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 MedicineAHRQ 2011 Annual Conference

September 19, 2011

Single-Port Donor Nephrectomy for Living-Donor Kidney Transplantation

Renal Transplantation as Therapy for End Stage Renal Disease

2000 - 2009

The Organ Procurement and Transplantation Network (OPTN). www.optn.org. 2009.

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

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

Access DevicesSILS Port Device

(Covidien)

Gelport/Gelpoint Device (Applied Medical)

Transumbilical Renal ExtractionMinimizes apparent length of incision

BMI 30 HealingPOD 0 POD 15 POD 22

6 Months Post-Op

2 Years Post-Op

Anatomical Variants2 Arteries 2 Arteries Lumbar Vein

Donor Demographics SILS(n=135) Multiport (n=100) pAge (yrs) 44±13 43±11 0.38Gender (F) 73.1% 71.0% 0.40Race (Non AA) 81.5% 81.0% 0.53BMI 27±4 28±4 0.19Renal Arteries 1.3±0.6 1.2±0.5 0.06Renal Veins 1.0±0.2 1.0±0.2 0.88Lumbar Veins 1.0±0.8 1.0±1.3 0.98       

Donor Surgical Outcomes SILS(n=135) Multiport (n=100) pCross Clamp Time (hrs) 2.8±0.7 2.6±0.5 0.12Estimated Blood loss (ml) 77±64 107±122 0.019Length of stay (days) 2.6±0.9 2.3±0.7 0.009       

Recipient Renal Function SILS(n=135) Multiport (n=100) pRecipient Post TX eGFR 1 week 59±19 55±19 0.23Recipient Post TX eGFR 1 month 60±18 52±16 0.003

Single vs. Multi-port

Operative Time Learning Curve

Average Multiple Port Donor Nephrectomy (2.6 hr)

Single Port Donor Nephrectomy Trendline

Donor SF-36 Results SILS(n=52) Multiport (n=39) pPhysical Health (Composite) 88.3±10.8 85.8±15.5 0.36Mental Health (Composite) 85.1±14.1 84.3±14.1 0.78TOTAL SF36 Score 88.8±12.1 87.1±14.1 0.54

Donor Pain LevelsNight of Surgery 6.0±2.8 6.1±2.8 0.85Post Op 1 5.5±2.6 5.3±2.7 0.73Day of Discharge 4.1±2.3 4.1±2.3 0.93Post Op 7 2.6±2.0 2.7±2.4 0.84Post Op 30 0.8±1.2 1.0±1.6 0.40Current 0.0±0.1 0.2±0.7 0.10

Donor Satisfication ResultsDonation Decision 9.9±0.5 9.4±1.9 0.07 Financial Burden 8.8±2.1 9.5±1.6 0.10Stress Level 7.7±2.5 7.5±3.1 0.68Cosmetic Outcome 9.2±1.7 7.4±2.9 <0.0001Overall Process 9.4±1.2 8.4±2.4 0.01

Donor Recovery PeriodWalked Without Difficulty 2.4±1.3 2.6±1.3 0.52Ate a Normal Diet 2.3±1.4 2.2±1.3 0.71Stopped Pain Medication 2.9±1.2 2.7±1.3 0.46Resumed Driving 4.0±1.0 4.0±0.9 0.92Resumed Normal Activities 4.6±0.8 4.6±0.8 0.94Re-Hospitalized due to donation 4.40% 3.30% 0.65

SF=36 and Survey Responses

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

Face Transplantation: Preclinical and Clinical Trials

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)

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

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

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

Vascularized Bone Marrow-Based Immunosuppression Inhibits Rejection of Vascularized Composite Allografts in

Nonhuman Primates

Vascularized Bone Marrow-Based Immunosuppression Inhibits Rejection of Vascularized Composite Allografts in

Nonhuman PrimatesMRI of Vascularized

Bone MarrowHistology of Vascularized

Bone Marrow

Facial CTA SummaryGroup Number

Immuno-suppression

Bone & VBM

Mean FK506Level (± SD)

Mean Survival(days)

End Point ChimerismDetected

Acute Rejection

Chronic Rejection

Notch Pathway

Expression

1 High FK506(n=6) Yes 45 ± 21 116 PTLD No No No No

2High FK506

Rapamycin(n=3)

Yes 40 ± 23 80 Rejection No Yes No No

3Low FK506/

MMF(n=4)

Yes 25 ± 13 310 Rejection Yes (3/4) Yes Yes Yes

4Low FK506/

MMF(n=3)

No 25 ± 12 112 Rejection Yes (1/3) Yes No No

5Low

FK506/Anti-CD28 (n= 3)

Yes 28 ± 12 101 Rejection No Yes No No

Plastic Reconstructive Surgery, 2011

Non-Human Primate Model of Fibula Vascularized Composite Tissue Allotransplantation

Demonstrates Donor-recipient Bony Union

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.

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

Craniofacial Composite Tissue Allotransplantation

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

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

CTA Immunosuppressive Regimen

Tacrolimus

POD 21

Day 0C1H

PrednisoneMMF

CTATeam

CTATeam

ThoracicTeam

ThoracicTeam

AbdominalTeam

AbdominalTeam

Anesthesia -Tracheostomy

& Circuit

ScrubNurse

Instruments

MayoStand

Multi-Organ Recovery Team