chemoembolization, cryotherapy and microwave thermotherapy fred t. lee jr., md university of...

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

UW coach's son gets 10 days for parrot's microwave death

Chad Alvarez will begin jail term on Dec. 20

By Dennis Chaptmanof the Journal Sentinel staff

Last Updated: Dec. 10, 1999

Madison - The microwave-oven killing of Iago, a Quaker parrot owned by a fraternity brother, landed Chad Alvarez two felony convictions and a sentence of probation and

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