AngioDynamics, Inc. Copyright © 2010. All rights reserved.

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AngioDynamics, Inc.

Goal and Objectives

The goal of this course is to provide you with a basic understanding of hepatocellular carcinoma (HCC) and

metastatic colorectal cancer (MCRC).

Colon AnatomyColon Anatomy

Liver AnatomyLiver Anatomy

Hepatocellular Carcinoma Hepatocellular Carcinoma

Metastatic Colorectal CancerMetastatic Colorectal Cancer

TreatmentsTreatments

Anatomy Anatomy

Goal and Objectives

Basic InformationBasic Information

Fundamental CausesFundamental Causes

SymptomsSymptoms

PrognosisPrognosis

Anatomy Anatomy

Goal and Objectives

Treatment OptionsTreatment Options

Determining TreatmentDetermining Treatment

Transarterial Chemoembolization Transarterial Chemoembolization

Surgery Surgery

Chemotherapy Chemotherapy

Palliative CarePalliative Care

Tissue AblationTissue Ablation

Anatomy Anatomy

Navigation

• Colon Anatomy• Liver Anatomy

Colon Anatomy

Colon Anatomy Colon Anatomy Colon AnatomyColon Anatomy

Colon Blood SupplyColon Blood Supply

Colon WallsColon Walls

Colon Anatomy

The colon is 150 cm long and divided into the:The colon is 150 cm long and divided into the:

Transverse Colon

Ascending Colon

DescendingColon

Sigmoid Colon

Colon Anatomy

Ascending Colon

Ileocecal Valve

Colon Blood Supply

Superior Mesenteric Artery

InferiorMesenteric Artery

Splenic Flexure

Ileocecal Valve

Colon Walls

Serosa

Muscularis Propia

Submucosa

Mucosa

Liver Anatomy

Liver Anatomy Liver Anatomy Liver AnatomyLiver Anatomy

Dual Blood SupplyDual Blood Supply

Blood FlowBlood Flow

Biliary TreeBiliary Tree

Liver FunctionsLiver Functions

Common Liver DisordersCommon Liver Disorders

Hepatitis B and Hepatitis CHepatitis B and Hepatitis C

Liver Anatomy

Falciform ligament

Pinkish brown organ in the right upper quadrant of the abdomen

Largest internal organLargest internal organ

Largest gland; weighs 3 – 4 lbs.Largest gland; weighs 3 – 4 lbs.

Divided into right and left lobes by the falciform ligament

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Blood Flow

Kupffer cellsKupffer cells

Remove pathogensRemove pathogens

MacrophagesMacrophages

Venous bloodVenous blood

Filters through the endothelial lining to the

hepatocytes

Filters through the endothelial lining to the

hepatocytes

Breaks down and metabolizes toxins

Blood returned to heart from the hepatic vein into the

inferior vena cava

Blood returned to heart from the hepatic vein into the

inferior vena cava

Liver Functions

Breaks down drugs

Stores and mobilizes

energy

Produces vitamins

Filters blood to eliminate bacteria and toxins

Produces and stores

Aids digestion by producing bile

Controls blood sugar and regulates fat storage

Regulates blood clotting by

manufacturing blood proteins

Differences Between Hepatitis B and C

Hepatitis B Hepatitis C

Virus Virus

Acute or chronic condition Chronic condition

Spreads through:– Blood– Semen – Vaginal fluids– Body fluids– Mother to newborn

Blood borne spread:– Hemodialysis patients– Hemophiliacs– IV drug abuse – Blood transfusion prior to 1990– Mother to newborn

25% of children infected die from liver cancer (or failure) as adults

Responsible for 50-76% of all liver cancers, which occur 30-40 years after infection

Vaccination available since 1982– 95% effective– Recommended for all

No vaccine available

The Colon:Is 150 cm longDivided into five

sectionsIncludes the

ileocecal valveIncludes superior

and inferior mesenteric arteries

Has a wall with four layers

The Colon:Is 150 cm longDivided into five

sectionsIncludes the

ileocecal valveIncludes superior

and inferior mesenteric arteries

Has a wall with four layers

Summary

The liver:Is the largest

internal organ and gland

Receives blood from two sources

Filters pathogens out of the blood

Secretes bile via the biliary tree

Has a number of common disorders

The liver:Is the largest

internal organ and gland

Receives blood from two sources

Filters pathogens out of the blood

Secretes bile via the biliary tree

Has a number of common disorders

• Basic Information• Fundamental Causes• Symptoms• Prognosis

HCC Basic Information

Basic Information Basic Information

HCC PreventionHCC Prevention

HCC StatisticsHCC Statistics

HCC DefinedHCC Defined

HCC Prevention

Hepatitis Prevention Hepatitis Prevention Cirrhosis Prevention Cirrhosis Prevention

Hepatitis B VaccinationHepatitis B Vaccination

Screening donated blood for hepatitis viruses

Proper hygieneProper hygiene

Avoiding alcohol abuseAvoiding alcohol abuse

Preventing viral hepatitisPreventing viral hepatitis

Goals Goals

No vaccine exists for Hepatitis CNo vaccine exists for Hepatitis C

HCC Prevention

Hepatitis B or CHepatitis B or C

Non-alcoholic Fatty Liver Disease (NAFLD)

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

HemochromatosisHemochromatosis

CirrhosisCirrhosis

Screen high risk patients Screen high risk patients

Reduce obesity and Type II diabetesReduce obesity and Type II diabetes

HCC Defined

InflammationInflammation

NecrosisNecrosis

FibrosisFibrosis

RegenerationRegeneration

Occurs in patients with chronic liver disease and cirrhosis

Defined byDefined by

Cancer starts during adulthoodCancer starts during adulthood

Hepatic stem cell thought to be cell origin

HCC Symptoms

Symptoms Symptoms

HCC PresentationHCC Presentation

HCC Growth PatternsHCC Growth Patterns

HCC Clinical PresentationHCC Clinical Presentation

Angiogram showing hypervascular lesions

HCC Growth Patterns

MultifocalMultifocal

Solitary massSolitary mass

DiffuseDiffuse

InfiltrativeInfiltrative

Hypervascular with neovascularity and

arteriovenous shunting

Hypervascular with neovascularity and

arteriovenous shunting

HCC Presentation

Weight lossWeight loss

Right upper quadrant painRight upper quadrant pain

Lump under the ribsLump under the ribs

Weakness or fatigueWeakness or fatigue

JaundiceJaundice

BruisingBruising

BleedingBleeding

HCC Presentation

CT scan of liver and abdomen

Early screening of cirrhosis patients using

3-phase CT scan3-phase CT scan

Measurement of a tumor marker (alpha-fetoprotein

level)

Measurement of a tumor marker (alpha-fetoprotein

level)

HCC Prognosis

Prognosis Prognosis

StagingStaging

Diagnostic MethodsDiagnostic Methods

ScoringScoring

PrognosisPrognosis

Treatments for HCCTreatments for HCC

Staging

SizeSize

Degree of liver diseaseDegree of liver disease

Tumor biologyTumor biology

LocationLocation

EvaluatesEvaluates

Determines prognosisDetermines prognosis

Bases treatments on the stageBases treatments on the stage

Uses Barcelona Clinic Liver Cancer (BLCL) Staging System

Staging and Scoring Interaction Staging and Scoring Interaction

Scoring − MELD

Model for End Stage Liver Disease (MELD)Model for End Stage Liver Disease (MELD)

Determines how liver transplants are allocated

Is a complex equationPredicts the likelihood of

mortality from cirrhosis complications

Gives liver transplant to highest MELD score

Gives HCC patients higher MELD scores

Determines how liver transplants are allocated

Is a complex equationPredicts the likelihood of

mortality from cirrhosis complications

Gives liver transplant to highest MELD score

Gives HCC patients higher MELD scores

HCC Treatment

HCC TreatmentHCC Treatment

Liver ResectionLiver Resection

Liver TransplantLiver Transplant

Liver Resection

Indicators Indicators

Tumor <5 cmTumor <5 cm

No cirrhosisNo cirrhosis

Hepatectomy Prognosis

HCC Recurrence HCC Recurrence

Tumor at the resection marginCirrhosisVascular involvementAdvanced tumor gradeNumber of tumorsAlpha-fetoprotein (AFP) level is

greater than 10,000Preoperative aspartate

aminotransferase test (AST) is two times normal

Patient has Hepatitis C

Tumor at the resection marginCirrhosisVascular involvementAdvanced tumor gradeNumber of tumorsAlpha-fetoprotein (AFP) level is

greater than 10,000Preoperative aspartate

aminotransferase test (AST) is two times normal

Patient has Hepatitis C

Diagnostic methods:Alpha-

fetoprotein (AFP) level

Biopsy Imaging

Diagnostic methods:Alpha-

fetoprotein (AFP) level

Biopsy Imaging

Presentation:AnemiaLow platelet

count Increased

creatinine level

Elevated liver enzymes

Increased bilirubin level

Lack of glycogen stores in liver

Presentation:AnemiaLow platelet

count Increased

creatinine level

Elevated liver enzymes

Increased bilirubin level

Lack of glycogen stores in liver

HCC:A tumor in which

the cancer starts during adulthood in cells in the liver

Primary malignancy of the liver; not metastasized from elsewhere

More prevalent in men than women

Associated with Hepatitis B and C, alcohol abuse, and metabolic liver disease

HCC:A tumor in which

the cancer starts during adulthood in cells in the liver

Primary malignancy of the liver; not metastasized from elsewhere

More prevalent in men than women

Associated with Hepatitis B and C, alcohol abuse, and metabolic liver disease

Prevention:Limit the

epidemic of Hepatitis B and C

Avoid alcohol abuse

Early screening

Prevention:Limit the

epidemic of Hepatitis B and C

Avoid alcohol abuse

Early screening

SummaryUses BCLC staging system, which considers tumor size and physical status, for scoring

Uses BCLC staging system, which considers tumor size and physical status, for scoring

Treatments:TACEAblationLiver

transplantationLiver resection

Treatments:TACEAblationLiver

transplantationLiver resection

• Basic Information• Fundamental Causes• Symptoms• Prognosis

Basic Information

Basic InformationBasic Information Colorectal Cancer StatisticsColorectal Cancer Statistics

Colorectal Cancer PathophysiologyColorectal Cancer Pathophysiology

Colorectal Cancer OccurrenceColorectal Cancer Occurrence

Colorectal Cancer Occurrence

AdenocarcinomaAdenocarcinoma

Cecum – 20%

Sigmoid – 25%

Rectum – 20%

Rectosigmoid junction – 10%

Mucosa

Colorectal Cancer Pathophysiology

Stem cells

Differentiated cells

Fundamental Causes

EnvironmentalHigh fat dietLow fiber dietAlcohol

consumptionCholecystectomy

EnvironmentalHigh fat dietLow fiber dietAlcohol

consumptionCholecystectomy

GeneticFamily history of

colorectal cancerAdenomatous

polyps•Familial

adenomatous polyposis (FAP)

•Hereditary nonpolyposis colon cancer (HNPCC)

GeneticFamily history of

colorectal cancerAdenomatous

polyps•Familial

adenomatous polyposis (FAP)

•Hereditary nonpolyposis colon cancer (HNPCC)

Fundamental Causes

Ulcerative ColitisUlcerative Colitis

Normal Colon Colon with Ulcerative Colitis

Symptoms

SymptomsSymptoms SymptomsSymptoms

Screening GuidelinesScreening Guidelines

Screening Guidelines

Colonoscopy every 3 yearsHigh-sensitivity fecal occult

blood test (FOBT) every year, orSigmoidoscopy every 5 years

with FOBT in between

Colonoscopy every 3 yearsHigh-sensitivity fecal occult

blood test (FOBT) every year, orSigmoidoscopy every 5 years

with FOBT in between

Colorectal Cancer Prognosis

Colorectal Cancer Prognosis Colorectal Cancer Prognosis

General Disease CourseGeneral Disease Course

StagesStages

Hepatic MetastasisHepatic Metastasis

Stages

Stage 0 – abnormal cells are found in the innermost lining of the colon. Stage 0 – abnormal cells are found in the innermost lining of the colon.

Stages

Stage I – cancer has formed and spread beyond the innermost tissue layer of the colon wall to the middle layers.

Stages

Stage II Stage II

Stage IIA – cancer has spread beyond the middle tissue layers of the colon wall or has spread to nearby tissues around the colon or rectum.

Stage IIB – cancer has spread beyond the colon wall into nearby organs and/or through the peritoneum.

Colorectal cancer has become metastatic colorectal cancer (MCRC).

Stages

Stage III Stage III

Stage IIIA – cancer has spread from the innermost tissue layer of the colon wall to the middle layers and has spread to as many as 3 lymph nodes.

Stage IIIB – cancer has spread to as many as 3 nearby lymph nodes and has spread:

• Beyond the middle tissue layers of the colon wall, or

• To nearby tissues around the rectum, or• Beyond the colon wall into nearby organs

and/or through the peritoneum.

Stage IIIB – cancer has spread to as many as 3 nearby lymph nodes and has spread:

• Beyond the middle tissue layers of the colon wall, or

• To nearby tissues around the rectum, or• Beyond the colon wall into nearby organs

and/or through the peritoneum.

Stage IIIC – Cancer has spread to 4 or more nearby lymph nodes and has spread:

• To or beyond the middle tissues of the colon wall, or

• To nearby tissues around the colon or rectum, or

• To nearby organs and/or through the peritoneum.

Stage IIIC – Cancer has spread to 4 or more nearby lymph nodes and has spread:

• To or beyond the middle tissues of the colon wall, or

• To nearby tissues around the colon or rectum, or

• To nearby organs and/or through the peritoneum.

Stages

Stage IV – Cancer may have spread to nearby lymph nodes and has spread to other parts of the body, such as the liver or the lungs.

General Disease CoursePrognosis – American Joint Committee on

Cancer (AJCC) Staging of Colorectal Cancer

Prognosis – American Joint Committee on Cancer (AJCC) Staging of Colorectal Cancer

T stage N stage M Stage

Five Year Survival Rate (%)

I T1 or T2 N0 M0 93.2

IIa T3 N0 M0 84.7

IIb T4 N0 M0 72.2

IIIa T1 or T2 N1 M0 83.4

IIIb T3 or T4 N1 M0 64.1

IIIc Any T N2 M0 44.3

IV Any T Any N M1 8.1

General Disease CoursePrognosis – American Joint Committee on

Cancer (AJCC) Staging of Colorectal Cancer

Prognosis – American Joint Committee on Cancer (AJCC) Staging of Colorectal Cancer

Hepatic Metastasis

Portal vein

Large intestine

Stomach

Small intestine

Gallbladder Hepatic artery

Symptoms and Screening Guidelines

PrognosisStagesGeneral

Disease Course

Hepatic Metastases

PrognosisStagesGeneral

Disease Course

Hepatic Metastases

Basic information

StatisticsOccurrencePathophysio

Basic information

StatisticsOccurrencePathophysio

Summary

Fundamental Causes

EnvironmentalGeneticUlcerative

Colitis

Fundamental Causes

EnvironmentalGeneticUlcerative

Colitis

• Treatment Options• Determining Treatment• Chemotherapy• Surgery• Transarterial

Chemoembolization• Tissue Ablation• Palliative Care

Determining Treatment

Determining TreatmentDetermining Treatment Diagnostic − ImagingDiagnostic − Imaging

HCCHCC

MCRCMCRC

New agentsNew agents

ChemoembolizationChemoembolization

ResectionResection

Tissue ablationTissue ablation

TransplantationTransplantation

Curative treatmentsCurative treatments

Randomized controlled trialsRandomized controlled trials

Palliative carePalliative care

Determining HCC Treatment

HCCHCC

Stage 0Stage 0 Stage A - CStage A - C Stage DStage D

Increased

Stage 0PST* 0, Okuda 1

*PST – performance status test

Very early stage (0)1 HCCCarcinoma in situ <2 cm

1 HCC1 HCC

Portal pressure/bilirubinPortal pressure/bilirubin

ResectionResection

Normal

3 nodules <3 cm3 nodules <3 cm

Associated diseasesAssociated diseases

No Yes

Liver TransplantLiver Transplant PEI/RFAPEI/RFA

Stage 0 Treatment Stage 0 Treatment

Stage A-COkuda 1-2, PST* 0-2, Child-Pugh A-B

Early stage (A)1 HCC or 3 nodules<3 cm, PST 0

3 nodules <3 cm3 nodules <3 cm

Associated diseasesAssociated diseases

Liver TransplantLiver Transplant

PEI/RFAPEI/RFA

Stage A Treatment Stage A Treatment

Intermediate stage (B)Multinodular PST 0

Stage B Treatment Stage B Treatment

New agentsNew agents

Advanced Stage (C)Portal invasionN1, M1, PST 1-2

Portal invasion, N1, M1

Stage C Treatment Stage C Treatment

Stage I (23%)Stage I (23%) Stage II (31%)Stage II (31%) Stage III (26%)Stage III (26%) Stage IV (20%)Stage IV (20%)

Determining Treatment for MCRC

Colorectal Cancer ( 94,700 cases)Colorectal Cancer ( 94,700 cases)

Local regional therapiesLocal regional therapies

Surgical resectionSurgical resection

Systemic chemotherapySystemic chemotherapy

RFARFA

Radiation microspheresRadiation microspheres

RadiationRadiation

CryoablationCryoablation

TACETACE

Recurrent (10%)Recurrent (10%)

See Stage IVSee Stage IV

5 year survival (90%)5 year survival (90%)

Surgical ResectionSurgical Resection

Stage I (23%)Stage I (23%)

Stage I Treatment Stage I Treatment

Stage II (31%)Stage II (31%)

SurgerySurgery Surgery andadjuvant

chemotherapy

Surgery andadjuvant

chemotherapy

5 year survival (66%)5 year survival (66%) Recurrent (34%)Recurrent (34%)

Stage II Treatment Stage II Treatment

Stage III (26%)Stage III (26%)

Surgery andadjuvant

chemotherapy

Surgery andadjuvant

chemotherapy

5 year survival (51%)5 year survival (51%) Recurrent (49%)Recurrent (49%)

Stage III Treatment Stage III Treatment

Stage IV (20%)Stage IV (20%)

Palliative chemotherapy

Recurrent (>95%)Recurrent (>95%)5 year survival (<5%)5 year survival (<5%)

Stage IV Treatment Stage IV Treatment

Surgery

SurgerySurgery

Hepatectomy PrognosisHepatectomy Prognosis

HepatectomyHepatectomy

MCRC SurgeryMCRC Surgery

Hepatectomy Prognosis

2% mortality rate2% mortality rate

Survival rate 44 monthsSurvival rate 44 months

75% recurrence in 5 years75% recurrence in 5 years

Transarterial Chemoembolization (TACE)

Transarterial ChemoembolizationTransarterial Chemoembolization OverviewOverview

PrognosisPrognosis

ProcessProcess

TACE is effective and well tolerated for palliation of hepatoma and

colon metastases

TACE is effective and well tolerated for palliation of hepatoma and

colon metastases

There are many new modalities, unanswered questions

Controlled studies are neededControlled studies are needed

Combined therapies may offer the best approach

MCRCMCRC

TACE Prognosis

Traditional TACE used as last resort

No survival benefit on patients with reselectable tumors

Survival ranges from 8.5 to 10 months after treatment

TACE Prognosis

Tumor volume: 42.9 cc

Before TACE 3 months after TACE

Tumor volume: 14.5 cc (-66%)

1 month after TACE

Tumor volume: 57.8 cc

Imaging evaluation: Case 1 R.R.Imaging evaluation: Case 1 R.R.

Tissue Ablation

Tissue AblationTissue Ablation Radiofrequency Ablation (RFA)Radiofrequency Ablation (RFA)

Percutaneous Ethanol Injection (PEI)Percutaneous Ethanol Injection (PEI)

CryotherapyMicrowaveLaserFocused UltrasoundRadiofrequency Ablation (RFA)Percutaneous Ethanol Injection

(PEI)Cryoablation

CryotherapyMicrowaveLaserFocused UltrasoundRadiofrequency Ablation (RFA)Percutaneous Ethanol Injection

(PEI)Cryoablation

Radiofrequency Ablation (RFA)Percutaneous Ethanol Injection (PEI)

Tissue Ablation Overview

Radiofrequency Ablation (RFA)

Radiofrequency Ablation (RFA)Radiofrequency Ablation (RFA) RFA OverviewRFA Overview

RFA ProcessRFA Process

Thermal Cell DeathThermal Cell Death

RF PrinciplesRF Principles

RFA ResultsRFA Results

RF Principles

Similar to electrocauterySimilar to electrocautery

Administers a high-frequency currentAdministers a high-frequency current

Electrical componentsElectrical components

Grounding padsGrounding pads

GeneratorGenerator

ProbeProbe

Thermal Cell Death

Temperature (°C)

Cellular Effect

<40 No significant cell damage

40 – 49 Reversible cell damage

49 – 70 Irreversible cell damage (denaturation)

70 – 100 Coagulation (collagens converted to glucose)

100 – 200 Dessication (boiling of intra- and extra-cellular water)

>200 Carbonization

49 – 70 Irreversible cell damage (denaturation)

RFA Results

All metastases must be treated completely

Entire tumor and surrounding 5 mm -10 mm of soft tissue must be ablated

Controlled studies are neededControlled studies are needed

RFA Prognosis

MCRC < 3 cm and HCC < 4 cmMCRC < 3 cm and HCC < 4 cm

28. 9 months (2.4 years) post RFA28. 9 months (2.4 years) post RFA

44.6 months from diagnosis of metastases (Kaplan Meier)

Chemotherapy

SurgeryTACETissue

AblationPEIRFAPalliative

Chemotherapy

SurgeryTACETissue

AblationPEIRFAPalliative

Treatment Options

Summary

MCRCHCC

TreatmentTreatmentAnatomyAnatomyHCC and MCRCHCC and MCRC

Basic InformationBasic Information

Fundamental CausesFundamental Causes

SymptomsSymptoms

PrognosisPrognosis

Treatment OptionsTreatment Options

Determining TreatmentDetermining Treatment

ChemotherapyChemotherapy

SurgerySurgery

TACETACE

Tissue AblationTissue Ablation

Palliative CarePalliative Care

Course Summary

Colon AnatomyColon Anatomy

Liver AnatomyLiver Anatomy

PROPERTIES

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Disease States and Cancers of the Liver and Colon

General Disease Course

Stage Definition

T1 Tumor invades submucosa.

T2 Tumor invades muscularis propria.

T3 Tumor invades through muscularis propria into the subserosa or nonperitonealized pericolonic tissues.

T4 Tumor invades other organs or structures and or perforates visceral peritoneum.

N0 No regional lymph node metastasis.

N1 Metastasis to 1 to 3 regional lymph nodes.

N2 Metastasis to 4 or more regional lymph nodes.

M0 No distant metastasis.

M1 Distant metastasis.

Back Back AJCC T, N, and M DefinedAJCC T, N, and M Defined

General Disease Course

Stage Description

0 Abnormal cells are found in the innermost lining of the colon.

I Cancer has formed and spread beyond the innermost tissue layer of the colon wall to the middle layers.

IIa Cancer has spread beyond the middle tissue layers of the colon wall or has spread to nearby tissues around the colon or rectum.

IIb Cancer has spread beyond the colon wall into nearby organs and/ or through the peritoneum.

IIIa Cancer has spread from the innermost tissue layer of the colon wall to the middle layers and has spread to as many as 3 lymph nodes.

IIIb Cancer has spread to as many as 3 nearby lymph nodes and has spread:• Beyond the middle tissue layers of the colon wall, or• To nearby tissues around the rectum, or• Beyond the colon wall into nearby organs and/or through the peritoneum.

IIIc Cancer has spread to 4 or more nearby lymph nodes and has spread:• To or beyond the middle tissues of the colon wall, or• To nearby tissues around the colon or rectum, or• To nearby organs and/ or through the peritoneum.

IV Cancer may have spread to nearby lymph nodes and has spread to other parts of the body, such as the liver or the lungs.

Back Back AJCC Stages DefinedAJCC Stages Defined

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