Hepatocellular Carcinoma

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Slide 1 :

HEPATOCELLULAR CARCINOMA: RECENT ADVANCES DR (MRS) AARTI B BHATTACHARYA

Slide 2 :

REFERENCES HCC ACKERMAN’S SURGICAL PATHOLOGY EIGTH EDITION VOL – I, PAGE 903 – 910 GENETIC MECHANISMS OF HEPATOCARCINOGENESIS MARK A FEITELSON, BILLSUN et all; DEPARTMENT OF PATHOLOGY, ANATOMY & CELL BIOLOGY, THOMAS JEFFERSON UNIVERSITY, PHILADELPHIA. JR- ONCOGENE (2002) 21, 2593 – 2604 RECENT ADVANCES : HEPATOLOGY BRITISH MEDICAL JOURNAL, MAY 8, 1999 BY M McCARTNY, M L WILKINSON

Slide 3 :

HEPATOCELLULAR CARCINOMA - SYNONYMS LIVER CELL CARCINOMA HEPATOMA

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HEPATOCELLULAR CARCINOMA - INCIDENCE AGE INCIDENCE > 50 YEARS MALE : FEMALE :: 2:1

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CLINICAL FEATURES ABDOMINAL PAIN ASCITIS HEPATOMEGALY OBSTRUCTIVE JAUNDICE (INVASION OF CBD) SYSTEMIC MANIFESTATIONS HYPOGLYCEMIA HYPERCHOLESTEROLEMIA HYPERCALCEMIA ERYTHROCYTOSIS CARCINOID SYNDROME DYSFIBROGENEMIA RAISED AFP LEVELS

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ASCITIS HEPATOMEGALY CLINICAL FEATURES - HCC

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HCC – RISK FACTORS INFECTIOUS AGENTS – HBV, HCV PATHOLOGY – CHRONIC LIVER DISEASE (MACRO NODULAR CIRRHOSIS) NEONATAL HEPATITIS DIETARY AFLATOXIN B1 CONSUMPTION DIETARY IRON OVERLOAD LOW VEGETABLE INTAKE CHRONIC ALCHOLISM HORMONE RELATED OC PILLS ANABOLIC STEROIDS ELEVATED SERUM LEVELS OF TESTOSTERONE

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HCC – RISK FACTORS OTHER ENVIRONMENTAL VINYL CHLORIDE CIGRATTE SMOKING INORGANIC ARSENIC INGESTION RADIOACTIVE THOROTRAST GENETIC ASSOCIATIONS HEREDITARY TYROSINEMIA a 1 ANTITRYPSIN DEFICIENCY HAEMOCHROMATOSIS

Slide 9 :

PREDISPOSING AND ASSOCIATED FACTORS CIRRHOSIS SECONDARY TO HBV, HCV, ALCOHOL, AFLATOXIN AND HAEMOCHROMATOSIS BILIARY CIRRHOSIS SECONDARY TO CONGENITAL BILEDUCT ATRESIA, A-1 ANTI-TRYPSIN DEFICIENCY, TYROSINEMIA AND CONGENITAL HEPATIC FIBROSIS. BOTH ARE SEEN TO RESULT IN HCC

Slide 10 :

PREDISPOSING AND ASSOCIATED FACTORS LIVERCELL DYSPLASIA LARGE CELL DYSPLASIA SMALL CELL DYSPLASIA ADENOMATOUS HYPERPLASIA MACROREGENERATIVE NODULE ATYPICAL ADENOMATOUS HYERPLASIA

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PREDISPOSING AND ASSOCIATED FACTORS HEPATOTROPIC VIRUSES THORIUM DIOXIDE EXPOSURE LATENT PERIOD 20 YRS. ANDROGENIC ANABOLIC STEROIDS HCC PROGESTATIONAL AGENTS LIVER CELL ADENOMA +HCC A-1 ANTITRYPSIN DEFICIENCY HCC TYROSINEMIA HIGH INCIDENCE OF HCC AFLATOXINS FUNGUS ASPERGILLUS FLAVUS

Slide 12 :

GROSS FEATURES CIRRHOSIS ALCOHOLIC CIRRHOSIS INFECTIVE CIRRHOSIS

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HCC GROSS FEATURES SOLITARY MULTINODULAR DIFFUSE MASSIVE

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GROSS FEATURES

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HCC – MICROSCOPIC FEATURES TRABECULAR SOLID TUBULAR IMMUNOHISTOCHEMISTRY AFP, KERATIN, EMA, ANTITRYPSIN, FIBRINOGEN, IGG, TRANSFERRIN RECEPTOR, FERRITIN, MALLORY’S BODY ANTIGEN, ALBUMIN, EPIDERMAL GROWTH FACTOR RECEPTOR, CRP

Slide 16 :

MICROSCOPIC FEATURES - HCC VASCULAR SINUSOIDS TRABECULAR PATTERN SOLID PATTERN

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MICROSCOPIC FEATURES - HCC H & E LOW POWER H & E HIGH POWER H & E HIGH POWER

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HCC - MOLECULAR PATHOLOGY DEVELOPMENT – MULTI-STEP PROCESS WITH CHANGES IN HOST GENE EXPRESSION PRE NEOPLASTIC GHANGES IN GENE EXPRESSION TUMOUR PROGRESSION – LOH MUTATIONS IN p53, Rb, INSULINE LIKE GROWTH FACTOR RECEPTOR 1 OVER EXPRESSION OF c-myc & cyclin D1

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HCC - GENE EXPRESSION MICRO ARRAY

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HCC - PROGNOSIS STAGE SIZE ENCAPSULATION NO. OF TUMOURS PORTAL VEIN INVOLVEMENT MICROSCOPIC TYPE – FIBRO LAMELLAR MITOTIC ACTIVITY CIRRHOSIS RAISED AFP LEVELS PROGESTATIONAL AGENTS SEX – GOOD PROGNOSIS IN FEMALES

Slide 21 :

HCC - TREATMENT SURGICAL RESECTION LIVER TRANSPLANTATION AUXILIARY SPLIT LIVE RELATED DONOR TRANSPLANTATION CHEMOTHERAPY

Slide 22 :

HCC GENE THERAPY ADINOVIRUS MEDIATED GENE TRANSFER OF HSV – 1 THYMIDINE KINASE GENE TO HCC CELL LINES – PRO DRUG GANCICLOVIR

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