Liver cancer diagnostics and Future trends
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Transcript of Liver cancer diagnostics and Future trends
Liver Cancer Diagnosis
Presented by Group 3Thet Su Wynn
Chawalit ChatupheeraphatLe Van Chuong
Contents
Liver Cancer1
Serum Tumor Markers2
Imaging Markers3
Biopsy4
Future Trend5
Liver CancerLiver cancer is a cancer which originates
in the liver
There are 4 main types Hepatocellular carcinoma (HCC) Cholangiocarcinoma Angiosarcoma Hepatoblastoma
The major types is Hepatocellular carcinoma (HCC)
Sign & Symptom Sign and symptom of liver cancer is no
specific abdominal mass abdominal pain emesis anemia back pain jaundice itching weight loss Fever
Diagnosis of Liver cancer Following medical guideline, The test should done
before liver cancer investigation Hepatitis B and C Cirrhosis
Viral Hepatitis HBV or HCV antibody detection Viral load
Cirrhosis Patient history (Alcohol, Drug) Liver function test Prothrombin time Imaging
Liver Cancer Diagnosis
HCC Diagnosis
Non-Invasive Methods
Serological markers
Imaging markers
Genetic markers
Invasive Methods
Biopsy
Serum tumor markersUse for early screening and low
invasiveness
Alpha-fetoprotein (AFP)
Gramma-glutamyl tranferase
Len culinaris agglutin reactive AFP (AFP-L3)
Prothrombin induced by vitamin K absense II (PIVKA-II)
α-Fetoprotein (AFP)Serum AFP, a fetal-specific glycoprotein
antigen, is the most widely used tumor marker for detecting patients with HCC
AFP level > 200 ng/ml in liver cancerAFP is not specific for HCC. Can high in
other diseases Other cancer eg. Testicular cancer, Germ line tumor,
Gastric cancer Viral hepatitis infection Pregnancy
ɣ-glutamyl transferase(GGT) Gamma-glutamyl transferase (GGT) is a membrane-
bound enzyme catabolizing reduced glutathione to cysteine and glycine
Primarily present in kidney, liver, and pancreatic cells
Normal value 9-48 U/L (Increase in aging)
GGT is not specific for HCC. Can high in other condition
Alcohol Phenytoin Phenobarbital Aging
Len culinaris agglutin reactive AFP (AFP-L3)
AFP can be fractionated by affinity electrophoresis into 3 glycoforms: L1, L2, and L3
The L3 isoform is specific to malignant tumors
Can bind to Lens culinaris agglutinin (LCA), which is isolated from Lens culinaris (lentil) seeds
Len culinaris agglutin reactive AFP (AFP-L3)
Results for AFP-L3 are represented as a ratio of LCA-reactive AFP to total AFP (AFP-L3%).
Cut-off > 15%
AFP-L3% was found to have sensitivity of 96.9%, specificity of 92.0%,
Khien VV, et al.,Int J Biol Markers. 2001 Apr-Jun;16(2):105-11.
Prothrombin induced by vitamin K absense II (PIVKA-II)
Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) is an abnormal prothrombin devoid of coagulation activity
Serum PIVKA-II was elevated with a high prevalence and with a high specificity in patients with HCC
The overall sensitivity and specificity of serum PIVKA-II in the detection of HCC have been shown to be 4862% and 8198%, respectively
YOUNG JOON YOONScandinavian Journal of Gastroenterology, 2009; 44: 861-866
Prothrombin induced by vitamin K absence II (PIVKA-II)
Sample Value (ng/ml)
Hepatocellular carcinoma 101.07 ± 78.30 ng/ml,
Cirrhosis 2.45 ± 4.25 ng/ml
Chronic hepatitis 1.50 ± 0.98 ng/ml
Healthy person 0.79 ± 0.75 ng/mlBalkrishan Sharma, Hepatol Lnt. 2010 4(3):569-576
Imaging techniques used for HCC diagnosis
Ultrasound
CT Scan
MRI Scan
Imaging techniques used for HCC diagnosis
Ultrasonography Contrast enhanced US (CEUS)
• Contrast agents– Sonazoid– SonoVue– Levovist
• Used to– Evaluate hypervascularity– Hypoechoic in the Kupffer phase of Sonazoid CEUS
Imaging techniques used for HCC diagnosis
Computed tomography (CT) scan Dynamic CT Dynamic contrast-
enhanced CT (Iodine) Multiphasic spiral CT Multi-detector CT
(MDCT) scan CT Angiography
Imaging techniques used for HCC diagnosis
Magnetic resonance imaging (MRI) scan Gadolinium ethoxybenzyl diethylenetriamine
pentaacetic acid-enhanced MRI (EOB-MRI)• Organic anion transporting polypeptide 1B3 (OATP1B3)
(major transporters of gadoxetic acid in human HCC) Super paramagnetic iron oxide agents for MRI (SPIO-
MRI)
Imaging techniques used for HCC diagnosis
Wash-in in the arterial phase
Wash-out in the late phase
Differential diagnosisBenign tumor of the liver
Hemangioma• 3 cm, multiple in up to 50% of patients• Lesions with well-defined margins
Focal nodular hyperplasia (FNH) Hepatocellular adenoma
Cholangiocarcinomas
LCSGJ
Confirmation Test
Biopsy is the definitive diagnosis
Percutaneous FNA
Needle core biopsy
Under US or CT
guidance
Laboratory ProceduresFixation, Tissue processing and embeddingConventional staining – H&E stainSpecial staining – Trichrome staining for collagen
- Reticulin stain - Iron stain - PAS stain - Fat stain (oil red O) - Orcein stain
Immunofluorescence stain of AFP IHC (anti-AFP, pCEA, CK7, CK18, CK20, CA 19-9, CD34, etc)
Confirmation TestBiopsy is the definitive
diagnosis
• Trabeculae• Large nucleus• Deeply
eosinophilic cells
• Thick fibrous bands
• AFP expression significantly increased in HCC
Hepatocellular carcinoma showing strong cytoplasmic staining to CK 18
B
Cholangiocarcinomashowing positive cytoplasmic stain for CK-7
Sawan A.S. JKAU: Med. Sci., Vol. 16 No. 4, pp: 37-48 (2009)
IHC profile of HCC, CC and metastatic GIT carcinoma
Biopsy
A small biopsy can be representative of changes in the whole liver.
It is a safe and effective means to confirm suspicious lesions of cancers.
The sensitivity, specificity and accuracy are superior to any other diagnostic test. (>95%)
Genetic markers - 1
AFP mRNA will be the most valuable markers for HCC (in active HCC)
It could be used as significant HCC marker in blood
also serves as a predictor for HCC recurrence
Feng Y. et al (2005). Clinica ChimicaActa, vol 361(1-2), 119–127
Genetic markers - 2
miRNA is remarkably stable in both circulation and tissues.
The stability of circulating miRNA allows reliable enumeration, which is vital as a novel diagnostic biomarker.
They can be detected with RT-PCR, microarray and next-generation sequencing.
miRNAs – miR-500, miR-29, miR-122, miR-21, etc
Recurrence Related microRNAs in Hepatocellular Carcinoma
http://www.mdpi.com/1422-0067/14/1/1105
Genetic markers – 3 (related genes)
Δ-like 1 homolog (DLK1) is progenitor cell marker in fetal liver.
DLK1 expression is significantly elevated in HCC.Hepatoma-associated gene (HTA) is the tumor-
specific gene.Villin1 (Vil1) is the newly identified marker for HCC.They all are the potential candidate molecular
markers for HCC
To improve the early diagnostic tools To predict the transfer and recurrence of
tumors To improve sensitivity and specificity of
diagnosis
Novel markers
miRNA
Genetic
markers
Novel biomarkers
Effective combined methods
TGF-β1
GPC3
AFP
To be resulted in improved treatment and prognosis
FUTU
RE
TREN
DS
www.themegallery.com
OrganizationsAmerican Association for the Study of
Liver Diseases (AASLD)European Association for the Study of
the Liver and the European Organization for Research and Treatment of Cancer (EASL-EORTC)
Asian Pacific Association for the Study of the Liver (APASL)
Japan Society of Hepatology (JSH)
Imaging techniques used for HCC diagnosis