MALIGNANT LIVER TUMORS

MOHAMED A. SHARAAN
MBBch, MS, MD (Alexandria Univ) AFSA (Toulouse, France) Lecturer of Hepato-Pancreatico-Biliary Surgery Faculty of Medicine University of Alexandria

Outline
Classification. HCC : - Incidence. - Risk factors. - Pathological types. - Presentations. - Diagnosis. - Treatment. Hepatoblastoma. Liver metastasis. CRLM.

Classification
1. 2. 3. Benign Tumours: Heamangioma. Adenoma. Focal nodular hyperplasia.

1. 2. 3. 4. 5.

Malignant Tumours: Hepatocellular Carcinoma (HCC) Intra-hepatic cholangiocarcinoma. Hepatoblastoma. Liver metastasis. Sarcoma.

HCC
Incidence:

The 5th most common cancer worldwide. 3rd cause of cancer death. Asia, Africa (high incidence) South Europe, Japan (intermediate) North Europe, north America (low incidence). The mean annual incidence of HCC in cirrhotic pts in the west (3-4%) Male > Female. Advanced age, High AFP. Co-infection of HCV and HBV.
Bosch et al,2004, Parkin et al,2001, Tanaka et al, 2002, Bruix et al,2004

HCC (risk factors)

Genetic changes. Chronic hepatitis (HCV, HBV). Alcohol intake. Aflatoxin intake. Obesity (NASH) Cirrhosis.

Ferber et al,2003, Chang et al,1997, Chou et al,2004

HCC (patholgical types)

Nodular (nodule) Massive.(infitrates liver parenchyma) Diffuse. (much of the liver affected) -------------------------------------Diffuse (sclerosing HCC) Expanding.(encapsulated, fibrosis Spreading.(no demarcation) Focal (Fibrolamellar HCC) Multifocal. Intermediate. Pedunculated.

HCC (screening)
EASL recommendation: U/S abd, AFP every 6 months for high risk pts.

Aiming for detection of early HCC during asymptomatic stage. Early detection aids for effective treatment and so long-term cure.

HCC (tumor markers)

AFP, a normal serum protein synthesized by fetal liver cells and yolk sac cells, is the most widely studied screening test used as a tumour marker for HCC. The normal range for AFP is 1020 ng/ml and a level >400 ng/ml is usually regarded as diagnostic.

HCC (tumor markers)

AFP also produces false positives; levels 20250 ng/ml are frequently in regenerating nodules in viral cirrhosis. A rising AFP over time, is virtually diagnostic of HCC.

Natural history of HCC

HCCs develop as small nodules. The majority of their growth takes place in an asymptomatic phase which may be in years. Estimated doubling times of HCC vary between 1-19 m with a median of 6 m. The major factors influencing overall survival are severity of underlying liver dysfunction and tumour size at initial detection.

This suggests that if earlier diagnosis can be made, the opportunity for intervention may be greater.

HCV: Disease Progression

Time: 20-30 years

HCV infection

60-85%1
Chronic HCV Cirrhosis Hepatic Failure

20%-50%2

~ 20%3 ~20%4
Liver Transplant Candidates

Liver Cancer
1. NIH Consensus Development Conference Statement; March 24-26, 1997. 2. Davis GL et al. Gastroenterol Clin North Am. 1994;23:603-613. 3. Koretz RL et al. Ann Intern Med. 1993;119:110-115. 4. Takahashi M et al. Am J Gastroenterol. 1993;88:240-243.

HCC (presentations)
Aymptomatic.(discovered during screening). Wt loss and RUQ pain (most common) Worsening of pre-existing chronic liver dis Acute liver failure. O/E: Signs of cirrhosis Hard enlarged RUQ mass. Jaundice, ascites.

HCC (metastasis)
Rest of the liver Portal vein Lymph nodes Lung Bone

HCC (Lab. Profile)

Labs of liver cirrhosis AFP (Alfa feto protein) Is an HCC tumor marker >100ng/ml are highly suggestive of HCC Elevation seen in more than 70% of pt. >1000ng/dl (bad prognosis)

PIVKA (Protein induced by vitamin K absence) Glypican 3

HCC (diagnosis)
Clinical presentation Elevated AFP US Triphasic CT scan. MRI (with Gadolinium) Biopsy??

Guidelines for Diagnosis of HCC

A focal lesion in the liver of a patient with cirrhosis is highly likely to be HCC. Initial assessment should be by TRIPHASIC (CT) of the liver (local spread) and thorax (metastases). (MRI) with contrast enhancement or angiography with lipiodol injection and follow up CT may increase the accuracy of detection of other liver lesions. Biopsy is rarely required for diagnosis, and seeding of tumour in the needle tract occurs in 13%. Biopsy of potentially operable lesions should be avoided where possible. NO BIOPSY
Gut 2003;52; S D Ryder Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults

HCC (U/S)

HCC (Triphasic CT)

HCC (Triphasic CT)

HCC (Treatment options)

1. Hepatic resection. 2. Local Ablation (RFA, Ethanol injection, cryoablation) 3. TACE. 4. Liver Transplantation. 5. Sorafenib (Nexavar).

Guidelines for the Surgical Treatment of HCC

1. The only proven potentially curative therapy for HCC remains surgical, either hepatic resection or liver transplantation, and patients with single small HCC (<5 cm) or up to three lesions <3 cm should be referred for assessment for these treatment modalities. 2. Liver transplantation : patient with cirrhosis and a small (5 cm or less single nodule or up to three lesions of 3 cm or less) HCC., with liver insufficiency.

3. Hepatic resection : patient with HCC and a non-cirrhotic liver (including fibrolamellar variant).
4. Resection in highly selected patients with hepatic cirrhosis and well preserved hepatic function (Child-Pugh A) who are unsuitable for liver transplantation.

Such surgery carries a high risk of postoperative decompensation and should be undertaken in units with expertise in hepatic resection and management of liver failure.

Guidelines for the Non-Surgical Treatment of HCC

Non-surgical therapy used when surgical therapy is not possible.

- Percutaneous ethanol injection (PEI). It is best suited to peripheral lesions, less than 3 cm in diameter.
- Radiofrequency ablation may be a good alternative ablative therapy .

- Chemoembolisation can produce tumour necrosis and has been shown to affect survival in highly selected patients with good liver reserve.

- Systemic chemotherapy with standard agents has a poor response rate and should only be offered in the context of trials of novel agents.

Radio Frequency Ablation

Ethanol Injection

HCC
Chemoembolization

Inject chemotherapy selectively in hepatic artery Then inject an embolic agent Only in pt with early cirrhosis No role for systemic chemotherapy

HCC
Chemoembolization

HCC
Fibro-Lamellar Carcinoma
Presents in young pt (5-35 yrs). Not related to cirrhosis. AFP is normal. CT shows typical stellate scar with radial septa showing persistant enhancement. Has good prognosis. Rare type of HCC (10% of HCC)

HCC
Prognosis

Tumor size Extrahepatic spread Underlying liver disease Pt performance status

Llovet JM, Bru C, Bruix J. Prognosis of Hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999;19:329338

Hepatic metastasis

Liver metastases are malignant (cancerous) tumors that originated at sites remote from the liver and spread to the liver via the blood stream.

Liver Metastasis
Causes, incidence, and risk factors
Common primary tumors that may spread to the liver include GIT cancers (colorectal, pancreatic, stomach and esophageal), as well as breast cancer, lung cancer, melanoma, and a number of other cancers.
The reasons for such spread vary, and depend both on blood flow and on the characteristics of the different cancer cells. GIT cancers often spread to the liver because blood flows directly from these organs to the liver. Cancer cells, therefore, have a direct path to the liver. The risk of cancer spreading to the liver depends on the primary cancer site. Liver metastases may be present at the time the primary cancer is diagnosed, or they may occur months or years after the primary tumor is removed.

Liver metastasis
(symptoms and signs)
Symptoms : Symptoms vary, and many times liver metastasis is asymptomatic. When symptoms occur, they may include: - Weight loss - Pain, usually in the right upper quadrant of the abdomen - Jaundice - Fever - Sweating. Signs and tests : - Elevated bilirubin - Abnormal liver function tests - Elevated tumor markers (CEA). - Abdominal CT scan or MRI revealing liver masses - PET scan revealing liver masses - Ultrasound of the liver that reveals masse.

Liver Metastasis
Treatment
Treatment depends on the primary cancer site, extent of spread to the liver (for example, only one tumor in the liver versus many tumors in the liver), whether it has spread to other organs, and the condition of the patient. .In situations where cancer has spread not only to the liver but to other organs as well, systemic chemotherapy (directed at treating the entire body) is usually used. In situations in which spread is limited to the liver, systemic chemotherapy may be used, although other treatment methods may be effective. When the tumor is localized to only a few areas of the liver, the cancer may be removed surgically. Use of radiofrequency waves or injection of toxic substances may also be used to kill tumors. When larger areas of the liver are involved, embolization (blockage of blood flow to parts of the liver) may be used.

COLORECTAL LIVER METASTASIS

Metastatic disease in the liver is the primary determinant of survival in patients with colorectal cancer
Berger, Feig, Fuhrman 1995

CRLM
(Epidemiology )

25% of pts diagnosed with CRC will have liver metas. at presentation. 85% of CRLM are detected within 2.5 yrs after resection of the 1ry CRC and the remaining 15% are detected within the next 2.5 yrs.

Scientific Basis for Resection of Colorectal Liver Metastasis

Hematogenous metastases from primary CRC develop in a step-wise fashion. In most patients, the 1ry tumor disseminates to local LN, to the liver, or to peritoneal surfaces. This is considered a metachronous or step-wise progression of the malignant process. Only in a minority of patients is there synchronous spread of the malignancy.

Natural History of Colorectal Liver Metastasis

Death from CRC is often a result of liver metastasis.

Surgical resection of distant metas. can produce longterm survival and cure in some pts.

Liver resection is the only treatment that offers chance of cure for patients with colorectal liver metastases

Prognostic Variables for Liver Metastasis

Age >70 1ry tumor stage. 1ry tumor location (colon > rectum). Clinical presentation of metastasis (signs/symptoms, lab abn). Synchronous metastasis. Size of metastatic lesion(s). Extent of liver involvement. Interval between 1ry diagnosis and appearance of metachronous metastasis (diagnostic interval 1 year) Multiple metastases. Presence of satellite lesions. Presence of extrahepatic disease.

Pre-op Work-up for Candidates for Resection of Metastasis

Detailed history and physical exam. Labs including CBC and LFTs. CXR. CT or MRI of abdomen/pelvis. Colonoscopy (if none within 6 months). PET scan.

Portal vein embolisation before hepatic resection

Pre-PVE

Post-PVE

Hepatoblastoma

Hepatoblastoma
Over view

Hepatoblastoma is the most common liver cancer in children, it is relatively uncommon compared with other solid tumors in the pediatric age group . Hepatoblastomas are usually unifocal and affect the right lobe of the liver more often than the left lobe. Microvascular spread can extend beyond the apparently encapsulated tumor. Grossly, the tumor is a bulging mass with pseudocapsule. Metastases affect the lungs and the porta hepatis; bone metastases are very rare. .Hepatoblastoma usually affects children younger than 3 years, and the median age at diagnosis is 1 year.

Hepatoblastoma
Presentations Patients with hepatoblastoma are usually asymptomatic at diagnosis. Disease is advanced at diagnosis in 40%, and 20% have pulmonary metastases . Children with advanced disease may have anorexia . Severe osteopenia is present in most patients and regresses with resection of the tumor. Rarely, the tumor may ruptured present with symptoms of acute abdomen. Occasionally, patients present with severe anemia resulting from tumor rupture and hemorrhage .

Hepatoblastoma
workup

Lab: - Aneamia. - Platelets (high). - AFP (High). - Liver enzymes (moderately elevated) Rad: - U/S. - CT. - MRI. - PET scan. - Biopsy??

Hepatoblastoma
Treatment

Chemotherapy. Radiotherapy. Surgery (Liver resection, transplantation).

Summary
HCC is the commonest primary tumor of the liver. HCC is related to cirrhosis. Diagnosis (history, exam, lab, radiology) Assessment is important step before selecting proper treatment tool. Resection and transplantation are curable. CRLM is 2nd common. CRLM is on top of healthy liver. Multidisciplinary treatment policy should be offered in all kind of liver tumors. Metastasis > HCC

Thank you for your attention

Dr. Mohamed A. Sharaan