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HCC: Risk Factors
The most important risk factor is cirrhosis from any cause:
1. Hepatitis B
2. Hepatitis C
3. Alcohol
4. Aflatoxin
5. Other
HCC: Clinical Features
• Wt loss and RUQ pain (most common)
• Asymptomatic
• Worsening of pre-existing chronic liver dis
• Acute liver failure
PE:
• Signs of cirrhosis
• Hard enlarged RUQ mass
• Liver bruit (rare)
HCC: labs
• Labs of liver cirrhosis
AFP (Alpha feto protein)
• Is an HCC tumor marker
• Values more than 200ng/ml are highly suggestive of HCC
• Elevation seen in more than 70% of pt
HCC: Diagnosis
• Clinical presentation
• Elevated AFP
• US
• Triphasic CT scan: early enhancement in arterial phase, wash out in portovenous phase
• MRI with hepatobiliary-specific contrast
• Biopsy
HCC: Prognosis
• Tumor size
• Extrahepatic spread
• Underlying liver disease
• Pt performance status
Treatment/Management
• Surgical resection • Liver transplantation
• Percutaneous ablation – Alcohol injection – Radiofrequency ablation
• Transarterial embolization and chemoembolization
• Chemotherapy
“Radical”
“Potentially Curative”
“ Palliative ”
Very early stage (0)
Early stage (A)
Intermediate stage (B)
Advanced stage (C)
Terminalstage (D)
Liver transplantation Chemoembolisation SorafenibResection PEI/RF
Symptomatictreatment
Curative treatments Palliative treatments
Associated diseases
YesNo
Increased
Normal
Single HCC
Portal pressure/
bilirubin
HCC
3 nodules ≤3cm
Hepatology, vol 53, no. 3, 2011
Extrahepatic metastasisMain portal vein tumor thrombus
Solitary or multifocal tumor in noncirrhotic liver or Child A cirrhosis
Sorafenib or systemic therapy trial
Resection /
RFA (for
< 3 cm HCC)
Solitary tumor 5 cm 3 tumors 3 cm
No venous invasion
Child A Child B Child C Child A / B Child’s C
Transplantation TACE Supportive careRFA
HCC
Confined to the liverMain portal vein patent
APASL Consensus on Treatment Algorithm
Tumor 5 cm 3 tumors
Invasion of hepatic / portal vein branches
Yes No
Child A / B Child C
Asia-Pacific Association for Study of Liver Annual Congress, 2009
Tokyo Approach
Ascites
>2.0
Not indicated for hepatectomy
Not Controlled
Total Bilirubin
None or Controlled
1.1-1.5
Limited resection
1.6-1.9
Enucleation
Left hepatectomyRight sectorectomy
Normal
ICG-R15
TrisectorectomyBisectorectomy
Normal 10-19%
Segmentectomy
20-29%
Limited resection
30-39%
Enucleation
>40%
Imamura. J Hepatobiliary Pancreat Surg 2005; 12:16–22
HCC : Resection Surgery is the mainstay of HCC treatment and achieve the
best outcomes in well-selected candidates.
Factors affecting resectability: Size<5cm
number of tumors
involvement of major structures
hepatic function
no extra-hepatic spread
no portal hypertension
5 year survival 60%-70%
3 year recurrence 45 - 60%
Llovet JM. Hepatology 1999; 30: 1434–40.
Mazzaferro V, et al. N Engl J Med 1996; 334: 693–9.
HCC: Liver Transplantation
• Best available treatment
• Removes tumor and cirrhotic liver
• Recurrence rate is low
• Not widely available
• Only if single tumor less than 5cm, or less than 3 tumors less than 3 cm each ( Milan’s criteria )
HCC: Local Ablation
• For non-resectable pt• For pt with advanced liver cirrhosis• Alcohol injection• Radiofrequency ablation• Complete responses in more than 80% of tumors
smaller than 3 cm in diameter, but in 50% of tumors of 3-5 cm in size.
• 5-year survival rates of 40%-60%. reported in patients with small single tumors, commonly <2 cm in diameter.
Sala M, et al. Hepatology 2004; 40: 1352–60. Lencioni R, et al. Radiology 2005; 234: 961–7.
Omata M, et al. Gastroenterology 2004; 127: S159–66.
HCC: Chemoembolization• Primary treatment for unresectable HCC.• Embolization agents usually gelatin or
microspheres may be administered together with selective intra-arterial chemotherapy mixed with lipiodol (chemoembolization).
• Doxorubicin, mitomycin and cisplatin are the commonly used antitumoral drugs.
• Arterial embolization achieves partial responses in 15-55% of patients, and significantly delays tumour progression and vascular invasion.
Bruix J, et al. Gastroenterology 2004; 127: S179–88.Llovet JM, et al. Lancet 2002; 359: 1734–9.
Lo CM, et al. Hepatology 2002; 35: 1164–71.
HCC : Transarterial Chemoembolization
Meta-analysis of 7 randomized controlled trials
• 2 yr survival: 41% (19-63%)
• Treatment response: 35% (16-61%)
• Average no. of sessions: 1-4.5
• Risks: – Infection
– Tumor lysis syndrome
– Hepatic failure
Llovet J HepatoI 2003"37:429
Phase III Trials of Sorafenib for Advanced HCC
Llovet JM, et al. N Engl J Med 2008; 359; 378-90Cheng AL, et al. Lancet Oncol 2009; 10: 25-34
p < 0.001 p < 0.001
p < 0.001p = 0.014
Treatment Patient ObjectiveMedian Survival (m)
Level of
No. responseOS TTP
evidence
Llovet
et al
Sorafenib 299 RR : 2.3%
SD : 71%10.7 5.5 1b
Placebo 303 RR : 0.7%
SD: 67%7.9 2.8
Cheng
et al
Sorafenib 150 RR: 3.3%
SD : 54.0%6.5 2.8 1b
Placebo 76 RR 1.3%
SD: 27.6%4.2 1.4
Cholangiocarcinoma
• Incidence in Thailand
– North East 85 / 100,000 person/yr (ASR)
– North 14.6
– Central 14.4
– South 5.7
Khon Kaen 118.8
Sriamporn S, et al. Trop Med Int Health 9: 588-594.
Cholangiocarcinoma (CCA)
Intrahepatic (Peripheral) (IHC) 6-10%
Extrahepatic (Bile duct CA) (EHC) Upper third or Hilar (Klatskin
tumor) 40-60% Middle third
17-20% Lower third or Distal
18-27%
Ronald S, et al. Ann Surg Oncol 2000; 7,1:55-66
CCA : Risk Factors
Primary sclerosing cholangitis (5-15%) Congenital biliary cystic dz, choledochal cyst,
Caroli’s dz (5-7%) Parasitic biliary tract infection: Opisthorchis
viverrini, Clonorchis sinensis Cholelithiasis, hepatolithiasis, oriental
cholangiohepatitis (10%) Chronic typhoid carrier (X6) Exposure to chemical carcinogens: asbestos,
thorium dioxide, nitrosamines
CCA : Clinical Presentation
• Jaundice (90-98% of EHC)
• Weight loss (29%)
• Abdominal pain (20%)
• Fever (9%)
• Pruritus (30%)
• Unresectable pts usually die within 6-12 m.
CCA : Treatment
• Surgery– Resection: the only curative treatment– Liver transplantation: currently contraindicated
• Chemotherapy– No demonstrable survival benefit– Partial response 10-50% (5-FU, gemcitabine, cisplatin)
• Radiotherapy– No survival benefit– Palliative for painful localisable metastasis, uncontrol bleeding
• Palliation– Surgical bypass– Biliary stent or PTBD
Liver Metastases
• The most common site for blood born metastases
• Common primaries : colon, breast, lung, stomach, pancreases, and melanoma
• Dx imaging or FNA
• Treatment depends on the primary cancer
• In some cases resection or chemoembolization is possible
Colorectal Liver Metastases
• Develop in 50%
• Responsible for 2/3 of deaths
• 5-yr survival following liver resection: 25-58% compared with 0-5% for patients who cannot be operated
Faivre J, et al. Bull Acad Natl Med 2003
Wagner JS, et al. Ann Surg 1984Abdalla EK, et al. Ann Surg 2004
Rougier P, et al. Br J Surg 1995
Results of nonsurgically treated colorectal cancer metastasis
McLoughlin JM, et al. Cancer Control 2006
Contraindication for resection of CRLM
• When the clearance of all hepatic metastases is impossible
• Celiac LN involvement
• Non-resectable extrahepatic disease
• Inadequate future liver remnant volume
Van den Eynde M, et al. Reviews on Recent Clinical Trials 2009
Unresectable liver metastasesMethods to improve resectability
• Downsizing chemotherapy
• Portal vein embolization
• Hepatic resection + RFA
• 2-stage hepatectomy
Adam R, et al. Surg Clin N Am 2004
Neoadjuvant chemotherapyfor initially unresectable liver metastases
Fig.1. Initially unresectable, centrally located colorectal liver metastasis before chemotherapy.Fig.2. Downstaging after chemotherapy in the case of Fig.1. enabled further hepatectomy.
Adam R, et al. Surg Clin N Am 2004
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