Chemoembolization, Cryotherapy and

Microwave ThermotherapyFred T. Lee Jr., MD

University of Wisconsin Dept. of Radiology

• Chemoembolization• Chemoembolization+RF• Cryotherapy• Microwave thermotherapy• Comparison of techniques

Chemoembolization

• Delivery of concentrated chemotherapy to liver via hepatic artery

• Used for hepatocellular carcinoma and metastases (lobar or segmental)

• Less systemic side effects than IV chemotherapy

Chemoembolization

Indications• Unresectable HCC or liver mets• Nonsurgical candidates• Single or multiple lesions• Palliation/selective prolongation of life

Chemoembolization:Contraindications

• Total bilirubin>3.5

• Portal Vein Thrombosis

• Active Infection

Chemoembolization:

• Prep: bowel, skin, Abx, steroids, hydration

• Selective, superselective catherization of tumor vessels bypass GDA, cystic artery

• Slowly inject “cocktail”

Wisconsin “cocktail”Cisplatin 100 mg

Mitomycin C 10 mg

Adriamycin 50 mg

Ethiodol 10 cc

Contrast 8 cc

Ivalon particles 300-500 µ

McDermott J, Wojtowycz M, Sproat I, Omary R,Salem R, Wagner HJ

Results (many different cocktails, protocols)

• Mets: response rates, but probably no survival advantage. Palliation.

• HCC: High local tumor response rates. Probably no survival advantage vs. symptomatic rx. Less effective than surgery in resectable patients.

Pelletier. J Hep 1998

Kanematsu. Cancer 1993

RF Ablation: Why We Fail

• Mets: local failures=30-50%• Miss lesion• Cover, but don’t kill entire tumor• Most failures occur in the rim:

vessels!

Cooled-tip electrode: Porcine Liver Slice

Conventional RF: Current Density

tumorCurrent density=1/r 4

Conventional RF: Current Density

tumorCurrent density=1/r 4

vessel

Vessels as cause of RF failures

• Lu DS, RSNA 2000

• Gillams AR, Lees W. RSNA 1999, 2000

Better RF Lesion Size/Shape with Vascular Occlusion

• Bodie AW, Cancer Res 1986

• Goldberg SN, Radiology, JVIR 1998

• Patterson EJ, Ann Surg 1998

• Chinn SB, Lee FT, AJR 2001

Decreased local recurrence (19%) of HCC with bland vascular occlusion

• Rossi S, Garbagnati F, Lencioni R, et al. Radiology 2000;217

RF ablation+chemoembolization:Rationale

• Embo increases size, rounder

• Deposits chemo in tumor, EDGES!

• RF increases dwell time of chemo

• Need long term results

RF + Chembo: RSNA 2001

• Yamakado K

• Pereira P

Good local control of large HCC

Chemoembolization + RF ablation

Post Chemoembolization Post Chembo+RF

Pre-treatment Post chembo+RF

Microwave Coagulation Therapy

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Microwave Coagulation Therapy

• Used in Japan for >10 years

• No system currently available in the USA

• Microwave “field” causes tissue heating

• Net effect is much like RF

generatorCurrent drop 1/r4

Heating drop 1/r2

RF ablation

generator

MCT ablation

No grounding pads necessary

RF ablation

Microwave

Active zone

Several mm’s

2 cm

Microwave Coagulation Therapy

Microwave vs RF

• Microwave: Hotter, possibly faster, multiple probes, no ground pads. No USA experience

• RF: Available, robust technology, increasing lesion size

Microwave vs RF

RF

MW

Immediate 48o 4 Weeks

MW vs. RF

48 Hours 4 Weeks

RF

MW

Hepatic Cryoablation• Very powerful local ablation technique• Multiple probes can be used together to

ablate a tumor of virtually any size• Freezes tissue to app. -150 degrees C.• Tissue death due to cellular rupture,

vascular occlusion

Cryoablation of liver tumors

• First focal tumor ablation technology

• Performed clinically since the early 1960’s

• Combined with IOUS in 1980’s (Onik)

Courtesy of G. Onik, MD

In era of RF, is cryo still needed?

• Very powerful. Multiple probes make a large iceball in a short period of time, can ablate up to large vessels.

Precryo POD 5 4 months post

In era of RF, is cryo still needed?

• Very powerful. Multiple probes make a large iceball in a short period of time, can ablate adjacent to large vessels.

• Low local recurrence rates

Cryoablation: Local Recurrence

• Deaconess (Kane) 5-year followup: 12%

• Wisconsin (Lee) 28 mo f/u: 9% Surgical margin recurrences 11%

RSNA 97

J GI Surg, 2001

• RF local recurrence 54% (Livraghi, Radiology 2001)

Hepatic Cryoablation

Cryoablation RF ablation

In era of RF, is cryo still needed?

• Very powerful. Multiple probes make a large iceball in a short period of time, can ablate adjacent to large vessels.

• Low local recurrence rates

• Visualize area being ablated

In era of RF, is cryo still needed?

• Very powerful. Multiple probes make a large iceball in a short period of time, can ablate up to large vessels.

• Low local recurrence rates (10% vs 40-50%

• Intraoperative: Don’t miss lesions>3mm

Precryo

Precryo POD 5

Liver cryosurgery

• Laparotomy

• Mini-laparotomy

• Percutaneous

Liver cryosurgery• Laparotomy

Monitored by IOUSCan detect tumors<3.0 mmOften combined with hepatic

resectionPlace probes to cover lesion +

margin with iceball

Cryosurgery at open laparotomy

• Need to mobilize liver for many tumor locations

• Can access virtually any lesion

IVC

IVC

Hepatic Cryosurgery: Minilaparotomy

• Use transvaginal US transducer

• Small incision, direct puncture of lesion

Laparoscopic vs. Minilaparotomy

Cryosurgery via minilaparotomy

Percutaneous CT-guided cryosurgery

Percutaneous Cryotherapy

PrePre

2 - 3mm probes 2 - 3mm probes

Immediate Post Immediate Post Courtesy Peter J. Littrup, MD

Balloon Protection

Courtesy Peter J. Littrup, MD

MRI guided Cryotherapy

Courtesy Stuart Silverman, MD

Cryoablation - complications (n=869 pooled world’s literature)

Mortality = 1.6%

Hemorrhage = 3.9%

Coagulopathy = 3.8%

ARF = 1.4%

Biloma 2.9%

Seifert. J Roy Coll Surg Edin 1998

Survival statistics for hepatic cryosurgery

Ref N Med. F/u (mo)

Disease-free survival (%)

Alive with disease (%)

Overall survival (%)

Ravikumar 32 24 34 28 62

Ravikumar 24 24 29 33.5 62.5

Onik 18 28.8 (mean) 22 67 89

Onik 50 18 (mean) 27 25 52

Zhou* 75 60, 120 7.3, 0

Zhou + 32 60, 120 48.8, 17.1

*HCC >5.0 cm+HCC <=5.0 cm

Cryoablation vs. Resection: Survival

Cryo Resection

N 63 60

3 yr. 60 51

5 yr. 44 36

10 yr. 19 8

1Kane, RSNA 19972Korpan, Ann Surg 1997: 225

(20)1

2

Followup of cryolesions

• “Hole” in liver where tumor was

• Enhancing rim for several months

• Eventual shrinkage and scarring

1 month post 4 months post 1 year post

Cryoablation: Complications (n=869)

• Mortality:1.6%

• Hemorrhage 3.9%

• Coagulopathy 3.8%

• Renal Failure 1.4%

• Biloma 2.9%

Seifert, J Royal Coll Surg 1998

Summary:Chemoembolization

• Used alone for palliation of unresectable/unablatable tumor

• Powerful when used in combination with RF

Summary: Microwave

• Theoretical advantages over RF(hotter, faster, multiple probes)

• Extensive experience in Asia, little in USA

• Awaiting optimization of technology

Summary: Cryoablation

• Very powerful, easy to see (CT,US,MRI)

• Generally used at surgery, emerging percutaneous applications

• Probably few more complications than thermal ablation