SURGICAL MANAGEMENT OF HCC:
RESECTION & TRANSPLANTATION
Prof. Mahmoud El-Meteini
President of Ain-Shams University
Professor of HPB & liver Transplant Surgery
Ain Shams University
COLDA, Sept.6th, 2019
HCC represents 23.8% of all malignancies in Egypt.
Estimated annual number of cases exceeds 700,000, with a mean annual incidence of around 3-4%.
HCV used to be endemic in Egypt: 6.5 million Egyptians being infected and a prevalence of around 7%
(data reported from Egyptian Health Issues Survey (EHIS)).
The index indication for LDLT in EGYPT is HCV related ESLD, HCC is considered the 2nd leading indication for transplant with 26% of transplanted patients in Egypt being for HCC .
Reference:◆Kandeel A, Genedy M, El-Refai S, Funk AL, Fontanet A, Talaat M. The prevalence of hepatitis C virus infection in
Egypt 2015: implications for future policy on prevention and treatment. Liver Int. 2017;37:45–53.◆ Ibrahim AS, Khaled HM, Mikhail NN, et al. Cancer incidence in Egypt: results of the national population-based cancer
registry program. Journal of cancer epidemiology, 2014.◆Amer KE & Marwan I. Living donor liver transplantation in Egypt. Hepatobiliary surgery and nutrition, 2016;5(2), 98.
COLDA, Sept.6th, 2019
In Egypt, cadaveric LT is not yet implemented leaving LDLT as the only option for patients in need for transplantation.
Extending Milian criteria provide increased numbers of eligible candidates which help young age HCC patients provided equivalent outcomes could be achieved.
Hepatic Resection has become the standard treatment of primary liver cancer.
The EASL-EORTC- guidelines recommend hepatectomy as a treatment option for HCC patients at BCLC stage 0 or BCLC stage A and with normal portal blood pressure and bilirubin level.
Chinese & Japanese guideline including resection of portal vein tumor thrombus (PVTT) and concomitant splenectomy for cases with portal hypertension.
COLDA, Sept.6th, 2019
Modified BCLC staging system and treatment strategy
*Child–Pugh A without ascites. Applies to all treatment options apart from LT; †PS 1; tumour-induced modification of performance
capacity; ‡Multiparametric evaluation: compensated Child–Pugh class A liver function with MELD score <10, matched with grade
of portal hypertension, acceptable amount of remaining parenchyma and possibility to adopt a laparoscopic/minimally invasive
approach; §The stage migration strategy applies; ǁSorafenib has been shown to be effective in first line, while regorafenib is
effective in second line in case of radiological progression under sorafenib. Lenvatinib has been shown to be non-inferior to
sorafenib in first line, but no effective second-line option after lenvatinib has been explored. Cabozantinib has been demonstrated
to be superior to placebo in 2nd or 3rd line with an improvement in OS. Nivolumab has been approved in second line by FDA but
not EMA based on uncontrolled Phase 2 data. Please see notes for full details.
EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019
Very early stage (0)
Single <2 cm Preserved liver
function* PS 0
Early stage (A) Solitary or
2–3 nodules <3 cm
Preserved liver function*
PS 0
Intermediate stage (B)
Multinodular, unresectable
Preserved liver function*
PS 0
Advanced stage (C)
Portal invasion/ extrahepatic spread
Preserved liver function*
PS1†–2
Terminal stage (D)
Not transferable HCC End-stage
liver function PS 3–4
Prognostic stage
Solitary 2–3 nodules
≤3 cm
Optimal surgical
candidate‡
Yes No
Yes No
Transplant candidate
Treatment§
Survival >5 years >2.5 years ≥10 months 3 months
Chemoembolization Systemic therapyǁ BSC Ablation Resection Transplant
HCC in cirrhotic liver
Ablation
Conclusion: Partial Hepatectomy provided better OS for patients with RMHCC beyond Milan criteria than conventional TACE
Oncological appropriateness :Resection of liver tumourto achieve survival benefit
Host condition:General health of patient and fitness for surgery
Technical Resectability:▪ Location of tumour (number
and size) ▪ Vascular inflow/outflow▪ Biliary drainage ▪ Future liver remnant
quantity and quality COLDA, Sept.6th, 2019
Our group participates in the liver group for liver resection with 29 patients from Jan.- Mar. 2019;with Zero 90 days mortality & Blood transfusion in 2 patients
COLDA, Sept.6th, 2019
283 centers, 192 cities & 57 countries
COLDA, Sept.6th, 2019
Concluded that these 2 strategies ensure similar 5-year intention-to-treat OS. Salvage LT still achieves better DFS.
It should be a shared- decision process between the doctors and the patient for recurrent HCC when both resection and transplantation are deemed feasible.
COLDA, Sept.6th, 2019
0
20
40
60
80
100
120
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
616
30 3441
25 21 2025
13 12 8 51
18 1725 27 26
41
39
4240
36
3235 41
38
31 3635
27
7
22
30
40
2536
34 33
47 36 42
23
ASCOT Total No
WA Total No
EA Total No
Ain-Shams Experience: 1230 LDLT2001- 2019
COLDA, Sept.6th, 2019
A-ALDLT: n= 1153Pediatric LDLT: n= 77
0
100
200
300
400
500
600
700
EA WA ASCOT
256
587
310
0
72
5
Pediatric
Adults
COLDA, Sept.6th, 2019
1230 LDLT: 2001- 2019
1230LDLT
1153
Adults
394 HCC (32%)
759 ESLD (68%)
77 Pediatric
COLDA, Sept.6th, 2019
HCC cases: n= 394 (32%)Age range: 28- 67 ; Mean Age: 52
69
187
138
Number of HCC cases in each center
EA
WA
ASCOT
COLDA, Sept.6th, 2019
Milan Criteria 19965cm
3cm
UCSF Criteria 2001
6.5
cm 4.5
Hangzhou Criteria 2008
< 8 cm
>8 cm
AFP < 400
(Grade I,II)
Up-to-Seven “New Milan”2008
7cm
“Metro Ticket” Paradigm
COLDA, Sept.6th, 2019
241 HCC cases transplanted for HCC
Age range: 28-67 ; Mean age: 52.8
Milan: n= 175 (72.6%)
Up to 7: n= 36 (14.9%)
BAC: n= 30 (12.4%) (BAC: beyond all criteria)
Milan (N=175)
Up to 7 (N=36)
BAC (N=30) P value
Recurrence:N(%) 22 (12.5) 6 (16.6) 6 (20.0) 0.517 NS
Death: N (%) 51 (29.5) 15 (41.7) 10 (33.3) 0.354 NS
NO statistically significant difference between the 3 groups regarding the Recurrence Rate .
COLDA, Sept.6th, 2019
Median time to Recurrence (TTR)within 3 Groups was NS (p=0.562 )
COLDA, Sept.6th, 2019
Survival Curve in the 3 groups ( NS (p=0.474))
COLDA, Sept.6th, 2019
Clinical Liver Disease, Volume: 13, Issue: 2, Pages: 46-50, First published: 04 March 2019, DOI:
(10.1002/cld.773)
COLDA, Sept.6th, 2019
❑Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied.
❑All patients better undergo locoregional therapy either as a bridging or a downsatging.
COLDA, Sept.6th, 2019
Recurrent HCC is a unique condition due to :
① Systemic nature
② Immuno-compromised state
③ Immune-maintenance phase of the transplant graft
The patient is jointly managed by the transplant surgeon, Hepatologist, oncologist and radiologist.
Immunosuppressant should be tapered to the lowest effective dose to protect against rejection.
The combination of a mammalian target of rapamycin inhibitor(mTOR) with a reduced CNI should be considered
Management of Recurrent HCC post transplant
COLDA, Sept.6th, 2019
Surgery: (Hepatectomy or Re-transplant)
Loco regional therapy: (RFA,Micrwave,TACE,SIRT)
Systemic therapy:
1st line (Sorafenib,Lenvatinib)
2nd line (Regorafenib,Cabozantinib & Ramucirumab)
Stereotactic body radiation therapy (SBRT)
Modulation of Immunosuppression drugs.
Treatment options for Recurrent HCC
COLDA, Sept.6th, 2019
Site of HCC Recurrence
Intrahepatic
25%
Extrahepatic
25%
Both
50%
HCC recurrence encompasses a large spectrum from intra- to extra-hepatic recurrences (lung, bone…etc) or both intra and extra-hepatic recurrence.
No pre-LT factors (clinical characteristics, histology of explant) had a prognostic value for survival after post- LT HCC recurrence.
COLDA, Sept.6th, 2019
Management of HCC Recurrence Post LDLT in our cases.
hepatectomy
25%
Sorafinib
37%
chemo/radiotherapy
25%
locoregional
13%
COLDA, Sept.6th, 2019
Proposed algorithm for management of HCC Recurrence Post LT
Reference:Au, K. P., & Chok, K. (2018). Multidisciplinary approach for post-liver transplant recurrence of hepatocellular carcinoma:
A proposed management algorithm. World journal of gastroenterology, 24(45), 5081–5094. doi:10.3748/wjg.v24.i45.5081
Post transplant HCC Recurrence
Review Immunosuppression:
Reduce overall IS
Reduce CNI - Consider mTOR
Staging
PET-CT
Contrast enhanced CT & Bone scan
Oligo-recurrence
Hepatic
Resection Ablation
Regional therapy
Extra-hepatic
Resection Ablation
SBRT
Disseminated recurrence
Sorafinib
Portal pressure/bilirubin
HCC
PEI/RFA Sorafenib
Stage 0PST 0, Child–Pugh A
Very early stage (0) 1 HCC < 2 cm
Carcinoma in situ
Early stage (A)1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
TACEResection Symptomatictreatment (20%)
Survival < 3 monthsCurative treatments (30%)5-year survival (40–70%)
Palliative treatments (50%)Median survival 11–20 months
Associated diseases
YesNo
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage DPST > 2, Child–Pugh C
Intermediate stage (B)Multinodular,
PST 0
Advanced stage (C) Portal invasion, N1, M1, PST 1–2
Stage A–CPST 0–2, Child–Pugh A–B
Adapted from Bruix J, Sherman M. Hepatology. 2010.
AASLD = American Association for the Study of Liver Diseases;PEI = percutaneous ethanol injection; PST = Performance Status test; RFA = radiofrequency ablation;TACE = transarterial chemoembolization.
BCLC Staging System
Liver transplantation
TARE
Combined
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