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  1. 1. LIVER RESECTION VERSUS LIVER RESECTION VERSUS TRANSPLANTATION FOR TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA HEPATOCELLULAR CARCINOMA L. DE CARLIS L. DE CARLIS DEPT. OF SURGERY AND ABDOMINAL DEPT. OF SURGERY AND ABDOMINAL ORGAN TRANSPLANTATION ORGAN TRANSPLANTATION NIGUARDA HOSPITAL -- MILAN (ITALY) NIGUARDA HOSPITAL MILAN (ITALY)
  2. 2. SURGICAL TREATMENT OF HCC SURGICAL TREATMENT OF HCC • Due to its direct link with liver cirrhosis, the • Due to its direct link with liver cirrhosis, the surgical therapy of HCC remains controversial. surgical therapy of HCC remains controversial. • Liver resection (LR) is limited by the severity of • Liver resection (LR) is limited by the severity of cirrhosis and tumor recurrence is a frequent cirrhosis and tumor recurrence is a frequent event in the cirrhotic liver remnant, which event in the cirrhotic liver remnant, which maintains its oncogenic potential. maintains its oncogenic potential. • Liver transplantation (LTx) is the only option to • Liver transplantation (LTx) is the only option to treat tumor and cirrhosis at the same time but treat tumor and cirrhosis at the same time but mortality and morbidity are higher and waiting mortality and morbidity are higher and waiting lists are crowded. lists are crowded.
  3. 3. • Absence of randomized controlled Absence of randomized controlled trials trials • Treatment of HCC is not yet well Treatment of HCC is not yet well codified codified
  4. 4. Aim of the study Aim of the study • Compare 2 large series of pts with HCC Compare 2 large series of pts with HCC treated with LR or OLTx treated with LR or OLTx • Determine tumor and patients chara- Determine tumor and patients chara- cteristic on survival and recurrence cteristic on survival and recurrence • Verify whether these parameters can Verify whether these parameters can identify the most appropriate treatment identify the most appropriate treatment option option
  5. 5. LR and LTx for HCC LR and LTx for HCC (casistics 1985-2003) (casistics 1985-2003) • Liver Resection Liver Resection 282 282 • Liver Transplantation Liver Transplantation 187/654 187/654 (28,5%) (28,5%)
  6. 6. LR and OLTx for HCC LR and OLTx for HCC analysis 1985-1999 analysis 1985-1999 • Liver Resection Liver Resection 154 154 • Liver Transplantation Liver Transplantation 121 121
  7. 7. LTx - Indication (121 pts) LTx - Indication (121 pts) • Unresectable single nodule <5 Unresectable single nodule <5 cm or 1-3 nodules ≤ 3 cm cm or 1-3 nodules ≤ 3 cm • Child B9 to C pts Child B9 to C pts 28 pts with incidental HCC 28 pts with incidental HCC Median diameter of the nodules → 3.7 cm Median diameter of the nodules → 3.7 cm (±2.5) (±2.5)
  8. 8. LR - Indication (154 pts) LR - Indication (154 pts) • Child A-(B) pts Child A-(B) pts • Absence of portal hypertension Absence of portal hypertension • Single or multiple nodules in Single or multiple nodules in resectable position resectable position Major liver resections Major liver resections 27 pts 27 pts Segmentectomies Segmentectomies 90 pts 90 pts Wedge resection Wedge resection 27 pts 27 pts Multiple procedures Multiple procedures 10 pts 10 pts
  9. 9. Patients characteristics Patients characteristics p Age NS Gender NS Ethiology of liver disease NS Child classification 0.05 pTNM 0.05 Tumor size 0.05 Number of nodules NS Vascular infiltration NS Presence of capsule NS αFP / Histologic Grade NS
  10. 10. Perioperative mortality * Perioperative mortality * • LTx LTx 22/121 (18.1%) 22/121 (18.1%) • LR LR 7/154 (4.5%) 7/154 (4.5%) * (1996-2001 OLTx = 9% - LR ~ 0) * (1996-2001 OLTx = 9% - LR ~ 0)
  11. 11. Causes of perioperative deaths Causes of perioperative deaths LTx (22 pts) LTx (22 pts) • Sepsis Sepsis 5 5 • MOF MOF 4 4 • Vascular complication Vascular complication 4 4 • Haemorrhagic shock Haemorrhagic shock 3 3 • Graft-non-function Graft-non-function 2 2 • Cerebrovascular accidents Cerebrovascular accidents 2 2 • Myocardial infarction Myocardial infarction 1 1 • Irreversible rejection Irreversible rejection 1 1
  12. 12. Causes of perioperative deaths Causes of perioperative deaths LR (7 pts) LR (7 pts) • Hepatic Failure Hepatic Failure 5 5 • Haemorrhagic shock Haemorrhagic shock 1 1 • Cerebrovascular accidents Cerebrovascular accidents 1 1
  13. 13. Late Mortality Late Mortality Tumor Unrelated Tumor Unrelated • LTx LTx 12 12 • LR LR 21 21 Tumor Related Tumor Related • LTx LTx 10 10 • LR LR 55 (p0.0001) 55 (p0.0001)
  14. 14. Data at the end of follow-up Data at the end of follow-up Overall Recurrence Overall Recurrence • LTx LTx 11 11 (9%) (9%) • LR LR 74 74 (47.4%) (47.4%) Pts Survival With Recurrence Pts Survival With Recurrence • LTx LTx 1* 1* (9%) (9%) • LR LR 19 19 (25.6%) (25.6%) * 8,3 yrs
  15. 15. Final results of statistical analysis II Final results of statistical analysis Univariate Analysis Univariate Analysis • Capsule, Vascular Invasion, pTNM, αFP, • Capsule, Vascular Invasion, pTNM, αFP, seem important factors for 5 yrs survival and seem important factors for 5 yrs survival and recurrence rate in both groups recurrence rate in both groups • in LR number of nodules and age were • in LR number of nodules and age were significant for recurrence and 5 yrs survival significant for recurrence and 5 yrs survival while Child and size only for survival while Child and size only for survival • in LTx size of tumor was significant for • in LTx size of tumor was significant for recurrence and survival while viral cirrhosis recurrence and survival while viral cirrhosis for survival for survival
  16. 16. Final results of statistical analysis II Final results of statistical analysis II Multivariate Analysis Multivariate Analysis • At multivariate analysis only αFP, At multivariate analysis only αFP, histological grade and vascular invasion histological grade and vascular invasion were indipendent variables for tumor were indipendent variables for tumor recurrence in both groups recurrence in both groups • In LR pTNM, αFP, Child and age were In LR pTNM, αFP, Child and age were indipendent variables for 5 yrs survival indipendent variables for 5 yrs survival • In LTx capsula, αFP, viral cirrhosis were In LTx capsula, αFP, viral cirrhosis were indipendent variables for 5 yrs survival indipendent variables for 5 yrs survival
  17. 17. Multivariate Analysis Multivariate Analysis Variable Risk Ratio Confidence Interval 95% P     Capsule 2.45 0.99 , 6.13 0.05 LTx AFP 2.32 1.11 , 4.86 0.02 Viral Cirrhosis 2.26 1.11 , 4.61 0.02   Histologic Grade 2.22 1.07 , 5.00 0.03   SURVIVAL             Child 2.89 1.82 , 4.61 0.001 Age 1.79 0.98 , 3.26 0.05 LR PTNM 2.79 1.73 , 4.50 0.0001 AFP 2.20 1.34 , 3.62 0.0001             Vascular Infiltration 11.11 2.86 , 43.22 0.0005 LTx AFP 2.68 2.13 , 8.58 0.0001 FREEDOM Histologic Grade 2.99 2.46 , 9.75 0.0002 FROM RECURRENCE           Vascular Infiltration 2.52 1.59 , 4.01 0.0001 LR AFP 3.99 2.38 , 6.69 0.0001 Histologic Grade 2.79 1.26 , 5.39 0.001
  18. 18. SURVIVAL SURVIVAL 1.0 LR (n= 154) Survival Distribution 0.8 LTx (n=121) Function 0.6 0.4 0.2 p=0.08 0.0 0 1000 2000 3000 4000 5000 Days After Transplantation
  19. 19. DISEASE FREE SURVIVAL DISEASE FREE SURVIVAL (perioperative mortality censored) (perioperative mortality censored) 1.0 LTx (n=99) Survival Distr.Funct. Recurrence-Free 0.8 LR (n=147) 0.6 0.4 0.2 p.0001 0.0 0 1000 2000 3000 4000 5000 Days After Transplantation
  20. 20. pT 1/2 pT 1/2 1.0 LR pT 1/2 Survival Distr.Funct. LTx pT 1/2 0.8 0.6 0.4 0.2 p=0.3 0.0 0 1000 2000 3000 4000 5000 Days After Transplantation
  21. 21. SMALL TUMOR ( 5 cm) SMALL TUMOR ( 5 cm) 1.0 LR 5cm Survival Distr.Funct. 0.8 LTx 5cm 0.6 0.4 0.2 p=0.4 0.0 0 1000 2000 3000 4000 5000 Days After Transplantation
  22. 22. SMALL, ENCAPSULATED WITH SMALL, ENCAPSULATED WITH LOW αFP LEVELS LOW αFP LEVELS 1.0 LR (n=32) Survival Distr.Funct. LT (n=26) 0.8 0.6 0.4 0.2 p=0.3 0.0 0 1000 2000 3000 4000 5000 Days After Transplantation
  23. 23. The best options for small The best options for small HCC HCC • Liver resection Liver resection • Liver transplantation Liver transplantation The same 3-5 years survival The same 3-5 years survival HCC recurrence in liver resection HCC recurrence in liver resection
  24. 24. Conclusions II Conclusions • LTx appears to offer a better recurrence LTx appears to offer a better recurrence freedom than LR in patients with HCC. freedom than LR in patients with HCC. Nevertheless, many patients still live a long Nevertheless, many patients still live a long time after recurrence and mortality is often time after recurrence and mortality is often related to the progression of cirrhosis related to the progression of cirrhosis • Shortage of organs limits the possibility of Shortage of organs limits the possibility of offering this option to every pts with HCC offering this option to every pts with HCC • A strict selection should be made to A strict selection should be made to optimise organ allocation optimise organ allocation
  25. 25. Conclusions II Conclusions II • LR should be considered a good therapeutic • LR should be considered a good therapeutic alternative in pts who do not fulfill LTx criteria alternative in pts who do not fulfill LTx criteria • The HCCs most suitable for LR are the same • The HCCs most suitable for LR are the same tumors that should have the best results when tumors that should have the best results when treated by LTx,, i.e. small, encapsulated tumors treated by LTx i.e. small, encapsulated tumors with low AFP levels. with low AFP levels. • In these cases other risk factors should be • In these cases other risk factors should be considered like the etiology of the disease, the considered like the etiology of the disease, the age of the patients, the severity of the cirrhosis age of the patients, the severity of the cirrhosis and, when available, the grade of the neoplasm. and, when available, the grade of the neoplasm.
  26. 26. Conclusions III Conclusions III • Size and multifocality are not ‘per se’ signs of an • Size and multifocality are not ‘per se’ signs of an aggressive behavior of the tumor. aggressive behavior of the tumor. • AFP, vascular invasion, histological grade and an • AFP, vascular invasion, histological grade and an aggressive behavior during the waiting period, aggressive behavior during the waiting period, more likely reflect the risk of recurrence of the more likely reflect the risk of recurrence of the disease. disease. • Criteria for transplantation may undoubtedly be • Criteria for transplantation may undoubtedly be widened by including larger tumors in young widened by including larger tumors in young patients, but the length of the waiting time and patients, but the length of the waiting time and the appropriateness of the organ allocation limit the appropriateness of the organ allocation limit this procedure only to selected cases. this procedure only to selected cases.
  27. 27. Open Problems Open Problems • Expanding indication for resectable HCC? Expanding indication for resectable HCC? • Expanding selection criteria for LTx ? Expanding selection criteria for LTx ? • LTx after downstaging the tumor ? LTx after downstaging the tumor ? “Nowadays the main problem of LTx is not the “Nowadays the main problem of LTx is not the definition of the best selection criteria, but the definition of the best selection criteria, but the low applicability of the treatment because of the low applicability of the treatment because of the lack of donors” lack of donors” (Lowet. Hepatology 1999; 30, 6, 1434) (Lowet. Hepatology 1999; 30, 6, 1434)
  28. 28. Transplantation of a right lobe from a living donor.

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