90.07 Financial Burden8.8±2.19.5±1.60.10 Stress Level7.7±2.57.5±3.10.68 Cosmetic Outcome9.2±1.77.4±2.9<0.0001 Overall Process9.4±1.28.4±2.40.01 Donor Recovery Period Walked Without Difficulty2.4±1.32.6±1.30.52 Ate a Normal Diet2.3±1.42.2±1.30.71 Stopped Pain Medication2.9±1.22.7±1.30.46 Resumed Driving4.0±1.04.0±0.90.92 Resumed Normal Activities4.6±0.8 0.94 Re-Hospitalized due to donation4.40%3.30%0.65 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. Donor Recipient Tumor = 87% Donor Barth et al, Trans. 2009, 88: 1242 Prolonged Survival of Composite Facial Allografts in Non-Human Primates Associated With Posttransplant Lymphoproliferative Disorder

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

24. MRI of Vascularized Bone Marrow Histology of Vascularized Bone Marrow

25. Facial CTA Summary Group Number Immuno- suppression Bone & VBM Mean FK506 Level (± SD) Mean Survival (days) End Point Chimerism Detected Acute Rejection Chronic Rejection Notch Pathway Expression 1 High FK506 (n=6) Yes45 ± 21116PTLDNo 2 High FK506  Rapamycin (n=3) Yes40 ± 2380RejectionNoYesNo 3 Low FK506/ MMF (n=4) Yes25 ± 13310RejectionYes (3/4)Yes 4 Low FK506/ MMF (n=3) No25 ± 12112RejectionYes (1/3)YesNo 5 Low FK506/Anti- CD28 (n= 3) Yes 28 ± 12 101RejectionNoYesNo

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

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. 200920102011 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 Craniofacial Composite Tissue Allotransplantation

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 Tx Int 19 (2006): 885-892

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

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