tbl 6: hepatocellular carcinoma (HCC) Flashcards
Hepatocellular carcinoma (HCC) – primary tumour of the liver that usually develops in the setting of chronic liver disease, particularly in patients with cirrhosis and chronic hepatitis B virus or hepatitis C virus infection - Risk factors for HCC include \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
- Clinical features of HCC
o Asymptomatic – picked up on routine screening in high risk patients
o Symptomatic – abdominal pain, weight loss, early satiety
o Paraneoplastic syndromes –
§ ___________ – usually occurs in late HCC, thought to result from the tumor’s high metabolic needs, usually asymptomatic
§ _____________ – PTH-related protein
§ _____________ – associated electrolyte disturbances, may be related to secretion of peptides that cause intestinal secretion
o __________________ due to tumour rupture – often associated with sudden onset of severe abdominal pain with distension, an acute drop in the hemoglobin and hypotension
o Obstructive jaundice caused by invasion of the biliary tree
o Decompensated liver disease
hepatitis B and C, liver cirrhosis and aflatoxin;
Hypoglycemia;
Hypercalcemia;
Diarrhea;
Intra-peritoneal bleeding
Diagnosis of hepatocellular carcinoma
- In at-risk patients with abnormal surveillance test results or a clinical suspicion of HCC, __________ is
recommended for initial diagnostic testing – classical features of HCC are detected with triphasic multidetector CT scan
o Injection of venous contrast for CT scan with sequential scanning to observe the different phases of uptake of contrast and blood flow
o For multiphase CT and MRI, key imaging features include ________________, and, depending on exact size, a combination of washout, threshold growth, and capsule appearance
§ Arteriole hyperenhancement – tumour cells take up more contrast and will appear much brighter than the surrounding tissue
§ Washout – _______________________
o If these criteria are not present but HCC or other malignancy is considered probable, a liver biopsy should be considered for diagnosis
- Diagnosis of HCC cannot be made by imaging in patients without cirrhosis even if enhancement and washout are present – biopsy is required in these cases
- Liver Imaging Reporting and Data System (LI-RADS) – both a set of standardised terminology and a classification system for imaging findings in liver lesions o LI-RADS score for a liver lesion is an indication of its relative risk for hepatocellular carcinoma (HCC)
o ______(100% benign) to _____ (100% HCC) and LR-M (malignant, not definitely HCC)
multiphase CT or MRI;
size ≥1 cm, arterial phase hyper-enhancement;
hypodense appearance of the lesion during the portovenous phase
LR-1 ; LR-5
Pathology and HCC
- Liver biopsy should be considered in patients with a liver mass whose appearance is not typical for HCC on contrast-enhanced imaging, especially for observations categorized as ____________________
- A high-grade dysplastic nodule is characterized by the presence of ______________, but the atypia is insufficient for a diagnosis of HCC
o A combination of increased ________, irregular ___________, small cell change, and unpaired arteries, but should not have any evidence of stromal invasion
LR-4 or LR-M;
cytologic atypia and architectural changes;
cell density; trabeculae
Staging and management of HCC Barcelona Clinic Liver Cancer (BCLC)
- For very early and early stages (0 and A) – if other comorbidities are present, __________ is used instead of a liver transplant
Surgical resection of HCC – treatment of choice for resectable HCC occurring in ______________ or resectable HCC in a _______________________
- For patients with single tumours, well-preserved liver function, and no evidence of portal hypertension (normal bilirubin and hepatic venous pressure gradient <10 or platelet count >100,000), surgical resection offers a low perioperative mortality and is associated with survival rates of nearly 70% at 5 years
- Technically, there is no size cut-off for tumour diameter, and large tumours can be safely resected if there is sufficient functional liver remnant
- In cases where a large volume of resection is anticipated such as with greater than three __________________ can be utilized to increase the size of the contralateral lobe and reduce the risk of hepatic insufficiency
- The risk of recurrence following resection is up to 70% at 5 years, with the most important predictors being tumour differentiation, micro- and macrovascular invasion, and the presence of satellite nodules
o Patients should undergo surveillance after resection with imaging and alphafetoprotein (AFP) at least every 3 to 6 months, with consideration of shorter intervals during the first year given higher risk of recurrence during that time
ablation;
patients without cirrhosis; cirrhotic patient with intact liver function and absence of clinically significant portal hypertension
segments, portal vein embolization;
Liver transplant – treatment of choice for patients with early-stage HCC occurring in the setting of clinically significant __________________
- Criteria used include Milan criteria or UCSF criteria
USCF criteria
- 1 tumour ≤ 6.5cm
- 3 tumours with the largest diameter ≤ 4.5cm
- Total tumour diameter ≤ ________
Milan criteria
- One lesion smaller than 5cm (or up to 3 lesions, each smaller than 3cm)
- No extra-hepatic spread
- No evidence of ________________
portal hypertension and/or decompensated cirrhosis
8cm;
vascular invasion
Thermal ablative techniques
- Destruction or ablation of tumour cells can be achieved by the injection of chemical substances (______________________) or by modifying local tumour temperature (radiofrequency [RFA], microwave, laser, cryotherapy)
- Can be done percutaneously with minimal invasiveness or during laparoscopy – currently considered the best option for patients with ______________ who are not candidates for surgical intervention
- Overall, RFA has become the preferred approach for the ablation of HCC over ethanol injection
o However, there are specific locations (____________________) where the application of RFA is contraindicated because of the risk of severe complications, as well as the ______________ leading to a loss of efficacy – other kinds of ablation may be a better choice
- RFA – RFA probe is placed inside the tumour
o Radiofrequency wave passing through the probe increases the temperature within the tumour tissue and results in destruction of the tumour
ethanol, acetic acid, and boiling saline;
BCLC stage A;
near to the main biliary tree, abdominal organs, or heart;
heat-sink effect
Trans-arterial chemo-embolization (TACE)
- Considered if HCC is unresectable and not
amenable to ablation
- Can be used as a bridging manoeuvre in patients awaiting liver transplant
- Generally combined with injection of _________________ into the hepatic artery
chemotherapeutic agents
SIRT-Y90 – involves injection of tiny microspheres of radioactive material (Y90) into the arteries that supply the tumour, indications listed –
- BCLC stage B with _______________________
- BCLC stage B with ___________________
- HCC invading _______________ (Child’s Pugh class A or ≤B7)
o Second line after failing TACE
o To downsize to surgery or transplantation – for patients who are slightly beyond Milan criteria
unilobar disease or few (1 to 5) nodules;
bilobar disease and/or multiple (>5) nodules; tumour larger than 5cm;
main portal vein
Systemic treatment (First-line)
Sorafenib
- Oral multikinase inhibitor
- Standard of care in patients with _______________________
- First-line therapy for patients with advanced HCC metastasis
- Side effects – ______________ (most common), diarrhoea, weight loss, and hypertension
Levantinib
- Multi receptor tyrosine kinase inhibitor that inhibits the kinase activities of ___________________
advanced HCC with vascular invasion and/or extrahepatic spread;
hand-foot skin reaction;
vascular endothelial growth factor receptors (VEGFR)
Systemic treatment (Second-line )
_________________
- Approved as second line drug for HCC
- Binds and inhibits VEGFR and kinases which result in the inhibition of tumour angiogenesis and tumour cell proliferation
_____________
- Immuno-oncologic agent – restores T cell anti-tumour immunity directed against tumour cells
- FDA approved for advanced HCC patients who fail first line treatment with sorafenib
Cabozantnib
- Multi-receptor tyrosine kinase inhibitor
- Side effects – _______________ , hypertension, increased AST, fatigue, diarrhea
Regorafenib ;
Nivolumab ;
palmar-plantar erythrodysaesthesia
