The document provides information on hepatocellular carcinoma (HCC) including its epidemiology, etiology, risk factors, staging systems, surveillance, diagnosis, treatment options and surgical approaches. It discusses that HCC is the 5th most common cancer worldwide with the major risk factors being hepatitis B, cirrhosis, and alcohol. Staging systems covered include TNM, Okuda, CLIP and BCLC. Treatment options depend on tumor stage and liver function/reserve and may include resection, ablation, transarterial chemoembolization or transplantation. Surgical approaches to resection involve either anatomical or atypical resections.

1. DEPARTMENT OF
SURGICAL ONCOLOGY-
GOVERNMANT
ROYAPETTAH HOSPITAL
PROF DR.R.RAJARAMAN ‘S
UNIT

2. Hepatocellular Carcinoma
Dr Sujay Susikar
Post Graduate Student
Department of Surgical Oncology
Government Royapettah Hospital

3. Epidemiology
 551000 cases per year worldwide
 Estimated new cases in India – 2011 – 14533
 5th most common cancer
 83 % of all HCC - seen in developing countries
 Male predominance > 2 times

4. Etiology
Major Risk Factors Other risk factors
 Hepatitis B  Male gender
 Age
 Cirrhosis
 Tobacco smoking
 HBV And HCV  DM/ Insulin resistance
 Aflatoxin β 1  Radiation exposure
 Inorganic arsenic
 Hereditary
 Radioactive thorium
hemochromatosis
 OC pills use > 8 years
 α 1 antitrypsin  Glycogen storage diseases
deficiency
 Membranous obstruction of IVC
 Hereditary tyrosinemia  Saffrole oil
 Alcohol
 Non Alcoholic Steato
Hepatitis

5. Global distribution of HCC
 < 8 / 100000
 8 – 15/ 100000
 > 15 / 100000

6. HCC surveillance
Cirrhosis Without cirrhosis
 HBV and HCV  Hepatitis B carriers
 Alcoholic  Asian males > 40 yrs
 NASH  Asian females > 50 yrs
 Family h/o HCC
 Genetic
 Africans > 20 years
hemochromatosis
 Autoimmune hepatitis
 Primary biliary cirrhosis

7. Surveillance
 USG + α FP – every 6 months
Nodule < 1cm FU 3 – 4 months till 2 years
No growth – 6 monthly
Nodule 1 -2 cm Triphasic imaging on 2 modalities,
Biopsy or FNAC
Nodule > 2 cm Triphasic CT on single modality,
FNAC or biopsy not be necessary
Only increased α FP R/O GCT,.
CT, MRI other markers

8. Clinical presentation
 Asymptomatic
 Non specific symptoms
 Tumor related – upper quadrant pain, hepatomegaly,
acute abdomen, jaundice etc
 CLD related – UGI bleed, splenomegaly, ascites,
encephalopathy
 Paraneoplastic syndromes- Hypoglycemia,
Hypercalcemia, Polycythemia, PUO,
Hypercholesterolemia, Gynaecomastia
 Metastasis related

9. Work up
Imaging:
UGG, CT, MRI
Labs:
CBC, LFTs, Chemistries, Biopsy:
Cioag panel, Hep B, C May not be required
panel, αFP

10. Criteria for Non Invasive Diagnosis
Lesions > 2 cm
 Arterial enhancement and venous washout on 1
imaging modality either on CT/MRI/USG or
angiogram
 Only arterial enhancement on 2 contrast studies
Lesions 1 – 2 cm
 Arterial enhancement and venous washout on 2
imaging modalities
 Arterial enhancement alone and αFP > 200 ng/ml

11. Clinical staging
 Numerous staging systems ( no consensus)
 TNM
 Okuda
 CLIP
 BCLC
 Incorporate 4 determinants of survival:
1. Severity of underlying liver disease
2. Size of the tumor
3. Extension of tumor into adjacent structures
4. Presence of metastasis
Recent trials – BCLC and CLIP

12. TNM - AJCC
T – primary tumor
 T1 - solitary tumor without vascular invasion
 T2 – solitary tumor with vascular invasion or
multiple tumors, none more than 5 cm Stage I T1 N0 M0
 T3 – multiple tumors
 T3a - any more than 5 cms or Stage II T2 N0 M0
 T3b - involving a major branch of the portal or hepatic
veins Stage IIIA T3a N0 M0
 T4 – tumors with direct invasion of adjacent Stage IIIB T3b N0 M0
organs other than the gall bladder or with
perforated visceral peritoneum Stage IIIC T4 N0 M0
N – regional lymph nodes Stage IVA Any T N1 M0
 Nx – regional nodes cannot be assessed
Stage IVB Any T Any N M1
 N0 – no regional nodal metastases
 N1 – regional nodal metastases
M – distant metastasis
 M0 – no distant metastases
 M1 – distant metastases

13. Okuda staging system
Criteria Positive Negative
Tumor size > 50% < 50%
Ascites + _
Albumin g/dl < 30 >30
Bilirubin mg/dl >3 <3
Stage I All negative
Stage II 1 or 2 positive
Stage III 3 or 4 positive

14. CLIP score
Criteria Points
Child – Pugh stage
A 0
B 1
C 2
Tumor morphology
Uninodular and extension <50% 0
Multinodular and extension < 50% 1
Massive or extension > 50% 2
Alpha feto protein level
< 400 ng/ml 0
> 400 ng/ml 1
Portal vein thrombosis
No 0
Yes 1

15. Barcelona Clinic Liver Cancer
(BCLC) staging system
BCLC STAGE PERFORMANCE TUMOR LIVER
STATUS FEATURES FUNCTION
0 0 Single < 2cm No portal Htn
A1 0 Single < 5 cm No portal Htn
A2 0 Single < 5 cm Portal Htn, normal
bilirubin
A3 0 Single < 5 cm Portal Htn,
abnormal bilirubin
A4 0 3 tumors, < 3cm Not applicable
B 0 Large multinodular CP A-B
C 1–2 Vascular invasion or CP A - B
metastases
D 3–4 Any CP C

16. BCLC treatment flow chart

17. Treatment options
Operable Inoperable
 Resection  Ablation
 Anatomical  Transarterial embolization
 Non anatomical  TAE
 Liver transplantation  TACE
 TARE
 Radiotherapy
 Systemic therapy

18. Resection
 Criteria :
 Medically fit for major surgery
 Single lesion < 3 – 5 cm , suitable location, no major vascular invasion
 Preserved liver function
 No portal hypertension, normal bilirubin
 20% FLV in non cirrhotic liver and 30 – 40 % in child A cirrhotic liver
 Usually for non cirrhotics
 Recurrence 5 yrs – 70 %
 Pre resection portal vein embolization – doubtful benefits
All resectable patients are eligible for liver transplantation

19. Functional liver reserve
For quantitative assessment of hepatic reserve
 Assessment of presence of portal hypertension –
Clinically and Hepatic vein catheterization
 CT volumetric studies
 Most validated – Indocyanin green clearance test

20. Liver resection
 Liver resections (hepatectomies) can be separated
into two groups.
1. Typical (anatomic) hepatectomies, the resection of
hepatic parenchyma follows one or more anatomic
scissurae.
2. Atypical (nonanatomic) hepatectomies, the resection
is not limited by anatomic scissurae.

21. Typical hepatectomies
The resection of hepatic parenchyma follows
one or more anatomic scissurae.

22. Classification of Hepatectomies
According to Anatomy
 Anatomic hepatectomies classified according to The
Brisbane 2000 Terminology of Liver Anatomy and
Resections.
 The classification based on the hepatic artery and bile
duct and division of the portal vein.

23. Anatomic hepatectomies
Right Hemiliver Right anterior section Right Trisectionectomy Segments 1-8
Left Hemiliver Right Posterior Section Left Trisectionectomy Contiguous

24. Classification According to Surgical
Technique
1. Hepatectomy with Preliminary Vascular Section
2. Hepatectomy by Primary Parenchymal Transection
3. Hepatectomy by Selective Clamping
4. Hepatectomy with Total Vascular Exclusion
5. Hepatectomy by Pedicular Clamping
6. Hepatectomy by Suprahilar Clamping
7. Hepatectomy by Intrahepatic Portal Control

25. Hepatectomy with Preliminary Vascular
Section
 First step consists of ligating and
dividing the glissonian pedicle (vein and
artery), followed by ligation and section
of the right hepatic vein before
transecting the parenchyma.
Advantages
 Darkening of the devascularized
parenchyma permits demarcation of
 Decreased intraoperative bleeding from
the portal and arterial branches.
Disadvantages
 Risk of injury to the right hepatic vein
 Difficulty in controlling the middle and
inferior branches of the right hepatic
vein.

26. Hepatectomy by Primary Parenchymal
Transection
 Begins with an incision of the
parenchyma along the line of
the scissura.
 The hilar elements are
approached and ligated from Advantages
within the liver during the •Excises an amount of liver parenchyma à
parenchymal transection. la demande, according to the nature and
the location of the lesion
 Section of the hepatic vein is •Ligation of the vessels is not hampered by
performed at the end of the anatomic abnormalities
procedure, also inside the Disadvantages
liver. •Lack of preliminary vascular control can
lead to considerable intraoperative
bleeding,

27. Hepatectomy by Primary Parenchymal
Transection
Dissecting sealer Techniques and devices used to perform
hepatic parenchymal dissection:
 Kelly clamp and bipolar forceps
 Water jet dissection
 Ultrasonic dissection
 Ultrasound cutting
 Dissecting sealer
Kelly clamp and
bipolar forceps
Ultrasonic dissection
Ultrasound
Water jet cutting
dissection

28. Hepatectomy by Selective Clamping
 Described by Morel - combines the
advantages of both.
 Begin with a hilar dissection,gain
separate control of the arterial and
portal elements of the pedicle and
clamp these without ligation.
 Right side of the retrohepatic inferior
vena cava is freed without attempting
to dissect the vena cava or the right
hepatic vein
 Right hepatic vein is ligated from inside
the liver.
 This technique provides control of the
vessels before opening the
parenchyma, and the vessels are ligated
and divided inside the parenchyma,
avoids the risks related to anatomic
vascular variants.

29. Hepatectomy with Total Vascular
Exclusion
 Completely preventing the
inflow of blood to the
liver.
 Total vascular exclusion is
achieved by simultaneous
clamping of the hepatic
pedicle and the vena cava
below and above the liver.
 At normal body
temperature, normal liver
parenchyma can tolerate
60 to 90 minutes of
devascularization.

30. Hepatectomy by Pedicular Clamping
Interrupts all inflow to the liver
parenchyma from the portal vein
and hepatic artery but leaves intact
the outflow from the hepatic veins.
It is useful in all types of
hepatectomy, but the anatomic
margins are not visible.

31. Hepatectomy by Suprahilar Clamping
 Allows superselective clamping at the
suprahilar level after dissecting the hilar
plate and exposing the sectorial
branches of the glissonian pedicle .
 The anterior right sectorial
portal branch is the easiest to
control because the sectorial
devascularization is apparent
on the liver surface, which
greatly facilitates right
anterior and right posterior
bisegmentectomies.

32. Hepatectomy by Intrahepatic Portal
Control
 Useful for anatomic segmentectomy or
subsegmentectomy
 Occlusion of the portal branch to the segment to be
resected can be achieved by transhepatic balloon
catheter placement.
 Segmental or subsegmental devascularization is
accompanied by clear demarcation on the liver surface
of the corresponding parenchymal distribution.
 An alternative method of demarcation involves injection
of methylene blue dye into a tributary of the segmental
portal branch near the lesion.

33. Atypical
Hepatectomies
The resection is not limited by anatomic scissurae.

34. Atypical hepatectomies
 Wedge Resection (Limited Resection)
 Laparoscopic Liver Resection (also included
in typical hepatectomies).

35. Wedge Resection
 Non-anatomical complete removal of the tumor with
sufficient margin.
 Wide surgical margin (e.g., wider than 10mm) is not
necessary, but care should be taken not to expose the
tumor on the cut surface.

36. Laparoscopic Liver Resection
• The first laparoscopic
anatomical liver resection, a
left lateral sectionectomy, was
reported in 1996.More
recently, larger hepatectomies
and liver resections for
malignant tumors have been
described.
 Today, about 15–20% of
liver resections might be
considered for a laparoscopic
approach.

37. Indications
 Non-pedunculated
lesions less than 5cm in
diameter
 Lesions located in the
anterior segments of the
liver (segments 2–6)
 Pedunculated lesions of
any size

38. Contraindications
 Large non-pedunculated tumors (>5cm in dia.)
 Lesions of the hepatic dome (i.e.segments7&8)
 Lesions located in the vicinity of major hepatic veins, the
inferior vena cava and the hepatic hilum
 Severe portal hypertension (portal p. >12mm Hg)
 Severe coagulopathy (e.g. platelet count <30000 ml)

39. Postoperative Tests
(after liver resection)
 Postoperative surveillance in an intensive or intermediate
care unit
 Coagulation parameters and hemoglobin for at least 48hrs
 Check daily for clinical signs of liver failure such as jaundice
and encephalopathy

40. Postoperative Complications
Short term
 Pleural effusion
 Ascites
 Liver failure
 Intra-abdominal bleeding
 Bile leak
 Subphrenic abscess
 Portal vein thrombosis
Long term
 Biloma
 Biliary stricture
 Bronchobiliary fistula

41. Liver transplantation
 Milan’s criteria:
 Single lesion upto 5 cm
 Upto 3 lesions if each lesion <5 cm
 No extrahepatic disease
 UCSF criteria:
 Solitary lesion < 6.5 cm
 < 3 lesions each < 4.5 cm( total combined tumor diameter < 8 cm)
 No extrahepatic disease
 High cost
 Non availability of donors

42. Bridging or Downstaging
approach
 In HCC exceeding transplantation criteria
 Treated with locoregional therapy – TACE and
any ablation tharapy
 Disadvantage:
 Increasing pool of transplantation recipients
 Longer wait list times
 Higher drop out rates
 Greater wait list mortality

43. Adjuvant therapy
 Not recommended at present
 I 131 lipiodol – improved DFS but not OS
 Acyclic retinoid – improved OS – more
followup required
 Sorafenib – in trial

44. Ablation therapy
 Chemically mediated ablation
 Ethanol injection
 Acetic acid injection
 Energy mediated ablation
 Radiofrequency ablation
 Cryoablation
 Microwave ablation

45. Percutaneous injections
 Lesions > 3 cm  Ethanol 95%
 Up to 3 lesions  Acetic acid 15%
 No extrahepatic disease  Multiple sessions ( 3-4)
 No portal vein  USG guidance
thrombosis  Location suitable for
 Child Pugh class A/B injection
 Age > 75 yrs  Volume needed
V = 4/3п(r+0.5)3 for
ethanol and 1/3 for
acetic acid

46. Radiofrequency ablation
 Electrode insertion into the
lesion
 High frequency alternating
current at tip resulting in
high frictional energy and
cell death
 Less side effects than PEI
and better outcomes
Criteria
 Child Pugh A/B
 Solitary tumors < 4 cms
 3 yr OS 78 – 87%

47. Trans arterial embolization
TAE TACE TARE
 Dual blood supply
 Lipiodol concentrated by HCC
 Selective placement of a catheter
 Embolization with an emulsion of
anticancer drug with lipiodol
 Sealing embolization with
particulate material
 All sizes – provided arterial supply
can be isolated without target
embolization
 Contraindications – portal vein
thrombosis, CP - C

48. Radiotherapy
 Radiosensitive tumor ( at high doses) but in a
very radiosensitive organ, toxicity easily achieved
 Complications of liver failure can make
treatment planning difficult
 Whole liver – palliative RT (21 Gy in 7 #)
 Partial liver – definitive RT
 Treatment free liver > 800 cc
 No extrahepatic disease
 No gross ascites
 Child Pugh A/B
 No variceal bleed
 No thrombocytopenia
 Lesion <6

49. Radio isotopes
( Selective Internal Radio Therapy)
 Most common used –
yttrium-90 incoroporated
into glass (TheraSphere) or
resin (SIRTex)
 Delivered thro the hepatic
artery segmentally,
subsegmentally , regionally or
to the whole liver
 Typical dose 150Gy
 Specific toxicities:
 Liver toxicity
 Pneumonitis
 GI Bleeding

50. Systemic chemotherapy for advanced
HCC
 Relatively chemo refractory tumor
 Survival often determined by degree of hepatic
dysfunction
 Systemic chemo not well tolerated
 No survival benefit
 Only SORAFENIB has shown survival benefit
 NCCN and FDA approved for systemic treatment
 Bevacizumab and Erlotinib – promising early phase II
results

51. SHARP Trial
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52. Summary
 HCC remains one of the leading causes of death
 Improved screening and surveillance have led to early detection
and treatment with good outcomes
 Resection is feasible only in early tumors with well preserved
liver function
 While liver transplantation remains a definitive therapy, scarcity
of organs preclude this option
 Local ablation therapies and trans arterial treatment techniques
have shown good results though not as a definitive treatment
option
 Novel systemic agents – SORAFENIB- have shown encouraging
results with possible role in adjuvant setting in the near future