Innovations in Transplantation (Text Version)

Slide presentation from the AHRQ 2011 conference.

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

Slide 1. Innovations in Transplantation:  Single-Port Donor Nephrectomy for Living-Donor  Kidney Transplantation  Face Transplantation: Preclinical and Clinical Trials

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

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

Single-Port Donor Nephrectomy for Living-Donor Kidney Transplantation

Slide 3

Slide 3. Renal Transplantation as Therapy for End Stage Renal Disease 2000-2009

Renal Transplantation as Therapy for End Stage Renal Disease 2000-2009

Image: Line graph displays the following data:

YearKidney WaitlistDeceased DonorLiving Donor
200050,4265,9855,941
200153,5606,0806,616
200256,5206,1906,630
200359,6886,4576,828
200464,3107,1507,004
200568,4297,5936,902
200673,4698,0196,732
200778,3378,0856,315
200883,1127,9906,218
200988,5038,0226,610

 

Slide 4

Slide 4. Rationale for Single-Port Donor Nephrectomy Program

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

Slide 5. University of Maryland Experience

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

Slide 6. Access Devices

Access Devices

  • SILS Port Device (Covidien).
  • Gelport/Gelpoint Device (Applied Medical).

Images: The SILS Port Device and Gelport/Gelpoint Device are shown.

Slide 7

Slide 7. Images: The SILS Port Device and Gelport/Gelpoint Device are shown.

Image: An operating room is shown.

Slide 8

Slide 8. Transumbilical Renal Extraction Minimizes Apparent Length of Incision

Transumbilical Renal Extraction Minimizes Apparent Length of Incision

Images: Photographs of the incision site are shown.

Slide 9

Slide 9. BMI 30 Healing

BMI 30 Healing

Images: Photographs of the incision site on Postoperative Day (POD) 0, POD 15, and POD 22 are shown.

Slide 10

Slide 10. 6 Months Post-Op

6 Months Post-Op

Image: A photograph of the incision site 6 months after the surgery is shown.

Slide 11

Slide 11. 2 Years Post-Op

2 Years Post-Op

Image: A photograph of the incision site 2 years after the surgery is shown.

Slide 12

Slide 12. Anatomical Variants

Anatomical Variants

Images: Three MRI image variants are shown: 2 arteries, 2 arteries, and lumbar vein.

Slide 13

Slide 13. Single vs. Multi-port

Single vs. Multi-port

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±0.21.0±0.20.88
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

 

Slide 14

Slide 14. Operative Time Learning Curve

Operative Time Learning Curve

Image: A graph labeled Operative Time Learning Curve is shown.

Slide 15

Slide 15. SF=36 and Survey Responses

SF=36 and Survey Responses

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 LevelsSILS (n=52)Multiport (n=39)p
Night of Surgery6.0±2.86.1±2.80.85
Post Op 15.5±2.65.3±2.70.73
Day of Discharge4.1±2.34.1±2.30.93
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 ResultsSILS (n=52)Multiport (n=39)p
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 PeriodSILS (n=52)Multiport (n=39)p
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±0.84.6±0.80.94
Re-Hospitalized due to donation4.40%3.30%0.65

 

Slide 16

Slide 16. Conclusions

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

Slide 17. Face Transplantation: Preclinical and Clinical Trials

Face Transplantation: Preclinical and Clinical Trials

Slide 18

Slide 18. Incidence of Facial Trauma

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

Slide 19. Images: Photographs of six patients with facial trauma are shown.

Images: Photographs of six patients with facial trauma are shown.

Slide 20

Slide 20. Vascularized Composite Allograft (VCA)

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

Slide 21. 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.

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

Slide 22. Prolonged Survival of Composite Facial Allografts in Non-Human Primates Associated with Posttransplant Lymphoproliferative Disorder

Prolonged Survival of Composite Facial Allografts in Non-Human Primates Associated with Posttransplant Lymphoproliferative Disorder

Image: Photographs and 3 graphs are shown.

Slide 23

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

Vascularized Bone Marrow-Based Immunosuppresion Inhibits Rejection of Vascularized Composite Allografts in Nonhuman Primates

Image: 3 graphs are shown.

Slide 24

Slide 24. Vascularized Bone Marrow-Based Immunosuppresion Inhibits Rejection of Vascularized Composite Allografts in Nonhuman Primates

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

Slide 25. Facial CTA Summary

Facial CTA Summary

Group NumberImmuno-suppressionBone & VBMMean FK506Level (± SD)Mean Survival(days)End PointChimerismDetectedAcute RejectionChronic RejectionNotch Pathway Expression
1High FK506
(n=6)
Yes45 ± 21116PTLDNoNoNoNo
2High FK506 à Rapamycin
(n=3)
Yes40 ± 2380RejectionNoYesNoNo
3Low FK506/ MMF
(n=4)
Yes25 ± 13310RejectionYes (3/4)YesYesYes
4Low FK506/ MMF
(n=3)
No25 ± 12112RejectionYes (1/3)YesNoNo
5Low FK506/Anti-CD28
(n= 3)
Yes28 ± 12101RejectionNoYesNoNo

 

Slide 26

Slide 26. Non-Human Primate Model of Fibula Vascularized Composite Tissue Allotransplantation Demonstrates Donor-recipient Bony Union

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

Slide 27. Clinical CTA Strategies

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

Slide 28. Craniofacial Composite Tissue Allotransplantation

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

Slide 29. Minimizing Chronic Immunosuppression

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

Slide 30. Immunosuppression Induction

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

Slide 31. CTA Immunosuppressive Regimen

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

Slide 32. Multi-Organ Recovery Team

Multi-Organ Recovery Team

Image: Chart shows the positions of the recovery team and equipment around the operating table.

Page last reviewed March 2012
Internet Citation: Innovations in Transplantation (Text Version). March 2012. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/news/events/conference/2011/barth/index.html