HEPATOMA

Dr Isbandiyah, SpPD

• Hepatocellular carcinoma (HCC) is a primary malignancy of the liver.

• It is now the third leading cause of cancer deaths worldwide, with over 500,000 people affected.

• More common in men than women (4:1)• Hepatitis (Hepatitis B or hepatitis C) and

excessive alcohol are the leading causes of HCC.

Malignant TransformationMultistep

Normal liver

Liver cirrhosis

Hepatitis CHepatitis B

EthanolNASH

Epigenetic alterationsGenetic alterations

HCC[2]

Dysplastic nodules[1]

Risk Factor

HBV HCV

Sirosis HatiAflaktosin B1

ObesitasDM

Alkoholisme

• Microscopically, there are four cytological types:– fibrolamellar, – pseudoglandular (adenoid), – pleomorphic (giant cell) and – clear cell.

HCC may present with • right upper quadrant pain, • weight loss,• jaundice, • bloating from ascites, • and signs of decompensated liver disease.

Diagnostic Procedures

• In patients with lesions less than 1 cm, >>>> conservative management with close follow-up and no biopsy is recommended.

• In patients with 1- to 2-cm lesions, a biopsy should be performed,.

• Patients with lesions greater than 2 cm, cirrhosis, characteristic imaging studies, and elevated AFP values can be managed without biopsy.

• Patients with large tumors who are not candidates for resection or transplantation, >>>>>> biopsy is frequently not indicated.

AJCC/UICC Classification System

Child-Pugh score

• The Child-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis. To determine treatment required and the necessity of liver transplantation.

• The score employs five clinical measures of liver disease. Each measure is scored 1-3, with 3 indicating most severe derangement.

Chronic liver disease is classified into Child-Pugh class A to C, employing the added score from above.

Management of Hepatocellular Carcinoma Requires a Multidisciplinary Approach

Radiation Oncology

Pathology

Oncology

Radiology

Hepatobiliary Surgery

Hepatology

Treatment/Management

• Surgical resection • Liver transplantation • Percutaneous ablation – Alcohol injection – Radiofrequency ablation

• Transarterial embolization and chemoembolization• Chemotherapy.

“Radical”

“Potentially Curative”

“ Palliative ”

Staging Strategy and Treatment for Patients With HCC

Liver transplant PEI/RF

Curative treatments

TACE

HCC

Single

Increased Associateddiseases

Normal No Yes No Yes

Terminalstage

PST 0-2, Child-Pugh A-B

Multinodular, PST 0

Portal invasion, N1, M1

Sorafenib

Portal pressure/bilirubin

3 nodules ≤ 3 cm

Intermediate stage

PST > 2, Child-Pugh C

Very early stageSingle < 2 cm

Early stageSingle or 3 nodules

≤ 3 cm, PST 0

Advanced stagePortal invasion,N1, M1, PST 1-2

PST 0, Child-Pugh A

Resection

Symptomatic (unless LT)

Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711.Bruix J, et al. Hepatology. 2005;42:1208-1236.

• Important features that guide treatment include: -– Size– Spread (stage)– Involvement of liver vessels– Presence of a tumor capsule– Presence of extrahepatic metastases– Vascularity of the tumor

Surgery: Resection and Transplantation

• Surgery is the mainstay of HCC treatment and achieve the best outcomes in well-selected candidates.

• Less than 5% patients resectable • Factors affecting resectability:

– Size<5cm – number of tumors – involvement of major structures – hepatic function – no extra-hepatic spread – no portal hypertension ·

• Requires experienced surgical and supporting team · • 5 year survival 60%-70% · • 3 year recurrence 45 - 60%

Transplantation

• Milan Criteria : Single HCC ≤5 cm or Up to three nodules ≤3 cm No extra hepatic spread• About 10 % qualify for listing• The major drawback of transplantation is

The scarcity of donors. The long waiting time.

.

Percutaneous Treatments

• For patients who cannot undergo resection.• 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.

• Although these treatments provide good results, they are unable to achieve response rates and outcomes comparable with surgical treatments.

• Transarterial Embolization and Chemoembolization is recommended as first line non-curative therapy for non-surgical patients with large/multifocal HCC who do not have vascular invasion or extrahepatic spread.

Percutaneous Ethanol Injection

• 207 patients with cirrhosis + HCC < 5 cm ·

• 100% Ethanol • Follow up was 25 months • No complications • 4.3 sessions per patient • 88% complete necrosis • 1 ,2,3-year survival rates: 90,80,63%

Cancer 1992;69:925

Radiofrequency Ablation

Palliative Therapies• 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.

Transarterial Chemoembolization

Meta-analysis of 7 randomized controlled trials • 2 yr survival: 41% (19-63%)• Treatment response: 35% (16-61%) • Risks:

– Infection – Tumor lysis syndrome – Hepatic failure

• Llovel J He aloI2003"37:429

Systemic Treatments

• A meta-analysis of seven RCTs comparing tamoxifen vs. conservative management, comprising 898 patients, showed neither antitumoral effect nor survival benefit of tamoxifen. Thus, this treatment is discouraged in advanced HCC.

• Systemic chemotherapy has been tested in nine RCT. The most active agents in vitro and in vivo are doxorubicin and cisplatin. Systemic doxorubicin has been tested in more than 1000 patients within clinical trials and provides partial responses in around 10% of cases, without any evidence of survival advantages .

Chemotherapy

• Palliative not Curative.• Regional (Intra-arterial) better that systemic.• Resistant to many agents.

Summary• Early-stage hepatocellular carcinoma is typically clinically silent, and HCC is

often advanced at first manifestation. • Without treatment, the 5-year survival rate is less than 5%. • Complete surgical resection followed by hepatic transplantation offers the

best long-term survival, but few patients are eligible for this therapy. • Radiofrequency ablation is the preferred method for managing

unresectable small HCCs that are few in number. More widespread disease is treated with percutaneous therapies such as chemoembolization.

• Systemic administration of biologic and chemotherapeutic agents is minimally successful in slowing the growth of HCC and typically is used to control symptoms in patients with overwhelming disease.

• A multidisciplinary approach that includes surgery, systemic therapy, and radiation therapy and that is based on the cooperation of radiation oncologists, interventional and diagnostic radiologists, hepatologists, and pathologists offer the best chance of a cure or at least a longer and more normal life.

hepatoma