1. Region 10 and In situ Split of the Deceased Donor Liver OSOTC Education Conference September 11, 2015

2. History In late 1980’s early 1990’s, pediatric waiting list mortality significant –Development of reduced size liver transplantation Both living donor (LDLT) and deceased donor split liver transplantation (DDSLT) evolved from reduced size liver transplantation –Imbalance between recipients and available donors drove the innovation with the goal of reducing waiting list mortality while maximizing utilization of resources –DDSLT – 1989, LDLT – 1991 –Outcomes following whole organ is best but given imbalance, alternative techniques must be employed

3. Anatomic Liver segments

4. Reduced Size Liver Transplantation

5. Left Lateral Segment – Extended Right Lobe Split

6. Left Lobe – Right Lobe Split

7. In Situ Split – Left Lateral Segment Dissection Middle Hepatic Vein Left Portal Vein Left Hepatic Artery Left Hepatic Vein

8. Left Lateral Segment Graft

10. Abdominal Position - LLS GRAFT

11. Donor Criteria for Split Liver Consideration Age < 40 ICU Stay < 5 days Liver biochemical profile within normal limits No more than 1 vasopressor agent Serum electrolytes within normal limits

12. Who should get a Split segment? Pediatric Recipient Donor : Recipient Weight Ratio –Left Lobe Graft – 2-5 : 1 –Left Lateral Segment Graft - 6-10 : 1 Disease Severity –Status I –PELD>15 –Any patient for whom a reduced size graft is being considered

13. Who should get a Split segment? Adolescent / Adult Recipient Donor : Recipient Weight Ratio –Extended Right Lobe Graft Size match –Right Lobe Graft Graft weight : Recipient weight (GWRW) –Living donor > 0.8 % –Deceased donor > 1% Recipient Disease Severity –Lower MELD –Less portal hypertension /hyperdynamic splanchnic circulation

14. Where to Split? In situ versus Ex vivo In Situ –Benefits Clearer sense of both grafts perfusion Cut surface controlled Less cold ischemia time –Risks Longer donor OR time Potential risk of hemodynamic instability which could effect other organs Ex Vivo –Benefits Shorter OR time Less risk to other organs –Risks Perfusion of both grafts unknown Longer cold ischemia time Cut surface

15. Operative Considerations Local OPO preparation –Appropriate donor selection and organ allocation –Communication with different donor teams – timing and length of operation OR team –Anesthesia aware with more blood available OR Equipment –Essential – Bovie, slush, patience –Helpful – Intra-op cholangiography, laparoscopic staplers, harmonic, argon beam, experienced scrub tech

16. Allocation of Vessels and Biliary Tract Hepatic artery Portal vein Hepatic veins / Inferior vena cava Bile duct Vessels for reconstruction –Iliac artery and vein –Others - Inferior mesenteric and carotid artery

17. Region 10 Allocation of Structures Working agreement The center allocated organ decides vessel distribution –Hepatic artery – Celiac axis –Portal vein - variable –Bile duct – left hepatic duct –Hepatic veins / IVC LLS – left hepatic vein Left Lobe - Vena cava

18. Allocation of Hepatic Veins and IVC

19. Split grafts - Complications Biliary tract –Cut surface –Major bile duct Vascular – HAT/PVT Small for size –Ascites –Jaundice –Failure to thrive

20. In situ Split – the UCLA experience Single Center experience where they mostly split with themselves 100 donors yielded 190 grafts transplanted into 105 pediatric patients and 60 adults at UCLA, 25 shared within region Compared outcomes with whole organs and living donor grafts for both LLS and right trisegs Yersiz et al, Ann Surg, 2003

21. In situ Split – the UCLA experience Yersiz et al, Ann Surg, 2003

22. In situ Split – the UCLA experience Amongst pediatric recipients, biliary and vascular complications similar between LLS, LD and whole organ recipients Amongst adult recipients, increased rate of biliary and vascular complications Mechanism to get pediatric recipients transplanted while still giving adults access to a slightly higher risk but viable alternative Reduce need for living donor transplantation Yersiz et al, Ann Surg, 2003

23. Annual Trend Split Liver Transplantation Lee KW, Cameron AM, Maley WR et al. Am J Transpl 2008;8:1186-1196.

24. SPLIT Registry Survival Diamond IR, Fecteau A, Millis JM et al. Ann Surg. 2007;246:301-310.

25. Factors affecting graft survival – LLS Split Liver Risk FactorHazard Ratio (95%)P value Recipients Factors Dx Tumor / No Tumor1.904 (Tumor +)0.03 Dialysis 1 wk of Tx2.935 (Dialysis +)0.004 Wt 6 Kg2.05 (<6Kg)0.001 Donor Factors 30 yrs1.448 (Age > 30)0.041 CA post DBD3.792 (cardiac arrest +)0.001 Transplant Factors CIT > 6 hr1.6880.008 CIT > 12 hrs3.0030.001 Pediatric Specific Ctr1.0 No share vs share1.666 vs 2.2310.009 Lee KW, Cameron AM, Maley WR et al. Am J Transpl 2008;8:1186-1196.

26. In situ Right Lobe:Left Lobe split – Cleveland Clinic Experience Reviewed their experience using a right:left lobe split comparing outcomes to whole organ recipients Excluded Right Triseg:LLS in situ splits Sixteen donors – 32 grafts –25 used at CCF, six by other programs in the region, 1 discarded for technical reasons Hashimoto et al, AJT, 2014

27. In situ split Hemi livers – Cleveland Clinic Experience Hashimoto et al, AJT, 2014

28. In situ split Hemi livers – Cleveland Clinic Experience Primary and secondary recipients with similar outcomes Biliary complications increased 32% versus 10.7% Two cases of PNF salvaged by retransplantation Hashimoto et al, AJT, 2014

29. Meta-analysis of In situ split right lobe grafts Review encompassed all articles before December 2014 time period PubMed, Embase and Cochrane Library search Seventeen studies with a total of 48457 patients utilized in analysis Wan et al, Liver Transpl, 2015

30. Meta-analysis of In situ split right lobe grafts Patient and graft survival similar Complications not identified in study found to be statistically significant –Biliary complications and outflow obstruction more common in split liver graft Ex vivo split worse outcome then in situ split Should match appropriate recipient with risk of graft OutcomeOdds Ratio Confidence Interval p value Patient Survival (One year) 0.850.62-1.160.31 Graft Survival (One year) 0.910.76-1.080.27 Biliary Complications 1.661.29-2.15<0.001 Bile leaks4.32.97-6.23<0.001 Vascular complications 1.811.29-2.53<0.001 HAT1.711.17-2.5<0.005 Outflow Obstruction 4.171.75-9.940.001 Wan et al, Liver Transpl, 2015

31. CCHMC Graft use 2004-2015 Increased use of Split segments starting in 2004 Number of transplant 248 Whole – 123, Technical variants - 125 Reduced Size – 90 Split – 25 Living related – 10 Split – 25 –Extended Right - 2, Right Lobe - 2 –Left Lobe - 10, LLS - 11 –Donor age range - 7 - 45 –In situ vs ex vivo – 18 in situ, 7 ex vivo –Local - 2, Region - 23

32. CCHMC Outcomes Graft SurvivalPatient Survival

33. Conclusions In situ split livers is an alternative to increase donor pool but should be used in a select population In our region, allocation to pediatric patient is logical trigger for in situ split liver consideration Requires significant cooperation between OPO, transplant teams

34. The Risk of any Journey must be appreciated by all parties….. (Prior to beginning the Journey !)