Hepatocellular Carcinoma. Incidence One of the most common malignancies worldwide More common in Asia and Africa than in the United States Highest.

Hepatocellular Hepatocellular CarcinomaCarcinoma

IncidenceIncidence

One of the most common malignancies worldwideOne of the most common malignancies worldwide More common in Asia and Africa than in the United More common in Asia and Africa than in the United

StatesStates Highest incidence of HCC is in Japan (4-5%) Highest incidence of HCC is in Japan (4-5%) Other high-incidence regions (sub-Saharan Africa)Other high-incidence regions (sub-Saharan Africa) Internationally, the common causes of HCC are Internationally, the common causes of HCC are

hepatitis B, hepatitis C, and aflatoxin exposurehepatitis B, hepatitis C, and aflatoxin exposure Annual global incidence of 1 Million casesAnnual global incidence of 1 Million cases Male: Female = 4:1Male: Female = 4:1 Incidence rate = death rateIncidence rate = death rate

http://emedicine.medscape.com/article/369226-overviewHarrison’s Principles of Internal Medicine 17th ed

IncidenceIncidence Most patients die within 1 year after diagnosisMost patients die within 1 year after diagnosis Survival dependent on :Survival dependent on :

tumor sizetumor size associated diseases at the time of diagnosisassociated diseases at the time of diagnosis

Patients with cirrhosis have a shorter survival. Surgical cure is Patients with cirrhosis have a shorter survival. Surgical cure is possible in less than 5% of patients.possible in less than 5% of patients.

Annual Death Rates in MalesAnnual Death Rates in Males Low-incidence countries (US)Low-incidence countries (US)

1.9 per 100,0001.9 per 100,000 Intermediate-incidence (Austria and South Africa)Intermediate-incidence (Austria and South Africa)

5.1-20.0 per 100,0005.1-20.0 per 100,000 High-incidence (Asia, China, Korea)High-incidence (Asia, China, Korea)

23.1-150 per 100,00023.1-150 per 100,000 http://emedicine.medscape.com/article/369226-overviewHarrison’s Principles of Internal Medicine 17th ed

IncidenceIncidenceAge: Patients with cirrhosis may present earlier.Age: Patients with cirrhosis may present earlier. In high-incidence regions of the world (ie, Asia, In high-incidence regions of the world (ie, Asia,

Africa), patients present at age 30-50 yearsAfrica), patients present at age 30-50 years

In low-incidence regions (ie, Western In low-incidence regions (ie, Western Hemisphere), patients present at age 70-80 Hemisphere), patients present at age 70-80 yearsyears

United StatesUnited States 4 Million chronic HCV carriers4 Million chronic HCV carriers 400,000 will likely develop cirrhosis400,000 will likely develop cirrhosis 20,000 may develop HCC annually 20,000 may develop HCC annually

http://emedicine.medscape.com/article/369226-overviewHarrison’s Principles of Internal Medicine 17th ed

EpidemiologyEpidemiology

Endemic hot spots:Endemic hot spots: in areas of China and sub-Saharan Africain areas of China and sub-Saharan Africa associated with both high endemic hepatitis B associated with both high endemic hepatitis B

carrier rates and mycotoxin contamination of carrier rates and mycotoxin contamination of foodstuffs, stored grains, drinking water, and soilfoodstuffs, stored grains, drinking water, and soil

Environmental factors are important: Environmental factors are important: Japanese in Japan have a higher incidence Japanese in Japan have a higher incidence

than those living in Hawaii, who in turn have a than those living in Hawaii, who in turn have a higher incidence than those living in California.higher incidence than those living in California.

Fauci, et al. 2008. Harrison’s Principles of Internal Medicine, 17th ed.

Etiologic FactorsEtiologic Factors

Chemical carcinogensChemical carcinogens HepatitisHepatitis Others Others

Chemical CarcinogensChemical Carcinogens

Aflatoxin B1Aflatoxin B1 Product of Product of Aspergillus flavus Aspergillus flavus and and parasiticusparasiticus Most potent ubiquitous natural chemical carcinogenMost potent ubiquitous natural chemical carcinogen Found in stored grains in hot, humid places where Found in stored grains in hot, humid places where

peanut and rice are stored in unrefrigerated peanut and rice are stored in unrefrigerated conditionsconditions

Pyrrollizidine alkaloidsPyrrollizidine alkaloids Plant sources such as comfrey; used in herbal food Plant sources such as comfrey; used in herbal food

supplementssupplements Tannic acid and safroleTannic acid and safrole

Fauci, et al. 2008. Harrison’s Principles of Internal Medicine, 17th ed.Goldman, Ausiello. 2007. Cecil Medicine, 23rd ed. http://www.fda.gov/Food/DietarySupplements/Alerts/ucm111219.htm

Etiologic Factors of HCCEtiologic Factors of HCC


HepatitisHepatitis

Hepatitis BHepatitis BHBsAg positive = 98-fold greater risk for HCC HBsAg positive = 98-fold greater risk for HCC

(a study on Taiwanese male postal carriers) (a study on Taiwanese male postal carriers)

HCC may arise from rounds of hepatic HCC may arise from rounds of hepatic destruction with subsequent proliferationdestruction with subsequent proliferation

Only half of patients have cirrhosis; other half, Only half of patients have cirrhosis; other half, chronic active hepatitischronic active hepatitis

Vaccine against hepatitis B – reduced the Vaccine against hepatitis B – reduced the incidence of HBV-associated HCC high-incidence of HBV-associated HCC high-prevalence regions (Alaska, Africa)prevalence regions (Alaska, Africa)

Fauci, et al. 2008. Harrison’s Principles of Internal Medicine, 17th ed.Goldman, Ausiello. 2007. Cecil Medicine, 23rd ed.

HepatitisHepatitis Hepatitis CHepatitis C

Patients tend to have more frequent advanced Patients tend to have more frequent advanced cirrhosiscirrhosis

Approximately 80% will develop chronic hepatitis Approximately 80% will develop chronic hepatitis C, and of this 20-30% will develop cirrhosisC, and of this 20-30% will develop cirrhosis

HCC then develops in up to 20% of individuals HCC then develops in up to 20% of individuals with cirrhosis from chronic HCV, at a rate of 2 to with cirrhosis from chronic HCV, at a rate of 2 to 6% per year. 6% per year.

A typical interval between HCV-associated A typical interval between HCV-associated transfusion and subsequent HCC is ~30 years.transfusion and subsequent HCC is ~30 years.


CirrhosisCirrhosis

It is still not clear whether It is still not clear whether Cirrhosis itself is a predisposing factor to the Cirrhosis itself is a predisposing factor to the

development of HCC, or development of HCC, or Underlying causes of the cirrhosis are the Underlying causes of the cirrhosis are the

carcinogenic factorscarcinogenic factors

~20% of patients with HCC do not have ~20% of patients with HCC do not have underlying cirrhosisunderlying cirrhosis Etiology is unclearEtiology is unclear


Cirrhosis in the PatientCirrhosis in the Patient

Physical stigmata of cirrhosis:Physical stigmata of cirrhosis: Spider angiomataSpider angiomata Palmar erythemaPalmar erythema AscitesAscites EdemaEdema ClubbingClubbing Enlarged parotid glandsEnlarged parotid glands GynecomastiaGynecomastia Prominent venous collaterals on the abdomenProminent venous collaterals on the abdomen


Cirrhosis in the PatientCirrhosis in the Patient


Etiologic Factors of HCCEtiologic Factors of HCC


OthersOthers More common risk factorsMore common risk factors

HepatitisHepatitis Alcohol abuseAlcohol abuse Autoimmune chronic active hepatitisAutoimmune chronic active hepatitis Cryptogenic cirrhosisCryptogenic cirrhosis Nonalcoholic steatohepatitis (NASH)Nonalcoholic steatohepatitis (NASH)

Less common risk factorsLess common risk factors Primary biliary cirrhosisPrimary biliary cirrhosis Metabolic diseasesMetabolic diseases

Hemochromatosis, Wilson’s dse, Hemochromatosis, Wilson’s dse, αα1-antitrypsin deficiency, 1-antitrypsin deficiency, tyrosinemia, porphyria cutanea tarda, glycogenesis types 1 & tyrosinemia, porphyria cutanea tarda, glycogenesis types 1 & 3, citrullinemia, orotic aciduria3, citrullinemia, orotic aciduria


HCC Risk Factors Present in HCC Risk Factors Present in the Patientthe Patient

CommonCommon Cirrhosis from any Cirrhosis from any

causecause Hepatitis B or C chronic Hepatitis B or C chronic

infectioninfection Ethanol chronic Ethanol chronic

consumptionconsumption Nonalcoholic Nonalcoholic

steatohepatitis (NASH)steatohepatitis (NASH) Aflatoxin B1 or other Aflatoxin B1 or other

mycotoxinsmycotoxins

UnusualUnusual Primary biliary cirrhosisPrimary biliary cirrhosis HemochromatosisHemochromatosis Wilson’s dseWilson’s dse αα1-antitrypsin deficiency1-antitrypsin deficiency TyrosinemiaTyrosinemia Porphyria cutanea tardaPorphyria cutanea tarda Glycogen storage diseasesGlycogen storage diseases CitrullinemiaCitrullinemia


Clinical FeaturesClinical Features

Patients who develop HCC usually have no Patients who develop HCC usually have no symptoms other than those related to their chronic symptoms other than those related to their chronic liver diseaseliver disease

Mild to moderate abdominal pain with fullness and Mild to moderate abdominal pain with fullness and swellingswelling

Weight loss or early satietyWeight loss or early satiety Jaundice due to invasion of biliary tree, compression Jaundice due to invasion of biliary tree, compression

of the intrahepatic duct or as a result of hemobiliaof the intrahepatic duct or as a result of hemobilia Bone pain or dyspnea due to metastasesBone pain or dyspnea due to metastases Intraperitoneal bleedingIntraperitoneal bleeding

Physical signsPhysical signs

Hepatomegaly is the most common physical Hepatomegaly is the most common physical sign occurring in 50-90% of patientssign occurring in 50-90% of patients

Splenomegaly due to portal hypertensionSplenomegaly due to portal hypertension Muscle wasting and weight lossMuscle wasting and weight loss AscitesAscites Signs of chronic liver diseaseSigns of chronic liver disease: jaundice, : jaundice,

dilated abdominal veins, palmar erythema, dilated abdominal veins, palmar erythema, gynecomastia, testicular atrophy and gynecomastia, testicular atrophy and peripheral edemaperipheral edema

Paraneoplastic Paraneoplastic syndromessyndromes

Disorders that are triggered by an Disorders that are triggered by an altered immune system response to a altered immune system response to a neoplasmneoplasm

defined as clinical syndromes involving defined as clinical syndromes involving nonmetastatic systemic effects that nonmetastatic systemic effects that accompany malignant disease.accompany malignant disease.

may result from production and release may result from production and release of antibodies and physiologically active of antibodies and physiologically active substances or it may be idiopathicsubstances or it may be idiopathic

DiagnosisDiagnosis

History & PEHistory & PE Serologic AssaysSerologic Assays RadiologyRadiology Pathologic DiagnosisPathologic Diagnosis

History & PEHistory & PE

HistoryHistory Evaluating positive predisposing factorsEvaluating positive predisposing factors

History of hepatitis or jaundiceHistory of hepatitis or jaundice Blood transfusionBlood transfusion Use of intravenous drugsUse of intravenous drugs

Family history of HCC or hepatitisFamily history of HCC or hepatitis Social historySocial history

Job descriptions/ industrial exposure to Job descriptions/ industrial exposure to carcinogenic drugscarcinogenic drugs

Contraceptive hormonesContraceptive hormones

Fauci et.al. Harrison’s principles of Internal Medicine 2008 17th edition. McGraw-Hill USA

History & PEHistory & PE Physical ExaminationPhysical Examination

Assessing stigmata of underlying liver diseaseAssessing stigmata of underlying liver disease JaundiceJaundice AscitesAscites Peripheral edemaPeripheral edema Spider neviSpider nevi Palmar erythemaPalmar erythema Weight lossWeight loss

Evaluation of abdomenEvaluation of abdomen Hepatic sizeHepatic size Masses or ascitesMasses or ascites Hepatic nodularityHepatic nodularity Tenderness Tenderness SplenomegalySplenomegaly


Serologic AssaysSerologic Assays• AFP (AFP (αα- fetoprotein)- fetoprotein)• DCP (des-DCP (des-γγ-carboxy prothrombin)-carboxy prothrombin)• CEA, Vitamin B12, AFP, Ferritin, PIVKA-2 CEA, Vitamin B12, AFP, Ferritin, PIVKA-2

antimitochondrial Abantimitochondrial Ab• Standard liver function tests (PT, PTT, Standard liver function tests (PT, PTT,

albumin,transaminases, albumin,transaminases, γγ-glutamyl -glutamyl transpeptidase, alkaline phosphatase)transpeptidase, alkaline phosphatase)

• Hepatitis A, B, C serologyHepatitis A, B, C serology


RadiologyRadiology UltrasoundUltrasound

Excellent screening toolExcellent screening tool Findings:Findings:

Hypervascularity of the tumor massHypervascularity of the tumor mass Thrombosis by tumor invasion of normal portal Thrombosis by tumor invasion of normal portal

veinsveins Echogenic massesEchogenic masses

Fauci et.al. Harrison’s principles of Internal Medicine 2008 17th edition. McGraw-Hill USANovelline, R. Squire’s Fundamentals of Radiology 6th edition.Harvard University Press

RadiologyRadiology CT (Helical/ Triphasic)CT (Helical/ Triphasic)

To determine tumor size and extent and To determine tumor size and extent and presence of portal vein invasion presence of portal vein invasion

Accurately localizes the tumor and determine Accurately localizes the tumor and determine whether resection is possiblewhether resection is possible

Findings:Findings: Portal vein invasion is detected as an obstruction Portal vein invasion is detected as an obstruction

and expansion of the vesseland expansion of the vessel Liver tumors tend to have ill-defined margins and Liver tumors tend to have ill-defined margins and

sometimes necrotic centers and calcificationsometimes necrotic centers and calcification


RadiologyRadiology MRIMRI

- indicated if CT is inconclusive- indicated if CT is inconclusive

- can provide detailed information of the mass- can provide detailed information of the mass

- Findings:- Findings:

- mass will typically be hypo-intense or iso-- mass will typically be hypo-intense or iso-intense on a T1 weighted imageintense on a T1 weighted image

- brighten markedly with T2 weighting- brighten markedly with T2 weighting


Pathologic DiagnosisPathologic Diagnosis

Histologic proof of the presence of HCCHistologic proof of the presence of HCC Core liver biopsy of the mass under ultrasound Core liver biopsy of the mass under ultrasound

guidanceguidance Bleeding risk is increased compared to other Bleeding risk is increased compared to other

cancers because:cancers because:(1)(1) Tumors are hypervascularTumors are hypervascular(2)(2) Px often have thrombocytopenia & decreased clotting Px often have thrombocytopenia & decreased clotting

factorsfactors

* For patients suspected of having portal vein involvement, * For patients suspected of having portal vein involvement, a core biopsy of the portal vein may also be indicateda core biopsy of the portal vein may also be indicated


StagingStagingVariablesVariables 00 11 22

I. Tumor numberI. Tumor number singlesingle multiplemultiple --

Hepatic Hepatic replacement by replacement by tumor (%)tumor (%)

<50<50 <50<50 >50>50

II. Child-pugh II. Child-pugh scorescore

AA BB CC

III. III. ΑΑ-fetoprotein -fetoprotein level (ng/ml)level (ng/ml)

<400<400 >/- 400>/- 400 --

IV. Portal Vein IV. Portal Vein Thrombosis (CT)Thrombosis (CT)

NoNo Yes Yes __

CLIP ClassificationClip stages(= sum of points): CLIP 0, )points; CLIP1, 1 point; CLIP2, 2 points; CLIP 3, 3 points

Harrison’s Principle of Internal Medicine 17th edition 2008

StagingStaging

Tumor size Tumor size AscitesAscites Albumin(g/L)Albumin(g/L) Bilirubin (mg/dl)Bilirubin (mg/dl)

>/- 50% <50%>/- 50% <50% + -+ - </-3 >3</-3 >3 >/- 3 <3>/- 3 <3

(+) (-)(+) (-) (+) (-)(+) (-) (+) (-)(+) (-) (+) (-)(+) (-)

Okuda ClassificationOkuda stages: stage 1, all (-); stage 2, 1 or 2(+); stage 3, 3 or 4(+)

Harrison’s Principle of Internal Medicine 17th edition 2008

StagingStaging

The best prognosis is Stage I, solitary The best prognosis is Stage I, solitary tumor ,2cm in diameter without vascular tumor ,2cm in diameter without vascular invasion.invasion.

Adverse prognostic features include:Adverse prognostic features include: Ascites, vascular invasion, and lymph node spreadAscites, vascular invasion, and lymph node spread Most large tumors have microscopic vascular Most large tumors have microscopic vascular

invasion, so full staging can only be made after invasion, so full staging can only be made after surgical resection. surgical resection.

Stage III – contains a mixture of lymph node- Stage III – contains a mixture of lymph node- positive and –negative tumorspositive and –negative tumors Patients with lymph node positive have a poor Patients with lymph node positive have a poor

prognosis and few patients survive one yearprognosis and few patients survive one yearHarrison’s Principle of Internal Medicine 17th edition 2008

StagingStaging

Stage IVStage IV Poor after either resection or transplantation, Poor after either resection or transplantation,

and 1-year survival is rare.and 1-year survival is rare. A working staging system based entirely on A working staging system based entirely on

clinical grounds that incorporates the clinical grounds that incorporates the contribution of the underlying liver disease contribution of the underlying liver disease was developed by Okuda et al.was developed by Okuda et al. Patients with Okuda stage III have a dire Patients with Okuda stage III have a dire

prognosis, because they usually cannot be prognosis, because they usually cannot be curatively resected and the condition of their curatively resected and the condition of their liver typically precludes chemotherapy liver typically precludes chemotherapy

Harrison’s Principle of Internal Medicine 17Harrison’s Principle of Internal Medicine 17thth edition 2008 edition 2008

TreatmentTreatment

Stage I and II HCCStage I and II HCC

Important principle is to use liver-sparing Important principle is to use liver-sparing treatments and to focus on treatment of treatments and to focus on treatment of both tumor and cirrhosisboth tumor and cirrhosis Surgical resectionSurgical resection Local ablation (thermal or radiofrequency)Local ablation (thermal or radiofrequency) Local injection therapies (ethanol or acetic Local injection therapies (ethanol or acetic

acid)acid)

Surgical ExcisionSurgical Excision Only Child A patients should be considered Only Child A patients should be considered

for surgical resectionfor surgical resection Child B and C stage I and II including patients Child B and C stage I and II including patients

with ascitis and history of variceal bleeding with ascitis and history of variceal bleeding should be referred for OLTXshould be referred for OLTX Open surgical incision is most reliableOpen surgical incision is most reliable Laparoscopic resection: RFA or PEILaparoscopic resection: RFA or PEI

***No adequate comparison of techniques and ***No adequate comparison of techniques and choice of treatment depends on physician choice of treatment depends on physician skillskill

Local Ablation StrategiesLocal Ablation Strategies

RFA – uses heat to ablate tumor which can RFA – uses heat to ablate tumor which can be performed percutaneously with CT, US be performed percutaneously with CT, US guidance or by laparoscopy with USguidance or by laparoscopy with US

Maximum probe size allows 7 cm zone of Maximum probe size allows 7 cm zone of necrosis adequate for 3-4 cm of tumornecrosis adequate for 3-4 cm of tumor

Heat kills cells within zone of necrosisHeat kills cells within zone of necrosis Limitation: treatment of tumors close to Limitation: treatment of tumors close to

main portal pedicles are can lead to bile main portal pedicles are can lead to bile duct injury and obstructionduct injury and obstruction

Local Injection TherapyLocal Injection Therapy

Percutaneous Ethanol Injection – most Percutaneous Ethanol Injection – most common agent usedcommon agent used

- causes direct destruction of cancer - causes direct destruction of cancer cells but is not selective and will destroy cells but is not selective and will destroy normal cells in the vicinitynormal cells in the vicinity

- requires multiple injection (average -- requires multiple injection (average -33))

- maximum size of tumor reliably - maximum size of tumor reliably treated – treated – 33cmcm

Liver TransplantationLiver Transplantation

UNOS for Organ sharing point system for priority UNOS for Organ sharing point system for priority scoring of OLTX recipientsscoring of OLTX recipients

OLTX for patients with a single </=5 or 3 or fewer OLTX for patients with a single </=5 or 3 or fewer nodules with each </=3 (Milan criteria ) resulted in nodules with each </=3 (Milan criteria ) resulted in excellent tumor-free survival ( >/= 70% at 5 years)excellent tumor-free survival ( >/= 70% at 5 years)

Therapies as “bridge” to OLTXTherapies as “bridge” to OLTX RFARFA PEIPEI TACETACE

***These pretransplant treatments allow patients to ***These pretransplant treatments allow patients to remain in the waiting list longer, giving them greater remain in the waiting list longer, giving them greater opportunities to be transplanted opportunities to be transplanted

Adjuvant TherapyAdjuvant Therapy

The role of adjuvant chemotherapy for The role of adjuvant chemotherapy for patients after resection or OLTX remains patients after resection or OLTX remains unclear. unclear.

No clear advantage in disease-free or No clear advantage in disease-free or overall survival overall survival

Stages III and IV HCCStages III and IV HCC

Stage III tumorsStage III tumors without cirrhosiswithout cirrhosis

major hepatectomy is feasiblemajor hepatectomy is feasible prognosis is poorprognosis is poor

Child's A cirrhosis Child's A cirrhosis may be resectedmay be resected long-term prognosis is poor. long-term prognosis is poor.

even successful resection can be even successful resection can be followed by rapid recurrence. followed by rapid recurrence.

not considered candidates for not considered candidates for transplantation because of the high transplantation because of the high tumor recurrence ratestumor recurrence rates

Stage IV tumorsStage IV tumors prognosis is poor prognosis is poor no surgical no surgical

treatment is treatment is recommendedrecommended

Systemic ChemotherapySystemic Chemotherapy

No single agent or combination of agents No single agent or combination of agents given systemically reproducibly leads to given systemically reproducibly leads to even a 25% response rate or has any even a 25% response rate or has any effect on survivaleffect on survival

Regional ChemotherapyRegional Chemotherapy The legitimate goal of regional therapies: The legitimate goal of regional therapies: improving patient improving patient

quality of lifequality of life Given via the hepatic artery have activity in HCC confined to Given via the hepatic artery have activity in HCC confined to

the liverthe liver Only 2 randomized controlled trials that showed a survival Only 2 randomized controlled trials that showed a survival

advantage for TACE advantage for TACE One that used Doxorubicin and the other CisplatinOne that used Doxorubicin and the other Cisplatin

Uses also an embolizing agentUses also an embolizing agent Eg. ethiodol, gelatin sponge particles (Gelfoam), starch (Spherex), or Eg. ethiodol, gelatin sponge particles (Gelfoam), starch (Spherex), or

microspheresmicrospheres Advantage: showed higher objective response rates for arterial Advantage: showed higher objective response rates for arterial

administration of drugs together with some form of hepatic artery administration of drugs together with some form of hepatic artery occlusion compared with any form of systemic chemotherapy to dateocclusion compared with any form of systemic chemotherapy to date

Disadvantage: Increased toxicitiesDisadvantage: Increased toxicities

Regional ChemotherapyRegional Chemotherapy Toxicities seen with addition of embolizing agents:Toxicities seen with addition of embolizing agents:

transient fever, abdominal pain, anorexia, transient fever, abdominal pain, anorexia, increased ascites or transient elevation of transaminasesincreased ascites or transient elevation of transaminases cystic artery spasm and cholecystitiscystic artery spasm and cholecystitis

The hepatic toxicities associated with embolization The hepatic toxicities associated with embolization may be ameliorated by the use of degradable starch may be ameliorated by the use of degradable starch microspheres, with 50–60% response rates.microspheres, with 50–60% response rates.

““A major problem in showing a survival advantage in A major problem in showing a survival advantage in patients responding to TACE is that many patients patients responding to TACE is that many patients die of their underlying cirrhosis, not the tumor. “die of their underlying cirrhosis, not the tumor. “

Table 88-6 Some Novel Medical Treatments for Table 88-6 Some Novel Medical Treatments for Hepatocellular CarcinomaHepatocellular CarcinomaEGF receptor antibody EGF receptor antibody Erlotinib, GefitinibErlotinib, GefitinibKinase antagonists, SorafenibKinase antagonists, SorafenibVitamin KVitamin KIL-2IL-2131131I – ethiodol (Lipiodol)I – ethiodol (Lipiodol)

131131I – FerritinI – Ferritin

9090Yttrium microspheresYttrium microspheres

166166HolmiumHolmium

Three-dimensional conformal radiationThree-dimensional conformal radiationProton beam high-dose radiotherapyProton beam high-dose radiotherapyAnti-angiogenesis strategies, BevacizumabAnti-angiogenesis strategies, Bevacizumab

Experimental TherapiesExperimental Therapies

Experimental TherapiesExperimental Therapies Therapies that show encouraging survival effects:Therapies that show encouraging survival effects:

pure beta emitter pure beta emitter 9090yttrium attached to either glass or resin microspheres yttrium attached to either glass or resin microspheres (in Phase II trials of HCC) (in Phase II trials of HCC)

Oral sorafenib - increases median survival from 6 to 9 months in Oral sorafenib - increases median survival from 6 to 9 months in advanced, unresectable HCC. advanced, unresectable HCC.

Therapy that show decreased tumor occurrenceTherapy that show decreased tumor occurrence Vitamin K (high dosage) (in clinical trials)Vitamin K (high dosage) (in clinical trials)

Therapy that show no effects on survival Therapy that show no effects on survival Epidermal growth factor (EGF) receptor antibodies and EGF receptor Epidermal growth factor (EGF) receptor antibodies and EGF receptor

kinase inhibitors (in clinical trials)kinase inhibitors (in clinical trials) anti-angiogenesis therapies (in clinical trials)anti-angiogenesis therapies (in clinical trials)

Other forms of Other forms of radiation therapy radiation therapy used in HCCused in HCC external beam external beam conformal radiation therapyconformal radiation therapy significant dose-limiting problem: Radiation hepatitissignificant dose-limiting problem: Radiation hepatitis

Summary of TherapySummary of Therapy

1.1. HCC < 2 cm: RFA ablation, PEI, or resectionHCC < 2 cm: RFA ablation, PEI, or resection2.2. HCC > 2 cm, no vascular invasion: liver HCC > 2 cm, no vascular invasion: liver

resection, RFA, or OLTXresection, RFA, or OLTX3.3. Multiple unilobar tumors or tumor with vascular Multiple unilobar tumors or tumor with vascular

invasion: TACEinvasion: TACE4.4. Bilobar tumors, no vascular invasion: TACE Bilobar tumors, no vascular invasion: TACE

with OLTX for patients whose tumors have a with OLTX for patients whose tumors have a responseresponse

5.5. Extrahepatic HCC or elevated bilirubin: Phase I Extrahepatic HCC or elevated bilirubin: Phase I and II studies.and II studies.

ReferencesReferences

Fauci, et al. 2008. Harrison’s Principles of Internal Fauci, et al. 2008. Harrison’s Principles of Internal Medicine, 17Medicine, 17thth ed. ed.

Goldman, Ausiello. 2007. Cecil Medicine, 23Goldman, Ausiello. 2007. Cecil Medicine, 23 rdrd ed. ed.

Novelline, R. Squire’s Fundamentals of Radiology Novelline, R. Squire’s Fundamentals of Radiology 6th edition.Harvard University Press6th edition.Harvard University Press

http://www.fda.gov/Food/DietarySupplements/http://www.fda.gov/Food/DietarySupplements/Alerts/ucm111219.htmAlerts/ucm111219.htm

http://emedicine.medscape.com/article/369226-http://emedicine.medscape.com/article/369226-overviewoverview

Hepatocellular Carcinoma. Incidence One of the most common malignancies worldwide More common in Asia and Africa than in the United States Highest.

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