Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer

Training Module 5 – Version 1.1

For Internal Use Only

®

Liver Cancer

Training Module 5 – Version 1.1

For Internal Use Only

®

Liver Cancer

Training Module 5 – Version 1.1

For Internal Use Only

®

Liver Cancer

Primary Liver Cancer

Secondary Liver Cancer

Hepatic neuroendocrine metastasis

Training Module 5 – Version 1.1

For Internal Use Only

®

Liver Cancer

Primary Liver Cancer

Secondary Liver Cancer

Hepatic neuroendocrine metastasis

Training Module 5 – Version 1.1

For Internal Use Only

®

Primary Liver Cancer

Incidence and mortality

Worldwide primary liver cancer is considered the fifth most significant cancer in terms of number of cases (437,000 or 5.4% of new cancer cases)

It is the fourth most significant in terms of mortality (427,000 deaths or 8.2% of the total)

The small difference in incidence and mortality reflects the extremely poor prognosis of primary liver cancer

D.Parkin et al, CA Cancer J.Clin 1999: 49(1) 33-64

Training Module 5 – Version 1.1

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Primary Liver Cancer

hepatocellular carcinoma (HCC)

cholangiocarcinoma

haemangioendothelioma

haemangioblastoma

angiosarcoma

primary sarcoma

HCC is the most common primary malignancy of the liver (85%)

Types of primary liver cancer:

Training Module 5 – Version 1.1

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Primary Liver Cancer

hepatitis virus infections (HBV, HCV)drugs (mostly alcohol and tobacco)mycotoxins or phytotoxinsliver diseasesmetabolic diseaseschemical agents and inorganic substancesmedicationionizing radiation

HCC - Risk factors:

Training Module 5 – Version 1.1

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Primary Liver Cancer

pain in the upper abdomenbloating, flatulenceanorexia, nauseaweight lossfatigue, weaknessstool irregularities

HCC - Symptoms:

HCC develops without subjective complaints and is therefore usually detected (too) late!

Complains - if any - are very varied:

Training Module 5 – Version 1.1

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Primary Liver Cancer

feversubicterusasciteslatent encephalopathyarterial murmurtenderness upon pressurepalpable tumourperihepatic friction

HCC - Clinical findings:

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Primary Liver Cancer

laboratory findings (incl. alpha-fetoprotein=AFP)

sonography

computer tomography

percutaneous fine-needle biopsy (FNB)

laparoscopy

HCC - Diagnosis:

Training Module 5 – Version 1.1

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Primary Liver Cancer

HCC - Diagnosis – Computer Tomography (CT):

Training Module 5 – Version 1.1

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Primary Liver Cancer

HCC - Diagnosis - Laparoscopy:

Training Module 5 – Version 1.1

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Primary Liver Cancer

HCC - Prognosis:

The prognosis is determined by the tumour mass and its speed of growth at the time of diagnosis.

Signs of poor prognosis are:

considerable size of tumour (>5cm)

infiltrative growth

multilocular growth

metastatic spread

Training Module 5 – Version 1.1

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Primary Liver Cancer

HCC - Prognosis:

The natural course of disease shows an average survival rate of 5 months (2-8 months).

Some 3% of patients survive for 5 years

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Liver Cancer

TNM staging of primary liver cancer:

T0 Disease freeT1 <2cm, no vascular invasionT2 <2cm, vascular invasion

or: >2cm, no vascular invasionT3 >2cm with vascular invasion

or: multiple lesionsT4 multiple lobes, macrovascular invasion

N0 no regional lymph node involvementN1 regional lymph node involvement

M0 no metastasisM1 metastasis

Training Module 5 – Version 1.1

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Primary Liver Cancer

HCC – Staging:

0 points 1 point

Liver invasion <= 50% > 50%

Ascites no yes

Bilirubin <= 3mg/dl > 3mg/dl

Albumin > 3g/dl <= 3g/dl

stage 1: 0 points, stage 2: 1-2 points, stage 3: 3-4 points

K.Okuda et al., 1993

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Primary Liver Cancer

HCC - Complications:

acute liver failure

portal hypertension

The cause of death is anorexia with tumour cachexia, accompanied by signs of circulatory and renal failure.

Occasionally there is intraperitoneal hemorrhage and a tumour rupture with formation of hemorrhagic ascites

Training Module 5 – Version 1.1

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Liver Cancer

Primary Liver Cancer

Secondary Liver Cancer

Hepatic neuroendocrine metastasis

Training Module 5 – Version 1.1

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Secondary Liver Cancer

Many Patients with cancer will develop hepatic metastases

Liver metastases develops via the portal vein, via the hepatic artery or via lymphatic permeation.

In many cases there will be widespread dissemination and liver involvement will not be a separate medical problem

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Secondary Liver Cancer

If the metastases are widespread the expectation of life is only 2-3 months

Metastatic carcinoid tumours may be very slow growing, and in this disease hepatic metastases are compatible with survival of 3-5 years

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Secondary Liver Cancer

Blood circulation

Training Module 5 – Version 1.1

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Secondary Liver Cancer

Most common ‘feeding’ primary tumours

breastlungmelanoma

colorectal

Only portal hepatic metastases have a low probability of extrahepatic disease

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Secondary Liver Cancer

Hepatic colorectal metastasis

Approximately 160,000 new cases of colorectal cancer (CRC) are diagnosed each year in the United States

Approximately 62,000 deaths are expected due to colorectal cancer (CRC) in 2006 (US)

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Secondary Liver Cancer

50% of patients in whom the primary tumour drains into the portal vein will develop hepatic metastases!

50

50

Hepatic colorectal metastasis

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Secondary Liver Cancer

cancer umbilicusmetastases

Training Module 5 – Version 1.1

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Secondary Liver Cancer

Training Module 5 – Version 1.1

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Secondary Liver Cancer

Number of nodes / lobes affected

A solitary node is found in some 10% of patients at the time of diagnosis

In 15-20% of cases only one lobe is effected

At the time of diagnosis most patients have multiple nodes in both lobes

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Secondary Liver Cancer

increasing malaisefeeling of weaknessfebrile attacksupper abdominal painanorexiaweight loss

Symptoms:

But: Metastases are characteristically asymptomatic.

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Secondary Liver Cancer

hepatomegaly (liver growth)hardening of the liveroccasional palpability of tumour nodesoccasional ascitesoccasional thrombosis of the portal veinoccasional swelling of the lymph nodes

Clinical findings:

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Secondary Liver Cancer

biochemistry: rise in γ-GT is characteristictumour markerssonographycomputer tomography (CT)MRIexplorative laparoscopyfine needle biopsy (FNB)

Diagnosis:

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Secondary Liver Cancer

Laboratory findings:

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Secondary Liver Cancer

Prognosis (CRC-Metastasis):

The natural course of disease shows an average survival rate of 3-10 months

The 5-year survival rate is 2% to 8%

In almost all cases the patients die because of their metastatic liver disease

Training Module 5 – Version 1.1

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Liver Cancer

Primary Liver Cancer

Secondary Liver Cancer

Hepatic neuroendocrine metastasis

Training Module 5 – Version 1.1

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Secondary Liver Cancer

Hepatic neuroendocrine metastasis:

Neuroendocrine tumours (NET) are rare tumours arising from cells within the gastrointestinal mucosa and pancreatic islet that normally secret regulatory hormones

Up to 93% of patients with neuroendocrine tumours develop liver metastasis.

A mean survival up to 8.1 years has been reported

Training Module 5 – Version 1.1

For Internal Use Only

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Liver Cancer

Primary Liver Cancer

Secondary Liver Cancer

Hepatic neuroendocrine metastasis

Training Module 5 – Version 1.1

For Internal Use Only

®

Liver Cancer

What is most important to remember?

HCC – Incidence and Prognosis

CRC – Liver Metastasis

NET