What does Hepatobiliary malignancies include?
hepatocellular carcinoma (HCC)
Epidimeology of Liver cancer
eastern Asia, middle Africa, and western Africa have higher incidence of liver cancer than those who live in developed countries.
Presentation of liver cancer
Patients with liver cancer usually are asymptomatic except those symptoms related to their chronic liver disease. Clinical symptoms are associated with advanced disease
Prognosis of liver cancer
5-year survival of 0% to 10%
what is the percentage of resection rate in liver cancer?
what attributes to that increase?
30% to 50%
With the implementation of screening programs with α-fetoprotein (AFP) and ultrasonography, improvement of surgical technique, and liver transplantation
Treatment modalities of hepatobiliary malignancies
surgical resection primary curable treatment
unresectable disease - modalities such as transplantation, chemoembolization, local ablation, systemic chemotherapy, and molecular target therapy
Topographic anatomy of liver
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.
Describe segmental division of liver proposed by Couinaud
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.
Draw segmental division of liver proposed by Couinaud
Which number does liver cancer stand in the world?
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.
Incidence rate in high risk and low risk countries
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.
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?
great prevalence of hepatitis C infection
Risk factors of liver cancer
HCC is clearly associated with hepatitis B (HBV) and hepati- tis C (HCV) viral infections and chronic liver disease
Increased relative risk factor of incidence of HCC in liver cancer patient
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
Chemical injury induction associated with HCC
ethanol - most common culpable chemical agent
nitrites, hydrocarbons, solvents, organochlorine pesticides, primary metals, and polychlorinated biphenyls
amount of chronic alcohol consumption associated with risk of HCC
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
Environmental toxins associated with the pathogenesis of HCC
aflatoxin, contaminated drinking water, and betel nut chewing
hereditary liver disease at high risk of developing HCC
hemochromatosis, Wilson disease, hereditary tyrosinemia, and type I glycogen storage disease
strategy to prevent HCV infection
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.
practice guideline of American Association for the Study of Liver Diseases (AASLD), surveillance
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.
Current recommendations for surveillance according to the AASLD
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.
HCC clinical presentation in early stage
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
Clinical presentation with symptoms in HCC
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
Diagnostics in a patient who is suspected of having HCC
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
Diagnostic blood tests in a patient who is suspected of having HCC
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.
Noninvasive criteria for diagnosing HCC suggested by the AASLD in 2005
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
what is the reported magnitude of the risk over the possibility of tumor seeding from biopsy or fine-needle aspiration in liver cancer?
1.6% to 5%
contraindication of biopsy or fine-needle aspiration in liver cancer?
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.
What are the most common modalities used to evaluate tumors in the liver.
Ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI)
Ultrasound examination of the liver
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.
Role of CT/MRI in liver cancer diagnostics
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
The most common sites of metastases in liver cancer
lung, abdominal lymph nodes, and bone.
BARCELONA CLINIC LIVER CANCER TAGING SYSTEM FOR HEPATOCELLULAR CARCINOMA
Several factors dentified as being important determinants of survival in HCC
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.
Histologic classification of malignant tumors of the liver
HCC (fibrolamellar variant)
cholangiocarcinoma (intrahepatic bile duct carcinoma)
mixed hepatocellular cholangiocarcinoma
Age distribution of fibrolamellar variant of HCC and Hepatoblastoma
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
treatment modalities in liver cancer
radiofrequency ablation (RFA)
percutaneous ethanol or acetic acid ablation
transcatheter arterial chemoembolization (TACE)
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 risk of multicentric occur- rence increases with progression chronic liver disease and cirrhosis.55 although multiple tumors occur less often hbv-associated hcv-associated inci- dence intrahepatic recurrence is significantly higher patients a sustained hbeag-positive high serum concentration hbv dna.57 despite these observations mainstay therapy surgical resection. majority however are not eligible for surgery because>