Hepatocellular Carcinoma Flashcards
Whta is the MC primary Malignancy of the Liver
- HCC is the most common primary malignant neoplasm of the liver
- Hepatitis B is the most common cause of HCC worldwide.
MC cause of HCC in the US
HCV is the most common cause of HCC, accounting for more than half of all cases in the United States
Other RF ?
- obese patients
- nonalcoholic fatty liver disease
- nonalcoholic steatohepatitis
- Men due to
> HBV infection, cirrhosis, smoking, alcohol abuse, and higher hepatic DNA synthesis in cirrhosis - OCP
Which HBV has the highest risk for HCC ?
- greater HBV replication
> presence of hepatitis B e antigen (HBeAg)
> higher levels of HBV DNA
HCV pathogenesis to HCC
- HCV is an RNA virus that does not integrate into the host genome
- the pathogenesis of HCV-related HCC may be related more to chronic inflammation and cirrhosis than to direct carcinogenesis.
should patients have cirrhosis to develop HCC
Cirrhosis is not required for the development of HCC
and hepatocarcinogenesis is not an inevitable result of cirrhosis
What association with cirrhosis has more risk for HCC and which one is Less??
- HBV infection
- hemochromatosis
are associated with higher risk of HCC - alcohol
- primary biliary cirrhosis
are associated with a lower risk of HCC
What can have a synergistic effect with HBV and HCV infection
Chronic ALCOHOL
What is Aflatoxin , and how they get it ?
- Aflatoxin, produced by Aspergillus spp.,
- powerful hepatotoxin.
- acts as a carcinogen and increases the risk of HCC.
- grow on grains, peanuts, and food products in tropical and subtropical regions.
- Ingestion of contaminated foods results in aflatoxin exposure.
Rare Presentations of HCC
- rupture
- hypovolemic shock
- hepatic vein occlusion (Budd-Chiari syndrome)
- obstructive jaundice
- hemobilia
- fever of unknown origin
Typical imaging criteria for HCC
- Rapid arterial enhancement followed by washout in the delayed phase.
- An enhancing capsule supports the diagnosis of HCC.
What about AFP ?
- Helpful in the diagnosis of HCC.
- Low sensitivity and specificity
- Specificity and positive predictive values improve with higher cutoff levels (e.g., 400 ng/mL) but at the cost of sensitivity.
- False-positive elevations with inflammatory disorders > chronic active viral hepatitis
- can be elevated with intrahepatic cholangiocarcinoma (IHC)
- Useful in monitoring for recurrence after normalization of levels.
When to do CT and MRI ?
- For hepatic nodules 1 to 2 cm on a background of cirrhosis
- a contrast-enhanced triple-phase CT and MRI scan is now recommended.
- Also for difficult cases
what is a typical feature of HCC on CT?
- arterially enhancing mass with washout of contrast material in delayed phases
when is a single study is recommended
- Lesions larger than 2 cm
» a single study may suffice.
any role for Bx ? and what are the complications ?
- do not require preoperative biopsy unless the diagnosis is in question.
- Complications:
» small risk of tumor cell spillage (estimated to be ∼1%)»_space; rupture or bleeding :
especially in cirrhotic livers and subcapsular tumors
Common Site for Mets ?
HCC largely metastasizes to the
lung, bone, and peritoneum.
what to do as part of staging ?
- Preoperative chest CT
- bone scans If there are suggestive symptoms or signs.
Risk of post op liver failure and death depends on ?
- degree of cirrhosis
- portal hypertension
- amount of liver resected (functional liver reserve)
- regenerative potential response.
which child class can go for resection ?
Child-Pugh class C patients are not candidates for resectional therapy
Child-Pugh class A patients can usually tolerate some extent of liver resection.
Child-Pugh class B patients candidates for operation, but they are generally borderline, and therapy must be individualized.
role of Laparoscopy
The yield of laparoscopy is dictated by the extent of disease and is only selectively used.
The presence of clinically apparent
- cirrhosis
- radiologic evidence of vascular invasion
- bilobar tumors
increases the yield to 30%,
The Okuda staging system
It adds up a single point for the
presence of tumor involving more than 50% of the liver
presence of ascites
albumin level less than 3 g/dL
bilirubin level higher than 3 mg/dL
Cancer of the Liver Italian Program Scoring System for HCC
see
How to grade HCC ? and what are the growth patterns?
- Graded as well, moderately, or poorly differentiated.
- hanging type > connected to the liver by a small vascular stalk and is easily resected
- pushing type > fibrous capsule.
> growth that displaces vascular structures rather than invading them > usually resectable - infiltrative type > Invade vascular structures, Positive margins are common
Tumors < 5 cm , fall into which group
Non of them
Hepatic resection is indicated for
- Child-Pugh Class A without portal hypertension
- Solitary HCC without major vascular invasion.
When to use Preoperative portal vein embolization
- Effective strategy to increase the volume function of the FLR
- Used liberally in patients with Child-Pugh class A cirrhosis with a small FLR (i.e., <30%–40% of the total liver volume) who are being considered for a major resection.
The most commonly cited negative prognostic factors are
- Tumor size
- Cirrhosis
- Infiltrative growth pattern
- Vascular invasion
- Intrahepatic metastases
- Multifocal tumors
- Lymph node metastases
- Margin less than 1 cm
- Lack of a capsule
Multifocal HCC Resection Vs TACE
In this study
resection provided better overall survival for patients with multifocal HCC compared with transarterial chemoembolization,
suggesting that resection may be an option for these patients
For respectable Tumor with High Risk features ?
a period of observation and tumor control with intraarterial therapies (e.g., transarterial chemoembolization/radioembolization) may help select patients who will benefit most from resection.
which patients have good outcome with transplant
Refinements in patient selection—namely, patients with single tumors smaller than 5 cm or no more than three tumors 3 cm in size—have resulted in improved outcomes
While the enlisted patient with HCC and cirrhosis awaits organ availability, what can u do ?
The progression of HCC is typically controlled with locoregional therapy including ablation and transarterial therapies
Who is considered for transplant
Considered For Transplant :
- Advanced cirrhosis (Child class B and C)
- Early-stage HCC
- Child class A cirrhosis have similar results with transplantation and resection and should probably be resected.
When to use Percutaneous ethanol injection (PEI)
- ablating small tumors
- cellular dehydration, coagulative necrosis, and vascular thrombosis
- tumors < 2 cm can be ablated with a single application of PEI
- larger tumors may require multiple injections
- Long-term survival after PEI for tumors smaller than 5 cm range from 24% to 40%.
Percutaneous injection of acetic acid
technique similar to PEI but has stronger necrotizing abilities, making it more useful in septated tumors.
Cryotherapy
- usually performed at laparotomy or laparoscopically
- also by percutaneous techniques
- One advantage > ice ball formed is easily monitored with ultrasound
- Disadvantages > heat sink effect, limiting the usefulness of freezing near major blood vessels
Radiofrequency ablation (RFA)
- Results in temperatures higher than 60°C (140°F) and immediate cell death.
- Able to ablate tumors as large as 7 cm.
- Efficacy of RFA for HCCs larger than 3 cm is limited because of increased local recurrence rates.
- Also limited by the protective effect of blood vessels
For small Tumors , which is better resection or RFA ?
- Resection may be superior to RFA for small HCCs in terms of both disease-free and overall survival.
Transarterial therapy for HCC is based on the fact that most of the tumor’s blood supply is from
the hepatic artery.
arterial embolization
- induce ischemic necrosis
- response rates as high as 50%
- improve the efficacy included adding chemotherapeutic agents (chemoembolization) to the bland embolization particles and oils, such as ethiodized oil (Ethiodol)
External beam radiation therapy (EBRT) is limited why ?
> > damage to normal liver parenchyma and to surrounding organs
Systemic chemotherapy effective ?
NO
Patients with resectable disease with maintained liver reserve and absence of portal hypertension are best treated with
resection
Patients with advanced underlying liver disease and with portal hypertension are best treated with
liver transplantation
In patients with very small tumors and with multiple comorbidities, Tx ?
percutaneous ablative techniques may be applied
For multifocal disease in the absence of macrovascular invasion and extrahepatic disease,
neither resection nor transplantation is applicable
and transarterial therapies offer the best results.
For symptomatic patients with advanced disease, with macrovascular involvement, and in the presence of extrahepatic disease
sorafenib is an option
> > molecular targeted therapy that inhibits the serine-threonine kinases Raf-1 and B-Raf and the receptor tyrosine kinase activity of vascular endothelial growth factor receptors 1, 2, and 3 and platelet-derived growth factor β
Standarf HCC vs Fibrolamellar
see
Postoperative adjuvant treatment
there is no recommended adjuvant treatment after HCC resection. This is largely due to lack of effective chemotherapy for HCC.
what about if patient has HBV ?
antiviral treatment in patients with HBV infection has been shown to decrease the risk of HCC recurrence and HCC-related deaths.
Fibrolamellar HCC
- younger patients
- without a history of cirrhosis.
- well demarcated
- encapsulated
- central fibrotic area.
- The central scar can make distinguishing this tumor from FNH difficult
- Elevated neurotensin levels (NOT AFP)
- Better Prognosis
- High Recurrence rates
what the pathogenesis of it ?
protein kinase A
» gain of kinase activity may have a role in the pathogenesis of fibrolamellar HCC
mixed hepatocellular-cholangiocellular tumor
- These mixed tumors tend to have a prognosis that is worse than for standard HCC but better than expected for intrahepatic cholangiocarcinoma.
A clear cell variant of HCC
- cells contain a clear cytoplasm.
- These tumors can resemble renal cell neoplasms.
- The clear cell variant may have a better prognosis than standard HCC,
Other Types of HCC
- pleomorphic or giant cell variant
» multinucleated, pleomorphic, and large - sarcomatoid differentiation (sarcomatoid variant or carcinosarcoma)
» These tumors tend not to produce AFP and have a higher incidence of metastases at presentation.
