1. Surgical Management of Hepatocellular
Carcinoma in Egypt in the Era of Liver
Transplantation and of Interventional Radiology
Refaat Kamel
Honorary Fellow of the European Board of
Transplantation
2. INTRODUCTION
• HCC is reaching epidemic proportions in
Egypt and will be on the rise.
• After controlling HCV, it will be the main
indication for LDLT in the coming years.
• Surgical Management of HCC should be
seen in the context of the various
modalities of treatment i.e. surgical
resection, transplantation and
interventional radiology.
• These should not be looked at in a
mutually exclusive way but rather in a
complimentary way
• An educated choice should be applied
with the added ingredient of wisdom
The Aim of the presentation is to demonstrate the place of surgical resection
Among the various modalities of treatment
3. Combinations of Therapy
• Careful Mapping
• Alters surgical
management plan in
18% of cases.
• Directs towards
Multiple resections,
wider resections,
combined resection
and RFA
RELATION TO MAIN
VASCULAR STRUCTURES
4. Rationale for Liver Transplantation
• Most HCC multifocal
• Best Oncologic resection
• Treats Cirrhosis
• Restores normal portal pressure
• Restores normal hepatic function
6. BREAKTHROUGH: MILAN CRITERIA
The treatment of choice for small HCC in
patients with Cirrhosis
Mazzaferro, N Engl J Med,1996
Survival > 85%
at 4 years
Recurrence 8%
5
cm 3
7. • Tumors within
UCSF criteria
– 1 yr survival 90%
– 5 yr survival 75%
• Tumors outside
UCSF criteria
– 1 yr survival 50%
– 5 yr survival < 30% Yao, Hepatology, 2001
UCSF Criteria: Results
6.5
cm 4.5
Total ≤ 8 cm
8. “Up To Seven” Criteria
Largest tumor + tumor number ≤ 7
Mazzafero, Lancet Oncol, 2009
3
cm
3 + 3 = 6
10. Mazzafero, Lancet Oncol, 2009
The bigger the size the worse the grade of differentiation
and the higher the incidence of microvascular invasion.
LIMITATION of TRANSPLANTATION
11. Jonas S, et al. Hepatology. 2001;33:1080-6.
Vascular Invasion & Histopathological Grading
determine outcome after Liver Tx for HCC
100
80
60
40
20
0
1 2 3 4 5 6 7 8 9 10 11
G1 (n = 40)
G2 (n = 60)
G3 (n = 20)
41%
73%
84%
27%
63%
68%
Survival (%)
Years post treatment
G = histological grade of tumor
12. The Limitations of Transplantation
• Age >65
• Size of the Tumour
• Outside criteria??
• AFP
• PET CT
• Availability of donor
• Drop out rate
• Vascular invasion
• Physiological age
13. The Limitations Of Interventional Radiology
• Size ???
• Technical
• Patient with Arterio-portal shunting??
• The need for repeated TACE??
• Vascular invasion
• Location: Peripheral, near vessels, near
intestine and colon, dome of the liver, left
lobe lesions, bleeding tendency?, close to GB
14. SURGERY
CURATIVE RESECTION
BRIDGE TO TRANSPLANT
Patients within the Milan
POST TRANSPLANT RESECTION
With or without interventional radiology,
+/- adjuvant therapy??
Different Roles for Surgical Resection
DOWNSTAGING PATIENTS
Patients outside Milan
15. Gold standard for liver resections
Evaluating alternative treatments, we should
consider the main outcome of liver resection
• Operative mortality 1.5%
• 5-year survival 50%
• 5-year recurrence rate > 60%
• 5-year tumor-free survival 28%
Grazi GL, et al. Ann Surg. 2001;234:71-8.
Subject to PATH Program Disclaimer
16. • These good results were not
achieved through major
breakthroughs but rather through
ATTENTION TO DETAILS
• Better selection criteria
– functional tests
– preoperative diagnosis
• Better surgical technique
– intraoperative care (low CVP)
– parenchyma mapping
(intraoperative echography)
– vascular control
– tissue division (bloodless surgery)
– tumor-free margin > 1 cm
• Better postoperative management
0
25
50
75
100
0 12 24 36 48 60
Months
Survival(%)
Before and After 92
17. Resection In Child A Patients Offers
Good Survival
Best candidates for resection
Solitary HCC
Child–Pugh A
Absence of portal
hypertension
Normal bilirubin
0
20
40
60
80
100
0 12 24 36 48 60 72 84 96
Portal hypertension and normal bilirubin (n=15)
No portal hypertension (n= 35)
Portal hypertension and bilirubin ≥1mg/dL (n=27)
Log rank 0.00001
Survival(%)
Time (months)
74%
50%
25%
Llovet JS, et al. Hepatology 1999;30:14 34–40
18. Pushing the boundaries
Multiple Tumours and portal hypertension
Ishizawa T, et al. Gastroenterology. 2008;134:1908-16.
• 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
19. Cescon M, et al. Arch Surg. 2009;144:57-63.
Simple Algorithm
20. a Presence of vascular invasion or extrahepatic metastasis to be indicated separately
b Selected when the severity of liver damage is class B and the tumor diameter is ≤ 2 cm
c Tumor diameter ≤ 5 cm, when there is only one tumor
Kokudo N, Makuuchi MJ. Gastroenterology. 2009;44 Suppl XIX:119-21.
22. BCLC staging system
Bruix J, Sherman M. Hepatology. 2005;42:1208-36.
Llovet J, Bruix J Semin in Liver Cancer. 1999;19:329-338.
23. Torzilli G, et al. Arch Surg. 2008;143:1082-90.
• Patients with BCLC stage B and stage C HCC can tolerate
hepatic resection with low mortality, acceptable
morbidity, and survival benefits if resection is performed
under strict intraoperative ultrasonographic guidance
• These results indicate that BCLC recommendations need
revision Torzilli G, et al. Arch Surg. 2008;143:1082-90.
24. 3. Surgical Bridging the patient to LT
• For HCC within Milan Criteria the risk of drop out
is 12-56% within 6-12 months (lesion >3cm)
versus 0-10% for lesions <3 cm. This justifies
primary resection followed by bridge or salvage
transplantation for tumours <5cm.
• Also allows to know unfavourable pathologies
with a minimal waiting time of 3 months and up
to 6 months
25. Tumor Doubling Time
Majima Y. 1995
22 16 39 6 (Months)
5
10
15
20
30
40
•for 5mm nodule, 2 year
•for 1.5 cm nodule, 1 year
•for 2cm nodule, 9 month !!!
•What about a 5cm lesion ??
26. 1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Time-Months6 12 2418Numbers at risk
32 21 6 2
CumulativeProbabilitiesofDropout
Single lesion > 3 cm, or 2 to 3 lesions
Single lesion ≤ 3 cm
HR 9.0, P=0.004
Dropout according to HCC characteristics..
SO BRIDGING TO TRANSPLANTATION
26 15 9 7 3
0
27. Advantages
• Best possible complete
control of the tumour
• Possibility of selecting
patients with poor
prognostic signs in the
pathology such as
undifferentiated tumour,
satellite lesions,
microvascular ivasion,
capsular effraction
Disadvantages
• Higher cost
• Higher Periprocedural
risks
• Limited number of
suitable patients.
• Can Render the
transplant more
technically demanding
Surgical Bridging
Plays a role in well compensated patients with low pressure gradients with lesions not amenable
to other forms of treatment as lesions near the gall bladder pedunculated lesions, surface
and left lobe lesions
28. Bridging Resection followed by Transplantation
• In selected patients, liver
resection prior to
transplantation does not
increase the morbidity or
decrease the long term
survival following LT.
Therefore, liver resection can
be integrated in the treatment
strategy of HCC.
• The 5 year survival after
transplantation was 61% for
the primary transplant group
compared to 59% for the
secondary transplant group.
Belghiti et al, Ann Surg 2003
29.
30. Vitale A, et al. Ann Surg Oncol. 2010;17:2290-302.
Siegel AB, et al. Hepatology. 2010;52:360-9.
Response to therapy can be Used as a Crude
Surrogate marker of Tumour Biology
Months post-liver transplantation
Intention-to-treat survival
1.0
0.8
0.6
0.4
0.2
0 12 24 36 48 60
Responder (n = 85)
Non-responder (n = 62)
p < 0.01
Months
Freedomfromrecurrence
31. • Biologic behavior is probably as important as size and
number of tumors in terms of predicting post liver
transplantation events in the setting of hepatocellular
carcinoma and also risk of drop out
• Biopsy of HCC or use of advanced biomarkers
should be moved to a more common use in evaluating
patients with HCC outside of the Milan criteria. The
histopathology and the biomarkers may assist in
defining patients who have a poor prognosis and are
more likely to have recurrence of disease, and thus
practitioners can appropriately modify treatment options
opting more for surgical resections and interventional
radiology.
The Missing Link
32. 4. SURGICAL DOWNSTAGING
• The term applies to treatment aimed
at converting patients with tumour
burdens beyond conventional criteria
(for number, size, AFP, and viable
tissue at image) to within the limits of
Milan and UCSF criteria with the
purpose of making patients originally
excluded suitable for transplant
candidacy
33. Criteria for downstaging
• 1 lesion > 5 cm and up to 8 cm
• 2–3 lesions with 1 or more lesions > 3 cm
and not > 5 cm, with total tumor diameter
up to 8 cm
• 4–5 lesions with none > 3 cm, with total
tumor diameter up to 8 cm
Yao FY, et al. Hepatology. 2008;48:819-27.
36. Post Transplant Resection
A NEW CHALLENGE
Previously ablated lesion Newly developed lesion resected
With or without interventional radiology, Role of adjuvant therapy??
10-20%
37. Reporting on 500 cases
500 cases
498 primary
2 retransplants
Primary
495 right lobes
3 left lobes
2 Retransplants
Right lobe
38. Hepatocellular Carcinoma: A growing
indication (23.6%)
1244 HCC pt
Advanced 974
(78%)
palliative
Early and
Intermediate 270
(22%)
Within Milan142
(52%)
Outside Milan128
(48%)
HCC Multidisciplinary Clinic
39. 142 within
Milan
50 bridging
(35%)
3 Resections
20 DROPOUT
(40%)
30 LDLT (60%)
No bridging 92
(65%)
83LDLT(90%)
9DROPOUT
(10%)
128 OUTSIDE
103 (80%)
Palliative
25 (20%)
Downstaged
3 resections
5 LDLT (20%)
20 Dropout
(80%)
Bridging Therapies should be applied whenever possible to minimise dropouts
40. SURGERY
CURATIVE RESECTION
Child A, early B,
Size of no importance, lesions close to viscera
left lobe lesions, dome lesions
and large sized lesions, peripheral lesions
BRIDGE TO TRANSPLANT
Patients within the Milan
Child A, difficulty in finding a donor,
single tumour reaching the limits of Milan
Tumours close to vessels
POST TRANSPLANT RESECTION
With or without interventional radiology,
+/- adjuvant therapy??
DOWNSTAGING PATIENTS
Tumours extending beyond Milan
Different Roles for Surgical Resection
41. Take Home Message
• A multidisciplinary approach for the management of patients
with HCC is ideal for optimising their choices.
• Multimodality treatments are not exclusive but rather
complimentary.
• The choice should be an educated one
• SURGERY RETAINS ITS ROLE AT THE LIMITATIONS OF
OTHER MODES OF TREATMENT
• Pushing the boundaries is a human habit!!
• The scene in HCC is very dynamic
• New players all the time (adjuvant therapy, TARE, etc.)
• Allow aggressive tumours to announce themselves
