HEPATOCELLULAR CARCINOMA & IT’S

MANAGEMENT

DR.ASHIRWAD K

PG 2ND YEAR

DR.C K DURGA UNIT

DR RML HOSPITAL DELHI

ANATOMY OF LIVER

• LIVER IS THE LARGEST ORGAN IN BODY WEIGHING ABOUT 1.5 KGS .

• IT HAS DUAL BLOOD SUPPLY WITH 80% OF IT BEING FROM PORTAL VEIN AND 20% FROM HEPATIC ARTERY.

• THE RIGHT HEPATIC AETRERY SUPPLIES THE MAJORITY OF LIVER PARENCHYMA AND IS THE LARGEST OF TWO.

• MAJOR VENOUS DRAINAGE IS BY 3 MAJOR HEPATIC VEINS THAT JOIN IVC BELOW THE DIAPHRAGM

• THE LIVER IS HELD IN POSITION IN RUQ BY PERITONEAL REFLECTIONS WHICH ARE TRIANGULAR LIGAMENTS AND FALCIFORM LIGAMENT.

ANATOMY CONT…

ANATOMY CONT…

A)COUINAUD CLASSIFICATION:

1. EIGHT SEGMENTS

2.EACH SEGMENT IS A FUNCTIONAL UNIT WITH ITS OWN BRANCH OF HEPATIC

ARTERY,

PORTAL VEIN AND BILE DUCT AND DRAINED BY A BRANCH OF HEPATIC

VEIN.

B)CANTLIE’S LINE DIVIDES LIVER INTO FUNCTIONAL RIGHT AND LEFT UNIT.

C)HEPATIC LOBULES- FUNCTIONAL UNIT OF LIVER SEGMENTS.

INTRODUCTION

• HEPATOCELLULAR CARCINOMA (HCC) IS THE SIXTH MOST COMMON

MALIGNANCY IN THE WORLD AND THIRD COMMONEST CAUSE OF DEATH FROM

CANCER.

• INCIDENCE – 5 PER 100000 POPULATION.

• MALE>FEMALE (2:1 TO 4:1)

• BECAUSE OF THE TIME NECESSARY FOR CANCER TO DEVELOP IN INFECTED

PATIENTS AND THE INCREASED RISK IN OLDER PATIENTS, THE NUMBER OF

PATIENTS WITH HCC HAS RISEN RAPIDLY .

ETIOLOGY

MAJOR RISK FACTORS FOR HEPATOCELLULAR CARCINOMA

• INFECTION: HEPATITIS B, HEPATITIS C INFECTION.

• TOXIN/DRUG: ALCOHOLIC CIRRHOSIS, ALFATOXINS ,ANABOLIC STEROIDS .

• GENETIC: HEMOCHROMATOSIS, Α1-ANTITRYPSIN DEFICIENCY.

• IMMUNOLOGIC: AUTOIMMUNE CHRONIC ACTIVE HEPATITIS, PRIMARY BILIARY

CIRRHOSIS.

• OTHER: OBESITY ,NONALCOHOLIC STEATOHEPATITIS, CIRRHOSIS (OTHER

CAUSES AND IDIOPATHIC)

• THE INCIDENCE OF HEPATOCELLULAR CARCINOMA RELATED TO RISK FACTORS

OTHER THAN VIRAL HEPATITIS, AFLATOXIN, AND STEATOHEPATITIS IS

RELATIVELY SMALL. AND IT IS PROBABLY TRUE THAT ANY PATIENT WITH

CIRRHOSIS FROM ANY ETIOLOGY IS AT RISK FOR HEPATOCELLULAR CARCINOMA.

IN CHILDREN, THE VIRAL ETIOLOGIES ARE THE MOST COMMON CAUSES OF HCC.

PATHOGENESIS

• A) CIRRHOSIS :

1. MORE THAN 90% OF PATIENTS WHO DEVELOP HCC HAVE EVIDENCE OF

FIBROSIS IN THE LIVER.

2. RISK OF DEVELOPING HEPATOCELLULAR CARCINOMA ONCE CIRRHOSIS IS

ESTABLISHED IS ABOUT 3% TO 5% PER YEAR.

3. BECAUSE THE RISK OF LIVER CANCER IS GENERALIZED TO THE ENTIRE ORGAN,

THE CARCINOGENIC POTENTIAL IS TERMED A “FIELD EFFECT.” THIS “FIELD

EFFECT” IS RESPONSIBLE FOR THE HIGH RATE OF RECURRENCE AFTER

RESECTION OF HCC BECAUSE OF THE REMAINING UNRESECTED LIVER BEING

AT RISK.

4. THE RECURRENCES AFTER RESECTION ARE MOST COMMONLY SECOND

PRIMARY LESIONS RATHER THAN RECURRENCE OF THE RESECTED LESION.

PATHOGENESIS CONT…..

B)ARTERIAL ANGIOGENESIS :

1. HCC GETS ITS BLOOD SUPPLY FROM THE HEPATIC ARTERY. THUS ON

COMPUTED TOMOGRAPHY (CT), THE HCC LESION APPEARS HYPERDENSE

DURING THE ARTERIAL PHASE.

2. ON ANGIOGRAPHIC IMAGING, THE VESSELS HAVE AN UNUSUAL AND

IRREGULAR PATTERN IN BOTH SIZE AND BRANCH PATTERN, WHICH IS

DIFFERENT THAN NORMAL HEPATIC ARTERIAL SUPPLY. THIS ABNORMAL

ARTERIAL PERFUSION ALLOWS FOR TREATMENT OF HCC VIA EMBOLIZATION

OF THE FEEDING ARTERY(IES).

PATHOGENESIS CONT…..

C) PORTAL VEIN INVASION

1. ANOTHER CHARACTERISTIC OF HCC IS ITS PROPENSITY TO INVADE THE

PORTAL VEIN.

2. TUMORS MEASURING MORE THAN 2 CM HAVE AN INCREASED RISK OF PORTAL

VEIN INVASION.

3. IT IS LIKELY THAT PORTAL VENOUS INVASION IS EITHER A MECHANISM FOR A

DIFFUSION OF THE TUMOR ELSEWHERE IN THE LIVER AND THE BODY AND/OR

THAT THE PHENOTYPES OF THE CELLS THAT CAN INVADE THE PORTAL VEIN

ARE CELLS THAT CAN DISSEMINATE AND IMPLANT IN OTHER ORGANS SUCH

AS THE LUNG OR BONE.

CLINICAL PRESENTATION

A) BECAUSE OF THE KNOWN RISK FACTORS FOR HCC, THERE IS USUALLY A

HISTORY OF VIRAL HEPATITIS, ALCOHOL OR DRUG ABUSE, OBESITY AND/OR

DIABETES, OR PAST HISTORY OF HCC.

B) AS AN INCIDENTAL FINDING DURING ULTRASOUND ABDOMEN.

C) THE FINDING OF SMALL ASYMPTOMATIC LIVER LESIONS DURING THE

RADIOLOGIC EVALUATION FOR LIVER TRANSPLANTATION IS ANOTHER

COMMON PRESENTATION.

PHYSICAL EXAMINATION

-JAUNDICE, ASCITES, CACHEXIA, SPLENOMEGALY, HEPATOMEGALY, OR IT MAY BE

NORMAL.

-WITH SUBTLE STIGMATA OF LIVER DISEASE, SUCH AS SPIDER ANGIOMATA OR

PALMAR ERYTHEMA.

LABORATORY INVESTIGATIONS

1. ABNORMAL LIVER FUNCTION TESTS AND ENZYMES.

2. VIRAL SEROLOGY

3. CIRRHOTICS MAY HAVE THROMBOCYTOPENIA, WHICH IS A MARKER OF PORTAL

HYPERTENSION.

4. Α-FETOPROTEIN (AFP): A LEVEL >400 NG/ML IS DIAGNOSTIC WHEN THERE IS A

LIVER MASS >2 CM PRESENT. IN LESIONS <2 CM THE LEVELS MAY BE NORMAL.

5. DES-CARBOXYPROTHROMBIN (DCP):SPECIFIC IN DIFFERENTIATING BENIGN FROM

MALIGNANT LESIONS, AND IS ELEVATED IN ABOUT 40% OF PATIENTS WITH HCC

LESIONS LESS THAN 2 CM.

IMAGING MODALITIES

A) USG:

1.PRIMARY USE FOR ULTRASONOGRAPHY IS IN SCREENING POPULATIONS FOR

HCC.

2.SENSITIVITY IS 65-85% AND SPECIFICITY IS > 90%.

3. SURVEILLANCE OF HIGH-RISK INDIVIDUALS WITH ULTRASOUND AND AFP EVERY

6 MONTHS REDUCES HCC-RELATED MORTALITY BY CLOSE TO 40%.

4.LESION <1CM- FOLLOW UP.

5.LESION 1-2CM/>2CM – CONFIRM WITH ANOTHER IMAGING MODALITY.

6.CANNOT DIFFERENTIATE B/W BENIGN & MALIGNANT LESIONS BUT USING

CONTRAST AGENTS WITH MICROBUBBLES CAN HELP DIFFERENTIATING B/W THE

LIVER MASSES.

B.COMPUTED TOMOGRAPHY

1.ACCURATELY DIAGNOSE & STAGE THE EXTENT OF DISEASE.

2. SENSITIVITY OF MDCT IS ABOUT 86%, WHICH DROPS TO ABOUT 60% WITH

LESIONS <2 CM IN SIZE.

3. INVASIVE COMBINATION TECHNIQUES SUCH AS INTRAARTERIAL CT

ANGIOGRAMS AND CT ARTERIAL PORTOGRAPHY HAVE SHOWN A SENSITIVITY AND

SPECIFICITY OF UP TO 93% AND 97%, RESPECTIVELY.

4.LIPIODOL (IONIZED POPPY SEED OIL)- HETEROGENEOUS UPTAKE OF LIPIODOL ON

FOLLOWUP CT WITH RESIDUAL TUMOR ENHANCEMENT IS SUGGESTIVE OF

PRESENCE OF VIABLE TUMOR.

C . MRI

1. HIGH SIGNAL INTENSITY ON T2-WEIGHTED SEQUENCES WITH STRONG EARLY

ARTERIAL ENHANCEMENT AND DELAYED WASHOUT.

2. EARLY MALIGNANT GROWTH WITHIN DYSPLASTIC NODULES -“NODULE

WITHIN A NODULE” APPEARANCE.

3. CONTRAST AGENTS - GADOLINIUM CHELATES, SUPERPARAMAGNETIC IRON

OXIDE, AND HEPATOCYTE-DIRECTED AGENTS (MANGAFODIPIR TRISODIUM).

STAGING SYSTEMS

STAGING HELPS PLAN MANAGEMENT AND PREDICT PROGNOSIS AND OUTCOME,

WHICH ARE:

1.BCLC

2.TNM

3.OKUDA

4.CLIP

MANAGAEMENT

- AS WITH MOST CANCERS, TREATMENT DECISIONS IN PATIENTS WITH HCC NEED TO BE BASED ON THE OVERALL HEALTH STATUS OF THE PATIENT, THE EXTENT OF THE DISEASE, AND THE DATA REGARDING THE RESULTS OF ANY PARTICULAR TREATMENT.

- HCC FREQUENTLY ARISES IN A CIRRHOTIC LIVER. DECOMPENSATION OR THE RISK OF DECOMPENSATION BECAUSE OF THE CHOSEN THERAPY OF THE CIRRHOSIS CAN LIMIT POTENTIAL THERAPIES.

- BECAUSE OF FIELD EFFECT THE RISK OF DEVELOPING A SECOND PRIMARY AFTER RESECTION FOR HCC IS ABOUT 35% AT 1 YEAR, 40% TO 50% OVER 3 YEARS, AND AS HIGH AS 70% AT 5 YEARS.

- UNFORTUNATELY, 80% OF PATIENTS WILL PRESENT AT A STAGE TOO ADVANCED FOR SURGICAL RESECTION OR TRANSPLANTATION.

MANAGEMENT MODALITIES

A)SYSTEMIC THERAPY: SORAFENIB

B)ABLATIVE PROCEDURES:

1.RADIOFREQUENCY ABLATION(RFA) 6.TACE + RFA

2.PERCUTANEOUS ETHANOL INJECTION(PEI) 7.LASER ABLATION

3. MICROWAVE THERAPY

4. CRYOTHERAPY

5.TAE/TACE

CONT…

C)TRANSPLANTATION:

1.MILAN CRITERIA

2.UNIVERSITY OF CALIFORNIA SAN FRANSISCO(UCSF)

CONT…

D.RESECTION

-ASSESSMENT OF HEAPTIC FUNCTION AND RESERVE

1)ICG- AT 15 MINS IF RETENTION >20% - 1/6TH OF LIVER RESECTION

AT 15 MINS IF RETENTION >30%- RFA OR LIMITED RESECTION IS

APPROPRIATE.

2)CTP- A- 50% RESECTION

B-25% RESECTION

C- NO RESECTION

3)PORTAL VENOUS PRESSURE ASSESED BY HVWP AND ABNORMAL BILIRUBIN

LEVELS.

4)PORTAL VEIN EMBOLISATION.

5)INTRA OPERATIVE USG WITH PRE-OP TUMOR VASCULATURE PATTERN

KNOWLEDGE.

CONT….

THE APPROPRIATE TECHNIQUE DEPENDS ON THE LOCATION OF THE TUMOR, THE

DEGREE OF CIRRHOSIS, AND THE EXPERIENCE OF THE SURGEON. THE PRINCIPLES

ARE THE PREVENTION OF BLOOD LOSS AND THE PRESERVATION OF AS MUCH

FUNCTIONAL LIVER AS POSSIBLE. IT DOES APPEAR THAT MARGINS GREATER THAN

5 TO 10 MM ARE ADEQUATE.

BCLC

THANK YOU