Innovations in Transplantation (Text Version)
On September 19, 2011, Rolf Barth made this presentation at the 2011 Annual Conference. Select to access the PowerPoint® presentation (10.3 MB). Plugin Software Help.
Slide 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
Slide 2
Single-Port Donor Nephrectomy for Living-Donor Kidney Transplantation
Slide 3
Renal Transplantation as Therapy for End Stage Renal Disease 2000-2009
Image: Line graph displays the following data:
| Year | Kidney Waitlist | Deceased Donor | Living Donor |
|---|---|---|---|
| 2000 | 50,426 | 5,985 | 5,941 |
| 2001 | 53,560 | 6,080 | 6,616 |
| 2002 | 56,520 | 6,190 | 6,630 |
| 2003 | 59,688 | 6,457 | 6,828 |
| 2004 | 64,310 | 7,150 | 7,004 |
| 2005 | 68,429 | 7,593 | 6,902 |
| 2006 | 73,469 | 8,019 | 6,732 |
| 2007 | 78,337 | 8,085 | 6,315 |
| 2008 | 83,112 | 7,990 | 6,218 |
| 2009 | 88,503 | 8,022 | 6,610 |
Slide 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.
Slide 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.
Slide 6
Access Devices
- SILS Port Device (Covidien).
- Gelport/Gelpoint Device (Applied Medical).
Images: The SILS Port Device and Gelport/Gelpoint Device are shown.
Slide 7
Image: An operating room is shown.
Slide 8
Transumbilical Renal Extraction Minimizes Apparent Length of Incision
Images: Photographs of the incision site are shown.
Slide 9
BMI 30 Healing
Images: Photographs of the incision site on Postoperative Day (POD) 0, POD 15, and POD 22 are shown.
Slide 10
6 Months Post-Op
Image: A photograph of the incision site 6 months after the surgery is shown.
Slide 11
2 Years Post-Op
Image: A photograph of the incision site 2 years after the surgery is shown.
Slide 12
Anatomical Variants
Images: Three MRI image variants are shown: 2 arteries, 2 arteries, and lumbar vein.
Slide 13
Single vs. Multi-port
| Donor Demographics | SILS (n=135) | Multiport (n=100) | p |
|---|---|---|---|
| Age (yrs) | 44±13 | 43±11 | 0.38 |
| Gender (F) | 73.1% | 71.0% | 0.40 |
| Race (Non AA) | 81.5% | 81.0% | 0.53 |
| BMI | 27±4 | 28±4 | 0.19 |
| Renal Arteries | 1.3±0.6 | 1.2±0.5 | 0.06 |
| Renal Veins | 1.0±0.2 | 1.0±0.2 | 0.88 |
| Lumbar Veins | 1.0±0.8 | 1.0±1.3 | 0.98 |
| Donor Surgical Outcomes | SILS (n=135) | Multiport (n=100) | p |
|---|---|---|---|
| Cross Clamp Time (hrs) | 2.8±0.7 | 2.6±0.5 | 0.12 |
| Estimated Blood loss (ml) | 77±64 | 107±122 | 0.019 |
| Length of stay (days) | 2.6±0.9 | 2.3±0.7 | 0.009 |
| Recipient Renal Function | SILS (n=135) | Multiport (n=100) | p |
|---|---|---|---|
| Recipient Post TX eGFR 1 week | 59±19 | 55±19 | 0.23 |
| Recipient Post TX eGFR 1 month | 60±18 | 52±16 | 0.003 |
Slide 14
Operative Time Learning Curve
Image: A graph labeled Operative Time Learning Curve is shown.
Slide 15
SF=36 and Survey Responses
| Donor SF-36 Results | SILS (n=52) | Multiport (n=39) | p |
|---|---|---|---|
| Physical Health (Composite) | 88.3±10.8 | 85.8±15.5 | 0.36 |
| Mental Health (Composite) | 85.1±14.1 | 84.3±14.1 | 0.78 |
| TOTAL SF36 Score | 88.8±12.1 | 87.1±14.1 | 0.54 |
| Donor Pain Levels | SILS (n=52) | Multiport (n=39) | p |
|---|---|---|---|
| Night of Surgery | 6.0±2.8 | 6.1±2.8 | 0.85 |
| Post Op 1 | 5.5±2.6 | 5.3±2.7 | 0.73 |
| Day of Discharge | 4.1±2.3 | 4.1±2.3 | 0.93 |
| Post Op 7 | 2.6±2.0 | 2.7±2.4 | 0.84 |
| Post Op 30 | 0.8±1.2 | 1.0±1.6 | 0.40 |
| Current | 0.0±0.1 | 0.2±0.7 | 0.10 |
| Donor Satisfication Results | SILS (n=52) | Multiport (n=39) | p |
|---|---|---|---|
| Donation Decision | 9.9±0.5 | 9.4±1.9 | 0.07 |
| Financial Burden | 8.8±2.1 | 9.5±1.6 | 0.10 |
| Stress Level | 7.7±2.5 | 7.5±3.1 | 0.68 |
| Cosmetic Outcome | 9.2±1.7 | 7.4±2.9 | <0.0001 |
| Overall Process | 9.4±1.2 | 8.4±2.4 | 0.01 |
| Donor Recovery Period | SILS (n=52) | Multiport (n=39) | p |
|---|---|---|---|
| Walked Without Difficulty | 2.4±1.3 | 2.6±1.3 | 0.52 |
| Ate a Normal Diet | 2.3±1.4 | 2.2±1.3 | 0.71 |
| Stopped Pain Medication | 2.9±1.2 | 2.7±1.3 | 0.46 |
| Resumed Driving | 4.0±1.0 | 4.0±0.9 | 0.92 |
| Resumed Normal Activities | 4.6±0.8 | 4.6±0.8 | 0.94 |
| Re-Hospitalized due to donation | 4.40% | 3.30% | 0.65 |
Slide 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.
Slide 17
Face Transplantation: Preclinical and Clinical Trials
Slide 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).
Slide 19
Images: Photographs of six patients with facial trauma are shown.
Slide 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.
Slide 21
Experimental
Image: Figures from Barth et al, Plast Reconstr Surg 123:493, 2009, captioned "Facial Subunit Composite Tissue Allografts in Nonhuman Primates: I. Technical and Immunosuppressive Requirements for Prolonged Graft Survival," are shown.
Slide 22
Prolonged Survival of Composite Facial Allografts in Non-Human Primates Associated with Posttransplant Lymphoproliferative Disorder
Image: Photographs and 3 graphs are shown.
Slide 23
Vascularized Bone Marrow-Based Immunosuppresion Inhibits Rejection of Vascularized Composite Allografts in Nonhuman Primates
Image: 3 graphs are shown.
Slide 24
Vascularized Bone Marrow-Based Immunosuppresion Inhibits Rejection of Vascularized Composite Allografts in Nonhuman Primates
- MRI of Vascularized Bone Marrow.
- Histology of Vascularized Bone Marrow.
Images: Photographs of vascularized bone marrow are shown.
Slide 25
Facial CTA Summary
| Group 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 |
| 2 | High FK506 à Rapamycin (n=3) |
Yes | 40 ± 23 | 80 | Rejection | No | Yes | No | No |
| 3 | Low FK506/ MMF (n=4) |
Yes | 25 ± 13 | 310 | Rejection | Yes (3/4) | Yes | Yes | Yes |
| 4 | Low FK506/ MMF (n=3) |
No | 25 ± 12 | 112 | Rejection | Yes (1/3) | Yes | No | No |
| 5 | Low FK506/Anti-CD28 (n= 3) |
Yes | 28 ± 12 | 101 | Rejection | No | Yes | No | No |
Slide 26
Non-Human Primate Model of Fibula Vascularized Composite Tissue Allotransplantation Demonstrates Donor-recipient Bony Union
Images: Illustrations and photographs of non-human primate bones.
Slide 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.
Slide 28
Craniofacial Composite Tissue Allotransplantation
Image: Timeline shows 3 phases from 2009 to 2012: research and preclinical model, clinical programs development, and active clinical center.
Slide 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.
Slide 30
Immunosuppression Induction
Images: Illustration of antibody and line graph of induction and graft survival are shown.
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
Slide 31
CTA Immunosuppressive Regimen
Image: Chart shows the immunosuppressive regimen from Day 0 onward. Prednisone is given until POD 21; Tacrolimus and MMF continue to the end of the chart.
Slide 32
Multi-Organ Recovery Team
Image: Chart shows the positions of the recovery team and equipment around the operating table.
