New Advances in the Treatment of New Advances in the Treatment of Liver Tumors: Liver Tumors:

Laparoscopic Resections Laparoscopic Resections

Cancer Care InnovationsCancer Care InnovationsDorothy E. Schneider Cancer CenterDorothy E. Schneider Cancer Center

Mills-Peninsula HospitalMills-Peninsula HospitalApril 23, 2011April 23, 2011

Kimberly Moore Dalal, MD, FACSKimberly Moore Dalal, MD, FACSSurgical Oncology and General SurgerySurgical Oncology and General Surgery

Peninsula Medical ClinicPeninsula Medical ClinicBruce Allen, MD; Aziz Ahmad, MD; Dirk Baumann, MD; John Beare, Bruce Allen, MD; Aziz Ahmad, MD; Dirk Baumann, MD; John Beare,

MD; Pamela Foster, MD; Stephanie Lin, MD; Andrea Metkus, MD; John MD; Pamela Foster, MD; Stephanie Lin, MD; Andrea Metkus, MD; John Rosenman, MD; Randolph Wong, MD; Albert Wetter, MD Rosenman, MD; Randolph Wong, MD; Albert Wetter, MD

Historical PerspectiveHistorical Perspective

“…“…the liver is so friable, so full of gaping the liver is so friable, so full of gaping

vesselsvessels and so evidently incapable of and so evidently incapable of

being sutured that it seems impossible to being sutured that it seems impossible to

successfully manage large wounds of its successfully manage large wounds of its

substance.” substance.” JW Elliot 1897JW Elliot 1897

Liver cancer

Historical PerspectiveHistorical Perspective

“…“…20% of patients died in the operating room 20% of patients died in the operating room

because of exsanguinating hemorrhage… because of exsanguinating hemorrhage…

Another 14% died post-operatively as a Another 14% died post-operatively as a

direct consequence of enormous blood loss direct consequence of enormous blood loss

during operation…15% died of liver failure during operation…15% died of liver failure

caused by technical factors other than caused by technical factors other than

hemostasis, including 3 bile duct injuries…”hemostasis, including 3 bile duct injuries…”

Foster JH, Berman MM. Major Problems in Clincal Surgery 1977;1-342.

Liver cancer

OR Team, Bagram, Afghanistan 2007OR Team, Bagram, Afghanistan 2007

Liver cancer

MASCAL, October 14, 2007MASCAL, October 14, 200719 Americans injured19 Americans injured

Liver cancer

Liver Resection TodayLiver Resection TodayAuthorAuthor NN Operative Mortality (%)Operative Mortality (%)

Scheele ‘91Scheele ‘91 219219 66Rosen ‘92Rosen ‘92 280280 44Gayowski ’94Gayowski ’94 204204 00 Scheele ‘95Scheele ‘95 469469 44 Nordlinger ’95Nordlinger ’95 568568 22 Jamison, ‘97Jamison, ‘97 280280 44Fong ’99Fong ’99 10011001 33

Normal livers

Liver cancer

OutlineOutline

Laparoscopic liver resections for benign and malignant Laparoscopic liver resections for benign and malignant tumorstumors– Benign lesionsBenign lesions– Hepatocellular carcinomaHepatocellular carcinoma– Colorectal cancer metastasesColorectal cancer metastases

Liver cancer

AnatomyAnatomy

Liver cancer

Benign Hepatic LesionsBenign Hepatic Lesions

Liver cancer

Tumor Malignant Potential Spontaneous Hemorrhage

Focal nodular hyperplasia No No

Hemangioma No Rare

Cystadenoma Yes No

Adenoma Yes Yes

Case 1: Cystic Lesion of the LiverCase 1: Cystic Lesion of the Liver

51 year old woman51 year old woman

3.5 cm Liver Cyst, Seg 4, first noted on chest CT in 20013.5 cm Liver Cyst, Seg 4, first noted on chest CT in 2001

Presented with 3 days RUQ painPresented with 3 days RUQ pain

RUQ ultrasound (2/07): complex cystic structure of the RUQ ultrasound (2/07): complex cystic structure of the liver with layeringliver with layering

Triple phase liver CT (2/07): Cystic lesion, Seg 4, 6x8x6 Triple phase liver CT (2/07): Cystic lesion, Seg 4, 6x8x6 cm; Hounsfield units 6 (noncontrast), 11 (iv contrast)cm; Hounsfield units 6 (noncontrast), 11 (iv contrast)

Liver cancer

UltrasoundComplex cystic structure of liver with layering

Liver cancer

Triple phase liver CT: Triple phase liver CT: Cystic lesion, Seg 4, 6x8x6 cmCystic lesion, Seg 4, 6x8x6 cm

Liver cancer

Case 2: Hepatic Adenoma Case 2: Hepatic Adenoma

43 yo F with incidentally discovered right liver 43 yo F with incidentally discovered right liver mass detected on CT of chest for workup of mass detected on CT of chest for workup of cough. cough.

AFP and CEA normal. LFTs normal.AFP and CEA normal. LFTs normal.

CT and MRI CT and MRI – 4.2x2.1x2.0 cm mass, Seg 7, consistent with a 4.2x2.1x2.0 cm mass, Seg 7, consistent with a

hepatic adenoma.hepatic adenoma.

Liver cancer

Liver cancer

Triple phase liver CT: Seg 7, 4x2x2 cmTriple phase liver CT: Seg 7, 4x2x2 cm

Traditional Open “Chevron” IncisionTraditional Open “Chevron” Incision

Liver cancer

Exposure in an Open ResectionExposure in an Open Resection

Liver cancer

Laparoscopic Port Placement for Laparoscopic Port Placement for Right Liver LesionsRight Liver Lesions

Cho JY, et al., Arch Surg 2009; 144(1):25-29.

Liver cancer

Laparoscopic View of the LiverLaparoscopic View of the Liver

Liver cancer

Machado MA, et al., Surg Endosc, 2009; 23:2615-2619.

Case 2: Hepatic Adenoma, Segment 7 Case 2: Hepatic Adenoma, Segment 7 Laparoscopic Resection…9 Months LaterLaparoscopic Resection…9 Months Later

Liver cancer

EstablishedEstablishedDiagnosis/StagingDiagnosis/StagingFenestration of Simple CystsFenestration of Simple Cysts

EvolvingEvolvingMinor resections (≤ 2 segments) for tumorMinor resections (≤ 2 segments) for tumorMajor hepatic resections Major hepatic resections Tumor ablationTumor ablation

Laparoscopic Liver SurgeryLaparoscopic Liver Surgery

Liver cancer

Laparoscopic Liver ResectionLaparoscopic Liver ResectionTheoretical AdvantagesTheoretical Advantages

Less post-operative painLess post-operative pain

Less post-operative morbidityLess post-operative morbidity

Shorter hospital stayShorter hospital stay

Improved cosmesisImproved cosmesis

Quicker return to normal activityQuicker return to normal activity

Quicker initiation of adjuvant therapiesQuicker initiation of adjuvant therapies

Liver cancer

Laparoscopic Liver ResectionLaparoscopic Liver ResectionTheoretical DisadvantagesTheoretical Disadvantages

Loss of tactile senseLoss of tactile senseMarginsMarginsStagingStaging

Limited access/instrumentationLimited access/instrumentationExposureExposureControl of major pedicles/hepatic Control of major pedicles/hepatic veinsveins

Time and moneyTime and money

Liver cancer

Laparoscopic Liver ResectionLaparoscopic Liver ResectionSolutionsSolutions

Loss of tactile senseLoss of tactile senseMarginsMargins

StagingStaging

LaparoscopicUltrasound

Hand-assisted techniques

Liver cancer

Laparoscopic Liver ResectionLaparoscopic Liver ResectionSolutionsSolutions

Limited access/instrumentationLimited access/instrumentationExposureExposure

Control of major pedicles/hepatic veinsControl of major pedicles/hepatic veins

Fear of major hemorrhageFear of major hemorrhage

• Hand-assisted techniques

• Ligaments intact• Improved

retractors

HarmonicScalpel

VascularStapler

LigasureDevice

Tissuelink

Argon Beam Coagulator

Water Jet

Liver cancer

Laparoscopic Liver ResectionLaparoscopic Liver ResectionSolutionsSolutions

Time and moneyTime and money

Comparison to open surgery in trials

Liver cancer

•Segmental resection: 27 pts (61%)

2

7853

•1 segment: 17 pts (38%)

•>1segment: 10 pts (22%)

•Left lateral: 6 pts (13%)

Laparoscopic Hepatectomy

MSKCC Results (n=44)

D’Angelica, MD, et al., AHPBA 2006

Liver cancer

Benign 21 pts (47%)

Malignant 23 pts (53%)

23 pts: Negative margins (100%). No local recurrence.

1 tumor 36 pts (81%)

> 1 tumor 8 pts (18%)

Laparoscopic Hepatectomy

MSKCC Results (n=44)

Liver cancer

D’Angelica, MD, et al., AHPBA 2006

LLR(n=44)

OLR(n=91) p

OR time (minutes) 199 161 0.01

Pringle time (minutes) 31 22 0.04

Pringle 45% 75% <0.01

EBL (ml) 161 521 <0.01

Transfusion 2.2% 26% <0.01

Operative Outcome

Laparoscopic Hepatectomy

MSKCC Results: Comparison to Open

Liver cancer

D’Angelica, MD, et al., AHPBA 2006

LLR(n=44)

OLR(n=91) p

Length of stay (days) 5.1 6.7 <0.01

Morbidity 13% 28% 0.08

Regular diet (days) 3 3 0.7

Oral analgaesia (days) 3.1 3.5 0.1

Mortality 0% 0% 0

Laparoscopic Hepatectomy

MSKCC Results: Comparison to Open

Post-operative Outcome

Liver cancer

D’Angelica, MD, et al., AHPBA 2006

For well-selected patients, laparoscopic liver For well-selected patients, laparoscopic liver resection is safe and does not compromise resection is safe and does not compromise operative or oncologic outcomes. operative or oncologic outcomes.

While laparoscopic liver resection is associated While laparoscopic liver resection is associated with some benefits, these can only be with some benefits, these can only be definitively proven in randomized controlled definitively proven in randomized controlled trials. trials.

SummarySummary

Liver cancer

OutlineOutline

Laparoscopic liver resections for benign and malignant Laparoscopic liver resections for benign and malignant tumorstumors– Benign lesionsBenign lesions– Hepatocellular carcinomaHepatocellular carcinoma– Colorectal cancer metastasesColorectal cancer metastases

Liver cancer

Epidemiology of Hepatobiliary CancerEpidemiology of Hepatobiliary Cancer

Estimated U.S. incidence in 2010: 24,120 Estimated U.S. incidence in 2010: 24,120 cases/yearcases/year11

Annual incidence of HCC with Hepatitis Annual incidence of HCC with Hepatitis C cirrhosis is 2-8%, Hepatitis B cirrhosis C cirrhosis is 2-8%, Hepatitis B cirrhosis 2.5%.2.5%.

18,910 deaths in men and women18,910 deaths in men and women

Jemal A, et al., CA Cancer J Clin, 2010; 60:27-300.

Liver cancer

Diagnosis and Workup for HCCDiagnosis and Workup for HCC

Often asymptomatic.Often asymptomatic.

Nonspecific symptoms: Nonspecific symptoms: anorexia, weight loss, malaise, anorexia, weight loss, malaise, upper abdominal pain. upper abdominal pain.

Paraneoplastic syndromes: Paraneoplastic syndromes: hypercholesterolemia, hypercholesterolemia, erythrocytosis, hypercalcemia, erythrocytosis, hypercalcemia, hypoglycemia. hypoglycemia.

Physical signs: Physical signs: jaundice, jaundice, ascitesascites

AFP>200 ng/mL + liver AFP>200 ng/mL + liver mass =HCCmass =HCC

Liver cancer

Zhang BH et al., J Cancer Res Clin Oncol. 2004; 130:417-422.

Child-Pugh Class A Patients are Child-Pugh Class A Patients are Candidates for ResectionCandidates for Resection

Liver cancer

1 2 3

Encephalopathy None 1-2 3-4

Ascites None Slight Moderate

Albumin (g/dL) >3.5 2.8-3.5 <2.8

Prothrombin time (sec) 1-4 4-6 >6

Bilirubin (mg/dL) 1-2 2-3 >3

Class A = 5-6 points Good operative riskClass B = 7-9 points Moderate operative riskClass C = 10-15 points Poor operative risk

Case 3: Hepatocellular CarcinomaCase 3: Hepatocellular Carcinoma

74 yo M with Hepatitis C x 30 years from a blood 74 yo M with Hepatitis C x 30 years from a blood transfusion, treated with interferon for one yeartransfusion, treated with interferon for one year

Developed pneumonia and asked PCP to Developed pneumonia and asked PCP to investigate for cirrhosis.investigate for cirrhosis.

AFP: 4690.AFP: 4690.

Abd US: 3.4 x 2.4 x 3.1 cm mass, left lateral Abd US: 3.4 x 2.4 x 3.1 cm mass, left lateral segment of liver.segment of liver.

Triple phase Liver CT: 3.5 x 2.5 cm mass, Triple phase Liver CT: 3.5 x 2.5 cm mass, segment 3. segment 3. (CT of abdomen and pelvis 3 months earlier negative).(CT of abdomen and pelvis 3 months earlier negative).

Liver cancer

Triphasic Liver CT: Segment III 3.5 cm massTriphasic Liver CT: Segment III 3.5 cm mass

Liver cancer

Principles of Surgery for HCCPrinciples of Surgery for HCC

Mortality <5%Mortality <5%

Five-year survival rates > 50%Five-year survival rates > 50%– 70% in patients with early 70% in patients with early

stage HCC and preserved stage HCC and preserved liver function. liver function.

Recurrence at 5 yrs>75%Recurrence at 5 yrs>75%

Careful patient selection: Careful patient selection: – ComorbiditiesComorbidities– Tumor characteristicsTumor characteristics– Size and function of future Size and function of future

liver remnantliver remnant

Liver transplantation for Liver transplantation for patients meeting UNOS criteria patients meeting UNOS criteria – Single lesion Single lesion << 5cm 5cm– 2 or 3 lesions 2 or 3 lesions << 3 cm 3 cm

Liver cancer

Case 3: Hepatocellular CarcinomaCase 3: Hepatocellular Carcinoma

Laparoscopic resection of Laparoscopic resection of segment IIIsegment III

Length of stay 5 daysLength of stay 5 days

Bone metastasis @ 7 mos Bone metastasis @ 7 mos

Liver cancer

Epidemiology of Colorectal CancerEpidemiology of Colorectal Cancer

Estimated U.S. incidence of Estimated U.S. incidence of colorectal cancer: 142,570/yearcolorectal cancer: 142,570/year11

51,370 deaths51,370 deaths

50% of patients will be 50% of patients will be diagnosed with liver metastases diagnosed with liver metastases

Liver resection->long-term Liver resection->long-term survivalsurvival – 5 year survival: 25-58%5 year survival: 25-58%

– Surgical techniquesSurgical techniques

– ChemotherapyChemotherapy

– Unresectable->resectableUnresectable->resectable

1Jemal A, et al., CA Cancer J Clin, 2010; 60:27-300.2 http://www.hopkinsmedicine.org.

Liver cancer

Determinants of Outcome for CRC Determinants of Outcome for CRC Liver Metastases: Fong ScoreLiver Metastases: Fong Score

• Extrahepatic disease• Positive margins• Node (+) colorectal primary• Disease-free interval < 1 year• More than 1 hepatic tumor• Largest hepatic tumor > 5 cm• CEA > 200 ng/mL

Fong et al Ann Surg 1999;230:309

Liver cancer

Fong Y, et al., Ann Surg. 1999 Sep;230(3):309-318.

Preoperative Portal Vein Embolization Can Preoperative Portal Vein Embolization Can Increase the Future Liver RemnantIncrease the Future Liver Remnant

PVEPVE

1Chun YS, et al., J Gastrointest Surg. 2008 Jan;12(1):123-8.

Liver cancer

Percent ResectionPercent Resection– FLR/TLV 0.20 (20%)FLR/TLV 0.20 (20%)11

>40% for cirrhotics, Child’s A>40% for cirrhotics, Child’s A

>1 cm Margins are Preferred, >1 cm Margins are Preferred, but > 1 mm Margins are Favorablebut > 1 mm Margins are Favorable

• Multivariate analysis (n=1019)• > 1 tumor

• Size > 5 cm

• Node positive primary

• Bilateral resection

• Margins

Margin N (%) Median survival (mo) P

Involved/<1mm 112 (11) 30 mos Ref

1 – 10 mm 563 (55) 42 mos <0.01

> 10 mm 344 (33) 55 mos <0.01

1Are C, et al., Ann Surg. 2007 Aug;246(2):295-300.

Liver cancer

SummarySummary

Laparoscopic liver resections are safe and oncologically Laparoscopic liver resections are safe and oncologically sound in highly selected patients in the hands of surgeons sound in highly selected patients in the hands of surgeons with a laparoscopic skill set.with a laparoscopic skill set.

Patients with malignant liver tumors (primary or metastatic) Patients with malignant liver tumors (primary or metastatic) can be considered for resection based on tumor can be considered for resection based on tumor characteristics, future liver remnant size and function, and characteristics, future liver remnant size and function, and patient comorbidities.patient comorbidities.

Liver cancer

Radiofrequency AblationRadiofrequency Ablation

High-frequency alternating current flows High-frequency alternating current flows from electrical probe through tissue to from electrical probe through tissue to groundground– Ionic agitation results in frictional heating and Ionic agitation results in frictional heating and

coagulation of surrounding tissuecoagulation of surrounding tissue

Probe insertion

Extension of prongs

RF current application

Liver cancer

Radiofrequency AblationRadiofrequency Ablation

Liver cancer

Pre-ablation 3-days post 2 months post

Radiofrequency AblationRadiofrequency Ablation

Liver cancer

Radiofrequency AblationRadiofrequency Ablation

AdvantagesAdvantages– Performed Performed

percutaneously, percutaneously, laparoscopically, or at laparoscopically, or at laparotomylaparotomy

– Low complication rateLow complication rateMay be related to size May be related to size of ablation (<3 cm)of ablation (<3 cm)

DisadvantagesDisadvantages– Poor performance Poor performance

near blood vesselsnear blood vessels– One probeOne probe

Many tumors require Many tumors require multiple, overlapping multiple, overlapping ablationsablations

– SlowSlow

Liver cancer

Microwave AblationMicrowave Ablation

Theoretical advantages over RFATheoretical advantages over RFA– Larger zone of active heatingLarger zone of active heating

Possibly better performance near blood vesselsPossibly better performance near blood vessels

– Hotter temperatureHotter temperature– Use of multiple probesUse of multiple probes

Liver cancer

Microwave AblationMicrowave Ablation

Liver cancer

Factors Determining Factors Determining Resectability of CRC MetsResectability of CRC Mets

Fong Score (CRC mets)Fong Score (CRC mets)– Fong et al. Fong et al. Ann Surg Ann Surg 19991999

••Functional hepatic reserveFunctional hepatic reserve– Child-Pugh scoreChild-Pugh score– MELD scoreMELD score– Volumetric calculationsVolumetric calculations

Resectability of Colorectal Cancer Resectability of Colorectal Cancer MetastasesMetastases

Liver cancer

After portal vein embolization, left liver hypertrophied and right liver atrophied

Metastases resected

Staged ResectionsStaged Resections

Hepatocellular CarcinomaHepatocellular CarcinomaRisk FactorsRisk Factors

Hepatitis B viral infectionHepatitis B viral infection– Asia and AfricaAsia and Africa

Hepatitis C viral infectionHepatitis C viral infection– Europe, Japan, North AmericaEurope, Japan, North America

Inherited errors of metabolismInherited errors of metabolism– Hemochromatosis, alpha 1-antitrypsin deficinecy, Wilson’s diseaseHemochromatosis, alpha 1-antitrypsin deficinecy, Wilson’s disease

Autoimmune hepatitisAutoimmune hepatitis

Primary biliary cirrhosisPrimary biliary cirrhosis

Excessive alcohol intakeExcessive alcohol intake

Aflatoxin exposureAflatoxin exposure

Non-alcoholic fatty liver diseaseNon-alcoholic fatty liver disease

Liver cancer

Margins and HCCMargins and HCCRandomized prospective trialRandomized prospective trial

169 patients randomized169 patients randomized

2 cm vs 1 cm margin2 cm vs 1 cm margin

Actual margin 1.9 vs 0.7 cmActual margin 1.9 vs 0.7 cm

Well matchedWell matched

Improved survival in wide marginImproved survival in wide margin

Shi M, et al., Ann Surg 2007, 245(1):36-43.

Liver cancer

Local Recurrence Rates for RFALocal Recurrence Rates for RFA

Mulier S, et al., Ann Surg. 2005 Aug;242(2):158-71.

Liver cancer

Liver cancer