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SMALL FOR SIZE IN LIVER SURGERY Ghent, 11 th March 2005

THE HEMIPORTOCAVAL SHUNT R. Troisi, MD PhD. Hepatobiliary and Liver Transplantation Service Ghent University Hospital Medical School GHENT - BELGIUM. SMALL FOR SIZE IN LIVER SURGERY Ghent, 11 th March 2005. Living Donor Liver Transplantation. The Evolution

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SMALL FOR SIZE IN LIVER SURGERY Ghent, 11 th March 2005

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  1. THE HEMIPORTOCAVAL SHUNT R. Troisi, MD PhD Hepatobiliary and Liver Transplantation Service Ghent University Hospital Medical School GHENT - BELGIUM SMALL FOR SIZE IN LIVER SURGERY Ghent, 11th March 2005

  2. Living Donor Liver Transplantation • The Evolution • 3 D Reconstructive imaging for graft selection • - precise 3D map of vascular and biliary anatomy • and calculation of remnant at risk • Strategies for small for size grafts • - intragraft responses to shear stress • - inflow modulation techniques • Operational Tolerance • - induction with policlonal AB’s • - combined stem cells / living donor Tx

  3. 197 200 190 Adults : 696 Children : 590 148 150 93 100 84 74 66 60 58 49 50 46 35 35 34 42 22 0 16 15 1 6 4 3 3 3 2 0 0 0 90 91 92 93 94 95 96 97 98 99 2000 2001 2002 June 2003 Evolution of the Number of Living Related Liver Transplantations in Europe (n = 1286)

  4. Left liver (seg. 2,3,4) : 25 (4%) Left lobe (S 2, 3) : 16 (3%) Right liver (5, 6, 7, 8): 540 (93%) Type of Graft used for Adult LRLT 540 377 231 25 18 12

  5. Graft Survival according to the Type of Living Related Graft in LRLT- Adults (%) 100 Right liver : 537 Total Log rank test p< 0.001 Left lobe : 15 Left liver : 29 80 73 65 61 57 60 41 40 33 20 0 0 1 2 3 4 5 Yrs

  6. Living Donor Liver Transplantation Causes of Graft Loss / Mortality in Adults Sepsis 53% Hemorrhage 14% Vascular 14% Recurrent Disease 2-3% Other 16% (Broelsch, LT 2003) Graft dysfunction (?) SFSS (?) Outflow insufficiency (?)

  7. Living Donor Liver Transplantation Relationships between Techniques and Complications Small for Size Syndrome • Vascular thrombosis • Bleeding • Biliary complications • leaks • stenosis • Venous outflow insufficiency New surgical techniques

  8. Small-For-Size Syndrome • FUNCTIONAL GRAFT MASS • GV • Fatty liver / Age • Parenchymal disease • GRAFT INJURY • WI / CI • Rejection • Venous Outflow • Graft Inflow • METABOLIC DEMAND • Pre-Tx status • Post-Tx complications

  9. Manifestations of the SFSS ENHANCED HEPATOCYTE INJURY DELAYED SYNTHETIC FUNCTION PROLONGED CHOLESTASIS RENAL FAILURE ASCITES FORMATION SEPTIC COMPLICATIONS SEVERE GRAFT DYSFUNCTION REDUCED GRAFT SURVIVAL LESS OUTCOME

  10. Pathology of SFSG: Parenchymal Cells Lines • Macroscopic appearance • Sinusoidal congestion • Biliary thrombi • vacuolar degeneration • Single apoptotic change in hepatocytes Man K, Ann Surg 2003

  11. Pathology of SFSG: Parenchymal Cells Lines • Microscopic features • sinusoidal disruption • hepatocytes ballooning • vacuolar degeneration • mitochondrial swelling Man K, Ann Surg 2003

  12. The Intragraft Responses CONGESTION Intragraft Responses SHEAR STRESS UP DOWN Small functional mass HSPs (a) HO-1 (b,c) Egr – 1 (a) ET-1 (c) Portal hyperperfusion Cytokines Macrophages Adhesion molecules • Ting-Bo Liang, Transplantation 2003 • Zhen-Fan Yang, AJT 2003 • Man K, Ann Surg 2003

  13. Variations in Graft Arterial and Portal Flow between the Physiological Setting (Donors) and following Graft Reperfusion (Recipients) (Troisi R, Ann Surg 2003)

  14. Effects of Splenic Artery Ligation on Graft Inflow (Troisi R, Ann Surg 2003)

  15. Effects of Splenic Artery Ligation on Outcome (n = 14) (n = 10) (Troisi R, Liver Transplantation 2003)

  16. Transit Time Flow Measurement (TTFM) • Mean flows  diastolic / systolic • Diastolic filling  patency • Pulsatile index  quality anastomosis • Flow curve Outflow • Spasm • Kinking

  17. Rationale for HPCS Mean of 90 ml/min/100 g liver = Normal PVF in donors Mean of 270 – 350 ml/min/100 g liver = ± 3 x PVF after reperfusion → SAL Mean PVF of > 360 ml/min/100 g liver = SAL + PVB or HEMI PORTO CAVAL SHUNT

  18. HPCS: Standard Technique for SFSG

  19. Left Lobe LDLT: Outflow Reconstruction • Advantages of a Left Liver • No congestion (since including the MHV) • Liver function less depressed (bigger remnant) • Less overall donor morbidity • Disadvantages of a Left Liver • Difficult position/risks of HV twist • Artery smaller • Less liver mass

  20. Calibration of HPCS in Left Lobe

  21. Hemodynamic Features in Shunted Left Lobe HPCS LPV HPCS LHA

  22. Effects of HPCS for Inflow Modulation on the Outcome of SFSG in LDLT • Graft hemodynamics in SFSG • Features of non-parenchymal cell lines following portal shunt • Clinical outcome (Troisi R, Am J Transplantation 2005)

  23. Patient’s Demographics Parameter G1 (n = 5) G2 (n = 10) P* Mean age (years  SD) 52.6 ± 2.1 56.6 ± 4.8 0.09 Median FU (months  SD) 5 ± 13 17 ± 5 0.52 UNOS Status 2(n) 5/5 9/10 - MELD score (SD) 20 ± 6 18 ± 4 0.9 Esoph Varices gr. II/III(n) 5 8 - Right Liver (n) 4 5 - Left Liver (n) 1 5 0.56** * Mann-Whitney U-test; ** Fisher exact test

  24. Donor’s Characteristics *Spearman rank order correlation

  25. Donor’s Graft Hemodynamics: Left vs Right Livers Parameter Left Livers (n = 6) Right Livers (n = 9) P* dPVF 462 ± 75 719 ± 216 0.04 (ml/min) dPVF/GW 121  40 116 ± 13 0.87 (ml/min/100 g liver) * Wilcoxon matched pairs test.

  26. Inflow Modulation by HPCS Parameter G1 (n=5) Parameter G2 (n = 10) P* Cardiac Index a 4.7 ± 1.6 Cardiac Index 4.6 ± 0.9. 0.8 HPCS/GW b - HPCS/GW 330 ± 230 (60-620) - rPVF1/GW 460 ± 30 (140-1080) rPVF2/GW 190 ± 70 (15-260) 0.002 rPVF1/GW/CI c 80 ± 20 (50-100) rPVF2/GW/CI 50 ± 160 (3-71) 0.018 rHAF1/GW 9 ± 8 (2-20) rHAF2/GW 32 ± 20 (10-63) 0.030 rHAF1/GW/CI 2 ± 1 (0.6-1) rHAF2/GW/CI 7 ± 3 (2-16) 0.030 * Mann-Whitney U-test; a L/min/m2; b Graft Weight (ml/min/100 g liver); c Cardiac index HPCS: portal flow shunted away; rPVF 1: total portal vein flow to the graft; rPVF 2: portal flow to the graft after opening of the HPCS; rHAF 1: hepatic artery flow to the graft; rHAF 2: hepatic artery flow to the graft after opening of the HPCS.

  27. US-Doppler in Non-Shunted vs Shunted Grafts • Portal vein flow (cm/sec.) G1 (no shunt) G2 (shunt) P* • POD 1 73.4 ± 18.1 32.4 ± 17.6 0.006 • POD 7 70.8 ± 9.5 31 ± 12.5 0.004 • > 1 month 65 ± 7 37.8 ± 9 0.095 • Hepatic artery flow • POD 1 32.6 ± 7.5 62 ± 25.1 0.065 • POD 7 31 ± 3.4 58.7 ± 20.2 0.004 • > 1 month 30 ±14.1 61.8 ± 12.5 0.095 • * Mann-Whitney U-test; POD: postoperative day

  28. ** *** * * p = 0.005 ** p = 0.008 *** p = 0.001 * ** *** G1 G2 Graph.1: Evolution of total bilirubin *, **, *** Mann-Whitney U-test

  29. ** *** * * ** *** * p = 0.272 ** p = 0.012 *** p = 0.008 G1 G2 Graph.2: Evolution of prothrombin time *, **, *** Mann-Whitney U-test

  30. ** *** * p = 0.067 ** p = 0.372 *** p = 0.018 * * ** *** G1 G2 Graph.3: Evolution of ascites leak *, **, *** Mann-Whitney U-test

  31. * * p = 0.005 * Graph.4: Serum creatinine at POD 21 * Mann-Whitney U-test

  32. * * Relative changes in liver volume (%) Fig. 1: Serial relative changes in liver volume. *p = ns

  33. Overall Results * Fisher’s exact test

  34. OVERALL GRAFT SURVIVAL 80% HPCS (n = 10) Log Rank P = 0.0289 20% No HPCS (n = 5)

  35. Conclusions (1) • Enhanced portal graft hyperperfusion in SFSG is significantly correlated to postoperative graft dysfunction and SFSS • The RE system is irreversibly damaged in these grafts whereas HPCS do preserve lobular architecture • Hemi-Porto-Caval shunt permits an extensive reduction of the graft inflow improving hepatic artery flow • HPCS do not worsens postoperative graft function, graft regeneration. General outcome is generally improved • Careful perioperative management is however recommended (i.e. risks of sepsis)

  36. Conclusions (2) • Basing on the Asian data on reduced donor morbidity with the use of the left livers, upon this experience could we implement the use of left liver grafts for adult recipients?

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