Joint Hospital Surgical Grand Round Radiofrequency Ablation of Hepatic Tumor (Factors affect local recurrence rate) Dr K Y Yuen United Christian Hospital

Joint Hospital Surgical Joint Hospital Surgical Grand RoundGrand Round

Radiofrequency Ablation of Hepatic TumorRadiofrequency Ablation of Hepatic Tumor

(Factors affect local recurrence rate)(Factors affect local recurrence rate)

Dr K Y YuenDr K Y Yuen

United Christian HospitalUnited Christian Hospital

IntroductionIntroduction

• Hepatocellular carcinoma (HCC) is the Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the fifth most common malignancy in the world world

• Global annual incidence is one million Global annual incidence is one million new patientsnew patients

• 70% in Asia and 12% in Africa70% in Asia and 12% in Africa

IntroductionIntroduction

• Surgery is the only known curative Surgery is the only known curative option for either primary or secondary option for either primary or secondary hepatic carcinomahepatic carcinoma

• Resection or transplantation is the gold Resection or transplantation is the gold standard of treatment for liver tumorstandard of treatment for liver tumor

• Only 20% to 37% of patients is suitable Only 20% to 37% of patients is suitable for hepatectomy for hepatectomy

Fan et la, Annals of Surgery 1999Fan et la, Annals of Surgery 1999

IntroductionIntroductionFactors limit the surgical intervention:Factors limit the surgical intervention:• multiple / diffuse tumorsmultiple / diffuse tumors• tumor in unresectable locations (proximity of the tumors to tumor in unresectable locations (proximity of the tumors to

major vascular and biliary structures)major vascular and biliary structures)• Poor co-morbidity Poor co-morbidity • inadequate liver reserveinadequate liver reserve• significant portal hypertensionsignificant portal hypertension

5- year survival rate for resectable HCC or 5- year survival rate for resectable HCC or liver metastasis is only 20 - 40 %liver metastasis is only 20 - 40 %

Loco-regional therapies have been developed Loco-regional therapies have been developed for the treatment of unresectable liver for the treatment of unresectable liver tumortumor

Nguyen et la, Clinical Gastroenterology 2005

Radio Frequency AblationRadio Frequency Ablation

• First described by Rossi et al in 1993First described by Rossi et al in 1993• High-frequency (450- 500KHz) High-frequency (450- 500KHz)

alternating RF current causes alternating RF current causes oscillatory movement of ions in oscillatory movement of ions in tissue tissue

• The mechanism of tissue heating is The mechanism of tissue heating is frictional heat caused by the motion frictional heat caused by the motion from the ionic currentfrom the ionic current

• Cause coagulation necrosis at Cause coagulation necrosis at temperature between 50-80temperature between 50-80ooCC

Radio Frequency AblationRadio Frequency AblationIndications:Indications:• Alterative to surgery in poor liver function patient Alterative to surgery in poor liver function patient

with primary or secondary liver tumor with primary or secondary liver tumor • Supplementary to surgery in bilobal tumorsSupplementary to surgery in bilobal tumors• Liver transplant candidates (bridge)Liver transplant candidates (bridge)

Some transplant surgeons are using percutaneous or Some transplant surgeons are using percutaneous or laparoscopic RFA to treat HCCs detected in patients with laparoscopic RFA to treat HCCs detected in patients with cirrhosis on the transplant waiting list in an attempt to cirrhosis on the transplant waiting list in an attempt to attain local control of tumor and prevent progressionattain local control of tumor and prevent progression

Robert Goldstein, MD, personal communication, April 2000Robert Goldstein, MD, personal communication, April 2000


Contraindications:Contraindications:– Child’C cirrhosis (gross ascites)Child’C cirrhosis (gross ascites)– Excessive tumor burdenExcessive tumor burden– Extrahepatic diseasesExtrahepatic diseases– Active infectionActive infection– Renal insufficiencyRenal insufficiency– CoagulopathyCoagulopathy– Near major ductal confluenceNear major ductal confluence


•Complications (0-12%):Complications (0-12%):● Abscess formationAbscess formation● Bleeding(delayed bleeding into the ablated area, Bleeding(delayed bleeding into the ablated area,

subcutaneous/ subcapsular haematoma)subcutaneous/ subcapsular haematoma)● Needle tract seeding (up to 12.5%)Needle tract seeding (up to 12.5%)● Bile leakageBile leakage● Bile duct strictureBile duct stricture● hydropneumothroraxhydropneumothrorax● Liver failureLiver failure● Grounding pad burnGrounding pad burn● Acute renal failureAcute renal failure● Mortality: 0 -1%Mortality: 0 -1%


• RFA may be a superior option amount RFA may be a superior option amount the locoreginal ablation therapy:the locoreginal ablation therapy:

Lower complication rateLower complication rate

Less recurrence rateLess recurrence rate

Shorter hospital stayShorter hospital stay

R Poon et la, Annals of Surgery 1999


Question to answerQuestion to answer

• What determine the efficacy of RFA in What determine the efficacy of RFA in liver tumor patient ?liver tumor patient ?

• Local Recurrence is one of the Local Recurrence is one of the important aspectsimportant aspectsLocal recurrenceLocal recurrence was defined as radiological (CT, MRI or was defined as radiological (CT, MRI or

contrast-enhanced ultrasound) and/or histological (tumor contrast-enhanced ultrasound) and/or histological (tumor cells with intact mitochondrial enzyme staining) detection cells with intact mitochondrial enzyme staining) detection of residual or recurrent viable tumor at the site of the of residual or recurrent viable tumor at the site of the original tumor, during follow-up and after completion of all original tumor, during follow-up and after completion of all (one or more) sessions.(one or more) sessions.

Pre OT

Post OT 1 week

Post OT 3 months

Siperstein A et la, Annals of Surgical Oncology 2005

Local Recurrence After Hepatic Local Recurrence After Hepatic Radiofrequency CoagulationRadiofrequency CoagulationMultivariate Meta-Analysis and Multivariate Meta-Analysis and Review of Contributing FactorsReview of Contributing Factors

Stefaan Mulier, MD, Yicheng Ni, PhD, Jacques Jamart, Stefaan Mulier, MD, Yicheng Ni, PhD, Jacques Jamart, MD,Theo Ruers, PhD, Guy Marchal, PhD, and Luc Michel, MD,Theo Ruers, PhD, Guy Marchal, PhD, and Luc Michel, MDMD

Annals of Surgery, Annals of Surgery, August 2005August 2005

Local RecurrenceLocal Recurrence• Local recurrence rate after RFA of liver Local recurrence rate after RFA of liver

tumors varies widely between 2% and 60%tumors varies widely between 2% and 60%• A local recurrence seriously jeopardizes A local recurrence seriously jeopardizes

the chances of curethe chances of cure• Re-treatment is often Re-treatment is often impossibleimpossible or has a or has a

high risk of failurehigh risk of failure• From From Solbiati L et al 1999Solbiati L et al 1999, only 55% , only 55%

recurrent tumors were re-treated and a recurrent tumors were re-treated and a complete coagulation was obtained in only complete coagulation was obtained in only cases 36%.cases 36%.

• Reasons for not considering re-treatment:Reasons for not considering re-treatment:unfavorable geometry unfavorable geometry diffuse metastasesdiffuse metastases

Local Recurrence Rate: Local Recurrence Rate: Univariable Analysis of Univariable Analysis of Contributing FactorsContributing Factors• 9 factors:9 factors:

DiameterDiameter (size) (size)PathologyPathologyProximity of major vesselProximity of major vesselLocationLocationApproachApproach (surgery Vs percutaneous)(surgery Vs percutaneous)Intentional MarginIntentional MarginVascular occlusionVascular occlusionAnaethesiaAnaethesiaImagingImagingPhysician’s experiencePhysician’s experience

Diameter (Size)Diameter (Size)• Current recommended tumor size Current recommended tumor size <5cm<5cm

• Nearly all authors agree tumor size Nearly all authors agree tumor size determining determining local recurrence /efficacylocal recurrence /efficacy

• Goletti O et al, Montorsi M et al , Livraghi T Goletti O et al, Montorsi M et al , Livraghi T et al, et al, showed that complete tumor necrosis showed that complete tumor necrosis in 80% to 90% of HCCs smaller than 3 to 5 in 80% to 90% of HCCs smaller than 3 to 5 cm cm

• Livraghi T et alLivraghi T et al, complete ablation rate for , complete ablation rate for larger tumors is less favorable: a study of larger tumors is less favorable: a study of RFA for 126 HCCs 3.1 to 9.5 cm (mean 5.4 RFA for 126 HCCs 3.1 to 9.5 cm (mean 5.4 cm) reported a complete necrosis rate of cm) reported a complete necrosis rate of 48% with the use of a clustered electrode.48% with the use of a clustered electrode.

Diameter (Size)Diameter (Size)

Size of individual RFA is limitedSize of individual RFA is limited• Single coagulation cannot cover a large Single coagulation cannot cover a large

lesion lesion i.ei.e.< 100% necrosis – higher risk of .< 100% necrosis – higher risk of local recurrencelocal recurrence

Adam R et la, Arch Surg 2002Adam R et la, Arch Surg 2002

• For large tumors, overlapping coagulations For large tumors, overlapping coagulations is necessary, however, technically is necessary, however, technically difficulty –Ultrasonogram is difficult to difficulty –Ultrasonogram is difficult to visualize the tumor after 1st coagulation – visualize the tumor after 1st coagulation – hyperechoeic microbubble cloudhyperechoeic microbubble cloud

R Poon et la, Annals of Surgery 2000R Poon et la, Annals of Surgery 2000


Large tumors have irregular Large tumors have irregular borders and present satellite borders and present satellite lesionslesions

Livraghi T et la, Radiology 2000Livraghi T et la, Radiology 2000

• If the coagulation is restricted to the If the coagulation is restricted to the main tumor without safety margin, main tumor without safety margin, spiky irregular extensions and spiky irregular extensions and satellites will be left untreated.satellites will be left untreated.

Effect of Tumor Size on Effect of Tumor Size on Outcome of RF AblationOutcome of RF Ablation

TumorsTumors 100% 100% NecrosisNecrosis

<100% <100% NecrosisNecrosis

p p valuevalue

3.1-5.0 cm 3.1-5.0 cm 49(61%)49(61%) 31(39%)31(39%) .001.001

>5cm>5cm 11(24%)11(24%) 35(76%)35(76%)

Livraghi T et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions.Radiology 2000; 214:761–768.


ConclusionConclusion• There is no consensus for the optimal There is no consensus for the optimal

size for RFAsize for RFA

• Smaller tumor size ( < 3 cm diameter ), Smaller tumor size ( < 3 cm diameter ), the better the outcome, the lesser the the better the outcome, the lesser the local recurrance ratelocal recurrance rate

• Due the advancing technology, future Due the advancing technology, future electrode may tackle with larger tumorelectrode may tackle with larger tumor

ApproachApproach

• Surgical (open / laparoscopic) Vs Surgical (open / laparoscopic) Vs PercutaneousPercutaneous

• Absence of RCT Absence of RCT

• No consensusNo consensus

Surgical (open / laparoscopic) Surgical (open / laparoscopic) Vs PercutaneousVs Percutaneous

• From From Steven A. Curley et laSteven A. Curley et la, complete , complete ablations in the 65 HCCs treated during ablations in the 65 HCCs treated during laparotomy or laparoscopy, however, 7.1% laparotomy or laparoscopy, however, 7.1% (6/84) incidence of incomplete RFA in the (6/84) incidence of incomplete RFA in the HCCs treated percutaneously. HCCs treated percutaneously.

• From From Rhim H et alRhim H et al, incomplete tumor , incomplete tumor destruction has been reported in up to 18% destruction has been reported in up to 18% of liver cancers treated percutaneously with of liver cancers treated percutaneously with RFARFA

Surgical (open / laparoscopic) Surgical (open / laparoscopic) Vs PercutaneousVs Percutaneous• One disadvantage to RFA is the One disadvantage to RFA is the

difficulty in difficulty in determine accurately determine accurately the exact areathe exact area that has been that has been coagulatedcoagulated

• Intraoperative or laparoscopic Intraoperative or laparoscopic ultrasonography provides ultrasonography provides better better resolutionresolution of the tumor and RFA of the tumor and RFA treatment compared with treatment compared with transabdominal ultrasonography for transabdominal ultrasonography for percutaneous treatmentpercutaneous treatment

Steven A. Curley et la, Annals of Surgery 2000Steven A. Curley et la, Annals of Surgery 2000

Surgical (open / laparoscopic) Surgical (open / laparoscopic) Vs PercutaneousVs Percutaneous• Better tumor visualization compared with Better tumor visualization compared with

external ultrasound especially of tumors external ultrasound especially of tumors located in the located in the superior right lobesuperior right lobe of the liver of the liver

• ~30% increase in tumor detection rate by ~30% increase in tumor detection rate by intraoperative ultrasound during laparoscopy intraoperative ultrasound during laparoscopy or laparotomy compared with preoperative or laparotomy compared with preoperative imaging imaging

Siperstein T et la, Annals of Surgical Oncology 2002Siperstein T et la, Annals of Surgical Oncology 2002

• Accurate tumor staging Accurate tumor staging K K-C Ng et la, Journal of Gastro-Hepatology 2003K K-C Ng et la, Journal of Gastro-Hepatology 2003


• Easy access to tumors located in the Easy access to tumors located in the superior superior right loberight lobe of the liver of the liver

• Improved visibility will lead to a more Improved visibility will lead to a more correct correct insertioninsertion of the electrodes and an increased of the electrodes and an increased chance of complete covering of the tumor, chance of complete covering of the tumor, including its irregular margins, satellites, and a including its irregular margins, satellites, and a 1-1-cm safety margincm safety margin

• Mobilization of the liverMobilization of the liver allows larger degree of allows larger degree of freedom for inserting the electrodes under an freedom for inserting the electrodes under an optimal angleoptimal angle

Rossi S et la, AJR AM J Roent-genol. 1996Rossi S et la, AJR AM J Roent-genol. 1996


• Laparoscopic approach, pneumoperitoneum Laparoscopic approach, pneumoperitoneum and the and the upward movementupward movement of the of the diaphragm, liver movement is diaphragm, liver movement is minimalminimal, , facilitating precise electrode placement.facilitating precise electrode placement.

Siperstein A et la, Surgical Endoscopy 2002Siperstein A et la, Surgical Endoscopy 2002

• Surgical route, allows Surgical route, allows multiple parallel multiple parallel reinsertionsreinsertions of the electrode when of the electrode when overlapping coagulations are necessaryoverlapping coagulations are necessary

Rossi S et la, AJR AM J Roent-genol. 1996Rossi S et la, AJR AM J Roent-genol. 1996


• Intraoperative RFA allows the use of Intraoperative RFA allows the use of Pringle maneuverPringle maneuver to minimize the to minimize the “heat sink” effect of the hepatic vessels“heat sink” effect of the hepatic vessels

Mulier S et la, Eur J Surgical Oncology 2003Mulier S et la, Eur J Surgical Oncology 2003

• During laparoscopy, a 12-mm Hg During laparoscopy, a 12-mm Hg pneumoperitoneumpneumoperitoneum by itself causes a by itself causes a 40% 40% decrease of portal vein flowdecrease of portal vein flow

Smith MK et la, Surgical Endoscopy 2004Smith MK et la, Surgical Endoscopy 2004

A 5-cm A 5-cm hepatocellular hepatocellular carcinoma at the carcinoma at the dome of the liver dome of the liver (A,arrow) treated (A,arrow) treated by intraoperative by intraoperative radiofrequency radiofrequency ablation using a ablation using a clustered probe clustered probe (B). (B).


Intraoperative ultrasound Intraoperative ultrasound provides guidance to provides guidance to positioning of the positioning of the probe (C, arrow shows probe (C, arrow shows the tip of the probe) in the tip of the probe) in the tumor before the tumor before starting starting radiofrequency radiofrequency ablation, but the exact ablation, but the exact margin of ablation is margin of ablation is obscured by obscured by hyperechoic shadow hyperechoic shadow resulting from thermal resulting from thermal changes in the tissue changes in the tissue after starting the after starting the ablation (D, arrows).ablation (D, arrows).



• Intended Intended safety margin of 1 cmsafety margin of 1 cm, was , was used used much lessmuch less in the percutaneous in the percutaneous approach than in the surgical approachapproach than in the surgical approach

• Subcapsular tumorsSubcapsular tumors are often are often undertreated by a percutaneous approach undertreated by a percutaneous approach because of fear of burning adjacent because of fear of burning adjacent organs, diaphragm, or the abdominal wallorgans, diaphragm, or the abdominal wall

R Poon et la, Annals of Surgery 2002R Poon et la, Annals of Surgery 2002


ApproachApproach No. No. of of CaseCasess

No No MargiMarginn

0.5 cm 0.5 cm MargiMarginn

1 cm 1 cm MargiMarginn

pp

PercutaneoPercutaneousus

30463046 88.4%88.4%

(2692)(2692)5.4%5.4%

(165)(165)6.2%6.2%

(189)(189)<0.00<0.0011

SurgicalSurgical 12481248 28.8%28.8%

(360)(360)13.6%13.6%

(170)(170)57.5557.55%%

(718)(718)

<0.00<0.0011

Intentional Margin According to Approach

tumor 10 mm

Ablation zone


ConclusionConclusion• Laparoscopic or open approach is Laparoscopic or open approach is

recommended in patients with a high recommended in patients with a high risk of bleeding from severe risk of bleeding from severe coagulopathycoagulopathy, , large HCCslarge HCCs (5 cm), (5 cm), superficial nodulessuperficial nodules adjacent to adjacent to other visceral organsother visceral organs at risk of at risk of thermal injury, or thermal injury, or deeply located deeply located lesionslesions not accessible to not accessible to percutaneous puncturepercutaneous puncture



• The percutaneous route remains The percutaneous route remains valuable for certain indications:valuable for certain indications: For patients that are tooFor patients that are too fragile fragile to to

undergo laparoscopy or laparotomy. undergo laparoscopy or laparotomy.

Tumors that are Tumors that are invisible on ultrasoundinvisible on ultrasound imaging can be treated by a CT- or MRI-imaging can be treated by a CT- or MRI-guided percutaneous procedure.guided percutaneous procedure.

May be performed as a May be performed as a day procedureday procedure


50.060.0>5 cm

21.725.93-5 cm

3.616.0<3 cm

Laparoscopy/ Laparotomy (%)

Percuteneous (%)

Local Recurrence Rate According to Size and Approach

ConclusionConclusion• SurgerySurgery remain the gold standard of remain the gold standard of

treating liver tumortreating liver tumor

• RFA is RFA is superior optionsuperior option in treating in treating unresectable primary and secondaryunresectable primary and secondary

• Surgical approachSurgical approach have less local have less local recurrance rate and better outcome recurrance rate and better outcome when compared with percutaneous when compared with percutaneous routeroute

• Small size tumorSmall size tumor have better have better outcome, however, advance technology outcome, however, advance technology may overcome this problem in futuremay overcome this problem in future

RFA Vs CryoablationRFA Vs Cryoablation

• Local recurrence rate:Local recurrence rate:

• 2.2% Vs 13.6%2.2% Vs 13.6%

• Treatment mortality:Treatment mortality:

• 0% Vs 2%0% Vs 2%

• Complication rate:Complication rate:

• 3.3% Vs 40%3.3% Vs 40%Pearson AS et al. Am. J. Surg. 1999Pearson AS et al. Am. J. Surg. 1999

RFA Vs Microwave Coagulation RFA Vs Microwave Coagulation TherapyTherapy

• Complete ablation:Complete ablation:

• 91% Vs 85%91% Vs 85%

• Local recurrence Local recurrence

• 4%Vs 17%4%Vs 17%Lencioni et al. Radiology 1999Lencioni et al. Radiology 1999

RFA Vs PEIRFA Vs PEI

• Complete necrosis :Complete necrosis :

• RFA Vs PEI – 90% Vs 80%RFA Vs PEI – 90% Vs 80%

• Treatment section:Treatment section:

• Mean 1.2 Vs 4.8 sessionsMean 1.2 Vs 4.8 sessions

• Complication rate:Complication rate:

• 12% Vs 0%12% Vs 0%Livraghi T et al. Radiology 1999Livraghi T et al. Radiology 1999

RFA Vs TACERFA Vs TACE

• Complete control of tumor growth:Complete control of tumor growth:

• 50% Vs 30%50% Vs 30%

• Mortality:Mortality:

• 0% Vs 4%0% Vs 4%

Livraghi et al. Radiology 2002Livraghi et al. Radiology 2002

RFA Vs ResectionRFA Vs Resection• RecurrenceRecurrence• 53% Vs 30%53% Vs 30%• Resection recurrence – distant recurrence Resection recurrence – distant recurrence • RFA recurrence – local recurrenceRFA recurrence – local recurrence

Montorsi M et la,Montorsi M et la,The Society for Surgery of the Alimentary Tract 2005The Society for Surgery of the Alimentary Tract 2005

• Resection is more effective, in terms of Resection is more effective, in terms of overall and disease-free survival, in overall and disease-free survival, in Child’s AChild’s A patient with a patient with a singlesingle tumour tumour >3cm>3cm

Vivarelli M et la, Annals of Surgery 2004Vivarelli M et la, Annals of Surgery 2004

RFA – Bridge therapyRFA – Bridge therapy

• Retrospective studyRetrospective study• 1414 cirrhotic patients with small HCC ( cirrhotic patients with small HCC ( 3.5cm) 3.5cm)• RFA prior to transplanatationRFA prior to transplanatation• Median follow-up: 16 monthsMedian follow-up: 16 months• Histology :Histology :

– complete necrosis: 71%complete necrosis: 71%– incomplete necrosis: 29%incomplete necrosis: 29%– tumour satellites < 1cm from main tumour: 57%tumour satellites < 1cm from main tumour: 57%

• No complication/ death/ recurrenceNo complication/ death/ recurrence

Documents

Joint Hospital Surgical Grand Round Radiofrequency Ablation of Hepatic Tumor (Factors affect local recurrence rate) Dr K Y Yuen United Christian Hospital