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Cancers hépatiques métastatiques : Actualité 2013-2014

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Conférence du Dr. Maximiliano GELLI (Chirurgien hépatique, AP-HP Hôpital Paul Brousse, Villejuif, France) aux Journées de Chirurgie Hépato-Biliaire, juin 2014, Paris.

Publié dans : Santé & Médecine
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Cancers hépatiques métastatiques : Actualité 2013-2014

  1. 1. Quoi de neuf dans les métastases hépatiques ? Dr Maximiliano Gelli
  2. 2. Study period 2011-2013 255 pts in 56 centers (Pts/Center = 8) Tumor type Number (%) CRLM 141 (70%) HCC 17 (8%) PHCC 11 (5%) IHCC 8 (4%) NET 8 (4%) Gallbladder cancer 6 (3%) Right Hepatectomy Right Trisectionectomy Right Trisectionectomy + S1 N (%) 106 (52%) 69 (34%) 17 (8%) Preop sFLR (%) 0.25 0.20 0.19 CRLM Population Number (%) Median ± SD Synchronous LM 106 (75%) Preop CT 128 (91%) Number lesions 7 ± 6 Diameter (cm) 5.7 ± 3.4 Liver first approach 31 (22%) Additional EH procedures 12% ALPPS Hamady, Ann Surg (on press)
  3. 3. ALPPS Tumor type Stage I Stage II Feasability 100% 98% FLR (cc) 337 612 sFLR (ratio) 0.21 0.40 FLR/BW (ratio) 0.34 0.61 Hypertrophy 80 % (49-116) Time interval (dd) 7 (6-13) Predictors of failure
  4. 4. ALPPS Morbidity Number (%) Highest complication ≥Grade IIIb All patients 56 (26%) in CRLM group 30 (21%) in subgroup CRLM + ≤60 years 12 (16%) Liver failure (stage I or II) reported by clinicians 10 (5%) 50/50 criteria 16 (9%) Bile leak (stage I or II) 34 (17%) Renal failure (stage I or II) 32 (16%) Mortality Number (%) 90-day mortality All patients 19 (9%) in CRLM group 11 (8%) in subgroup ≤60 years + CRLM 4 (5.1%)
  5. 5. ALPPS Survival % All patients 1-yr 2-ys 73% 59% in CRLM group 1-yr 2-ys 77% 63% Other than CRLM 1-yr 2-ys 67% 56% p NS
  6. 6. ALPPS variations Segment IV-I ALPPS De Santibanes, J Am Coll Surg 2014 Laparoscopic microwave Ablation and PV ligation for Staged hepatec (LAPS) Gringeri, Ann Surg 2014
  7. 7. ALPPS variations Vessel identifications tags for ALPPS Brustia, J Am Coll Surg 2014 RF-assisted Liver Partition with PV ligation (RALPP) Long, Ann Surg 2014
  8. 8. PVE improves resection rate Resectable or potentially resectable CRLM Shindoh, BJS 2013 Ext RH (n=265) Cut-off: sFLR 20% for normal liver sFLR 30% for CT liver injury Adequate sFLR (n=126) Inadeqaute sFLR (n=139) Ipsilateral Right PVE + Segm IV Surgery (n=123) Surgery (n=87) PVE Success rate 96.5% Median volume increase 52.4% (-60 to 381) with a median interval 27 dd Severe PVE complication 0.7% (PV thrombosis) Drop out (n=52) 62.7% 96.7% Strategy Resection rate increases from 46.4% to 79.2% … Drop-out Disease progression 23 Inadequate sFLR growth 6 Non-therapeutic lap 16 …
  9. 9. PVE improves resection rate
  10. 10. Chemotherapy after PVE Volume increase Mean growth of controlateral liver: CT 24% vs No CT 22% (p NS) No Chemotherapy (n=39) Chemotherapy (n=25) Systemic CT 68% Regional + Syst CT 32% PVE for 208 CRLMs (n=64) Surgery (n=16) 69% Surgery (n=27) 53% Oncological Impact p < .001Mean (SD) +8% (3%) - 13% (8%) Fischer, JAMA Surg 2013
  11. 11. Chemotherapy after PVE Fischer, JAMA Surg 2013 Volume increase Mean growth of controlateral liver: CT 24% vs No CT 22% (p NS) No Chemotherapy (n=39) Chemotherapy (n=25) Systemic CT 68% Regional + Syst CT 32% PVE for 208 CRLMs (n=64) Surgery (n=16) 69% Surgery (n=27) 53% Oncological Impact
  12. 12. Post-hepatectomy PV pression Population Major hepatectomy (> 3 segm) without severe fibrosis or cirrhosis (1988-2011) Indications: CRLM 29%, LDLR 29%, IHCC 14% End-point Post-operative Liver Failure (“50-50 criteria”, Bil peak > 120, Grade C ISGLS) 90-Mortality Allard, Ann Surg 2013
  13. 13. Post-hepatectomy PV pression Population Major hepatectomy (> 3 segm) without severe fibrosis or cirrhosis (1988-2011) Indications: CRLM 29%, LDLR 29%, IHCC 14% End-point: Post-operative Liver Failure (“50-50 criteria”, Bil peak > 120, Grade C ISGLS) 90-Mortality Allard, Ann Surg 2013
  14. 14. 1-mm Cancer-Free Margin Bias of Meta-analysis: - Sample size of majority studies included - Different technique of parenchymal treansection - 0-mm margin included in <1cm-margin - “Center effect” (> 25% patients included from a single center) Hamady, Ann Surg 2014 Study design 2715 pts (1987-2010) at Hampshire Hospitals, Basingstoke, and at St James’s University Hospital, Leeds Cavitron Ultrasonic Surgical Aspiration® Stratification of margin wide: <1 (including R1), 1-4.9, 5-9.9 and > 10 mm End point: Overall survival and DFS Characteristics Median Number (%) Age 64 Period (<2000/>2000) 529/2186 N+ 1810 (67%) Extrahepatic disease 224 (8%) Synchronous 1355 (49.9%) Preop CT 1340 (49%) Number of lesion 2 (1-20) Largest diameter (cm) 4 Type of liver resection (minor/major) 1055/1660 Margin status <1 mm >1 mm 663 (24%) 2052 (76%)
  15. 15. 1-mm Cancer-Free Margin Hamady, Ann Surg 2014 Disease-free Survival Overall Disease Recurrence (Propensity score match after exclusion margin <1-mm) cut off 5 mm cut off 10 mm
  16. 16. Early Recurrence LiverMetSurvey Registry (n=6025) Inclusion criteria: R0/R1 resection, no post-operative death, no TSH Early recurrence (<6 months): 639 of 2734 recurrences (23.3%) Viganò, Ann Surg Onc 2014 Multivariate Analysis OR p T3/T4 Primary tumour 2.017 p .0002 Synchronous CRLM 1.578 p .0001 >3 CRLM 1.835 p .0001 0-mm margin 1.564 p .003 Associated i.o. RF 1.768 p .005 Histological response to CT 0.588 p .003 Adjuvant CT 0.430 p .0001 Early Recurrence After Liver Resection for Colorectal Metastases: Risk Factors, Prognosis, and Treatment. A LiverMetSurvey-Based Study of 6,025 Patients
  17. 17. Early recurrence 26.9% 49.4% p .0001 Resected (n=234) 8.9% 47.2% p < .0001 Late recurrence Not resected Recurrence (n=2734) Early Recurrence (n=639) Multivariate Analysis OR p CT before re-resection 0.529 p .028 36.6% Early Recurrence
  18. 18. Study protocol HAI (FUDR) + System ChT (Ox/Iri) + Bevacizumab Definition of irresectability (2 surg & 1 radio) technical or biological Resectability assessement after the 4th cycle and then every 2 cycles End-point Primary: Conversion to resection rate D’Angelica, Ann Surg (on press) Baseline Characterisitics Median (SD) Number (%) Age 56 (48-64) Sex (M/F) 29/20 Synchronous CRLM 46 (94%) Number of lesions 14 (7-23) Diameter > 5 cm 16 (33%) Chemotherapy history Naïve 2nd or 3rd line 17 (35%) 32 (65%) Irinotecan+5FU-LV /Ox-Iri 29/20 Bevacizumab 24 (50%) Phase II Trial of Hepatic Artery Infusional and Systemic Chemotherapy for Patients With Unresectable Hepatic Metastases From Colorectal Cancer Conversion to Resection and Long-term Outcomes HAI + Systemic CT for Unresect CRLM
  19. 19. D’Angelica, Ann Surg (on press) Results ChT history Naïve ChT 2nd/3rd line 72% 82% 72% NS Bev +/- 75%/76% NS Conversion to resection 23 (47%) Interval to conversion (m) 6 (3-22) Severe p.o. complication (≥ grade 3) 1 (14%) 90-dd mortality 0 Median Survival 38 m Disease-Free Survival 13 m HAI + Systemic CT for Unresect CRLM PR/CR 36/1 Overall RR 76%
  20. 20. Management Synchronous CRLM The Liver-First Approach to the Management of Colorectal Cancer With Synchronous Hepatic Metastases A Systematic Review Jegatheeswaran, JAMA Surg 2013 Lykoudis, BJS 2014 Systematic review of surgical management of synchronous colorectal liver metastases Conclusion None of the three surgical strategies (Primary first, Liver first or simultaneous resection) is inferior to the others. ….In absence of high-level evidence, guideline regarding timing of surgical management of synchronous CRLM are not feasible.

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