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Two-Stage Hepatectomy for Unresectable Metastases :

Two-Stage Hepatectomy for Unresectable Metastases :. R. Adam, D.A. Wicherts, R. Miller, R.J. de Haas, G. Bitsakou, E. Vibert, L.A. Veilhan, D. Azoulay, H. Bismuth, D. Castaing. Hôpital Paul Brousse, Université Paris-Sud, France. Resectable 10–20%. Non resectable 80–90%. 1-2%. 15–30 %.

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Two-Stage Hepatectomy for Unresectable Metastases :

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  1. Two-Stage Hepatectomy for Unresectable Metastases : R. Adam, D.A. Wicherts, R. Miller, R.J. de Haas, G. Bitsakou, E. Vibert, L.A. Veilhan, D. Azoulay, H. Bismuth, D. Castaing Hôpital Paul Brousse, Université Paris-Sud, France

  2. Resectable 10–20% Non resectable 80–90% 1-2% 15–30 % Survival benefit40% at 5 yrs RESECTABILITY: a new end point of the strategy

  3. MULTINODULAR COLORECTAL LIVER METASTASES HOW TO MAKE A COMPLETE RESECTION WHILE SAVING 30% LIVER REMNANT ?

  4. BILATERAL HUGE LIVER METASTASES HOW TO MAKE A COMPLETE RESECTION ?

  5. TWO-STAGE HEPATECTOMY Concept • Two sequential liver resectionsaiming to • resect multinodular hepatic tumors • irresectable by a single procedure • Regenerationfollowing hepatectomy • Planned strategyat the time of 1st hepatectomy • - (1) Adam R, et al. Ann Surg 2000; 232:777-85

  6. Two-Stage Hepatectomy 155 cc 1 I 440 cc IV I 2 (1) Adam R, et al. Ann Surg 2000; 232:777-85

  7. Two-Stage Hepatectomy: Patients and Methods Oct. 1992 - Oct. 2006: 817 pts resected for CLM 100% 262 Pts initially Unresectable 100% 32% 51 Pts 2-stage hepatectomy 20% 6%

  8. 2% 5% 7% 8% 14% % Two-stage Conventional Hepatectomy Two-Stage Hepatectomy: Evolution in time

  9. Two-Stage Hepatectomy: Results Feasibility 35/51 (69%) • 16 patients ineligible for a second resection because: • Disease Progression • - Intrahepatic • - Intra- and extrahepatic • Bad Performance Status 15 (29%) 6 (12%) 9 (18%) 1 (2%)

  10. Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Outcome of failed patients (N = 16) Alive with disease (13%) (N=2) Dead (88%) (N=14) Median time to death 12.3 mo (3.6 - 18.8)

  11. Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Patient and Primary tumor characteristics N = 35 57.5 + 10.3 17 (49%) 18 (51%) 27 (77%) 8 (23%) 5 (26%) 14 (74%) 4 (22%) 14 (78%) Mean age + SD Female Male Colon Rectum T - 0-2 T - 3-4 N - 0 N - 1-2

  12. Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Liver Metastases Diagnosis N = 35 28 (80%) 7 (20%) 9.6 + 5.4 50.2 + 25.1 290.6 + 655.4 187.2 + 320.0 6 (17%) Synchronous Metachronous Mean number + SD Mean max size + SD Mean CEA + SD Mean CA 19.9 + SD Extrahepatic disease

  13. Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Chemotherapy N =35 1.5 + 0.7 11.0 + 3.8 4.2 + 1.8 Before 1st Hepatectomy (N = 34) (97%) Mean number of lines + SD Mean number of cycles + SD Before 2nd Hepatectomy (N = 27) (77%) All patients received 1 line. Mean number of cycles + SD After 2nd Hepatectomy (N = 26) (74%)

  14. N = 35 4.3+ 3.1 13 (37%) 17 (49%) 5 (14%) Mean + SD (months) < 3 months 3-6 months > 6 months Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Time interval between 1st and 2nd hepatectomy

  15. Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Hepatic resection 1st 4 (11%) 0 (0%) 2 (6%) 27 (77%) 2nd 26 (74%) 1 (3%) 4 (11%) - P < 0.001 0.41 - Major resection (> 3 segm) Local treatment RFA Cryotherapy Portal Vein Embolization

  16. Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Short-term outcome 1st - 8 (23%) 3 (9%) 6 (17%) 1 (3%) 1 (3%) 11.7 + 4.2 2nd 3 (9%) 22 (63%) 10 (29%) 20 (57%) 2 (6%) 9 (26%) 20.6 + 17.1 P - < 0.01 0.03 < 0.01 0.56 < 0.01 < 0.01 60-day Mortality Morbidity General complications Hepatic complications Relaparotomy Percutaneous drainage Mean hospital stay + SD

  17. Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Recurrences after second hepatectomy N = 19 (54%) Intra- and Extrahepatic (31%) No (46%) Extrahepatic (9%) Hepatic (14%) Median follow-up 26.0 months (range: 3.7 - 130.3)

  18. Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Repeat hepatectomy Extrahepatic resection Both Recurrence N = 19 (54%) 6 (32%) 4 (21%) 3 (16%)

  19. Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Total number of procedures 35 Pts 81 Hepatectomies 34 Adjuvant Procedures (PVE + Local Ablation) 15 EH Resections 130 Procedures in 35 Patients 3,7 Procedures per Patient

  20. 1 .8 .6 Overall Survival .4 44% 30% .2 0 Years 0 1 2 3 4 5 Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Overall Survival - Intention to treat (N = 51)

  21. 1 Two-stage effective (N = 35) Two-stage failed (N = 16) .8 .6 Overall Survival 57% .4 39% .2 Log rank P < 0.001 0 Years 0 1 2 3 4 5 Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Overall Survival

  22. P HR [95% CI] > 6 Metastases at diagnosis Concomitant Extrahepatic Disease No chemotherapy after second hepatectomy 0.01 0.02 < 0.01 18.4 [2.1-161.3] 5.3 [1.3-21.0] 12.8 [2.9-56.0] Two-Stage Hepatectomy (Oct 1992 - Oct 2006) Multivariate Analysis Prognostic Factors of Overall Survival after effective Two-Stage procedure

  23. Two-Stage Hepatectomy Conclusions 1) Established strategy to increase resectability in selected patients with advanced bilobar disease 2) Feasibility rate: 69% 3) Second resection (more extensive) had higher morbidity than first resection 4) Five-year survival 39% for patients that completed the total strategy, close to that of patients with a single procedure.

  24. NON RESECTABLE « HEPATIC » PATIENTS Multi Bilobar Multi Unilobar Multi Bilobar Remnant Liver<30% ≤3 nod. ≤30 mm >3 nod >30 mm Portal Embolization Hepatectomy + RxF or Cryo 2-Stage Hepatectomy

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