Surgical treatment of hepatocellular carcinoma

Gian Luca Grazi
Hepato-Biliary-Pancreatic Surgery
National Cancer Institute Regina Elena
Rome
Surgical treatment of hepatocellular
carcinoma

Surgical treatment of hepatocellular carcinoma
Definition
Surgery Surgery (from the Greek:
χειρουργική cheirourgikē (composed of χείρ, "hand",
and ργον, "work"), via Latin: chirurgiae, meaningἔ
"hand work") is a medical specialty that uses operative
manual and instrumental techniques on a patient to
investigate or treat a pathological condition such as a
disease or injury, to help improve bodily function or
appearance or to repair unwanted ruptured areas.
Surgical treatment A surgical intervention performed after the appropriate
medical evaluation and diagnostic
tests have determined the need for procedure.

Shindoh J, J Hepatol 2016; 64:594-600

Natural History

J Hepatol 2012;56:908-943

• In patients with locally advanced or intermediate-stage hepatocellular
carcinoma after unsuccessful transarterial chemoembolisation, overall survival
did not significantly differ between the two groups.
• Quality of life and tolerance might help when choosing between the two
treatments.
• Better local efficacy of SIRT suggests that it might be appropriate to evaluate
SIRT in patients with less-advanced hepatocellular carcinoma.

Single nodule > 5 cm?

• Hepatic Resection has been shown to result in greater survivability and has the potential to increase
time to disease progression when compared to TACE for solitary HCC greater than 5 cm in diameter.
• Where a patient is fit for surgery, has adequate liver function and the tumor is favorable, resection
should be considered.
• An update of the BCLC staging system should be considered firstly, to better define the appropriate
course of treatment for a solitary large (5 cm) HCC and secondly, to expand the criteria for hepatic
resection.

• The outcome of PH as an initial treatment for patients with tumor outside of
Milan Criteria was superior to conventional TACE.
• The number of tumor and gender were also found to be independent risk
factors associated with OS for these patients.
• To achieve good results of PH, patients should be carefully selected to minimize
postoperative mortality and major morbidity.

Advances in the treatment of hepatocellular carcinoma
Huang J et al. Ann Surg 2010; 252: 903-912

Kudo M, Dig Dis 2011, 29: 339-364

Torzilli G, et al. Arch Surg. 2008;143:1082-90.

Cucchetti A, et al. Ann Surg. 2009;250:922-8.
Overall survival curves of the whole
study population of 241 cirrhotic
patients undergoing liver resection for
hepatocellular carcinoma with and
without portal hypertension (p = 0.008)
Overall survival curves of the matched
study population of 156 cirrhotic
patients undergoing liver resection for
hepatocellular carcinoma with and
without portal hypertension (p =
0.453)

Retrospective evaluation of 455 consecutive patients who
had undergone an initial curative liver resection for HCC
without extrahepatic metastasis at Tokyo University Hospital
between November 1994 and December 2004
Ishizawa T, et al. Gastroenterology. 2008;134:1908-

• Liver resection can provide a survival benefit
for patients with multiple HCCs associated
with Child–Pugh class A cirrhosis
• Resection for HCC also may be indicated for
patients with PHT

• Complication rates differed significantly at a cut-off
HVPG value of 5 mmHg
• HVPG exceeding 5 mmHg was associated with
• worse liver fibrosis (P = 0·004),
• higher rates of postoperative liver dysfunction (5 of
13 versus 1 of 18; P = 0·022) and
• ascites (7 of 14 versus 3 of 21; P = 0·022), and
• a longer hospital stay (median (range) 11 (7–26)
versus 8 (4–20) days; P = 0·034).
• Overall postoperative morbidity did not differ between
patients who had preoperative HVPG assessment and
those who did not (P = 0·142).
Stremitzer S et al. Br J Surg 2011, 98: 1752-1758

 Liver resection for HCC can be performed safely in
patients with HVPG between 1 and 5 mmHg.
 In contrast, patients with portal hypertension
(HVPG 6–10 mmHg) are at risk of postoperative
complications, but mortality is still low.
Stremitzer S et al. Br J Surg 2011, 98: 1752-1758

HCC
131
Intrahepatic
Cholangiocarcinoma
45
Metastases
259
Perihilar
Cholangiocarcinoma
26
Others
70
551 Liver Resections
(June 2010 – April 2017)
Gallbladder
20

5,6%
40,7%
45,4%
8,3%

• BRIDGE is a multiregional cohort study including HCC patients
diagnosed between January 1, 2005 and June 30, 2011.
• A total of 8,656 patients from 20 sites were classified into four
groups:
a) 718 ideal resection candidates who were resected;
b) 144 ideal resection candidates who were not resected;
c) 1,624 nonideal resection candidates who were resected; and
d) 6,170 nonideal resection candidates who were not resected.
• Median follow-up was 27 months.
Roayaie S, Hepatology 2015; 62: 440-451

Roayaie S, Hepatology 2015; 62: 440-451
Survival curves of patients stratified by whether they met
AASLD/EASL criteria for resection and type of treatment used.
All patients

≈ 20% of candidates who meet current EASL/AASLD criteria for LR are
denied surgery, and this is associated with a 2-fold increase in mortality.
A common practice is to offer surgery to patients beyond the
recommended criteria (majority of patients undergoing resection did not
meet criteria)
The current criteria might be expanded to include pts with either
moderate PH or slightly elevated total bilirubin >1 mg/dL, but not both,
without increase in mortality.
Expansion of criteria along other lines, such as tumor characteristics,
liver function, and performance status, is associated with significantly
lower survival.
For patients who do not meet criteria for surgery, LR may still associated
with longer survival, when compared to TACE and “other” treatments,
and shorter survival, in comparison to RFA and LT, when controlling for
other relevant factors.

Bruix J, Lancet Oncol 2015;16:1344-1354

Have we arrived at our destination?

Murali AR, Transplantation 2017; 101:e249-e257
• 48 studies involving 9835 patients
• Five-year overall survival (OS) and disease-free
survival (DFS) were worse for all categories of CLRT,
than for primary LT (odd ratio (OR) for OS: 0.59
(0.48-0.71). p<0.01)
• Primary liver transplantation has better overall
survival than curative locoregional therapy in Child
Pugh class B/C cirrhosis. In patients with Child-Pugh
class A cirrhosis and a single HCC lesion, primary LT
was not superior to CRLT on primary efficacy testing.
• About 70% of patients had recurrence of HCC after
CLRT, of which only 30% were eligible for salvage LT

Center Morphologic Criteria Biomarker Criteria Survival
Milan 1 lesion ≤ 6.5 cm
2-3 lesions ≤ 4.5 cm each
None 4 yr OS: 85%
UCSF 1 lesion ≤ 6.5 cm
2-3 lesions ≤ 4.5 cm each
Total tumor diameter ≤ 8 cm
None 5 yr OS: 72.4%
Pamplona 1 lesion ≤ 6 cm
2-3 lesions ≤ 5 cm each
None 5 yr OS: 79%
Edmonton 1 lesion ≤ 7.5 cm
Multiple lesions < 5 cm each
None 4 yr OS: 82.9%
4 yr RFS: 76.8%
Dallas 1 lesion ≤ 6cm
2-4 lesions ≤ 5 cm each
None 5 yr RFS: 1 lesion ≤ 6 cm:
63.9%/or 2-4 lesion 3.1 cm- 5
cm each: 64.6%
Valencia 1-3 lesions ≤ 5 cm each
Total tumor diameter ≤ 10 cm
None 5 yr OS: 67%
Up to 7 The sum of the size and number of tumors not exceeding 7 in
the absence of microvascular invasion
None 5 yr OS: 71.2%
Selection Criteria for LT in HCC
cadaveric donor liver transplantation (CDLT)
Center Morphologic Criteria Biomarker Criteria Survival
Hangzhou Total tumor diameter ≤ 8 cm
Total tumor diameter > 8 cm with histopathologic grade I or II
If total tumor diameter
> 8 cm AFP ≤ 400 ng/ml
5 yr OS: 70,7%
5 yr DFS: 62.4%
Rome Total tumor diameter ≤ 8 cm AFP ≤ 400 ng/ml 5 yr DFS: 74.4%
Warsaw UCSF or Up-to-7 criteria AFP ≤ 100 ng/ml 5 yr OS: 100%
Geneve (TTV) Total tumor volume ≤ 115 cm3
AFP ≤ 400 ng/ml 4 yr OS: 74,6%
Metroticket
2.0
Up-to-Seven
Up-to-Five
Up-to-Four
AFP ≤ 200 ng/ml
AFP ≤ 400 ng/ml
AFP ≤ 1000 ng/ml
5 yr Cancer Specific
Survival: 75%

Mazzaferro V, Gastroenterology. 2017 Oct 5. [Epub ahead of print]
HCC-specific survival estimates (contour plot) can be determined on the last available HCC
features along the patients’ follow-up, namely before/after neo-adjuvant treatments,
while on the transplant waiting list.
To obtain the individual prediction of overall survival, an additional 8.6% (for HCV-negative patients)
or 18.1% (for HCV-positive patients) should be subtracted from the individual HCC-specific survival.

Mazzaferro V, Hepatol 2016; 5:1707-1717
Staging and allocation for HCC within the spectrum of LT eligibility. Classes of progression and
allocation priority within the TT stages identified for HCC in well-compensated cirrhosis. LT eligibility
and priority are not determined completely up front, but they both come into focus after the best
available therapy has been applied.

Mazzaferro V, Hepatol 2016; 5:1707-1717

Cillo U, Am J Transplant. 2015;15:2552-61

Current guidelines recommend resection only for single nodules of any
size in patients without tumor related symptoms and clinically significant
portal hypertension (CSPH) and with normal bilirubin (<1 mg/dL).
If this profile is not fulfilled, postoperative morbidity increases and long-
term survival is significantly reduced.
An extension of the recommendation has been repeatedly suggested
because in patients with CSPH multiple nodules or intrahepatic vascular
invasion resection can be attempted with high rates of technical success
in experienced centers, even though tumor elimination by surgery
translates into improved survival only in properly selected candidates.
Actually, while tumor removal would be technically feasible in patients
with a large tumor burden or impaired liver function, resection may not
be worth attempting as survival could even be decreased.
In real life the decision to resect HCC is based on individual patient
components and local conditions that are not captured by guidelines.
Romagnoli R, Bruix J, Mazzaferro V, Hepatology 2015, 62: 340-342
Some Final Considerations on Resections

Gian Luca Grazi
Hepato Biliary Pancreatic Surgery
National Cancer Institute “Regina Elena”, Rome, Italy
gianluca.grazi@ifo.gov.it
www.chirurgiadelfegato.it
Follow us on Twitter @Chirurgiafegato

Surgical treatment of hepatocellular carcinoma

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