SURGICAL MANAGEMENT OF HCC - Virology...

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.


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.


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


PS 0

Advanced stage (C)

Portal invasion/ extrahepatic spread


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


283 centers, 192 cities & 57 countries


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.

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


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


1230 LDLT: 2001- 2019

1230LDLT

1153

Adults

394 HCC (32%)

759 ESLD (68%)

77 Pediatric


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


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


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 .


Median time to Recurrence (TTR)within 3 Groups was NS (p=0.562 )


Survival Curve in the 3 groups ( NS (p=0.474))


Clinical Liver Disease, Volume: 13, Issue: 2, Pages: 46-50, First published: 04 March 2019, DOI:

(10.1002/cld.773)


❑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.


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


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


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.


Management of HCC Recurrence Post LDLT in our cases.

hepatectomy

25%

Sorafinib

37%

chemo/radiotherapy

25%

locoregional

13%


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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