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Eleonora De Martin1.2.3. Michel Rayar 4. 5. 6. Damien Bergeat 7. Luis Carvalho 4. Maximiliano Gelli 1. Rene Adam 1. 8. 9. Denis Castaing 1. Daniel Cherqui 1. 8. 9.
Antonio Sa Cunha 1. 8. 9. Didier Samuel 1.2.3. Emmanuel Boleslawski 10. 11. Karim Boudjema 4. 5. 6. Eric Vibert1.2.3
1Centre Hepato Biliaire. AP-HP Hopital Paul Brousse. 2 Univ Paris-Sud. 3 Unit 1193. Inserm. VILLEJUIF. 4 Service de Chirurgie Hepatobiliaireet Digestive. CHU de Rennes - Hopital Pontchaillou. 5 Universite de Rennes. 6 UMR991. Inserm. 7 Service de Chirurgie Digestive et
Transplantations. CHU de Lille - Hopital Claude Huriez. Rennes. 8 Univ Paris-Sud. 9Inserm. VILLEJUIF. 10 Service de Chirurgie Digestive et Transplantations. CHU de Lille - Hopital Claude Huriez. 11 Univ Nord-de-France. Lille. France
Liver Transplantation versus Resection for Small Intrahepatic Cholangiocarcinomaor Hepatocholangiocarcinoma on Cirrhosis
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Bridgewater. ILCA guidelines. J Hepatol 2014
Background
Liver Transplantation (LT) is not recommendedfor Intrahepatic Cholangiocarcinoma (iCCA) orHepatocholangiocarcinoma (HCA) becauseresults are well below those published forstandard indications
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Actual Policy in small iCCA on cirrhosis
Surgery
Child A Child C
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Sapisochin. Am J Transpl 2014
Overall survival of patients with iCCA on native liver
Patient survivial with an iCCA≤ 2 cm « very early » versus > 2 cm
45%
71%
34%
P=0.2
Multicentric Spanish Study – 29 pts
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Multicentric US Study – 32 pts including 16 iCCA and 16 HCA
Facciuto. Transplantation 2014
Overall survival
78%
32%
P=0.0457%
Disease-free survival / Milan criteria
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iCCA + HCCiCCA
Patients transplanted for HCC on cirrhosis…
HCA
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Aim of this study• Compare survival of cirrhotic patients who
underwent a liver transplantation or a liverresection with iCAA or HCA inferior to 5 cm
VS
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2002 – 2014 : 60 cirrhotic patients (F4) with iCCA or HCA on the specimen
L
N=38
N=22
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Methods
• Retrospective analysis of pathological reports of cirrhotic patient (F4) transplanted or resected for primary liver cancer in 3 French HPB centers
• Selection of patients with iCAA and/or HCA witha maximal 5 cm diameter
• Comparison of the outcomes of 2 groups
• Uni- and Multivariate analysis for OS. DFS et TTR
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iCCA and/or HCA in transplanted group were always discovered on the specimen
2002 – 2012 : 38/1060 of pts transplanted for HCC on cirrhosis in the 3 HPB centers 3.5%
HCC in Milan…iCCA and/or HCA
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Transplant (n=38) Surgery (n=22) p
Age 59 (41-71) 61 (48-72) .326
Gender M/F N(%) 32 (84)/6 (16) 17 (77)/5 (23) .391
BMI 27 (17-43) 27 (24-33) .512
Diabetes N(%) 17 (45) 18 (82) .038
Etiology of cirrhosis
.350- alcoholic N(%) 24 (63) 16 (82)
- viral N(%) 7 (18) 4 (18)
- others N(%) 7 (18) 2 (9)
MELD score 14 (5-39) 9 (6-14) .035
Results are expressed as median (range)
Preop. Demographic Data
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TransplantN=38
SurgeryN=22
p
iCCA N(%) 25 (66) 19 (85) 0.77
HCA N(%) 13 (34) 3 (14) 0.08
Single nodule N(%) 24 (63) 18 (82) .133
Nodules number 2 (1-11) 1 (1-9) .000
Diameter max. mm 19 (5-40) 31 (15-50) .000
Delay before LT or Res 11 (1-40) 4 (1-95) .005
Alfa-fetoprotein (ng/ml) 7 (2-338) 6 (1-53) .526
In Milan (specimen) N(%) 25 (66) 17 (77) .396
Results are expressed as median (range)
Postoperative Data - I
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TransplantN=38
SurgeryN=22
p
90-Days Mortality 0% 0% 0.77
Adjuvant Gemox N(%) 5 (13) 3 (14) 1
Follow-up (Months) 59.0 64.7 0.86
Recurrence N(%) 16% 50% 0.005
Death without Recurrence N(%) 8% 18% 0.23
Alive without Recurrence N(%) 76% 32% 0.001
Results are expressed as median (range)
Postoperative Data - II
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74%
34%
P=0.03LT
RS
Median follow-up 59 (30-88) months
79%
59%
Overall Survival
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Median Survival
(months) p HR 95%CI p
LT vs RS 98 vs 59 0.04 0.19 0.06 - 0.55 0.003
Age > 65 86 vs 71 0.51
Diabetes 73 vs 93 0.21
ALD/NASH vs Viral vs Other 83 vs 9 vs 77 0.90
MELD > 14 105 vs 82 0.52
HCA vs iCCA 65 vs 87 0.09 3.42 1.26 - 9.33 0.016
Single nodule 82 vs 75 0.73
Nodule diameter < 2 cm 92 vs 76 0.37
Nodule diameter < 3 cm 94 vs 60 0.09
Milan IN 86 vs 72 0.14 0.33 0.12 - 0.9 0.03
Factors associated to OS
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P= 0.0001
75%
13%
LT
Surg
Median follow-up 59 (30-88) months
79%
33%
Disease Free Survival
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Median Survival
(months) p HR 95%CI pLT vs RS 98 vs 37 0.0001 0.25 0.068-0.952 0.004Age > 65 67 vs 78 0.39Diabetes 92 vs 63 0.14 -OH/NASH vs Viral vs Other 79 vs 57 vs 72 0.52TTT pre-op 93 vs 58 0.04 -MELD > 14 104 vs 73 0.30HCA vs iCCA 65 vs 76 0.35Single nodule 73 vs 70 0.50Nodule diameter < 2 cm 81 vs 69 0.45Nodule diameter < 3 cm 88 vs 42 0.01 -Milan IN 77 vs 74 0.25
Factors associated to DFS
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p = 0.001
66%
21%
LT
Surg
58%
16%
Median follow-up 59 (30-88) months
Recurrence to Time
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No Factors associated to DFS in liver transplant group
Median Survival (months) p HR 95%CI p
Age > 65 57 vs 96 0.79
Diabete 101 vs 92 0.65
OH/NASH vs Viral vs Other 102 vs 85 vs 91 0.76
MELD > 14 104 vs 91 0.82
CCA vs HCCA 104 vs 90 0.12
Nodule unique 98 vs 84 0.75
Nodule diameter < 2 cm 89 vs 104 0.4
Nodule diameter < 3 cm 100 vs 90 0.84
Milan In 102 vs 81 0.18
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2 Factors associated to DFS in liver transplant group
Median Survival
(months) p HR 95%CI p
Age > 65 30 vs 35 0.49
Diabete 8 vs 40 0.03
OH/NASH vs Viral vs Other 46 vs 13 vs 7 0.002 38.7 3.0-495.9 0.005
CCA vs HCCA 41 VS 13 0.15 6 0.83-43.2 0.007
Unique Nodule 41 vs 13 0.15
Nodule diameter < 2 cm 25 vs 39 0.68
Nodule diameter < 3 cm 38 vs 30 0.33
Milan In 43 vs 11 0.03
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Conclusions
• Liver transplantation improved drastically overalland recurrence free survival comparatively to surgery in cirrhotic patients with iCCA and/or HCA inferior to 5 cm
• These data justified
1. To reconsider LT for iCCA and/or HCA inferior to 5 cm
2. Randomized study : LT vs Surgery in iCCA/HCA < 5 cm