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

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

Actual Policy in small iCCA on cirrhosis

Surgery

Child A Child C

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

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

iCCA + HCCiCCA

Patients transplanted for HCC on cirrhosis…

HCA

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

2002 – 2014 : 60 cirrhotic patients (F4) with iCCA or HCA on the specimen

L

N=38

N=22

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

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

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

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

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

74%

34%

P=0.03LT

RS

Median follow-up 59 (30-88) months

79%

59%

Overall Survival

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

P= 0.0001

75%

13%

LT

Surg

Median follow-up 59 (30-88) months

79%

33%

Disease Free Survival

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

p = 0.001

66%

21%

LT

Surg

58%

16%

Median follow-up 59 (30-88) months

Recurrence to Time

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

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

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