M. Ravaioli, M.D., PhD

Quale è il futuro dei trapianti di organo solido? Con la bioingegneria e l utilizzo di cellule staminali potremo curare meglio le insufficienze d organo e di tessuto? M. Ravaioli, M.D., PhD Department of General Surgery and Transplantation Prof. AD Pinna Policlinico Sant Orsola Malpighi University of Bologna, Italy

Il fegato artificiale impiantabile? By-pass but not liver available to transplantation Use of partial cardiopulmonary bypass during the anhepatic phase of orthotopic liver grafting. Lancet 1979 R.Y. Calne Venous Bypass in Clinical Liver Transplantation B.W. Shaw Ann Surg 1984

Il fegato artificiale impiantabile?

European gap among donors and recipients Extended criteria donors Living donors Candidates to Liver or Kidney Tx Split NHBD Deceased donors available Domino Effective allocation system

Extended criteria liver = Artificial liver?

Extended criteria donors Graft with an increased risk of early failure or inferior graft and patient survival resulting from per-transplant factors Extended Criteria Donor/Graft = ECD

MELD era, ECD and

Balance among: MELD era, ECD and Marginal graft MELD Recipient Selective criteria MELD era Pre-MELD era Quality transplant programs

Liver transplantation strategies from Kidney experience 1-3 hours Liver biopsy Expert pathologists on liver disease available 24 hours per day at our hospital Donor aorta clamped Recipient on the operating room Decision to accept the liver: senior surgeons considers the histological assessment and the macroscopic aspect as depicted by the harvesting surgeon 30 minutes Histo-pathological report by telephone

Liver transplantation strategies from Kidney experience Dissection Hepatectomy Transplantation Increased graft ischemia

Liver transplantation strategies from Kidney experience Dissection Hepatectomy Transplantation Short graft ischemia

Liver transplantation strategies from Kidney experience Ravaioli et al.transplant International 2009

Surgical Techniques To-day and To-morrow How to improve outcome of E.C.D. different form partial grafts?

ECD, other strategies to improve the outcome?

ECD, other strategies to improve the outcome? Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs

ECD, other strategies to improve the outcome? Static Ice System Simple, reproducible technique Inexpensive Few supply needs Little technical expertise needed Allows for easy long distance transportation Acceptable immediate function rates with short ischemic times Pulsatile Perfusion More complicated to set up More expensive Need machine, perfusion cassette and liquid especially design Technical expertise Provides a monitoring capability Allows transportation

ECD, other strategies to improve the outcome? Flow effects on the endothelial cell Kamm R, Annu. Rev. Fluid Mech. 2002 Endothelial cells under no-flow conditions (a) and after exposure to 1.2 Pa of steady, laminar shear stress for 24 h (b).

Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation

Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation DGF 70 pts machine-perfusion group vs. 89 cold-storage group (P = 0.01) One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P = 0.04)

ECD, other strategies to improve the outcome? Infusion fluids Organ chamber Venous Reservoir Membrane oxygenator Centrifugal Pump Urinometer Temperature probe

ECD, other strategies to improve the outcome? The delayed graft function rate (DGF), defined as the requirement for dialysis within the first 7 days 1/18 (5.6%) EVNP group vs. 17/47 (36.2%) CS group p = 0.014 There was no difference in graft or patient survival at 12 months

ECD, other strategies to improve the outcome? steatotic livers can be successfully preserved using normothermic preservation for prolonged periods and that normothermic preservation facilitates a reduction in hepatic steatosis

ECD, other strategies to improve the outcome? 20 LTs HMP preserved vs. 20 a matched group transplanted with CS livers Early allograft dysfunction Rates were 5%in the HMP group versus 25% in controls (p = 0.08)

ECD, other strategies to improve the outcome? Donors after cardiac death (DCD) maintain with normothermic extracorporeal membrane oxygenation (NECMO)

ECD, other strategies Bologna researches..

ECD, other strategies Bologna researches.. T-0 T-1 T-2

Surgical Techniques To-day and To-morrow How will be future grafts?

Surgical Techniques To-day and To-morrow

Prospective fellows whom I trained in this field went on to pass on what we have learned to date from our research, not only as it applies to transplantation per se, but also to its broader implications for medicine as a whole

Conclusions: support donation and living donors