Chapter 60 Cancer of the Liver and Hepatobiliary Tract

Question 1

What does Hepatobiliary malignancies include?

Answer 1

hepatocellular carcinoma (HCC)

gallbladder cancer

intrahepatic cholangiocarcinoma

extrahepatic cholangiocarcinoma

rare neoplasms

sarcoma

hepatoblastoma.

Question 2

Epidimeology of Liver cancer

Answer 2

eastern Asia, middle Africa, and western Africa have higher incidence of liver cancer than those who live in developed countries.

Question 3

Presentation of liver cancer

Answer 3

Patients with liver cancer usually are asymptomatic except those symptoms related to their chronic liver disease. Clinical symptoms are associated with advanced disease

Question 4

Prognosis of liver cancer

Answer 4

5-year survival of 0% to 10%

Question 5

what is the percentage of resection rate in liver cancer?

what attributes to that increase?

Answer 5

30% to 50%

With the implementation of screening programs with α-fetoprotein (AFP) and ultrasonography, improvement of surgical technique, and liver transplantation

Question 6

Treatment modalities of hepatobiliary malignancies

Answer 6

surgical resection primary curable treatment

unresectable disease - modalities such as transplantation, chemoembolization, local ablation, systemic chemotherapy, and molecular target therapy

Question 7

Topographic anatomy of liver

Traditional

Surgical

Answer 7

Traditionally it is divided into left and right lobes separated by the falciform ligament.

The surgeon needs to understand the spatial relationship of a tumor to the hepatic vascular system preoperatively to determine resectability. Fortunately, progress in imag- ing techniques has made segmental division of the liver based on the anatomy of portal and hepatic veins feasible.

Question 8

Describe segmental division of liver proposed by Couinaud

Answer 8

liver parenchyma divided into right and left liver with four segments each.

left part of the liver

caudate lobe (segment I)

lateral segment (segments II and III)

medial segment (segment IV)

The anatomic landmark between the medial segment and lateral segment is drawn between the gallbladder and inferior vena cava (the falciform ligament).

right part of the liver comprises the anterior segments (segments V and VIII)

posterior segments (segments VI and VII)

The anatomic landmark that separates the anterior from the posterior segment is the right hepatic vein

the anatomic landmark that divides the anterior segment from the left medial segment is the middle hepatic vein.

No good anatomic landmarks exist that further divide the anterior and posterior segments into superior and inferior subsegments.

Question 9

Draw segmental division of liver proposed by Couinaud

Answer 9

Question 10

Which number does liver cancer stand in the world?

Answer 10

HCC is the most frequent primary cancer of the liver and ranks as the fifth most common cancer in the world and the third most common cause of cancer mortality.

Question 11

Incidence rate in high risk and low risk countries

Answer 11

The highest incidence rate is seen in the male population of South Korea, China, Gambia, and Senegal (28.5 to 48.8 per 100,000 populations).

In low- risk areas such as Canada, Columbia, and the United Kingdom, HCC occurs in only 1 to 3 persons per 100,000.

Question 12

incidence rates in some low-rate areas such as United States, United Kingdom, and Australia increased approximately doubled between 1976 and 2000 in United States due to?

Answer 12

great prevalence of hepatitis C infection

Question 13

Risk factors of liver cancer

Answer 13

HCC is clearly associated with hepatitis B (HBV) and hepati- tis C (HCV) viral infections and chronic liver disease

Question 14

Increased relative risk factor of incidence of HCC in liver cancer patient

Answer 14

persistent HBV infection

HBeAg (e antigen) positive (in compared to HBeAg (e antigen) negative)

chronic HCV infection and cirrhosis - 100 times the risk of uninfected persons

Question 15

Chemical injury induction associated with HCC

Answer 15

ethanol - most common culpable chemical agent

nitrites, hydrocarbons, solvents, organochlorine pesticides, primary metals, and polychlorinated biphenyls

Question 16

amount of chronic alcohol consumption associated with risk of HCC

Answer 16

80 g per day for more than 10 years increases the risk for HCC approximately fivefold.

In patients with HCV, alcohol use doubles the risk of HCC

Question 17

Environmental toxins associated with the pathogenesis of HCC

Answer 17

aflatoxin, contaminated drinking water, and betel nut chewing

Question 18

hereditary liver disease at high risk of developing HCC

Answer 18

hemochromatosis, Wilson disease, hereditary tyrosinemia, and type I glycogen storage disease

Question 19

strategy to prevent HCV infection

Answer 19

Because the development of HCV vaccination is difficult, the strategies to prevent HCV infection include blood screening, the use of disposable needles and syringes, the adoption of universal precaution for health care workers, and timely treatment of chronic HCV infection with interferon- alpha.

Question 20

practice guideline of American Association for the Study of Liver Diseases (AASLD), surveillance

Answer 20

deemed cost-effective if the expected HCC risk exceeds 1.5% per year in patients with hepatitis C and 0.2% per year in patients with hepatitis B.

Patients with hepatitis B virus, hepatitis C virus, and autoimmune hepatitis are candidates for surveillance.

Question 21

Current recommendations for surveillance according to the AASLD

Answer 21

Surveillance for HCC should be based on ultrasonography.

AFP alone should not be used for screening because of a lack of adequate sensitivity and specificity for effective surveillance and for diagnosis.

Patients should be screened at 6- to 12-month intervals.

The surveillance interval does not need to be shortened for patients at higher risk of HCC.

Question 22

HCC clinical presentation in early stage

Answer 22

asymptomatic

it is generally detected by elevation of AFP or ultrasonography screening or is an inci- dental finding in searching for other conditions such as chronic liver disease.33 Even in the advanced stage, some patients are still asymptomatic

Question 23

Clinical presentation with symptoms in HCC

Answer 23

Patients with symptoms usually suffer from chronic hepatitis and liver cirrhosis.

Clinical symptoms include general fatigue, poor appetite, ascites, jaundice, upper gastro- intestinal bleeding, splenomegaly, dilated abdominal veins, palmar erythema, gynecomastia, testicular atrophy, leg edema, and weight loss.

Tumor-related symptoms include palpable mass in the upper abdomen (hepatomegaly), acute onset of pain (hemorrhage from tumor rupture), and dull pain in the right upper quadrant of the abdomen, abdominal fullness, low-grade fever, obstructive jaundice, and splenomegaly

Question 24

Diagnostics in a patient who is suspected of having HCC

Answer 24

the clinical history frequently includes a history of hepatitis, jaundice, blood transfusion, use of intravenous drugs, or exposure to aflatoxins.

family history of hepatitis or hemochromatosis

alcohol abuse and job descriptions related to industrial exposure to possible carcinogenic agents

physical examination should include a search for signs of underlying liver disease such as jaundice, ascites, ankle edema, spider angioma on the anterior chest wall, palmar erythema, splenomegaly, increasing abdominal girth, and weight loss.

Evaluation of the abdomen for liver size, existence of tumor masses, tenderness, and abdominal bruits

Question 25

Diagnostic blood tests in a patient who is suspected of having HCC

Answer 25

serology for HBV and HCV, and AFP.

If HBV or HCV serology is positive, quantitative HBV DNA or HCV RNA should be obtained.

Evaluation of hepatic functional reserve includes prothrombin time, activated partial thromboplastin time, and serum albumin. Platelet, red cell, and white blood cell counts also should be obtained to look for simultaneous existence of portal hypertension and hypersplenism from liver cirrhosis.

Fifteen-minute retention rate of indocyanine green (ICG) before treatment is useful for determining resectability or the feasibility of radiation.

Question 26

Noninvasive criteria for diagnosing HCC suggested by the AASLD in 2005

Answer 26

serum AFP level >200 ng/mL or a typical enhancement pattern (arterial enhancement and portal or delayed washed out) on dynamic imaging of hepatic mass >2 cm in a cirrhotic liver.

The AASLD further validated the diagnostic accuracy of a single dynamic technique showing intense arterial uptake followed by “washout’’ of contrast in the venous- delayed phases in patients of chronic hepatitis B or cirrhosis of any etiology.

But histologic diagnosis of HCC is still recom- mended for patients who plan to have a nonsurgical therapy

Question 27

what is the reported magnitude of the risk over the possibility of tumor seeding from biopsy or fine-needle aspiration in liver cancer?

Answer 27

1.6% to 5%

Question 28

contraindication of biopsy or fine-needle aspiration in liver cancer?

Answer 28

coagulopathy or significant ascites

At the authors’ institution, fine-needle aspirations including cell- blocks under ultrasound guidance are routinely performed.

Core biopsy of the mass is reserved for patients in whom a definitive diagnosis cannot be made by fine-needle aspirations with cellblocks.

Coaxial cannula is used with fine-needle or core biopsies to reduce the chance of needle track seeding.

In patients who have small hepatic nodules with diagnostic possibilities ranging from well-differentiated malignancy to benign disease, ultrasonographically guided needle-core biopsy should be considered.

Question 29

What are the most common modalities used to evaluate tumors in the liver.

Answer 29

Ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI)

Question 30

Ultrasound examination of the liver

Answer 30

commonly used as a screening tool; small tumors are often hypoechoic.

As the tumor grows, the echo pattern tends to become isoechoic or hyperechoic, and HCC can be difficult to distinguish from the surrounding liver.

Nodules <1 cm should be followed with ultrasonography again at intervals of 3 months.

The contrast-enhanced ultrasound was not recommended in the diagnosis of HCC because it may provide false-positive result in patients with cholangiocarcinoma.

Question 31

Role of CT/MRI in liver cancer diagnostics

Answer 31

Nodules >1 cm in a cirrhotic liver should be investigated further with four-phase dynamic CT scan. If the four-phase dynamic CT scan cannot prove the diagnosis of HCC, contrast-enhanced MRI or biopsy is the next tool. Extrahepatic metastases are not common at presentation; they occur mainly in patients with T4 disease. Routine metastatic surveys in patients with early-stage HCC are not recommended

Question 32

The most common sites of metastases in liver cancer

Answer 32

lung, abdominal lymph nodes, and bone.

Question 33

BARCELONA CLINIC LIVER CANCER TAGING SYSTEM FOR HEPATOCELLULAR CARCINOMA

Answer 33

Question 34

Several factors dentified as being important determinants of survival in HCC

Answer 34

the severity of underlying liver disease, the size and number of the tumor, vascular invasion, regional lymph node metastasis, and the presence of distant metastases.

Question 35

Histologic classification of malignant tumors of the liver

Answer 35

HCC (conventional)

HCC (fibrolamellar variant)

cholangiocarcinoma (intrahepatic bile duct carcinoma)

mixed hepatocellular cholangiocarcinoma

undifferentiated carcinoma

hepatoblastoma.

Question 36

Age distribution of fibrolamellar variant of HCC and Hepatoblastoma

Answer 36

The fibrolamellar variant of HCC has a relatively better prognosis. It occurs more frequently in adolescents or young adults and has a more indolent clinical course than conventional HCC.

Hepatoblastoma occurs most commonly in young children (median age, 13 to 16 months) and usually presents in an advanced stage

Question 37

treatment modalities in liver cancer

Answer 37

Surgery

liver transplantation

radiofrequency ablation (RFA)

percutaneous ethanol or acetic acid ablation

transcatheter arterial chemoembolization (TACE)

cryoablation

radiation therapy

systemic chemotherapy.

Answer 38

HCC is often a multicentric disease, especially when it is asso- ciated with HCV. The incidence of multicentric disease in HCV- related HCC (53.3%) is significantly higher (P <.05) than in the non-HCV-related HCC (7.7%).54 The risk of multicentric occur- rence increases with the progression of chronic liver disease and cirrhosis.55,56 Although multiple tumors occur less often in HBV-associated HCC than in HCV-associated HCC, the inci- dence of intrahepatic recurrence of HCC is significantly higher in patients with a sustained HBeAg-positive and high serum concentration of HBV DNA.57 Despite these observations, the mainstay of therapy is surgical resection. The majority of patients, however, are not eligible for surgery because of the