1. New Strategies in Split Liver Transplantation R. Mark Ghobrial M.D., Ph.D. Professor of Surgery Division of Liver and Pancreas Transplantation The Dumont-UCLA Transplant Center David Geffen School of Medicine at UCLA

2. Reduced-sized orthotopic liver graft in hepatic transplantation in children H. Bismuth, M.D., and D. Houssin, M.D., Villejuif, France Because of the rarity of child donors, in cases of adult donors room requirement for the liver graft is a major technical obstacle to liver transplantation in children. To overcome this difficulty in a child, the authors performed an orthotopic transplantation with an adult liver that had been reduced to the left lobe. The absence of technically-related complications suggests that this procedure might facilitate the performance of liver transplantation in children. From the Unite de Chirurgie hepato-biliaire and Groupe de Recherche de chirurgie hepatique INSERM U17, Hopital Paul Brousse, Villejuif, France Surgery 1984

3. Transplantation einer spenderbeber auf zwei empfanger(splitting-transplantation): eine neue methode in der weiterentwicklung der lebersegment transplantation. Pichlmayr R, Ringe B, Gubernatis G. Klinik fur Abdominal- und Transplantationschirurgie der Medizinischen Hochschule Hannover, Kostanty-Gutschow- StraBe 8, D-3000 Hannover 61 Langenbecks Arch Chir 1988

4. First attempt by Pichlmayr et al., 1988 Second split performed by Bismuth et al., 1989 First series by Broelsch et al., 1990 SLT in Europe, De Ville De Goyet, 1995 In situ modification of ex situ, Rogiers 1995 Kings College Experience, Rela 1998 Progress of Split Liver Transplantation

5. Outcomes of Conventional Split Liver Transplantation AuthorYearTechniqueNPt Sr %Gt Sr % Reyes2000Ex / In situ548572 Spada2000In situ398476 Ghobrial2000In situ11079- Kilic2001In situ2410096 Sauer2001-369387 Deshpande*2002Ex situ809490 Girdelli*2003In situ909183 Yersiz2003In situ1637868 Broering2004Ex / In situ2458375 * Pediatric

6. Split Versus LDLT in the U.S. LD SLT Merion RM, Am J Transpl 2004

7. 1.00 1.47 1.59 0.5 1.0 1.5 2.0 Whole Cadaveric Partial/Split Cadaveric Living REF * P <0.05 * * Adjusted Relative Risk of Graft Failure for Living Donor Recipients UNOS - 1998-2001 (N=16,595) Adjusted for recipient age, race, ethnicity, sex, and diagnosis; donor age, race, and sex; recipient medical urgency status, creatinine, bilirubin, medical condition, on life support, on dialysis, on ventilator, and NYHA functional status at transplant; ABO compatibility

8. 0 12 24 20 40 60 80 100 20 40 60 80 100 pediatric SLT - 3.7 pediatric wait list adult whole - 5.8* adult wait list Merion RM et al, Am J Transpl 2004 Predicted Lifetimes After SLT adult SLT - 5.2 * months/first 2 years post-transplant

9. Rising demands for liver organs and increased wait list deaths Overcomes concerns of living donor safety Increases the total number of grafts Prolongs lifetimes of SLT recipients Adult to Adult Split Liver Transplantation Rationale

10. Adult to Adult Split Liver Transplantation Outcomes and predictors donor and recipient matching Techniques Technical challenges

11. ANNALS OF SURGERY Vol. 224, No. 6, 737-748 1996 Lippincott-Raven Publishers Split-Liver Transplantation The Paul Brousse Policy Daniel Azoulay, M.D., Ibrahim Astarcioglu, M.D., Henri Bismuth, M.D., F.A.C.S. (Hon), Denis Castaing, M.D., Pietro Majno, M.D., F.R.C.S., Rene Adam, M.D., and Marc Johann, M.D. From the Hepatobiliary Surgery and Liver Transplant Center, Hopital Paul Brousse, Universite Paris Sud, Villejuif, France

12. Adult to Adult Split Liver Transplantation CharacteristicRL Recip (17)LL Recip (17)P Recip Wt (kg)72 (35-97)50 (40-83)0.003 Donor/Recip WR1.06 (0.8-2.2)1.55 (1.1-2.1)0.02 GRWR1.6 (1-3.3)1.0 (0.7-1.7)0.004 CIT (min)678515NS Pt Srv (1 yr)74%87%NS Gft Srv (1 yr)74%75%NS Azoulay D, et al Ann Surg 2001

13. Adult to Adult Split Liver Transplantation ComplicationsRLGLLGP PNF030.07 Bleeding10NS HAT2NS PVT02NS Biliary34NS Venous outflow00NS Azoulay D, et al Ann Surg 2001

14. Factors Affecting Survival After ASLT Azoulay D, et al Ann Surg 2001 Univariately recipient status graft steatosis, donor GGT GRWR <1% ICU and hospital stay Multivariately recipient status graft steatosis ICU and hospital stay

15. Adult to Adult Split Liver Transplantation Humar A, et al Am J Transpl 2001 CharacteristicRL Recip (6)LL Recip (6) Donor age (yrs)19.7 Donor weight (kg)8979 Recip age4637 Recip weight8960 GRWR0.88%0.86% UNIOS status2B Pt and Grft Sr83.3%

16. Adult-to-Adult Split Liver Transplantation YearAuthorN%Pt %Grft %Compl 2002Zamir683%83%N/A 2002Goss8100%100%N/A 2001Humar1283%83%58% 2001Azoulay3481%75%24% 2001Broering1293%85%N/A 2001Andorno10100%80%N/A 2001Colledan 887%63%75% 2000Gundlach4100%100%N/A Published or Presented Series

17. Adult to Adult Split Liver Transplantation Outcomes and predictors donor and recipient matching Techniques in situ ex situ Technical challenges

18. IVC IRHV RHV

19. Right hepatic duct division by sharp dissection RHA CBD

20. RHA CBD RPV

22. RHA RPV CBD RL

23. In Situ Splitting of the Liver V-VIII I-IV celiac CBD MPV Humar A, et al. Liver Transpl 2002

24. In Situ Splitting of the Liver Sommacale, et al. Transplantation 2002

25. Ex Situ Splitting of the Liver Back bench cholangiography and arteriography Hilar dissection: Celiac axis to left graft portal trunk usually to left Main bile duct to right side Parenchymal transection straight along middle of segment IV MHV usually to right side Management of cut surface of liver Azoulay D, et al. Arch Surg 2001

26. Alternative Cutting Lines in Ex Situ Splitting celiac axis portal trunk IVC CBD MHV

27. Adult to Adult Split Liver Transplantation Outcomes and predictors donor and recipient matching Techniques Technical challenges small for size syndrome bile duct

28. Technical Challenges in ASLT Small for Size Syndrome portal inflow versus venous outflow GRWR Avoid sick recipients Optimize outflow Reduce inflow

29. Nakamura S and Tsuzuki T, Surg Gyn & Obst; 1981 Venous Drainage Patterns of Right Lobe Posterior Segments Type I 38.6 % RHVlarge IRHV absent / <0.5 cm RHV IRHV MHV

30. Nakamura S and Tsuzuki T, Surg, Gyn & Obst 1981 Venous Drainage Patterns of Right Lobe Posterior Segments RHVmediumsmall IRHV 0.5 - 1cm1- 1.5 cm Type III 24.1 % RHV IRHV MHV RHV IRHV MHV Type II 37.3 % 6 6

31. Venous Drainage Patterns of Right Lobe Anterior Segments RHV MHV RHVsmall - medium MHV Large proximal tributary 5 8

32. 5 6 7 MHV Dominant MHV Drainage of Right Lobe LHV RHV 8 MHV

33. Right versus Extended Right Lobe Grafts RHV MHV 5 IVC 4

34. MHV Outflow Reconstruction in Right Hemigrafts MHV RHV IRHV Ghobrial et al., Liver Transpl 2001 IVC IVC RHV MHV

35. Venous Outflow Reconstruction in Right Lobe Grafts

36. Optimization of Venous Outflow in Right Lobe Grafts Humar A, et al. Liver Transpl 2004

37. Vessel loop LBD RBD Gundalch et al, Liver Transplantation; 2000 Split-Cava Technique to Optimize Venous Outflow of Both Hemiliver Grafts

38. Gundalch et al, Liver Transplantation; 2000 Split-Cava Technique to Optimize Venous Outflow of Both Hemiliver Grafts IVC MHV LHV RHV

39. Split-Cava Technique Solves the issue of minor hepatic veins draining into the retrohepatic IVC Does not resolve the MHV issue, especially when there is dominant MHV drainage of the right lobe

40. Broering et al, Liver Transplantation; 2000 MHV Splitting in Left/Right Split for Two Adults

41. Small-for-size partial liver graft In an adult recipient; a new transplant technique Olivier Boillot, Bertrand Delafosse, Isabelle Mechet, Catherine Boucaud, Michel Pouyet Liver Transplant Unit, Edouard Herriot Hospital, Lyon, France Boillot et al, Lancet; 2002 Inflow Reduction in Small for Size Grafts

42. Biliary Complications in SLT Incidence of 10-25% Tends higher in ex situ splits Ischemia of the bile ducts with extensive dissection Variant biliary anatomy

43. TWO DUCTS 28 cases (60.9 %) ONE DUCT 16 cases (34.8 %) THREE DUCTS 2 cases (4.3 %) Bile Duct Anatomy in Donors

44. Balzan Silvio, Liver Transpl 2004 Bile Duct Visualization During Split Liver Preparation

45. AASLT is the logical approach for expansion of the adult donor pool Successful splitting requires precise matching of split donor livers with adequately sized recipients Technical advances that overcome SFSS are critical to successful future implementation of the procedure Conclusions